Closing the Last Mile Gap in Access to Multimodality Imaging in Rural Settings: Design of the Imaging Core of the Risk Underlying Rural Areas Longitudinal Study.

Achieving optimal cardiovascular health in rural populations can be challenging for several reasons including decreased access to care with limited availability of imaging modalities, specialist physicians, and other important health care team members. Therefore, innovative solutions are needed to optimize health care and address cardiovascular health disparities in rural areas. Mobile examination units can bring imaging technology to underserved or remote communities with limited access to health care services. Mobile examination units can be equipped with a wide array of assessment tools and multiple imaging modalities such as computed tomography scanning and echocardiography. The detailed structural assessment of cardiovascular and lung pathology, as well as the detection of extracardiac pathology afforded by computed tomography imaging combined with the functional and hemodynamic assessments acquired by echocardiography, yield deep phenotyping of heart and lung disease for populations historically underrepresented in epidemiological studies. Moreover, by bringing the mobile examination unit to local communities, innovative approaches are now possible including engagement with local professionals to perform these imaging assessments, thereby augmenting local expertise and experience. However, several challenges exist before mobile examination unit-based examinations can be effectively integrated into the rural health care setting including standardizing acquisition protocols, maintaining consistent image quality, and addressing ethical and privacy considerations. Herein, we discuss the potential importance of cardiac multimodality imaging to improve cardiovascular health in rural regions, outline the emerging experience in this field, highlight important current challenges, and offer solutions based on our experience in the RURAL (Risk Underlying Rural Areas Longitudinal) cohort study.

Comparing Costs of Noninvasive Cardiac Diagnostic Tests-a Population-Based Study.

INTRODUCTION: Noninvasive cardiac diagnostic tests (NITs) for the diagnosis of coronary artery disease have been estimated to cost >$3 billion annually in the United States alone and have recently undergone scrutiny over concerns of overuse. Consequently, comparing costs of different NIT testing strategies is of urgent importance to health care planning. METHODS: We utilized population-based administrative and clinical data from Ontario, Canada, to compare downstream costs between 4 available NIT testing strategies (graded exercise stress testing [GXT], stress echocardiography, cardiac computed tomography angiography [CCTA], and myocardial perfusion imaging [MPI] as well as no testing), among patients evaluated for chest pain. To compare costs among the tested (overall and by testing strategy) and nontested groups, we used a log-gamma generalized linear model to account for the skewed distribution of health care cost data, adjusting for relevant clinical covariates. RESULTS: A total of 2,340,699 patients were included in our cohort, of whom 481,170 (21%) patients received 1 of the 4 NITs. Among patients who received a NIT, 254,492 (53%) received a GXT as their initial test, 154,137 (32%) received MPI, 69,160 (14%) received a stress echo, and 3,381 (<1%) received a CCTA. After adjustment for differences in baseline patient characteristics, receipt of any NIT was associated with an approximate 12% reduction in downstream 1-year mean costs (cost ratio = 0.88; 95% CI, 0.87, 0.89) compared with those without any testing. Comparing the different testing strategies with no testing, both GXT (cost ratio = 0.80; 95% CI, 0.79-0.81) and stress echocardiography (cost ratio = 0.82; 95% CI, 0.81-0.83) were associated with the lower downstream costs, while both MPI (cost ratio = 1.26; 95% CI, 1.25, 1.27) and CCTA (cost ratio = 1.29; 95% CI, 1.23, 1.35) were associated with higher downstream costs. CONCLUSIONS: In a large population-based cohort consisting of >2 million people evaluated for chest pain, we report that receipt of noninvasive testing was associated with a 12% reduction in downstream costs when compared with no testing. Graded exercise stress testing and stress echocardiography were associated with the least downstream costs, whereas CCTA and MPI were associated with higher costs when compared with no testing. These findings may help inform testing decisions in chest pain patients.

Diagnostic Strategies for the Assessment of Suspected Stable Coronary Artery Disease : A Systematic Review and Meta-analysis.

