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Shah T, Zhang Z, Shah H, Fanaroff AC, Nathan AS, Parise H, Lutz J, Sugeng L, Bellumkonda L, Redfors B, Omerovic E, Petrie MC, Vora AN, Fiorilli PN, Kobayashi T, Ahmad Y, Forrest JK, Giri JS, Herrmann HC, Lansky AJ. Effect of Sodium-Glucose Cotransporter-2 Inhibitors on the Progression of Aortic Stenosis. JACC Cardiovasc Interv 2025; 18:738-748. [PMID: 39985508 DOI: 10.1016/j.jcin.2024.11.036] [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: 06/27/2024] [Revised: 11/21/2024] [Accepted: 11/26/2024] [Indexed: 02/24/2025]
Abstract
BACKGROUND Aortic stenosis (AS) is the leading cause of valvular heart disease-related morbidity and mortality, but there are no medical treatments to slow its progression. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have pleiotropic effects which could be disease modifying in AS. OBJECTIVES The purpose of this study was to determine if SGLT2i usage is associated with slower progression of AS. METHODS A target trial emulation comparing the effect of the initiation of SGLT2i compared with no SGLT2i in patients with nonsevere AS was performed using retrospective electronic medical record data from the Yale New Haven Health System from January 2016 to September 2022. Patients with native aortic valve sclerosis or nonsevere AS with at least 12 months of echocardiographic follow-up were included. Patients were excluded if they had an estimated glomerular filtration rate <30 mL/min/1.73 m2 or had initiated SGLT2i >1 year before the index echocardiogram. The prespecified primary outcome was progression to severe AS. RESULTS A total of 458 patients prescribed SGLT2i and 11,240 patients never prescribed SGLT2i were included. Patients were on SGLT2i for a median of 0.9 years. Patients on SGLT2i were younger and had higher rates of diabetes and chronic kidney disease. Patients on SGLT2i were more likely to have ejection fraction ≤40%. There were no differences between groups in baseline AS severity (66% sclerosis, 23% mild stenosis, and 11% moderate in overall cohort). Patients ever prescribed SGLT2i were less likely to progress to severe AS (HR: 0.61; 95% CI: 0.39-0.94; P = 0.03) with a progressively lower risk among patients on SGLT2i for >3, 6, and 12 months (HR: 0.54, 0.48, and 0.27, respectively). CONCLUSIONS This retrospective, multicenter, observational study suggests that SGLT2i may slow the progression of nonsevere AS.
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Affiliation(s)
- Tayyab Shah
- The Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA; Yale Cardiovascular Research Group, New Haven, Connecticut, USA
| | - Zhiyuan Zhang
- Yale Cardiovascular Research Group, New Haven, Connecticut, USA
| | | | | | - Ashwin S Nathan
- The Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Helen Parise
- Yale Cardiovascular Research Group, New Haven, Connecticut, USA
| | - John Lutz
- Yale New Haven Hospital, New Haven, Connecticut, USA
| | | | | | - Björn Redfors
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden; Cardiovascular Research Foundation, New York, New York, USA
| | - Elmir Omerovic
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Mark C Petrie
- School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom
| | - Amit N Vora
- Yale Cardiovascular Research Group, New Haven, Connecticut, USA
| | - Paul N Fiorilli
- The Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Taisei Kobayashi
- The Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Yousif Ahmad
- Yale Cardiovascular Research Group, New Haven, Connecticut, USA
| | - John K Forrest
- Yale Cardiovascular Research Group, New Haven, Connecticut, USA
| | - Jay S Giri
- The Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Howard C Herrmann
- The Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Otto CM, Newby DE, Hillis GS. Calcific Aortic Stenosis: A Review. JAMA 2024; 332:2014-2026. [PMID: 39527048 DOI: 10.1001/jama.2024.16477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Importance Calcific aortic stenosis (AS) restricts the aortic valve opening during systole due to calcification and fibrosis of either a congenital bicuspid or a normal trileaflet aortic valve. In the US, AS affects 1% to 2% of adults older than 65 years and approximately 12% of adults older than 75 years. Worldwide, AS leads to more than 100 000 deaths annually. Observations Calcific AS is characterized by aortic valve leaflet lipid infiltration and inflammation with subsequent fibrosis and calcification. Symptoms due to severe AS, such as exercise intolerance, exertional dyspnea, and syncope, are associated with a 1-year mortality rate of up to 50% without aortic valve replacement. Echocardiography can detect AS and measure the severity of aortic valve dysfunction. Although progression rates vary, once aortic velocity is higher than 2 m/s, progression to severe AS occurs typically within 10 years. Severe AS is defined by an aortic velocity 4 m/s or higher, a mean gradient 40 mm Hg or higher, or a valve area less than or equal to 1.0 cm2. Management of mild to moderate AS and asymptomatic severe AS consists of patient education about the typical progression of disease; clinical and echocardiographic surveillance at intervals of 3 to 5 years for mild AS, 1 to 2 years for moderate AS, and 6 to 12 months for severe AS; and treatment of hypertension, hyperlipidemia, and cigarette smoking as indicated. When a patient with severe AS develops symptoms, surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) is recommended, which restores an average life expectancy; in patients aged older than 70 years with a low surgical risk, 10-year all-cause mortality was 62.7% with TAVI and 64.0% with SAVR. TAVI is associated with decreased length of hospitalization, more rapid return to normal activities, and less pain compared with SAVR. However, evidence supporting TAVI for patients aged younger than 65 years and long-term outcomes of TAVI are less well defined than for SAVR. For patients with symptomatic severe AS, the 2020 American College of Cardiology/American Heart Association guideline recommends SAVR for individuals aged 65 years and younger, SAVR or TAVI for those aged 66 to 79 years, and TAVI for individuals aged 80 years and older or those with an estimated surgical mortality of 8% or higher. Conclusions Calcific AS is a common chronic progressive condition among older adults and is diagnosed via echocardiography. Symptomatic patients with severe AS have a mortality rate of up to 50% after 1 year, but treatment with SAVR or TAVI reduces mortality to that of age-matched control patients. The type and timing of valve replacement should be built on evidence-based guidelines, shared decision-making, and involvement of a multidisciplinary heart valve team.
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Affiliation(s)
- Catherine M Otto
- Division of Cardiology, University of Washington School of Medicine, Seattle
| | - David E Newby
- University of Edinburgh, British Heart Foundation Centre of Research Excellence, Royal Infirmary, Edinburgh, United Kingdom
| | - Graham S Hillis
- Department of Cardiology, Royal Perth Hospital and Medical School, University of Western Australia, Perth
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Mengi S, Januzzi JL, Cavalcante JL, Avvedimento M, Galhardo A, Bernier M, Rodés-Cabau J. Aortic Stenosis, Heart Failure, and Aortic Valve Replacement. JAMA Cardiol 2024; 9:1159-1168. [PMID: 39412797 DOI: 10.1001/jamacardio.2024.3486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2024]
Abstract
Importance Heart failure (HF) and aortic stenosis (AS) frequently coexist, presenting a complex clinical challenge due to their intertwined pathophysiology and associated high morbidity and mortality. Despite numerous advancements in transcatheter and surgical aortic valve replacement (AVR), HF decompensation remains the leading cause of cardiac rehospitalization and a major predictor of mortality in patients with AS, before or after AVR. This review aims to provide a comprehensive analysis of the interplay between AS and HF, delving into myocardial changes caused by stenotic insult, the impact of AVR on these changes, and the prevalence and contributing elements of HF before and after AVR. Observations The prevalence of HF remains high before and after AVR, particularly among patients with left ventricular dysfunction. Increased afterload from AS causes cardiac remodeling, which is initially benign but over time these changes become maladaptive, contributing to HF and increased mortality. The progression of HF is influenced by the degree of reverse cardiac remodeling, which can be affected by comorbid conditions, the hemodynamic performance of the valve prosthesis, and vascular stiffness. Several blood and imaging biomarkers offer insights into underlying AS pathophysiology, serving as mortality predictors and predicting HF in this patient population. Conclusions and Relevance HF development in AS is multifactorial and its link to left ventricular dysfunction is a complex process. Delineating the determinants of HF admissions in AS is crucial for identifying individuals at high risk. Identifying the early signs of left ventricular decompensation by using surrogate markers may be the key, even before left ventricular function becomes impaired. Translating multimodality imaging techniques and biomarkers into routine clinical practice for evaluating cardiac damage and integrating these markers with patient and procedural factors that affect HF before and after AVR can facilitate timely intervention, minimizing the likelihood of HF progression and influencing future guidelines.
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Affiliation(s)
- Siddhartha Mengi
- Quebec Heart & Lung Institute, Laval University, Quebec City, Quebec, Canada
| | - James L Januzzi
- Harvard Medical School, Boston, Massachusetts
- Massachusetts General Hospital, Boston, Massachusetts
- Baim Institute for Clinical Research, Boston, Massachusetts
| | - João L Cavalcante
- Minneapolis Heart Institute, Abbott Northwestern Hospital, Minneapolis, Minnesota
| | - Marisa Avvedimento
- Quebec Heart & Lung Institute, Laval University, Quebec City, Quebec, Canada
| | - Attilio Galhardo
- Quebec Heart & Lung Institute, Laval University, Quebec City, Quebec, Canada
| | - Mathieu Bernier
- Quebec Heart & Lung Institute, Laval University, Quebec City, Quebec, Canada
| | - Josep Rodés-Cabau
- Quebec Heart & Lung Institute, Laval University, Quebec City, Quebec, Canada
- Clínic Barcelona, Barcelona, Spain
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Chong T, Lan NSR, Courtney W, He A, Strange G, Playford D, Dwivedi G, Hillis GS, Ihdayhid AR. Medical Therapy to Prevent or Slow Progression of Aortic Stenosis: Current Evidence and Future Directions. Cardiol Rev 2024; 32:473-482. [PMID: 36961371 DOI: 10.1097/crd.0000000000000528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/25/2023]
Abstract
Degenerative aortic stenosis is a growing clinical problem owing to the high incidence in an aging population and its significant morbidity and mortality. Currently, aortic valve replacement remains the only treatment. Despite promising observational data, pharmacological management to slow or halt progression of aortic stenosis has remained elusive. Nevertheless, with a greater understanding of the mechanisms which underpin aortic stenosis, research has begun to explore novel treatment strategies. This review will explore the historical agents used to manage aortic stenosis and the emerging agents that are currently under investigation.
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Affiliation(s)
- Travis Chong
- From the Department of Cardiology, Fiona Stanley Hospital, Perth, Australia
- Harry Perkins Institute of Medical Research, Perth, Australia
| | - Nick S R Lan
- From the Department of Cardiology, Fiona Stanley Hospital, Perth, Australia
- Harry Perkins Institute of Medical Research, Perth, Australia
- Internal Medicine, Medical School, The University of Western Australia, Perth, Australia
| | - William Courtney
- Internal Medicine, Medical School, The University of Western Australia, Perth, Australia
- Department of Cardiology, Royal Perth Hospital, Perth, Australia
| | - Albert He
- From the Department of Cardiology, Fiona Stanley Hospital, Perth, Australia
- Harry Perkins Institute of Medical Research, Perth, Australia
| | - Geoff Strange
- School of Medicine, University of Notre Dame, Fremantle, Australia
| | - David Playford
- School of Medicine, University of Notre Dame, Fremantle, Australia
| | - Girish Dwivedi
- From the Department of Cardiology, Fiona Stanley Hospital, Perth, Australia
- Harry Perkins Institute of Medical Research, Perth, Australia
- Internal Medicine, Medical School, The University of Western Australia, Perth, Australia
| | - Graham S Hillis
- Internal Medicine, Medical School, The University of Western Australia, Perth, Australia
- Department of Cardiology, Royal Perth Hospital, Perth, Australia
| | - Abdul Rahman Ihdayhid
- From the Department of Cardiology, Fiona Stanley Hospital, Perth, Australia
- Harry Perkins Institute of Medical Research, Perth, Australia
- Curtin Medical School, Curtin University, Perth, Australia
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Takeji Y, Tada H, Taniguchi T, Sakata K, Kitai T, Shirai S, Takamura M. Current Management and Therapy of Severe Aortic Stenosis and Future Perspective. J Atheroscler Thromb 2024; 31:1353-1364. [PMID: 39111841 PMCID: PMC11456350 DOI: 10.5551/jat.rv22023] [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: 06/11/2024] [Accepted: 06/12/2024] [Indexed: 10/04/2024] Open
Abstract
Intervention for severe aortic stenosis (AS) has dramatically progressed since the introduction of transcatheter aortic valve replacement (TAVR). Decades ago, controversies existed regarding comparing clinical outcomes between TAVR and surgical aortic valve replacement (SAVR) in various risk profiles. Recently, we discussed the durability of transcatheter heart valves and their lifetime management after aortic valve replacement (AVR). Regarding the management of AS, we discuss the appropriate timing of intervention for severe aortic stenosis, especially in asymptomatic patients. In spite of dramatic progression of intervention for AS, there are no established medications available to prevent or slow the progression of AS at present. Basic research and genome studies have suggested several targets associated with the progression of aortic valve calcification. Randomized controlled trials evaluating the efficacy of medications to prevent AS progression are ongoing, which might lead to new strategies for AS management. In this review, we summarize the current management of AS and the drugs expected to prevent the progression of AS.
