|
1
|
von Känel R, Usseglio J, Rojas DA, David ML, Khan I, Goyal P, Edmondson D, Kronish IM, Birk JL. Peripheral physiologic responses to acute psychological stress in Takotsubo syndrome: A systematic review and meta-analysis. Neurosci Biobehav Rev 2025; 172:106129. [PMID: 40158555 DOI: 10.1016/j.neubiorev.2025.106129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Revised: 03/01/2025] [Accepted: 03/26/2025] [Indexed: 04/02/2025]
Abstract
Takotsubo syndrome (TTS) can be triggered by emotional stress, particularly in postmenopausal women, the primary patient group. However, the psychobiological mechanisms remain elusive. This systematic review aimed to synthesize the literature on peripheral physiological responses to acute psychological stress in TTS patients compared to controls. A meta-analysis was performed when data allowed. The review followed PRISMA guidelines and was registered on PROSPERO (CRD42023393222). PubMed, Embase, APA PsycInfo, Cochrane CENTRAL, ClinicalTrials.gov, and WHO ICTRP were searched from inception to February 2023, with PubMed re-searched in May 2024. Eligible studies involved adult TTS patients, included a control group, used standardized acute psychological stress induction, and measured at least one peripheral physiological marker pre- and post-stress. Risk of bias was assessed with the BIOCROSS tool. Meta-analysis used the R package metafor. Of 5752 records screened, 13 studies (k = 13) comprising 176 TTS patients and 197 controls were included. In the meta-analysis, TTS patients had higher post-stress plasma norepinephrine levels [Hedges' g= 0.50, 95 % CI (0.17, 0.84), p = 0.003, k = 5] and a marginally significant increase in stress-induced norepinephrine [g= 0.28, 95 % CI (-0.05, 0.61), p = 0.09, k = 5] compared to controls without established cardiovascular disease. They showed a smaller left ventricular ejection fraction change [g= -0.44, 95 % CI (-0.87, -0.02), p = .043, k = 3]. The systematic review additionally supported endothelial/vasomotor dysfunction (k = 3), wall motion abnormalities (k = 2), and impaired myocardial perfusion (k = 2) in TTS patients. TTS patients may exhibit distinct physiological responses to psychological stress, particularly in catecholamine levels and cardiac function. Limited studies and unclear bias reduce evidence strength.
Collapse
Affiliation(s)
- Roland von Känel
- Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Center for Behavioral Cardiovascular Health, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
| | - John Usseglio
- Augustus C. Long Health Sciences Library, Columbia University Irving Medical Center, New York, NY, USA
| | - Danielle A Rojas
- Center for Behavioral Cardiovascular Health, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
| | - Michelle L David
- Center for Behavioral Cardiovascular Health, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
| | - Issa Khan
- Center for Behavioral Cardiovascular Health, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
| | - Parag Goyal
- Department of Medicine, Weill Cornell Medical College, Cornell University, New York, NY, USA
| | - Donald Edmondson
- Center for Behavioral Cardiovascular Health, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
| | - Ian M Kronish
- Center for Behavioral Cardiovascular Health, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
| | - Jeffrey L Birk
- Center for Behavioral Cardiovascular Health, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
| |
Collapse
|
|
2
|
Bruns B, Elsous N, Burghaus I, Steyrer K, Joos M, Krämer T, Scheffel M, Blankenberg S, Eitel I, Massberg S, Thiele H, Meder B, Backs J, Frey N. Rationale and design of the Cyclosporine In Takotsubo syndrome (CIT) trial. Am Heart J 2025:S0002-8703(25)00133-4. [PMID: 40268179 DOI: 10.1016/j.ahj.2025.04.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Revised: 04/13/2025] [Accepted: 04/14/2025] [Indexed: 04/25/2025]
Abstract
BACKGROUND Takotsubo syndrome (TTS) is associated with substantial morbidity and mortality, even though ejection fraction frequently recovers spontaneously. TTS has been suggested to be caused by catecholamine excess leading to myocardial inflammation as an additional driver of cardiac damage and impaired outcome. Currently, no evidence-based treatment exists. In a preclinical model of catecholamine-driven TTS, cyclosporine A (CsA) bolus therapy significantly improved outcome, likely mediated via suppression of calcineurin-driven inflammation. The Cyclosporine In Takotsubo (CIT) trial is a pilot multicenter double-blinded randomized placebo-controlled trial (RCT) to investigate the impact of CsA bolus therapy in patients suffering from acute TTS. STUDY DESIGN AND OBJECTIVES This RCT is designed to investigate the impact of repetitive CsA bolus therapy vs. placebo in acute high-risk TTS patients with an increased risk of intrahospital complications and long-term mortality. The main goal is to reduce the myocardial damage quantified by AUC of a centrally measured high-sensitive cardiac Troponin T (hs-cTnT) over 72 h (primary endpoint). Therefore, patients with TTS will be randomized 1:1 after angiography and receive an intravenous bolus of 2.5 mg/kg CsA or an equivalent amount of placebo immediately after baseline measurements. At 12 h and 24 h additional doses of the study drug will be applied accumulating to 7.5 mg/kg in the intervention group. After baseline laboratory measurements (including hs-cTnT) and echocardiography (TTE), serum parameters will be measured again at 3 h and every 12 h from baseline. TTE imaging will be performed at 24, 48 and 72 h, and cardiac magnetic resonance imaging (CMR) at 24-96h. Left ventricular function recovery, myocardial edema (CMR), in-hospital complications, length of hospital stay, 30-day and 1-year composite cardiovascular outcome, as well as Kansas City Cardiomyopathy Questionnaire self-assessment are included as secondary endpoints. CONCLUSIONS The CIT trial is designed to assess the safety and potential benefit of CsA on hs-cTnT release as an established marker of myocardial injury in high-risk TTS patients. The results of this trial may reveal CsA as a first pathophysiology-driven treatment option of TTS and enable a phase III follow-up trial powered for clinical outcome parameters as primary endpoint. CLINICAL TRIALS IDENTIFIER NCT05946772.
Collapse
Affiliation(s)
- Bastian Bruns
- Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany; Institute of Experimental Cardiology, Heidelberg University Hospital, Heidelberg, Germany; Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site, Heidelberg/Mannheim, Germany
| | - Nesrin Elsous
- Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site, Heidelberg/Mannheim, Germany
| | - Ina Burghaus
- Coordinating Center for Clinical Trials (KKS) Heidelberg, Heidelberg, Germany
| | - Kathleen Steyrer
- Coordinating Center for Clinical Trials (KKS) Heidelberg, Heidelberg, Germany
| | - Maximilian Joos
- Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany; Institute of Experimental Cardiology, Heidelberg University Hospital, Heidelberg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site, Heidelberg/Mannheim, Germany
| | - Tobias Krämer
- Coordinating Center for Clinical Trials (KKS) Heidelberg, Heidelberg, Germany
| | - Marina Scheffel
- Coordinating Center for Clinical Trials (KKS) Heidelberg, Heidelberg, Germany
| | - Stefan Blankenberg
- University Heart Center Hamburg, Clinic of general and interventional Cardiology, University Hospital Hamburg-Eppendorf, Hamburg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Lübeck/Kiel, Hamburg, Germany
| | - Ingo Eitel
- University Medical Center Schleswig-Holstein/Campus Lübeck, Lübeck, Germany; German Center for Cardiovascular Research (DZHK), Partner site Hamburg - Kiel - Lübeck, Lübeck, Germany
| | - Steffen Massberg
- Medical Clinic and Polyclinic I, Hospital of the Ludwig-Maximilians-University Munich, Munich, Germany; German Center for Cardiovascular Research (DZHK), Partner site Munich
| | - Holger Thiele
- Heart Center Leipzig at University of Leipzig and Leipzig Heart Science, Leipzig, Germany
| | - Benjamin Meder
- Institute for Cardiomyopathies Heidelberg, Heart Center Heidelberg, Heidelberg University Hospital, Heidelberg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site, Heidelberg/Mannheim, Germany
| | - Johannes Backs
- Institute of Experimental Cardiology, Heidelberg University Hospital, Heidelberg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site, Heidelberg/Mannheim, Germany
| | - Norbert Frey
- Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site, Heidelberg/Mannheim, Germany.
| |
Collapse
|
|
3
|
Ekenbäck C, Persson J, Tornvall P, Forsberg L, Spaak J. Sympathetic nerve activity and response to physiological stress in Takotsubo syndrome. Clin Auton Res 2025; 35:205-214. [PMID: 39546154 PMCID: PMC12000160 DOI: 10.1007/s10286-024-01082-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Accepted: 10/29/2024] [Indexed: 11/17/2024]
Abstract
PURPOSE The prevailing hypothesis posits that Takotsubo syndrome (TTS) is caused by massive sympathetic activation, yet supporting evidence remains inconsistent. The objectives of the present study were to determine whether sympathetic activity and reactivity are enhanced in the recovery phase of TTS, and to evaluate the effect of selective β1-receptor blockade on sympathetic reactivity. METHODS We conducted a case-control study that included 18 female patients with TTS and 13 age- and sex-matched controls. Muscle sympathetic nerve activity was measured through microneurography of the peroneal nerve at rest and during the cold pressor test. In the TTS group, recordings were repeated after randomisation to intravenous metoprolol or placebo. In 10 TTS patients, cardiac sympathetic activity was assessed using iodine 123-metaiodobenzylguanidine scintigraphy. Blood samples were collected during hospitalisation. RESULTS Microneurography was performed a median of 27.5 days after patient admission. There were no significant differences in burst incidence, burst frequency, burst height or burst area between the TTS patients and the controls at rest, during stress or after administration of intravenous metoprolol. Iodine 123-metaiodobenzylguanidine scintigraphy was performed a median of 12.5 days after admission, revealing decreased early 1.54 ± 0.13 and late 1.40 ± 0.13 heart-to-mediastinum ratios, and an increased washout rate of 41.8 ± 12.1%. Catecholamine metabolites were comparable between the study groups. CONCLUSION General sympathetic hyperactivity or hyperreactivity unlikely contributes to TTS, as catecholamine levels and muscle sympathetic nerve activity at rest and during stress were similar between the TTS patients and the controls. As scintigraphy showed increased cardiac sympathetic activity, a pathological cardiac adrenergic response and vulnerability to sympathetic activation may be crucial for the development of the syndrome.
Collapse
Affiliation(s)
- Christina Ekenbäck
- Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
- Department of Cardiology, Danderyd University Hospital, Stockholm, Sweden.
| | - Jonas Persson
- Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden
- Department of Cardiology, Danderyd University Hospital, Stockholm, Sweden
| | - Per Tornvall
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
| | - Lena Forsberg
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Department of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden
| | - Jonas Spaak
- Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden
- Department of Cardiology, Danderyd University Hospital, Stockholm, Sweden
| |
Collapse
|
|
4
|
Arcari L, Camastra G, Ciolina F, Belmonte E, De Santis D, Danti M, Caruso D, Maestrini V, Santoro F, Brunetti ND, Laghi A, Sbarbati S, Cacciotti L. Cardiac magnetic resonance in patients with Takotsubo syndrome: Clinical correlates of T2 mapping. Int J Cardiol 2025; 419:132716. [PMID: 39532257 DOI: 10.1016/j.ijcard.2024.132716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 10/25/2024] [Accepted: 11/04/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Extensive myocardial edema is a key feature of acute takotsubo syndrome (TTS) and it can be quantitatively assessed by T2 mapping cardiac magnetic resonance (CMR) imaging. Clinical correlates of myocardial edema in TTS are not well characterized. METHODS Sixty patients with acute TTS underwent CMR with T2 mapping within one week of hospitalization. Disease severity was assessed by a validated risk score (GEIST-score). RESULTS Mean age of the study population was 71 ± 12 years (92 % females). Mean mid-septal T2 time was 58 ± 6 ms. Higher T2 mapping values were found in patients with left ventricular ejection fraction (LVEF) ≤40 % (60 ± 6 ms vs 56 ± 5 ms; p = 0.006), male sex (66 ± 7 ms vs 58 ± 6 ms; p = 0.010), dyspnea on admission (63 ± 7 ms vs 58 ± 6 ms; p = 0.006), absence of an emotional trigger (60 ± 7 ms vs 57 ± 5 ms; p = 0.039), intermediate-to-severe GEIST-score (63 ± 7 ms vs 58 ± 6 ms; p = 0.045) and in-hospital complications (61 ± 1 ms vs 58 ± 6 ms; p = 0.009). A trend towards higher values was observed in patients who died at follow-up (62 ± 8 ms vs 58 ± 6 ms; p = 0.098). On linear regression analysis, T2 mapping did not correlate with the timing of CMR (Beta -0.182, p = 0.170), whereas after multivariable correction, lack of emotional trigger (Beta 0.262, p = 0.031), decreasing LVEF (Beta -0.254, p = 0.024) and increasing GEIST score (Beta 0.282, p = 0.024) remained independently associated with T2 mapping. CONCLUSIONS In patients with acute TTS undergoing a timely CMR within the first week after admission, T2 mapping was not affected by timing of the examination, was higher in patients displaying high-risk features, and independently associated with the GEIST risk score.
Collapse
Affiliation(s)
- Luca Arcari
- Cardiology Unit, Madre Giuseppina Vannini Hospital, Rome, Italy; Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University, Rome, Italy.
| | | | | | | | - Domenico De Santis
- Department of Medical-Surgical Sciences and Translational Medicine, Radiology Unit, Sant'Andrea University Hospital, Sapienza University of Rome, Via Di Grottarossa, 1035-1039, 00189 Rome, Italy
| | | | - Damiano Caruso
- Department of Medical-Surgical Sciences and Translational Medicine, Radiology Unit, Sant'Andrea University Hospital, Sapienza University of Rome, Via Di Grottarossa, 1035-1039, 00189 Rome, Italy
| | - Viviana Maestrini
- Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University, Rome, Italy
| | - Francesco Santoro
- Department of Medical and Surgical Sciences, Università degli Studi di Foggia, Foggia, Italy
| | - Natale Daniele Brunetti
- Department of Medical and Surgical Sciences, Università degli Studi di Foggia, Foggia, Italy
| | - Andrea Laghi
- Department of Medical-Surgical Sciences and Translational Medicine, Radiology Unit, Sant'Andrea University Hospital, Sapienza University of Rome, Via Di Grottarossa, 1035-1039, 00189 Rome, Italy
| | | | - Luca Cacciotti
- Cardiology Unit, Madre Giuseppina Vannini Hospital, Rome, Italy
| |
Collapse
|
|
5
|
Madias JE. Diabetes mellitus and takotsubo syndrome: An unsettled association. J Mol Cell Cardiol 2024; 194:1-2. [PMID: 38897562 DOI: 10.1016/j.yjmcc.2024.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Revised: 06/01/2024] [Accepted: 06/14/2024] [Indexed: 06/21/2024]
Affiliation(s)
- John E Madias
- Icahn School of Medicine at Mount Sinai, New York, NY, and the Division of Cardiology, Elmhurst Hospital Center, Elmhurst, NY, USA.
| |
Collapse
|
|
6
|
Tzerefos S, Aloizou D, Nikolakopoulou S, Aloizos S. Takotsubo Syndrome: Differences between Peripartum Period and General Population. Healthcare (Basel) 2024; 12:1602. [PMID: 39201162 PMCID: PMC11354156 DOI: 10.3390/healthcare12161602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 08/07/2024] [Accepted: 08/07/2024] [Indexed: 09/02/2024] Open
Abstract
Takotsubo syndrome (TTS) was first described in postmenopausal women with transient regional wall motion abnormalities. The trigger is usually an emotional or physical stress. The catecholamine hypothesis seems to be the most prevailing. The main difference between TTS and acute coronary syndromes is that there is no obstructive coronary disease to explain the regional abnormalities. In this form, the left ventricle resembles the fishing jar which is used to trap octopus in Japan. However, to date more atypical forms are recognized. Also, the syndrome is not limited to older women. Nowadays, TTS is presented even in pregnancy and postpartum females. Our experience revealed cases of patients during these periods and some of them suffered from reverse Takotsubo. Additionally, the initial diagnosis in some patients was other than TTS. Due to these findings, we suggest that this type of TTS is not very rare but underestimated. For this reason, further studies are needed to support and explain this condition.
Collapse
Affiliation(s)
- Stavros Tzerefos
- ICU Department, IASO General and Maternity Hospital, 151 23 Athens, Greece; (D.A.); (S.A.)
| | - Dimitra Aloizou
- ICU Department, IASO General and Maternity Hospital, 151 23 Athens, Greece; (D.A.); (S.A.)
| | | | - Stavros Aloizos
- ICU Department, IASO General and Maternity Hospital, 151 23 Athens, Greece; (D.A.); (S.A.)
| |
Collapse
|
|
7
|
De Filippo O, Peano V, Pasquero M, Templin C, Cammann VL, D'Ascenzo F, De Ferrari GM. Takotsubo syndrome: Impact of medical therapies on prognosis. A state of art review. Curr Probl Cardiol 2024; 49:102623. [PMID: 38718931 DOI: 10.1016/j.cpcardiol.2024.102623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Accepted: 05/05/2024] [Indexed: 05/20/2024]
Abstract
Tako-Tsubo syndrome (TTS) presents as transient ventricular dysfunction, yet its underlying pathophysiology remains enigmatic. The prognosis of patients presenting with TTS appears to be impaired as compared to the general population and is similar to patients with acute coronary syndromes. Recent investigations have predominantly focused on elucidating therapeutic strategies associated with improved outcomes, particularly among post-menopausal female patients. Current evidence suggests that angiotensin-converting enzyme inhibitors (ACEi) may confer a survival advantage in TTS. Notably, ACEi emerges as the sole therapeutic modality demonstrating efficacy in both acute and chronic clinical courses of TTS. Despite this, the magnitude of survival benefit remains less pronounced than anticipated. This underscores the need for further research to explore additional therapeutic pathways and optimize management strategies for this unique patient cohort. Randomized clinical trials and meta-analysis are paramount in discerning the most effective therapeutic interventions aimed at enhancing survival and ameliorating outcomes in TTS. This review aims to comprehensively synthesize evidence pertaining to the prognostic implications of cardiovascular medications in TTS management.
