Publications

BACKGROUND: Although mitral transcatheter edge-to-edge repair (MTEER) was approved for secondary mitral regurgitation after the COAPT trial, findings of other MTEER trials have been mixed, raising questions about the applicability of the COAPT results to contemporary clinical practice.

OBJECTIVES: We used transportability methods to estimate the treatment effects of COAPT trial interventions applied to 2 target populations: 1) trial-eligible patients representative of U.S. clinical practice; and 2) treatment-candidate patients with secondary mitral regurgitation representative of U.S. clinical practice, regardless of trial eligibility.

METHODS: We identified patients from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry who were treated with MTEER for secondary mitral regurgitation from March 14, 2019 to September 30, 2023. To select trial-eligible individuals, we applied COAPT trial eligibility criteria to the TVT Registry sample. We used inverse odds of participation weighting to standardize patient-level COAPT data to the data distribution of each target population sample and estimated treatment-specific outcomes. The primary outcome was heart failure hospitalization at 2 years. We also examined 10 secondary outcomes, including all-cause death.

RESULTS: Our analyses included 614 COAPT trial patients and 15,275 TVT Registry patients, of which 7,289 were COAPT trial-eligible. Trial-eligible TVT Registry patients were less likely to have ischemic cardiomyopathy (34.1% vs 60.8%) and more likely to have 4+ mitral regurgitation (79.4% vs 47.9%) compared with trial patients. We estimated that compared with medical therapy alone, MTEER in conjunction with other COAPT interventions (eg, optimization of medical therapy) in the trial-eligible population would result in 2-year absolute risk reductions of 17.0% for heart failure hospitalizations (95% CI: -28.7% to -5.7%) and 15.4% for all-cause death (95% CI: -26.6% to -5.2%), effect sizes similar to those estimated in the trial (P for difference between the trial and target populations >0.05 for both outcomes). The estimated treatment effect for heart failure hospitalizations in the broader treatment-candidate target population was also similar to that in the COAPT trial (P for difference = 0.90).

CONCLUSIONS: Although COAPT trial patients had different baseline characteristics than patients undergoing MTEER in contemporary U.S. practice, we estimated that treatment effects would be similar had real-world patients received COAPT trial interventions, under the assumptions required for transportability (eg, conditional exchangeability across data sources, positivity of trial participation).

It has long been accepted that observational analyses have an important role in evaluating use patterns and assessing the safety of different treatments, including cardiovascular devices, in clinical practice. With the proliferation of large electronic databases, there has been increasing interest in using observational analyses to also examine the comparative effectiveness of devices. However, these analyses are often met with skepticism because of concerns about whether they can generate credible evidence about causal effects. This is in part a result of the difficulty in meeting the assumptions necessary to interpret observational associations as causal effects and of the wide variability in analytic rigor. In this review, we outline frameworks and review methods for using observational analyses to answer questions about the effectiveness and safety of cardiovascular devices. We highlight the target trial framework as a practical tool for guiding observational comparative effectiveness analyses. We illustrate how the framework allows investigators planning and conducting observational analyses to organize their activities as responses to 3 prompting questions. First, what is the research question of the study (ie, "What do we want?")? Second, what are the resources-including background knowledge, research concepts, principles and methods, and available data-that can be brought to bear on the research question (ie, "What do we have?")? And third, what specific steps should be taken to use the available resources to answer the research question (ie, "What do we do?")? We focus our exposition on the evaluation of cardiovascular devices, for which randomized trial data are often limited and there is a strong need for real-world evidence. In this setting, real-world evidence is usually derived from observational comparisons of the treatment of interest with relevant comparator groups using data captured during routine care. A principled approach to the planning and conduct of observational analyses can improve the quality of real-world evidence generation and ensure that the results of observational studies on medical devices can support meaningful conclusions about the risks and benefits of new devices.

BACKGROUND: Conduction system pacing (CSP) has emerged as an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT), with potential clinical benefits and lower costs. PhysioSync-HF is a multicenter, randomized trial comparing these strategies from both clinical and economic perspectives in patients with heart failure with reduced ejection fraction (HFrEF).

