Faculty Bibliography

BACKGROUND/UNASSIGNED:Cardiac stress testing is a cornerstone of risk stratification and management in patients with chronic coronary disease, yet the consistency and accuracy of its interpretation remain poorly defined. This analysis evaluated variation in the interpretation of myocardial ischemia between enrollment sites and core laboratories in the ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches). METHODS/UNASSIGNED:ISCHEMIA was a global (37 countries, 2012-2018) randomized trial of an initial invasive versus conservative strategy in patients with chronic coronary disease and moderate or severe ischemia. This analysis included participants with site-interpreted qualifying stress tests-nuclear, echocardiography (echo), cardiac magnetic resonance, or exercise tolerance test-and independent core laboratory adjudication. Core laboratories, serving as the reference standard, reinterpreted tests blinded to site results. A trinary outcome variable (site underestimation, concordance, or overestimation) was defined by comparing site-determined ischemia levels to standardized core lab assessments. Adjusted mixed-effects logistic regression models with random site intercepts assessed variability. RESULTS/UNASSIGNED:Among 6971 participants (mean age, 62.8 years; 73% men), site interpretations showed 0% no/mild (by design), 43% moderate, and 57% severe ischemia. Core labs reclassified these as 8% none, 11% mild, 30% moderate, and 51% severe ischemia. For the imaging modalities, median site-core lab agreement rates were ≈55%; nearly 25% of site-classified moderate/severe cases were downgraded to no or mild ischemia by core labs. Adjusted median odds ratios for site overestimation were 2.36 (95% CI, 2.02-2.82; nuclear), 1.98 (95% CI, 1.62-2.60; echo), 1.89 (95% CI, 1.0-5.41; cardiac magnetic resonance), and 2.15 (95% CI, 1.76-2.79; exercise tolerance test). Adjusted median odds ratios for underestimation ranged from 1.25 to 1.77. CONCLUSIONS/UNASSIGNED:In ISCHEMIA, enrollment sites frequently overestimated or underestimated the severity of myocardial ischemia compared with core laboratory assessments, highlighting the need for strategies to improve the consistency and accuracy of stress testing interpretation in patients with chronic coronary disease. REGISTRATION/UNASSIGNED:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

BACKGROUND:Infection with the severe acute respiratory syndrome coronavirus-2 (SARSCoV-2), the virus which causes the corona virus disease-2019 (COVID-19) has substantial evidence that patients with pre-existing coronary artery disease (CAD) have an increased risk of serious illness, adverse coronary events, and mortality following infection. The COVID-CT registry will assess whether COVID-19 alters progression of coronary atherosclerotic plaque in patients with previously defined anatomic CAD on coronary computed tomographic angiography (CCTA). Mediators and covariates such as disease severity, inflammation, and neighborhood deprivation will also be assessed. DESIGN/METHODS:The COVID-CT registry is a multicenter, longitudinal observational registry enrolling patients including patients with pre-pandemic atherosclerosis observed by CCTA from New York City and Long Island to determine the impact of COVID-19 infection. The primary aim is to test the hypothesis that patients with previously defined anatomic CAD by CCTA who are subsequently infected with SARS-CoV-2 have accelerated progression of total and noncalcified atherosclerotic plaque volumes when compared to uninfected patients. We hypothesize that systemic inflammation is a key promoter in the formation and progression of atherosclerotic plaque. Additionally, we will test whether measurement of the perivascular fat attenuation index detects high risk, coronary artery inflammation following COVID infection. SUMMARY/CONCLUSIONS:The impact of this first in-kind registry will be foundational for revising standard diagnostic pathways and risk assessment used to guide preventive care for millions of patients with CAD at increased risk from viral infection.

BACKGROUND/OBJECTIVE/OBJECTIVE:Studies show an association between elevated blood pressure, obesity, and insulin resistance with a higher risk of developing diabetes. As sodium is closely linked to elevated blood pressure and hypertension, and potassium is a counterbalancing nutrient to sodium, this study examines the association between intake of sodium, potassium, and sodium: potassium (Na:K) ratio and the incidence of diabetes. DESIGN SETTING AND PARTICIPANTS/METHODS:Retrospective data analysis of dietary intake measured by a validated food frequency questionnaire in a prospective cohort of veterans participating in the Million Veteran Program (MVP) between 2011 and 2020, who were free of diabetes at baseline. MAIN OUTCOME MEASUREMENT/METHODS:The main outcome is clinically diagnosed diabetes defined by phenotyping algorithms applied to electronic health records. RESULTS:In this study of 198,049 veterans (mean age: 63.8 ± 13.1 years, 89 % male), 7260 were diagnosed with diabetes over a mean follow-up of 4.3 years. The mean sodium intake was 1218 mg/day. A higher sodium intake was associated with an 11 % higher rate of developing diabetes (hazard ratio, HR) comparing extreme quintiles: 1.11, 95 % CI: 1.03-1.20). The average daily potassium intake was 2589 mg and the highest quintile of potassium intake was associated with a 13 % lower rate of diabetes (HR: 0.87, 95 % CI: 0.81, 0.94) compared to the lowest quintile of potassium. Highest quintile of Na:K ratio was associated with a 21 % higher rate for diabetes (HR: 1.21, 95% CI: 1.12, 1.30). The pattern of associations between Na:K ratio and diabetes closely followed the pattern of dietary sodium intake and diabetes associations. CONCLUSION/CONCLUSIONS:A higher sodium intake and a higher Na:K ratio were associated with a higher risk of diabetes in this large cohort of veterans. These findings may be applied in future work to identify personalized lifestyle and dietary supports to prevent and treat T2DM.