Collapse
Affiliation(s)
- Ovidio De Filippo
- Division of Cardiology, Cardiovascular and Thoracic Department, "Citta della Salute e della Scienza" Hospital, Turin, Italy
| | - Vanessa Peano
- Division of Cardiology, Cardiovascular and Thoracic Department, "Citta della Salute e della Scienza" Hospital, Turin, Italy; Department of Medical Sciences, University of Turin, Turin, Italy
| | - Marta Pasquero
- Division of Cardiology, Cardiovascular and Thoracic Department, "Citta della Salute e della Scienza" Hospital, Turin, Italy; Department of Medical Sciences, University of Turin, Turin, Italy
| | - Christian Templin
- Department of Cardiology, University Heart Center Zurich, University Hospital Zurich, Zurich, Switzerland
| | - Victoria L Cammann
- Department of Cardiology, University Heart Center Zurich, University Hospital Zurich, Zurich, Switzerland
| | - Fabrizio D'Ascenzo
- Division of Cardiology, Cardiovascular and Thoracic Department, "Citta della Salute e della Scienza" Hospital, Turin, Italy; Department of Medical Sciences, University of Turin, Turin, Italy.
| | - Gaetano Maria De Ferrari
- Division of Cardiology, Cardiovascular and Thoracic Department, "Citta della Salute e della Scienza" Hospital, Turin, Italy; Department of Medical Sciences, University of Turin, Turin, Italy
| |
Collapse
|
|
8
|
Pillitteri M, Brogi E, Piagnani C, Bozzetti G, Forfori F. Perioperative management of Takotsubo cardiomyopathy: an overview. JOURNAL OF ANESTHESIA, ANALGESIA AND CRITICAL CARE 2024; 4:45. [PMID: 39010210 PMCID: PMC11247845 DOI: 10.1186/s44158-024-00178-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Accepted: 07/03/2024] [Indexed: 07/17/2024]
Abstract
Resembling the morphology of Japanese polyp vessels, the classic form of Takotsubo cardiomyopathy is characterized by the presence of systolic dysfunction of the mid-apical portion of the left ventricle associated with basal hyperkinesia. It is believed that this may be due to a higher density of β-adrenergic receptors in the context of the apical myocardium, which could explain the greater sensitivity of the apex to fluctuations in catecholamine levels.The syndrome is precipitated by significant emotional stress or acute severe pathologies, and it is increasingly diagnosed during the perioperative period. Indeed, surgery, induction of general anaesthesia and critical illness represent potential harmful trigger of stress cardiomyopathy. No universally accepted guidelines are currently available, and, generally, the treatment of TTS relies on health care personal experience and/or local practice. In our daily practice, anaesthesiologists can be asked to manage patients with the diagnosis of new-onset Takotsubo before elective surgery or an emergent surgery in a patient with a concomitant stress cardiomyopathy. Even more, stress cardiomyopathy can arise as a complication during the operation.In this paper, we aim to provide an overview of Takotsubo syndrome and to discuss how to manage Takotsubo during surgery and in anaesthesiologic special settings.
Collapse
Affiliation(s)
- Marta Pillitteri
- Department of Anaesthesia and Intensive Care, University of Pisa, Pisa, Italy
| | - Etrusca Brogi
- Neuroscience Intensive Care Unit, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore, 3, 20162, Milan, Italy.
| | - Chiara Piagnani
- Department of Anaesthesia and Intensive Care, University of Pisa, Pisa, Italy
| | - Giuseppe Bozzetti
- Department of Anaesthesia, Peri Operative Medicine and Critical Care, NHS Golden Jubilee, Glasgow, UK
| | - Francesco Forfori
- Department of Anaesthesia and Intensive Care, University of Pisa, Pisa, Italy
| |
Collapse
|
|
9
|
Crea F, Iannaccone G, La Vecchia G, Montone RA. An update on the mechanisms of Takotsubo syndrome: "At the end an acute coronary syndrome". J Mol Cell Cardiol 2024; 191:1-6. [PMID: 38641224 DOI: 10.1016/j.yjmcc.2024.04.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 03/13/2024] [Accepted: 04/10/2024] [Indexed: 04/21/2024]
Abstract
Takotsubo syndrome (TTS) is an acute reversible form of myocardial dysfunction, often preceded by a physical or emotional stressful event, that acts as a trigger. Despite, recent advances in the comprehension of the mechanisms leading to TTS, its pathophysiology is far from being completely understood. However, several studies seem to suggest that an acute coronary microvascular dysfunction may represent a crucial pathogenic mechanism involved in TTS occurrence. In this article, we aim to review the complex pathophysiology of TTS and the possible different mechanisms underlying this clinical condition, focusing on the role of coronary microvascular dysfunction and the remaining knowledge's gaps in the field.
Collapse
Affiliation(s)
- Filippo Crea
- Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy.
| | - Giulia Iannaccone
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Giulia La Vecchia
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Rocco A Montone
- Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| |
Collapse
|
|
10
|
Frank N, Herrmann MJ, Lauer M, Förster CY. Exploratory Review of the Takotsubo Syndrome and the Possible Role of the Psychosocial Stress Response and Inflammaging. Biomolecules 2024; 14:167. [PMID: 38397404 PMCID: PMC10886847 DOI: 10.3390/biom14020167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 01/24/2024] [Accepted: 01/29/2024] [Indexed: 02/25/2024] Open
Abstract
Takotsubo syndrome (TTS) is a cardiomyopathy that clinically presents as a transient and reversible left ventricular wall motion abnormality (LVWMA). Recovery can occur spontaneously within hours or weeks. Studies have shown that it mainly affects older people. In particular, there is a higher prevalence in postmenopausal women. Physical and emotional stress factors are widely discussed and generally recognized triggers. In addition, the hypothalamic-pituitary-adrenal (HPA) axis and the associated glucocorticoid-dependent negative feedback play an important role in the resulting immune response. This review aims to highlight the unstudied aspects of the trigger factors of TTS. The focus is on emotional stress/chronic unpredictable mild stress (CUMS), which is influenced by estrogen concentration and noradrenaline, for example, and can lead to changes in the behavioral, hormonal, and autonomic systems. Age- and gender-specific aspects, as well as psychological effects, must also be considered. We hypothesize that this leads to a stronger corticosteroid response and altered feedback of the HPA axis. This may trigger proinflammatory markers and thus immunosuppression, inflammaging, and sympathetic overactivation, which contributes significantly to the development of TTS. The aim is to highlight the importance of CUMS and psychological triggers as risk factors and to make an exploratory proposal based on the new knowledge. Based on the imbalance between the sympathetic and parasympathetic nervous systems, transcutaneous vagus nerve stimulation (tVNS) is presented as a possible new therapeutic approach.
Collapse
Affiliation(s)
- Niklas Frank
- Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, Würzburg University, 97080 Würzburg, Germany
| | - Martin J. Herrmann
- Center of Mental Health, Department of Psychiatry and Psychotherapy, University Hospital Würzburg, 97080 Würzburg, Germany; (M.J.H.); (M.L.)
| | - Martin Lauer
- Center of Mental Health, Department of Psychiatry and Psychotherapy, University Hospital Würzburg, 97080 Würzburg, Germany; (M.J.H.); (M.L.)
| | - Carola Y. Förster
- Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, Würzburg University, 97080 Würzburg, Germany
| |
Collapse
|
|
11
|
Celeski M, Nusca A, De Luca VM, Antonelli G, Cammalleri V, Melfi R, Mangiacapra F, Ricottini E, Gallo P, Cocco N, Rinaldi R, Grigioni F, Ussia GP. Takotsubo Syndrome and Coronary Artery Disease: Which Came First-The Chicken or the Egg? J Cardiovasc Dev Dis 2024; 11:39. [PMID: 38392253 PMCID: PMC10889783 DOI: 10.3390/jcdd11020039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Revised: 01/22/2024] [Accepted: 01/23/2024] [Indexed: 02/24/2024] Open
Abstract
Takotsubo syndrome (TTS) is a clinical condition characterized by temporary regional wall motion anomalies and dysfunction that extend beyond a single epicardial vascular distribution. Various pathophysiological mechanisms, including inflammation, microvascular dysfunction, direct catecholamine toxicity, metabolic changes, sympathetic overdrive-mediated multi-vessel epicardial spasms, and transitory ischemia may cause the observed reversible myocardial stunning. Despite the fact that TTS usually has an acute coronary syndrome-like pattern of presentation, the absence of culprit atherosclerotic coronary artery disease is often reported at coronary angiography. However, the idea that coronary artery disease (CAD) and TTS conditions are mutually exclusive has been cast into doubt by numerous recent studies suggesting that CAD may coexist in many TTS patients, with significant clinical and prognostic repercussions. Whether the relationship between CAD and TTS is a mere coincidence or a bidirectional cause-and-effect is still up for debate, and misdiagnosis of the two disorders could lead to improper patient treatment with unfavourable outcomes. Therefore, this review seeks to provide a profound understanding of the relationship between CAD and TTS by analyzing potential common underlying pathways, addressing challenges in differential diagnosis, and discussing medical and procedural techniques to treat these conditions appropriately.
Collapse
Affiliation(s)
- Mihail Celeski
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Roma, Italy
- Research Unit of Cardiovascular Sciences, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy
| | - Annunziata Nusca
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Roma, Italy
- Research Unit of Cardiovascular Sciences, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy
| | - Valeria Maria De Luca
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Roma, Italy
- Research Unit of Cardiovascular Sciences, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy
| | - Giorgio Antonelli
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Roma, Italy
- Research Unit of Cardiovascular Sciences, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy
| | - Valeria Cammalleri
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Roma, Italy
- Research Unit of Cardiovascular Sciences, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy
| | - Rosetta Melfi
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Roma, Italy
- Research Unit of Cardiovascular Sciences, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy
| | - Fabio Mangiacapra
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Roma, Italy
- Research Unit of Cardiovascular Sciences, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy
| | - Elisabetta Ricottini
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Roma, Italy
- Research Unit of Cardiovascular Sciences, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy
| | - Paolo Gallo
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Roma, Italy
- Research Unit of Cardiovascular Sciences, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy
| | - Nino Cocco
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Roma, Italy
- Research Unit of Cardiovascular Sciences, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy
| | - Raffaele Rinaldi
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Roma, Italy
- Research Unit of Cardiovascular Sciences, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy
| | - Francesco Grigioni
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Roma, Italy
- Research Unit of Cardiovascular Sciences, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy
| | - Gian Paolo Ussia
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Roma, Italy
- Research Unit of Cardiovascular Sciences, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy
| |
Collapse
|
|
12
|
Chong TK, Chen J, Lyu L, Wei Y, Liu Y, Wu L, Tao Y, Jiang L, Sun Z, Li D, Guan Q, Cheng F, Ding Y, Miao P, Lu C, Lei J, Wei T, Zhu T, Liu K. Clinical characteristics and outcome correlates of Chinese patients with takotsubo syndrome: Results from the first Chinese takotsubo syndrome registry. Int J Cardiol 2023; 387:131129. [PMID: 37355242 DOI: 10.1016/j.ijcard.2023.131129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 06/07/2023] [Accepted: 06/20/2023] [Indexed: 06/26/2023]
Abstract
OBJECTIVE To investigate clinical features and outcomes of Chinese patients with Takotsubo syndrome (TTS). METHODS We established the first Chinese Registry of Takotsubo Syndrome (ChiTTS Registry) and analyzed demographic, clinical, therapeutical, and outcome data to characterize clinical and outcome features of Chinese TTS patients. RESULTS In 112 enrolled patients in the ChiTTS registry from 02/01/2016 to 12/28/2021, the mean age was 59.4 ± 18.7 years old, and 27.7% were men. A total of 41.1% patients experienced respiratory and circulatory complications during hospitalization, and 17.3% patients developed cardiogenic shock. Physical triggers, dyspnea, tachycardia, and younger age (< 70 years old) predicted in-hospital complications. The MACCE rate during follow up was 13.9% per patient per year and the rate of all-cause death was 12.8% per patient per year. TTS patients with in-hospital complications developed more long-term MACCE (24.6% vs. 6.6% per patient-year, P < 0.001) and higher all-cause mortality (21.9% vs. 6.6% per patient-year, P = 0.001) than those without. The Kaplan-Meier survival analysis showed that more MACCE occurred in TTS patients with tachycardia during 3-year follow-up (HR 4.18; 95% CI 1.80-9.74; log-rank test P < 0.001). Among all medications at discharge, only beta-blocker was associated with reduced long-term MACCE (HR: 0.35; 95% CI: 0.12-0.996; P = 0.049). CONCLUSION We investigated clinical and outcome features of patients in the first Chinese TTS Registry. Tachycardiac TTS patients developed more inpatient and long-term adverse cardiovascular events.
Collapse
Affiliation(s)
- Tou Kun Chong
- Department of Cardiology, Kiang Wu Hospital, Macao Special Administrative Region of the People's Republic of China, PR China
| | - Jian Chen
- Department of Cardiology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong 519000, PR China
| | - Lingchun Lyu
- Department of Cardiology, Lishui Hospital of Zhejiang University School of Medicine, Lishui, Zhejiang 323000, PR China
| | - Yulin Wei
- Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510000, PR China
| | - Yusheng Liu
- Department of Cardiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250033, PR China
| | - Liwen Wu
- Department of Ultrasound, The sixth affiliated hospital of Guangzhou Medical University/Qingyuan People's Hospital, Qingyuan, Guangdong 511500, PR China
| | - Yuan Tao
- Department of Cardiology, Sheng Zhou People's Hospital, Shengzhou, Zhejiang 312400, PR China
| | - Lingzhi Jiang
- Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310000, PR China
| | - Zhongxia Sun
- Department of Ultrasound Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, PR China
| | - Dabin Li
- Department of Cardiology, Kiang Wu Hospital, Macao Special Administrative Region of the People's Republic of China, PR China
| | - Qianglin Guan
- Department of Cardiology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong 519000, PR China
| | - Fangyuan Cheng
- Department of Cardiology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong 519000, PR China
| | - Yongmin Ding
- Department of Respiratory and Critical Care Medicine, Sheng Zhou People's Hospital, Shengzhou, Zhejiang 312400, PR China
| | - Pengfei Miao
- Department of Cardiology, Linfen Central Hospital, Linfen, Shanxi 041000, PR China
| | - Chenying Lu
- Department of Radiology, Lishui Hospital of Zhejiang University School of Medicine, Lishui, Zhejiang 323000, PR China
| | - Juan Lei
- Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510000, PR China
| | - Tiemin Wei
- Department of Cardiology, Lishui Hospital of Zhejiang University School of Medicine, Lishui, Zhejiang 323000, PR China
| | - Tiangang Zhu
- Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction; Center for Cardiovascular Translational Research, Department of Cardiology, Peking University People's Hospital, Beijing 100000, PR China.
| | - Kan Liu
- Division of Cardiology, Heart and Vascular Center, Washington University in St Louis, Barnes-Jewish Hospital, St Louis, MO, United States of America.
| |
Collapse
|
|
13
|
Bruns B, Antoniou M, Baier I, Joos M, Sevinchan M, Moog MC, Dieterich C, Friederich HC, Khan H, Wilson H, Herzog W, Dawson DK, Frey N, Schultz JH, Backs J. Calcineurin signaling promotes takotsubo syndrome. NATURE CARDIOVASCULAR RESEARCH 2023; 2:645-655. [PMID: 39195924 PMCID: PMC11358029 DOI: 10.1038/s44161-023-00296-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 05/31/2023] [Indexed: 08/29/2024]
Abstract
Takotsubo syndrome (TTS) is an acute heart failure syndrome that mimics the symptoms of acute myocardial infarction and is often preceded by emotional and/or physical stress. There is currently no treatment for TTS. Here we show that injection of 2.5 mg kg-1 of epinephrine (EPI) into mice recapitulates numerous features of human TTS, including increased myocardial damage and mortality in males. Gene set enrichment analysis of myocardial RNA sequencing after EPI injection revealed significant enrichment of calcineurin-dependent pro-inflammatory gene networks, which was more pronounced in male than in female mice, in agreement with observed sex discrepancies in the mouse phenotype. An increase in calcineurin activity was detected in the circulating cells of patients with TTS, suggesting a systemic nature of the syndrome. Preventive and therapeutic treatment of mice injected with EPI using calcineurin inhibitors cyclosporine and tacrolimus improved heart function and reduced myocardial injury. Our findings suggest that calcineurin inhibition could be a potential therapy for TTS.