BACKGROUND: There is uncertainty about which diagnostic strategy for detecting coronary artery disease (CAD) provides better outcomes. PURPOSE: To compare the effect on clinical management and subsequent health effects of alternative diagnostic strategies for the initial assessment of suspected stable CAD. DATA SOURCES: PubMed, Embase, and Cochrane Central Register of Controlled Trials. STUDY SELECTION: Randomized clinical trials comparing diagnostic strategies for CAD detection among patients with symptoms suggestive of stable CAD. DATA EXTRACTION: Three investigators independently extracted study data. DATA SYNTHESIS: The strongest available evidence was for 3 of the 6 comparisons: coronary computed tomography angiography (CCTA) versus invasive coronary angiography (ICA) (4 trials), CCTA versus exercise electrocardiography (ECG) (2 trials), and CCTA versus stress single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) (5 trials). Compared with direct ICA referral, CCTA was associated with no difference in cardiovascular death and myocardial infarction (relative risk [RR], 0.84 [95% CI, 0.52 to 1.35]; low certainty) but less index ICA (RR, 0.23 [CI, 0.22 to 0.25]; high certainty) and index revascularization (RR, 0.71 [CI, 0.63 to 0.80]; moderate certainty). Moreover, CCTA was associated with a reduction in cardiovascular death and myocardial infarction compared with exercise ECG (RR, 0.66 [CI, 0.44 to 0.99]; moderate certainty) and SPECT-MPI (RR, 0.64 [CI, 0.45 to 0.90]; high certainty). However, CCTA was associated with more index revascularization (RR, 1.78 [CI, 1.33 to 2.38]; moderate certainty) but less downstream testing (RR, 0.56 [CI, 0.45 to 0.71]; very low certainty) than exercise ECG. Low-certainty evidence compared SPECT-MPI versus exercise ECG (2 trials), SPECT-MPI versus stress cardiovascular magnetic resonance imaging (1 trial), and stress echocardiography versus exercise ECG (1 trial). LIMITATION: Most comparisons primarily rely on a single study, many studies were underpowered to detect potential differences in direct health outcomes, and individual patient data were lacking. CONCLUSION: For the initial assessment of patients with suspected stable CAD, CCTA was associated with similar health effects to direct ICA referral, and with a health benefit compared with exercise ECG and SPECT-MPI. Further research is needed to better assess the relative performance of each diagnostic strategy. PRIMARY FUNDING SOURCE: None. (PROSPERO: CRD42022329635).

Clinical and cost implications of deferred testing in low-risk patients with stable chest pain: a simulation using the PROMISE trial.

Current guidelines recommend a deferred testing approach in low-risk patients presenting with stable chest pain. After simulating a deferred testing approach using the PROMISE Minimal Risk Score to identify 915 minimal risk participants with cost data from the PROMISE trial, a deferred testing strategy was associated with an adjusted cost savings of -$748.74 (95% CI: -1646.97, 158.06) per participant and 74.6% of samples had better clinical outcomes and lower mean cost. This supports the current guideline recommended deferred testing approach in low-risk patients with stable chest pain.

Randomized comparison of chest pain evaluation with FFRCT or standard care: Factors determining US costs.

BACKGROUND: FFRCT assesses the functional significance of lesions seen on CTCA, and may be a more efficient approach to chest pain evaluation. The FORECAST randomized trial found no significant difference in costs within the UK National Health Service, but implications for US costs are unknown. The purpose of this study was to compare costs in the FORECAST trial based on US healthcare cost weights, and to evaluate factors affecting costs. METHODS: Patients with stable chest pain were randomized either to the experimental strategy (CTCA with selective FFRCT), or to standard clinical pathways. Pre-randomization, the treating clinician declared the planned initial test. The primary outcome was nine-month cardiovascular care costs. RESULTS: Planned initial tests were CTCA in 912 patients (65%), stress testing in 393 (28%), and invasive angiography in 94 (7%). Mean US costs did not differ overall between the experimental strategy and standard care (cost difference +7% (+$324), CI -12% to +26%, p â€‹= â€‹0.49). Costs were 4% lower with the experimental strategy in the planned invasive angiography stratum (p for interaction â€‹= â€‹0.66). Baseline factors independently associated with costs were older age (+43%), male sex (+55%), diabetes (+37%), hypertension (+61%), hyperlipidemia (+94%), prior angina (+24%), and planned invasive angiography (+160%). Post-randomization cost drivers were coronary revascularization (+348%), invasive angiography (267%), and number of tests (+35%). CONCLUSIONS: Initial evaluation of chest pain using CTCA with FFRCT had similar US costs as standard care pathways. Costs were increased by baseline coronary risk factors and planned invasive angiography, and post-randomization invasive procedures and the number of tests. Registration at ClinicalTrials.gov (NCT03187639).

