To evaluate the utility of higher dose intracoronary acetylcholine (ACh) during invasive coronary function testing (CFT) in women with suspected ischemia and no obstructive coronary artery disease (INOCA) for detection of epicardial vasospasm, relation to quality of life (QoL) and the presence of scar by late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMRI).

CFT is an established method for diagnosis of coronary microvascular dysfunction (CMD). The utility of epicardial vasospasm provocation testing with higher dose ACh infusion is not fully understood.

Women with suspected INOCA undergoing invasive CFT were enrolled in the Women's Ischemia Syndrome Evaluation-Pre-Heart Failure with Preserved Ejection Fraction (WISE Pre-HFpEF) study (NCT03876223). Incremental infusions of 0.364, 36.4 μg and 108 μg ACh were used for vasospasm provocation. Vasospasm was defined as ≥75 % artery diameter reduction compared to post-nitroglycerin diameter and related to QoL and LGE on CMRI.

Among 73 women (56 ± 11 years), epicardial vasospasm was detected in 17 (23 %). Among women with vasospasm, the vast majority (94 %) had coronary endothelial dysfunction and few (12 %) had other abnormal CFT measures. Those with vasospasm had more nocturnal angina symptoms, calcium channel blocker use, poorer QoL (all p = 0.001) and disease perception (p = 0.02) than those without. LGE scar by CMRI was not associated with vasospasm (p = 0.22).

Among women with suspected INOCA, intracoronary Ach spasm testing provoked epicardial vasospasm in one fourth. Women with epicardial vasospasm overwhelmingly had concomitant endothelial dysfunction, worse QoL but not more frequent myocardial scar on CMRI.

Sex differences in ST-segment elevation myocardial infarction (STEMI) due to obstructive coronary artery disease (CAD) are well-established, but limited research exists on sex differences in STEMI patients with nonobstructive coronary arteries (MINOCA) and MINOCA mimickers.

We analyzed 8560 consecutive STEMI patients, enrolled in the Midwest STEMI Consortium from 2003 to 2020. Patients with non-obstructive CAD were classified into MINOCA (defined as < 50% coronary artery stenosis and confirmed or suspected coronary artery plaque disruption, epicardial coronary spasm, or coronary embolism/thrombosis) and MINOCA mimickers (takotsubo cardiomyopathy, myocarditis, or non-ischemic cardiomyopathy). The primary outcome was 5-year all-cause mortality.

Of the 8560 patients, 409 (4.8%) had non-obstructive CAD, including 120 (1.4%) MINOCA and 289 (3.4%) MINOCA mimickers. Females were more likely to have MINOCA and MINOCA mimickers (49.2% and 56.4%, respectively). There were no significant sex differences in in-hospital or 5-year mortality in MINOCA, but females with MINOCA mimickers had higher unadjusted 5-year mortality (HR 2.90, 95% CI 1.53-5.53). After adjusting for age and comorbidities, the long-term mortality risk was similar between sexes (adjusted HR 1.16, 95% CI: 0.61-2.24). Females with obstructive CAD had higher 5-year mortality in unadjusted models (HR 1.66, 95% CI 1.48, 1.86), but the difference was not significant after adjustment (adjusted HR 1.1, 95% CI: 0.98-1.24).

Our findings highlight important sex-based differences in the prevalence, treatment, and long-term outcomes of STEMI patients with MINOCA, MINOCA mimickers, and obstructive CAD. Despite clinical disparities, mortality risks were similar across sexes after adjusting for comorbidities.

Myocardial infarction without obstructive coronary artery disease (MINOCA) is a challenging condition which requires appropriate management and therapy. Although specific guidelines and recommendations for this condition have been introduced, there are few data about management implementation over time. The aim of this study is to compare two cohorts of patients affected by suspected MINOCA to assess the temporal trends change in the clinical characteristics and management.

Two patient cohorts were retrospectively selected from a single centre (Cardiology Department of Perugia University Hospital) and compared to investigate the differences in characteristics and management before and after the release of 2018 MINOCA guidelines. The Group included patients enrolled from January 2006 to December 2014, and the Group 2 from July 1st, 2020, to July 31st, 2023.

Group 1 included 150 patients and Group 2 83 patients. Compared to group 1, group 2 showed higher prevalence of hypercholesterolemia (57 % vs 27 % p < 0,001), prior acute myocardial infarction (23 % vs 5 %, p <0,001), preserved left ventricular ejection fraction (90 % vs 67 %, p = 0,03), use of cardiovascular magnetic resonance (27 % vs 0 %,p < 0.001), prescription of beta-blockers (69 % vs 31 %,p < 0.001), calcium channel blockers (46 % vs 16 %, p < 0.001), statins (81 % vs 59 %, p = 0.03) and a less frequent occurrence of ST-elevation on admission ECG (9 % vs 24 %, p = 0.005), prescription of dual antiplatelet therapy (20 % vs 58 %, p < 0.001) and nitrates (12 % vs 54 %, p < 0.001).

In the present study, characteristics and management of patients with suspected MINOCA has significantly changed over time. However, discrepancies with guidelines recommendation still exist and implementation strategies are needed to fill this gap and improve clinical practice.

Cardiomyopathies are a significant cause of heart failure, arrhythmia, and cardiac morbidity in the general population. Cardiovascular magnetic resonance (CMR) is a valuable tool for the diagnostic work-up of patients with acute cardiac events.

This study evaluated the diagnostic value of CMR and the yield of cardiomyopathies in hospitalized cardiac patients with acute presentation.

A retrospective analysis was conducted with 535 consecutive hospitalized patients who underwent CMR at Hippokration Hospital, Athens, Greece, to identify a subset of scans performed on an urgent basis of hospitalized patients. Demographic data, causes of admission, CMR findings, and plasma cardiac biomarkers (hs-Troponin I, NT-proBNP, and CRP) were systematically recorded.