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Affiliation(s)
- Yasuaki Takeji
- Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
| | - Hayato Tada
- Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
| | - Tomohiko Taniguchi
- Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Kenji Sakata
- Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
| | - Takeshi Kitai
- Department of Heart Failure and Transplantation, National Cerebral and Cardiovascular Center, Osaka, Japan
| | - Shinichi Shirai
- Division of Cardiology, Kokura Memorial Hospital, Fukuoka, Japan
| | - Masayuki Takamura
- Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
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Le Nezet E, Marqueze-Pouey C, Guisle I, Clavel MA. Molecular Features of Calcific Aortic Stenosis in Female and Male Patients. CJC Open 2024; 6:1125-1137. [PMID: 39525825 PMCID: PMC11544188 DOI: 10.1016/j.cjco.2024.06.002] [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: 01/23/2024] [Accepted: 06/06/2024] [Indexed: 11/16/2024] Open
Abstract
Over the past 15 years, sex-related differences in aortic valve (AV) stenosis (AS) have been highlighted, affecting various aspects of AS, such as the pathophysiology, AV lesions, left ventricle remodelling, and outcomes. Female patients were found to present a more profibrotic pattern of leaflet remodelling and/or thickening, whereas male patients have a preponderance of calcification within stenosed leaflets. The understanding of these sex differences is still limited, owing to the underrepresentation of female patients in many basic and clinical research studies and trials. A better understanding of sex differences in the pathophysiology of AS may highlight new therapeutic targets that potentially could be sex-specific. This review aims to summarize sex-related differences in AS, as discovered from basic research experiments, covering aspects of the disease ranging from leaflet composition to signalling pathways, sex hormones, genetics and/or transcriptomics, and potential sex-adapted medical treatments.
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Affiliation(s)
- Emma Le Nezet
- Institut universitaire de cardiologie et pneumologie de Québec [Quebec Heart & Lung Institute], Université Laval, Québec City, Québec, Canada
| | - Chloé Marqueze-Pouey
- Institut universitaire de cardiologie et pneumologie de Québec [Quebec Heart & Lung Institute], Université Laval, Québec City, Québec, Canada
| | - Isabelle Guisle
- Institut universitaire de cardiologie et pneumologie de Québec [Quebec Heart & Lung Institute], Université Laval, Québec City, Québec, Canada
| | - Marie-Annick Clavel
- Institut universitaire de cardiologie et pneumologie de Québec [Quebec Heart & Lung Institute], Université Laval, Québec City, Québec, Canada
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7
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Derda AA, Abelmann M, Sonnenschein K, Sieweke JT, Bavendiek U, Bauersachs J, Thum T, Berliner D. Discontinuation of afterload-reducing drugs decreases left ventricular outflow tract obstruction in hypertrophic obstructive cardiomyopathy. Front Cardiovasc Med 2024; 11:1403422. [PMID: 39081367 PMCID: PMC11286422 DOI: 10.3389/fcvm.2024.1403422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Accepted: 07/02/2024] [Indexed: 08/02/2024] Open
Abstract
Background Hypertrophic cardiomyopathy (HCM), the most common genetic heart disease, is classified into hypertrophic non-obstructive and hypertrophic obstructive cardiomyopathy (HOCM). Patients with HOCM and coexisting heart failure or arterial hypertension are often prescribed afterload-reducing drugs. Although recommended in current guidelines, data on the direct effect of discontinuing afterload-reducing medication are scarce. This study aims to demonstrate the benefit of discontinuing afterload-reducing medication in HOCM patients. Methods This monocentric retrospective analysis included 24 patients with HOCM with afterload-reducing medication, including angiotensin-converting enzyme inhibitors, angiotensin-1 receptor blocker and dihydropyridine-calcium channel blocker, at their first outpatient visit. Effects of discontinuing this medication on LVOTO were examined compared to patients with persistent use despite medical advice. Results 16 patients discontinued their afterload-reducing drugs, resulting in a significant decrease in median LVOT gradient from 86.5 [60.5-109.3] mmHg to 61.5 [28.3-97.50] mmHg (p = 0.0004). In 6 patients, beta-blocker therapy was initiated simultaneously, or the dose was increased. Regardless, LVOT gradient reduction was also significant in the remaining 10 patients (p = 0.001). The gradient was not changed significantly in the 8 patients continuing their afterload-reducing medication. Conclusions Discontinuation of afterload-reducing drugs significantly decreases LVOTO. Our study underscores the significance of abstaining from afterload-reducing drugs in HOCM patients, particularly in patients with concomitant hypertension or heart failure. According to recently published European guidelines, HOCM patients should preferably be treated with beta-blockers or non-dihydropyridine-calcium channel blockers.
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Affiliation(s)
- Anselm A. Derda
- Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
- Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany
| | - Malin Abelmann
- Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
- Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany
| | - Kristina Sonnenschein
- Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
- Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany
| | - Jan-Thorben Sieweke
- Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
| | - Udo Bavendiek
- Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
| | - Johann Bauersachs
- Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
| | - Thomas Thum
- Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany
| | - Dominik Berliner
- Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
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Hmadeh S, Trimaille A, Matsushita K, Marchandot B, Carmona A, Zobairi F, Sato C, Kindo M, Hoang TM, Toti F, Zibara K, Hamade E, Schini-Kerth V, Kauffenstein G, Morel O. Human Aortic Stenotic Valve-Derived Extracellular Vesicles Induce Endothelial Dysfunction and Thrombogenicity Through AT1R/NADPH Oxidases/SGLT2 Pro-Oxidant Pathway. JACC Basic Transl Sci 2024; 9:845-864. [PMID: 39170957 PMCID: PMC11334416 DOI: 10.1016/j.jacbts.2024.02.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 02/22/2024] [Accepted: 02/22/2024] [Indexed: 08/23/2024]
Abstract
Pathological tissues release a variety of factors, including extracellular vesicles (EVs) shed by activated or apoptotic cells. EVs trapped within the native pathological valves may act as key mediators of valve thrombosis. Human aortic stenosis EVs promote activation of valvular endothelial cells, leading to endothelial dysfunction, and proadhesive and procoagulant responses.
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Affiliation(s)
- Sandy Hmadeh
- UR 3074 Translational Cardiovascular Medicine, CRBS, Strasbourg, France
| | - Antonin Trimaille
- UR 3074 Translational Cardiovascular Medicine, CRBS, Strasbourg, France
- Department of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France
| | - Kensuke Matsushita
- UR 3074 Translational Cardiovascular Medicine, CRBS, Strasbourg, France
- Department of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France
| | - Benjamin Marchandot
- Department of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France
| | - Adrien Carmona
- Department of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France
| | - Fatiha Zobairi
- UR 3074 Translational Cardiovascular Medicine, CRBS, Strasbourg, France
| | - Chisato Sato
- UR 3074 Translational Cardiovascular Medicine, CRBS, Strasbourg, France
- Department of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France
| | - Michel Kindo
- Department of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France
| | - Tam Minh Hoang
- Department of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France
| | - Florence Toti
- UR 3074 Translational Cardiovascular Medicine, CRBS, Strasbourg, France
| | - Kazem Zibara
- Faculty of Sciences, Laboratory of Genomics and Health, Lebanese University, Hadath, Lebanon
| | - Eva Hamade
- Faculty of Sciences, Laboratory of Genomics and Health, Lebanese University, Hadath, Lebanon
| | | | | | - Olivier Morel
- UR 3074 Translational Cardiovascular Medicine, CRBS, Strasbourg, France
- Department of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France
- Hanoï Medical University, Hanoi, Vietnam
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Desideri G, Pegoraro V, Cipelli R, Ripellino C, Miroddi M, Meto S, Gori M, Fabrizzi P. Extemporaneous combination therapy with nebivolol/ramipril for the treatment of hypertension: a real-world evidence study in Europe. Curr Med Res Opin 2024; 40:1093-1102. [PMID: 38832726 DOI: 10.1080/03007995.2024.2362276] [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: 02/22/2024] [Revised: 05/23/2024] [Accepted: 05/28/2024] [Indexed: 06/05/2024]
Abstract
OBJECTIVES To describe the clinical characteristics and treatment adherence in European adult hypertensive patients starting treatment with the extemporaneous combination of nebivolol and ramipril (NR-EXC). METHODS Retrospective database analysis of patients receiving NR-EXC treatment across five European countries (Italy, Germany, France, Poland, Hungary) over a period ranging from 3 to 9 years (until 30 June 2020) according to data availability for the different data sources. Patient demographics, comorbidities, and treatment adherence were evaluated. RESULTS We identified 592,472 patients starting NR-EXC. Most of them were over 60 years of age, with ramipril most commonly prescribed at 5 mg (from 30.0 to 57.2% of patients across the databases). Notable comorbidities included diabetes (19.2%) and dyslipidemia (18.2%). The study population was also highly subjected to polytherapy with antithrombotics, lipid-lowering agents, and other lowering blood pressure agents as the most co-prescribed medications, as resulted from Italian database. Up to 59% of the patients did not request a cardiologic visit during the study period. Adherence to therapy was low in 56.3% of the patients, and it was high only in 11.1% of them. CONCLUSIONS The combination of nebivolol and ramipril is frequently prescribed in Europe, but adherence to treatment is suboptimal. The transition to a single pill combination could enhance treatment adherence and streamline regimens, potentially leading to significant benefits. Improved adherence not only correlates with better blood pressure control but also reduces the risk of cardiovascular events, underscoring the importance of this development.
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Affiliation(s)
- Giovambattista Desideri
- Department of Clinical, Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | | | | | | | - Marco Miroddi
- A. Menarini Farmaceutica Internazionale S.r.l., Florence, Italy
| | - Suada Meto
- A. Menarini Industrie Farmaceutiche Riunite S.r.l., Florence, Italy
| | | | - Paolo Fabrizzi
- A. Menarini Industrie Farmaceutiche Riunite S.r.l., Florence, Italy
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10
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Kirchner J, Rudolph TK. [Conservative treatment of valvular heart disease in adults]. INNERE MEDIZIN (HEIDELBERG, GERMANY) 2024; 65:425-430. [PMID: 38436690 DOI: 10.1007/s00108-024-01676-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/02/2024] [Indexed: 03/05/2024]
Abstract
Currently, there is no specific medication approved for the treatment of valvular heart disease per se. Except for secondary mitral valve insufficiency and tricuspid valve insufficiency in pulmonary hypertension, drug therapy for higher-grade valvular heart disease is limited to diuretic therapy for symptom control. Conservative therapy for comorbidities and potential heart failure can be beneficial regardless of the specific valve lesion. In cases of aortic valve stenosis or insufficiency, controlling arterial hypertension is important. Patients with mitral valve stenosis benefit from rhythm and rate control. Diuretics can help reduce regurgitant volume in patients with primary mitral valve insufficiency and tricuspid valve insufficiency. In addition to drug therapy, maintaining functional capacity is crucial for the outcome of patients. Therefore, it is recommended to engage in active physical activity whenever possible, despite the presence of valvular heart disease.
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Affiliation(s)
- Johannes Kirchner
- Klinik für Allgemeine und Interventionelle Kardiologie/Angiologie, Herz- und Diabeteszentrum NRW, Ruhr-Universität Bochum, Georgstr. 11, 32545, Bad Oeynhausen, Deutschland
| | - Tanja K Rudolph
- Klinik für Allgemeine und Interventionelle Kardiologie/Angiologie, Herz- und Diabeteszentrum NRW, Ruhr-Universität Bochum, Georgstr. 11, 32545, Bad Oeynhausen, Deutschland.
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11
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Tajdini M, Behnoush AH, Pashang M, Jameie M, Khalaji A, Sadeghian S, Vasheghani-Farahani A, Poorhosseini H, Masoudkabir F, Hosseini K, Davoodi S, Sahebjam M, Barkhordari K, Ashraf H, Shafiei A, Karimi A. Heart surgery over two decades: what we have learned about results and changing risks. BMC Cardiovasc Disord 2024; 24:195. [PMID: 38580959 PMCID: PMC10996112 DOI: 10.1186/s12872-024-03860-9] [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: 01/25/2024] [Accepted: 03/25/2024] [Indexed: 04/07/2024] Open
Abstract
OBJECTIVES Using the cardiac surgery database is of high importance in referral centers and can lead to a better quality of care for patients. Tehran Heart Center (THC) is a cardiovascular referral center that was inaugurated in 2001. In this report, we aimed to present the third report of trends in patients' cardiovascular risk factors and surgical procedures from 2002 to 2021 that have been gathered for all THC patients. METHODS This serial cross-sectional study was conducted at Tehran Heart Center from 2002 to 2021. All patients undergoing cardiac surgeries were eligible to enter the study (N = 63,974). Those with miscellaneous types of surgeries were excluded (N = 9556). The distribution of cardiac surgeries (including isolated coronary artery bypass graft (CABG), isolated valve, and CABG + valve surgeries) and their respective in-hospital mortality were recorded. Furthermore, 20-year trends in the prevalence of various cardiovascular risk factors (CVRFs) among the following groups were evaluated: a) isolated CABG, b) aortic valve replacement/repair for aortic stenosis (AS/AVR/r), and c) isolated other valve surgeries (IVS). RESULTS A total of 54,418 patients (male: 70.7%, age: 62.7 ± 10.8 years) comprised the final study population, with 84.5% prevalence of isolated CABG. Overall, the AS/AVR/r group was in between the CABG and IVS groups concerning CVRFs distribution. Excluding some exceptions for the AS/AVR/r group (in which the small sample size (N = 909) precluded observing a clear trend), all studied CVRFs demonstrated an overall rising trend from 2002 to 2021 in all three groups. Regarding in-hospital mortality, the highest rate was recorded as 4.0% in 2020, while the lowest rate was 2.0% in 2001. CONCLUSIONS Isolated CABG remained the most frequent procedure in THC. Notable, increasing trends in CVRFs were observed during this 20-year period and across various types of cardiac surgeries, which highlights the clinical and policy-making implications of our findings.