OBJECTIVE: To describe the rationale and design of the trial-based economic evaluation embedded within the PhysioSync-HF trial.

METHODS: The PhysioSync-HF trial enrolled 179 patients with 1-year follow-up. Procedural cost data will be collected using a time-driven activity-based costing approach. Costs associated with the device, adverse clinical events, and ambulatory care during follow-up will be estimated using resource-based accounting methods. Appropriate methods will address missing data, and statistical analyses will account for the skewed distribution of cost variables.

RESULTS: The primary economic outcome is the between-group difference in total direct medical costs per patient over the 1-year follow-up (CSP vs BVP). Secondary outcomes include component-level cost breakdowns of direct medical expenses and a budget impact analysis estimating the annual effect on Brazil's health care system if all eligible patients received CSP instead of BVP.

CONCLUSION: By leveraging a multicenter cardiovascular trial to measure costs of CSP versus BVP, this economic evaluation aims to identify cost-saving opportunities that could expand equitable access to CRT for individuals with HFrEF in Brazil, while providing insights relevant to other health care settings worldwide.

TRIAL REGISTRATION: NCT05572736.

BACKGROUND: Veterans are at an increased cardiovascular risk compared to age- and sex-matched non-Veterans. Cardiac rehabilitation (CR) can improve outcomes in cardiovascular disease, but its use in men and women Veterans is not well understood.

OBJECTIVES: This study aimed to examine CR participation by sex and socioeconomic status among Veterans.

METHODS: The authors conducted a retrospective cohort study from January 1, 2021, to December 31, 2023, using a national electronic health record database. The primary outcome was participation in at least 1 CR session among patients within 1 year of myocardial infarction, percutaneous coronary intervention, or coronary artery bypass surgery. Multivariable logistic regression models accounted for patient-level (demographics, medical/psychiatric comorbidities) and community-level factors. Area deprivation indices (ADIs) (analyzed as quartiles) assessed socioeconomic status.

RESULTS: Among 82,496 CR-eligible Veterans (3.6% women), CR participation was low (10.4%) and similar by sex (women = 10.2%, men = 10.4%). Women Veterans did not differ significantly in CR participation compared to men Veterans after adjusting for patient-level and community-level characteristics, including age, race, cardiac and comorbidities, mental health risk factors, rural-urban status, and ADI (adjusted OR: 0.90; 95% CI: 0.79-1.03; P = 0.121). Veterans in the most deprived ADI quartile were less likely to participate vs the least deprived quartile (adjusted OR: 0.82; 95% CI: 0.75-0.89; P < 0.001).

CONCLUSIONS: CR participation among U.S. Veterans remains low, far below that of the Medicare population (10.4% vs 28%), with no significant differences in initiation by sex. However, low socioeconomic status is associated with decreased uptake. Further research is needed to explore innovative, Veteran-specific CR delivery models.

IMPORTANCE: The prevalence of obesity and cardiovascular-kidney-metabolic (CKM) syndrome continues to rise. Indications for novel CKM therapies, including glucagonlike peptide 1 receptor agonists (GLP-1RAs), sodium-glucose cotransporter-2 inhibitors (SGLT2is), and nonsteroidal mineralocorticoid antagonists (nsMRAs) continue to expand, yet the proportion of adults meeting expanded indications, including for multiple medications remains unclear.

OBJECTIVE: To examine proportion of adults meeting US Food and Drug Administration (FDA)-approved indications for GLP1-RAs, SGLT2is, and nsMRAs across national survey, community-based, and ambulatory health care samples.