Diet in a global cohort of adults with HIV at low-to-moderate traditional cardiovascular disease risk.

OBJECTIVE: To characterize diet quality across a global cohort of people with HIV (PWH). DESIGN: Cross-sectional analysis. METHODS: Leveraging REPRIEVE data from baseline across five Global Burden of Disease (GBD) regions, we analyzed participant responses to the Rapid Eating Assessment for Participants questionnaire. An overall diet quality score and scores for specific diet components were generated. Higher scores indicate better diet quality. RESULTS: Among 7736 participants (median age 50 years, 30% women, median BMI 25.8 kg/m 2 ) overall diet quality score (max score 30) was optimal in 13% of participants and good, suboptimal or poor in 45%, 38%, and 4% of participants, respectively; saturated fat score (max score 18) was good, suboptimal, or poor in 38%, 40%, or 7% of participants, respectively. Diet quality scores differed across GBD region with the highest scores reported in the South Asia region [median 23 (21-25)] and lowest in the sub-Saharan Africa region [median 15 (12-18)]; 61% of participants in the South Asia region reported optimal diet quality compared with only 6% in the sub-Saharan Africa region. Higher atherosclerotic cardiovascular risk scores were seen with worsening diet quality. CONCLUSION: Among PWH eligible for primary CVD prevention, diet quality was suboptimal or poor for almost half of participants, and there were substantial variations in diet quality reported by GBD region. TRIAL REGISTRATION: NCT02344290.

Are risk factors necessary for pretest probability assessment of coronary artery disease? A patient similarity network analysis of the PROMISE trial.

BACKGROUND: Pretest probability (PTP) calculators utilize epidemiological-level findings to provide patient-level risk assessment of obstructive coronary artery disease (CAD). However, their limited accuracies question whether dissimilarities in risk factors necessarily result in differences in CAD. Using patient similarity network (PSN) analyses, we wished to assess the accuracy of risk factors and imaging markers to identify ≥50% luminal narrowing on coronary CT angiography (CCTA) in stable chest-pain patients. METHODS: We created four PSNs representing: patient characteristics, risk factors, non-coronary imaging markers and calcium score. We used spectral clustering to group individuals with similar risk profiles. We compared PSNs to a contemporary PTP score incorporating calcium score and risk factors to identify ≥50% luminal narrowing on CCTA in the CT-arm of the PROMISE trial. We also conducted subanalyses in different age and sex groups. RESULTS: In 3556 individuals, the calcium score PSN significantly outperformed patient characteristic, risk factor, and non-coronary imaging marker PSNs (AUC: 0.81 vs. 0.57, 0.55, 0.54; respectively, p â€‹< â€‹0.001 for all). The calcium score PSN significantly outperformed the contemporary PTP score (AUC: 0.81 vs. 0.78, p â€‹< â€‹0.001), and using 0, 1-100 and â€‹> â€‹100 cut-offs provided comparable results (AUC: 0.81 vs. 0.81, p â€‹= â€‹0.06). Similar results were found in all subanalyses. CONCLUSION: Calcium score on its own provides better individualized obstructive CAD prediction than contemporary PTP scores incorporating calcium score and risk factors. Risk factors may not be able to improve the diagnostic accuracy of calcium score to predict ≥50% luminal narrowing on CCTA.

Nativity-Related Disparities in Preeclampsia and Cardiovascular Disease Risk Among a Racially Diverse Cohort of US Women.