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Affiliation(s)
- Masih Tajdini
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Hossein Behnoush
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mina Pashang
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mana Jameie
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Amirmohammad Khalaji
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Saeed Sadeghian
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Vasheghani-Farahani
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamidreza Poorhosseini
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Farzad Masoudkabir
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Kaveh Hosseini
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Saeed Davoodi
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Sahebjam
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Khosro Barkhordari
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Haleh Ashraf
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Akbar Shafiei
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Abbasali Karimi
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
- Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
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12
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Shelbaya K, Arthur V, Yang Y, Dorbala P, Buckley L, Claggett B, Skali H, Dufresne L, Yang TY, Engert JC, Thanassoulis G, Floyd J, Austin TR, Bortnick A, Kizer J, Freitas RCC, Singh SA, Aikawa E, Hoogeveen RC, Ballantyne C, Yu B, Coresh J, Blaha MJ, Matsushita K, Shah AM. Large-Scale Proteomics Identifies Novel Biomarkers and Circulating Risk Factors for Aortic Stenosis. J Am Coll Cardiol 2024; 83:577-591. [PMID: 38296402 DOI: 10.1016/j.jacc.2023.11.021] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 11/06/2023] [Accepted: 11/08/2023] [Indexed: 02/08/2024]
Abstract
BACKGROUND Limited data exist regarding risk factors for aortic stenosis (AS). The plasma proteome is a promising phenotype for discovery of novel biomarkers and potentially causative mechanisms. OBJECTIVES The aim of this study was to discover novel biomarkers with potentially causal associations with AS. METHODS We measured 4,877 plasma proteins (SomaScan aptamer-affinity assay) among ARIC (Atherosclerosis Risk In Communities) study participants in mid-life (visit 3 [V3]; n = 11,430; age 60 ± 6 years) and in late-life (V5; n = 4,899; age 76 ± 5 years). We identified proteins cross-sectionally associated with aortic valve (AV) peak velocity (AVmax) and dimensionless index by echocardiography at V5 and with incident AV-related hospitalization after V3 with the use of multivariable linear and Cox proportional hazard regression. We assessed associations of candidate proteins with changes in AVmax over 6 years and with AV calcification with the use of cardiac computed tomography, replicated analysis in an independent sample, performed Mendelian randomization, and evaluated gene expression in explanted human AV tissue. RESULTS Fifty-two proteins cross-sectionally were associated with AVmax and dimensionless index at V5 and with risk of incident AV-related hospitalization after V3. Among 3,413 participants in the Cardiovascular Health Study, 6 of those proteins were significantly associated with adjudicated moderate or severe AS, including matrix metalloproteinase 12 (MMP12), complement C1q tumor necrosis factor-related protein 1 (C1QTNF1), and growth differentiation factor-15. MMP12 was also associated with greater increase in AVmax over 6 years, greater degree of AV calcification, and greater expression in calcific compared with normal or fibrotic AV tissue. C1QTNF1 had consistent potential causal effects on both AS and AVmax according to Mendelian randomization analysis. CONCLUSIONS These findings identify MMP12 as a potential novel circulating biomarker of AS risk and C1QTNF1 as a new putative target to prevent AS progression.
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Affiliation(s)
| | | | - Yimin Yang
- Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Pranav Dorbala
- Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Leo Buckley
- Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Brian Claggett
- Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Hicham Skali
- Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Line Dufresne
- McGill University Health Centre, Montreal, Quebec, Canada
| | - Ta-Yu Yang
- McGill University Health Centre, Montreal, Quebec, Canada
| | - James C Engert
- McGill University Health Centre, Montreal, Quebec, Canada
| | | | - James Floyd
- Cardiovascular Health Research Unit, Seattle, Washington, USA
| | - Thomas R Austin
- Cardiovascular Health Research Unit, Seattle, Washington, USA
| | - Anna Bortnick
- Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York, USA
| | - Jorge Kizer
- Veterans Affairs Medical Center, San Francisco, California, USA
| | | | - Sasha A Singh
- Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Elena Aikawa
- Brigham and Women's Hospital, Boston, Massachusetts, USA
| | | | | | - Bing Yu
- University of Texas Health Science School of Public Health, Houston, Texas, USA
| | - Josef Coresh
- Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Michael J Blaha
- Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | | | - Amil M Shah
- Brigham and Women's Hospital, Boston, Massachusetts, USA; University of Texas Southwestern Medical Center, Dallas, Texas, USA.
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13
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Zhou Y, Yuan Z, Wang M, Zhang Z, Tan C, Yu J, Bi Y, Liao X, Zhou X, Ali Sheikh MS, Yang D. Liraglutide Attenuates Aortic Valve Calcification in a High-Cholesterol-Diet-Induced Experimental Calcific Aortic Valve Disease Model in Apolipoprotein E-Deficient Mice. J Cardiovasc Dev Dis 2023; 10:386. [PMID: 37754815 PMCID: PMC10531705 DOI: 10.3390/jcdd10090386] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 09/02/2023] [Accepted: 09/04/2023] [Indexed: 09/28/2023] Open
Abstract
BACKGROUND Calcific aortic valve disease (CAVD) is a significant cause of morbidity and mortality among elderly people. However, no effective medications have been approved to slow or prevent the progression of CAVD. Here, we examined the effect of liraglutide on aortic valve stenosis. METHODS Male Apoe-/- mice were fed with a high-cholesterol diet for 24 weeks to generate an experimental CAVD model and randomly assigned to a liraglutide treatment group or control group. Echocardiography and immunohistological analyses were performed to examine the aortic valve function and morphology, fibrosis, and calcium deposition. Plasma Glucagon-like peptide-1 (GLP-1) levels and inflammatory contents were measured via ELISA, FACS, and immunofluorescence. RNA sequencing (RNA-seq) was used to identify liraglutide-affected pathways and processes. RESULTS Plasma GLP-1 levels were reduced in the CAVD model, and liraglutide treatment significantly improved aortic valve calcification and functions and attenuated inflammation. RNA-seq showed that liraglutide affects multiple myofibroblastic and osteogenic differentiations or inflammation-associated biological states or processes in the aortic valve. Those liraglutide-mediated beneficial effects were associated with increased GLP-1 receptor (GLP-1R) expression. CONCLUSIONS Liraglutide blocks aortic valve calcification and may serve as a potential therapeutic drug for CAVD treatment.
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Affiliation(s)
- Yangzhao Zhou
- Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.Z.); (Z.Y.); (M.W.); (Z.Z.); (C.T.); (J.Y.); (Y.B.); (X.L.); (X.Z.)
| | - Zhaoshun Yuan
- Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.Z.); (Z.Y.); (M.W.); (Z.Z.); (C.T.); (J.Y.); (Y.B.); (X.L.); (X.Z.)
| | - Min Wang
- Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.Z.); (Z.Y.); (M.W.); (Z.Z.); (C.T.); (J.Y.); (Y.B.); (X.L.); (X.Z.)
| | - Zhiyuan Zhang
- Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.Z.); (Z.Y.); (M.W.); (Z.Z.); (C.T.); (J.Y.); (Y.B.); (X.L.); (X.Z.)
| | - Changming Tan
- Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.Z.); (Z.Y.); (M.W.); (Z.Z.); (C.T.); (J.Y.); (Y.B.); (X.L.); (X.Z.)
| | - Jiaolian Yu
- Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.Z.); (Z.Y.); (M.W.); (Z.Z.); (C.T.); (J.Y.); (Y.B.); (X.L.); (X.Z.)
| | - Yanfeng Bi
- Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.Z.); (Z.Y.); (M.W.); (Z.Z.); (C.T.); (J.Y.); (Y.B.); (X.L.); (X.Z.)
| | - Xiaobo Liao
- Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.Z.); (Z.Y.); (M.W.); (Z.Z.); (C.T.); (J.Y.); (Y.B.); (X.L.); (X.Z.)
| | - Xinmin Zhou
- Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.Z.); (Z.Y.); (M.W.); (Z.Z.); (C.T.); (J.Y.); (Y.B.); (X.L.); (X.Z.)
| | - Md Sayed Ali Sheikh
- Department of Internal Medicine, Cardiology, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia;
| | - Dafeng Yang
- Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.Z.); (Z.Y.); (M.W.); (Z.Z.); (C.T.); (J.Y.); (Y.B.); (X.L.); (X.Z.)
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14
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Bouhamida E, Morciano G, Pedriali G, Ramaccini D, Tremoli E, Giorgi C, Pinton P, Patergnani S. The Complex Relationship between Hypoxia Signaling, Mitochondrial Dysfunction and Inflammation in Calcific Aortic Valve Disease: Insights from the Molecular Mechanisms to Therapeutic Approaches. Int J Mol Sci 2023; 24:11105. [PMID: 37446282 DOI: 10.3390/ijms241311105] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 06/26/2023] [Accepted: 06/29/2023] [Indexed: 07/15/2023] Open
Abstract
Calcific aortic valve stenosis (CAVS) is among the most common causes of cardiovascular mortality in an aging population worldwide. The pathomechanisms of CAVS are such a complex and multifactorial process that researchers are still making progress to understand its physiopathology as well as the complex players involved in CAVS pathogenesis. Currently, there is no successful and effective treatment to prevent or slow down the disease. Surgical and transcatheter valve replacement represents the only option available for treating CAVS. Insufficient oxygen availability (hypoxia) has a critical role in the pathogenesis of almost all CVDs. This process is orchestrated by the hallmark transcription factor, hypoxia-inducible factor 1 alpha subunit (HIF-1α), which plays a pivotal role in regulating various target hypoxic genes and metabolic adaptations. Recent studies have shown a great deal of interest in understanding the contribution of HIF-1α in the pathogenesis of CAVS. However, it is deeply intertwined with other major contributors, including sustained inflammation and mitochondrial impairments, which are attributed primarily to CAVS. The present review aims to cover the latest understanding of the complex interplay effect of hypoxia signaling pathways, mitochondrial dysfunction, and inflammation in CAVS. We propose further hypotheses and interconnections on the complexity of these impacts in a perspective of better understanding the pathophysiology. These interplays will be examined considering recent studies that shall help us better dissect the molecular mechanism to enable the design and development of potential future therapeutic approaches that can prevent or slow down CAVS processes.
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Affiliation(s)
- Esmaa Bouhamida
- Translational Research Center, Maria Cecilia Hospital GVM Care & Research, 48033 Cotignola, Italy
| | - Giampaolo Morciano
- Translational Research Center, Maria Cecilia Hospital GVM Care & Research, 48033 Cotignola, Italy
- Department of Medical Sciences, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 44121 Ferrara, Italy
| | - Gaia Pedriali
- Translational Research Center, Maria Cecilia Hospital GVM Care & Research, 48033 Cotignola, Italy
| | - Daniela Ramaccini
- Translational Research Center, Maria Cecilia Hospital GVM Care & Research, 48033 Cotignola, Italy
| | - Elena Tremoli
- Translational Research Center, Maria Cecilia Hospital GVM Care & Research, 48033 Cotignola, Italy
| | - Carlotta Giorgi
- Department of Medical Sciences, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 44121 Ferrara, Italy
| | - Paolo Pinton
- Translational Research Center, Maria Cecilia Hospital GVM Care & Research, 48033 Cotignola, Italy
- Department of Medical Sciences, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 44121 Ferrara, Italy
| | - Simone Patergnani
- Translational Research Center, Maria Cecilia Hospital GVM Care & Research, 48033 Cotignola, Italy
- Department of Medical Sciences, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 44121 Ferrara, Italy
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15
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Prosperi-Porta G, Willner N, Messika-Zeitoun D. Aortic stenosis progression: Still a long way to go. Arch Cardiovasc Dis 2023; 116:113-116. [PMID: 36774270 DOI: 10.1016/j.acvd.2023.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 01/18/2023] [Indexed: 02/02/2023]
Affiliation(s)
- Graeme Prosperi-Porta
- Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7 Ontario, Canada
| | - Nadav Willner
- Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7 Ontario, Canada
| | - David Messika-Zeitoun
- Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7 Ontario, Canada.
