Faculty Bibliography

BACKGROUND:Chronic coronary syndromes (CCS) occur commonly in the absence of flow-limiting epicardial coronary stenoses. Ischemia or angina with no obstructive coronary arteries (INOCA/ANOCA) may be caused by coronary microvascular disease, coronary artery spasm, myocardial bridging, diffuse atherosclerosis, or a combination of disorders. METHODS & RESULTS/RESULTS:We highlight the new recommendations in the 2024 European Society of Cardiology (ESC) guidelines on CCS relevant to the diagnosis and management of INOCA/ANOCA. The guidelines place a new emphasis on consideration of INOCA/ANOCA early during cardiovascular risk stratification and the initial diagnostic workup for chest pain. There is a new class I recommendation for the availability of invasive coronary function testing (CFT) at the time of initial coronary angiography, when mechanisms of chest pain are uncertain after non-invasive testing, and in patients with established INOCA/ANOCA who have persistent symptoms and poor quality of life despite medical therapy. Once underlying disorders have been identified based on the results of invasive CFT, the ESC guidelines emphasize a patient-centered, mechanism-based approach to medical treatment of INOCA/ANOCA to improve symptoms and quality of life. CONCLUSIONS:The 2024 ESC CCS guidelines provide a new vision for the diagnosis and management of ANOCA/INOCA, with an expanded role for invasive CFT and targeted medical therapy to improve symptoms and quality of life in patients with angina.

BACKGROUND/UNASSIGNED:The relationship between the extent and severity of stress-induced ischemia and the extent and severity of anatomic coronary artery disease (CAD) in patients with obstructive CAD is multifactorial and includes the intensity of stress achieved, type of testing used, presence and extent of prior infarction, collateral blood flow, plaque characteristics, microvascular disease, coronary vasomotor tone, and genetic factors. Among chronic coronary disease participants with site-determined moderate or severe ischemia, we investigated associations between ischemia severity on stress testing and the extent of CAD on coronary computed tomography angiography. METHODS/UNASSIGNED:Clinically indicated stress testing included nuclear imaging, echocardiography, cardiac magnetic resonance imaging, or nonimaging exercise tolerance test. Among those with preserved renal function who underwent coronary computed tomography angiography, we examined relationships between ischemia and CAD by coronary computed tomography angiography, overall, and by stress test modality, regardless of subsequent randomization. Core laboratories categorized ischemia as severe, moderate, mild, or none, while the extent and severity of anatomic CAD were categorized based on the modified Duke prognostic index. RESULTS/UNASSIGNED:Among 3601 participants with interpretable stress tests and coronary computed tomography angiography, ischemia severity was weakly associated with CAD extent/severity (r=0.27), with modest variability in strength of association by modality: nuclear (n=1532; r=0.40), echocardiography (n=827; r=0.15), cardiac magnetic resonance imaging (n=108; r=0.31), and exercise tolerance test (n=1134; r=0.18). The extent of infarction on nuclear imaging and echocardiography was weakly associated with CAD extent/severity. CONCLUSIONS/UNASSIGNED:Overall, ischemia severity on stress testing showed weak to moderate associations with the anatomic extent of CAD in this cohort with moderate or severe ischemia on local interpretation and controlled symptoms. REGISTRATION/UNASSIGNED:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

BACKGROUND:Myocardial infarction with nonobstructive coronary arteries (MINOCA) occurs in 6-15 % of MI patients. Cardiac magnetic resonance (CMR) imaging identifies MINOCA etiologies, but access may be limited. METHODS:We assessed associations between the index electrocardiogram (ECG) and CMR in MINOCA. Women with MI and < 50 % angiographic stenosis in all vessels were prospectively enrolled at 16 sites. CMR (median 6d from MI) was analyzed for late gadolinium enhancement (LGE), myocardial edema, and wall motion. We assessed ECGs for T-wave inversions (TWI), Q-waves (QW), ST-elevations (STE), ST-depressions (STD), and fragmented QRS complexes (fQRS). We calculated the DETERMINE score (# leads TWI + # fQRS +2*[# QW], excluding aVR, V1). RESULTS:Among 112 women with interpretable ECG, 81.3 % (91/112) had abnormal ECG; 50 % (56/112) had ≥1 TWI. CMR was abnormal in 74.1 % (83/112), with LGE in 49.1 % (55/112) and myocardial edema in 61.6 % (69/112). DETERMINE score ≥ 3 was associated with abnormal CMR (adjusted odds ratio [aOR] aOR 6.06 [1.89, 24.6], p = 0.002) and LGE (aOR 3.10 [1.26, 8.00], p = 0.013), but not edema (aOR 1.86 [0.80, 4.43], p = 0.152). TWI was also associated with abnormal CMR and LGE after adjustment (aOR 3.13 [1.08, 10.1], p = 0.036, aOR 3.23 [1.27, 8.63], p = 0.013, respectively), but not edema (aOR 1.26 [0.54, 2.96], p = 0.589). Specificity for abnormal CMR was 0.83 for DETERMINE score ≥ 3 and 0.75 for TWI. No other ECG findings were associated with CMR abnormality. CONCLUSION/CONCLUSIONS:DETERMINE score ≥ 3 and the presence of any TWI were associated with abnormal CMR and with LGE in MINOCA. Our findings demonstrate that the index ECG can provide insight on CMR findings but without sensitivity or specificity required to forgo the CMR. We reaffirm the central role of CMR in elucidating MINOCA pathophysiology.