DESIGN, SETTING, AND PARTICIPANTS: This study used a representative cross-sectional survey of US adults (National Health and Nutrition Examination Survey [NHANES], weighted 245 million; mean [SD] age, 47 [18] years; 126.8 million [52%] female), 5 pooled community-based cohort studies (the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, the Prevention of Renal and Vascular Endstage Disease Study, the Atherosclerosis Risk in Communities Study, and the Cardiovascular Health Study; n = 30 929; mean [SD] age, 63 [14] years; 16 749 [54%] female), and 2 ambulatory health care samples (the Beth Israel Deaconess Medical Center cohort [BIDMC], n = 84 714; mean [SD] age, 46 [17] years; 51 113 [60%] female] and the Mass General Brigham cohort [MGB], n = 362 485; mean [SD] age, 48 [17] years; 227 206 [61%] female). Data were analyzed from November 2024 to November 2025.

EXPOSURES: FDA-approved indications for GLP-1RAs, SGLT2is, and nsMRAs.

MAIN OUTCOMES AND MEASURES: Medication class eligibility within each study sample.

RESULTS: The proportion of individuals who met current FDA-approved indications for 1 or more CKM medication was 60% in NHANES (representing 148 million US adults), 61% in the pooled cohorts, 42% in the BIDMC ambulatory cohort, and 46% in the MGB ambulatory cohort. Eligibility for GLP-1RA therapy was most common, with 56% (representing 137.1 million US adults) in NHANES, 49% in the pooled cohorts, 41% in the BIDMC cohort, and 46% in the MGB cohort. This was followed by SGLT2i therapy (24% [57.9 million] in NHANES, 33% in the pooled cohorts, 14% for both BIDMC and MGB) and nsMRA (5% [11.7 million] in NHANES, 5% in the pooled cohorts, and 1% to 2% in ambulatory samples). Overlapping eligibility for multiple classes was common, with 12% to 17% for GLP1-RA and SGLT2i therapies and 1% to 5% for all 3 classes (an estimated 11.7 million US adults in NHANES).

CONCLUSIONS AND RELEVANCE: This study found that up to 61% of adults met FDA-approved indications for at least 1 of 3 novel CKM therapy classes. This represents an estimated 148 million US adults, including 11.7 million US adults with potential FDA indications for triple therapy, highlighting the urgent need to optimize implementation and utilization of CKM syndrome therapies.

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: 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.

BACKGROUND: The American Heart Association annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and cardiovascular-kidney-metabolic syndrome) that contribute to cardiovascular health. The 2026 Heart Disease and Stroke Statistics Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs).

METHODS: The American Heart Association, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistics Update with review of published literature through the year before writing. The 2026 Statistics Update is the product of a full year's worth of effort in 2025 by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes a new chapter on cardiovascular-kidney-metabolic syndrome, as well as an expanded chapter on tobacco and nicotine use and exposure.

RESULTS: Each of the chapters in the Statistics Update focuses on a different topic related to heart disease and stroke statistics.

CONCLUSIONS: The Statistics Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

OBJECTIVE: Identifying social and economic factors associated with initiation of semaglutide or tirzepatide may inform strategies to support equitable uptake.

RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted using 100% of Medicare claims of patients ≥65 years with type 2 diabetes mellitus (T2DM). The outcome was initiation of semaglutide or tirzepatide. We calculated adjusted odds ratios (aORs) for each exposure (self-reported race and ethnicity, dual enrollment in Medicare and Medicaid, rurality, and social vulnerability index), accounting for demographic and clinical characteristics.

RESULTS: Among 13,922,387 patients with T2DM, 673,776 (4.8%) initiated semaglutide or tirzepatide in 2023. Minoritized racial and ethnic identity (e.g., non-Hispanic Black compared with White; aOR 0.72; 95% CI 0.71-0.72), dual enrollment (aOR 0.90; 0.89-0.91), and residence in the most versus least vulnerable socially vulnerable neighborhoods (aOR 0.93; 0.92-0.93) were associated with lower initiation.

CONCLUSIONS: Minoritized racial and ethnic identity and adverse socioeconomic factors were associated with lower odds of initiation among Medicare beneficiaries with T2DM.