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16
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Aziminia N, Nitsche C, Mravljak R, Bennett J, Thornton GD, Treibel TA. Heart failure and excess mortality after aortic valve replacement in aortic stenosis. Expert Rev Cardiovasc Ther 2023; 21:193-210. [PMID: 36877090 PMCID: PMC10069375 DOI: 10.1080/14779072.2023.2186853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 02/28/2023] [Indexed: 03/07/2023]
Abstract
INTRODUCTION In aortic stenosis (AS), the heart transitions from adaptive compensation to an AS cardiomyopathy and eventually leads to decompensation with heart failure. Better understanding of the underpinning pathophysiological mechanisms is required in order to inform strategies to prevent decompensation. AREAS COVERED In this review, we therefore aim to appraise the current pathophysiological understanding of adaptive and maladaptive processes in AS, appraise potential avenues of adjunctive therapy before or after AVR and highlight areas of further research in the management of heart failure post AVR. EXPERT OPINION Tailored strategies for the timing of intervention accounting for individual patient's response to the afterload insult are underway, and promise to guide better management in the future. Further clinical trials of adjunctive pharmacological and device therapy to either cardioprotect prior to intervention or promote reverse remodeling and recovery after intervention are needed to mitigate the risk of heart failure and excess mortality.
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Affiliation(s)
- Nikoo Aziminia
- Institute of Cardiovascular Science, University College London, London, England
- Barts Heart Centre, London, England
| | - Christian Nitsche
- Institute of Cardiovascular Science, University College London, London, England
- Barts Heart Centre, London, England
| | | | - Jonathan Bennett
- Institute of Cardiovascular Science, University College London, London, England
- Barts Heart Centre, London, England
| | - George D Thornton
- Institute of Cardiovascular Science, University College London, London, England
- Barts Heart Centre, London, England
| | - Thomas A Treibel
- Institute of Cardiovascular Science, University College London, London, England
- Barts Heart Centre, London, England
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17
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Calcific aortic valve disease: mechanisms, prevention and treatment. Nat Rev Cardiol 2023:10.1038/s41569-023-00845-7. [PMID: 36829083 DOI: 10.1038/s41569-023-00845-7] [Citation(s) in RCA: 75] [Impact Index Per Article: 37.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/01/2023] [Indexed: 02/26/2023]
Abstract
Calcific aortic valve disease (CAVD) is the most common disorder affecting heart valves and is characterized by thickening, fibrosis and mineralization of the aortic valve leaflets. Analyses of surgically explanted aortic valve leaflets have shown that dystrophic mineralization and osteogenic transition of valve interstitial cells co-occur with neovascularization, microhaemorrhage and abnormal production of extracellular matrix. Age and congenital bicuspid aortic valve morphology are important and unalterable risk factors for CAVD, whereas additional risk is conferred by elevated blood pressure and plasma lipoprotein(a) levels and the presence of obesity and diabetes mellitus, which are modifiable factors. Genetic and molecular studies have identified that the NOTCH, WNT-β-catenin and myocardin signalling pathways are involved in the control and commitment of valvular cells to a fibrocalcific lineage. Complex interactions between valve endothelial and interstitial cells and immune cells promote the remodelling of aortic valve leaflets and the development of CAVD. Although no medical therapy is effective for reducing or preventing the progression of CAVD, studies have started to identify actionable targets.
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18
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Guan Y, Kong X, Zhu H, Li H, Zhao L, Guo F, Lv Q. Association of renin-angiotensin system inhibitors use with short- and long-term mortality in patients with aortic stenosis: A systematic review and meta-analysis. Front Cardiovasc Med 2023; 9:917064. [PMID: 36756641 PMCID: PMC9901501 DOI: 10.3389/fcvm.2022.917064] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Accepted: 12/30/2022] [Indexed: 01/24/2023] Open
Abstract
Purpose The present study aimed to investigate the association of renin-angiotensin system inhibitors (RASi) with short- and long-term mortality in patients with aortic stenosis (AS). Methods A systematic search was performed in PubMed, Embase, and Cochrane library databases for relevant studies published before March 2022. Studies meeting the inclusion criteria were included to assess the effect of RASi on short-term (≤30 days) and long-term (≥1 year) mortality in patients with AS. Results A total of 11 studies were included in the meta-analysis. Our results demonstrated that RASi reduced short-term mortality (OR = 0.76, 95% CI 0.63-0.93, p = 0.008) after aortic valve replacement (AVR). Subgroup analysis revealed that RASi was still associated with lower short-term mortality after transcatheter aortic valve replacement (TAVR); however, the association was relatively weak in patients who underwent surgical aortic valve replacement (SAVR). For long-term mortality, the pooled OR was 1.04 (95% CI 0.88-1.24, p = 0.63) after sensitivity analysis in patients who did not undergo AVR. In addition, our study confirmed that RASi significantly reduced long-term mortality (OR = 0.57, 95% CI 0.44-0.74, p < 0.0001) in patients who underwent AVR. Subgroup analysis showed that both TAVR and SAVR groups treated with RASi had lower long-term mortality. Conclusion Renin-angiotensin system inhibitors did not change long-term mortality in AS patients who did not undergo AVR. However, RASi reduced short- and long-term mortality in patients who underwent AVR.
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Affiliation(s)
- Yang Guan
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Xiangyun Kong
- Department of General Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Huagang Zhu
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Hong Li
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China,*Correspondence: Hong Li,
| | - Lihan Zhao
- Department of General Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Fei Guo
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Qiang Lv
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
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19
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Lauder L, Mahfoud F, Azizi M, Bhatt DL, Ewen S, Kario K, Parati G, Rossignol P, Schlaich MP, Teo KK, Townsend RR, Tsioufis C, Weber MA, Weber T, Böhm M. Hypertension management in patients with cardiovascular comorbidities. Eur Heart J 2022:6808663. [DOI: 10.1093/eurheartj/ehac395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 06/23/2022] [Accepted: 07/08/2022] [Indexed: 11/09/2022] Open
Abstract
Abstract
Arterial hypertension is a leading cause of death globally. Due to ageing, the rising incidence of obesity, and socioeconomic and environmental changes, its incidence increases worldwide. Hypertension commonly coexists with Type 2 diabetes, obesity, dyslipidaemia, sedentary lifestyle, and smoking leading to risk amplification. Blood pressure lowering by lifestyle modifications and antihypertensive drugs reduce cardiovascular (CV) morbidity and mortality. Guidelines recommend dual- and triple-combination therapies using renin–angiotensin system blockers, calcium channel blockers, and/or a diuretic. Comorbidities often complicate management. New drugs such as angiotensin receptor-neprilysin inhibitors, sodium–glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and non-steroidal mineralocorticoid receptor antagonists improve CV and renal outcomes. Catheter-based renal denervation could offer an alternative treatment option in comorbid hypertension associated with increased sympathetic nerve activity. This review summarises the latest clinical evidence for managing hypertension with CV comorbidities.
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Affiliation(s)
- Lucas Lauder
- Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University , Kirrberger Str. 1, 66421 Homburg , Germany
| | - Felix Mahfoud
- Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University , Kirrberger Str. 1, 66421 Homburg , Germany
| | - Michel Azizi
- Université Paris Cité, INSERM CIC1418 , F-75015 Paris , France
- AP-HP, Hôpital Européen Georges-Pompidou, Hypertension Department, DMU CARTE , F-75015 Paris , France
- FCRIN INI-CRCT , Nancy , France
| | - Deepak L Bhatt
- Brigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School , Boston, MA , USA
| | - Sebastian Ewen
- Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University , Kirrberger Str. 1, 66421 Homburg , Germany
| | - Kazuomi Kario
- Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine , Tochigi , Japan
| | - Gianfranco Parati
- Department of Medicine and Surgery, Cardiology Unit, University of Milano-Bicocca and Istituto Auxologico Italiano, IRCCS , Milan , Italy
| | - Patrick Rossignol
- FCRIN INI-CRCT , Nancy , France
- Université de Lorraine, INSERM, Centre d'Investigations Cliniques - Plurithématique 14-33 and INSERM U1116 , Nancy , France
- CHRU de Nancy , Nancy , France
| | - Markus P Schlaich
- Dobney Hypertension Centre, Medical School—Royal Perth Hospital Unit, Medical Research Foundation, The University of Western Australia , Perth, WA , Australia
- Departments of Cardiology and Nephrology, Royal Perth Hospital , Perth, WA , Australia
| | - Koon K Teo
- Population Health Research Institute, McMaster University , Hamilton, ON , Canada
| | - Raymond R Townsend
- Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA , USA
| | - Costas Tsioufis
- National and Kapodistrian University of Athens, 1st Cardiology Clinic, Hippocratio Hospital , Athens , Greece
| | | | - Thomas Weber
- Department of Cardiology, Klinikum Wels-Grieskirchen , Wels , Austria
| | - Michael Böhm
- Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University , Kirrberger Str. 1, 66421 Homburg , Germany
- Cape Heart Institute (CHI), Faculty of Health Sciences, University of Cape Town , Cape Town , South Africa
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20
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Pipilas A, Martyn T, Lindenfeld J. Heart Failure Medical Therapy: A Review for Structural/Interventional Cardiologists. STRUCTURAL HEART : THE JOURNAL OF THE HEART TEAM 2022; 6:100082. [PMID: 37288122 PMCID: PMC10242575 DOI: 10.1016/j.shj.2022.100082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 07/11/2022] [Accepted: 07/22/2022] [Indexed: 11/06/2022]
Abstract
Medical therapy for heart failure (HF) has expanded rapidly in the last decade contributing to improved morbidity and mortality for patients living with HF. The indicated treatments have been traditionally stratified based on left ventricular ejection fraction. The optimization of HF medical therapy is important for interventional and structural cardiologists as HF remains among the most common causes of periprocedural hospitalization and death. Additionally, optimization of medical therapy for HF prior to the utilization of device-based therapies as well as enrollment in clinical trials is crucial. This review will serve to highlight medical therapy indicated across the left ventricular ejection fraction strata.
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Affiliation(s)
- Alexandra Pipilas
- Department of Cardiovascular Medicine, Boston University, Boston, Massachusetts, USA
| | - Trejeeve Martyn
- Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA
| | - JoAnn Lindenfeld
- Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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21
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Sun YX, Wang J, Zhu JH, Yuan W, Wu L. Follicular lymphoma with cardiac involvement in a 90-year-old patient: A case report. World J Clin Cases 2022; 10:10208-10213. [PMID: 36246818 PMCID: PMC9561574 DOI: 10.12998/wjcc.v10.i28.10208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 06/11/2022] [Accepted: 08/24/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The incidence of cardiac lymphoma is low, and it mainly occurs secondary to non-Hodgkin’s lymphoma, particularly diffuse large B-cell lymphoma. Here, we report a case of follicular lymphoma with cardiac involvement and severe heart failure as the sole clinical manifestation.
CASE SUMMARY A 90-year-old male patient was first admitted to our hospital due to an accidentally discovered painless mass in the right lower abdomen. A biopsy of the mass revealed a follicular lymphoma. Positron emission tomography-computed tomography confirmed mild pericardial effusion, and echocardiography showed no structural abnormalities with normal ejection fraction at the time of diagnosis. The patient refused our recommendation of chemotherapy and was re-admitted 4 mo later due to heart failure. A series of subsequent echocardiographic examinations showed thickening of the left ventricular walls and increasing pericardial effusion over the following 2 mo. His heart failure exacerbated despite all symptomatic and supportive treatments. He passed away after an episode of aspiration pneumonia.
CONCLUSION The diagnosis of cardiac lymphoma is difficult as its clinical manifestations are nonspecific, and prognosis is poor.
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Affiliation(s)
- Yi-Xuan Sun
- Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jia Wang
- Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Ji-Heng Zhu
- Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Wei Yuan
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Lin Wu
- Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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22
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Spilias N, Martyn T, Denby KJ, Harb SC, Popovic ZB, Kapadia SR. Left Ventricular Systolic Dysfunction in Aortic Stenosis: Pathophysiology, Diagnosis, Management, and Future Directions. STRUCTURAL HEART : THE JOURNAL OF THE HEART TEAM 2022; 6:100089. [PMID: 37288060 PMCID: PMC10242576 DOI: 10.1016/j.shj.2022.100089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 08/03/2022] [Accepted: 08/08/2022] [Indexed: 06/09/2023]
Abstract
Degenerative calcific aortic stenosis (AS) is the most common valvular heart disease and often co-exists with left ventricular (LV) systolic dysfunction at the time of diagnosis. Impaired LV systolic function has been associated with worse outcomes in the setting of AS, even after successful aortic valve replacement (AVR). Myocyte apoptosis and myocardial fibrosis are the 2 key mechanisms responsible for the transition from the initial adaptation phase of LV hypertrophy to the phase of heart failure with reduced ejection fraction. Novel advanced imaging methods, based on echocardiography and cardiac magnetic resonance imaging, can detect LV dysfunction and remodeling at an early and reversible stage, with important implications for the optimal timing of AVR especially in patients with asymptomatic severe AS. Furthermore, the advent of transcatheter AVR as a first-line treatment for AS with excellent procedural outcomes, and evidence that even moderate AS portends worse prognosis in heart failure with reduced ejection fraction patients, has raised the question of early valve intervention in this patient population. With this review, we describe the pathophysiology and outcomes of LV systolic dysfunction in the setting of AS, present imaging predictors of LV recovery after AVR, and discuss future directions in the treatment of AS extending beyond the traditional indications defined in the current guidelines.