BACKGROUND:Whether revascularisation (REV) improves outcomes in patients with three-vessel coronary artery disease (3V-CAD) is uncertain. AIMS/OBJECTIVE:Our objective was to evaluate outcomes with REV (percutaneous coronary intervention [PCI] or coronary artery bypass graft surgery [CABG]) versus medical therapy in patients with 3V-CAD. METHODS:ISCHEMIA participants with 3V-CAD on coronary computed tomography angiography without prior CABG were included. Outcomes following initial invasive management (INV) with REV (PCI or CABG) versus initial conservative management (CON) with medical therapy alone were evaluated. Regression modelling was used to estimate the outcomes if all participants were to undergo prompt REV versus those assigned to CON. Outcomes were cardiovascular (CV) death/myocardial infarction (MI), death, CV death, and quality of life. Bayesian posterior probability for benefit (Pr [benefit]) for 1 percentage point lower 4-year rates with REV versus CON were evaluated. RESULTS:Among 1,236 participants with 3V-CAD (612 INV/624 CON), REV was associated with lower 4-year CV death/MI (adjusted 4-year difference: -4.4, 95% credible interval [CrI] -8.7 to -0.3 percentage points, Pr [benefit]=94.8%) when compared with CON, with similar results for PCI versus CON (-5.8, 95% CrI: -10.8 to -0.5 percentage points, Pr [benefit]=96.4%) and CABG versus CON (-3.7, 95% CrI: -8.8 to 1.5 percentage points, Pr [benefit]=84.7%). Adjusted 4-year REV versus CON differences were as follows: death -1.2 (95% CrI: -4.7 to 2.2) percentage points, CV death -2.3 (95% CrI: -5.5 to 0.8) percentage points, with similar results for PCI and for CABG. The Pr (benefit) for death with REV (PCI or CABG) versus CON was 49-63%. The adjusted 12-month Seattle Angina Questionnaire-7 summary score differences favoured REV: REV versus CON 4.6 (95% CrI: 2.7-6.4) percentage points; PCI versus CON 3.6 (95% CrI: 1.2-5.8) percentage points and CABG versus CON 4.3 (95% CrI: 1.5-6.9) percentage points with high Pr (benefit). CONCLUSIONS:In participants with 3V-CAD, REV (either PCI or CABG) was associated with a lower 4-year CV death/MI rate and improved quality of life, with similar results for PCI versus CON and CABG versus CON. The differences in all-cause mortality between REV and CON were small with wide confidence intervals. (ClinicalTrials.gov: NCT01471522).

BACKGROUND/UNASSIGNED:Clinical trials suggest that therapeutic-dose heparin may prevent critical illness and vascular complications due to COVID-19, but knowledge gaps exist regarding the efficacy of therapeutic heparin including its comparative effect relative to intermediate-dose anticoagulation. OBJECTIVES/UNASSIGNED:The authors performed 2 complementary secondary analyses of a completed randomized clinical trial: 1) a prespecified per-protocol analysis; and 2) an exploratory dose-based analysis to compare the effect of therapeutic-dose heparin with low- and intermediate-dose heparin. METHODS/UNASSIGNED:Patients who received initial anticoagulation dosed consistently with randomization were included. The primary outcome was organ support-free days (OSFDs), a combination of in-hospital death and days free of organ support through day 21. RESULTS/UNASSIGNED:Among 2,860 participants, 1,761 (92.8%) noncritically ill and 857 (89.1%) critically ill patients were treated per-protocol. Among noncritically ill per-protocol patients, the posterior probability that therapeutic-dose heparin improved OSFDs as compared with usual care was 99.3% (median adjusted OR: 1.36; 95% credible interval [CrI]: 1.07-1.74). Therapeutic heparin had a high posterior probability of efficacy relative to both low- (94.6%; adjusted OR: 1.26; 95% CrI: 0.95-1.64) and intermediate- (99.8%; adjusted OR: 1.80; 95% CrI: 1.22-2.62) dose thromboprophylaxis. Among critically ill per-protocol patients, the posterior probability that therapeutic heparin improved outcomes was low. CONCLUSIONS/UNASSIGNED:Among noncritically ill patients hospitalized for COVID-19 who were randomized to and initially received therapeutic-dose anticoagulation, heparin, compared with usual care, was associated with improved OSFDs, a combination of in-hospital death and days free of organ support. Therapeutic heparin appeared superior to both low- and intermediate-dose thromboprophylaxis.