Importance: Preeclampsia is an independent risk factor for future cardiovascular disease and disproportionally affects non-Hispanic Black women. The association of maternal nativity and duration of US residence with preeclampsia and other cardiovascular risk factors is well described among non-Hispanic Black women but not among women of other racial and ethnic groups. Objective: To examine differences in cardiovascular risk factors and preeclampsia prevalence by race and ethnicity, nativity, and duration of US residence among Hispanic, non-Hispanic Black, and non-Hispanic White women. Design, Setting, and Participants: This cross-sectional analysis of the Boston Birth Cohort included a racially diverse cohort of women who had singleton deliveries at the Boston Medical Center from October 1, 1998, to February 15, 2016. Participants self-identified as Hispanic, non-Hispanic Black, or non-Hispanic White. Data were analyzed from March 1 to March 31, 2021. Exposures: Maternal nativity and duration of US residence (<10 vs ≥10 years) were self-reported. Main Outcome and Measures: Diagnosis of preeclampsia, the outcome of interest, was retrieved from maternal medical records. Results: A total of 6096 women (2400 Hispanic, 2699 non-Hispanic Black, and 997 non-Hispanic White) with a mean (SD) age of 27.5 (6.3) years were included in the study sample. Compared with Hispanic and non-Hispanic White women, non-Hispanic Black women had the highest prevalence of chronic hypertension (204 of 2699 [7.5%] vs 65 of 2400 [2.7%] and 28 of 997 [2.8%], respectively), obesity (658 of 2699 [24.4%] vs 380 of 2400 [15.8%] and 152 of 997 [15.2%], respectively), and preeclampsia (297 of 2699 [11.0%] vs 212 of 2400 [8.8%] and 71 of 997 [7.1%], respectively). Compared with their counterparts born outside the US, US-born women in all 3 racial and ethnic groups had a significantly higher prevalence of obesity (Hispanic women, 132 of 556 [23.7%] vs 248 of 1844 [13.4%]; non-Hispanic Black women, 444 of 1607 [27.6%] vs 214 of 1092 [19.6%]; non-Hispanic White women, 132 of 776 [17.0%] vs 20 of 221 [9.0%]), smoking (Hispanic women, 98 of 556 [17.6%] vs 30 of 1844 [1.6%]; non-Hispanic Black women, 330 of 1607 [20.5%] vs 53 of 1092 [4.9%]; non-Hispanic White women, 382 of 776 [49.2%] vs 42 of 221 [19.0%]), and severe stress (Hispanic women, 76 of 556 [13.7%] vs 85 of 1844 [4.6%]; non-Hispanic Black women, 231 of 1607 [14.4%] vs 120 of 1092 [11.0%]; non-Hispanic White women, 164 of 776 [21.1%] vs 26 of 221 [11.8%]). After adjusting for sociodemographic and cardiovascular risk factors, birth status outside the US (adjusted odds ratio [aOR], 0.74 [95% CI, 0.55-1.00]) and shorter duration of US residence (aOR, 0.62 [95% CI, 0.41-0.93]) were associated with lower odds of preeclampsia among non-Hispanic Black women. However, among Hispanic and non-Hispanic White women, maternal nativity (aOR for Hispanic women, 1.07 [95% CI, 0.72-1.60]; aOR for non-Hispanic White women, 0.98 [95% CI, 0.49-1.96]) and duration of US residence (aOR for Hispanic women <10 years, 1.04 [95% CI, 0.67-1.59]; aOR for non-Hispanic White women <10 years, 1.20 [95% CI, 0.48-3.02]) were not associated with preeclampsia. Conclusions and Relevance: Nativity-related disparities in preeclampsia persisted among non-Hispanic Black women but not among Hispanic and non-Hispanic White women after adjusting for sociodemographic and cardiovascular risk factors. Further research is needed to explore the interplay of factors contributing to nativity-related disparities in preeclampsia, particularly among non-Hispanic Black women.

Assessment of Obesity and Cardiometabolic Status by Integrase Inhibitor Use in REPRIEVE: A Propensity-Weighted Analysis of a Multinational Primary Cardiovascular Prevention Cohort of People With Human Immunodeficiency Virus.

