Faculty Bibliography

BACKGROUND:Ischemia with nonobstructive coronary arteries (INOCA) is common clinically, particularly among women, but its prevalence among patients with at least moderate ischemia and the relationship between ischemia severity and non-obstructive atherosclerosis severity are unknown. OBJECTIVES/OBJECTIVE:The authors investigated predictors of INOCA in enrolled, nonrandomized participants in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), sex differences, and the relationship between ischemia and atherosclerosis in patients with INOCA. METHODS:Core laboratories independently reviewed screening noninvasive stress test results (nuclear imaging, echocardiography, magnetic resonance imaging or nonimaging exercise tolerance testing), and coronary computed tomography angiography (CCTA), blinded to results of the screening test. INOCA was defined as all stenoses <50% on CCTA in a patient with moderate or severe ischemia on stress testing. INOCA patients, who were excluded from randomization, were compared with randomized participants with ≥50% stenosis in ≥1 vessel and moderate or severe ischemia. RESULTS:Among 3,612 participants with core laboratory-confirmed moderate or severe ischemia and interpretable CCTA, 476 (13%) had INOCA. Patients with INOCA were younger, were predominantly female, and had fewer atherosclerosis risk factors. For each stress testing modality, the extent of ischemia tended to be less among patients with INOCA, particularly with nuclear imaging. There was no significant relationship between severity of ischemia and extent or severity of nonobstructive atherosclerosis on CCTA. On multivariable analysis, women female sex was independently associated with INOCA (odds ratio: 4.2 [95% CI: 3.4-5.2]). CONCLUSIONS:Among participants enrolled in ISCHEMIA with core laboratory-confirmed moderate or severe ischemia, the prevalence of INOCA was 13%. Severity of ischemia was not associated with severity of nonobstructive atherosclerosis. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

BACKGROUND:Male sex, elevated troponin levels, and elevated D-dimer levels are associated with more complicated COVID-19 illness and greater mortality; however, while there are known sex differences in the prognostic value of troponin and D-dimer in other disease states, it is unknown whether they exist in the setting of COVID-19. OBJECTIVE:We assessed whether sex modified the relationship between troponin, D-dimer, and severe COVID-19 illness (defined as mechanical ventilation, ICU admission or transfer, discharge to hospice, or death). METHODS:We conducted a retrospective cohort study of patients hospitalized with COVID-19 at a large, academic health system. We used multivariable regression to assess associations between sex, troponin, D-dimer, and severe COVID-19 illness, adjusting for demographic, clinical, and laboratory covariates. To test whether sex modified the relationship between severe COVID-19 illness and troponin or D-dimer, models with interaction terms were utilized. RESULTS:Among 4,574 patients hospitalized with COVID-19, male sex was associated with higher levels of troponin and greater odds of severe COVID-19 illness, but lower levels of initial D-dimer when compared with female sex. While sex did not modify the relationship between troponin level and severe COVID-19 illness, peak D-dimer level was more strongly associated with severe COVID-19 illness in male patients compared to female patients (males: OR=2.91, 95%CI=2.63-2.34, p<0.001; females: OR=2.31, 95%CI=2.04-2.63, p<0.001; p-interaction=0.005). CONCLUSION/CONCLUSIONS:Sex did not modify the association between troponin level and severe COVID-19 illness, but did modify the association between peak D-dimer and severe COVID-19 illness, suggesting greater prognostic value for D-dimer in males with COVID-19.