INTRODUCTION: Self-measured blood pressure (SMBP) monitoring with clinical support is an evidence-based practice to improve hypertension control. However, it can be challenging to implement in safety-net systems that disproportionately serve low-income and/or racial/ethnic minority populations at risk of worse hypertension outcomes. We therefore propose a hybrid effectiveness-implementation trial to evaluate the effectiveness of multi-level implementation strategies to increase the use of SMBP monitoring in two urban safety-net systems.

METHODS: We will conduct a patient-level randomized controlled trial with 330 English-, Spanish-, and Chinese (Cantonese)-speaking patients with uncontrolled hypertension across six study sites with patients randomized to a low-intensity (SMBP education, text message education and reminders) vs high-intensity intervention (adds group classes and engagement of identified caregivers). To support increased use of SMBP data by the clinical team, we will concurrently deliver a staggered roll-out of a clinic-level implementation strategy (clinic education, shadowing, auditing with feedback, and optimization of electronic health record [EHR] use).

RESULTS: The primary outcomes will be clinic-measured systolic BP (SBP) among enrolled participants for the patient-level intervention and among all patients assigned to the clinic for the clinic-level intervention. We will additionally collect secondary clinical outcomes (BP control, home SBP), implementation outcomes (adoption, reach, and costs), and patient-reported outcomes (patient activation).

DISCUSSION: The results of this trial will address gaps in identifying cost-conscious implementation strategies for increasing adoption of SMBP in safety-net systems with the overarching goal of improving blood pressure control in low-income, diverse patient populations. Trial registration NCT, NCT06871462. Registered 4 March 2025, https://clinicaltrials.gov/study/NCT06871462.

BACKGROUND: Elevated low-density lipoprotein cholesterol (LDL-C) levels are a leading risk factor for atherosclerotic cardiovascular disease (ASCVD), a major global cause of illness and death. Patients' qualitative insights about experiences, priorities, and needs are essential for creating more targeted, patient-centered quality improvement interventions.

OBJECTIVES: To document the experiences of people with high levels of low-density LDL-C in three countries.

METHODS: Qualitative study of 60-min in-depth interviews with 50 adult patients from Australia, Brazil, and the United States. The study was overseen by a Steering Committee comprising patients, patient advocates, researchers, and cardiologists. The interviews explored pathways and barriers to high LDL-C diagnosis; the burden of managing high LDL-C and the awareness of the association between high LDL-C and cardiovascular risks. The data were analyzed by applying a structured, team-based approach to coding qualitative data.

RESULTS: There were three main pathways to diagnosing high cholesterol: routine physical exams conducted by primary care providers; symptomatic presentations or incidental findings during emergency visits and through a healthcare visit for another condition, frequently diabetes. Healthcare providers' communication styles influenced patients' perceptions of their conditions. Two-thirds of participants (n = 33) attempted lifestyle changes after their high cholesterol diagnosis, but work schedules and daily routines posed barriers to maintaining healthy habits. Some participants who experienced ASCVD events waited hours or days before seeking care, assuming their symptoms were not serious. After diagnosis of an ASCVD event, many patients feared death and worried about their families' futures. When asked about potential improvements to their current therapy, 21 patients mentioned reduced administration frequency.

CONCLUSIONS: This pilot study provides insights into patients' experiences living with and managing elevated LDL-C. It describes opportunities for policymakers and healthcare providers to improve the detection of elevated LDL-C and support patients in understanding risks and strategies for reducing the risk of ASCVD events.

BACKGROUND: Obesity is an established risk factor for venous thromboembolism (VTE). Observational data suggest that glucagon-like peptide 1 receptor agonists (GLP-1RAs) may reduce the risk of VTE. However, the effects of GLP-1RAs on VTE have not been tested in randomized controlled trials (RCTs).

OBJECTIVES: To investigate the impact of GLP-1RAs on VTE risk using data from RCTs.

METHODS: We conducted a systematic review and meta-analysis of placebo-controlled RCTs focusing on GLP-1RA use in patients with type 2 diabetes mellitus (T2DM) or obesity. Five databases were searched from inception to October 2024. The primary outcome was VTE, which was a composite of pulmonary embolism (PE), deep vein thrombosis (DVT), and VTE at other sites, and the secondary outcomes were the individual events.