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Affiliation(s)
| | | | | | | | | | - Samir R. Kapadia
- Address correspondence to: Samir Kapadia, MD, Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Mail Code J2-3, 9500 Euclid Ave, Cleveland, OH 44195.
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23
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Ito S, Oh JK. Aortic Stenosis: New Insights in Diagnosis, Treatment, and Prevention. Korean Circ J 2022; 52:721-736. [PMID: 36217595 PMCID: PMC9551229 DOI: 10.4070/kcj.2022.0234] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 09/07/2022] [Indexed: 12/02/2022] Open
Abstract
Aortic stenosis (AS) is one of the most common valvular heart diseases and the number of patients with AS is expected to increase globally as the older population is growing fast. Since the majority of patients are elderly, AS is no longer a simple valvular heart disease of left ventricular outflow obstruction but is accompanied by other cardiac and comorbid conditions. Because of the significant variations of the disease, identifying patients at high risk and even earlier detection of patients with AS before developing symptomatic severe AS is becoming increasingly important. With the proven of efficacy and safety of transcatheter aortic valve replacement (TAVR) in the severe AS population, there is a growing interest in applying TAVR in those with less than severe AS. A medical therapy to reduce or prevent the progression in AS is actively investigated by several randomized control trials. In this review, we will summarize the most recent findings in AS and discuss potential future management strategies of patients with AS.
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Affiliation(s)
- Saki Ito
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA
| | - Jae K Oh
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
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24
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Wang S, Lin X, Guan Y, Huang J. The clinical outcomes of reni-angiotensin system inhibitors for patients after transcatheter aortic valve replacement: A systematic review and meta-analysis. Front Cardiovasc Med 2022; 9:963731. [PMID: 36035924 PMCID: PMC9402980 DOI: 10.3389/fcvm.2022.963731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 07/18/2022] [Indexed: 11/13/2022] Open
Abstract
Aims The objective of our systematic reviews and meta-analysis is to evaluate the clinical outcomes of RAS inhibitors for patients after TAVR. Methods and results We performed a comprehensive search for Embase, Pubmed, and Cochrane databases from inception to May 1, 2022. The analysis of all outcomes was performed using the random-effects model. In total, 7 articles with a total of 32,585 patients (RAS inhibitor, N = 14,871; Controls, N = 17,714) were included in our study. There was a significantly lower rates of all-cause mortality (RR = 0.76, 95%Cl = 0.68 to 0.86, P < 0.01), cardiovascular death (RR = 0.66, 95%Cl = 0.59-0.74, P < 0.01) and HF readmission (RR = 0.87, 95%Cl = 0.80-0.94, P < 0.01) in patients with RAS inhibitors compared with controls. Patients with RAS inhibitors also had lower rates of all-cause mortality (RR = 0.82, 95%Cl = 0.76-0.89, P < 0.01) and cardiovascular death (RR = 0.73, 95%Cl, 0.62-0.85, P < 0.01) after propensity matching. Conclusions In conclusion, our systematic reviews and meta-analysis demonstrated that RAS inhibitors could improve the clinical outcomes for patients after TAVR. Further large and high-quality trials should be conducted to support the use of RAS inhibitors for patients after TAVR.
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Affiliation(s)
- Shuai Wang
- Department of Translation Medicine Center, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Department of Cardiology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaoxiao Lin
- The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yihong Guan
- The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jinyu Huang
- Department of Cardiology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
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25
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Phua K, Chew NWS, Kong WKF, Tan RS, Ye L, Poh KK. The mechanistic pathways of oxidative stress in aortic stenosis and clinical implications. Theranostics 2022; 12:5189-5203. [PMID: 35836811 PMCID: PMC9274751 DOI: 10.7150/thno.71813] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 06/03/2022] [Indexed: 02/06/2023] Open
Abstract
Despite the elucidation of the pathways behind the development of aortic stenosis (AS), there remains no effective medical treatment to slow or reverse its progress. Instead, the gold standard of care in severe or symptomatic AS is replacement of the aortic valve. Oxidative stress is implicated, both directly as well as indirectly, in lipid infiltration, inflammation and fibro-calcification, all of which are key processes underlying the pathophysiology of degenerative AS. This culminates in the breakdown of the extracellular matrix, differentiation of the valvular interstitial cells into an osteogenic phenotype, and finally, calcium deposition as well as thickening of the aortic valve. Oxidative stress is thus a promising and potential therapeutic target for the treatment of AS. Several studies focusing on the mitigation of oxidative stress in the context of AS have shown some success in animal and in vitro models, however similar benefits have yet to be seen in clinical trials. Statin therapy, once thought to be the key to the treatment of AS, has yielded disappointing results, however newer lipid lowering therapies may hold some promise. Other potential therapies, such as manipulation of microRNAs, blockade of the renin-angiotensin-aldosterone system and the use of dipeptidylpeptidase-4 inhibitors will also be reviewed.
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Affiliation(s)
- Kailun Phua
- Department of Cardiology, National University Heart Centre, National University Hospital, Singapore, Singapore
| | - Nicholas WS Chew
- Department of Cardiology, National University Heart Centre, National University Hospital, Singapore, Singapore,✉ Corresponding authors: A/Prof Kian-Keong Poh, . Dr Nicholas Chew, MBChB, MMED (Singapore), MRCP (UK) . Department of Cardiology, National University Heart Centre Singapore, National University Health System, Singapore. 1E Kent Ridge Rd, NUHS Tower Block, Level 9, Singapore 119228. Fax: (65) 68722998 Telephone: (65) 67722476
| | - William KF Kong
- Department of Cardiology, National University Heart Centre, National University Hospital, Singapore, Singapore
| | - Ru-San Tan
- Department of Cardiology, National Heart Centre Singapore, Singapore, 169609, Singapore
| | - Lei Ye
- National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore, 169609, Singapore
| | - Kian-Keong Poh
- Department of Cardiology, National University Heart Centre, National University Hospital, Singapore, Singapore,Yong Loo Lin School of Medicine, National University of Singapore, Singapore,✉ Corresponding authors: A/Prof Kian-Keong Poh, . Dr Nicholas Chew, MBChB, MMED (Singapore), MRCP (UK) . Department of Cardiology, National University Heart Centre Singapore, National University Health System, Singapore. 1E Kent Ridge Rd, NUHS Tower Block, Level 9, Singapore 119228. Fax: (65) 68722998 Telephone: (65) 67722476
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26
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The Haemodynamic and Pathophysiological Mechanisms of Calcific Aortic Valve Disease. Biomedicines 2022; 10:biomedicines10061317. [PMID: 35740339 PMCID: PMC9220142 DOI: 10.3390/biomedicines10061317] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 05/13/2022] [Accepted: 05/18/2022] [Indexed: 11/17/2022] Open
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27
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Tavenier AH, Nicolas J, Mehran R. The Final Word: Current Strategies for the Lifetime Management of Patients with Aortic Valve Stenosis. US CARDIOLOGY REVIEW 2022; 16:e13. [PMID: 39600830 PMCID: PMC11588165 DOI: 10.15420/usc.2022.07] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 03/07/2022] [Indexed: 11/04/2022] Open
Affiliation(s)
- Anne H Tavenier
- The Zena and Michael A Wiener Cardiovascular Institute, Icahn School of Medicine at Mount SinaiNew York, NY
- Department of Cardiology, Isala HospitalZwolle, the Netherlands
| | - Johny Nicolas
- The Zena and Michael A Wiener Cardiovascular Institute, Icahn School of Medicine at Mount SinaiNew York, NY
| | - Roxana Mehran
- The Zena and Michael A Wiener Cardiovascular Institute, Icahn School of Medicine at Mount SinaiNew York, NY
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28
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Greenberg HZE, Zhao G, Shah AM, Zhang M. Role of oxidative stress in calcific aortic valve disease and its therapeutic implications. Cardiovasc Res 2022; 118:1433-1451. [PMID: 33881501 PMCID: PMC9074995 DOI: 10.1093/cvr/cvab142] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Accepted: 04/19/2021] [Indexed: 12/12/2022] Open
Abstract
Calcific aortic valve disease (CAVD) is the end result of active cellular processes that lead to the progressive fibrosis and calcification of aortic valve leaflets. In western populations, CAVD is a significant cause of cardiovascular morbidity and mortality, and in the absence of effective drugs, it will likely represent an increasing disease burden as populations age. As there are currently no pharmacological therapies available for preventing, treating, or slowing the development of CAVD, understanding the mechanisms underlying the initiation and progression of the disease is important for identifying novel therapeutic targets. Recent evidence has emerged of an important causative role for reactive oxygen species (ROS)-mediated oxidative stress in the pathophysiology of CAVD, inducing the differentiation of valve interstitial cells into myofibroblasts and then osteoblasts. In this review, we focus on the roles and sources of ROS driving CAVD and consider their potential as novel therapeutic targets for this debilitating condition.
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Affiliation(s)
- Harry Z E Greenberg
- Department of Cardiology, Cardiovascular Division, King's College London British Heart Foundation Centre of Research Excellence, James Black Centre, 125 Coldharbour Lane, London SE5 9NU, UK
| | - Guoan Zhao
- Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, Heart Center of Xinxiang Medical University, Henan, China
| | - Ajay M Shah
- Department of Cardiology, Cardiovascular Division, King's College London British Heart Foundation Centre of Research Excellence, James Black Centre, 125 Coldharbour Lane, London SE5 9NU, UK
| | - Min Zhang
- Department of Cardiology, Cardiovascular Division, King's College London British Heart Foundation Centre of Research Excellence, James Black Centre, 125 Coldharbour Lane, London SE5 9NU, UK
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29
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Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, Capodanno D, Conradi L, De Bonis M, De Paulis R, Delgado V, Freemantle N, Gilard M, Haugaa KH, Jeppsson A, Jüni P, Pierard L, Prendergast BD, Rafael Sádaba J, Tribouilloy C, Wojakowski W. Guía ESC/EACTS 2021 sobre el diagnóstico y tratamiento de las valvulopatías. Rev Esp Cardiol 2022. [DOI: 10.1016/j.recesp.2021.11.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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30
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Dayawansa NH, Baratchi S, Peter K. Uncoupling the Vicious Cycle of Mechanical Stress and Inflammation in Calcific Aortic Valve Disease. Front Cardiovasc Med 2022; 9:783543. [PMID: 35355968 PMCID: PMC8959593 DOI: 10.3389/fcvm.2022.783543] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 02/15/2022] [Indexed: 12/24/2022] Open
Abstract
Calcific aortic valve disease (CAVD) is a common acquired valvulopathy, which carries a high burden of mortality. Chronic inflammation has been postulated as the predominant pathophysiological process underlying CAVD. So far, no effective medical therapies exist to halt the progression of CAVD. This review aims to outline the known pathways of inflammation and calcification in CAVD, focussing on the critical roles of mechanical stress and mechanosensing in the perpetuation of valvular inflammation. Following initiation of valvular inflammation, dysregulation of proinflammatory and osteoregulatory signalling pathways stimulates endothelial-mesenchymal transition of valvular endothelial cells (VECs) and differentiation of valvular interstitial cells (VICs) into active myofibroblastic and osteoblastic phenotypes, which in turn mediate valvular extracellular matrix remodelling and calcification. Mechanosensitive signalling pathways convert mechanical forces experienced by valve leaflets and circulating cells into biochemical signals and may provide the positive feedback loop that promotes acceleration of disease progression in the advanced stages of CAVD. Mechanosensing is implicated in multiple aspects of CAVD pathophysiology. The mechanosensitive RhoA/ROCK and YAP/TAZ systems are implicated in aortic valve leaflet mineralisation in response to increased substrate stiffness. Exposure of aortic valve leaflets, endothelial cells and platelets to high shear stress results in increased expression of mediators of VIC differentiation. Upregulation of the Piezo1 mechanoreceptor has been demonstrated to promote inflammation in CAVD, which normalises following transcatheter valve replacement. Genetic variants and inhibition of Notch signalling accentuate VIC responses to altered mechanical stresses. The study of mechanosensing pathways has revealed promising insights into the mechanisms that perpetuate inflammation and calcification in CAVD. Mechanotransduction of altered mechanical stresses may provide the sought-after coupling link that drives a vicious cycle of chronic inflammation in CAVD. Mechanosensing pathways may yield promising targets for therapeutic interventions and prognostic biomarkers with the potential to improve the management of CAVD.
