Faculty Bibliography

BACKGROUND:The frequency of residual angina and its impact on health status and death following anatomic complete revascularization in symptomatic patients with chronic coronary disease are unknown. METHODS:Data were analyzed from ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial participants randomized to invasive management with baseline angina (Seattle Angina Questionnaire Angina Frequency score <100), no prior coronary artery bypass graft surgery, and anatomic complete revascularization within 90 days of randomization. The primary outcome was frequency of residual angina after revascularization, defined as a Seattle Angina Questionnaire Angina Frequency score <100 within 6 months of randomization. Secondary outcomes included 6-month health status and medication use and 5-year all-cause and cardiovascular death. RESULTS:=0.006). Five-year all-cause and cardiovascular death did not differ significantly between groups. CONCLUSIONS:Residual angina is common (>40%) following anatomic complete revascularization for chronic coronary disease and is associated with reduced quality of life and greater antianginal medication use but no increase in death. REGISTRATION/BACKGROUND:Unique Identifier: NCT01471522.

BACKGROUND:Guidelines on primary prevention of atherosclerotic cardiovascular disease (ASCVD) recommend considering risk enhancing factors (REFs) to inform decisions on use of lipid-lowering therapies for the 44 million Americans with borderline or intermediate estimated ASCVD risk. OBJECTIVE:To quantify REF burden and estimate whether REFs are associated with higher likelihood of statin use. DESIGN/METHODS:Cross-sectional using National Health and Nutrition Examination Survey pooled 2015 to March 2020. PARTICIPANTS/METHODS:Adults aged 40-75 without known ASCVD. MAIN MEASURES/METHODS:Nine REFs were measurable in NHANES including family history of premature ASCVD, rheumatoid arthritis, metabolic syndrome, premature menopause, chronic kidney disease and biomarkers of hypercholesteremia, hypertriglyceridemia, elevated low-density lipoprotein cholesterol and elevated C-reactive protein. Prevalence of REFs and association with statin use were calculated overall and across ASCVD treatment categories based on diabetes and 10-year ASCVD risk.  KEY RESULTS: In the sample of 3,111 participants (mean age 56 years; 52.6% female) weighted to represent 115.7 million US adults, 77% had at least one REF and 28% had at least three. The most common REFs were elevated high sensitivity C-reactive protein (49.6%) metabolic syndrome (48.3%), and hypertriglyceridemia (18.9%). The presence of any REF was associated with a 2.17 (95% CI, 1.42-3.33) greater odds of statin use. Metabolic syndrome, family history of premature ASCVD, hypertriglyceridemia and hypercholesteremia were associated with greater odds of statin use (aORs ranging from 1.5 to 2.3). The presence of any REF was associated with higher likelihood of statin use in participants with low (< 5%), intermediate (7.5-19%), and high ASCVD risk (≥ 20%), but not borderline ASCVD risk (5-7.4%) or diabetes categories. CONCLUSIONS:REFs are highly prevalent and inconsistently associated with statin use. Achieving the potential benefit of individualizing ASCVD risk estimates will require clearer guidance on when and how to incorporate REFs into primary prevention prescribing decisions.

BACKGROUND:In the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial, women had worse angina than men despite less severe coronary artery disease (CAD) and ischemia. We examined which patient and treatment factors might explain sex-based differences in angina. METHODS:ISCHEMIA randomized patients with moderate or severe ischemia to an initial invasive strategy of cardiac catheterization with complete revascularization plus guideline-directed medical therapy (GDMT), or an initial conservative strategy of GDMT alone with invasive management reserved for GDMT failure. Coronary CT angiography was performed in most participants. Angina-related health status was collected at baseline and 1-year using the Seattle Angina Questionnaire (SAQ). RESULTS:Of 4,617 ISCHEMIA participants with complete SAQ data, women averaged 6.5 points (95% CI 5.2-7.8) lower (worse) baseline SAQ summary scores (SS) than men. This difference was not reduced by adjustment for demographics and clinical characteristics. Women had lower unadjusted 1-year SAQ-SS than men (Invasive -3.8 points, Conservative -5.7 points). These sex-based differences were attenuated but not eliminated by adjustment for baseline SAQ-SS. Adjustment for post-randomization treatment (GDMT intensity, risk factor goal achievement and, in the invasive strategy, complete revascularization) did not narrow the sex difference. CONCLUSIONS:Women with chronic CAD in ISCHEMIA had worse angina-related health status than men at baseline and 1-year. Differences were not explained by demographic or clinical characteristics, intensity of GDMT, or completeness of revascularization. It is thus important to consider other factors that may mediate these results, including differences in nociception, coronary microvascular dysfunction and/or vasospasm.