BACKGROUND:We present the case of a 74-year-old woman diagnosed with obstructive hypertrophic cardiomyopathy. CASE SUMMARY/METHODS:Amyloidosis was initially considered because she was genotype positive in the transthyretin gene. However, because of 2 negative 99m technetium pyrophosphate radionuclide scans, this diagnosis was considered unlikely, and endomyocardial biopsy was deferred. She had an adverse response to all attempted medical therapies for her left ventricular outflow tract obstruction and ultimately underwent surgical myectomy. Surgical pathology revealed transthyretin (TTR) amyloidosis. DISCUSSION/CONCLUSIONS:This case highlights the limitations of diagnostic testing and reinforces the consideration of more invasive procedures to determine the true underlying cause of disease. This helps clinicians provide the most advanced level of treatment available. TAKE-HOME MESSAGES/CONCLUSIONS:TTR amyloidosis can mimic hypertrophic cardiomyopathy with left ventricular outflow tract obstruction. 99m Technetium pyrophosphate scans are useful to investigate the presence of TTR amyloid, but if suspicion persists despite negative testing, it is reasonable to perform an endomyocardial biopsy.

BACKGROUND:Limited contemporary evidence exists on risk prediction by stress imaging and exercise electrocardiography (ECG) among patients with chronic coronary syndromes (CCS). Objectives From the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) study, prognosis was examined by core laboratory-defined stress imaging and exercise ECG findings in CCS patients. METHODS:A total of 5,179 patients (qualifying by stress nuclear imaging [n = 2,567], echocardiography [n = 1,085], cardiac magnetic resonance [CMR] [n = 257], and ECG [n = 1,270]) were randomized. Cox models assessed associations between trial endpoints and the number of scarred and ischemic segments, rest/stress left ventricular ejection fraction (LVEF), and ST-segment depression. HRs and 95% CIs were calculated per millimeter, segment, or 5% of LVEF. We examined prognostic models for the following trial endpoints: 1) the trial's primary endpoint of cardiovascular (CV) death, myocardial infarction (MI), resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure; 2) CV death; 3) spontaneous MI; 4) procedural MI; and 5) type 2 MI. RESULTS:The number of scarred segments (HR: 1.07 [95% CI: 1.02-1.13]; P = 0.0209), rest LVEF (HR: 0.88 [95% CI: 0.83-0.93]; P < 0.001), and stress LVEF (HR: 0.87 [95% CI: 0.83-0.91]; P < 0.001) predicted the trial's primary endpoint of CV death, MI, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure. The extent of scar and rest/stress LVEF on echocardiography and nuclear imaging predicted several trial endpoints. The number of ischemic segments predicted spontaneous (HR: 1.08 [95% CI: 1.03-1.14]; P = 0.0104) and procedural MI (HR: 1.14 [95% CI: 1.03-1.25]; P = 0.0015) but was of borderline significance for the trial's primary endpoint (P = 0.0746). Ischemia extent by CMR predicted the trial's primary endpoint (P = 0.0068) and spontaneous MI (P = 0.0042). CONCLUSIONS:ISCHEMIA trial findings from 320 worldwide centers revealed that stress imaging and exercise ECG measures exhibited a variable association with key trial endpoints delineating risk patterns for ischemia and infarction. Stress CMR ischemia predicted several trial endpoints, supporting an expanded role in the evaluation of patients with CCS (ISCHEMIA [International Study of Comparative Health Effectiveness With Medical and Invasive Approaches]; NCT01471522).

BACKGROUND:Previous studies evaluated the ability of large language models (LLMs) in medical disciplines; however, few have focused on image analysis, and none specifically on cardiovascular imaging or nuclear cardiology. This study assesses four LLMs-GPT-4, GPT-4 Turbo, GPT-4omni (GPT-4o) (Open AI), and Gemini (Google Inc.)-in responding to questions from the 2023 American Society of Nuclear Cardiology Board Preparation Exam, reflecting the scope of the Certification Board of Nuclear Cardiology (CBNC) examination. METHODS:We used 168 questions: 141 text-only and 27 image-based, categorized into four sections mirroring the CBNC exam. Each LLM was presented with the same standardized prompt and applied to each section 30 times to account for stochasticity. Performance over six weeks was assessed for all models except GPT-4o. McNemar's test compared correct response proportions. RESULTS:GPT-4, Gemini, GPT-4 Turbo, and GPT-4o correctly answered median percentages of 56.8% (95% confidence interval 55.4% - 58.0%), 40.5% (39.9% - 42.9%), 60.7% (59.5% - 61.3%), and 63.1% (62.5%-64.3%) of questions, respectively. GPT-4o significantly outperformed other models (P = .007 vs GPT-4 Turbo, P < .001 vs GPT-4 and Gemini). GPT-4o excelled on text-only questions compared to GPT-4, Gemini, and GPT-4 Turbo (P < .001, P < .001, and P = .001), while Gemini performed worse on image-based questions (P < .001 for all). CONCLUSION/CONCLUSIONS:GPT-4o demonstrated superior performance among the four LLMs, achieving scores likely within or just outside the range required to pass a test akin to the CBNC examination. Although improvements in medical image interpretation are needed, GPT-4o shows potential to support physicians in answering text-based clinical questions.