Collapse
Affiliation(s)
- Bastian Bruns
- Institute of Experimental Cardiology, Heidelberg University Hospital, Heidelberg, Germany
- Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany
- Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Heidelberg/Mannheim, Heidelberg, Germany
| | - Marilena Antoniou
- Institute of Experimental Cardiology, Heidelberg University Hospital, Heidelberg, Germany
- Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Heidelberg/Mannheim, Heidelberg, Germany
| | - Irena Baier
- Institute of Experimental Cardiology, Heidelberg University Hospital, Heidelberg, Germany
- Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Heidelberg/Mannheim, Heidelberg, Germany
| | - Maximilian Joos
- Institute of Experimental Cardiology, Heidelberg University Hospital, Heidelberg, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Heidelberg/Mannheim, Heidelberg, Germany
| | - Meryem Sevinchan
- Institute of Experimental Cardiology, Heidelberg University Hospital, Heidelberg, Germany
- Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Heidelberg/Mannheim, Heidelberg, Germany
| | - Marie-Christine Moog
- Institute of Experimental Cardiology, Heidelberg University Hospital, Heidelberg, Germany
- Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Heidelberg/Mannheim, Heidelberg, Germany
| | - Christoph Dieterich
- Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Heidelberg/Mannheim, Heidelberg, Germany
- Klaus Tschira Institute for Integrative Computational Cardiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Hans-Christoph Friederich
- Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg, Germany
| | - Hilal Khan
- Cardiology Research Group, Aberdeen Cardiovascular and Diabetes Centre, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK
| | - Heather Wilson
- Cardiology Research Group, Aberdeen Cardiovascular and Diabetes Centre, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK
| | - Wolfgang Herzog
- Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg, Germany
| | - Dana K Dawson
- Cardiology Research Group, Aberdeen Cardiovascular and Diabetes Centre, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK
| | - Norbert Frey
- Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Heidelberg/Mannheim, Heidelberg, Germany
| | - Jobst-Hendrik Schultz
- Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Heidelberg/Mannheim, Heidelberg, Germany
| | - Johannes Backs
- Institute of Experimental Cardiology, Heidelberg University Hospital, Heidelberg, Germany.
- DZHK (German Centre for Cardiovascular Research), Partner Site, Heidelberg/Mannheim, Heidelberg, Germany.
| |
Collapse
|
|
14
|
Akhtar MM, Cammann VL, Templin C, Ghadri JR, Lüscher TF. Takotsubo syndrome: getting closer to its causes. Cardiovasc Res 2023:7161872. [PMID: 37183265 DOI: 10.1093/cvr/cvad053] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Revised: 01/18/2023] [Accepted: 02/07/2023] [Indexed: 05/16/2023] Open
Abstract
Takotsubo syndrome (TTS) accounts for between 1 and 4% of cases presenting clinically as an acute coronary syndrome. It typically presents as a transient cardiac phenotype of left ventricular dysfunction with spontaneous recovery. More dramatic presentations may include cardiogenic shock or cardiac arrest. Despite progress in the understanding of the condition since its first description in 1990, considerable questions remain into understanding underlying pathomechanisms. In this review article, we describe the current published data on potential underlying mechanisms associated with the onset of TTS including sympathetic nervous system over-stimulation, structural and functional alterations in the central nervous system, catecholamine secretion, alterations in the balance and distribution of adrenergic receptors, the additive impact of hormones including oestrogen, epicardial coronary or microvascular spasm, endothelial dysfunction, and genetics as potentially contributing to the cascade of events leading to the onset. These pathomechanisms provide suggestions for novel potential therapeutic strategies in patients with TTS including the role of cognitive behavioural therapy, beta-blockers, and endothelin-A antagonists. The underlying mechanism of TTS remains elusive. In reality, physical or emotional stressors likely trigger through the amygdala and hippocampus a central neurohumoral activation with the local and systemic secretion of excess catecholamine and other neurohormones, which exert its effect on the myocardium through a metabolic switch, altered cellular signalling, and endothelial dysfunction. These complex pathways exert a regional activation in the myocardium through the altered distribution of adrenoceptors and density of autonomic innervation as a protective mechanism from myocardial apoptosis. More research is needed to understand how these different complex mechanisms interact with each other to bring on the TTS phenotype.
Collapse
Affiliation(s)
- Mohammed Majid Akhtar
- Royal Brompton and Harefield Hospitals, Imperial College and King's College, London SW3 6NP, UK
| | - Victoria L Cammann
- University Heart Center, Department of Cardiology, University Hospital Zürich, Zürich 8091, Switzerland
| | - Christian Templin
- University Heart Center, Department of Cardiology, University Hospital Zürich, Zürich 8091, Switzerland
| | - Jelena R Ghadri
- University Heart Center, Department of Cardiology, University Hospital Zürich, Zürich 8091, Switzerland
| | - Thomas F Lüscher
- Royal Brompton and Harefield Hospitals, Imperial College and King's College, London SW3 6NP, UK
- Center for Molecular Cardiology, University of Zürich, Zürich 8952, Switzerland
| |
Collapse
|
|
15
|
Limonova AS, Germanova KN, Gantman MV, Nazarova MA, Davtyan KV, Novikov PA, Sukmanova AA, Tarasov AV, Kharlap MS, Ershova AI, Drapkina OM. Neurovisceral interactions within the brain-heart axis as the basis of neurocardiology. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2022. [DOI: 10.15829/1728-8800-2022-3435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
The use of a systematic approach to the study of the etiology of a certain pathology makes it possible to improve the understanding of its pathogenesis, as well as to develop more effective diagnostic and therapeutic approaches, including improving the prediction of its risk. Within this review, we will consider such an area of interdisciplinary research as neurocardiology, which studies the brain-heart axis. Examples of cardiovascular diseases associated with organic and functional disorders of this axis will be considered, as well as the prospects for research in this area and their translational significance for clinical medicine.
Collapse
Affiliation(s)
- A. S. Limonova
- National Medical Research Center for Therapy and Preventive Medicine
| | - K. N. Germanova
- National Medical Research Center for Therapy and Preventive Medicine; National Research University Higher School of Economics
| | - M. V. Gantman
- National Research University Higher School of Economics
| | - M. A. Nazarova
- National Research University Higher School of Economics; Harvard Medical School
| | - K. V. Davtyan
- National Medical Research Center for Therapy and Preventive Medicine
| | - P. A. Novikov
- National Research University Higher School of Economics
| | - A. A. Sukmanova
- National Medical Research Center for Therapy and Preventive Medicine; National Research University Higher School of Economics
| | - A. V. Tarasov
- National Medical Research Center for Therapy and Preventive Medicine
| | - M. S. Kharlap
- National Medical Research Center for Therapy and Preventive Medicine
| | - A. I. Ershova
- National Medical Research Center for Therapy and Preventive Medicine
| | - O. M. Drapkina
- National Medical Research Center for Therapy and Preventive Medicine
| |
Collapse
|
|
16
|
Fiserova I, Trinh MD, Elkalaf M, Vacek L, Heide M, Martinkova S, Bechynska K, Kosek V, Hajslova J, Fiser O, Tousek P, Polak J. Isoprenaline modified the lipidomic profile and reduced β-oxidation in HL-1 cardiomyocytes: In vitro model of takotsubo syndrome. Front Cardiovasc Med 2022; 9:917989. [PMID: 36072861 PMCID: PMC9441769 DOI: 10.3389/fcvm.2022.917989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 08/01/2022] [Indexed: 11/13/2022] Open
Abstract
Recent studies have suggested a pathogenetic link between impaired mitochondria and Takotsubo syndrome (TTS), which is closely connected with catecholamine overstimulation, poor outcomes, and changes in lipid metabolism. We investigated the changes in lipid metabolism at the level of fatty acid β-oxidation and changes in the intracellular lipidomic spectrum. The immortalized cell line of HL-1 cardiomyocytes was used in this study as an established in vitro model of TTS. The cells were exposed to the non-selective β-agonist isoprenaline (ISO) for acute (2 h) and prolonged (24 h) periods. We investigated the impact on mitochondrial adenosine 5’-triphosphate (ATP) production and β-oxidation using real-time cell metabolic analysis, total lipid content, and changes in the lipidomic spectrum using high-performance liquid chromatography (HPLC) and mass spectrometry. Furthermore, modifications of selected lipid transporters were determined using real-time – polymerase chain reaction (RT-PCR) and/or Western blot techniques. By choosing this wide range of targets, we provide a detailed overview of molecular changes in lipid metabolism during catecholamine overstimulation. The present study demonstrates that acute exposure to ISO decreased ATP production by up to 42.2%, and prolonged exposure to ISO decreased β-oxidation by 86.4%. Prolonged exposure to ISO also increased lipid accumulation by 4%. Lipid spectrum analysis of prolonged exposure to ISO showed a reduced concentration of cardioprotective and an increased concentration of lipotoxic lipid molecules during long-term exposure. Decreased lipid utilization can lead to higher intracellular lipid accumulation and the formation of lipotoxic molecules. Changes in the lipid spectrum can induce pathophysiological signaling pathways leading to cardiomyocyte remodeling or apoptosis. Thus, changes in lipid metabolism induced by excessive doses of catecholamines may cause TTS and contribute to a progression of heart failure, which is at increased risk after a TTS episode.
Collapse
Affiliation(s)
- Ivana Fiserova
- Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czechia
- Department of Cardiology, Third Faculty of Medicine, Charles University and University Hospital Královské Vinohrady, Prague, Czechia
| | - Minh Duc Trinh
- Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czechia
- Department of Cardiology, Third Faculty of Medicine, Charles University and University Hospital Královské Vinohrady, Prague, Czechia
| | - Moustafa Elkalaf
- Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czechia
- Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University, Hradec Kralove, Czechia
| | - Lukas Vacek
- Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czechia
| | - Marek Heide
- Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czechia
| | - Stanislava Martinkova
- Department of Biochemistry, Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czechia
| | - Kamila Bechynska
- Department of Food Analysis and Nutrition, University of Chemistry and Technology Prague, Prague, Czechia
| | - Vit Kosek
- Department of Food Analysis and Nutrition, University of Chemistry and Technology Prague, Prague, Czechia
| | - Jana Hajslova
- Department of Food Analysis and Nutrition, University of Chemistry and Technology Prague, Prague, Czechia
| | - Ondrej Fiser
- Department of Biomedical Technology, Faculty of Biomedical Engineering, Czech Technical University in Prague, Prague, Czechia
| | - Petr Tousek
- Department of Cardiology, Third Faculty of Medicine, Charles University and University Hospital Královské Vinohrady, Prague, Czechia
| | - Jan Polak
- Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czechia
- *Correspondence: Jan Polak,
| |
Collapse
|
|
17
|
Marcucci R, Mannini L, Andrei V, Bandinelli B, Gori AM, Fatucchi S, Giglioli C, Romano SM, Piazzai C, Marchionni N, Cecchi E. Transient stress-related hyperviscosity and endothelial dysfunction in Takotsubo syndrome: a time course study. Heart Vessels 2022; 37:1776-1784. [PMID: 35451602 DOI: 10.1007/s00380-022-02071-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Accepted: 03/31/2022] [Indexed: 11/04/2022]
Abstract
Takotsubo syndrome (TTS) is an acute and usually reversible heart failure syndrome, frequently associated with emotional or physical stress. Its pathophysiology remains largely unclear, although several mechanisms related to catecholaminergic storm have been proposed. In this study we analyzed during the acute phase of TTS and at follow-up both hemorheological parameters and biomarkers of endothelial damage, whose time course has never been fully explored. In 50 TTS women, we analyzed several hemorheological parameters [whole blood viscosity (WBV) at 0.512 s-1 and at 94.5 s-1, plasma viscosity (PLV), erythrocyte deformability and aggregation index] as well as biomarkers of endothelial dysfunction [von Willebrand Factor (vWF), Plasminogen activator inhibitor-1 and factor VIII levels] during the acute phase and after a median 6 months follow-up. These variables were also assessed in 50 age-matched healthy women. Respect to follow-up, in the acute phase of TTS we observed higher values of white blood cell count, fibrinogen, WBV at low and high shear rates, PLV, erythrocyte aggregation index and lower values of erythrocyte elongation index. Moreover, all biomarkers of endothelial dysfunction resulted significantly higher in the acute phase. During follow-up WBV at 94.5 s-1, erythrocyte elongation index and vWF resulted significantly altered with respect to controls. The results of this study confirm the role of hyperviscosity and endothelial dysfunction in TTS pathophysiology. Moreover, they suggest the persistence of alterations of erythrocyte deformability and endothelial dysfunction even beyond the acute phase that could be the target of therapeutic strategies also during follow-up.
Collapse
Affiliation(s)
- Rossella Marcucci
- Department of Cardiac Thoracic and Vascular Medicine, Center for Atherothrombotic Diseases, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.,Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy
| | - Lucia Mannini
- Department of Cardiac Thoracic and Vascular Medicine, Center for Atherothrombotic Diseases, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
| | - Valentina Andrei
- General Cardiology Unit, Department of Cardiac Thoracic and Vascular Medicine, Azienda Ospedaliero-Universitaria Careggi, Viale Morgagni, 85, 50141, Florence, Italy
| | - Brunella Bandinelli
- Department of Cardiac Thoracic and Vascular Medicine, Center for Atherothrombotic Diseases, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
| | - Anna Maria Gori
- Department of Cardiac Thoracic and Vascular Medicine, Center for Atherothrombotic Diseases, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.,Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy
| | - Serena Fatucchi
- General Cardiology Unit, Department of Cardiac Thoracic and Vascular Medicine, Azienda Ospedaliero-Universitaria Careggi, Viale Morgagni, 85, 50141, Florence, Italy
| | - Cristina Giglioli
- General Cardiology Unit, Department of Cardiac Thoracic and Vascular Medicine, Azienda Ospedaliero-Universitaria Careggi, Viale Morgagni, 85, 50141, Florence, Italy
| | - Salvatore Mario Romano
- Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy.,General Cardiology Unit, Department of Cardiac Thoracic and Vascular Medicine, Azienda Ospedaliero-Universitaria Careggi, Viale Morgagni, 85, 50141, Florence, Italy
| | - Chiara Piazzai
- General Cardiology Unit, Department of Cardiac Thoracic and Vascular Medicine, Azienda Ospedaliero-Universitaria Careggi, Viale Morgagni, 85, 50141, Florence, Italy
| | - Niccolo' Marchionni
- General Cardiology Unit, Department of Cardiac Thoracic and Vascular Medicine, Azienda Ospedaliero-Universitaria Careggi, Viale Morgagni, 85, 50141, Florence, Italy
| | - Emanuele Cecchi
- General Cardiology Unit, Department of Cardiac Thoracic and Vascular Medicine, Azienda Ospedaliero-Universitaria Careggi, Viale Morgagni, 85, 50141, Florence, Italy.
| |
Collapse
|
|
18
|
Bairashevskaia AV, Belogubova SY, Kondratiuk MR, Rudnova DS, Sologova SS, Tereshkina OI, Avakyan EI. Update of Takotsubo cardiomyopathy: Present experience and outlook for the future. IJC HEART & VASCULATURE 2022; 39:100990. [PMID: 35281752 PMCID: PMC8913320 DOI: 10.1016/j.ijcha.2022.100990] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 02/24/2022] [Accepted: 03/01/2022] [Indexed: 11/21/2022]
Abstract
Takotsubo cardiomyopathy (TTS) has become a recognised clinical entity since the Japanese scientist Sato first described it in 1990. Despite an increasing number of confirmed cases, especially during the COVID-19 pandemic, its pathophysiology remains incompletely understood, and decision-making differs in the diagnosis and treatment. In addition, it is not evident whether a significant increase in TTS is due to better understanding among practitioners and widespread access to coronary angiography, or if it is a reflection of an actual increase in incidence. We analysed a series of international research studies from 1990 to 2021. Beyond epidemiology and clinical presentation, we evaluated and summarised fundamental knowledge about various predisposing factors, with particular attention to the iatrogenic impact of certain drugs, namely antidepressants, chemotherapy, and antiarrhythmics. Furthermore, we highlighted the main pathophysiological theories to date. In addition, based on published studies and clinical cases, we investigated the role of numerous diagnostic approaches in the differential diagnosis of TTS and identified predictors of TTS complications, such as cardiogenic shock, ventricular fibrillation, and left ventricular thrombi. Accordingly, we sought to propose a diagnostic algorithm and further treatment management of TTS under the presence of possible complications to help practitioners make more informed decisions, as the initial presentation continues to pose a challenge due to its close similarity to acute coronary syndrome with ST-elevation. In conclusion, this article examines Takotsubo cardiomyopathy from different perspectives and, along with future systematic reviews and meta-analyses, can be of particular interest to practising cardiologists and researchers in developing clinical guidelines.
Collapse
Affiliation(s)
- Anastasiia V. Bairashevskaia
- Department of Paediatrics, Institute of Child’s Health, Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia
| | - Sofiya Y. Belogubova
- Department of Faculty Therapy, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
- AMEE International Networking Centre, Sechenov First Moscow State Medical University (Sechenov University), 123242 Moscow, Russia
| | - Mikhail R. Kondratiuk
- Department of Faculty Therapy, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
| | - Daria S. Rudnova
- International School “Medicine of the Future”, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
| | - Susanna S. Sologova
- Department of Pharmacology, Institute of Pharmacy, Sechenov First Moscow State Medical University (Sechenov University), 119571 Moscow, Russia
| | - Olga I. Tereshkina
- Department of Pharmacology, Institute of Pharmacy, Sechenov First Moscow State Medical University (Sechenov University), 119571 Moscow, Russia
| | - Esma I. Avakyan
- Department of Faculty Therapy, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
- AMEE International Networking Centre, Sechenov First Moscow State Medical University (Sechenov University), 123242 Moscow, Russia
| |
Collapse
|
|
19
|
Singh T, Khan H, Gamble DT, Scally C, Newby DE, Dawson D. Takotsubo Syndrome: Pathophysiology, Emerging Concepts, and Clinical Implications. Circulation 2022; 145:1002-1019. [PMID: 35344411 PMCID: PMC7612566 DOI: 10.1161/circulationaha.121.055854] [Citation(s) in RCA: 144] [Impact Index Per Article: 48.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Takotsubo syndrome is a condition characterized by acute transient left ventricular systolic dysfunction, which at presentation can be challenging to distinguish from acute myocardial infarction. Although previously thought to be a benign, self-limiting condition, recent studies have confirmed that patients with takotsubo syndrome have persistent subtle ongoing cardiac dysfunction, and many continue to have limiting symptoms despite restoration of left ventricular ejection fraction. Moreover, these patients have a substantial burden of morbidity as well as mortality with high rates of subsequent major adverse cardiovascular events that approach those of patients with acute coronary syndrome. The mechanisms behind this condition remain elusive. Despite substantial research, the medical community continues to have an incomplete understanding of its underlying etiology and pathophysiology. Catecholamine-induced myocardial injury is the most established and well-known theory, but this does not explain all of the clinical features and presentations of the condition, and numerous other pathways and abnormalities are emerging. Because of the poor understanding of its underlying pathophysiology, there is a lack of evidence-based interventions to treat the acute episode, to avoid recurrences and to prevent major adverse cardiovascular events. This highlights the need for further research to gain a better understanding of the underlying pathophysiology in order to inform appropriate randomized controlled trials of interventions targeting the causative pathways. Only then can evidence-based management strategies be established to improve clinical outcomes of this potentially lethal condition.
