Dunlay, Shannon M.

Abstract Background The Charlson comorbidity index (CCI) is a validated weighted measure of comorbidity burden, but has an unclear role in heart failure (HF). Objectives To characterize age-adjusted CCI (ACCI) in HF, its association with the use of guideline-directed medical therapy (GDMT) and with outcomes. Methods In the Swedish HF registry, patients were divided into 3 groups based on ACCI scores (low 1-3, intermediate 4-6, and high ≥7). We studied its association with clinical characteristics and GDMT use. Multivariable multinominal and Cox regressions were used to analyze ACCI and its association with ejection fraction (EF) category (reduced [HFrEF], mildly reduced [HFmrEF], preserved [HFpEF]), and with outcomes up to 3 years. Results Among 117,419 patients (age 75 [66-82], 36% women, 53% HFrEF, 24% HFmrEF, 23% HFpEF, median ACCI was 5, 6 and 6 respectively. ACCI ≥7 was present in 31% with HFrEF, 35% with HFmrEF and 42% with HFpEF. A higher ACCI score was associated with higher EF category, NYHA class, serum NT-proBNP, diuretic use, and lower quality of life and GDMT use (p<0.05 for all). The risk of composite CV mortality/first HF hospitalization was higher with intermediate (adjusted HR 1.34, 95% CI 1.29-1.39) and high vs low ACCI (1.76, 1.69-1.83). High ACCI category (vs low) was significantly associated with non-CV (adjusted HR 6.36, 95% CI 5.75-7.04), but also, CV mortality (4.35, 3.99-4.74), and total hospitalizations (adjusted IRR 2.16, 2.11-2.22) but also HF hospitalizations 1.23 (1.17-1.28) Conclusion The ACCI discriminates well in HF, with higher ACCI being associated with greater severity of HF, lesser GDMT use and worse quality of life. Higher ACCI was more strongly associated with death than hospitalization. Higher ACCI was more strongly associated with non-CV outcomes but also with CV and HF outcomes.

Abstract Background Recent studies suggested that treating obesity and its comorbidities with glucagon-like peptide-1 (GLP-1) receptor agonists may improve outcomes in patients with heart failure with preserved ejection fraction (HFpEF). The randomized SUMMIT trial found that tirzepatide use was associated with a lower risk of heart failure (HF) events or cardiovascular death in adults with HFpEF and obesity compared with placebo. Purpose We aimed to examine whether tirzepatide use in clinical practice was associated with risks of HF events and all-cause mortality among adults with HFpEF and obesity. Methods This was a retrospective cohort study leveraging the Optum Labs Data Warehouse (OLDW), a de-identified administrative claims database of commercial and Medicare Advantage enrollees across the United States. We identified all adults with HFpEF and obesity from January 1, 2022, to December 31, 2024. Our primary exposure was tirzepatide use, and our primary outcome was a composite of a HF event (ED visits or hospitalization for HF) or mortality. Secondary outcomes included hospitalization for angina, atrial fibrillation or atrial flutter (AF/AFL), acute myocardial infarction (MI), cardiac arrest, and cardiogenic shock. Patients were followed from the index date, defined as the tirzepatide treatment start date after HFpEF diagnosis or pseudo-index date in tirzepatide non-users, to the end of enrollment or death using the intention-to-treat framework. Inverse probability of treatment weighting (IPTW) was used to balance groups. Fracture, conjunctivitis, ear infection, and fungal skin infection were used as falsification endpoints. Cox-proportional and Fine-Gray subdistribution hazard models were used to estimate a hazard ratio (HR) and subdistribution hazard ratio (SHR), respectively. Results Among our total cohort of 99,270 patients, the mean age was 73 years, 58,616 (59.1%) were female, 8,839 (8.9%) used tirzepatide, and the mean follow-up time was about 385 days. Patients using tirzepatide had a significantly lower risk of a HF event or mortality (HR=0.73; 95% confidence interval [CI]=0.66–0.80; p<0.001) compared to patients not using tirzepatide. Patients using tirzepatide had a lower risk of a HF event (SHR=0.80; 95% CI=0.73–0.88; p<0.001) and all-cause mortality (HR=0.48; 95% CI=0.38–0.60; p<0.001). Tirzepatide use was associated with lower risks of hospitalization for acute MI (SHR=0.67; 95% CI=0.52–0.85; p=0.001) and cardiogenic shock (SHR=0.56; 95% CI=0.38–0.83; p=0.003), but not angina, AF/AFL, or cardiac arrest (Figure 1). Conclusion Among adults with HFpEF and obesity, tirzepatide use in real-world clinical practice was associated with a lower risk of HF events, hospitalizations for acute cardiovascular disease, and all-cause mortality.For image description, please refer to the figure legend and surrounding text.