BACKGROUND: Emerging data demonstrate that the use of integrase inhibitor (INSTI)-based antiretroviral treatment (ART) is associated with increased weight, but the cardiometabolic health consequences of increased weight remains poorly understood. METHODS: This analysis examined INSTI use (>6 months) at entry among REPRIEVE participants enrolled in High Income and Latin America/Caribbean Global Burden of Disease regions. Primary analyses used linear and logistic regression; secondary analyses used quantile regression to examine differences across the full data distribution. Characteristics of those with and without INSTI use were balanced using inverse probability of treatment weighting. RESULTS: Among 4500 REPRIEVE participants, 1848 were on an INSTI-based regimen at entry for an average of 2.1 ±â€…1.8 years. Integrase inhibitor use (vs no INSTI use) was associated with higher odds of obesity (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.4-1.9) and higher mean body mass index ([BMI] +1.5kg/m2; 95% CI, 1.0-1.9) and waist circumference (+3.6cm; 95% CI, 2.6-4.6). Differences in weight related to INSTI use were greater in the upper tails of the distribution (+3.1kg/m2 [95% CI, 1.9-4.4] at the 90th centile vs +0.7kg/m2 [95% CI, 0.2-1.2] at the 50th centile) and among women and nonwhite participants, with sex and race having an additive effect on BMI. Conversely, INSTI use was not associated with differences in glucose, low-density lipoprotein cholesterol, or higher odds of metabolic syndrome or hypertension. CONCLUSIONS: Differences in weight and waist circumference associated with INSTI use are (1) not uniform across people with human immunodeficiency virus, (2) greatest among women and nonwhites, and (3) concentrated at the upper tails of weight distribution. These data identify at-risk subgroups for whom long-term cardiovascular disease outcomes should be carefully assessed.

Fractional flow reserve derived from computed tomography coronary angiography in the assessment and management of stable chest pain: the FORECAST randomized trial.

AIMS: Fractional flow reserve (FFRCT) using computed tomography coronary angiography (CTCA) determines both the presence of coronary artery disease and vessel-specific ischaemia. We tested whether an evaluation strategy based on FFRCT would improve economic and clinical outcomes compared with standard care. METHODS AND RESULTS: Overall, 1400 patients with stable chest pain in 11 centres were randomized to initial testing with CTCA with selective FFRCT (experimental group) or standard clinical care pathways (standard group). The primary endpoint was total cardiac costs at 9 months. Secondary endpoints were angina status, quality of life, major adverse cardiac and cerebrovascular events, and use of invasive coronary angiography. Randomized groups were similar at baseline. Most patients had an initial CTCA: 439 (63%) in the standard group vs. 674 (96%) in the experimental group, 254 of whom (38%) underwent FFRCT. Mean total cardiac costs were higher by £114 (+8%) in the experimental group, with a 95% confidence interval from -£112 (-8%) to +£337 (+23%), though the difference was not significant (P = 0.10). Major adverse cardiac and cerebrovascular events did not differ significantly (10.2% in the experimental group vs. 10.6% in the standard group) and angina and quality of life improved to a similar degree over follow-up in both randomized groups. Invasive angiography was reduced significantly in the experimental group (19% vs. 25%, P = 0.01). CONCLUSION: A strategy of CTCA with selective FFRCT in patients with stable angina did not differ significantly from standard clinical care pathways in cost or clinical outcomes, but did reduce the use of invasive coronary angiography.

Assessment of Coronary Artery Disease With Computed Tomography Angiography and Inflammatory and Immune Activation Biomarkers Among Adults With HIV Eligible for Primary Cardiovascular Prevention.