Collapse
Affiliation(s)
- Trisha Singh
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (T.S., C.S., D.E.N.).,Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen, United Kingdom (H.K., D.T.G., D.D.)
| | - Hilal Khan
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (T.S., C.S., D.E.N.).,Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen, United Kingdom (H.K., D.T.G., D.D.)
| | - David T Gamble
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (T.S., C.S., D.E.N.).,Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen, United Kingdom (H.K., D.T.G., D.D.)
| | - Caroline Scally
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (T.S., C.S., D.E.N.).,Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen, United Kingdom (H.K., D.T.G., D.D.)
| | - David E Newby
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (T.S., C.S., D.E.N.).,Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen, United Kingdom (H.K., D.T.G., D.D.)
| | - Dana Dawson
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (T.S., C.S., D.E.N.).,Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen, United Kingdom (H.K., D.T.G., D.D.)
| |
Collapse
|
|
20
|
Koniari I, Papageorgiou A, Artopoulou E, Velissaris D, Mplani V, Kounis N, Hahalis G, Tsigkas G. Prevalence and Impact of Atrial Fibrillation on Prognosis in Takotsubo Cardiomyopathy Patients. Angiology 2022; 73:800-808. [PMID: 35236144 DOI: 10.1177/00033197221079331] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The purpose of this review is to describe the impact of atrial fibrillation (AF) on the cardiovascular outcomes and prognosis in patients with Takotsubo Cardiomyopathy (TTC). The pathophysiological basis of TTC is set on the release of catecholamines, occurring post an emotional or stressful event. The cardiovascular system of patients with TTC is affected by the high concentrations of catecholamines, creating the ideal background for the development of AF: inflammation, myocardial stress, and excessive sympathetic activity. AF is considered to be the most frequent arrhythmia in TTC patients and is associated with higher rates of cardiovascular and all-cause mortality. AF is also linked with a worse prognosis concerning the hemodynamic status, cardiac fibrosis, lethal arrhythmias, thromboembolic events, and adverse heart failure associated outcomes. The early diagnosis of AF in these patients plays significant role in the prevention of adverse events, the reversibility of left ventricular function, and the restoration of sinus rhythm.
Collapse
Affiliation(s)
- Ioanna Koniari
- Department of Cardiology, NHS Foundation Trust, University Hospital of South Manchester, Manchester, UK
| | | | - Eleni Artopoulou
- Department of Internal Medicine, 37795University Hospital of Patras, Patras, Greece
| | - Dimitrios Velissaris
- Department of Internal Medicine, 37795University Hospital of Patras, Patras, Greece
| | - Virginia Mplani
- Department of Cardiology, 37795University Hospital of Patras, Patras, Greece
| | - Nicholas Kounis
- Department of Cardiology, 37795University Hospital of Patras, Patras, Greece
| | - George Hahalis
- Department of Cardiology, 37795University Hospital of Patras, Patras, Greece
| | - Grigorios Tsigkas
- Department of Cardiology, 37795University Hospital of Patras, Patras, Greece
| |
Collapse
|
|
21
|
Fan X, Yang G, Kowitz J, Akin I, Zhou X, El-Battrawy I. Takotsubo Syndrome: Translational Implications and Pathomechanisms. Int J Mol Sci 2022; 23:ijms23041951. [PMID: 35216067 PMCID: PMC8875072 DOI: 10.3390/ijms23041951] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 02/04/2022] [Accepted: 02/05/2022] [Indexed: 02/07/2023] Open
Abstract
Takotsubo syndrome (TTS) is identified as an acute severe ventricular systolic dysfunction, which is usually characterized by reversible and transient akinesia of walls of the ventricle in the absence of a significant obstructive coronary artery disease (CAD). Patients present with chest pain, ST-segment elevation or ischemia signs on ECG and increased troponin, similar to myocardial infarction. Currently, the known mechanisms associated with the development of TTS include elevated levels of circulating plasma catecholamines and their metabolites, coronary microvascular dysfunction, sympathetic hyperexcitability, inflammation, estrogen deficiency, spasm of the epicardial coronary vessels, genetic predisposition and thyroidal dysfunction. However, the real etiologic link remains unclear and seems to be multifactorial. Currently, the elusive pathogenesis of TTS and the lack of optimal treatment leads to the necessity of the application of experimental models or platforms for studying TTS. Excessive catecholamines can cause weakened ventricular wall motion at the apex and increased basal motion due to the apicobasal adrenoceptor gradient. The use of beta-blockers does not seem to impact the outcome of TTS patients, suggesting that signaling other than the beta-adrenoceptor-associated pathway is also involved and that the pathogenesis may be more complex than it was expected. Herein, we review the pathophysiological mechanisms related to TTS; preclinical TTS models and platforms such as animal models, human-induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) models and their usefulness for TTS studies, including exploring and improving the understanding of the pathomechanism of the disease. This might be helpful to provide novel insights on the exact pathophysiological mechanisms and may offer more information for experimental and clinical research on TTS.
Collapse
Affiliation(s)
- Xuehui Fan
- First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), University of Heidelberg, 68167 Mannheim, Germany; (X.F.); (J.K.); (I.A.)
- Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China
- DZHK (German Center for Cardiovascular Research), Partner Site, Heidelberg-Mannheim, 68167 Mannheim, Germany
| | - Guoqiang Yang
- Department of Acupuncture and Rehabilitation, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, China;
- Research Unit of Molecular Imaging Probes, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Jacqueline Kowitz
- First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), University of Heidelberg, 68167 Mannheim, Germany; (X.F.); (J.K.); (I.A.)
| | - Ibrahim Akin
- First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), University of Heidelberg, 68167 Mannheim, Germany; (X.F.); (J.K.); (I.A.)
- DZHK (German Center for Cardiovascular Research), Partner Site, Heidelberg-Mannheim, 68167 Mannheim, Germany
| | - Xiaobo Zhou
- First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), University of Heidelberg, 68167 Mannheim, Germany; (X.F.); (J.K.); (I.A.)
- Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China
- DZHK (German Center for Cardiovascular Research), Partner Site, Heidelberg-Mannheim, 68167 Mannheim, Germany
- Correspondence: (X.Z.); (I.E.-B.)
| | - Ibrahim El-Battrawy
- First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), University of Heidelberg, 68167 Mannheim, Germany; (X.F.); (J.K.); (I.A.)
- DZHK (German Center for Cardiovascular Research), Partner Site, Heidelberg-Mannheim, 68167 Mannheim, Germany
- Correspondence: (X.Z.); (I.E.-B.)
| |
Collapse
|
|
22
|
Omerovic E, Citro R, Bossone E, Redfors B, Backs J, Bruns B, Ciccarelli M, Couch LS, Dawson D, Grassi G, Iacoviello M, Parodi G, Schneider B, Templin C, Ghadri JR, Thum T, Chioncel O, Tocchetti CG, van der Velden J, Heymans S, Lyon AR. Pathophysiology of Takotsubo syndrome - a joint scientific statement from the Heart Failure Association Takotsubo Syndrome Study Group and Myocardial Function Working Group of the European Society of Cardiology - Part 1: overview and the central role for catecholamines and sympathetic nervous system. Eur J Heart Fail 2022; 24:257-273. [PMID: 34907620 DOI: 10.1002/ejhf.2400] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Revised: 12/04/2021] [Accepted: 12/07/2021] [Indexed: 11/11/2022] Open
Abstract
This is the first part of a scientific statement from the Heart Failure Association (HFA) of the European Society of Cardiology focused upon the pathophysiology of Takotsubo syndrome and is complimentary to the previous HFA position statement on Takotsubo syndrome which focused upon clinical management. In part 1 we provide an overview of the pathophysiology of Takotsubo syndrome and fundamental questions to consider. We then review and discuss the central role of catecholamines and the sympathetic nervous system in the pathophysiology, and the direct effects of high surges in catecholamines upon myocardial biology including β-adrenergic receptor signalling, G-protein coupled receptor kinases, cardiomyocyte calcium physiology, myofilament physiology, cardiomyocyte gene expression, myocardial electrophysiology and arrhythmogenicity, myocardial inflammation, metabolism and energetics. The integrated effects upon ventricular haemodynamics are discussed and integrated into the pathophysiological model.
Collapse
Affiliation(s)
- Elmir Omerovic
- Department of Cardiology, Sahlgrenska University Hospital and Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
| | - Rodolfo Citro
- Heart Department, University Hospital 'San Giovanni di Dio e Ruggi d'Aragona', Salerno, Italy
| | - Eduardo Bossone
- Division of Cardiology, A. Cardarelli Hospital, Naples, Italy
| | - Bjorn Redfors
- Department of Cardiology, Sahlgrenska University Hospital and Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
| | - Johannes Backs
- Institute of Experimental Cardiology, Heidelberg University, Heidelberg, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Heidelberg/Mannheim, Germany
| | - Bastian Bruns
- Institute of Experimental Cardiology, Heidelberg University, Heidelberg, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site, Heidelberg/Mannheim, Germany
- Department of General Internal Medicine and Psychosomatics, University of Heidelberg, Heidelberg, Germany
| | - Michele Ciccarelli
- Department of Medicine, Surgery, and Dentistry, University of Salerno, Salerno, Italy
| | - Liam S Couch
- National Heart and Lung Institute, Imperial College, London, UK
| | - Dana Dawson
- Aberdeen Cardiovascular and Diabetes Centre, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK
| | - Guido Grassi
- Clinica Medica, University of Milano Bicocca, Milan, Italy
| | - Massimo Iacoviello
- University Cardiology Unit, Cardiothoracic Department, University Hospital, Bari, Italy
| | - Guido Parodi
- Clinical and Interventional Cardiology, Sassari University Hospital, Sassari, Italy
| | | | - Christian Templin
- University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
| | - Jelena R Ghadri
- University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
| | - Thomas Thum
- Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany
| | - Ovidiu Chioncel
- Emergency Institute for Cardiovascular Diseases 'Prof. C.C. Iliescu', Bucharest, Romania and University of Medicine Carol Davila, Bucharest, Romania
| | - C Gabriele Tocchetti
- Department of Translational Medical Sciences and Interdepartmental Center for Clinical and Translational Research (CIRCET), Federico II University, Naples, Italy
| | - Jolanda van der Velden
- Department of Physiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Stephane Heymans
- Department of Cardiology, CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands
- Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology and Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium
| | - Alexander R Lyon
- National Heart and Lung Institute, Imperial College, London, UK
- Department of Cardiology, Royal Brompton Hospital, London, UK
| |
Collapse
|
|
23
|
Assad J, Femia G, Pender P, Badie T, Rajaratnam R. Takotsubo Syndrome: A Review of Presentation, Diagnosis and Management. CLINICAL MEDICINE INSIGHTS-CARDIOLOGY 2022; 16:11795468211065782. [PMID: 35002350 PMCID: PMC8733363 DOI: 10.1177/11795468211065782] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Accepted: 11/02/2021] [Indexed: 11/16/2022]
Abstract
Takotsubo Syndrome (TTS) is a condition of transient left ventricular dysfunction that is typically triggered by emotional or physical stress. Since first described in Japan in 1990, it has increasingly been recognised in clinical practice, accounting for up to 2% of Acute Coronary Syndrome (ACS) presentations. In fact, the clinical presentation can be indistinguishable from a myocardial infarction. Although current evidence suggests a catecholamine induced myocardial stunning, the pathophysiological mechanisms remain unknown. Interestingly, it is more common in woman, particularly those who are post-menopausal. This review aims to summarise the current research and provide an overview of the diagnostic strategies and treatment options.
Collapse
Affiliation(s)
- Joseph Assad
- Department of Cardiology, Liverpool Hospital, Liverpool, NSW, Australia.,School of Medicine, Western Sydney University, Penrith, NSW, Australia.,South-West Clinical School, University of New South Wales, Kensington, NSW, Australia
| | - Giuseppe Femia
- Department of Cardiology, Liverpool Hospital, Liverpool, NSW, Australia.,Department of Cardiology, Campbelltown Hospital, Campbelltown, NSW, Australia.,Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - Patrick Pender
- Department of Cardiology, Liverpool Hospital, Liverpool, NSW, Australia.,School of Medicine, Western Sydney University, Penrith, NSW, Australia.,South-West Clinical School, University of New South Wales, Kensington, NSW, Australia
| | - Tamer Badie
- Department of Cardiology, Liverpool Hospital, Liverpool, NSW, Australia.,School of Medicine, Western Sydney University, Penrith, NSW, Australia.,South-West Clinical School, University of New South Wales, Kensington, NSW, Australia.,Department of Cardiology, Campbelltown Hospital, Campbelltown, NSW, Australia
| | - Rohan Rajaratnam
- Department of Cardiology, Liverpool Hospital, Liverpool, NSW, Australia.,School of Medicine, Western Sydney University, Penrith, NSW, Australia.,South-West Clinical School, University of New South Wales, Kensington, NSW, Australia.,Department of Cardiology, Campbelltown Hospital, Campbelltown, NSW, Australia
| |
Collapse
|
|
24
|
Madias JE. Blood norepinephrine/epinephrine/dopamine measurements in 108 patients with takotsubo syndrome from the world literature: pathophysiological implications. Acta Cardiol 2021; 76:1083-1091. [PMID: 33300464 DOI: 10.1080/00015385.2020.1826703] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Release of norepinephrine (NE) from neuronal cardiac nerve endings and/or blood-borne catecholamines (CATs), mainly epinephrine (EPI), may mediate TTS. The aim of this study was to document the levels of NE, EPI, and dopamine (DA) in patients with TTS. MATERIALS AND METHODS A qualitative/quantitative meta-analysis of CATs and their relationship to age, gender, and triggers, was carried out, employing the world literature on TTS, published in PubMed. RESULTS NE/EPI/DA in108 patients with TTS, 65.2 ± 16.4 years old, 89 (82.4%) women, revealed that: NE was measured more frequently than EPI, and EPI than DA; the timing of the measurements was variable; CATs were reported variably (qualitatively/quantitatively/with/without upper limits of normal); NE/EPI or NE/EPI/DA rose to the same degree; CATs were normal, or mildly/moderately elevated, with only 6 patients showing markedly elevated NE/EP/DA; NE, EPI, and DA were similar in patients with physical triggers and NE was similar in patients with physical, emotional, or no triggers (p = 0.47); EPI was higher than NE in patients with emotional triggers and EPI was higher in patients with emotional than physical triggers (p = 0.012); NE, EPI, and DA rose to the same proportion in men and women; types of TTS triggers were distributed proportionally in men and women. CONCLUSION NE, EPI, and DA rise proportionally in patients with TTS; CATs are mildly/moderately, and rarely markedly elevated; measurements of CATs should become more systematised; although CATs may not be essential for TTS diagnosis, they may contribute to prognosis and elucidation of the pathophysiology of TTS.
Collapse
Affiliation(s)
- John E. Madias
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Division of Cardiology, Elmhurst Hospital Center, Elmhurst, NY, USA
| |
Collapse
|
|
25
|
Kinno R, Ono K. Takotsubo Syndrome: Optimizing Care with a Multidisciplinary Approach. J Multidiscip Healthc 2021; 14:2487-2499. [PMID: 34531661 PMCID: PMC8439972 DOI: 10.2147/jmdh.s283667] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 08/23/2021] [Indexed: 12/19/2022] Open
Abstract
Symptoms of takotsubo syndrome (TTS) include acute and transient regional systolic dysfunction of the left ventricle, as well as a variety of wall-motion abnormalities. The clinical features of TTS, including initial symptoms, cardiac biomarkers, and electrocardiogram (ECG) changes, are similar to those of acute coronary syndrome, with the exception that TTS patients typically have no obstructive coronary artery disease. TTS primarily affects elderly women, and emotional or physical stress is a common cause of the disease. Exaggerated sympathetic stimulation associated with dysfunction of the limbic system has also been reported to be related to TTS occurrence. Cancer also induces emotional and physical stress. Therefore, optimization of TTS care should involve cardiac, neurological, psychiatric, and oncological approaches. The first step in optimizing TTS care is to diagnose it by cardiac means. Multimodality imaging, including ECG, echocardiogram, angiography, ventriculography, and cardiac magnetic resonance imaging, is indispensable for diagnosis, therapy management, and the evaluation of prognosis in the acute and chronic phases of TTS. The current cardiac approach during the acute phase is primarily supportive, with the goal of preventing life-threatening complications. As central nervous system diseases frequently trigger TTS, a neurological approach is also required. Appropriate psychiatric medication may reduce the risk of TTS recurrence, as not only psychiatric disorders themselves but also psychiatric medications can be the trigger for TTS. Several conditions are associated with TTS, including the novel coronavirus disease 2019. We present current knowledge of TTS in this review and describe how to optimize TTS care through a multidisciplinary approach.