BACKGROUND:The ISCHEMIA and the ISCHEMIA-CKD trials found no statistical difference in the primary clinical endpoint between initial invasive management and initial conservative management of patients with chronic coronary disease and moderate to severe ischemia on stress testing without or with advanced chronic kidney disease (CKD). In ISCHEMIA, there was numerically lower cardiovascular mortality but higher non-cardiovascular mortality with no significant difference in all-cause death with an initial invasive strategy when compared with a conservative strategy. However, an invasive strategy increased peri-procedural myocardial infarction (MI) but decreased spontaneous MI with continued separation of curves over time, which potentially may lead to reduced risk of cardiovascular and all-cause mortality. Thus, the long-term effect of invasive management strategy on mortality remains unclear. In ISCHEMIA-CKD, the treatment and cause-specific mortality rates were similar during follow-up. METHODS:Funded by the National Heart, Lung, and Blood Institute, the ISCHEMIA-EXTEND observational study is the long-term follow-up of surviving participants (projected median of 10 years) with chronic coronary disease from the ISCHEMIA trial. In the ISCHEMIA trial, 5,179 participants with moderate or severe stress-induced ischemia were randomized to initial invasive management with angiography, revascularization when feasible, and guideline-directed medical therapy (GDMT), or initial conservative management with GDMT alone and angiography reserved for failure of medical therapy. ISCHEMIA-CKD EXTEND is the long-term follow-up of surviving participants (projected median of 9 years) from the ISCHEMIA-CKD trial, a companion trial that included 777 patients with advanced CKD. Ascertainment of death will be conducted via direct participant contact, medical record review, and/or vital status registry search. The overarching objective of long-term follow-up is to assess whether there are between-group differences in long-term all-cause, cardiovascular, and non-cardiovascular mortality, and increase precision around the treatment effect estimates for risk of all-cause, cardiovascular, and non-cardiovascular mortality. We will conduct Bayesian survival modeling to take advantage of rich inferences using the posterior distribution of the treatment effect. CONCLUSIONS:The long-term effect of an initial invasive versus conservative strategy on all-cause, cardiovascular, and non-cardiovascular mortality will be assessed. The findings of ISCHEMIA-EXTEND and ISCHEMIA-CKD EXTEND will inform patients, practitioners, practice guidelines, and health policy.

Since optical coherence tomography (OCT) was first performed in humans two decades ago, this imaging modality has been widely adopted in research on coronary atherosclerosis and adopted clinically for the optimization of percutaneous coronary intervention. In the past 10 years, substantial advances have been made in the understanding of in vivo vascular biology using OCT. Identification by OCT of culprit plaque pathology could potentially lead to a major shift in the management of patients with acute coronary syndromes. Detection by OCT of healed coronary plaque has been important in our understanding of the mechanisms involved in plaque destabilization and healing with the rapid progression of atherosclerosis. Accurate detection by OCT of sequelae from percutaneous coronary interventions that might be missed by angiography could improve clinical outcomes. In addition, OCT has become an essential diagnostic modality for myocardial infarction with non-obstructive coronary arteries. Insight into neoatherosclerosis from OCT could improve our understanding of the mechanisms of very late stent thrombosis. The appropriate use of OCT depends on accurate interpretation and understanding of the clinical significance of OCT findings. In this Review, we summarize the state of the art in cardiac OCT and facilitate the uniform use of this modality in coronary atherosclerosis. Contributions have been made by clinicians and investigators worldwide with extensive experience in OCT, with the aim that this document will serve as a standard reference for future research and clinical application.

OBJECTIVE:This study aims to examine the incidence of pregnancy-related cardiometabolic conditions and severe cardiovascular outcomes, and their relationship in US Medicaid-funded women. METHODS:Medicaid is a government-sponsored health insurance programme for low-income families in the USA. We report the incidence of pregnancy-related cardiometabolic conditions (hypertensive disorders and diabetes in, or complicated by, pregnancy) and severe cardiovascular outcomes (myocardial infarction, stroke, acute heart failure, cardiomyopathy, cardiac arrest, ventricular fibrillation, ventricular tachycardia, aortic dissection/aneurysm and peripheral vascular disease) among Medicaid-funded women with a birth (International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis code O80 or O82) over the period January 2015-June 2019, from the states of Georgia, Ohio and Indiana. In this cross-sectional cohort, we examined the relationship between pregnancy-related cardiometabolic conditions and severe cardiovascular outcomes from pregnancy through to 60 days after birth using multivariable models. RESULTS:Among 74 510 women, mean age 26.4 years (SD 5.5), the incidence per 1000 births of pregnancy-related cardiometabolic conditions was 224.3 (95% CI 221.3 to 227.3). The incidence per 1000 births of severe cardiovascular conditions was 10.8 (95% CI 10.1 to 11.6). Women with pregnancy-related cardiometabolic conditions were at greater risk of having a severe cardiovascular condition with an age-adjusted OR of 3.1 (95% CI 2.7 to 3.5). CONCLUSION/CONCLUSIONS:This US cohort of Medicaid-funded women have a high incidence of severe cardiovascular conditions during pregnancy. Cardiometabolic conditions of pregnancy conferred threefold higher odds of severe cardiovascular outcomes.