Out of the initial 535 CMR scans evaluated, a further analysis was conducted with 104 patients who were in hospital and underwent CMR on an urgent basis. From the total population of hospitalized patients, 33% had CMR findings indicative of underlying cardiomyopathy, with dilated cardiomyopathy being the most common subtype (36%), followed by arrhythmogenic cardiomyopathy (27%), hypertrophic cardiomyopathy (15%), or other subtypes (e.g., cardiac amyloidosis, sarcoidosis, endomyocardial fibrosis, EGPA, or unclassified). CMR led to the reclassification of the initial diagnosis into that of underlying cardiomyopathy in 32% of cases. The highest reclassification rate was observed within the subgroup with heart failure (71%), followed by that of acute myocardial infarction/ischemic heart disease (24%) and myocarditis (22%).

CMR imaging effectively contributed to the differential diagnosis of hospitalized patients with acute cardiac events that remained without a definitive diagnosis after their initial work-up and uncovered underlying cardiomyopathy in almost one-third of this cohort.

Pathological mechanisms of myocardial infarction with non-obstructive coronary arteries (MINOCA) are heterogeneous, with an unknown impact on prognosis, and often remain unrecognised in clinical practice. This study aimed to evaluate the prevalence and prognostic impact of pathological findings by invasive coronary angiography (ICA), optical coherence tomography (OCT), and coronary function testing in MINOCA.

Studies published until August 2023 were searched on PubMed and SCOPUS and included if reporting the prevalence of patients with non-obstructive coronary arteries (NObs-CA; 1-49% coronary stenosis) versus normal coronary arteries (NCA; 0% coronary stenosis) by ICA, pathological findings by OCT, and/or coronary vasomotor tests in MINOCA. Newcastle-Ottawa Scale was used for quality assessment. The pooled prevalence of pathological findings was estimated with random-effects models. Pooled risk ratios (RRs) with 95% CIs of all-cause death, MI and the composite of both in patients with NObs-CA versus NCA were calculated at short-term (<1 month), 1-year and long-term follow-up (> 1 year).

Forty-five studies including 17 539 patients were analysed. The pooled prevalence of NObs-CA at ICA was 53% (95% CI 0.47 to 0.60). OCT showed acute pathological findings in 62% (95% CI 0.44 to 0.78) of patients and coronary vasomotor tests were positive in 49% (95% CI 0.31 to 0.67). NObs-CA compared with NCA was associated with an increased 1-year risk of all-cause death or MI (RR=1.49 (95% CI 1.17 to 1.90)) and MI alone (RR=1.80 (95% CI 1.26 to 2.59)), whereas the risk of all-cause death was comparable. Similar results were seen at long-term, but not at short-term follow-up.

Stratification of MINOCA into NObs-CA versus NCA has prognostic value. OCT and vasospasm testing, often informative about the pathological mechanism of MINOCA, should be part of an invasive diagnostic algorithm.

CRD42023468183.

Clinical characteristics and outcomes of patients with myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) are not fully understood, particularly in Japan.

We enrolled a total of 8881 patients with acute MI from the Miyagi Acute Myocardial Infarction Registry Study (2012-2020), with a median age of 69 years. Among them, 239 patients (2.7%) were diagnosed with MINOCA. Compared with those with MI with obstructive coronary artery disease (MI-CAD), patients with MINOCA were more often women, had a higher incidence of non-ST-segment-elevation MI and a lower prevalence of dyslipidemia. Compared with patients with MI-CAD, patients with MINOCA in all age groups (<59, 60-69, 70-79, >80 years of age) had a higher incidence of non-ST-segment-elevation MI. Additionally, those ≤59 years of age were more often women and had a lower prevalence of diabetes and dyslipidemia. In-hospital mortality increased with age in patients with MI-CAD (3.9% for <59 years of age, 5.6% for 60-69 years of age, 8.3% for 70-79 years of age, and 15.2% for >80 years of age; P<0.01), but not in patients with MINOCA (4.5%, 7.4%, 6.0%, and 9.6%, respectively; P=0.36). Compared with patients with MI-CAD, patients with MINOCA had lower in-hospital mortality for Killip class IV (40.7% versus 20.0%; adjusted odds ratio [OR], 0.31 [95% CI, 0.10-0.94]; P=0.04) and renal dysfunction (20.0% versus 7.1%; adjusted OR, 0.29 [95% CI, 0.09-0.96]; P=0.04).

Patients with MINOCA exhibit distinct clinical characteristics and outcomes compared with those with MI-CAD, particularly in terms of age, sex, prevalence of comorbidities, and in-hospital mortality. These findings underscore the importance of tailored clinical approaches for patients with MINOCA.

Although platelets play a critical pathogenic role in myocardial infarction (MI), few studies have characterized the MI platelet transcriptome in the acute or chronic setting in women. We report that transcripts associated with the actin cytoskeleton, Rho family GTPases, mitochondrial dysfunction, and inflammatory signaling are enriched in platelets from MI patients in the acute setting (n = 40, MI; n = 38, control) and do not significantly change over time. Furthermore, 79 platelet genes chronically elevated or suppressed after MI are associated with future cardiovascular events in an independent high-risk cohort (n = 135). Compared with women with MI with nonobstructive coronary arteries, platelets from women with MI and obstructive coronary artery disease were enriched in neutrophil activation and proinflammatory signaling pathways driven by increased tumor necrosis factor (TNF)-α signaling. Hierarchic clustering of the MI transcriptomic profile identified 3 subgroups with distinctive biological pathways and MI correlates. Our data demonstrate that platelets from MI patients are phenotypically different from MI-naïve patients in the acute and chronic settings and reveal a platelet transcriptomic signature with distinct clinical features.

The aim of the present retrospective study was to evaluate the prognostic role of the extracellular volume fraction (ECV) in patients with myocardial infarction (MI) and myocardial infarction with nonobstructive coronary arteries (MINOCA). The present study hypothesized that ECV is associated with major adverse cardiovascular events (MACEs) in MI and MINOCA patients.