Collapse
Affiliation(s)
- Ryuta Kinno
- Division of Neurology, Department of Internal Medicine, Showa University Northern Yokohama Hospital, Yokohama City, Kanagawa, 224-8503, Japan
| | - Kenjiro Ono
- Division of Neurology, Department of Medicine, Showa University School of Medicine, Tokyo, 142-8555, Japan
| |
Collapse
|
|
26
|
Y-Hassan S, Sörensson P, Ekenbäck C, Lundin M, Agewall S, Brolin EB, Caidahl K, Cederlund K, Collste O, Daniel M, Jensen J, Hofman-Bang C, Lyngå P, Maret E, Sarkar N, Spaak J, Winnberg O, Ugander M, Tornvall P, Henareh L. Plasma catecholamine levels in the acute and subacute stages of takotsubo syndrome: Results from the Stockholm myocardial infarction with normal coronaries 2 study. Clin Cardiol 2021; 44:1567-1574. [PMID: 34490898 PMCID: PMC8571561 DOI: 10.1002/clc.23723] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Revised: 07/13/2021] [Accepted: 08/27/2021] [Indexed: 12/30/2022] Open
Abstract
AIMS It is well-accepted that takotsubo syndrome (TS) is characterized by a massive surge of plasma catecholamines despite lack of solid evidence. The objective of this study was to examine the hypothesis of a massive catecholamine elevation in TS by studying plasma-free catecholamine metabolites in patients participating in the Stockholm myocardial infarction (MI) with normal coronaries 2 (SMINC-2) study where TS constituted more than one third of the patients. METHODS AND RESULTS The patients included in the SMINC-2 study were classified, according to cardiac magnetic resonance (CMR) imaging findings (148 patients), which was performed at a median of 3 days after hospital admission. Plasma-free catecholamine metabolites; metanephrine, normetanephrine, and methoxy-tyramine were measured on day 2-4 after admission. Catecholamine metabolite levels were available in 125 patients. One hundred and ten (88%) of the 125 patients included in SMINC-2 study, and 38 (86.4%) of the 44 patients with TS had completely normal plasma metanephrine and normetanephrine levels. All patients had normal plasma methoxy-tyramine levels. Fourteen (11.2%) of the 125 patients included in SMINC-2 study, and 5 (11.6%) of the 43 patients with TS had mild elevations (approximately 1.2 times the upper normal limits) of either plasma metanephrine or normetanephrine. One patient with pheochromocytoma-triggered TS had marked elevation of plasma metanephrine and mild elevation of plasma normetanephrine. There were no significant differences between the number or degree of catecholamine metabolite elevations between the different groups of patients with CMR imaging diagnosis included in SMINC-2 study. CONCLUSION There was no evidence of massive catecholamine elevations in the acute and subacute stages of TS apart from one patient with pheochromocytoma-induced TS. Most of the TS patients had normal catecholamine metabolites indicating that blood-borne catecholamines do not play a direct role in the pathogenesis of TS.
Collapse
Affiliation(s)
- Shams Y-Hassan
- Coronary Artery Disease Area, Heart and Vascular Theme, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden
| | - Peder Sörensson
- Department of Medicine Solna, Karolinska Institutet, and Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
| | - Christina Ekenbäck
- Division of Cardiovascular Medicine, Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden
| | - Magnus Lundin
- Department of Clinical Physiology, Karolinska University Hospital, and Karolinska Institutet, Stockholm, Sweden
| | - Stefan Agewall
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Elin Bacsovics Brolin
- Department of Clinical Science, Division of Medical Imaging and Technology, Intervention and Technology at Karolinska Institutet, Stockholm, Sweden.,Department of Radiology, Capio S:t Görans Hospital, Stockholm, Sweden
| | - Kenneth Caidahl
- Department of Clinical Physiology, Karolinska University Hospital, and Karolinska Institutet, Stockholm, Sweden
| | - Kerstin Cederlund
- Department of Clinical Science, Division of Medical Imaging and Technology, Intervention and Technology at Karolinska Institutet, Stockholm, Sweden.,Department of Radiology, Södertälje Hospital, Södertälje, Sweden
| | - Olov Collste
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, and Cardiology Unit, Södersjukhuset, Stockholm, Sweden
| | - Maria Daniel
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, and Cardiology Unit, Södersjukhuset, Stockholm, Sweden
| | - Jens Jensen
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, and Department of Cardiology, Capio St: Görans Hospital, Stockholm, Sweden
| | - Claes Hofman-Bang
- Division of Cardiovascular Medicine, Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden
| | - Patrik Lyngå
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, and Cardiology Unit, Södersjukhuset, Stockholm, Sweden
| | - Eva Maret
- Department of Clinical Physiology, Karolinska University Hospital, and Karolinska Institutet, Stockholm, Sweden
| | - Nondita Sarkar
- Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
| | - Jonas Spaak
- Division of Cardiovascular Medicine, Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden
| | - Oscar Winnberg
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, and Department of Cardiology, Capio St: Görans Hospital, Stockholm, Sweden
| | - Martin Ugander
- Department of Clinical Physiology, Karolinska University Hospital, and Karolinska Institutet, Stockholm, Sweden.,Kolling Institute, Royal North Shore Hospital, and Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Sydney, Australia
| | - Per Tornvall
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, and Cardiology Unit, Södersjukhuset, Stockholm, Sweden
| | - Loghman Henareh
- Coronary Artery Disease Area, Heart and Vascular Theme, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden
| |
Collapse
|
|
27
|
Marino G, Michielon A, Musumeci MB, Autore C. Takotsubo syndrome: hyperthyroidism, pheochromocytoma, or both? A case report. EUROPEAN HEART JOURNAL-CASE REPORTS 2021; 5:ytab270. [PMID: 34423242 PMCID: PMC8374971 DOI: 10.1093/ehjcr/ytab270] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 02/16/2021] [Accepted: 05/18/2021] [Indexed: 11/26/2022]
Abstract
Background Takotsubo syndrome (TTS) is a transient left ventricular dysfunction usually with apical akinesia (classical pattern). Other less frequent variants have been described: the mid-ventricular pattern is characterized by hypokinesia of the mid-left ventricle and hypercontractile apical and basal segments; the inverted or basal pattern is characterized by basal and mid-ventricular segment hypokinesia or akinesia with preserved contractility or hypercontractility of apical segments and finally the focal pattern. There are also biventricular variants and forms with exclusive involvement of the right ventricle. There is a correlation between endocrine disorders and TTS, the one most frequently described is with pheochromocytoma. Catecholamine-mediated myocarditis, focal and diffuse myocardial fibrosis, and myocardial dysfunction are described in pheochromocytoma. Case summary We describe a case of a 69-year-old patient with a recent diagnosis of hypertension and Graves’ disease, hospitalized for persistent chest pain, hypertensive crisis, tachycardia, dyspnoea, and diaphoresis. Thyroid hormones, antibodies to TSH receptors, and hs-troponin I were increased. Electrocardiogram showed sinus tachycardia at 130 b.p.m., first-degree atrioventricular block, signs of left ventricular hypertrophy with inverted T wave in V4–V6. Echocardiogram demonstrated left ventricular apical and para-apical akinesia. Coronary angiography ruled out an obstructive coronary artery disease. Computed tomography angiogram aortic dissection ruled out aortic dissection but incidentally revealed a left adrenal mass compatible with a pheochromocytoma. Plasma and urinary metanephrines were increased. A TTS secondary to pheochromocytoma and hyperthyroidism was diagnosed. Pharmacological treatment included nitrates, urapidil and esmolol IV and methimazole at high doses. Type 2 multiple endocrine neoplasia has been excluded. After a complete haemodynamic stability on 20th day of hospitalization, the patient underwent an adrenalectomy. Discussion High levels of catecholamines in pheochromocytoma can lead to myocardial dysfunction. Similarly, an excess of thyroid hormones with up-regulation of adrenergic system can lead to myocardial dysfunction. These two conditions, if both present, define a high haemodynamic risk profile. How do catecholamines interact with the thyroid gland? The clinical case is of interest as a relationship has been hypothesized between the incretion of plasma catecholamines and Graves’ disease. We suppose an imbalance of the immune system with a predominance of the T helper-type 2 (Th2)-mediated response. Predominance of Th2-mediated immune response may induce humoral immunity causing Graves’ disease. In addition Th2 cytokines are strong inducers of M2 macrophages (alternatively activated) that are involved in autoimmune diseases, myocarditis, and myocardial fibrosis. Knowing the interaction between the cardiovascular system, immune response, and endocrine glands can help define the patient's risk class, possible complications, and follow-up.
Collapse
Affiliation(s)
- Gaetano Marino
- Cardiology Unit, Clinical and Molecular Medicine Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Via di Grottarossa 1035/1039, 00189 Rome, Italy
| | - Alberto Michielon
- Cardiology Unit, Clinical and Molecular Medicine Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Via di Grottarossa 1035/1039, 00189 Rome, Italy
| | - Maria Beatrice Musumeci
- Cardiology Unit, Clinical and Molecular Medicine Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Via di Grottarossa 1035/1039, 00189 Rome, Italy
| | - Camillo Autore
- Cardiology Unit, Clinical and Molecular Medicine Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Via di Grottarossa 1035/1039, 00189 Rome, Italy
| |
Collapse
|
|
28
|
Campos CM, Albanez RL. HIV and Takotsubo Cardiomyopathy: A Deadly Combination That Could Not Be Explained by the Viral Infection in Isolation. CARDIOVASCULAR REVASCULARIZATION MEDICINE 2021; 29:59-60. [PMID: 34420693 DOI: 10.1016/j.carrev.2021.06.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 06/14/2021] [Indexed: 10/20/2022]
Affiliation(s)
- Carlos M Campos
- Heart Institute (InCor), University of São Paulo Medical School, Sao Paulo, Brazil; Instituto Prevent Senior, Sao Paulo, Brazil.
| | - Rodrigo L Albanez
- Heart Institute (InCor), University of São Paulo Medical School, Sao Paulo, Brazil
| |
Collapse
|
|
29
|
Möller C, Stiermaier T, Meusel M, Jung C, Graf T, Eitel I. Microcirculation in Patients with Takotsubo Syndrome-The Prospective CIRCUS-TTS Study. J Clin Med 2021; 10:2127. [PMID: 34069038 PMCID: PMC8156359 DOI: 10.3390/jcm10102127] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 04/25/2021] [Accepted: 05/07/2021] [Indexed: 12/17/2022] Open
Abstract
The pathophysiology of Takotsubo syndrome (TTS) is incompletely understood. A sympathetic overdrive with coronary microvascular dysfunction might play a central role. The aim of our study was to assess the status of the systemic microcirculation (MC) of patients with TTS, compared to patients with myocardial infarction (MI) and healthy subjects. The systemic microvascular function of 22 TTS patients, 20 patients with MI and 20 healthy subjects was assessed via sublingual sidestream dark-field imaging. In TTS and MI patients, measurements were performed during the acute phase (day 1, 3 and 5) and after 3 months. The measurement in healthy subjects was performed once. The assessed parameters were number of vessel crossings, number of perfused vessel crossings, proportion of perfused vessels, total vessel density and perfused vessel density. The results did not show relevant differences between the investigated groups. Some minor, albeit statistically significant, differences occurred rather randomly. The MC parameters of the TTS group did not show any relevant changes in the temporal course. A systemic microvascular dysfunction could not be identified as a contributing factor in the pathogenesis of TTS. A possible microvascular dysfunction might instead be caused by a local effect restricted to the coronary microvascular bed.
Collapse
Affiliation(s)
- Christian Möller
- Department of Cardiology, Angiology, Pulmonology, Nephrology and Intensive Care Medicine, Medical Clinic I, Leopoldina Hospital Schweinfurt, 97422 Schweinfurt, Germany;
- Department of Cardiology, Angiology and Intensive Care Medicine, Medical Clinic II, University Heart Center Lübeck, 23538 Lübeck, Germany; (T.S.); (M.M.); (T.G.)
- German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, 23538 Lübeck, Germany
| | - Thomas Stiermaier
- Department of Cardiology, Angiology and Intensive Care Medicine, Medical Clinic II, University Heart Center Lübeck, 23538 Lübeck, Germany; (T.S.); (M.M.); (T.G.)
- German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, 23538 Lübeck, Germany
| | - Moritz Meusel
- Department of Cardiology, Angiology and Intensive Care Medicine, Medical Clinic II, University Heart Center Lübeck, 23538 Lübeck, Germany; (T.S.); (M.M.); (T.G.)
- German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, 23538 Lübeck, Germany
| | - Christian Jung
- Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University Hospital Düsseldorf, 40225 Düsseldorf, Germany;
| | - Tobias Graf
- Department of Cardiology, Angiology and Intensive Care Medicine, Medical Clinic II, University Heart Center Lübeck, 23538 Lübeck, Germany; (T.S.); (M.M.); (T.G.)
- German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, 23538 Lübeck, Germany
| | - Ingo Eitel
- Department of Cardiology, Angiology and Intensive Care Medicine, Medical Clinic II, University Heart Center Lübeck, 23538 Lübeck, Germany; (T.S.); (M.M.); (T.G.)
- German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, 23538 Lübeck, Germany
| |
Collapse
|
|
30
|
Lyon AR, Citro R, Schneider B, Morel O, Ghadri JR, Templin C, Omerovic E. Pathophysiology of Takotsubo Syndrome: JACC State-of-the-Art Review. J Am Coll Cardiol 2021; 77:902-921. [PMID: 33602474 DOI: 10.1016/j.jacc.2020.10.060] [Citation(s) in RCA: 162] [Impact Index Per Article: 40.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 10/13/2020] [Accepted: 10/19/2020] [Indexed: 01/09/2023]
Abstract
Takotsubo syndrome (TTS) has been a recognized clinical entity for 31 years, since its first description in 1990. TTS is now routinely diagnosed in patients who present with acute chest pain, electrocardiographic changes, troponin elevation, unobstructed coronary arteries, and a typical pattern of circumferential left ventricular wall motion abnormalities that usually involve the apical and midventricular myocardium. Increasing understanding of this intriguing syndrome stems from wider recognition, possible increasing frequency, and a rising number of publications focused on the pathophysiology in clinical and laboratory studies. A comprehensive understanding of TTS pathophysiology and evidence-based treatments are lacking, and specific and effective treatments are urgently required. This paper reviews the pathophysiology of this fascinating syndrome; what is known from both clinical and preclinical studies, including review of the evidence for microvascular dysfunction, myocardial beta-adrenergic signaling, inflammation, and electrophysiology; and where focused research needs to fill gaps in understanding TTS.
Collapse
Affiliation(s)
- Alexander R Lyon
- Department of Cardiology, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, United Kingdom.
| | - Rodolfo Citro
- Cardio-Thoracic and Vascular Department, University Hospital "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italy
| | | | - Olivier Morel
- Department of Cardiology, University of Strasbourg, UMR INSERM 1260 Regenerative Nanomedicine, Strasbourg, France
| | - Jelena R Ghadri
- Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland
| | - Christian Templin
- Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland
| | - Elmir Omerovic
- Department of Molecular and Clinical Medicine/Cardiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. https://twitter.com/ElmirOmerovic2
| |
Collapse
|
|
31
|
Madias JE. Is modulation (desensitization) of the beta-adrenergic receptors a cause or an epiphenomenon of takotsubo syndrome? J Cardiol 2021; 77:552. [PMID: 33618974 DOI: 10.1016/j.jjcc.2021.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 01/18/2021] [Indexed: 10/22/2022]
Affiliation(s)
- John E Madias
- Icahn School of Medicine at Mount Sinai, New York, NY, and the Division of Cardiology, Elmhurst Hospital Center, 79-01 Broadway, Elmhurst, NY 11373, United States.
| |
Collapse
|
|
32
|
Heart and brain interactions : Pathophysiology and management of cardio-psycho-neurological disorders. Herz 2021; 46:138-149. [PMID: 33544152 PMCID: PMC7966144 DOI: 10.1007/s00059-021-05022-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/08/2021] [Indexed: 12/22/2022]
Abstract
Cardiovascular diseases (CVD) and mental health disorders (MHD; e.g. depression, anxiety and cognitive dysfunction) are highly prevalent and are associated with significant morbidity and mortality and impaired quality of life. Currently, possible interactions between pathophysiological mechanisms in MHD and CVD are rarely considered during the diagnostic work-up, prognostic assessment and treatment planning in patients with CVD, and research addressing bidirectional disease mechanisms in a systematic fashion is scarce. Besides some overarching pathogenetic principles shared by CVD and MHD, there are specific syndromes in which pre-existing neurological or psychiatric illness predisposes and contributes to CVD development (as in Takotsubo syndrome), or in which the distorted interplay between innate immune and central nervous systems and/or pre-existing CVD leads to secondary MHD and brain damage (as in peripartum cardiomyopathy or atrial fibrillation). Clinical manifestations and phenotypes of cardio-psycho-neurological diseases depend on the individual somatic, psychosocial, and genetic risk profile as well as on personal resilience, and differ in many respects between men and women. In this article, we provide arguments on why, in such conditions, multidisciplinary collaborations should be established to allow for more comprehensive understanding of the pathophysiology as well as appropriate and targeted diagnosis and treatment. In addition, we summarize current knowledge on the complex interactions between the cardiovascular and central nervous systems in Takotsubo syndrome and peripartum cardiomyopathy, and on the neurological and psychiatric complications of atrial fibrillation.
Collapse
|
|
33
|
Rawish E, Stiermaier T, Santoro F, Brunetti ND, Eitel I. Current Knowledge and Future Challenges in Takotsubo Syndrome: Part 1-Pathophysiology and Diagnosis. J Clin Med 2021; 10:jcm10030479. [PMID: 33525539 PMCID: PMC7865728 DOI: 10.3390/jcm10030479] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 01/08/2021] [Accepted: 01/15/2021] [Indexed: 02/06/2023] Open
Abstract
First recognized in 1990, takotsubo syndrome (TTS) constitutes an acute cardiac condition that mimics acute myocardial infarction commonly in the absence of obstructive coronary artery disease; it is characterized by temporary left ventricular dysfunction, regularly in a circumferential apical, midventricular, or basal distribution. Considering its acute clinical presentation, coronary angiography with left ventriculography constitutes the gold standard diagnostic tool to exclude or confirm TTS. Frequently, TTS is related to severe emotional or physical stress and a subsequent increased adrenergic stimulation affecting cardiac function. Beyond clinical presentation, epidemiology, and novel diagnostic biomarkers, this review draws attention to potential pathophysiological mechanisms for the observed reversible myocardial dysfunction such as sympathetic overdrive-mediated multi-vessel epicardial spasms, microvascular dysfunction, the direct toxicity of catecholamines, lipotoxicity, and inflammation. Considering the long-term prognosis, further experimental and clinical research is indispensable to elucidate further pathophysiological mechanisms underlying TTS before randomized control trials with evidence-based therapeutic management can be performed.
