Visual Estimates of Coronary Slow Flow Are Not Associated With Invasive Wire-Based Diagnoses of Coronary Microvascular Dysfunction.

BACKGROUND: Coronary slow flow (CSF) by invasive coronary angiography is frequently understood to be an indicator of coronary microvascular dysfunction (CMD) in patients with ischemia with nonobstructive coronary arteries. However, the relationship between visual estimates of CSF and quantitative wire-based invasive diagnosis of CMD is uncertain. METHODS: We prospectively enrolled adults aged ≥18 years with stable ischemic heart disease who were referred for invasive coronary angiography. Individuals with ≥50% epicardial coronary artery stenosis were excluded. Invasive coronary angiography was reviewed for CSF, defined as ≥3 cardiac cycles to opacify distal vessels with contrast. Coronary function testing was performed in the left anterior descending coronary artery using bolus coronary thermodilution techniques to measure coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR). Invasively determined CMD was defined as abnormal CFR (<2.5), abnormal IMR (≥25), or both. RESULTS: Among 104 participants, the median age was 61.5 years and 79% were female. The median CFR was 3.6 (interquartile range, 2.5-4.7) and the median IMR was 21 (interquartile range, 13.3-28.0). Overall, 24.0% of participants had abnormal CFR, 34.6% had abnormal IMR, and 48.1% had a final diagnosis of invasively determined CMD. CSF was present in 23 participants (22.1%). The proportions of patients with CMD (56.5% versus 45.7%; P=0.36), abnormal CFR (17.4% versus 25.9%; P=0.40), and abnormal IMR (43.5% versus 32.1%; P=0.31) were not different in patients with versus without CSF. CONCLUSIONS: Among patients with ischemia with nonobstructive coronary artery, CSF was not associated with abnormal CFR, IMR, or either abnormal CFR or IMR. CSF is not a reliable angiographic surrogate of abnormal CFR or IMR as determined by invasive, wire-based physiology testing. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03537586.

Psychosocial Factors of Women Presenting With Myocardial Infarction With or Without Obstructive Coronary Arteries.

BACKGROUND: Women with myocardial infarction (MI) are more likely to have elevated stress levels and depression than men with MI. OBJECTIVES: We investigated psychosocial factors in women with myocardial infarction with nonobstructive coronary arteries (MINOCA) and those with MI and obstructive coronary artery disease (CAD). METHODS: Women with MI enrolled in a multicenter study and completed measures of perceived stress (Perceived Stress Scale-4) and depressive symptoms (Patient Health Questionnaire-2) at the time of MI (baseline) and 2 months later. Stress, depression, and changes over time were compared between MI subtypes. RESULTS: We included 172 MINOCA and 314 MI-CAD patients. Women with MINOCA were younger (age 59.4 years vs 64.2 years; P < 0.001) and more diverse than those with MI-CAD. Women with MINOCA were less likely to have high stress (Perceived Stress Scale-4 ≥6) at the time of MI (51.0% vs 63.0%; P = 0.021) and at 2 months post-MI (32.5% vs 46.3%; P = 0.019) than women with MI-CAD. There was no difference in elevated depressive symptoms (Patient Health Questionnaire-2 ≥2) at the time of MI (36% vs 43%; P = 0.229) or at 2 months post-MI (39% vs 40%; P = 0.999). No differences in the rate of 2-month decline in stress and depression scores were observed between groups. CONCLUSIONS: Stress and depression are common among women at the time of and 2 months after MI. MINOCA patients were less likely to report high stress compared with MI-CAD patients, but the frequency of elevated depressive symptoms did not differ between the 2 groups. Stress and depressive symptoms decreased in both MI-CAD and MINOCA patients over time.

Characteristics of Premature Myocardial Infarction Among Women With Prior Adverse Pregnancy Outcomes.