Importance: Cardiovascular disease (CVD) is increased among people with HIV (PWH), but little is known regarding the prevalence and extent of coronary artery disease (CAD) and associated biological factors in PWH with low to moderate traditional CVD risk. Objectives: To determine unique factors associated with CVD in PWH and to assess CAD by coronary computed tomography angiography (CTA) and critical pathways of arterial inflammation and immune activation. Design, Setting, and Participants: This cohort study among male and female PWH, aged 40 to 75 years, without known CVD, receiving stable antiretroviral therapy, and with low to moderate atherosclerotic cardiovascular disease (ASCVD) risk according to the 2013 American College of Cardiology/American Heart Association pooled cohort equation, was part of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), a large, ongoing primary prevention trial of statin therapy among PWH conducted at 31 US sites. Participants were enrolled from May 2015 to February 2018. Data analysis was conducted from May to December 2020. Exposure: HIV disease. Main Outcomes and Measures: The primary outcome was the prevalence and composition of CAD assessed by coronary CTA and, secondarily, the association of CAD with traditional risk indices and circulating biomarkers, including insulin, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL) 6, soluble CD14 (sCD14), sCD163, lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), and high-sensitivity C-reactive protein (hsCRP). Results: The sample included 755 participants, with a mean (SD) age of 51 (6) years, 124 (16%) female participants, 267 (35%) Black or African American participants, 182 (24%) Latinx participants, a low median (interquartile range) ASCVD risk (4.5% [2.6%-6.8%]), and well-controlled viremia. Overall, plaque was seen in 368 participants (49%), including among 52 of 175 participants (30%) with atherosclerotic CVD (ASCVD) risk of less than 2.5%. Luminal obstruction of at least 50% was rare (25 [3%]), but vulnerable plaque and high Leaman score (ie, >5) were more frequently observed (172 of 755 [23%] and 118 of 743 [16%], respectively). Overall, 251 of 718 participants (35%) demonstrated coronary artery calcium score scores greater than 0. IL-6, LpPLA2, oxLDL, and MCP-1 levels were higher in those with plaque compared with those without (eg, median [IQR] IL-6 level, 1.71 [1.05-3.04] pg/mL vs 1.45 [0.96-2.60] pg/mL; P = .008). LpPLA2 and IL-6 levels were associated with plaque in adjusted modeling, independent of traditional risk indices and HIV parameters (eg, IL-6: adjusted odds ratio, 1.07; 95% CI, 1.02-1.12; P = .01). Conclusions and Relevance: In this study of a large primary prevention cohort of individuals with well-controlled HIV and low to moderate ASCVD risk, CAD, including noncalcified, nonobstructive, and vulnerable plaque, was highly prevalent. Participants with plaque demonstrated higher levels of immune activation and arterial inflammation, independent of traditional ASCVD risk and HIV parameters.

Disparities in Cardiovascular Research Output and Disease Outcomes among High-, Middle- and Low-Income Countries - An Analysis of Global Cardiovascular Publications over the Last Decade (2008-2017).

Background: Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. Health research is crucial to managing disease burden. Previous work has highlighted marked discrepancies in research output and disease burden between high-income countries (HICs) and low- and lower-middle-income countries (LI-LMICs) and there is little data to understand whether this gap has bridged in recent years. We conducted a global, country level bibliometric analysis of CVD publications with respect to trends in disease burden and county development indicators. Methods: A search filter with a precision and recall of 0.92 and 0.91 respectively was developed to extract cardiovascular publications from the Web of Science (WOS) for the years 2008-2017. Data for disease burden and country development indicators were extracted from the Global Burden of Disease and the World Bank database respectively. Results: Our search revealed 847,708 CVD publications for the period 2008-17, with a 43.4% increase over the decade. HICs contributed 81.1% of the global CVD research output and accounted for 8.1% and 8.5% of global CVD DALY losses deaths respectively. LI-LMICs contributed 2.8% of the total output and accounted for 59.5% and 57.1% global CVD DALY losses and death rates. Conclusions: A glaring disparity in research output and disease burden persists. While LI-LMICs contribute to the majority of DALYs and mortality from CVD globally, their contribution to research output remains the lowest. These data call on national health budgets and international funding support to allocate funds to strengthen research capacity and translational research to impact CVD burden in LI-LMICs.

Evaluation of Women and Underrepresented Racial and Ethnic Group Representation in a General Cardiology Fellowship After a Systematic Recruitment Initiative.