Collapse
Affiliation(s)
- Elias Rawish
- Medical Clinic II (Cardiology/Angiology/Intensive Care Medicine) University Heart Center, 23538 Lübeck, Germany; (E.R.); (T.S.)
- DZHK (German Centre for Cardiovascular Research), 23538 Lübeck, Germany
| | - Thomas Stiermaier
- Medical Clinic II (Cardiology/Angiology/Intensive Care Medicine) University Heart Center, 23538 Lübeck, Germany; (E.R.); (T.S.)
- DZHK (German Centre for Cardiovascular Research), 23538 Lübeck, Germany
| | - Francesco Santoro
- Department of Medical & Surgery Sciences, University of Foggia, 71121 Foggia, Italy
| | - Natale D. Brunetti
- Department of Medical & Surgery Sciences, University of Foggia, 71121 Foggia, Italy
| | - Ingo Eitel
- Medical Clinic II (Cardiology/Angiology/Intensive Care Medicine) University Heart Center, 23538 Lübeck, Germany; (E.R.); (T.S.)
- DZHK (German Centre for Cardiovascular Research), 23538 Lübeck, Germany
- Correspondence: ; Tel.: +49-451-500-44501
| |
Collapse
|
|
34
|
Bagnall T, Tow YR, Bunce N, Astroulakis Z. Takotsubo cardiomyopathy associated with adrenal insufficiency in the context of long-term steroid use mimicking acute coronary syndrome. BMJ Case Rep 2021; 14:14/1/e234983. [PMID: 33495195 PMCID: PMC7839885 DOI: 10.1136/bcr-2020-234983] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Takotsubo cardiomyopathy (TCMP) is an important, though under-recognised, syndrome which mimics acute coronary syndrome (ACS) presenting with similar clinical, biochemical and ECG features. A 68-year-old man was referred as ACS for emergency coronary angiography; however, a history of lethargy, weight loss and electrolyte abnormalities prompted further investigations. Angiography was postponed, adrenal insufficiency confirmed and steroid replacement commenced. Echocardiography demonstrated reduced left ventricular (LV) function (45%) with regional wall motion abnormalities, although angiography confirmed unobstructed arteries. Steroid replacement induced a rapid improvement in symptoms and LV function. Few cases of TCMP associated with adrenal insufficiency have been reported. This appears to be the first case describing TCMP precipitated by new-onset secondary adrenal insufficiency following long-term steroid use in a male patient, and highlights the importance of considering TCMP in patients presenting with suspected ACS. Here, prompt recognition and treatment of a serious underlying disorder prevented a potentially life-threatening Addisonian crisis.
Collapse
Affiliation(s)
- Timothy Bagnall
- Cardiology Department, Kingston Hospital NHS Foundation Trust, London, UK
| | - Ying Ran Tow
- Accident and Emergency Department, North Middlesex University Hospital, London, UK
| | | | | |
Collapse
|
|
35
|
Lau C, Chiu S, Nayak R, Lin B, Lee MS. Survival and risk of recurrence of takotsubo syndrome. Heart 2021; 107:1160-1166. [PMID: 33419884 DOI: 10.1136/heartjnl-2020-318028] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 11/22/2020] [Accepted: 11/27/2020] [Indexed: 12/30/2022] Open
Abstract
OBJECTIVE The goal of this study is to evaluate the long-term outcomes of patients with takotsubo syndrome and assess factors associated with death or recurrence. METHODS This is a retrospective population-based cohort study of consecutive patients who presented to an integrated health system in Southern California with takotsubo syndrome between 2006 and 2016. Medical records were manually reviewed to confirm diagnosis and to identify predisposing factors, medication treatment and long-term outcomes. Factors associated with death or recurrent takotsubo syndrome were tested using Cox regression models. RESULTS Between 2006 and 2016, there were 519 patients with a confirmed diagnosis of takotsubo syndrome. Patients were followed for 5.2 years (IQR 3.0-7.2). During the follow-up period, 39 (7.5%) had recurrent takotsubo syndrome and 84 (16.2%) died. In multivariate modelling, factors associated with higher risk of recurrence or death were age (HR 1.56 per 10-year increase, 95% CI 1.29 to 1.87), male sex (HR 2.52, 95% CI 1.38 to 4.60), diabetes (HR 1.6, 95% CI 1.06 to 2.43), pulmonary disease (HR 2.0, 95% CI 1.37 to 2.91) and chronic kidney disease (HR 1.58, 95% CI 1.01 to 2.47). Treatment with beta-blockers were associated with lower risk of recurrence or death (HR 0.46, 95% CI 0.29 to 0.72). No association was observed between treatment with ACE inhibitors or angiotensin-receptor blockers and recurrence or death (HR 0.92, 95% CI 0.59 to 1.42). CONCLUSIONS Recurrent takotsubo syndrome occurred in a minor subset of patients. Treatment with beta-blocker was associated with higher event-free survival.
Collapse
Affiliation(s)
- Christopher Lau
- Internal Medicine, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California, USA
| | - Sarah Chiu
- Internal Medicine, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California, USA
| | - Rohith Nayak
- Internal Medicine, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California, USA
| | - Bryan Lin
- Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California, USA
| | - Ming-Sum Lee
- Cardiology, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California, USA
| |
Collapse
|
|
36
|
Cammann VL, Szawan KA, Stähli BE, Kato K, Budnik M, Wischnewsky M, Dreiding S, Levinson RA, Di Vece D, Gili S, Citro R, Bossone E, Neuhaus M, Franke J, Meder B, Jaguszewski M, Noutsias M, Knorr M, Heiner S, D'Ascenzo F, Dichtl W, Burgdorf C, Kherad B, Tschöpe C, Sarcon A, Shinbane J, Rajan L, Michels G, Pfister R, Cuneo A, Jacobshagen C, Karakas M, Koenig W, Pott A, Meyer P, Roffi M, Banning A, Wolfrum M, Cuculi F, Kobza R, Fischer TA, Vasankari T, Airaksinen KEJ, Napp LC, Dworakowski R, MacCarthy P, Kaiser C, Osswald S, Galiuto L, Chan C, Bridgman P, Beug D, Delmas C, Lairez O, Gilyarova E, Shilova A, Gilyarov M, El-Battrawy I, Akin I, Poledniková K, Toušek P, Winchester DE, Galuszka J, Ukena C, Poglajen G, Carrilho-Ferreira P, Hauck C, Paolini C, Bilato C, Kobayashi Y, Shoji T, Ishibashi I, Takahara M, Himi T, Din J, Al-Shammari A, Prasad A, Rihal CS, Liu K, Schulze PC, Bianco M, Jörg L, Rickli H, Pestana G, Nguyen TH, Böhm M, Maier LS, Pinto FJ, Widimský P, Felix SB, Braun-Dullaeus RC, Rottbauer W, Hasenfuß G, Pieske BM, Schunkert H, Borggrefe M, Thiele H, Bauersachs J, Katus HA, Horowitz JD, et alCammann VL, Szawan KA, Stähli BE, Kato K, Budnik M, Wischnewsky M, Dreiding S, Levinson RA, Di Vece D, Gili S, Citro R, Bossone E, Neuhaus M, Franke J, Meder B, Jaguszewski M, Noutsias M, Knorr M, Heiner S, D'Ascenzo F, Dichtl W, Burgdorf C, Kherad B, Tschöpe C, Sarcon A, Shinbane J, Rajan L, Michels G, Pfister R, Cuneo A, Jacobshagen C, Karakas M, Koenig W, Pott A, Meyer P, Roffi M, Banning A, Wolfrum M, Cuculi F, Kobza R, Fischer TA, Vasankari T, Airaksinen KEJ, Napp LC, Dworakowski R, MacCarthy P, Kaiser C, Osswald S, Galiuto L, Chan C, Bridgman P, Beug D, Delmas C, Lairez O, Gilyarova E, Shilova A, Gilyarov M, El-Battrawy I, Akin I, Poledniková K, Toušek P, Winchester DE, Galuszka J, Ukena C, Poglajen G, Carrilho-Ferreira P, Hauck C, Paolini C, Bilato C, Kobayashi Y, Shoji T, Ishibashi I, Takahara M, Himi T, Din J, Al-Shammari A, Prasad A, Rihal CS, Liu K, Schulze PC, Bianco M, Jörg L, Rickli H, Pestana G, Nguyen TH, Böhm M, Maier LS, Pinto FJ, Widimský P, Felix SB, Braun-Dullaeus RC, Rottbauer W, Hasenfuß G, Pieske BM, Schunkert H, Borggrefe M, Thiele H, Bauersachs J, Katus HA, Horowitz JD, Di Mario C, Münzel T, Crea F, Bax JJ, Lüscher TF, Ruschitzka F, Ghadri JR, Opolski G, Templin C. Age-Related Variations in Takotsubo Syndrome. J Am Coll Cardiol 2021; 75:1869-1877. [PMID: 32327096 DOI: 10.1016/j.jacc.2020.02.057] [Show More Authors] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 02/06/2020] [Accepted: 02/28/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Takotsubo syndrome (TTS) occurs predominantly in post-menopausal women but is also found in younger patients. OBJECTIVES This study aimed to investigate age-related differences in TTS. METHODS Patients diagnosed with TTS and enrolled in the International Takotsubo Registry between January 2011 and February 2017 were included in this analysis and were stratified by age (younger: ≤50 years, middle-age: 51 to 74 years, elderly: ≥75 years). Baseline characteristics, hospital course, as well as short- and long-term mortality were compared among groups. RESULTS Of 2,098 TTS patients, 242 (11.5%) patients were ≤50 years of age, 1,194 (56.9%) were 51 to 74 years of age, and 662 (31.6%) were ≥75 years of age. Younger patients were more often men (12.4% vs. 10.9% vs. 6.3%; p = 0.002) and had an increased prevalence of acute neurological (16.3% vs. 8.4% vs. 8.8%; p = 0.001) or psychiatric disorders (14.1% vs. 10.3% vs. 5.6%; p < 0.001) compared with middle-aged and elderly TTS patients. Furthermore, younger patients had more often cardiogenic shock (15.3% vs. 9.1% vs. 8.1%; p = 0.004) and had a numerically higher in-hospital mortality (6.6% vs. 3.6% vs. 5.1%; p = 0.07). At multivariable analysis, younger (odds ratio: 1.60; 95% confidence interval: 0.86 to 3.01; p = 0.14) and older age (odds ratio: 1.09; 95% confidence interval: 0.66 to 1.80; p = 0.75) were not independently associated with in-hospital mortality using the middle-aged group as a reference. There were no differences in 60-day mortality rates among groups. CONCLUSIONS A substantial proportion of TTS patients are younger than 50 years of age. TTS is associated with severe complications requiring intensive care, particularly in younger patients.
Collapse
Affiliation(s)
- Victoria L Cammann
- University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
| | - Konrad A Szawan
- University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
| | - Barbara E Stähli
- University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
| | - Ken Kato
- University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
| | - Monika Budnik
- Department of Cardiology, Medical University of Warsaw, Warsaw, Poland
| | | | - Sara Dreiding
- University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
| | - Rena A Levinson
- University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
| | - Davide Di Vece
- University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
| | | | - Rodolfo Citro
- Heart Department, University Hospital "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italy
| | - Eduardo Bossone
- Division of Cardiology, "Antonio Cardarelli" Hospital, Naples, Italy
| | - Michael Neuhaus
- Department of Cardiology, Kantonsspital Frauenfeld, Frauenfeld, Switzerland
| | - Jennifer Franke
- Department of Cardiology, Heidelberg University Hospital, Heidelberg, Germany
| | - Benjamin Meder
- Department of Cardiology, Heidelberg University Hospital, Heidelberg, Germany
| | - Miłosz Jaguszewski
- First Department of Cardiology, Medical University of Gdansk, Gdansk, Poland
| | - Michel Noutsias
- Mid-German Heart Center, Department of Internal Medicine III, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
| | - Maike Knorr
- Center for Cardiology, Cardiology 1, University Medical Center Mainz, Mainz, Germany
| | - Susanne Heiner
- Center for Cardiology, Cardiology 1, University Medical Center Mainz, Mainz, Germany
| | - Fabrizio D'Ascenzo
- Division of Cardiology, Department of Medical Sciences, AOU Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Wolfgang Dichtl
- University Hospital for Internal Medicine III (Cardiology and Angiology), Medical University Innsbruck, Innsbruck, Austria
| | | | - Behrouz Kherad
- Department of Cardiology, Charité, Campus Rudolf Virchow, Berlin, Germany
| | - Carsten Tschöpe
- Department of Cardiology, Charité, Campus Rudolf Virchow, Berlin, Germany
| | - Annahita Sarcon
- Section of Cardiac Electrophysiology, Department of Medicine, University of California-San Francisco, San Francisco, California
| | - Jerold Shinbane
- University of Southern California, Keck School of Medicine, Los Angeles, California
| | - Lawrence Rajan
- TJ Health Partners Heart and Vascular, Glasgow, Kentucky
| | - Guido Michels
- Department of Internal Medicine III, Heart Center University of Cologne, Cologne, Germany
| | - Roman Pfister
- Department of Internal Medicine III, Heart Center University of Cologne, Cologne, Germany
| | - Alessandro Cuneo
- Krankenhaus "Maria Hilf" Medizinische Klinik, Stadtlohn, Germany
| | - Claudius Jacobshagen
- Clinic for Cardiology and Pneumology, Georg August University Goettingen, Goettingen, Germany
| | - Mahir Karakas
- Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, Hamburg, Germany
| | - Wolfgang Koenig
- Deutsches Herzzentrum München, Technische Universität München, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
| | - Alexander Pott
- Department of Internal Medicine II-Cardiology, University of Ulm, Medical Center, Ulm, Germany
| | - Philippe Meyer
- Service de cardiologie, Hôpitaux Universitaires de Genève, Geneva, Switzerland
| | - Marco Roffi
- Service de cardiologie, Hôpitaux Universitaires de Genève, Geneva, Switzerland
| | - Adrian Banning
- Department of Cardiology, John Radcliffe Hospital, Oxford University Hospitals, Oxford, United Kingdom
| | - Mathias Wolfrum
- Department of Internal Medicine, Cardiology and Angiology, Magdeburg University, Magdeburg, Germany
| | - Florim Cuculi
- Department of Cardiology, Kantonsspital Lucerne, Lucerne, Switzerland
| | - Richard Kobza
- Department of Cardiology, Kantonsspital Lucerne, Lucerne, Switzerland
| | - Thomas A Fischer
- Department of Cardiology, Kantonsspital Winterthur, Winterthur, Switzerland
| | - Tuija Vasankari
- Heart Center, Turku University Hospital and University of Turku, Turku, Finland
| | | | - L Christian Napp
- Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
| | - Rafal Dworakowski
- Department of Cardiology, King's College Hospital, London, United Kingdom
| | - Philip MacCarthy
- Department of Cardiology, King's College Hospital, London, United Kingdom
| | - Christoph Kaiser
- Department of Cardiology, University Hospital Basel, Basel, Switzerland
| | - Stefan Osswald
- Department of Cardiology, University Hospital Basel, Basel, Switzerland
| | - Leonarda Galiuto
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Christina Chan
- Department of Cardiology, Christchurch Hospital, Christchurch, New Zealand
| | - Paul Bridgman
- Department of Cardiology, Christchurch Hospital, Christchurch, New Zealand
| | - Daniel Beug
- Department of Cardiology and Internal Medicine B, University Medicine Greifswald, Greifswald, Germany; DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany
| | - Clément Delmas
- Department of Cardiology and Cardiac Imaging Center, University Hospital of Rangueil, Toulouse, France
| | - Olivier Lairez
- Department of Cardiology and Cardiac Imaging Center, University Hospital of Rangueil, Toulouse, France
| | - Ekaterina Gilyarova
- Intensive Coronary Care Unit, Moscow City Hospital #1 named after N. Pirogov, Moscow, Russia
| | - Alexandra Shilova
- Intensive Coronary Care Unit, Moscow City Hospital #1 named after N. Pirogov, Moscow, Russia
| | - Mikhail Gilyarov
- Intensive Coronary Care Unit, Moscow City Hospital #1 named after N. Pirogov, Moscow, Russia
| | - Ibrahim El-Battrawy
- First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim (UMM) University of Heidelberg, Mannheim, Germany; DZHK (German Center for Cardiovascular Research), partner site, Heidelberg-Mannheim, Mannheim, Germany
| | - Ibrahim Akin
- First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim (UMM) University of Heidelberg, Mannheim, Germany; DZHK (German Center for Cardiovascular Research), partner site, Heidelberg-Mannheim, Mannheim, Germany
| | - Karolina Poledniková
- Cardiocenter, Third Faculty of Medicine, Charles University in Prague and University Hospital Královské Vinohrady, Prague, Czech Republic
| | - Petr Toušek
- Cardiocenter, Third Faculty of Medicine, Charles University in Prague and University Hospital Královské Vinohrady, Prague, Czech Republic
| | - David E Winchester
- Division of Cardiovascular Medicine, Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida
| | - Jan Galuszka
- Department of Internal Medicine I - Cardiology, University Hospital Olomouc, Olomouc, Czech Republic
| | - Christian Ukena
- Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
| | - Gregor Poglajen
- Advanced Heart Failure and Transplantation Center, University Medical Center Ljubljana, Ljubljana, Slovenia
| | - Pedro Carrilho-Ferreira
- Santa Maria University Hospital, CHULN, Center of Cardiology of the University of Lisbon, Lisbon School of Medicine, Lisbon Academic Medical Center, Lisboa, Portugal
| | - Christian Hauck
- Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, Regensburg, Germany
| | - Carla Paolini
- Local Health Unit n.8, Cardiology Unit, Arzignano, Vicenza, Italy
| | - Claudio Bilato
- Local Health Unit n.8, Cardiology Unit, Arzignano, Vicenza, Italy
| | - Yoshio Kobayashi
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Toshihiro Shoji
- Department of Cardiology, Chiba Emergency Medical Center, Chiba, Japan
| | - Iwao Ishibashi
- Department of Cardiology, Chiba Emergency Medical Center, Chiba, Japan
| | | | - Toshiharu Himi
- Division of Cardiology, Kimitsu Central Hospital, Kisarazu, Japan
| | - Jehangir Din
- Dorset Heart Centre, Royal Bournemouth Hospital, Bournemouth, United Kingdom
| | - Ali Al-Shammari
- Dorset Heart Centre, Royal Bournemouth Hospital, Bournemouth, United Kingdom
| | - Abhiram Prasad
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
| | - Charanjit S Rihal
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
| | - Kan Liu
- Division of Cardiology, Heart and Vascular Center, University of Iowa, Iowa City, Iowa
| | - P Christian Schulze
- Department of Internal Medicine I, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany
| | - Matteo Bianco
- Division of Cardiology, A.O.U San Luigi Gonzaga, Orbassano, Turin, Italy
| | - Lucas Jörg
- Department of Cardiology, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | - Hans Rickli
- Department of Cardiology, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | - Gonçalo Pestana
- Department of Cardiology, Centro Hospitalar Universitário de São João, E.P.E., Porto, Portugal
| | - Thanh H Nguyen
- Department of Cardiology, Basil Hetzel Institute, Queen Elizabeth Hospital, University of Adelaide, Adelaide, South Australia, Australia
| | - Michael Böhm
- Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
| | - Lars S Maier
- Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, Regensburg, Germany
| | - Fausto J Pinto
- Santa Maria University Hospital, CHULN, Center of Cardiology of the University of Lisbon, Lisbon School of Medicine, Lisbon Academic Medical Center, Lisboa, Portugal
| | - Petr Widimský
- Cardiocenter, Third Faculty of Medicine, Charles University in Prague and University Hospital Královské Vinohrady, Prague, Czech Republic
| | - Stephan B Felix
- Department of Cardiology and Internal Medicine B, University Medicine Greifswald, Greifswald, Germany; DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany
| | | | - Wolfgang Rottbauer
- Department of Internal Medicine II-Cardiology, University of Ulm, Medical Center, Ulm, Germany
| | - Gerd Hasenfuß
- Clinic for Cardiology and Pneumology, Georg August University Goettingen, Goettingen, Germany
| | - Burkert M Pieske
- Department of Cardiology, Charité, Campus Rudolf Virchow, Berlin, Germany; DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin Institute of Health (BIH), Berlin, Germany
| | - Heribert Schunkert
- Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, Regensburg, Germany; Local Health Unit n.8, Cardiology Unit, Arzignano, Vicenza, Italy
| | - Martin Borggrefe
- First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim (UMM) University of Heidelberg, Mannheim, Germany; DZHK (German Center for Cardiovascular Research), partner site, Heidelberg-Mannheim, Mannheim, Germany
| | - Holger Thiele
- Heart Center Leipzig - University Hospital, Department of Internal Medicine/Cardiology, Leipzig, Germany
| | - Johann Bauersachs
- Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
| | - Hugo A Katus
- Department of Cardiology, Heidelberg University Hospital, Heidelberg, Germany
| | - John D Horowitz
- Department of Cardiology, Basil Hetzel Institute, Queen Elizabeth Hospital, University of Adelaide, Adelaide, South Australia, Australia
| | - Carlo Di Mario
- Structural Interventional Cardiology, Careggi University Hospital, Florence, Italy
| | - Thomas Münzel
- Center for Cardiology, Cardiology 1, University Medical Center Mainz, Mainz, Germany
| | - Filippo Crea
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Jeroen J Bax
- Department of Cardiology, Leiden University Medical Centre, Leiden, the Netherlands
| | - Thomas F Lüscher
- Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Zurich, Switzerland; Royal Brompton and Harefield Hospitals Trust and Imperial College, London, United Kingdom
| | - Frank Ruschitzka
- University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
| | - Jelena R Ghadri
- University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
| | - Grzegorz Opolski
- Department of Cardiology, Medical University of Warsaw, Warsaw, Poland
| | - Christian Templin
- University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland.