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Affiliation(s)
- Nalin H. Dayawansa
- Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
- Department of Cardiology, Alfred Hospital, Melbourne, VIC, Australia
- Department of Medicine, Monash University, Melbourne, VIC, Australia
| | - Sara Baratchi
- Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
- School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia
- Department of Cardiometabolic Health, The University of Melbourne, Melbourne, VIC, Australia
| | - Karlheinz Peter
- Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
- Department of Cardiology, Alfred Hospital, Melbourne, VIC, Australia
- Department of Medicine, Monash University, Melbourne, VIC, Australia
- Department of Cardiometabolic Health, The University of Melbourne, Melbourne, VIC, Australia
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31
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Xiong T, Han S, Pu L, Zhang TC, Zhan X, Fu T, Dai YH, Li YX. Bioinformatics and Machine Learning Methods to Identify FN1 as a Novel Biomarker of Aortic Valve Calcification. Front Cardiovasc Med 2022; 9:832591. [PMID: 35295271 PMCID: PMC8918776 DOI: 10.3389/fcvm.2022.832591] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 01/28/2022] [Indexed: 12/14/2022] Open
Abstract
AimThe purpose of this study was to identify potential diagnostic markers for aortic valve calcification (AVC) and to investigate the function of immune cell infiltration in this disease.MethodsThe AVC data sets were obtained from the Gene Expression Omnibus. The identification of differentially expressed genes (DEGs) and the performance of functional correlation analysis were carried out using the R software. To explore hub genes related to AVC, a protein–protein interaction network was created. Diagnostic markers for AVC were then screened and verified using the least absolute shrinkage and selection operator, logistic regression, support vector machine-recursive feature elimination algorithms, and hub genes. The infiltration of immune cells into AVC tissues was evaluated using CIBERSORT, and the correlation between diagnostic markers and infiltrating immune cells was analyzed. Finally, the Connectivity Map database was used to forecast the candidate small molecule drugs that might be used as prospective medications to treat AVC.ResultsA total of 337 DEGs were screened. The DEGs that were discovered were mostly related with atherosclerosis and arteriosclerotic cardiovascular disease, according to the analyses. Gene sets involved in the chemokine signaling pathway and cytokine–cytokine receptor interaction were differently active in AVC compared with control. As the diagnostic marker for AVC, fibronectin 1 (FN1) (area the curve = 0.958) was discovered. Immune cell infiltration analysis revealed that the AVC process may be mediated by naïve B cells, memory B cells, plasma cells, activated natural killer cells, monocytes, and macrophages M0. Additionally, FN1 expression was associated with memory B cells, M0 macrophages, activated mast cells, resting mast cells, monocytes, and activated natural killer cells. AVC may be reversed with the use of yohimbic acid, the most promising small molecule discovered so far.ConclusionFN1 can be used as a diagnostic marker for AVC. It has been shown that immune cell infiltration is important in the onset and progression of AVC, which may benefit in the improvement of AVC diagnosis and treatment.
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Affiliation(s)
- Tao Xiong
- Cardiovascular Surgery, Yan'an Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China
| | - Shen Han
- Cardiovascular Surgery, Yan'an Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China
- Key Laboratory of Cardiovascular Disease of Yunnan Province, Yan'an Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China
| | - Lei Pu
- Cardiovascular Surgery, Yan'an Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China
- Key Laboratory of Cardiovascular Disease of Yunnan Province, Yan'an Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China
| | - Tian-Chen Zhang
- Cardiovascular Surgery, Yan'an Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China
| | - Xu Zhan
- Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Tao Fu
- Cardiovascular Surgery, Yan'an Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China
| | - Ying-Hai Dai
- Cardiovascular Surgery, Yan'an Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China
| | - Ya-Xiong Li
- Cardiovascular Surgery, Yan'an Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China
- Key Laboratory of Cardiovascular Disease of Yunnan Province, Yan'an Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China
- *Correspondence: Ya-Xiong Li ;
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32
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Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, Capodanno D, Conradi L, De Bonis M, De Paulis R, Delgado V, Freemantle N, Haugaa KH, Jeppsson A, Jüni P, Pierard L, Prendergast BD, Sádaba JR, Tribouilloy C, Wojakowski W. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. EUROINTERVENTION 2022; 17:e1126-e1196. [PMID: 34931612 PMCID: PMC9725093 DOI: 10.4244/eij-e-21-00009] [Citation(s) in RCA: 186] [Impact Index Per Article: 62.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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33
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Mazur P, Kopytek M, Ząbczyk M, Undas A, Natorska J. Towards Personalized Therapy of Aortic Stenosis. J Pers Med 2021; 11:1292. [PMID: 34945764 PMCID: PMC8708539 DOI: 10.3390/jpm11121292] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 11/23/2021] [Accepted: 11/29/2021] [Indexed: 12/18/2022] Open
Abstract
Calcific aortic stenosis (CAS) is the most common cause of acquired valvular heart disease in adults with no available pharmacological treatment to inhibit the disease progression to date. This review provides an up-to-date overview of current knowledge of molecular mechanisms underlying CAS pathobiology and the related treatment pathways. Particular attention is paid to current randomized trials investigating medical treatment of CAS, including strategies based on lipid-lowering and antihypertensive therapies, phosphate and calcium metabolism, and novel therapeutic targets such as valvular oxidative stress, coagulation proteins, matrix metalloproteinases, and accumulation of advanced glycation end products.
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Affiliation(s)
- Piotr Mazur
- Department of Cardiovascular Surgery, Mayo Clinic, Rochester, MN 55902, USA;
- Institute of Cardiology, Jagiellonian University Medical College, 80 Pradnicka St, 31-202 Kraków, Poland; (M.K.); (M.Z.); (A.U.)
| | - Magdalena Kopytek
- Institute of Cardiology, Jagiellonian University Medical College, 80 Pradnicka St, 31-202 Kraków, Poland; (M.K.); (M.Z.); (A.U.)
- Center for Research and Medical Technologies, John Paul II Hospital, 31-202 Kraków, Poland
| | - Michał Ząbczyk
- Institute of Cardiology, Jagiellonian University Medical College, 80 Pradnicka St, 31-202 Kraków, Poland; (M.K.); (M.Z.); (A.U.)
- Center for Research and Medical Technologies, John Paul II Hospital, 31-202 Kraków, Poland
| | - Anetta Undas
- Institute of Cardiology, Jagiellonian University Medical College, 80 Pradnicka St, 31-202 Kraków, Poland; (M.K.); (M.Z.); (A.U.)
- Center for Research and Medical Technologies, John Paul II Hospital, 31-202 Kraków, Poland
| | - Joanna Natorska
- Institute of Cardiology, Jagiellonian University Medical College, 80 Pradnicka St, 31-202 Kraków, Poland; (M.K.); (M.Z.); (A.U.)
- Center for Research and Medical Technologies, John Paul II Hospital, 31-202 Kraków, Poland
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Basile C, Fucile I, Lembo M, Manzi MV, Ilardi F, Franzone A, Mancusi C. Arterial Hypertension in Aortic Valve Stenosis: A Critical Update. J Clin Med 2021; 10:5553. [PMID: 34884254 PMCID: PMC8658702 DOI: 10.3390/jcm10235553] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Revised: 11/23/2021] [Accepted: 11/24/2021] [Indexed: 02/04/2023] Open
Abstract
Aortic stenosis (AS) is a very common valve disease and is associated with high mortality once it becomes symptomatic. Arterial hypertension (HT) has a high prevalence among patients with AS leading to worse left ventricle remodeling and faster degeneration of the valve. HT also interferes with the assessment of the severity of AS, leading to an underestimation of the real degree of stenosis. Treatment of HT in AS has not historically been pursued due to the fear of excess reduction in afterload without a possibility of increasing stroke volume due to the fixed aortic valve, but most recent evidence shows that several drugs are safe and effective in reducing BP in patients with HT and AS. RAAS inhibitors and beta-blockers provide benefit in selected populations based on their profile of pharmacokinetics and pharmacodynamics. Different drugs, on the other hand, have proved to be unsafe, such as calcium channel blockers, or simply not easy enough to handle to be recommended in clinical practice, such as PDE5i, MRA or sodium nitroprusside. The present review highlights all available studies on HT and AS to guide antihypertensive treatment.
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Affiliation(s)
| | | | | | | | | | | | - Costantino Mancusi
- Department of Advanced Biomedical Science, Federico II University of Naples, 80131 Naples, Italy; (C.B.); (I.F.); (M.L.); (M.V.M.); (F.I.); (A.F.)
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35
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Kraler S, Blaser MC, Aikawa E, Camici GG, Lüscher TF. Calcific aortic valve disease: from molecular and cellular mechanisms to medical therapy. Eur Heart J 2021; 43:683-697. [PMID: 34849696 DOI: 10.1093/eurheartj/ehab757] [Citation(s) in RCA: 106] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 09/12/2021] [Accepted: 10/20/2021] [Indexed: 12/12/2022] Open
Abstract
Calcific aortic valve disease (CAVD) is a highly prevalent condition that comprises a disease continuum, ranging from microscopic changes to profound fibro-calcific leaflet remodelling, culminating in aortic stenosis, heart failure, and ultimately premature death. Traditional risk factors, such as hypercholesterolaemia and (systolic) hypertension, are shared among atherosclerotic cardiovascular disease and CAVD, yet the molecular and cellular mechanisms differ markedly. Statin-induced low-density lipoprotein cholesterol lowering, a remedy highly effective for secondary prevention of atherosclerotic cardiovascular disease, consistently failed to impact CAVD progression or to improve patient outcomes. However, recently completed phase II trials provide hope that pharmaceutical tactics directed at other targets implicated in CAVD pathogenesis offer an avenue to alter the course of the disease non-invasively. Herein, we delineate key players of CAVD pathobiology, outline mechanisms that entail compromised endothelial barrier function, and promote lipid homing, immune-cell infiltration, and deranged phospho-calcium metabolism that collectively perpetuate a pro-inflammatory/pro-osteogenic milieu in which valvular interstitial cells increasingly adopt myofibro-/osteoblast-like properties, thereby fostering fibro-calcific leaflet remodelling and eventually resulting in left ventricular outflow obstruction. We provide a glimpse into the most promising targets on the horizon, including lipoprotein(a), mineral-binding matrix Gla protein, soluble guanylate cyclase, dipeptidyl peptidase-4 as well as candidates involved in regulating phospho-calcium metabolism and valvular angiotensin II synthesis and ultimately discuss their potential for a future therapy of this insidious disease.
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Affiliation(s)
- Simon Kraler
- Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland.,University Heart Center, Department of Cardiology, University Hospital, Rämistrasse 100, 8091 Zurich, Switzerland
| | - Mark C Blaser
- Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 3 Blackfan Street, Boston, MA 02115, USA
| | - Elena Aikawa
- Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 3 Blackfan Street, Boston, MA 02115, USA.,Center for Excellence in Vascular Biology, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Ave Louis Pasteur, NRB7, Boston, MA 02115, USA
| | - Giovanni G Camici
- Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland.,University Heart Center, Department of Cardiology, University Hospital, Rämistrasse 100, 8091 Zurich, Switzerland.,Department of Research and Education, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
| | - Thomas F Lüscher
- Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland.,Heart Division, Royal Brompton & Harefield Hospitals, Sydney Street, London SW3 6NP, UK.,National Heart and Lung Institute, Imperial College, Guy Scadding Building, Dovehouse Street, London SW3 6LY, UK
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36
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Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, Capodanno D, Conradi L, De Bonis M, De Paulis R, Delgado V, Freemantle N, Gilard M, Haugaa KH, Jeppsson A, Jüni P, Pierard L, Prendergast BD, Sádaba JR, Tribouilloy C, Wojakowski W. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur J Cardiothorac Surg 2021; 60:727-800. [PMID: 34453161 DOI: 10.1093/ejcts/ezab389] [Citation(s) in RCA: 346] [Impact Index Per Article: 86.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
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37
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Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, Capodanno D, Conradi L, De Bonis M, De Paulis R, Delgado V, Freemantle N, Gilard M, Haugaa KH, Jeppsson A, Jüni P, Pierard L, Prendergast BD, Sádaba JR, Tribouilloy C, Wojakowski W. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J 2021; 43:561-632. [PMID: 34453165 DOI: 10.1093/eurheartj/ehab395] [Citation(s) in RCA: 2902] [Impact Index Per Article: 725.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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38
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Jin XY, Petrou M, Hu JT, Nicol ED, Pepper JR. Challenges and opportunities in improving left ventricular remodelling and clinical outcome following surgical and trans-catheter aortic valve replacement. Front Med 2021; 15:416-437. [PMID: 34047933 DOI: 10.1007/s11684-021-0852-7] [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: 10/17/2020] [Accepted: 02/20/2021] [Indexed: 11/26/2022]
Abstract
Over the last half century, surgical aortic valve replacement (SAVR) has evolved to offer a durable and efficient valve haemodynamically, with low procedural complications that allows favourable remodelling of left ventricular (LV) structure and function. The latter has become more challenging among elderly patients, particularly following trans-catheter aortic valve implantation (TAVI). Precise understanding of myocardial adaptation to pressure and volume overloading and its responses to valve surgery requires comprehensive assessments from aortic valve energy loss, valvular-vascular impedance to myocardial activation, force-velocity relationship, and myocardial strain. LV hypertrophy and myocardial fibrosis remains as the structural and morphological focus in this endeavour. Early intervention in asymptomatic aortic stenosis or regurgitation along with individualised management of hypertension and atrial fibrillation is likely to improve patient outcome. Physiological pacing via the His-Purkinje system for conduction abnormalities, further reduction in para-valvular aortic regurgitation along with therapy of angiotensin receptor blockade will improve patient outcome by facilitating hypertrophy regression, LV coordinate contraction, and global vascular function. TAVI leaflet thromboses require anticoagulation while impaired access to coronary ostia risks future TAVI-in-TAVI or coronary interventions. Until comparable long-term durability and the resolution of TAVI related complications become available, SAVR remains the first choice for lower risk younger patients.