Cardiac magnetic resonance (CMR) imaging was performed on 351 consecutive patients (mean age: 58 ± 12 years; 252 [71.8%] males) who were diagnosed with MI between October 2015 and November 2023. From CMR imaging, the extent of late gadolinium enhancement (LGE), native T1 and ECV were derived. Patients were categorized into groups according to the degree of coronary artery stenosis, namely, patients with MINOCA and patients with obstructive MI. Follow-up was performed to assess MACEs.

The final cohort consisted of 61 MINOCA patients and 290 obstructive MI patients. During a mean follow-up of 27 ± 16 months, there was no statistically significant difference in the incidence of MACEs between patients with MINOCA and those with obstructive MI, and the two groups of patients had similar ECVs (32.2 ± 3.6 vs. 32.3 ± 6.0, p = 0.864). According to the multivariate Cox regression, ECV was an independent predictor of MACEs (HR: 1.13; p < 0.001) and significantly improved the prognostic value of the baseline multivariate models (C-statistic improvement: 0.816-0.864, p = 0.001). Similarly, ECV maintained an independent association with MACEs in the MINOCA (HR: 1.35; p < 0.001) and obstructive MI (HR: 1.13; p < 0.001) groups.

In MI and MINOCA patients, ECV is an independent predictor of MACEs. MINOCA is not a benign disease, and its long-term prognosis is as poor as that of patients with obstructive MI.

Preoperative evaluation identifies unique patient characteristics with an impact on perioperative care. Sex-based differences in cardiovascular disease are particularly important. Diseases in women can go unrecognized and yet have long-term implications for cardiovascular risk. Peripartum cardiomyopathy and hypertensive disorders of pregnancy affect cardiovascular risk in young women long after pregnancy. Sex-hormone therapy in women, men, and transgender patients carries minimal perioperative risk, except in select patients at high risk for venous thromboembolism. The unique challenges facing patients experiencing homelessness in accessing care mean underlying comorbidities are common and additional resources may be required to provide effective perioperative care.

Myocardial infarction with nonobstructive coronary arteries (MINOCA) is an important, often underrecognized working diagnosis. MINOCA is defined as an acute MI in a patient whose coronary angiography reveals no significant obstructive coronary artery disease. A comprehensive diagnostic approach beyond the initial coronary angiogram is essential for identifying this heterogeneous infarction pathophysiology. Distinguishing disease-specific causes affects patient management and prognosis, especially in female patients. This article provides an evidence-based overview of the tailored management strategies and ongoing clinical research likely to shape future guidelines.

MINOCA (Myocardial Infarction with Non-Obstructive Coronary Arteries) represents a unique subset of acute coronary syndrome, distinct from MIOCA (Myocardial Infarction with Obstructive Coronary Arteries) and a control group. This study systematically compares their prevalence, clinical characteristics, management strategies, and outcomes to improve understanding and treatment approaches.

This systematic review and meta-analysis followed PRISMA guidelines across multiple databases up to 2024. STATA 17 was used for statistical analyses, and the Newcastle-Ottawa Scale was employed to assess study quality.

One-hundred and twelve studies, including 5,908,768 patients, were analyzed. The pooled prevalence of MINOCA among patients undergoing coronary angiography was 8.92% (95% CI: 8.90-8.94). MINOCA patients were generally younger, predominantly female, and more likely to present with atypical chest pain and dyspnea compared to MIOCA patients. Laboratory findings showed higher levels of CRP, BNP, and fibrinogen in MINOCA patients, suggesting inflammation and microvascular dysfunction as key mechanisms. In contrast, MIOCA patients had higher rates of diabetes and dyslipidemia, highlighting differences in pathophysiological processes. Medication use differed between the groups, with MINOCA patients more likely to be prescribed anticoagulants and β-blockers. Prognostically, MINOCA patients experienced significantly lower rates of adverse short- and long-term outcomes, including major adverse cardiac events (MACE) and cardiovascular death, compared to MIOCA patients.

This study demonstrated that patients with MINOCA have a better prognosis compared to those with MIOCA and are at a lower risk of serious cardiac events. Based on the findings of this study, we emphasize that microcirculation and vascular spasm are the main mechanisms involved in MINOCA. Considering these findings, it is suggested that a better management strategy for MINOCA patients can be established by precisely defining diagnostic criteria and focusing on anti-inflammatory treatments and risk factor control.

Few studies have investigated the clinical characteristics and in-hospital outcomes of patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) using real-world databases in the coronary intervention era.

We conducted a retrospective analysis of 22,236 patients (mean [±SD] age 68±13 years, 23.4% female) enrolled in the Japan Acute Myocardial Infarction Registry (JAMIR) between 2011 and 2016. Based on urgent coronary angiography findings, 286 (1.3%) patients were diagnosed as MINOCA, and the remaining 21,950 (98.7%) as MI with obstructive coronary artery disease (MI-CAD). MINOCA patients were characterized by younger age, fewer coronary risk factors, lower rate of ST-elevation myocardial infarction, lower Killip classification, and lower peak creatinine phosphokinase levels than MI-CAD patients. In-hospital all-cause mortality did not differ between the MINOCA and MI-CAD groups (5.2% vs. 5.7%, respectively; P=0.82). Comparing cause-specific mortality, non-cardiac mortality was higher in the MINOCA than MI-CAD group (4.2% vs. 1.6%; P<0.01). Importantly, non-cardiac death was more prevalent among elderly (≥65 years) than younger (<65 years) patients in the MI-CAD group, whereas this trend was not observed in the MINOCA group.

Analysis of the real-world JAMIR database revealed a relatively high prevalence of non-cardiac death among MINOCA patients, underscoring the need for comprehensive management to improve disease prognosis, particularly in younger patients.