BACKGROUND: Adverse pregnancy outcomes (APOs), hypertensive disorders of pregnancy, gestational diabetes mellitus, and preterm birth are associated with ischemic heart disease in later life. OBJECTIVES: The authors aimed to study the features of premature myocardial infarction (MI) among women with and without prior APOs. METHODS: We performed a retrospective analysis of women with premature MI (<65 years of age) referred for left heart catheterization matched with a database of abstracted pregnancy data. We compared MI characteristics and epicardial coronary anatomy between women with and without APOs during their index pregnancy and evaluated time from delivery to MI. RESULTS: Of 391 women with premature MI and associated coronary angiography (age: 49 ± 8 years), 154 (39%) had a prior APO (hypertensive disorders of pregnancy n = 78, preeclampsia n = 35, gestational diabetes mellitus n = 28, and preterm birth n = 48). Women with APO history had a higher prevalence of diabetes (33% vs 16% without APO; P = 0.001) and presented earlier with MI following delivery (19.6 [IQR: 14.3-23.5] years vs those without APO 21.5 [IQR: 17.0-25.4] years; P = 0.012), driven by preeclampsia (17.1 [IQR: 12.7-22.4] years, P = 0.010). Women with and without APOs had similar MI features including rates of ST-segment elevation MI, obstructive and multi-vessel coronary artery disease, percutaneous coronary intervention, and shock. CONCLUSIONS: Among women with premature MIs, 39% had a history of an APO. Women with APO history presented sooner after pregnancy but had similar MI characteristics vs those without APOs. Pregnancy history may identify women who warrant early, aggressive cardiovascular disease prevention.

Role of Resilience in the Psychological Recovery of Women With Acute Myocardial Infarction.

Background Psychological well-being is important among individuals with myocardial infarction (MI) given the clear links between stress, depression, and adverse cardiovascular outcomes. Stress and depressive disorders are more prevalent in women than men after MI. Resilience may protect against stress and depressive disorders after a traumatic event. Longitudinal data are lacking in populations post MI. We examined the role of resilience in the psychological recovery of women post MI, over time. Methods and Results We analyzed a sample from a longitudinal observational multicenter study (United States, Canada) of women post MI, between 2016 and 2020. Perceived stress (Perceived Stress Scale-4 [PSS-4]) and depressive symptoms (Patient Health Questionnaire-2 [PHQ-2]) were assessed at baseline (time of MI) and 2 months post MI. Demographics, clinical characteristics, and resilience (Brief Resilience Scale [BRS]) were collected at baseline. Low and normal/high resilience groups were established as per published cutoffs (BRS scores <3 or ≥3). Mixed-effects modeling was used to examine associations between resilience and psychological recovery over 2 months. The sample included 449 women, mean (SD) age, 62.2 (13.2) years, of whom 61.1% identified as non-Hispanic White, 18.5% as non-Hispanic Black, and 15.4% as Hispanic/Latina. Twenty-three percent had low resilience. The low resilience group had significantly higher PSS-4 and PHQ-2 scores than the normal/high resilience group at all time points. In adjusted models, both groups showed a decrease in PSS-4 scores over time. Conclusions In a diverse cohort of women post MI, higher resilience is associated with better psychological recovery over time. Future work should focus on developing strategies to strengthen resilience and improve psychological well-being for women with MI. Registration URL: https://clinicaltrials.gov/ct2/show/NCT02905357; Unique identifier: NCT02905357.

Cancer and Myocardial Infarction in Women.

Women who present with myocardial infarction (MI) are more likely to be diagnosed with nonobstructive coronary arteries (MINOCAs), spontaneous coronary artery dissection (SCAD), and takotsubo syndrome (TS) than men. Malignancy may predispose to MI and TS through shared risk factors and inflammatory mediators. This study aimed to determine the prevalence of cancer in women presenting with clinical syndrome of MI and the association between cancer and mechanism of MI presentation. Among 520 women with MI who underwent coronary angiography at NYU Langone Health from March 2016 to March 2020 or September 2020 to September 2021, 122 (23%) had a previous diagnosis of cancer. Patients with cancer were older at MI presentation but had similar co-morbidity to those without a cancer history. The most common cancers were breast (39%), gynecologic (15%), and gastrointestinal (13%). Women with cancer history were more likely to have TS (17% vs 11% without cancer history p = 0.049). Among women with a final diagnosis of MI, the type of MI (MINOCA, MI-coronary artery disease, or SCAD) was not significantly different between groups (p = 0.374). History of cancer was present in nearly a quarter of women presenting with MI and was associated with a greater likelihood of TS than MI. MINOCA and SCAD were not more common among women with a cancer history.

Assisted Reproductive Technology Outcomes in Women With Heart Disease.