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Affiliation(s)
- Xu Yu Jin
- Surgical Echo-Cardiology Services, Oxford Heart Centre, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 9DU, UK.
- Cardiac Surgical Physiology and Genomics Group, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.
| | - Mario Petrou
- Department of Cardiac Surgery, Royal Brompton Hospital, London, SW3 6NP, UK
- National Heart and Lung Institute, Imperial College London, London, SW3 6LY, UK
| | - Jiang Ting Hu
- Cardiac Surgical Physiology and Genomics Group, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK
| | - Ed D Nicol
- National Heart and Lung Institute, Imperial College London, London, SW3 6LY, UK
- Department of Cardiology, Royal Brompton Hospital, London, SW3 6NP, UK
| | - John R Pepper
- Department of Cardiac Surgery, Royal Brompton Hospital, London, SW3 6NP, UK
- National Heart and Lung Institute, Imperial College London, London, SW3 6LY, UK
- NIHR Imperial Biomedical Research Centre, London, W2 1NY, UK
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Hypertension in aortic stenosis: a focused review and recommendations for clinical practice. J Hypertens 2021; 38:1211-1219. [PMID: 32205564 DOI: 10.1097/hjh.0000000000002426] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
: In patients with aortic stenosis, the presence of hypertension negatively affects the hemodynamic severity of the stenosis, and worsens adverse left ventricular remodeling. It accelerates the progression of the stenosis and is associated with worse prognosis. Proper management of hypertension is thus crucial but there are concerns about the safety and efficacy of antihypertensive medications as well as uncertainty about optimal blood pressure (BP) targets and their impact on left ventricular mass regression and survival benefits. In the present review, we discuss these issues based on the evidence available in the current literature. Focus is first directed on the consequences of a persistently elevated BP before and after surgical aortic valve replacement or transcatheter valve implantation, and the clinical significance of an abnormal BP response during exercise in patients with significant aortic stenosis. Available data on use of antihypertensive drugs are then critically addressed, the conclusion being that calcium channel blockers may be associated with lower survival, and that diuretics may have disadvantages in patients with left ventricular hypertrophy and smaller left ventricular cavity dimensions, β-blockers may be well tolerated and a better choice for patients with concomitant coronary artery disease and arrhythmias. Renin--angiotensin system blockers improve survival given either before or after valve intervention. Emphasis is placed on the fact that evidence is not derived from randomized trials but only from observational studies. Finally, we discuss the optimal SBP level to reach in patients with aortic stenosis. Again, randomized trials are not available but observational evidence suggests that values between 130 and 139 mmHg systolic and 70-90 mmHg diastolic might represent the best option, and lower BP targets should probably be avoided.
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40
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Chen S, Redfors B, Nazif T, Kirtane A, Crowley A, Ben-Yehuda O, Kapadia S, Finn MT, Goel S, Lindman BR, Alu MC, Chau KH, Thourani VH, Vahl TP, Douglas PS, Kodali SK, Leon MB. Impact of renin-angiotensin system inhibitors on clinical outcomes in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement: an analysis of from the PARTNER 2 trial and registries. Eur Heart J 2021; 41:943-954. [PMID: 31711153 DOI: 10.1093/eurheartj/ehz769] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 07/08/2019] [Accepted: 10/15/2019] [Indexed: 01/09/2023] Open
Abstract
AIMS Left ventricular pressure overload is associated with activation of the cardiac renin-angiotensin system, which may contribute to myocardial fibrosis and worse clinical outcomes. We sought to assess the association between treatment with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) at baseline and clinical outcomes in patients with symptomatic, severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) in the PARTNER 2 trial and registries. METHODS AND RESULTS A total of 3979 intermediate, high, or prohibitive risk patients who underwent TAVR in the PARTNER 2 trial and registries (excluding the valve in valve registry) were included in the study. Clinical outcomes at 2 years were compared according to baseline ACEI/ARB treatment status using Kaplan-Meier event rates and study-stratified multivariable Cox proportional hazards regression models. Sensitivity analysis was conducted using propensity score matching. Of 3979 patients who were included in the current analysis, 1736 (43.6%) were treated and 2243 (56.4%) were not treated with ACEI/ARB at baseline. Treatment with ACEI/ARB was associated with lower 2-year all-cause mortality (18.6% vs. 27.5%, P < 0.0001), cardiovascular mortality (12.3% vs. 17.9%, P < 0.0001), and non-cardiovascular mortality (7.2% vs. 11.7%, P < 0.0001). Angiotensin-converting enzyme inhibitor/ARB treatment at baseline remained independently associated with a lower hazard of 2-year all-cause and cardiovascular mortality after multivariable adjustment, and propensity score matching. CONCLUSION In a large cohort of patients with severe symptomatic AS from the PARTNER 2 trial and registries, ACEI/ARB treatment at baseline was independently associated with a lower risk of 2-year all-cause and cardiovascular mortality.
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Affiliation(s)
- Shmuel Chen
- Cardiovascular Research Foundation, 1700 Broadway, Floor 9, New York, NY 10019, USA.,Center for Interventional Vascular Therapy, Columbia University Irving Medical Center/ NewYork-Presbyterian Hospital, 161 Ft. Washington Ave. HIP-6, New York, NY 10032, USA
| | - Bjorn Redfors
- Cardiovascular Research Foundation, 1700 Broadway, Floor 9, New York, NY 10019, USA.,Center for Interventional Vascular Therapy, Columbia University Irving Medical Center/ NewYork-Presbyterian Hospital, 161 Ft. Washington Ave. HIP-6, New York, NY 10032, USA.,Department of Cardiology, Sahlgrenska University Hospital, Bruna Straket 16, 413 45 Gothenburg, Sweden
| | - Tamim Nazif
- Center for Interventional Vascular Therapy, Columbia University Irving Medical Center/ NewYork-Presbyterian Hospital, 161 Ft. Washington Ave. HIP-6, New York, NY 10032, USA
| | - Ajay Kirtane
- Center for Interventional Vascular Therapy, Columbia University Irving Medical Center/ NewYork-Presbyterian Hospital, 161 Ft. Washington Ave. HIP-6, New York, NY 10032, USA
| | - Aaron Crowley
- Cardiovascular Research Foundation, 1700 Broadway, Floor 9, New York, NY 10019, USA
| | - Ori Ben-Yehuda
- Cardiovascular Research Foundation, 1700 Broadway, Floor 9, New York, NY 10019, USA
| | - Samir Kapadia
- Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA
| | - Matthew T Finn
- Center for Interventional Vascular Therapy, Columbia University Irving Medical Center/ NewYork-Presbyterian Hospital, 161 Ft. Washington Ave. HIP-6, New York, NY 10032, USA
| | - Sachin Goel
- Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA
| | - Brian R Lindman
- Structural Heart and Valve Center, Cardiovascular Medicine Division, Vanderbilt University Medical Center, 1161 21st Ave S., Nashville, TN 37232, USA
| | - Maria C Alu
- Cardiovascular Research Foundation, 1700 Broadway, Floor 9, New York, NY 10019, USA.,Center for Interventional Vascular Therapy, Columbia University Irving Medical Center/ NewYork-Presbyterian Hospital, 161 Ft. Washington Ave. HIP-6, New York, NY 10032, USA
| | - Katherine H Chau
- Center for Interventional Vascular Therapy, Columbia University Irving Medical Center/ NewYork-Presbyterian Hospital, 161 Ft. Washington Ave. HIP-6, New York, NY 10032, USA
| | - Vinod H Thourani
- Department of Cardiac Surgery, Piedmont Heart Institute, 95 Collier Road NW, Atlanta, GA 30309, USA
| | - Torsten P Vahl
- Center for Interventional Vascular Therapy, Columbia University Irving Medical Center/ NewYork-Presbyterian Hospital, 161 Ft. Washington Ave. HIP-6, New York, NY 10032, USA
| | - Pamela S Douglas
- Duke Clinical Research Institute, Duke University School of Medicine, 300 W Morgan St, Durham NC 27701, USA
| | - Susheel K Kodali
- Center for Interventional Vascular Therapy, Columbia University Irving Medical Center/ NewYork-Presbyterian Hospital, 161 Ft. Washington Ave. HIP-6, New York, NY 10032, USA
| | - Martin B Leon
- Cardiovascular Research Foundation, 1700 Broadway, Floor 9, New York, NY 10019, USA.,Center for Interventional Vascular Therapy, Columbia University Irving Medical Center/ NewYork-Presbyterian Hospital, 161 Ft. Washington Ave. HIP-6, New York, NY 10032, USA
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41
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Xu C, Xu J, Yang J. Safety and efficacy of angiotensin-converting enzyme inhibitors in aortic stenosis: A protocol for systematic review and meta-analysis. Medicine (Baltimore) 2021; 100:e25537. [PMID: 33847680 PMCID: PMC8052040 DOI: 10.1097/md.0000000000025537] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 03/25/2021] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Although there are many studies showing potential benefit in aortic stenosis (AS) patients taking angiotensin-converting enzyme inhibitors (ACEI), but these studies are subject to significant selection and other biases, making the results challenging to interpret. Furthermore, the evidence on the use of ACEI in AS patients has not been reviewed systematically; we thus conducted this protocol assess the clinical effectiveness and safety of ACEI for patients with AS. METHODS The following search terms will be used in PUBMED, Scopus, EMBASE, and Cochrane Library databases on May, 2021, as the search algorithm: (angiotensin-converting enzyme inhibitors) OR (ACEI) AND (aortic stenosis) OR (AS). Two searchers will independently draft and carry out the search strategy, and the third member will further complete it. The studies on cohort study focusing on assessing the efficacy of ACEI on AS patients will be included in our meta-analysis. At least one of the following outcomes should have been measured: left ventricular mass, exercise tolerance, B-type natriuretic peptide, adverse event, functional outcomes, and aortic valve area. All outcomes are pooled on random-effect model. A P value of <.05 is considered to be statistically significant. RESULTS The results of this research will be delivered in a peer-reviewed journal. CONCLUSION Depending on the previous studies, we assumed that ACEI could possibly improve the clinical symptoms and outcomes of symptomatic AS. SYSTEMATIC REVIEW REGISTRATION NUMBER 10.17605/OSF.IO/G9KPT.
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Barry AR, Wang EHZ. Therapeutic Controversies in the Medical Management of Valvular Heart Disease. Ann Pharmacother 2021; 55:1379-1385. [PMID: 33550851 PMCID: PMC8495308 DOI: 10.1177/1060028021992329] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Objective: To evaluate the evidence for common therapeutic controversies in the medical management of valvular heart disease (VHD). Data Sources: A literature search of PubMed (inception to December 2020) was performed using the terms angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and aortic stenosis (AS); and adrenergic β-antagonists and aortic valve regurgitation (AR) or mitral stenosis (MS). Study Selection and Data Extraction: Randomized controlled trials (RCTs) and meta-analyses conducted in humans and published in English that reported ≥1 clinical outcome were included. Data Synthesis: Nine articles were included: 3 RCTs and 1 meta-analysis for ACE inhibitors/ARBs in AS, 1 RCT for β-blockers in AR, and 4 RCTs for β-blockers in MS. Evidence suggests that ACE inhibitors/ARBs do not increase the risk of adverse outcomes in patients with AS but may delay valve replacement. β-Blockers do not appear to worsen outcomes in patients with chronic AR and may improve left-ventricular function in patients with a reduced ejection fraction. β-Blockers do not improve and may actually worsen exercise tolerance in patients with MS in sinus rhythm. Relevance to Patient Care and Clinical Practice: ACE inhibitors/ARBs and β-blockers can likely be safely used in patients with AS or AR, respectively, who have a compelling indication. There is insufficient evidence to recommend routine use of β-blockers in patients with MS without atrial fibrillation. Conclusions: Common beliefs about the medical treatment of VHD are not supported by high-quality data. There remains a need for larger-scale RCTs in the medical management of VHD.