The growing prevalence in the diagnosis of INOCA (Ischemia with Non-Obstructive Coronary Arteries), ANOCA (Angina with Non-Obstructive Coronary Arteries), and MINOCA (Myocardial Infarction with Non-Obstructive Coronary Arteries) highlights the need to reassess their clinical relevance. Historically regarded as benign syndromes, emerging evidence suggests that these conditions may cause serious cardiovascular events and considerable long-term disability. Additionally, emerging studies suggest that non-obstructive coronary artery disease (CAD) may have a higher prevalence compared to traditional obstructive forms of CAD. This leads to the need to better clarify the underlying pathogenic mechanisms as well as the risk factors associated with these syndromes. This is precisely the aim of this review, which focuses on the complex and heterogeneous mechanisms underlying these syndromes as well as the associated risk factors. This review also sums up the diagnostic steps necessary to achieve an accurate diagnosis, along with the interventional and pharmacological approaches to be implemented in light of the latest evidence.

Although non-optimum ambient temperature is a major non-traditional risk factor for acute myocardial infarction, there is no prior knowledge on whether non-optimum ambient temperature could differentially affect myocardial infarction with obstructive coronary artery disease (MI-CAD) and myocardial infarction with non-obstructive coronary arteries (MINOCA).

Using the Chinese Cardiovascular Association database-Chest Pain Center Registry, a nationwide, time-stratified, case-crossover investigation was conducted from 2015 to 2021. Meteorological data were obtained from an established satellite-based model, and daily exposures were assigned according to the onset of myocardial infarction in each patient. A conditional logistic regression model combined with distributed lag non-linear models (10 days) was used to estimate the exposure-response relationships.

A total of 83 784 MINOCA patients and 918 730 MI-CAD patients were included. The risk of MINOCA and MI-CAD associated with low temperature occurred at lag 2 day and lasted to 1 week. Extremely low temperature was associated with a substantially greater odds ratio (OR) of MINOCA [OR 1.58, 95% confidence interval (CI) 1.31-1.90] than MI-CAD (unmatched: OR 1.32, 95% CI 1.23-1.43; equally matched by age and sex: OR 1.25, 95% CI 1.04-1.50), compared with the corresponding reference temperatures (30°C, 35°C, and 30°C). Stronger associations were observed for patients who were aged ≥65 years, female, or resided in the south. There was no significant difference for the impacts of high temperature on MINOCA and MI-CAD.

This nationwide study highlights the particular susceptibility of MINOCA patients to ambient low temperature compared with that of MI-CAD patients.

Approximately 10% of patients with myocardial infarction present with non-obstructive coronary arteries (MINOCA), whose characteristics differ from those with obstructive coronary lesions (MICAD). Inflammation plays a key role in myocardial infarction. This study aims to develop a biomarker-based index for accurate differentiation between MINOCA and MICAD.

A prospective, observational cohort study including 111 patients admitted for myocardial infarction: 46 with MINOCA and 65 with MICAD. Blood samples were collected within the first 24 h to measure high-sensitivity C-reactive protein, interleukin-6, asymmetric dimethylarginine, and peak high-sensitivity troponin T. The association of these biomarkers with MICAD risk was analyzed using logistic regression. Scoring systems were developed using optimization algorithms to predict the diagnosis before coronary angiography, applied to both individual biomarkers and a combined index.

Patients had a mean age of 67 years (SD 13.3), with a male predominance (68.5%). Higher levels of IL-6 and high-sensitivity troponin T were significantly associated with increased MICAD risk (OR: 1.58; 95% CI: 1.01-2.46, and OR: 2.27; 95% CI: 1.61-3.26, respectively). As score increases, interleukin-6 and high-sensitivity troponin T increase the likelihood of MICAD classification, while higher asymmetric dimethylarginine levels reduce it. Each one-point increase in the combined index multiplies MICAD risk by six (OR:6.16, 95%CI: 2.72-13.95; p < 0.001). While individual indexes improved the diagnostic performance of biomarkers, the combined index demonstrated superior accuracy (AUC: 0.918).

A biomarker-based scoring system was developed, achieving superior discriminatory capacity for differentiating MINOCA from MICAD compared to the individual analysis of biomarkers in absolute values or independent indexes.

What is the pathophysiology and clinical findings as well as management of patients presenting with INOCA/MINOCA (Ischemia/Myocardial Infarction with Non-Obstructive Coronary Arteries).

INOCA/MINOCA has a complex pathophysiology. In this review article, we aim to summarize the complex pathophysiology and clinical diagnosis, and review the current management options.

Ischemic heart disease is the most common cardiovascular cause of death in women worldwide. Obstructive coronary atherosclerosis is the primary cause of myocardial infarction (MI), however, non-atherosclerotic mechanisms of MI, such as spontaneous coronary artery dissection, vasospasm, microvascular dysfunction, embolization, inflammation, coronary anomalies, infectious and infiltrative causes are increasingly being recognized. Emerging data suggest that women are two to five times more likely to have an MI in the absence of coronary atherosclerosis compared to men, but they continue to remain underdiagnosed and undertreated, partly due to underdiagnosis and limited understanding of these mechanisms. Recent advancements in invasive and noninvasive imaging techniques and physiological testing allow for distinguishing these mechanisms from each other, providing a definitive diagnosis and tailored treatment. This review summarizes the existing literature on the non-atherosclerotic coronary causes of MI with a focus on evidence pertaining to women, offering a basis for future studies.

Myocardial infarction with nonobstructive coronary arteries (MINOCA) constitutes 3-15% of all acute myocardial infarctions. Women are more frequently diagnosed with MINOCA, although the influence of sex on long-term outcomes is still unclear. In this study we aimed to compare sex-based differences in baseline characteristics and clinical outcomes in patients with suspected MINOCA. We have retrospectively analyzed 6063 patients diagnosed with MINOCA (3220 females and 2843 male patients) from combined 3 large polish registries (PL-ACS, SILCARD and AMI-PL). Male patients were significantly younger (63 (55-74) vs. 71 (61-79) years, p < 0.05) and less frequently diabetic (20.1% vs. 24.1%, p < 0.05). Mortality was significantly higher in male population (11.8% vs. 10.2%, p < 0.05 at 1 year and 17.6% vs. 15.0%, p < 0.05 at 3 years). Male sex was an independent predictor of both mortality (HR = 1.29; CI 1.11-1.51; p < 0.05) and myocardial infarction (HR = 1.39; CI 1.1-1.75, p < 0.05) at 3 years follow-up. All-cause readmission rates were similar in male and female patients both at 1 year (46.0% vs. 44.4, p = 0.2) and 3 years follow-up (56.4% vs. 56.5%, p = 0.93). However, cardiovascular readmissions were more prevalent in male patients at both timepoints (33.9% vs. 29.10%, p < 0.05 at 1 year, and 41.0% vs. 37.6%, p < 0.05 at 3 years). This large-scale registry-based analysis demonstrated higher 3 years rates of adverse events, including death and MI among male patients with suspected MINOCA.