Importance: The proportion of women and underrepresented racial and ethnic groups (UREGs) matriculating into general cardiology fellowships remains low. Objective: To assess a systematic recruitment initiative aimed at ensuring adequate matriculation of women and UREGs in a general cardiology fellowship. Design, Setting, and Participants: This quality improvement study took place at a large, tertiary academic medical center and associated Accreditation Council for Graduate Medical Education Cardiovascular Disease fellowship. Participants included cardiology fellowship and divisional leadership and general cardiology fellow applicants to the Duke Cardiovascular Disease Fellowship Program from 2017 to 2019. Data analysis was performed from December 2019 to May 2020. Exposure: Multipronged initiative that created an environment committed to ensuring equity of opportunity. This included the creation of a fellowship diversity and inclusivity task force that drafted recommendations, which included reorganization of the fellowship recruitment committee, and changes to the applicant screening process, the interview day, applicant ranking process, and postmatch interventions. Main Outcomes and Measures: The percentage of matriculating and overall women and UREGs before and after the interventions were recorded. Results: The fellowship received a mean (SD) of 462 (55) applications annually before the interventions (2006-2016) and 611 (27) applications annually after the interventions (2017-2019). Between the 10-year period before the interventions and the 3-year period during the interventions, there was a significant increase in the annual mean (SD) percentage of women (22.4% [2.9%] vs 26.4% [0.07%]; P < .001) and UREG applicants (10.5% [1.1%] vs 12.5% [1.9%]; P = .01) to the program. Among applicants interviewed, the percentage of women increased from 20.0% to 33.5% (P = .01) and that of and UREGs increased from 14.0% to 20.0% (P = .01). Before the interventions, a mean (SD) of 23.2% (16.2%) women and 9.7% (7.8%) UREGs matriculated as first-year fellows, whereas after the interventions, a mean (SD) of 54.2% (7.2%) women and 33.3% (19.0%) UREGs matriculated as first-year fellows. The proportion of the entire fellowship who were women increased from a 5-year mean (SD) of 27.0% (8.8%) to 54.2% (7.2%) after 3 years of interventions, and that of UREGs increased from 5.6% (4.6%) to 33.3% (19.0%). Overall, the proportion of applicants in the entire population who were either women or from UREGs increased from 27.8% to 66.7%. Conclusions and Relevance: After implementing interventions to promote equity of opportunity in the cardiovascular disease fellowship, the percentage of women and UREGs significantly increased in the fellowship over a 3-year time period. These interventions may be applicable to other cardiovascular disease fellowships seeking to diversify training programs.

Cost-effectiveness Analysis of Anatomic vs Functional Index Testing in Patients With Low-Risk Stable Chest Pain.

Importance: Both noninvasive anatomic and functional testing strategies are now routinely used as initial workup in patients with low-risk stable chest pain (SCP). Objective: To determine whether anatomic approaches (ie, coronary computed tomography angiography [CTA] and coronary CTA supplemented with noninvasive fractional flow reserve [FFRCT], performed in patients with 30% to 69% stenosis) are cost-effective compared with functional testing for the assessment of low-risk SCP. Design, Setting, and Participants: This cost-effectiveness analysis used an individual-based Markov microsimulation model for low-risk SCP. The model was developed using patient data from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial. The model was validated by comparing model outcomes with outcomes observed in the PROMISE trial for anatomic (coronary CTA) and functional (stress testing) strategies, including diagnostic test results, referral to invasive coronary angiography (ICA), coronary revascularization, incident major adverse cardiovascular event (MACE), and costs during 60 days and 2 years. The validated model was used to determine whether anatomic approaches are cost-effective over a lifetime compared with functional testing. Exposure: Choice of index test for evaluation of low-risk SCP. Main Outcomes and Measures: Downstream ICA and coronary revascularization, MACE (death, nonfatal myocardial infarction), cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) of competing strategies. Results: The model cohort included 10 003 individual patients (median [interquartile range] age, 60.0 [54.4-65.9] years; 5270 [52.7%] women; 7693 [77.4%] White individuals), who entered the model 100 times. The Markov model accurately estimated the test assignment, results of anatomic and functional index testing, referral to ICA, revascularization, MACE, and costs at 60 days and 2 years compared with observed data in PROMISE (eg, coronary CTA: ICA, 12.2% [95% CI, 10.9%-13.5%] vs 12.3% [95% CI, 12.2%-12.4%]; revascularization, 6.2% [95% CI, 5.5%-6.9%] vs 6.4% [95% CI, 6.3%-6.5%]; functional strategy: ICA, 8.1% [95% CI, 7.4%-8.9%] vs 8.2% [95% CI, 8.1%-8.3%]; revascularization, 3.2% [95% CI, 2.7%-3.7%] vs 3.3% [95% CI, 3.2%-3.4%]; 2-year MACE rates: coronary CTA, 2.1% [95% CI, 1.7%-2.5%] vs 2.3% [95% CI, 2.2%-2.4%]; functional strategy, 2.2% [95% CI, 1.8%-2.6%] vs 2.4% [95% CI, 2.3%-2.4%]). Anatomic approaches led to higher ICA and revascularization rates at 60 days, 2 years, and 5 years compared with functional testing but were more effective in patient selection for ICA (eg, 60-day revascularization-to-ICA ratio, CTA: 53.7% [95% CI, 53.3%-54.0%]; CTA with FFRCT: 59.5% [95% CI, 59.2%-59.8%]; functional testing: 40.7% [95% CI, 40.4%-50.0%]). Over a lifetime, anatomic approaches gained an additional 6 months in perfect health compared with functional testing (CTA, 25.16 [95% CI, 25.14-25.19] QALYs; CTA with FFRCT, 25.14 [95% CI, 25.12-25.17] QALYs; functional testing, 24.68 [95% CI, 24.66-24.70] QALYs). Anatomic strategies were less costly and more effective; thus, CTA with FFRCT dominated and CTA alone was cost-effective (ICERs ranged from $1912/QALY for women and $3,559/QALY for men) compared with functional testing. In probabilistic sensitivity analyses, anatomic approaches were cost-effective in more than 65% of scenarios, assuming a willingness-to-pay threshold of $100 000/QALY. Conclusions and Relevance: The results of this study suggest that anatomic strategies may present a more favorable initial diagnostic option in the evaluation of low-risk SCP compared with functional testing.