Background: Women with infertility and heart disease (HD) are increasingly seeking assisted reproductive technology (ART). There is only one other study that examines the safety profile of ART in this population. This study aims to evaluate the cardiac, reproductive, and obstetric outcomes of ART in women with HD. Methods: We conducted a retrospective case-control study of women with underlying congenital or acquired HD who underwent ART at a single University fertility center from 1/2010-3/2019. Women undergoing in-vitro fertilization (IVF), oocyte cryopreservation (OC) or embryo banking (EB) with HD were included. Cases were matched 3:1 with age-, cycle type- and cycle start date- matched controls without HD. Outcomes included cardiovascular (CV), reproductive, and obstetric complications during or following ART. Results: Twenty women with HD were included. 15 (75%) had congenital HD, 1 (5%) had valvular disease, 1 (5%) had acquired cardiomyopathy, and 3 (15%) had arrhythmias. 90% were New York Heart Association class I. 55% of HD cases were modified WHO (mWHO) risk classification 1-2, 40% were mWHO 2-3 or 3, 5% were mWHO 4. Cases underwent 25 IVF, 5 OC, and 5 EB cycles and were compared with 79 controls who underwent 174 cycles. No CV complications or deaths occurred amongst cases following ART or pregnancy. There was no difference in risk of ART or obstetric outcomes amongst cases versus controls. Conclusion: For women with HD in this small, low -risk cohort, ART posed few risks that were similar in frequency to healthy controls.

Predictive Performance of the International Takotsubo Registry Score in the Diagnosis of Takotsubo Syndrome Among Women with Non-ST Segment Elevation Myocardial Infarction.

Background: The International Takotsubo Registry (InterTAK) score was developed to assess the probability of takotsubo syndrome (TTS) and to distinguish it from acute coronary syndrome, which has a similar clinical presentation. A European Society of Cardiology (ESC) consensus statement suggests invasive coronary angiography may be deferred in patients with non-ST segment elevation myocardial infarction (NSTEMI) and high probability of TTS. We aimed to determine the predictive performance of the InterTAK score in a real-world population of NSTEMIs. Materials and Methods: The InterTAK score was retrospectively calculated for consecutive female patients with NSTEMI who underwent invasive coronary angiography at two academic medical centers in New York City from March 2016 to August 2018. Results: Among 375 women with NSTEMI, 15 (4%) had InterTAK score >70, indicating high probability of TTS. Ten (67%) met ESC TTS criteria for a noninvasive strategy, among whom seven had TTS, two had spontaneous coronary artery dissection (SCAD), and one had coronary artery disease requiring revascularization. A total of 48 women (13% of cohort) had a final diagnosis of TTS. The InterTAK score had an area under the receiver operating characteristics curve (AUC) of 0.82 (95% confidence interval, 0.75-0.88) for TTS, with 21% sensitivity and 98% specificity at score >70. Conclusions: In this real-world sample of consecutive female NSTEMI patients, the InterTAK score was predictive of TTS but a high score was rare, and use of the score to obviate invasive angiography could have resulted in delay of revascularization and missed diagnosis of SCAD for a small number of patients. The InterTAK score should be used in conjunction with other clinical variables for angiographic referral.

Coronary Optical Coherence Tomography and Cardiac Magnetic Resonance Imaging to Determine Underlying Causes of Myocardial Infarction With Nonobstructive Coronary Arteries in Women.

BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA) occurs in 6% to 15% of myocardial infarctions (MIs) and disproportionately affects women. Scientific statements recommend multimodality imaging in MINOCA to define the underlying cause. We performed coronary optical coherence tomography (OCT) and cardiac magnetic resonance (CMR) imaging to assess mechanisms of MINOCA. METHODS: In this prospective, multicenter, international, observational study, we enrolled women with a clinical diagnosis of myocardial infarction. If invasive coronary angiography revealed <50% stenosis in all major arteries, multivessel OCT was performed, followed by CMR (cine imaging, late gadolinium enhancement, and T2-weighted imaging and T1 mapping). Angiography, OCT, and CMR were evaluated at blinded, independent core laboratories. Culprit lesions identified by OCT were classified as definite or possible. The CMR core laboratory identified ischemia-related and nonischemic myocardial injury. Imaging results were combined to determine the mechanism of MINOCA, when possible. RESULTS: Among 301 women enrolled at 16 sites, 170 were diagnosed with MINOCA, of whom 145 had adequate OCT image quality for analysis; 116 of these underwent CMR. A definite or possible culprit lesion was identified by OCT in 46.2% (67/145) of participants, most commonly plaque rupture, intraplaque cavity, or layered plaque. CMR was abnormal in 74.1% (86/116) of participants. An ischemic pattern of CMR abnormalities (infarction or myocardial edema in a coronary territory) was present in 53.4% (62/116) of participants undergoing CMR. A nonischemic pattern of CMR abnormalities (myocarditis, takotsubo syndrome, or nonischemic cardiomyopathy) was present in 20.7% (24/116). A cause of MINOCA was identified in 84.5% (98/116) of the women with multimodality imaging, higher than with OCT alone (P<0.001) or CMR alone (P=0.001). An ischemic cause was identified in 63.8% of women with MINOCA (74/116), a nonischemic cause was identified in 20.7% (24/116) of the women, and no mechanism was identified in 15.5% (18/116). CONCLUSIONS: Multimodality imaging with coronary OCT and CMR identified potential mechanisms in 84.5% of women with a diagnosis of MINOCA, 75.5% of which were ischemic and 24.5% of which were nonischemic, alternate diagnoses to myocardial infarction. Identification of the cause of MINOCA is feasible and has the potential to guide medical therapy for secondary prevention. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02905357.