BACKGROUND:In myocardial infarction with nonobstructive coronary arteries (MINOCA), there are limited patient-level data on outcomes by sex and race. OBJECTIVE:The aim of this study was to assess baseline demographics and 3-year outcomes by sex and race for MINOCA patients. METHODS: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. RESULTS: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). CONCLUSION/CONCLUSIONS: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.

Electronic health record (EHR)-embedded tools are known to improve prescribing of guideline-directed medical therapy (GDMT) for patients with heart failure. However, physicians may perceive EHR tools to be unhelpful, and may be therefore hesitant to implement these in their practice. We surveyed cardiologists about two effective EHR-tools to improve heart failure care, and they perceived the EHR tools to be easy to use, helpful, and improve the overall management of their patients with heart failure.

BACKGROUND:The ISCHEMIA trial found that patients with chronic coronary disease randomized to invasive strategy had better health status than those randomized to conservative strategy. It is unclear how best to translate these population-level results to individual patients. OBJECTIVES/OBJECTIVE:The authors sought to identify patient characteristics associated with health status from invasive and conservative strategies, and develop a prediction algorithm for shared decision-making. METHODS:One-year disease-specific health status was assessed in ISCHEMIA with the Seattle Angina Questionnaire (SAQ) Summary Score (SAQ SS) and Angina Frequency, Physical Limitations (PL), and Quality of Life (QL) domains (range 0-100, higher = less angina/better health status). RESULTS:Among 4,617 patients from 320 sites in 37 countries, mean SAQ SS was 74.1 ± 18.9 at baseline and 85.7 ± 15.6 at 1 year. Lower baseline SAQ SS and younger age were associated with better 1-year health status with invasive strategy (P interaction = 0.009 and P interaction = 0.004, respectively). For the individual domains, there were significant treatment interactions for baseline SAQ score (Angina Frequency, PL), age (PL, QL), anterior ischemia (PL), and number of baseline antianginal medications (QL), with more benefit of invasive in patients with worse baseline health status, younger age, anterior ischemia, and on more antianginal medications. Parsimonious prediction models were developed for 1-year SAQ domains with invasive or conservative strategies to support shared decision-making. CONCLUSIONS:In the management of chronic coronary disease, individual patient characteristics are associated with 1-year health status, with younger age and poorer angina-related health status showing greater benefit from invasive management. This prediction algorithm can support the translation of the ISCHEMIA trial results to individual patients. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

BACKGROUND AND AIMS/OBJECTIVE:The aim of this study was to determine the prognostic value of coronary computed tomography angiography (CCTA)-derived atherosclerotic plaque analysis in ISCHEMIA. METHODS:Atherosclerosis imaging quantitative computed tomography (AI-QCT) was performed on all available baseline CCTAs to quantify plaque volume, composition, and distribution. Multivariable Cox regression was used to examine the association between baseline risk factors (age, sex, smoking, diabetes, hypertension, ejection fraction, prior coronary disease, estimated glomerular filtration rate, and statin use), number of diseased vessels, atherosclerotic plaque characteristics determined by AI-QCT, and a composite primary outcome of cardiovascular death or myocardial infarction over a median follow-up of 3.3 (interquartile range 2.2-4.4) years. The predictive value of plaque quantification over risk factors was compared in an area under the curve (AUC) analysis. RESULTS:Analysable CCTA data were available from 3711 participants (mean age 64 years, 21% female, 79% multivessel coronary artery disease). Amongst the AI-QCT variables, total plaque volume was most strongly associated with the primary outcome (adjusted hazard ratio 1.56, 95% confidence interval 1.25-1.97 per interquartile range increase [559 mm3]; P = .001). The addition of AI-QCT plaque quantification and characterization to baseline risk factors improved the model's predictive value for the primary outcome at 6 months (AUC 0.688 vs. 0.637; P = .006), at 2 years (AUC 0.660 vs. 0.617; P = .003), and at 4 years of follow-up (AUC 0.654 vs. 0.608; P = .002). The findings were similar for the other reported outcomes. CONCLUSIONS:In ISCHEMIA, total plaque volume was associated with cardiovascular death or myocardial infarction. In this highly diseased, high-risk population, enhanced assessment of atherosclerotic burden using AI-QCT-derived measures of plaque volume and composition modestly improved event prediction.