Background The purpose of this study was to assess the clinical benefits of guideline‐directed medical therapy (GDMT) for heart failure (HF) in adults with congenital heart disease and HF with reduced ejection fraction. Methods HF with reduced ejection fraction was defined as stage B/C HF and systemic left ventricular ejection fraction <50%. GDMT score was assessed at baseline encounter (baseline GDMT score) and 1‐year follow‐up. GDMT uptitration was calculated as defined as ∆GDMT score from baseline. Cox regression was used to assess the relationship between HF therapy (baseline and ∆GDMT score) and outcomes (HF hospitalization and mortality). Results Of 778 patients (age 44±16, 480 [62%] males), baseline GDMT score was 2 (1, 3) and ∆GDMT score was 0.62 (95% CI, 0.55–0.69). Of 778, only 258 (33%) had GDMT uptitration (∆GDMT score >0). Higher use of GDMT at baseline (adjusted HR per 1 point increase in GDMT score 0.81, 95% CI, 0.74–0.88, P <0.001), and increased use of GDMT over time (adjusted HR for 1 point increase in ∆GDMT score HR 0.70, 95% CI, 0.61–0.79, P <0.001) were associated with lower risk of HF hospitalization. Higher baseline GDMT score (adjusted HR 0.85, 95% CI, 0.76–0.94, P <0.001), and ∆ GDMT score (adjusted HR 0.82, 95% CI, 0.71–0.94, P <0.000) were also associated with lower mortality. Conclusions GDMT use at baseline and GDMT uptitration were associated with improved outcomes and suggest a dose‐dependent relationship between use of GDMT and risk of adverse outcomes. Furthermore, 67% of patients did not receive GDMT uptitration, suggesting suboptimal therapy, and opportunities for improvement.

BACKGROUND: Among accepted US heart organs, listing centers accept organ offers earliest for White women, followed by Black women, White men, and Black men. Understanding the relationships of center- and geographic-level decisions is necessary to understand waitlist disparities. We sought to determine whether listing center and geography are associated with the first heart organ acceptance by candidate race, since race demographics vary regionally across the United States. METHODS: Using the United Network for Organ Sharing data sets, we identified first organ offers for Black and White candidates listed for heart transplant (October 18, 2018 to September 30, 2024) and compared models with and without listing center effects adjusted for candidate-, donor-, and offer-level variables. RESULTS: Among 20 668 candidates (31.6% Black, 68.4% White, 26.5% women), the adjusted odds of first offer acceptance were lower for Black candidates compared with White candidates (odds ratio, 0.84 [95% CI, 0.76–0.94]; P =0.001) when listing center was not included in the model; but after adjusting for listing center effects, odds were similar by race (odds ratio, 0.98 [95% CI, 0.88–1.10]; P =0.78). There were no clear geographic patterns by center, but centers with lower proportions of Black candidates had higher acceptance rates. CONCLUSIONS: Variability in overall acceptance rate among listing centers explains the lower first offer acceptance for Black compared with White heart candidates. Baseline acceptance rates were linked to the center-level proportion of Black candidates but not geography. Investigation of strategies to systemically improve early acceptance of good heart organs may reduce Black and White disparities in wait time duration.

Kidney dysfunction after heart transplantation (HT) is associated with significant morbidity and mortality. Recipient and perioperative factors may all influence the risk of kidney injury. Furthermore, data suggest that the incidence of kidney dysfunction, both acute and chronic, is increasing after the implementation of the United States’ 2018 allocation system due to increasing use of temporary mechanical circulatory support and changing recipient characteristics. While data are robust regarding nephroprotective therapies such as renin-angiotensin-aldosterone system inhibition and SGLT2i (sodium-glucose cotransporter 2 inhibitors) to minimize the progression of chronic kidney disease in patients with heart failure, data in HT recipients are beginning to emerge. This state-of-the-art review will critically examine the existing literature regarding the epidemiology of kidney dysfunction after HT, mitigation strategies for acute kidney injury and chronic kidney disease, including pharmacotherapeutics, the need for kidney transplantation after HT, and practical next steps for the larger HT community.

