Publications by Year: 2026

BACKGROUND: Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) reduces mortality rates but remains widely underused. A polypill for HFrEF has been proposed as an implementation strategy to improve GDMT delivery, but little is known about physicians' preferences in the design of HFrEF polypills. Discrete choice experiments (DCEs), in which survey respondents choose among hypothetical products, are a powerful tool in health economics research and can lend insight into key tradeoffs in HFrEF polypill design. However, the process of designing DCEs is complex and often poorly reported.

METHODS: We developed a survey instrument, including a DCE, through a 5-stage mixed-methods process including (1) literature review; (2) physician interviews and surveys; (3) attribute generation; (4) expert review; and (5) pilot testing. We applied a D-efficient design approach using a multinomial logic model to determine the number of choice tasks for the DCE.

RESULTS: We designed a DCE with 4 attributes: HFrEF polypill out-of-pocket cost, inclusion of an angiotensin converting enzyme inhibitor, angiotensin receptor blocker, or sacubitril/valsartan, ancillary support for polypill prescribing, and pharmacy availability. The final survey will be distributed to cardiologists in academic and Veterans Administration medical centers across the United States.

CONCLUSIONS: Through a rigorous multistage design process leveraging mixed methods, we developed a DCE that elicits cardiologists' preferences about HFrEF polypills and key tradeoffs in their design. Results from this DCE study will directly inform future HFrEF polypill cluster-randomized clinical trials.

AIM: The "2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome" retires, replaces, and expands upon the "2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults." The primary intended audience for this guideline is clinicians who care for patients across the spectrum of cardiovascular-kidney-metabolic syndrome, an interrelated condition characterized by the interconnections among metabolic risk factors (including obesity and type 2 diabetes), chronic kidney disease, and cardiovascular disease.

METHODS: A comprehensive literature search was conducted from October 29, 2024, to April 14, 2025, to identify clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human subjects that were published since 2015 in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

STRUCTURE: The focus of this clinical practice guideline is to create a living, working document that provides current knowledge in the field of cardiovascular-kidney-metabolic syndrome aimed at all practicing cardiologists, endocrinologists, nephrologists, and primary care and specialty clinicians who manage these patients.

AIM: The "2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome" retires, replaces, and expands upon the "2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults." The primary intended audience for this guideline is clinicians who care for patients across the spectrum of cardiovascular-kidney-metabolic syndrome, an interrelated condition characterized by the interconnections among metabolic risk factors (including obesity and type 2 diabetes), chronic kidney disease, and cardiovascular disease.

METHODS: A comprehensive literature search was conducted from October 29, 2024, to April 14, 2025, to identify clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human subjects that were published since 2015 in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

STRUCTURE: The focus of this clinical practice guideline is to create a living, working document that provides current knowledge in the field of cardiovascular-kidney-metabolic syndrome aimed at all practicing cardiologists, endocrinologists, nephrologists, and primary care and specialty clinicians who manage these patients.

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.