Angiography-derived microcirculatory resistance (AMR) is proposed as a novel, pressure- temperature-wire-free and less-invasive method to evaluate coronary microvascular dysfunction (CMD). This study aims to examine the prognostic role of CMD assessed by AMR in predicting adverse events in acute coronary syndrome (ACS) patients with chronic kidney disease (CKD).

This retrospective cohort study included ACS with CKD patients in the China-Japan Friendship Hospital from January 2016 to November 2022. The patients were divided into CMD and non-CMD groups based on AMR values of less than or greater than 250 mmHg*s/m.

A total of 345 eligible patients were included in this study. During a median follow-up of 23.0 months, higher prevalence rate of MACEs (28.3% vs. 15.1%, P = 0.003) and death (20.2% vs. 4.1%, P = 0.001) were observed in the CMD group. In multivariate Cox regression analysis, patients in the group of CMD had a 1.843 times higher hazard ratio (HR) for developing MACEs (HR: 1.843, 95% CI: 1.071-3.174, P = 0.027) and 5.325 times higher HR for developing death (HR: 5.325, 95% CI: 1.979-14.327, P < 0.001) for every 10 mmHg*s/m increment in AMR. The incorporation of AMR improved the predictive accuracy of the GRACE score for MACEs and death.

This study indicates that the AMR is significantly related to poor prognosis among patients with ACS and CKD. Furthermore, AMR could improve the predictive power of the GRACE risk score. These results indicated that AMR may serve as a valuable clinical tool for classification, risk stratification or therapy individualization in these patients.

Background/Objectives: Troponin level elevation without an obstructive culprit lesion is caused by heterogenous entities. The effect of aging on this condition has been poorly investigated. Methods: After screening 24,775 patients between 2010 and 2021, this study included a total of 373 patients with elevated troponin levels without an obstructive culprit lesion or suspected myocardial infarction with non-obstructive coronary arteries (MINOCAs) categorized into four age groups containing 78 patients (<51 years), 72 patients (51-60 years), 81 patients (61-70 years), and 142 patients (>70 years). This study analyzed the baseline characteristics, the in-hospital complications, in-hospital mortality, and the long-term outcomes. Results: The older patients exhibited a higher rate of major adverse cardiovascular in-hospital events than those of the other age groups (15.4% in the <51-year-old group vs. 36.1% in the 51-60-year-old group vs. 33.3% in the 61-70-year-old group vs. 47.2% in the >70-year-old group; p < 0.001). However, the rate of non-sustained ventricular tachycardia (nsVT) was higher in the 51-60-year-old patients than those of the other age groups (5.6% in the 51-60-year-old group vs. 1.3% in the 61-70-year-old group vs. 0.7% in the >70-year-old group; p = 0.027). At the 11-year follow-up, cardiovascular mortality was higher among the older patients compared to that of the younger patients (3.9% in the 61-70-year-old group vs. 4.2% in the >70-year-old group, p = 0.042), while non-cardiovascular mortality was comparable between the age groups. Conclusions: The older patients with troponin level elevation without an obstructive culprit lesion experienced a higher incidence of major adverse cardiovascular events during hospitalization compared to that of the younger groups. Additionally, higher cardiovascular mortality rates were revealed in the older patients at a long-term follow-up.

Angiographic evidence of the anatomy of coronary arteries and the type of coronary artery lesions in women with a history of hypertensive disorders of pregnancy (HDP) are poorly documented.

This study sought to determine the role of a history of HDP as a unique risk factor for early coronary artery disease (CAD) and type of acute coronary syndrome (ACS) (ie, atherosclerotic vs myocardial infarction with nonobstructive coronary arteries [MINOCA]) in women who underwent coronary angiography.

This study used a population-based cohort of parous female patients with incident CAD who underwent coronary angiography and age-matched control subjects. The SYNTAX (Synergy between PCI [percutaneous coronary intervention] with TAXUS [Boston Scientific] and Cardiac Surgery) score was assessed to determine the complexity and degree of CAD; MINOCA was diagnosed in the presence of clinical acute myocardial infarction in the absence of obstructive coronary disease.

A total of 506 parous female Olmsted County, Minnesota (USA) residents had incident CAD and angiographic data from November 7, 2002 to December 31, 2016. Women with HDP were younger than normotensive women at the time of the event (median: 64.8 years vs 71.8 years; P = 0.030). There was a strong association between HDP and ACS (unadjusted P = 0.018). Women with HDP compared with women with normotensive pregnancies were more likely to have a higher SYNTAX score (OR: 2.28; 95% CI: 1.02-5.12; P = 0.046), and MINOCA (OR: 2.08; 95% CI: 1.02-4.25; P = 0.044).

A history of HDP is associated with CAD earlier in life and with a future risk for myocardial infarction with both obstructive and nonobstructive coronary arteries. This study underscores the need for timely detection and treatment of nonobstructive disease, in addition to traditional risk factors.

Myocardial infarction without obstructive coronary artery disease (MINOCA) is a heterogeneous clinical condition presenting with myocardial necrosis not due to an obstruction of a major coronary artery. Recently, a relevant role of coronary microvascular dysfunction (CMD) in the pathogenesis of MINOCA has been suggested; however, data on this are scarce. Particularly, it is unclear if CMD is equally present in all subtypes of MINOCA or differentially identifies one or more of these conditions. Therefore, the aim of this study was to assess CMD in all three coronary vessels of MINOCA patients, relating it with the clinical subtype.