Myocarditis in Relation to Angiographic Findings in Patients With Provisional Diagnoses of MINOCA.

OBJECTIVES: The aim of this study was to determine the prevalence of myocarditis among patients presenting with myocardial infarction with nonobstructive coronary arteries (MINOCA) in relation to the angiographic severity of nonobstructive coronary artery disease (CAD). BACKGROUND: MINOCA represents about 6% of all cases of acute myocardial infarction. Myocarditis is a diagnosis that may be identified by cardiac magnetic resonance (CMR) imaging in patients with a provisional diagnosis of MINOCA. METHODS: A systematic review was performed to identify studies reporting the results of CMR findings in MINOCA patients with nonobstructive CAD or normal coronary arteries. Study-level and individual patient data meta-analyses were performed using fixed- and random-effects methods. RESULTS: Twenty-seven papers were included, with 2,921 patients with MINOCA; CMR findings were reported in 2,866 (98.1%). Myocarditis prevalence was 34.5% (95% confidence interval [CI]: 27.2% to 42.2%) overall and was numerically higher in studies that defined MINOCA as myocardial infarction with angiographically normal coronary arteries compared with a definition that permitted nonobstructive CAD (45.9% vs. 32.3%; p = 0.16). In a meta-analysis of individual patient data from 9 of the 27 studies, the pooled prevalence of CMR-confirmed myocarditis was greater in patients with angiographically normal coronary arteries than in those with nonobstructive CAD (51% [95% CI: 47% to 56%] vs. 23% [95% CI: 18% to 27%]; p < 0.001). Men and younger patients with MINOCA were more likely to have myocarditis. Angiographically normal coronary arteries were associated with increased odds of myocarditis after adjustment for age and sex (adjusted odds ratio: 2.30; 95% CI: 1.12 to 4.71; p = 0.023). CONCLUSIONS: Patients with a provisional diagnosis of MINOCA are more likely to have CMR findings consistent with myocarditis if they have angiographically normal coronary arteries.

Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Covid-19.

BACKGROUND: There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS: We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS: Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS: We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.

Spontaneous Coronary Artery Dissection in Patients With a Provisional Diagnosis of Takotsubo Syndrome.

Background Takotsubo syndrome (TTS) mimics acute myocardial infarction in the absence of culprit coronary artery disease and is more common in women. Spontaneous coronary artery dissection (SCAD) shares a predilection for women, can result in left ventricular wall motion abnormalities similar to TTS, and may manifest subtle angiographic findings. The aim of this study was to determine the frequency of SCAD misdiagnosed as TTS. Methods and Results Coronary angiograms of patients presenting with a provisional diagnosis of TTS were retrospectively reviewed by an independent expert blinded to left ventriculography and the specific purpose of the study to assess for SCAD. TTS was defined using European Society for Cardiology criteria. SCAD was categorized according to the Saw angiographic classification. Among 80 women with a provisional diagnosis of TTS, 2 (2.5%) met angiographic criteria for definite SCAD. Both dissections were located in the distal left anterior descending coronary artery and classified as type 2b. The wall motion abnormality was apical in both cases. An additional 7 patients (9%) had angiography that was indeterminate for SCAD. Clinical characteristics of patients with and without SCAD were similar. Conclusions Among patients with a provisional diagnosis of TTS, definite SCAD in the left anterior descending coronary artery was present in 2.5% of cases, and coronary angiography was indeterminate for SCAD in an additional 9%. Careful review of coronary angiography may avoid missed diagnoses of SCAD in patients with myocardial infarction, nonobstructive coronary arteries, and wall motion abnormalities consistent with TTS. Intracoronary imaging maybe considered to establish a definitive diagnosis of SCAD when angiography is inconclusive.

Myocardial Injury After Noncardiac Surgery: A Systematic Review and Meta-Analysis.