The Cardiovascular Disease in Women Committee of the American College of Cardiology convened a working group to develop a consensus regarding the continuing rise of mortality rates in young women aged 35 to 54 years. Heart disease mortality rates in young women continue to increase. Young women have increased mortality secondary to ischemic heart disease (IHD) compared with comparably aged men and similar mortality to that observed among older women. The authors reviewed the published evidence, including observational and mechanistic/translational data, and identified knowledge gaps pertaining to young women. This paper provides clinicians with pragmatic, evidence-based management strategies for young women at risk for IHD. Next-step research opportunities are outlined. This report presents highlights of the working group review and a summary of suggested research directions to advance the IHD field in the next decade.

Aims/UNASSIGNED:We aimed to use optical coherence tomography (OCT) to identify differences in atherosclerotic culprit lesion morphology in women with myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) compared with MI with obstructive coronary artery disease (MI-CAD). Methods and results/UNASSIGNED:Women with an OCT-determined atherosclerotic aetiology of non-ST segment elevation (NSTE)-MINOCA (angiographic diameter stenosis <50%) who were enrolled in the multicentre Women's Heart Attack Research Program (HARP) study were compared with a consecutive series of women with NSTE-MI-CAD who underwent OCT prior to coronary intervention at a single institution. Atherosclerotic pathologies identified by OCT included plaque rupture, plaque erosion, intraplaque haemorrhage (IPH, a region of low signal intensity with minimum attenuation adjacent to a lipidic plaque without fibrous cap disruption), layered plaque (superficial layer with clear demarcation from the underlying plaque indicating early thrombus healing), or eruptive calcified nodule.We analysed 58 women with NSTE-MINOCA and 52 women with NSTE-MI-CAD. Optical coherence tomography features of underlying vulnerable plaque (thin-cap fibroatheroma) were less common in MINOCA (3 vs. 35%) than in MI-CAD. Intraplaque haemorrhage (47 vs. 2%) and layered plaque (31 vs. 12%) were more common in MINOCA than MI-CAD, whereas plaque rupture (14 vs. 67%), plaque erosion (8 vs. 14%), and calcified nodule (0 vs. 6%) were less common in MINOCA. The angle of ruptured cavity was smaller and thrombus burden was lower in MINOCA. Conclusion/UNASSIGNED:The prevalence of atherothrombotic culprit lesion subtype varied substantially between MINOCA and MI-CAD. A majority of culprit lesions in MINOCA had the appearance of IPH or layered plaque. Clinical Trial Registration Information/UNASSIGNED:

BACKGROUND:The ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial randomized participants with chronic coronary disease (CCD) to guideline-directed medical therapy with or without angiography and revascularization. The study examined the association of nonadherence with health status outcomes. OBJECTIVES/OBJECTIVE:The study sought to compare 12-month health status outcomes of adherent and nonadherent participants with CCD with an a priori hypothesis that nonadherent patients would have better health status if randomized to invasive management. METHODS:Self-reported medication-taking behavior was assessed at randomization with a modified 4-item Morisky-Green-Levine Adherence Scale, and participants were classified as adherent or nonadherent. Twelve-month health status was assessed with the 7-item Seattle Angina Questionnaire (SAQ-7) summary score (SS), which ranges from 0 to 100 (higher score = better). The association of adherence with outcomes was evaluated using Bayesian proportional odds models, including an interaction by study arm (conservative vs invasive). RESULTS:Among 4,480 randomized participants, 1,245 (27.8%) were nonadherent at baseline. Nonadherent participants had worse baseline SAQ-7 SS in both conservative (72.9 ± 19.3 vs 75.6 ± 18.4) and invasive (71.0 ± 19.8 vs 74.2 ± 18.7) arms. In adjusted analyses, adherence was associated with higher 12-month SAQ-7 SS in both treatment groups (mean difference in SAQ-7 SS with conservative treatment = 1.6 [95% credible interval: 0.3-2.9] vs with invasive management = 1.9 [95% credible interval: 0.8-3.1]), with no interaction by treatment. CONCLUSIONS:More than 1 in 4 participants reported medication nonadherence, which was associated with worse health status in both conservative and invasive treatment strategies at baseline and 12 months. Strategies to improve medication adherence are needed to improve health status outcomes in CCD, regardless of treatment strategy. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).