Faculty Bibliography

Stress testing is among the most frequently performed cardiac diagnostic procedures and is widely utilized in both outpatient and inpatient settings performed with and without myocardial perfusion imaging (MPI). Since the 2016 American Society of Nuclear Cardiology (ASNC) guideline, clinical experience with cardiac stress testing has continued to expand and evolve necessitating updates to the previous guidelines. This guideline presents updated practice standards for cardiac stress testing intended to support safe and effective testing across a range of clinical environments, while allowing for individualized risk assessment and protocol adaptation based on patient characteristics, special populations, and site-specific logistics. The current guideline offers practical beginning-to-end guidance on the performance of cardiac stress testing, encompassing patient selection and preparation, stress modalities and protocols, safety considerations, and result interpretation and reporting. The utilization of single photon emission computed tomography (SPECT) and positron emission tomography (PET) in conjunction with stress testing are addressed for stress protocols for each available stressor. This revised guideline is intended for a broad, multidisciplinary audience involved in the performance, interpretation, and oversight of cardiac stress testing. ASNC has developed this updated guideline to recognize the evolution of diagnostic imaging that has taken place since the last iteration of the guideline. These updates are intended to support optimal test selection, standardized patient preparation, and individualized, patient-centric practice of nuclear stress testing in diverse clinical scenarios. Utilizing this guideline, clinicians will optimize diagnostic accuracy, maintain patient safety, and at the same time maximize clinical impact.

BACKGROUND:The ISCHEMIA trial randomized participants with chronic coronary disease and moderate or severe ischemia by site assessment to an initial invasive strategy plus guideline-directed medical therapy (GDMT) or to an initial conservative strategy of GDMT alone. This secondary analysis examines the association of pre-randomization ischemia severity, from stress testing assessed by a core laboratory, and anatomic severity of coronary artery disease (CAD), assessed by coronary computed tomography angiography (CCTA), with 1-year health status outcomes. METHODS:The associations of ischemia and CAD severity with 1-year health status were assessed using proportional odds models, adjusted for age, sex, and baseline health status and stratified by baseline angina; Seattle Angina Questionnaire (SAQ) Angina Frequency [AF] score < 100 (and angina) vs. 100 (no angina). RESULTS:Among 4,558 participants with baseline and 1-year SAQ assessments, 2936 (64.4%) had baseline angina. Among these, ischemia was categorized as no/mild (363), moderate (986) and severe (1587). Among participants reporting angina at baseline, those with severe baseline ischemia had more frequent angina compared with those having less ischemia (SAQ AF, 70.6 vs 73.0, p=0.029). However, the adjusted odds ratio for better 1-year overall health status, assessed by the SAQ Summary Score, was 1.29 (95% CI, CI 1.05-1.59, p=0.007) for participants with severe vs. those with less baseline ischemia. No differences in 1-year health status were observed by CAD severity or in asymptomatic patients categorized by ischemia or CAD severity. CONCLUSIONS:Among participants with baseline angina in the ISCHEMIA trial, severe ischemia was independently associated with more frequent angina at baseline and at 1 year, but also with better 1-year overall health status compared with less ischemia. Anatomic CAD severity was not associated with angina severity.

BACKGROUND:Previous studies evaluated large language model (LLM) performance on the American Society of Nuclear Cardiology (ASNC) Board Preparation Exam. Without domain-specific context, the best model (GPT-4o) achieved 63.1%, below the estimated 65% passing threshold and the 78% mean score of human fellows-in-training (FITs). Providing textbook context improved GPT-4o to 73.8% on text-only questions, but still fell short of human trainees. Whether next-generation LLMs with retrieval-augmented generation (RAG) can exceed this gap is unknown. METHODS:Claude Opus 4.7 and GPT-5.5 were administered all 168 questions (141 text-only, 27 image-based) from the 2023 ASNC Board Preparation Exam across 5 iterations each, using RAG with a nuclear cardiology textbook, companion atlas, and ASNC clinical guidelines. Claude used local FAISS-based semantic retrieval; GPT-5.5 used Azure's cloud-hosted vector store. Performance was compared to prior LLM results and 13 human FITs. RESULTS:Across 5 iterations, Claude Opus 4.7 achieved a mean accuracy of 86.3% ± 1.4% (text 88.8%, image 73.3%). GPT-5.5 achieved 86.7% ± 2.2% (text 88.5%, image 77.0%) but refused a mean of 12.2 questions (7.3%) per iteration due to safety filters. Both models surpassed the human FIT mean (78.0%) and the estimated passing threshold. Compared to GPT-4o without context (63.1%), this represents a 23-percentage-point improvement in 18 months. CONCLUSION/CONCLUSIONS:Next-generation LLMs with RAG now surpass average human trainee performance on nuclear cardiology board preparation questions, suggesting significant potential as educational tools and knowledge-reference aids in cardiovascular imaging.

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.