Myocardial injury after noncardiac surgery (MINS) is a common postoperative complication associated with adverse cardiovascular outcomes. The purpose of this systematic review was to determine the incidence, clinical features, pathogenesis, management, and outcomes of MINS. We searched PubMed, Embase, Central and Web of Science databases for studies reporting the incidence, clinical features, and prognosis of MINS. Data analysis was performed with a mixed-methods approach, with quantitative analysis of meta-analytic methods for incidence, management, and outcomes, and a qualitative synthesis of the literature to determine associated preoperative factors and MINS pathogenesis. A total of 195 studies met study inclusion criteria. Among 169 studies reporting outcomes of 530,867 surgeries, the pooled incidence of MINS was 17.9% [95% confidence interval (CI), 16.2-19.6%]. Patients with MINS were older, more frequently men, and more likely to have cardiovascular risk factors and known coronary artery disease. Postoperative mortality was higher among patients with MINS than those without MINS, both in-hospital (8.1%, 95% CI, 4.4-12.7% vs 0.4%, 95% CI, 0.2-0.7%; relative risk 8.3, 95% CI, 4.2-16.6, P < 0.001) and at 1-year after surgery (20.6%, 95% CI, 15.9-25.7% vs 5.1%, 95% CI, 3.2-7.4%; relative risk 4.1, 95% CI, 3.0-5.6, P < 0.001). Few studies reported mechanisms of MINS or the medical treatment provided. In conclusion, MINS occurs frequently in clinical practice, is most common in patients with cardiovascular disease and its risk factors, and is associated with increased short- and long-term mortality. Additional investigation is needed to define strategies to prevent MINS and treat patients with this diagnosis.

ST-segment elevation and cardiac magnetic resonance imaging findings in myocardial infarction with non-obstructive coronary arteries.

PURPOSE: Patients with myocardial infarction and non-obstructive coronary arteries (MINOCA) may present with or without ST-elevation (STE) on the electrocardiogram (ECG). Previous studies have shown that STE was associated with higher risk of early mortality and long-term major adverse coronary events, and that cardiac magnetic resonance imaging (CMR) can help to determine whether the cause of a MINOCA presentation is ischemic or non-ischemic. We set out to determine the relationship between STE and CMR findings in patients presenting with MINOCA. DESIGN: Patients who underwent CMR based on a provisional diagnosis of MINOCA were pooled from three prospective cohort studies: the multicenter Stockholm Myocardial Infarction with Normal Coronaries, a prospective University of Adelaide study, and a prospective NYU School of Medicine diagnostic imaging study. STE was defined as ≥1 mm in ≥2 contiguous leads. RESULTS: Among 292 patients, average age was 57.0 years (±11.9), and 68% were female. Fifty-seven had STE, 231 had no STE and four had left bundle branch block. There was no difference between patients with vs. without STE in the likelihood of the CMR findings of infarction (21% vs. 18%), myocarditis (10% vs. 14%), left ventricular wall motion pattern consistent with takotsubo syndrome on CMR (16% vs. 14%). CONCLUSION: STE on the presenting ECG was not associated with CMR findings in patients with a provisional diagnosis of MINOCA. Based on these findings, increased risk among MINOCA patients with STE does not appear to be related to variation in these CMR findings.

Hospital readmission following takotsubo syndrome.

AIMS: Takotsubo syndrome (TTS) is characterized by transient left ventricular dysfunction with symptoms and electrocardiographic changes mimicking acute myocardial infarction (AMI). The objective of this study was to evaluate in-hospital death and hospital readmission in patients with TTS and to compare outcomes to patients with AMI. METHODS AND RESULTS: Patients diagnosed with TTS and AMI were identified using the United States Nationwide Readmission Database from 2010 to 2014. In-hospital outcomes for the index admission, and rates and causes of 30 day readmissions were compared between TTS patients and AMI patients without TTS. Sixty-one thousand, four hundred, and twelve patients with TTS and 3 470 011 patients with AMI without TTS were identified. Patients with TTS were younger, more often women (89% vs. 41%), and less likely to have cardiovascular risk factors than AMI patients. Mortality during the index admission was lower in TTS compared with AMI (2.3% vs. 10.2%, P < 0.0001). Cardiogenic shock occurred at the same frequency (5.7%) with TTS or AMI. Among TTS survivors, 7132 patients (11.9%) were readmitted within 30 days, and mortality associated with readmission was 3.5%. The most common reason for readmission after TTS was heart failure (HF; 10.6% of readmissions). CONCLUSION: Takotsubo syndrome is associated with substantial morbidity and mortality. Although outcomes are more favourable than AMI, approximately 2% of patients died in hospital and approximately 12% of survivors were readmitted within 30 days; HF was the most frequent indication for rehospitalization. Careful outpatient follow-up of TTS patients may be warranted to avoid readmissions.