We retrospectively assessed coronary microvascular function in all three coronary territories by means of angiography-based index of microvascular resistance (aIMR) in 92 patients (64 with working diagnosis of MINOCA, 28 control patients). To further assess the association of CMD with MINOCA subtypes, MINOCA patients were subdivided according to clinical data in coronary cause (n = 13), takotsubo (n = 13), infiltrative or inflammatory cardiomyopathy (n = 9) or unclear (n = 29).

Patients with working diagnosis of MINOCA showed a significantly elevated average aIMR compared to control patients (30.5 ± 7.6 vs. 22.1 ± 5.9, p < 0.001) as a marker of a relevant CMD; these data were consistent in all vessels. Among MINOCA subtypes, no significant difference in average aIMR could be detected between patients with coronary cause (33.2 ± 6.6), takotsubo cardiomyopathy (29.2 ± 6.9), infiltrative or inflammatory cardiomyopathy (28.1 ± 6.8) or unclear cause (30.6 ± 8.5; p = 0.412). Interestingly, aIMR was significantly elevated in the coronary vessel supplying the diseased myocardium compared with other vessels (31.9 ± 11.4 vs. 27.8 ± 8.2, p = 0.049).

Coronary microvascular dysfunction is a hallmark of all MINOCA subtypes. This study adds to the pathophysiological understanding of MINOCA and sheds light into the role of CMD in MINOCA.

Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a complex clinical syndrome that is characterized by evidence of acute myocardial infarction in the absence of significant epicardial coronary artery disease on angiography. The term "MINOCA" encompasses a group of heterogeneous diseases with varying underlying mechanisms and each with its own pathophysiology. Overlooked plaque rupture or erosion and coronary vasospasm are the most common causes of MINOCA and can be diagnosed by routine intracoronary imaging and vasoreactivity testing, respectively. Coronary microvascular dysfunction is a less recognized, albeit an important cause of morbidity in patients presenting with MINOCA. Although MINOCA is a rare presentation of acute coronary syndrome, it is not a benign disorder and can have adverse consequences if untreated. In this article, we aim to review the pathogenesis, clinical characteristics, and finally propose a systematic approach in the diagnosis and management of patients with MINOCA.

In myocardial infarction with nonobstructive coronary arteries (MINOCA), there are limited patient-level data on outcomes by sex and race.

The aim of this study was to assess baseline demographics and 3-year outcomes by sex and race for MINOCA patients.

Patients admitted to a single center with acute myocardial infarction (MI) between 1 January 2012 and 31 December 2018, were identified by chart and angiographic review. The primary outcome was nonfatal MI with secondary outcomes including nonfatal cerebrovascular accident (CVA), chest pain readmission, and repeat coronary angiography.

During the study period, 304 patients were admitted with MINOCA. The cohort was predominantly female (66.4%), and women were significantly older (64.6 vs. 59.2). One-sixth of the total population were Black patients, and nearly half of Black patients (47.2%) were male. Prior CVA (19.7%) and comorbid anxiety, depression, or post-traumatic stress disorder (41.1%) were common. Rates of nonfatal MI were 6.3% without difference by sex or race. For secondary outcomes, rates of CVA were 1.7%, chest pain readmission was 22.4%, and repeat angiography was 8.9%. Men were significantly more likely to have repeat angiography (13.7 vs. 6.4%), and Black patients were more likely to be readmitted for angina (34.0 vs. 19.1%). Over one-quarter of patients underwent repeat stress testing, with 8.9% ultimately undergoing repeat angiograms and low numbers (0.7%) undergoing revascularization. Men were more likely to be referred for a repeat angiogram (13.7 vs. 6.4%, P  = 0.035). In multivariate analysis, Black race [odds ratio (OR), 2.31; 95% confidence interval (CI), 1.06-5.03] was associated with an increased risk of readmission for angina, while female sex was associated with decreased odds of repeat angiography (OR, 0.36; 95% CI, 0.14-0.90) and current smoking was associated with increased odds of repeat angiography (OR, 4.07; 95% CI, 1.02-16.29)] along with hyperlipidemia (OR, 4.65; 95% CI, 1.22-17.7).

White women presented more frequently with MINOCA than White men, however, Black men are equally as affected as Black women. Rates of nonfatal MI were low without statistical differences by sex or race.

Myocardial infarction (MI) can be caused by many factors. In addition to the typical obstruction or stenosis of the coronary arteries, there is heterogenic MI with non-obstructive coronary arteries (MINOCA). A rare cause of MINOCA is the thrombosis of a coronary artery aneurysm (CAA). This current case report describes a male patient with CAA thrombosis as the cause of MINOCA following surgery for a mucoepidermoid carcinoma. The patient underwent angiography that identified three CAAs that were located as follows: (i) in the proximal part of the left anterior descending artery (5.55 mm); (ii) in the distal part of the circumflex artery (8.05 mm); and (iii) in the distal part of the right coronary artery (6.61 mm). Thrombotic masses were identified within all three structures. The patient received balloon angioplasties without stent implanting and recovered well. The patient was also notable for the presence of two brain artery aneurysms that were the cause of the previous strokes that he had experienced. This case report also reviews the literature in order to: (i) summarize the aetiological factors and clinical manifestations of CAA; (ii) discuss the diagnostic methods for CAA; (iii) describe the medical and surgical management of CAA; and (iv) assess the prognosis of this rare clinical event.

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis usually affects small blood vessels and is characterized by the presence of circulating autoantibodies (c-ANCA or p-ANCA). The risk of cardiovascular events is threefold higher compared to general population, and cardiac manifestations include myocarditis, pericarditis, valvulitis, aortitis, or coronary arteritis. Coronary involvement is very rare, but it is a potentially life-threatening manifestation.

We present an atypical cardiac scenario of p-ANCA vasculitis.