| |
Collapse
|
|
37
|
Abstract
OBJECTIVE To explore the epidemiology and outcomes of takotsubo cardiomyopathy in children. METHODS A retrospective analysis of the Healthcare Cost and Utilization 2012 and 2016 Kids' Inpatient Database was performed. Patients admitted with the diagnosis of takotsubo cardiomyopathy in the age group of 1 month-20 years were identified using International Classification of Diseases (ICD)-9 code 429.83 and ICD-10 code I51.81. RESULTS Among a total of 4,860,859 discharges, there were 153 with the diagnosis of takotsubo cardiomyopathy (3.1 per 100,000 discharges). Among patients with takotsubo cardiomyopathy, 55.0% were male, 62.4% were white, and 16.7% were black. Eighty-nine percent of patients were between 12 and 20 years. Psychiatric diagnosis was documented in 46% and substance use disorder in 36.2%. Sepsis was documented in 22.8% of patients. The median length of stay was 5 days (interquartile range: 2.7-15), and median total charges were $75,080 (interquartile range: 32,176-198,336). The overall mortality for takotsubo cardiomyopathy was 7%. On multivariable regression analysis, mortality was higher in the presence of anoxic injury (odds ratio = 34.42, 95% confidence interval: 4.85-320.11, p = 0.00). CONCLUSIONS Takotsubo cardiomyopathy is uncommon in children and carries a mortality rate of 7%. Most children with takotsubo cardiomyopathy are adolescent males, many of whom have psychiatric disorder or substance use disorder or both. Takotsubo cardiomyopathy should be considered in the differential diagnosis for patients who present with cardiac dysfunction and have underlying psychiatric disorders or drug abuse.
Collapse
|
|
38
|
Nazir S, Ahuja KR, Soni RG, Raheja H, Saleem S, Hsiung I, Patel NJ, Eltahawy EA, Madias JE. Age-Related Variations in Takotsubo Syndrome in the United States. Am J Cardiol 2020; 133:168-170. [PMID: 32782068 DOI: 10.1016/j.amjcard.2020.07.023] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 07/17/2020] [Indexed: 01/31/2023]
Affiliation(s)
- Salik Nazir
- Division of Cardiology, University of Toledo, Toledo, Ohio
| | - Keerat Rai Ahuja
- Division of Cardiology, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
| | - Ronak G Soni
- Division of Cardiology, University of Toledo, Toledo, Ohio
| | - Hitesh Raheja
- Division of Cardiology, Maimonides Medical Center, Brooklyn, New York
| | - Sameer Saleem
- Division of Cardiology, University of Kentucky, Bowling Green, Kentucky
| | - Ingrid Hsiung
- Division of Cardiology, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
| | - Neha J Patel
- Division of Cardiology, University of Toledo, Toledo, Ohio
| | | | - John E Madias
- Icahn School of Medicine at Mount Sinai, New York, New York; Division of Cardiology, Elmhurst Hospital Center, Elmhurst, New York.
| |
Collapse
|
|
39
|
Abstract
Takotsubo cardiomyopathy or takotsubo syndrome (TTS) has become a well-known disease not only in Japan but also in the rest of the world. Early reports suggested that TTS is a self-limiting disease with better prognosis than acute coronary syndrome. However, recent data showed that TTS is not a benign disease as compared with acute coronary syndrome. In addition to the apical ballooning, several other types of wall motion abnormalities have been classified as variants of TTS. In particular, right ventricular involvement, or biventricular TTS, is not uncommon and is associated with poor in-hospital as well as long-term outcomes. With respect to the pathophysiology, modulation (desensitization) of the beta-adrenergic receptor is suspected as a possible mechanism for transiently depressed myocardial contraction. Although specific treatments to improve prognosis of TTS are still uncertain, observational data suggest favorable impact of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Finally, in the era of COVID-19, we should pay attention to a variety of cardiovascular conditions related to COVID-19. TTS is one of these conditions that can be triggered by both emotional and physical impact of the COVID-19 pandemic.
Collapse
Affiliation(s)
- Hiroyuki Okura
- Department of Cardiology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan.
| |
Collapse
|
|
40
|
Kanaoka K, Okayama S, Terasaki S, Nakano T, Ishii M, Nakai M, Onoue K, Nishimura K, Yasuda S, Tsujita K, Kawakami R, Miyamoto Y, Tsutsui H, Komuro I, Ogawa H, Saito Y. Role of climatic factors in the incidence of Takotsubo syndrome: A nationwide study from 2012 to 2016. ESC Heart Fail 2020; 7:2629-2636. [PMID: 32715646 PMCID: PMC7524088 DOI: 10.1002/ehf2.12843] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Revised: 05/01/2020] [Accepted: 05/29/2020] [Indexed: 11/15/2022] Open
Abstract
Aims This study aimed to investigate the influence of climatic factors on the onset of Takotsubo syndrome (TTS). Methods and results We performed a retrospective nationwide study among patients registered in the Japanese Registry of All Cardiac and Vascular Diseases and Diagnosis Procedure Combination (JROAD–DPC) discharge database, between 2012 and 2016. Before the analysis, a multicentre validation study was conducted for assessing the accuracy of the JROAD–DPC classification for TTS. First, we investigated the seasonal variation of incidences of TTS. Second, we analysed the associations between the incidence of TTS and climatic factors using the hierarchical Poisson regression modelling, and we also investigated the associations between typhoon landfalls and hospitalization for TTS, using the fixed‐effects conditional Poisson regression model. The sensitivity and specificity for diagnosis were 83% and 100%, respectively. Then we analysed 5643 patients with TTS. The mean patient age was 74 (standard deviation ± 11) years; 79% were female. TTS was diagnosed significantly more frequently in the summer and early autumn. The incidence of TTS was related to higher temperatures; adjusted incidence rate ratios were 1.46 [95% confidence interval (CI): 1.33–1.60, P < 0.01] and 1.47 (95% CI: 1.34–1.62, P < 0.01) for temperatures of 20–25°C and >25°C, respectively. The incidence rate ratio for the first 2 days after a typhoon landfall was 1.85 (95% CI: 1.07–3.19; P = 0.03). Conclusions This study demonstrates distinct patterns of seasonal variation in the incidence of TTS, as well as a significant association between its onset and climatic factors, including typhoon landfalls.
Collapse
Affiliation(s)
- Koshiro Kanaoka
- Department of Cardiovascular Medicine, Nara Medical University, 840 Shijo-cho, Kashihara City, Nara, Japan
| | - Satoshi Okayama
- Department of Cardiovascular Medicine, Nara Medical University, 840 Shijo-cho, Kashihara City, Nara, Japan
| | - Satoshi Terasaki
- Department of Cardiovascular Medicine, Nara Medical University, 840 Shijo-cho, Kashihara City, Nara, Japan
| | - Tomoya Nakano
- Department of Cardiovascular Medicine, Nara Medical University, 840 Shijo-cho, Kashihara City, Nara, Japan
| | - Masanobu Ishii
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | | | - Kenji Onoue
- Department of Cardiovascular Medicine, Nara Medical University, 840 Shijo-cho, Kashihara City, Nara, Japan
| | | | - Satoshi Yasuda
- National Cerebral and Cardiovascular Center, Suita, Japan
| | - Kenichi Tsujita
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Rika Kawakami
- Department of Cardiovascular Medicine, Nara Medical University, 840 Shijo-cho, Kashihara City, Nara, Japan
| | | | - Hiroyuki Tsutsui
- Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Issei Komuro
- Department of Cardiovascular Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
| | - Hisao Ogawa
- National Cerebral and Cardiovascular Center, Suita, Japan
| | - Yoshihiko Saito
- Department of Cardiovascular Medicine, Nara Medical University, 840 Shijo-cho, Kashihara City, Nara, Japan
| |
Collapse
|
|
41
|
Tarantino N, Santoro F, Di Biase L, Di Terlizzi V, Vitale E, Barone R, Della Rocca DG, De Leon De La Cruz NS, Di Biase M, Brunetti ND. Chromogranin-A serum levels in patients with takotsubo syndrome and ST elevation acute myocardial infarction. Int J Cardiol 2020; 320:12-17. [PMID: 32739447 DOI: 10.1016/j.ijcard.2020.07.040] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Revised: 06/20/2020] [Accepted: 07/28/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND Sympathergic hyperactivity is considered one of the main trigger precipitating takotsubo syndrome (TTS). Chromogranin-A (CgA), a prognostic biomarker of sympatho-adrenal activation, is markedly high in acute coronary syndrome (ACS) and heart failure (HF), but its role in TTS is unknown. METHODS CgA serum levels from patients with TTS and symptoms onset <24 hours were consecutively evaluated and compared with anterior ST-elevation myocardial infarction (STEMI) patients from November 2016 to December 2019. Short and long-term follow-up data were recorded. RESULTS Eleven women with TTS and 10 subjects with anterior STEMI were analyzed and compared; differences were not significant in terms of age, gender and cardiovascular risk factors. NT-pro-BNP levels were similar (9,887 ± 12,170 vs 8,969 ± 15,053 pg/ml, p = .88), while troponin-I levels were higher in patients with STEMI (4 ± 3.2 vs 13.3 ± 10 ng/dl, p = .03). CgA admission levels were significantly lower in TTS patients (2.2 ± 1.5 vs 7.3 ± 6.2 nMol/l, p = .017), even after multivariable correction for principal bias. CgA levels correlated with NTproBNP levels (p = .02) and were higher in subjects with in-hospital events (3.7 ± 1.1 vs 1.6 ± 1.2 nMol/l, p = .03), even after multivariable forward stepwise analysis (p < .01). CgA levels <3.25 nMol/l (AUC 0.754, 95% C.I. 0.54-0.968) were able to discriminate TTS from anterior STEMI (negative predictive power of 99%). CONCLUSIONS Systemic CgA levels in the acute phase of TTS are lower than in anterior STEMI, possibly indicating a greater myocardial catecholamine release rather than adrenal.
Collapse
Affiliation(s)
- Nicola Tarantino
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy; Arrhythmia Service, Division of Cardiology, Department of Medicine, Montefiore Medical Center, Bronx, NY, USA
| | - Francesco Santoro
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
| | - Luigi Di Biase
- Arrhythmia Service, Division of Cardiology, Department of Medicine, Montefiore Medical Center, Bronx, NY, USA; Texas Cardiac Arrhyhtmia Institute (TCAI) at St. David's Hospital, Austin, TX, USA; Department of Biomedical Engineering, Cockrell School of Engineering, University of Texas, Austin, TX, USA; Department of Internal Medicine, Dell Medical School, University of Texas, Austin, TX, USA
| | - Vito Di Terlizzi
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Enrica Vitale
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Roberta Barone
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | | | | | - Matteo Di Biase
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | | |
Collapse
|
|
42
|
Ali A, Redfors B, Lundgren J, Alkhoury J, Oras J, Gan LM, Omerovic E. The importance of heart rate in isoprenaline-induced takotsubo-like cardiac dysfunction in rats. ESC Heart Fail 2020; 7:2690-2699. [PMID: 32686334 PMCID: PMC7524126 DOI: 10.1002/ehf2.12858] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 05/25/2020] [Accepted: 06/09/2020] [Indexed: 11/30/2022] Open
Abstract
Aims Takotsubo syndrome (TS) is an acute cardiac syndrome characterized by regional myocardial akinesia that cannot be attributed to a culprit lesion in coronary arteries. Cardiac overstimulation by catecholamines in the setting of stress is implicated in the pathogenesis of TS. While catecholamine‐induced alterations in cardiac contractility have been studied as part of the causal pathway in TS, the importance of catecholamine‐mediated tachycardia has not been studied. Our aim was to explore whether the reduction in heart rate, either by pharmacological suppression of the sinoatrial node with ivabradine or by surgical induction of third‐degree atrioventricular block, prevents isoprenaline‐induced TS‐like akinesia in an experimental animal model. Methods and results We used 142 female Sprague–Dawley rats in two separate protocols. The TS‐like phenotype was induced by an intraperitoneal bolus dose of isoprenaline (ISO) 50 mg/kg. In the first protocol, we randomized 54 rats to ivabradine 10 min before ISO (IVAB1), ivabradine 10 min after ISO (IVAB2), or saline 10 min before ISO (CONTROL). In the second protocol, we randomized 88 rats to surgically induced complete heart block (CHB) or sham operation (CTRL) 10 min before the administration of ISO. All drugs were administered intraperitoneally. We recorded heart rate and blood pressure invasively in the right carotid artery. Cardiac morphology and function were evaluated by high‐resolution echocardiography (VisualSonics 770 VEVO, Toronto, Ontario, Canada) 90 min after ISO injection. IVAB1 and IVAB2 rats had significantly lower heart rate and less pronounced TS‐like cardiac dysfunction than CONTROL. CHB rats had a lower (54%) heart rate, and no animal developed left ventricular akinesia. In the first protocol, the CONTROL group had a median degree of akinesia of 10.2 [inter‐quartile range (IQR) 0.0–18.6]. The IVAB1 group showed a median of akinesia of 0% (IQR 0.0–0.0, P < 0.001 vs. CONTROL). In the IVAB2 group, 5% had TS‐like dysfunction (P = 0.001). Ejection fraction was higher in both the IVAB1 (92%, IQR 89–95) and IVAB2 groups (93%, IQR 87–96) than in the CONTROL group (78%, IQR 63–87, P < 0.05). In the second protocol, the median degree of akinesia in the CTRL group was 21.9% (IQR 8.9–24.6). In the CHB group, no rat developed akinesia (median 0%; IQR 0.0–0.0, P < 0.001 vs. CONTROL). Ejection fraction was higher in the CHB group (90%, IQR 87–92) than in the CTRL group (51%, IQR 87–92, P < 0.05). Conclusions Isoprenaline‐induced TS‐like cardiac dysfunction can be prevented by lowering heart rate. Tachycardia may be an important part of the causal pathway in TS.