BACKGROUND:Myocardial infarction with non-obstructive coronary arteries (MINOCA) has several underlying causes, including mimicking conditions in some cases. Imaging is recommended to identify MINOCA etiologies, but it remains unclear which patients are most likely to have abnormal findings. We characterized MINOCA mechanisms, analyzed predictors of imaging abnormalities and explored sex differences. METHODS:We enrolled patients with clinical diagnosis of MI in an international, prospective, diagnostic study at 28 sites in US, Canada and UK. After a women-only phase, we included both sexes. Individuals with ≥50% diameter stenosis or coronary dissection on angiography, or alternate causes for the clinical presentation, were excluded. Participants had multi-vessel coronary optical coherence tomography (OCT) during index coronary angiography and cardiac magnetic resonance imaging (CMR) within one week. Independent core laboratories interpreted imaging, blinded to other results. RESULTS:Among 754 patients enrolled, 389 had MINOCA and 336 with MINOCA underwent OCT (270 women and 66 men); CMR was completed in 284 (85%). An OCT-defined culprit lesion was identified in 45% (116/270 women [43% ] and 35/66 men [53%], p=0.18). CMR demonstrated an ischemic pattern in 114/284 (40%), similar by sex (96/225 women [43%] vs. 18/59 men [31%], p=0.12). A non-ischemic pattern was observed in 23% (23% of women, 25% of men, p=0.78). We identified a cause of the clinical presentation in 79% of patients with both tests completed: 59% had an ischemic cause of MINOCA and 20% had a non-ischemic mimicking condition. OCT alone found a MINOCA etiology in 151/336 (45%) and CMR alone in 180/284 (63%). Predictors of an OCT culprit lesion included age, abnormal angiogram, and number of vessels imaged, but 27% of normal angiograms harbored a culprit lesion. Predictors of abnormal CMR were peak troponin, shorter time to CMR, and non-Asian race, but CMR was abnormal in 40% when troponin was <4-fold above the upper reference limit. CONCLUSIONS:The combination of multi-vessel coronary OCT and CMR in patients with a clinical diagnosis of MINOCA confirmed MI in 59% and identified an alternate cause (MINOCA mimic) in 20%. Clinical factors had limited utility to predict imaging abnormalities. No sex differences in imaging results were detected.

BACKGROUND:Prior authorizations could hinder the filling of life-saving heart failure (HF) medications, such as angiotensin receptor neprilysin inhibitors (ARNIs) and sodium glucose cotransporter 2 inhibitors (SGLT2is). OBJECTIVES/OBJECTIVE:The aim of the study was to determine whether prior authorizations were associated with delayed or decreased filling for ARNI and SGLT2i. METHODS:This was a retrospective cohort study using electronic health record, pharmacy fill, and neighborhood-level data from a large, academic health system. We included patients with HF and a new prescription for ARNI or SGLT2i between April 1, 2021, and April 30, 2023, and assessed for presence of prior authorization requirement. Outcomes included days to first fill and never filling the prescription. Analyses were conducted using inverse probability weighting methods. RESULTS:Among 2,183 patients, 12.2% (152/1,243) and 14.3% (165/1,150) had a prior authorization requirement for ARNI or SGLT2i, respectively. Patients requiring prior authorization tended to be younger, identify as non-Hispanic Black or Hispanic, have non-Medicare insurance, and have fewer comorbidities. In weighted models, patients requiring prior authorization took 3.03 (95% CI: 2.16-4.25) times longer to fill ARNI, 6.75 (95% CI: 4.44-10.3) times longer to fill SGLT2i, and were 2.23 (95% CI: 1.37-3.65) times more likely to never fill SGLT2i prescriptions (all P < 0.001). CONCLUSIONS:Prior authorization requirements were more common for patients identifying as Black or Hispanic and were associated with decreased and delayed filling of ARNI and SGLT2i. Our findings highlight an important barrier to mortality-reducing, guideline-recommended medications for HF.

AIMS/OBJECTIVE:To assess whether baseline functional performance assessed by exercise treadmill stress testing (EST) has additive value to coronary computed tomography angiography (CCTA) for risk stratification among patients with chronic coronary disease (CCD) and moderate or severe ischemia. METHODS AND RESULTS/RESULTS:We performed a subgroup analysis of the ISCHEMIA trial including participants who underwent EST and CCTA. EST data and severity of coronary artery disease (CAD) on CCTA were evaluated by core laboratories, blinded to clinical data and results of the other test. The primary outcome for this analysis was all-cause death. Secondary outcomes were cardiovascular death, cardiovascular death or myocardial infarction (MI), MI and a composite of cardiovascular death, MI, or hospitalization for heart failure, unstable angina, or resuscitated cardiac arrest. EST and number of vessels diseased on CCTA were both interpretable in 1864 patients (median age 62 years, IQR 55-68, 83% males). During a median follow-up of 3.1 years, 69 patients died. Higher peak metabolic equivalents (METs) achieved on the qualifying stress test was associated with lower all-cause death (HR 0.86, CI 0.76-0.98; p=0.025). The addition of peak METs to CAD severity improved the predictive ability of the all-cause death and CV death models by 10-20% and 8-13% respectively, depending on the metrics used for CCTA. Adding peak METs to CCTA anatomical models resulted in better prediction of MI by 11-17%, cardiovascular death or MI by 10-14%, and 5-component composite outcome by 12-16%. CONCLUSION/CONCLUSIONS:Peak METs on EST, a marker of functional performance, added prognostic value to models including CCTA anatomical findings in patients with CCD and moderate or severe ischemia.