A 68-year-old woman with known p-ANCA vasculitis and stage 5 chronic kidney disease (CKD) on hemodialysis presented with dizziness accompanied by low blood pressure and chest pain. Electrocardiogram on arrival showed slightly ST-T changes, with negative cardiac biomarkers and no abnormalities in cardiac regional wall motion. Five hours after presentation, the patient repeated chest pain, accompanied by a drop in blood pressure and junctional escape rhythm. The highly sensitive cardiac troponin I (hs-cTnI) was raised at 560 ng/L. Coronary angiography showed coronary arteries without significant stenosis. The provocative test with intracoronary ergonovine demonstrated coronary vasospasm of the anterior descending artery accompanied by chest pain, with resolution after intracoronary nitroglycerin. Under amlodipine, nitrate, acetylsalicylic acid, statin and corticosteroids the patient did not experience the recurrence of angina.

This case illustrates coronary involvement, manifested as coronary spasm with favorable outcomes, in systemic vasculitis. The underlying mechanism is immune-mediated inflammation in vascular walls.

The literature analysis conducted in this review discusses the latest achievements in the identification of cardiovascular damage induced by oxidative stress with secondary platelet mitochondrial dysfunction. Damage to the platelets of mitochondria as a result of their interactions with reactive oxygen species (ROS) and reactive nitrogen species (RNS) can lead to their numerous ischemic events associated with hypoxia or hyperoxia processes in the cell. Disturbances in redox reactions in the platelet mitochondrial membrane lead to the direct oxidation of cellular macromolecules, including nucleic acids (DNA base oxidation), membrane lipids (lipid peroxidation process) and cellular proteins (formation of reducing groups in repair proteins and amino acid peroxides). Oxidative changes in biomolecules inducing tissue damage leads to inflammation, initiating pathogenic processes associated with faster cell aging or their apoptosis. The consequence of damage to platelet mitochondria and their excessive activation is the induction of cardiovascular and neurodegenerative diseases (Parkinson's and Alzheimer's), as well as carbohydrate metabolism disorders (diabetes). The oxidation of mitochondrial DNA can lead to modifications in its bases, inducing the formation of exocyclic adducts of the ethano and propano type. As a consequence, it disrupts DNA repair processes and conduces to premature neoplastic transformation in critical genes such as the p53 suppressor gene, which leads to the development of various types of tumors. The topic of new innovative methods and techniques for the analysis of oxidative stress in platelet mitochondria based on methods such as a nicking assay, oxygen consumption assay, Total Thrombus formation Analysis System (T-Tas), and continuous-flow left ventricular assist devices (CF-LVADs) was also discussed. They were put together into one scientific and research platform. This will enable the facilitation of faster diagnostics and the identification of platelet mitochondrial damage by clinicians and scientists in order to implement adequate therapeutic procedures and minimize the risk of the induction of cardiovascular diseases, including ischemic events correlated with them. A quantitative analysis of the processes of thrombus formation in cardiovascular diseases will provide an opportunity to select specific anticoagulant and thrombolytic drugs under conditions of preserved hemostasis.

The prognosis of myocardial infarction with non-obstructive coronary arteries (MINOCA) is reported to be as worse as myocardial infarction with obstructive coronary arteries. However, its mechanical complications are still poorly understood. A 71-year-old woman developed MINOCA after ascending aortic replacement surgery. During treatment, the patient experienced cardiogenic shock due to a ventricular septal rupture (VSR). The introduction of Impella devices reduced the left-to-right shunt and improved the patient's hemodynamics. Finally, a scheduled surgical repair was performed under stable conditions. In this report, we focused on the pathophysiology of MINOCA-related VSR and discussed the effectiveness of Impella devices as a bridge to surgical repair and circulatory backup during the perioperative period.

Intravascular imaging has become an integral part of the diagnostic and management strategies for intracoronary pathologies. In this White Paper we summarize current evidence and its implications on the use of intravascular imaging in interventional cardiology practice. The areas addressed are planning and optimization of percutaneous coronary intervention, management of stent failure, and evaluation of ambiguous coronary lesions and myocardial infarction with nonobstructive coronary disease. The findings presented followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system in an expert consensus process that involved a diverse writing group vetted by a review group. Expert consensus was achieved around 9 statements. Use of intravascular imaging in guiding percutaneous revascularization is supported by high-quality evidence, particularly for lesions with increased risk of recurrent events or stent failure. Specific considerations for intravascular imaging guidance of intervention in left main lesions, chronic occlusion lesions, and in patients at high risk of contrast nephropathy are explored. Use of intravascular imaging to identify pathologies associated with stent failure and guide repeat intervention, resolve ambiguities in lesion assessment, and establish diagnoses in patients who present with myocardial infarction with nonobstructive coronary disease is supported by moderate- to low-quality evidence. Each topic is accompanied by clinical pointers to aid the practicing interventional cardiologist in implementation of the White Paper findings. The findings presented in this White Paper will help to guide the use of intravascular imaging toward situations in which the balance of efficacy, safety, and cost are most optimal.

Real-world evidence on the relationship between delayed hospitalization and outcomes in myocardial infarction with nonobstructive coronary arteries (MINOCA) is lacking. Hence, we aimed to evaluate the clinical characteristics of patients with MINOCA and the 2-year mortality outcomes in this patient population according to the symptom-to-door time (SDT).

Overall, 861 patients with MINOCA from 2 Korean nationwide observational registries (2011-2020) were included and categorized as early or late presenters. Late presentation was defined as SDT ≥12 hours in patients with ST-segment elevation myocardial infarction (STEMI) and SDT ≥24 hours in patients with non-STEMI. The primary outcome was 2-year all-cause mortality. Propensity score matching (PSM) and age-sex adjusted analysis were used to determine whether late presentation independently affected mortality. Multivariate logistic regression analysis was used to examine the independent factors correlated with late presentation.