Collapse
Affiliation(s)
- Anwar Ali
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Björn Redfors
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Cardiology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Joel Lundgren
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Jessica Alkhoury
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Jonatan Oras
- Department of Anesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Li-Ming Gan
- Department of Cardiology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Early Clinical Development, Cardiovascular Renal and Metabolic Diseases, IMED Biotech Unit, AstraZeneca Gothenburg, Gothenburg, Sweden
| | - Elmir Omerovic
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Cardiology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| |
Collapse
|
|
43
|
Y-Hassan S. Autonomic neurocardiogenic syndrome is stonewalled by the universal definition of myocardial infarction. World J Cardiol 2020; 12:231-247. [PMID: 32774776 PMCID: PMC7383352 DOI: 10.4330/wjc.v12.i6.231] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 04/27/2020] [Accepted: 05/14/2020] [Indexed: 02/06/2023] Open
Abstract
Myocardial infarction (MI) is defined as myocardial cell death due to prolonged myocardial ischemia. Clinically, troponin rise and/or fall have become the “defining feature of MI” according to the universal definition of MI (UD-MI). Takotsubo syndrome (TS) and TS-related disease conditions also cause troponin elevation with typical rise and/or fall pattern but through a mechanism other than coronary ischemia. By strict application of the clinical diagnostic criteria for type-1 MI, type-2 MI, type-3 MI, and MI with non-obstructive coronary arteries according to the UD-MI including the fourth one published recently, TS and most of the 26 other causes of troponin elevation mentioned in the fourth UD-MI may erroneously be classified as MI. The existing evidence argues for the case that TS by itself is not a MI. Hyper-activation of the autonomic-sympathetic nervous system including local cardiac sympathetic hyper-activation and disruption with nor-epinephrine churn and spillover is the most probable cause of TS. This autonomic neuro-cardiogenic (ANCA) mechanism results in myocardial “cramp” (stunning), the severity and duration of which depend on the degree of the sympathetic-hyperactivation and nor-epinephrine spillover. The myocardial cramp may squeeze the cytosolic free troponin pools causing mild to moderate troponin elevation in TS and TS-related disease conditions. This ANCA syndrome, which has hitherto been enveloped by the UD-MI over more than one decade, may occur in acute, recurrent, and chronic forms. In this critical review, the controversies of UD-MI, evidence for ANCA syndrome, and a hypothetical mechanism for the troponin elevation in ANCA syndrome are provided.
Collapse
Affiliation(s)
- Shams Y-Hassan
- Coronary Artery Disease Area, Heart and Vascular Theme, Karolinska Institutet and Karolinska University Hospital, Stockholm S-141 86, Sweden
| |
Collapse
|
|
44
|
Borodzicz S, Czarzasta K, Opolski G, Cudnoch-Jędrzejewska A. Autonomic nervous system in Takotsubo syndrome. Heart Fail Rev 2020; 24:101-108. [PMID: 30058016 DOI: 10.1007/s10741-018-9729-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Takotsubo syndrome (TTS) is an acute and usually reversible heart failure syndrome with symptoms resembling acute myocardial infarction, however, without obstruction of coronary arteries. In the majority of cases, TTS is preceded by emotional or physical stress and the disease concerns mainly postmenopausal women. Although several hypotheses have been introduced, the pathogenesis of TTS is controversial and still remains to be determined. As reported in recent studies, the role of the autonomic nervous system (ANS) seems to be pivotal in the pathogenesis of TTS. Therefore, the aim of this article is to summarize and discuss the current knowledge of the pathogenesis of TTS with a special focus on the ANS.
Collapse
Affiliation(s)
- Sonia Borodzicz
- Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, 1b Banacha Street, 02-097, Warsaw, Poland.,1st Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, Poland
| | - Katarzyna Czarzasta
- Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, 1b Banacha Street, 02-097, Warsaw, Poland
| | - Grzegorz Opolski
- 1st Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, Poland
| | - Agnieszka Cudnoch-Jędrzejewska
- Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, 1b Banacha Street, 02-097, Warsaw, Poland.
| |
Collapse
|
|
45
|
The Brain-Heart Connection in Takotsubo Syndrome: The Central Nervous System, Sympathetic Nervous System, and Catecholamine Overload. Cardiol Res Pract 2020; 2020:4150291. [PMID: 32211202 PMCID: PMC7085406 DOI: 10.1155/2020/4150291] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 02/13/2020] [Indexed: 01/27/2023] Open
Abstract
Takotsubo syndrome (TTS), also known as stress cardiomyopathy, is a type of acute heart failure syndrome triggered by intense psychological or physiological stress. TTS typically manifests as acute chest pain, dyspnea or syncope that mimics an acute myocardial infarction but does not involve coronary artery obstruction. The current understanding of the pathogenesis of TTS suggests that sympathetic nervous system (SNS) activation plays a central role. Specifically, stress can activate the SNS and lead to the over-release of catecholamine, which have toxic effects on myocardial tissue when present at excessive levels. However, the brain changes associated with TTS and the connection between the brain and the heart in patients with this disease remain unclear. In recent years, several published reports have revealed the role of this brain-heart connection in the pathogenesis of TTS. This review summarizes recent studies regarding SNS activation, catecholamine overload, and the brain-heart connection in patients with TTS from both pathophysiological and mechanistic aspects.
Collapse
|
|
46
|
Vijiiac A, Ploscaru V, Vatasescu RG. The Great Myocardial Mimic - Takotsubo Syndrome. MAEDICA 2020; 15:111-121. [PMID: 32419871 PMCID: PMC7221266 DOI: 10.26574/maedica.2020.15.1.111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Takotsubo syndrome has been traditionally considered a reversible form of acute heart failure triggered by an emotional or physical stressor, mainly occurring in women of post-menopausal age and often mimicking an acute coronary syndrome. While its pathophysiology is still incompletely understood, sympathetic overstimulation is known to play a central role in the disease. The classical hallmark of the condition was the presence of wall motion abnormalities limited to the apical segments of the ventricle, leading to the so-called apical ballooning, but different patterns of wall motion abnormalities are nowadays recognised. Different definitions and diagnostic criteria for takotsubo syndrome were proposed during the last decades, reflecting the heterogeneity of the condition and the gaps in the thorough understanding of the disease. While initially it was believed to be a benign entity, takotsubo syndrome has in fact similar morbidity and mortality with acute coronary syndromes, both on short- and long-term, highlighting the importance of proper risk stratification. Many questions still remain unanswered concerning the pathophysiology of the syndrome and the optimal therapeutic strategy for these patients.
Collapse
Affiliation(s)
- Aura Vijiiac
- Cardiology Department, Emergency Clinical Hospital Bucharest, Romania
| | - Vlad Ploscaru
- Cardiology Department, Emergency Clinical Hospital Bucharest, Romania
| | | |
Collapse
|
|
47
|
Biccirè FG, Pannarale G, Acconcia MC, Torromeo C, Cardillo I, Chianta V, Ferrari I, Gaudio C, Barillà F. Clinical frailty and triggers in Takotsubo syndrome. J Cardiovasc Med (Hagerstown) 2020; 21:144-149. [DOI: 10.2459/jcm.0000000000000908] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
|
|
48
|
Ghadri JR, Wittstein IS, Prasad A, Sharkey S, Dote K, Akashi YJ, Cammann VL, Crea F, Galiuto L, Desmet W, Yoshida T, Manfredini R, Eitel I, Kosuge M, Nef HM, Deshmukh A, Lerman A, Bossone E, Citro R, Ueyama T, Corrado D, Kurisu S, Ruschitzka F, Winchester D, Lyon AR, Omerovic E, Bax JJ, Meimoun P, Tarantini G, Rihal C, Y-Hassan S, Migliore F, Horowitz JD, Shimokawa H, Lüscher TF, Templin C. International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology. Eur Heart J 2019; 39:2032-2046. [PMID: 29850871 PMCID: PMC5991216 DOI: 10.1093/eurheartj/ehy076] [Citation(s) in RCA: 980] [Impact Index Per Article: 163.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Accepted: 04/17/2018] [Indexed: 12/11/2022] Open
Abstract
Takotsubo syndrome (TTS) is a poorly recognized heart disease that was initially regarded as a benign condition. Recently, it has been shown that TTS may be associated with severe clinical complications including death and that its prevalence is probably underestimated. Since current guidelines on TTS are lacking, it appears timely and important to provide an expert consensus statement on TTS. The clinical expert consensus document part I summarizes the current state of knowledge on clinical presentation and characteristics of TTS and agrees on controversies surrounding TTS such as nomenclature, different TTS types, role of coronary artery disease, and etiology. This consensus also proposes new diagnostic criteria based on current knowledge to improve diagnostic accuracy.
Collapse
Affiliation(s)
- Jelena-Rima Ghadri
- University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
| | - Ilan Shor Wittstein
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Abhiram Prasad
- Division of Cardiovascular Diseases Mayo Clinic, Rochester, MN, USA
| | - Scott Sharkey
- Cardiovascular Research Division, Minneapolis Heart Institute Foundation, Minneapolis, MN, USA
| | - Keigo Dote
- Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan
| | - Yoshihiro John Akashi
- Division of Cardiology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Victoria Lucia Cammann
- University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
| | - Filippo Crea
- Department of Cardiovascular Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Leonarda Galiuto
- Department of Cardiovascular Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Walter Desmet
- Department of Cardiovascular Medicine, University Hospitals Leuven, Leuven, Belgium.,Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium
| | - Tetsuro Yoshida
- Department of Cardiovascular Medicine, Onga Nakama Medical Association Onga Hospital, Fukuoka, Japan
| | - Roberto Manfredini
- Clinica Medica, Department of Medical Sciences, University of Ferrara, Ferrara, Italy
| | - Ingo Eitel
- University Heart Center Luebeck, Medical Clinic II, Department of Cardiology, Angiology and Intensive Care Medicine, University of Luebeck, Luebeck, Germany
| | - Masami Kosuge
- Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan
| | - Holger M Nef
- Department of Cardiology, University Hospital Giessen, Giessen, Germany
| | | | - Amir Lerman
- Division of Cardiovascular Diseases Mayo Clinic, Rochester, MN, USA
| | - Eduardo Bossone
- Heart Department, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, Italy
| | - Rodolfo Citro
- Heart Department, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, Italy
| | - Takashi Ueyama
- Department of Anatomy and Cell Biology, Wakayama Medical University School of Medicine, Wakayama, Japan
| | - Domenico Corrado
- Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua Medical School, Padova, Italy
| | - Satoshi Kurisu
- Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan
| | - Frank Ruschitzka
- University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
| | - David Winchester
- Division of Cardiovascular Disease, Department of Medicine, University of Florida, Gainesville, FL, USA
| | - Alexander R Lyon
- NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, UK.,National Heart and Lung Institute, Imperial College, London, UK
| | - Elmir Omerovic
- Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.,Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
| | - Jeroen J Bax
- Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Patrick Meimoun
- Department of Cardiology and Intensive Care, Centre Hospitalier de Compiegne, Compiegne, France
| | - Guiseppe Tarantini
- Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua Medical School, Padova, Italy
| | - Charanjit Rihal
- Division of Cardiovascular Diseases Mayo Clinic, Rochester, MN, USA
| | - Shams Y-Hassan
- Department of Cardiology, Karolinska University Hospital, Huddinge, Stockholm, Sweden
| | - Federico Migliore
- Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua Medical School, Padova, Italy
| | - John D Horowitz
- Department of Cardiology, Basil Hetzel Institute, Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia
| | - Hiroaki Shimokawa
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Thomas Felix Lüscher
- Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Zurich, Switzerland.,Department of Cardiology, Royal Brompton & Harefield Hospital and Imperial College, London, UK
| | - Christian Templin
- University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
| |
Collapse
|
|
49
|
Kujime S, Hara H, Enomoto Y, Nakamura K, Yoshitama T, Noro M, Moroi M, Sugi K, Nakamura M. Analysis of Heart Rate Variability in a Patient with Takotsubo Cardiomyopathy Syndrome on the Actual Onset Day. Int Heart J 2019; 60:1444-1447. [PMID: 31666453 DOI: 10.1536/ihj.19-092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
A healthy 73-year-old woman unpredictably developed Takotsubo cardiomyopathy syndrome (TTS) during Holter-electrocardiogram (ECG) recording. Thus, the complete chronological ECG data on the actual onset day of TTS were obtained. Many heart rate variability (HRV) parameters, including the low-frequency components (LF) and the high-frequency components (HF), on the actual onset day and in the healing phase were calculated. The interesting facts on the actual onset day were that the suppression of both LF and HF appeared earlier than the changes of the ECG waveform; and the LF/HF ratio remained within the normal range, although both LF and HF were markedly suppressed. The abnormality on the actual onset day was clear compared with the healing phase. It is noteworthy to obtain the chronological ECG data on the actual onset day of TTS in a healthy patient. The present data are unique in terms of being analyzed on the actual onset day. Although the HRV parameters, including LF and HF, were obviously abnormal, there is some skepticism about using HRV parameters as indices of cardiac autonomic activity. In the present case, it was concluded that the abnormality of cardiac autonomic activity contributed to the onset of TTS. These data are unlikely to ever be replicated, and we hope that this report helps elucidate the TTS mechanism.
Collapse
Affiliation(s)
- Shingo Kujime
- Division of Cardiovascular Medicine, Toho University Ohashi Medical Center
| | - Hidehiko Hara
- Division of Cardiovascular Medicine, Toho University Ohashi Medical Center
| | - Yoshinari Enomoto
- Division of Cardiovascular Medicine, Toho University Ohashi Medical Center
| | - Keijiro Nakamura
- Division of Cardiovascular Medicine, Toho University Ohashi Medical Center
| | | | - Mahito Noro
- Division of Cardiovascular Medicine, Toho University Sakura Medical Center
| | - Masao Moroi
- Division of Cardiovascular Medicine, Toho University Ohashi Medical Center
| | - Kaoru Sugi
- Division of Cardiovascular Medicine, Odawara Cardiovascular Hospital
| | - Masato Nakamura
- Division of Cardiovascular Medicine, Toho University Ohashi Medical Center
| |
Collapse
|
|
50
|
Silva AR, Magalhães R, Arantes C, Moreira PS, Rodrigues M, Marques P, Marques J, Sousa N, Pereira VH. Brain functional connectivity is altered in patients with Takotsubo Syndrome. Sci Rep 2019; 9:4187. [PMID: 30862828 PMCID: PMC6414524 DOI: 10.1038/s41598-019-40695-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Accepted: 02/21/2019] [Indexed: 12/28/2022] Open
Abstract
Takotsubo syndrome (TTS) is an acute, reversible cardiomyopathy. The central autonomic nervous system (ANS) is believed to play a role in this disease. The aim of the present study was to investigate the patterns of brain functional connectivity in a sample of patients who had experienced a previous episode of TTS. Brain functional connectivity, both at rest and in response to the stressful stimulus of topical cold stimulation, was explored using functional magnetic resonance imaging (fMRI), network-based statistics (NBS) and graph theory analysis (GTA) in a population consisting of eight patients with a previous episode of TTS and eight sex- and age-matched controls. At rest, a network characterized by increased connectivity in the TTS group compared to controls and comprising elements of the central ANS was identified. GTA revealed increased local efficiency, clustering and strength in regions of the bilateral hippocampus in subjects with a previous episode of TTS. When stressed by local exposure to cold, the TTS group differed significantly from both a pre-stress baseline interval and from the control group, showing increased connectivity in a network that included the left amygdala and the right insula. Based on the results, patients with TTS display a reorganization of cortical and subcortical networks, including areas associated with the emotional response and autonomic regulation. The findings tend to support the hypothesis that a deregulation of autonomic control at the central level plays a significant role in this syndrome.
Collapse
Affiliation(s)
- Ana Rita Silva
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's - PT Government Associate Laboratory, Braga, Portugal
| | - Ricardo Magalhães
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's - PT Government Associate Laboratory, Braga, Portugal
- Clinical Academic Center (2CA - Braga), Braga, Portugal
| | - Carina Arantes
- Cardiology Department, Hospital of Braga, Braga, Portugal
| | - Pedro Silva Moreira
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's - PT Government Associate Laboratory, Braga, Portugal
- Algoritmi Centre, University of Minho, Braga, Portugal
| | - Mariana Rodrigues
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's - PT Government Associate Laboratory, Braga, Portugal
- Clinical Academic Center (2CA - Braga), Braga, Portugal
| | - Paulo Marques
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's - PT Government Associate Laboratory, Braga, Portugal
- Clinical Academic Center (2CA - Braga), Braga, Portugal
| | - Jorge Marques
- Cardiology Department, Hospital of Braga, Braga, Portugal
| | - Nuno Sousa
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's - PT Government Associate Laboratory, Braga, Portugal
- Clinical Academic Center (2CA - Braga), Braga, Portugal
| | - Vitor Hugo Pereira
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
- ICVS/3B's - PT Government Associate Laboratory, Braga, Portugal.
- Clinical Academic Center (2CA - Braga), Braga, Portugal.
- Cardiology Department, Hospital of Braga, Braga, Portugal.
| |
Collapse
|