Incorporating Coronary Calcification Into Pre-Test Assessment of the Likelihood of Coronary Artery Disease.

BACKGROUND: The prevalence of obstructive coronary artery disease (CAD) in symptomatic patients referred for diagnostic testing has declined, warranting optimization of individualized diagnostic strategies. OBJECTIVES: This study sought to present a simple, clinically applicable tool enabling estimation of the likelihood of obstructive CAD by combining a pre-test probability (PTP) model (Diamond-Forrester approach using sex, age, and symptoms) with clinical risk factors and coronary artery calcium score (CACS). METHODS: The new tool was developed in a cohort of symptomatic patients (n = 41,177) referred for diagnostic testing. The risk factor-weighted clinical likelihood (RF-CL) was calculated through PTP and risk factors, while the CACS-weighted clinical likelihood (CACS-CL) added CACS. The 2 calculation models were validated in European and North American cohorts (n = 15,411) and compared with a recently updated PTP table. RESULTS: The RF-CL and CACS-CL models predicted the prevalence of obstructive CAD more accurately in the validation cohorts than the PTP model, and markedly increased the area under the receiver-operating characteristic curves of obstructive CAD: for the PTP model, 72 (95% confidence intervals [CI]: 71 to 74); for the RF-CL model, 75 (95% CI: 74 to 76); and for the CACS-CL model, 85 (95% CI: 84 to 86). In total, 38% of the patients in the RF-CL group and 54% in the CACS-CL group were categorized as having a low clinical likelihood of CAD, as compared with 11% with the PTP model. CONCLUSIONS: A simple risk factor and CACS-CL tool enables improved prediction and discrimination of patients with suspected obstructive CAD. The tool empowers reclassification of patients to low likelihood of CAD, who need no further testing.

Leveraging a Landmark Trial of Primary Cardiovascular Disease Prevention in Human Immunodeficiency Virus: Introduction From the REPRIEVE Coprincipal Investigators.

The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) is the largest study of cardiovascular disease in human immunodeficiency virus. Enrolling 7770 participants from 2015 to 2019 with sites across 5 continents, REPRIEVE will assess the effects of a statin as a cardiovascular disease prevention strategy in people with HIV (PWH) receiving antiretroviral therapy (ART). Although the primary purpose of REPRIEVE, and its substudy assessing coronary plaque, is to assess cardiovascular outcomes, the trial is a rich source of data on population characteristics and critical comorbidities in PWH, particularly across Global Burden of Disease (GBD) regions, reflective of the ethnic, racial, and gender diversity in this global epidemic. The purpose of this Supplement is to leverage the rich phenotyping in REPRIEVE, to provide data on detailed patterns of baseline ART and immune function by GBD region, reproductive aging among cisgender women, and data on the participation and clinical characteristics of transgender participants. We also leveraged REPRIEVE to assess critical comorbidities, including renal dysfunction, muscle function and frailty, and myocardial steatosis. REPRIEVE is a remarkable collaboration between funders, trial networks, clinical research sites, clinical and data coordinating centers, and willing participants who devoted their time to make the trial possible.