RESULTS: Twenty-seven RCTs with 84,003 patients were analyzed. The median incidence of VTE was 1.1 and 2.5 per 1,000 patient-years in the GLP-1RA and placebo groups, respectively. There was no statistically significant difference in overall VTE risk between GLP-1RA and placebo groups (RR 0.70, 95% CI 0.46-1.07). However, GLP-1RAs were associated with a significantly lower risk of PE (RR 0.60, 95% CI 0.39-0.94). In contrast, there were no significant differences in the risk of DVT (RR 1.24, 95% CI 0.67-2.27) or VTE at other sites (RR 0.56, 95% CI 0.25-1.26).

CONCLUSIONS: In this meta-analysis of randomized trials, GLP-1RAs were not associated with a significant reduction in overall VTE risk but were associated with a lower risk of PE among patients with T2DM or obesity.

BACKGROUND: Studying trends in mortality is essential to advance understanding of population health. Further evaluation of long-term heart disease mortality trends and subtypes in the United States is needed to guide public health and clinical interventions.

METHODS: This study used the National Vital Statistics System Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research data for adults aged 25 years and older in the United States from 1970 to 2022. Outcomes included absolute number and age-adjusted mortality of total heart disease, ischemic heart disease, and other heart disease subtypes.

RESULTS: From 1970 to 2022, overall age-adjusted heart disease mortality decreased by 66% from 1970 to 2022 (from 761 to 258 per 100 000). In 1970, 91% of all heart disease deaths were ischemic, declining to 53% of all heart disease deaths in 2022. From 1970 to 2022, age-adjusted mortality decreased by 89% for acute myocardial infarction (from 354 to 40 per 100 000) and 81% for all ischemic heart disease (from 693 to 135 per 100 00). In contrast, from 1970 to 2022 age-adjusted mortality for other heart disease subtypes increased by 81% (from 68 to 123 per 100 000), with the greatest increases in heart failure (146% increase), hypertensive heart disease (106% increase) and arrhythmias (450% increase).

CONCLUSIONS: Heart disease mortality has decreased over the past 5 decades. There is an increasing burden of mortality from other heart conditions including heart failure, hypertensive heart disease, and arrhythmias. Further efforts must be undertaken to address the growing challenge of these other heart conditions.

BACKGROUND: Transcatheter edge-to-edge repair of the mitral valve (mTEER) reduced a hierarchical end point that included death and heart failure hospitalization in COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation Trial). However, the magnitude to which mTEER increases the number of days a patient spends at home (DAH) in the first few years after treatment, a patient-centered end point not captured routinely in clinical trials, has not been evaluated. We compared 1- and 2-year DAH among patients with functional mitral regurgitation and heart failure randomized to mTEER plus medical therapy versus medical therapy alone (control) by linking the COAPT trial to comprehensive health care claims data.

METHODS AND RESULTS: We linked data from COAPT trial participants to Medicare fee-for-service claims. DAH was calculated as the number of days alive and spent outside a hospital, skilled nursing facility, inpatient rehabilitation, long-term acute care hospital, emergency department, or observation stay after randomization. Treatment groups were compared using quantile regression to calculate the area under the curve of cumulative distribution functions. We linked 271 patients (mTEER 136/302, control 135/312) for a 2-year follow-up. Mean±SD DAH at 1 year was 312.0±95.6 in mTEER and 298.1±107.5 in controls with similar area under the curve (difference 13.9 days [-10.5 to 38.3], P=0.26). DAH at 2 years was 577.2±235.6 in mTEER and 518.2±253.0 in control with a higher area under the curve in mTEER (difference 59.0 days [0.07 to 117.9], P=0.0497).

CONCLUSIONS: In the COAPT trial linked to Medicare claims, patients randomized to mTEER spent a similar number of DAH at 1 year but more time at home at 2 years compared with medical therapy alone.