BACKGROUND:Research comparing the prognostic value of stress cardiac magnetic resonance (CMR) to other stress modalities in patients with coronary disease is limited. OBJECTIVES/OBJECTIVE:The authors compared the prognostic value of stress CMR vs alternative testing by either single-photon emission computed tomography or stress echocardiography (SPECT/echo) in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial. METHODS:CMR vs SPECT/echo was compared in 3,909 patients randomized in ISCHEMIA after sites' interpretation of moderate to severe ischemia. Ischemia and infarct extent, measured by either CMR or SPECT/echo, were each associated with the trial's primary outcome of cardiovascular death, nonfatal myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest, at a median follow-up of 3.37 years (Q1-Q3: 2.20-4.56 years). RESULTS:Compared with SPECT/echo (n = 5,627), CMR participants (n = 313) were not different in key demographic factors but were more likely to have severe ischemia (57% vs 38%; P < 0.001) and to be randomized (n = 257, 82%, vs n = 3,652, 65%; P < 0.001). Ischemia severity (no/mild, moderate, severe) by CMR core laboratory was associated with cumulative 4-year event rates of all trial-specific endpoints, including the primary outcome (P = 0.042), cardiovascular death/MI (P = 0.041), and nonfatal MI (P = 0.03), but SPECT/echo ischemia severity was not. No/mild, moderate, and severe ischemia by CMR were associated with 0%, 14%, and 23% 4-year primary outcome rates, respectively, compared with 18%, 15%, and 16%, by SPECT/echo. After adjustment for age, estimated glomerular filtration rate, and diabetes, the association between ischemia extent and the primary endpoint differed by imaging modality, with each additional ischemic segment on CMR associated with a 13% increase in hazard (interaction P = 0.02). In participants assigned to initial conservative management who had no/mild ischemia on imaging, 4-year rates of invasive referral and coronary revascularization were lower in the CMR than SPECT/echo group (16.7% and 0%, respectively, for CMR; and 31% and 13.3%, respectively, for SPECT/echo). CONCLUSIONS:Ischemia severity by CMR had a stronger association with all ISCHEMIA trial endpoints compared with SPECT/echo.

BACKGROUND:Coronary microvascular dysfunction (CMD) is present in approximately 40% of patients with ischemia with no obstructive coronary arteries (INOCA) and has been associated with inflammation. We investigated associations between measures of inflammation of the coronary perivascular adipose tissue assessed by coronary computed tomography angiography (CCTA) and results of invasive coronary function testing (CFT) to diagnose CMD. METHODS:Adults referred for clinically indicated invasive coronary angiography who had less than 50% stenosis in all epicardial arteries were prospectively enrolled. CMD was defined as a coronary flow reserve (CFR) less than 2.5 or index of microvascular resistance (IMR) greater than or equal to 25 using bolus thermodilution in the left anterior descending (LAD) coronary artery. Coronary perivascular fat attenuation index was assessed by CCTA in the right coronary artery (RCA) and LAD. T tests were used to evaluate differences in perivascular FAI by CMD status. RESULTS:A total of 31 participants underwent CFT and CCTA. The mean age was 58 ± 11.7 years, 77% were female, and 61% were white. CMD was present in 15 participants (48%). No differences in perivascular FAI were observed in patients with and without CMD, either in the RCA [-74.2 ± 9.8 vs. -69.9 ± 10.3 Hounsfield units (HU), P = 0.24] or LAD (-76.4 ± 10.2 vs. -74.8 ± 12.7 HU, P = 0.69). Perivascular FAI was not correlated with CFR or IMR measurements in the RCA or LAD. CONCLUSION/CONCLUSIONS:There were no associations between CMD diagnosed by invasive CFT and perivascular FAI by CCTA in patients with INOCA. Further research is needed to understand the relationship between vascular inflammation and CMD in INOCA.

BACKGROUND/UNASSIGNED:compared with the conventional index of microcirculatory resistance (IMR) in a cohort of individuals with INOCA. METHODS/UNASSIGNED:was calculated retrospectively, blinded to CFT results. CMD was defined by IMR ≥25 or CFR <2.5. RESULTS/UNASSIGNED:and IMR. CONCLUSIONS/UNASSIGNED:appears unreliable for identifying CMD in patients with INOCA.