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Affiliation(s)
- Arden R Barry
- University of British Columbia, Vancouver, BC, Canada.,Chilliwack General Hospital, Lower Mainland Pharmacy Services, Chilliwack, BC, Canada
| | - Erica H Z Wang
- St Paul's Hospital, Lower Mainland Pharmacy Services, Vancouver, BC, Canada
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Gill H, Chehab O, Allen C, Patterson T, Redwood S, Rajani R, Prendergast B. The advantages, pitfalls and limitations of guideline-directed medical therapy in patients with valvular heart disease. Eur J Heart Fail 2021; 23:1325-1333. [PMID: 33421239 DOI: 10.1002/ejhf.2097] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 12/15/2020] [Accepted: 01/01/2021] [Indexed: 11/05/2022] Open
Abstract
Heart failure is an inevitable end-stage consequence of significant valvular heart disease (VHD) that is left untreated and increasingly encountered in an ageing society. Recent advances in transcatheter procedures and improved outcomes after valve surgery mean that intervention can (and should) be considered in all patients - even the elderly and those with multiple comorbidities - at earlier stages of the natural history of primary VHD, before the onset of irreversible left ventricular dysfunction (and frequently before the onset of symptoms). All patients with known VHD should be monitored carefully in the setting of a heart valve clinic and those who meet guideline criteria for surgical or transcatheter intervention referred for intervention without delay. High quality evidence for the use of medical therapy in VHD is limited and achieving target doses in an elderly and comorbid population frequently challenging. Furthermore, determining whether the valve or ventricle is the principal disease driver is crucial (although the distinction is not always binary, and often unclear). Guideline-directed medical therapy remains the mainstay of treatment for secondary mitral regurgitation - although up to 50% of patients may fail to respond and should be considered for cardiac resynchronization, transcatheter or surgical valve intervention. Early and definitive management strategies are essential and should be overseen by a specialist Heart Team that includes a Heart Failure specialist. In this article, we provide an evidence-based summary of approaches to the medical treatment of VHD and clinical guidance for the best management of patients in situations where high quality evidence is lacking.
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Affiliation(s)
- Harminder Gill
- School of Bioengineering and Imaging Sciences, King's College London, London, UK
| | - Omar Chehab
- Cardiovascular Department, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Christopher Allen
- Cardiovascular Department, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Tiffany Patterson
- Cardiovascular Department, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Simon Redwood
- Cardiovascular Department, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Ronak Rajani
- School of Bioengineering and Imaging Sciences, King's College London, London, UK.,Cardiovascular Department, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Bernard Prendergast
- Cardiovascular Department, Guy's and St Thomas' NHS Foundation Trust, London, UK
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Sun Y, Li J, Li G, Fan R, Luo J. Impact of renin-angiotensin system inhibitors on outcomes after transcatheter aortic valve replacement: A meta-analysis. Catheter Cardiovasc Interv 2021; 97:E88-E94. [PMID: 32311209 DOI: 10.1002/ccd.28899] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 03/10/2020] [Accepted: 03/30/2020] [Indexed: 11/06/2022]
Abstract
OBJECTIVES We aimed to evaluate the impact of renin-angiotensin system (RAS) inhibitors on outcomes after transcatheter aortic valve replacement (TAVR). BACKGROUND The impact of RAS inhibitors on outcomes after TAVR was unclear. METHODS A systematic review of articles comparing outcomes of patients using and not using RAS inhibitors after TAVR was performed through PubMed, Embase, and Cochrane. Primary outcome was midterm all-cause mortality. Risk ratios (RRs) were calculated with the corresponding 95% confidence interval using random effect models. RESULTS Five studies with 23,319 patients were included. Patients treated with RAS inhibitors had lower midterm all-cause mortality after TAVR than those without RAS inhibitors in both the unmatched (13.3 vs. 17.2%, RR 0.77, p = .005) and propensity score matched cohorts (13.5 vs 16.2%, RR 0.83, p < .001). Cardiovascular mortality (10.4 vs. 15.6%, RR 0.68, p < .001), rate of heart failure readmission (12.2 vs. 14.5%, RR 0.80, p = .006), and new-onset atrial fibrillation (14.0 vs. 23.7%, RR 0.73, p = .003) were also lower with RAS inhibitors. No difference was found between two groups regarding cerebrovascular events, myocardial infarction, major bleeding, major vascular complications, acute kidney injury, permanent pacemaker implantation, and moderate/severe paravalvular aortic regurgitation. CONCLUSIONS RAS inhibitors were associated with lower midterm all-cause mortality after TAVR.
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Affiliation(s)
- Yinghao Sun
- Department of Cardiology, Vascular Center, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong, People's Republic of China
| | - Jie Li
- Department of Cardiology, Vascular Center, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong, People's Republic of China
| | - Guang Li
- Department of Cardiology, Vascular Center, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong, People's Republic of China
| | - Ruixin Fan
- Department of Cardiovascular surgery, Vascular Center, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong, People's Republic of China
| | - Jianfang Luo
- Department of Cardiology, Vascular Center, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong, People's Republic of China
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45
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Treating Moderate Aortic Stenosis: Too Early or Too Late? CURRENT TREATMENT OPTIONS IN CARDIOVASCULAR MEDICINE 2021. [DOI: 10.1007/s11936-020-00884-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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46
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Medical management of symptomatic severe aortic stenosis in patients non-eligible for transcatheter aortic valve implantation. J Geriatr Cardiol 2020; 17:704-709. [PMID: 33343649 PMCID: PMC7729185 DOI: 10.11909/j.issn.1671-5411.2020.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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47
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Donato M, Ferri N, Lupo MG, Faggin E, Rattazzi M. Current Evidence and Future Perspectives on Pharmacological Treatment of Calcific Aortic Valve Stenosis. Int J Mol Sci 2020; 21:ijms21218263. [PMID: 33158204 PMCID: PMC7663524 DOI: 10.3390/ijms21218263] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 10/31/2020] [Accepted: 11/02/2020] [Indexed: 02/07/2023] Open
Abstract
Calcific aortic valve stenosis (CAVS), the most common heart valve disease, is characterized by the slow progressive fibro-calcific remodeling of the valve leaflets, leading to progressive obstruction to the blood flow. CAVS is an increasing health care burden and the development of an effective medical treatment is a major medical need. To date, no effective pharmacological therapies have proven to halt or delay its progression to the severe symptomatic stage and aortic valve replacement represents the only available option to improve clinical outcomes and to increase survival. In the present report, the current knowledge and latest advances in the medical management of patients with CAVS are summarized, placing emphasis on lipid-lowering agents, vasoactive drugs, and anti-calcific treatments. In addition, novel potential therapeutic targets recently identified and currently under investigation are reported.
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Affiliation(s)
- Maristella Donato
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35122 Padova, Italy; (M.D.); (N.F.); (M.G.L.)
| | - Nicola Ferri
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35122 Padova, Italy; (M.D.); (N.F.); (M.G.L.)
| | - Maria Giovanna Lupo
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35122 Padova, Italy; (M.D.); (N.F.); (M.G.L.)
| | - Elisabetta Faggin
- Department of Medicine—DIMED, University of Padova, 35122 Padova, Italy;
| | - Marcello Rattazzi
- Department of Medicine—DIMED, University of Padova, 35122 Padova, Italy;
- Correspondence: ; Tel.: +39-0498-211-867 or +39-0422-322-207
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Sen J, Chung E, Neil C, Marwick T. Antihypertensive therapies in moderate or severe aortic stenosis: a systematic review and meta-analysis. BMJ Open 2020; 10:e036960. [PMID: 33020089 PMCID: PMC7537451 DOI: 10.1136/bmjopen-2020-036960] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 08/19/2020] [Accepted: 08/25/2020] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Hypertension confers a poor prognosis in moderate or severe aortic stenosis (AS), however, antihypertensive therapy (AHT) is often not prescribed due to the perceived deleterious effects of vasodilation and negative inotropes. OBJECTIVE To assess the efficacy and safety outcomes of AHT in adults with moderate or severe AS. DESIGN Systematic review and meta-analysis. DATA SOURCES The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and grey literature were searched without language restrictions up to 9 September 2019. STUDY ELIGIBILITY CRITERIA, APPRAISAL AND SYNTHESIS METHODS Two independent reviewers performed screening, data extraction and risk of bias assessments from a systematic search of observational studies and randomised controlled trials comparing AHT with a placebo or no AHT in adults with moderate or severe AS for any parameter of efficacy and safety outcomes. Conflicts were resolved by the third reviewer. Meta-analysis with pooled effect sizes using random-effects model, were estimated in R. MAIN OUTCOME MEASURES Mortality, Left Ventricular (LV) Mass Index, systolic blood pressure, diastolic blood pressure and LV ejection fraction RESULTS: From 3025 publications, 31 studies (26 500 patients) were included in the qualitative synthesis and 24 studies in the meta-analysis. AHT was not associated with mortality when all studies were pooled, but heterogeneity was substantial across studies. The effect size of AHT differed according to drug class. Renin-angiotensin-aldosterone system inhibitors (RAASi) were associated with reduced risk of mortality (Pooled HR 0.58, 95% CI 0.43 to 0.80, p=0.006), The differences in changes of haemodynamic or echocardiographic parameters from baseline with and without AHT did not reach statistical significance. CONCLUSION AHT appears safe, is well tolerated. RAASi were associated with clinical benefit in patients with moderate or severe AS.
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Affiliation(s)
- Jonathan Sen
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
- Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia
| | - Erin Chung
- Graduate Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada
| | - Christopher Neil
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
- Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia
| | - Thomas Marwick
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
- Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia
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Goel SS, Kleiman NS, Zoghbi WA, Reardon MJ, Kapadia SR. Renin-Angiotensin System Blockade in Aortic Stenosis: Implications Before and After Aortic Valve Replacement. J Am Heart Assoc 2020; 9:e016911. [PMID: 32893727 PMCID: PMC7727008 DOI: 10.1161/jaha.120.016911] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Aortic stenosis (AS) is a common valvular heart disease in the aging population that is characterized by a variable period of asymptomatic phase before development of symptoms and severe AS. Mortality and morbidity is substantial even after aortic valve replacement, in part related to persistent left ventricular hypertrophy, diastolic dysfunction, and heart failure. Renin-angiotensin system (RAS) blockade therapy is associated with modulation of adverse left ventricular remodeling, reduction in myocardial hypertrophy, and fibrosis, resulting in clinical improvements in patients with congestive heart failure There are emerging data to suggest benefit of RAS blockade in patients with AS before and after AVR with regard to potentially slower progression of aortic valve calcification, left ventricular mass and survival benefit in favor of RAS blockade group before AVR, and also survival benefit in patients after AVR. We review the available data to understand the role of RAS blockade before AVR and in patients undergoing surgical AVR and transcatheter AVR. There are significant survival advantages of RAS inhibition in patients with AS undergoing surgical AVR or transcatheter AVR. On the basis of existing literature, adequately powered randomized trials are needed to evaluate the role of RAS inhibition in patients with AS.
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Affiliation(s)
- Sachin S. Goel
- Department of CardiologyHouston Methodist DeBakey Heart & Vascular CenterHoustonTX
| | - Neal S. Kleiman
- Department of CardiologyHouston Methodist DeBakey Heart & Vascular CenterHoustonTX
| | - William A. Zoghbi
- Department of CardiologyHouston Methodist DeBakey Heart & Vascular CenterHoustonTX
| | - Michael J. Reardon
- Department of Cardiovascular SurgeryHouston Methodist DeBakey Heart & Vascular CenterHoustonTX
| | - Samir R. Kapadia
- Department of Cardiovascular MedicineCleveland ClinicClevelandOH
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Sia CH, Ho JSY, Chua JJL, Tan BYQ, Ngiam NJ, Chew N, Sim HW, Chen R, Lee CH, Yeo TC, Kong WKF, Poh KK. Comparison of Clinical and Echocardiographic Features of Asymptomatic Patients With Stenotic Bicuspid Versus Tricuspid Aortic Valves. Am J Cardiol 2020; 128:210-215. [PMID: 32534732 DOI: 10.1016/j.amjcard.2020.05.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 05/01/2020] [Accepted: 05/04/2020] [Indexed: 12/31/2022]
Abstract
The clinical and imaging differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients with medically managed asymptomatic moderate-to-severe aortic stenosis (AS) have not been studied previously. We aim to characterize these differences and their clinical outcomes in this study. A retrospective observational study was conducted on 836 consecutive cases of isolated asymptomatic moderate-to-severe AS, with median follow-up of 3.4 years. Clinical and echocardiographic characteristics were compared between BAV and TAV patients. Subgroup analysis stratified by AS severity were performed. Survival analysis of all-cause mortality was performed using Kaplan-Meier curves and Cox proportional hazards model. Compared to BAV patients, TAV patients were older (76 ± 11 vs 55 ± 16 years, p <0.001) and had more co-morbidities including hypertension (78% vs 56%; p <0.001), diabetes (41% vs 24%; p <0.001), and chronic kidney disease (20% vs 3%; p = 0.001). TAV patients had less severe aortic valve disease than BAV patients, with a higher aortic valve area index (0.71 ± 0.20 cm2/m2 vs 0.61 ± 0.18 cm2/m2, p <0.001) and less aortic dilation (sinotubular junction: 23.7 ± 4.0 mm vs 26.9 ± 4.8 mm, p <0.001; mid-ascending aorta: 31.4 ± 4.7 mm vs 36.3 ± 6.3 mm, p <0.001). TAV patients were more likely to have eccentric left ventricular hypertrophy and less likely to have a normal geometry (p = 0.003). Competing risk analysis identified increased age (hazard ratio 1.03, 95% confidence interval 1.02 to 1.05, p <0.001) and LVEF (hazard ratio 0.98, 95% confidence interval 0.97 to 0.99, p <0.001) as independent risk factors of all-cause mortality. Valve morphology was not a significant independent risk factor for aortic valve replacement or mortality. In conclusion, asymptomatic TAV patients had more cardiovascular risk factors, less severe aortic valve disease, less sinotubular and mid-ascending aortic dilation, more severe LV remodeling.
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