In unadjusted data, late presenters had a notably higher risk of 2-year all-cause mortality than early presenters (hazard ratio [HR], 2.44; 95% confidence interval [CI], 1.47-4.08). This trend persisted in age-sex adjusted analysis (adjusted HR, 2.29; 95% CI, 1.36-3.84) and PSM-adjusted analysis (adjusted HR, 2.18; 95% CI, 1.05-4.53). The positive independent factors for late presentation included female sex, no emergency medical service use and high creatinine level, whereas the negative independent factor was a dyslipidemia.

Late presentation is associated with higher mortality in patients with MINOCA. Multidisciplinary efforts are needed to reduce pre-hospital delay, thereby improving the clinical outcomes in these patients.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a clinical entity characterized by the absence of significant coronary artery obstruction in epicardial arteries (<50%) on coronary angiography in the setting of acute myocardial infarction (AMI). This article aims to provide a narrative review of the pathophysiological mechanisms, diagnostic challenges, and prognosis associated with MINOCA based on pathophysiology regarding the atherosclerotic and non-atherosclerotic causes. Etiological factors, including thromboembolism, coronary artery spasm, spontaneous coronary artery dissection, coronary microvascular disease, and supply-demand mismatch, are addressed. Imaging modalities such as echocardiography, advances in coronary angiography like intravascular ultrasound (IVUS) and optical coherence tomography (OCT), cardiac magnetic resonance (CMR), and coronary computed tomography angiography (CCTA) are also analyzed. MINOCA patients have a better short-term prognosis compared to those with obstructive coronary artery disease but face significant long-term risks, underscoring the need for precise diagnosis and management strategies. Elevated inflammatory markers and specific genetic predispositions are also associated with adverse outcomes in MINOCA. This review focused on MINOCA from a pathophysiological perspective on the diverse underlying mechanisms, the challenges in achieving accurate diagnosis, the importance of a tailored therapeutic approach and the necessity for further investigation of clinical outcomes.

Functional coronary angiography (FCA) is a novel modality for assessing the physiology of coronary lesions, going beyond anatomical visualization by traditional coronary angiography. FCA incorporates indices like fractional flow reserve (FFR) and instantaneous wave-free ratio (IFR), which utilize pressure measurements across coronary stenoses to evaluate hemodynamic impacts and to guide revascularization strategies. In this review, we present traditional and evolving modalities and uses of FCA. We will also evaluate the existing evidence and discuss the applicability of FCA in various clinical scenarios. Finally, we provide insight into emerging evidence, current challenges, and future directions in FCA.

To assess the prognostic value of cardiac MRI (CMR) parameters for the occurrence of major adverse cardiac events (MACE) in patients with infarct-like myocarditis.

In this retrospective single-center study, patients with CMR-confirmed acute myocarditis with infarct-like presentation were identified (2007-2020). Functional and structural parameters were analyzed including late gadolinium enhancement (LGE). The primary endpoint was the occurrence of MACE up to 5 years after discharge.

In total, 130 patients (mean age, 40 ± 19 years; 97 men, 75%) with infarct-like myocarditis were included. CMR was conducted a median of 3 days (interquartile range [IQR], 1-5) after symptom onset. MACE occurred in 18/130 patients (14%) during a median follow-up of 19.3 months (IQR, 4.5-53). The median extent of LGE was 7% (IQR, 4-10). LGE affected the subepicardium in 111/130 patients (85%), the midwall in 45/130 patients (35%), and both the subepicardium and midwall in 27/130 patients (21%). Transmural extension of non-ischemic LGE lesions was observed in 15/130 patients (12%) and septal LGE in 42/130 patients (32%). In univariable Cox regression analysis, a significant association was found between the occurrence of MACE and both, quantified LGE extent and transmural LGE pattern. In multivariable analysis, transmural extension of LGE was an independent predictor for MACE (hazard ratio, 6.34; 95% confidence interval: 2.29-17.49; p < 0.001). Patients with the transmural extension of LGE had a shorter event-free time on Kaplan-Meier analysis (log-rank p < 0.001).

MACE occurred in 14% of patients with infarct-like myocarditis during follow-up. A transmural extension of non-ischemic LGE was associated with a worse long-term prognosis.

CMR-based assessment of transmural extension of non-ischemic LGE holds the potential to serve as an easily assessable marker for risk stratification in patients with infarct-like myocarditis.

The prognostic value of CMR was studied in patients with infarct-like myocarditis. The extent of LGE and transmural extension were linked to adverse cardiac events. Transmural non-ischemic LGE can serve as an easily assessable prognostic marker.

To investigate whether feature tracking cardiac magnetic resonance (FT-CMR) can identify subclinical myocardial dysfunction in patients with myocardial infarction with non-obstructed coronary arteries (MINOCA).

Clinical data and CMR images of MINOCA patients (N = 46) and control individuals (N = 12) were compared. The infarct and edema volume to total myocardium, peak global longitudinal strain (GLS), global longitudinal strain rate (GLSR), peak global circumferential strain (GCS), global circumferential strain rate, peak global radial strain, and global radial strain rate were measured. Diagnostic performances of strain parameters for MINOCA were evaluated by logistic regression and receiver operating characteristics analysis.

Except smoking history, the two groups showed no significant differences in cardiovascular risk factors and traditional heart function. GLS (-14.67 ± 1.96% vs. -19.19 ± 2.05%), GLSR (-0.94 ± 0.16 S- 1 vs. -1.23 ± 0.14 S- 1) and GCS (-17.59 ± 1.81% vs. -19.22 ± 1.76%) were impaired in MINOCA patients compared with the control group. MINOCA patients with normal routine CMR showed abnormalities in GLS (-16.23 ± 1.16%) and GLSR (-1.04 ± 0.16 S- 1). GLS and GLSR were predictive for MINOCA diagnosis (P = 0.002 vs. P = 0.033). GLS correlated strongly with myocardial infarction and edema. The optimal diagnostic threshold for GLS was <-16.9% for MINOCA diagnosis (sensitivity 87.1%, specificity 92.9%); the area under the receiver operating characteristic curve was 0.968.

Myocardial strain by FT-CMR may effectively detect early myocardial impairment with MINOCA, especially in patients with normal routine MRI.