BACKGROUND: Recent randomized trials have demonstrated that for patients with severe tricuspid regurgitation (TR), transcatheter tricuspid valve interventions (TTVI) improve patients’ symptoms, function, and quality of life and that the amount of health status improvement correlates with the extent of TR reduction. Defining this relationship in greater detail can potentially provide insight into device selection and patient-specific treatment goals. We therefore sought to better understand the relationship between both baseline TR severity and change in TR after TTVI and the extent of improvement in health status after TTVI. METHODS: As part of the Tri-QOL (Kansas City Cardiomyopathy Questionnaire Validation in Tricuspid Valve Disease) study, data from 11 studies of TTVI devices were transferred to the US Food and Drug Administration to harmonize and anonymize before analysis by an independent center. This secondary, observational analysis used patient-level data from the 6 single-arm studies of patients who underwent TTVI to explore the association of change in KCCQ-OS with TR grade using multivariable models, adjusted for age, sex, chronic lung disease, and baseline KCCQ-OS. The primary model included TR grade at baseline, TR grade at 1 month, and the interaction between the two. RESULTS: Among 1056 patients with ≥severe TR who underwent TTVI, mean age was 79.1±7.1 years, 60.3% were female, and mean baseline Kansas City Cardiomyopathy Questionnaire-overall summary score [KCCQ-OS] was 49.5±22.3. Baseline TR grade was severe in 33.5%, massive in 35.9%, and torrential in 30.6%. One-month after TTVI, TR was none/trace in 21.7%, mild in 27.2%, moderate in 28.1%, and ≥evere in 23.1%, while the mean change in KCCQ-OS was 17.0±21.3 points. In a multivariable model that included TR grade at baseline, TR grade at 1 month, and their interaction, there was a strong association between reduction in TR and improvement in KCCQ-OS, with no consistent evidence of a threshold of TR grade below which there was no further improvement in KCCQ-OS. However, among patients with baseline torrential TR, the extent of health status improvement plateaued for patients achieving moderate or less TR at 1 month (ie, a 3-grade improvement from baseline). CONCLUSIONS: Health status improvement after TTVI was most strongly associated with the degree of TR reduction, although there was minimal additional improvement for most patients beyond a 3-grade reduction in TR. These findings support the goal of achieving mild or less TR with TTVI, although patients with torrential TR at baseline may be well served if moderate TR can be achieved.

Background Valvular heart disease contributes to symptomatic heart failure, but its prevalence and prognostic significance in advanced heart failure is not well understood. Methods This retrospective population‐based cohort study included adult residents of Olmsted County, Minnesota, with advanced heart failure (2007–2018). Patients were classified by echocardiographic regurgitation and stenosis of aortic, mitral, tricuspid, and pulmonic valves at the time of advanced heart failure. We examined the associations of aortic stenosis, mitral regurgitation, and tricuspid regurgitation with risks of cardiovascular and all‐cause death through 2023 using Cox proportional hazards models. Results There were 936 patients with advanced heart failure (mean age, 76.9 years; 44.5% women, 43.4% with heart failure with preserved ejection fraction). Moderate or greater regurgitation was observed in 2.8% (n=26) of aortic, 26% (n=244) of mitral, 42% (n=389) of tricuspid, and 4.3% (n=40) of pulmonic valves, while moderate or greater stenosis was observed in 9.7% (n=91) of aortic and 1.8% (n=17) of mitral valves. No patients had clinically significant tricuspid or pulmonic stenosis. After adjustment for age, sex, left ventricular ejection fraction, right ventricular function, serum sodium, Charlson comorbidity index, body mass index, and systolic blood pressure, moderate and severe aortic stenosis were associated with increased cardiovascular death compared with patients without aortic stenosis (hazard ratio [HR], 1.42 [95% CI, 1.01–2.01]; and HR, 1.55 [95% CI, 1.02–2.36]), respectively. Conclusions Tricuspid regurgitation, mitral regurgitation, and aortic stenosis were the most observed valvular pathologies of moderate or greater severity in advanced heart failure. Only moderate or greater aortic stenosis was independently associated with cardiovascular death in advanced heart failure.

Abstract Background Hospital‐at‐home programs (HaH) in the United States have evolved to include a virtual‐hybrid delivery model, where all physician encounters are virtual and partnered with a home care team. Objective To examine whether a virtual hybrid HaH program enabled by technology has similar clinical outcomes to traditional brick‐and‐mortar (B&M) hospital care. Methods We conducted a pragmatic trial at three hospitals, randomizing 1150 acutely ill patients requiring hospital care between July 10, 2023, and October 31, 2023 one‐to‐one into two groups: intervention (HaH) and control (B&M). The primary analysis was an intention‐to‐treat non‐inferiority analysis of the primary outcome, which was a composite of 30‐day all‐cause mortality and unplanned readmissions. Secondary outcomes included 30‐day readmission, all‐cause mortality, and patient experience. Results The mean age was 67.8 (standard deviation [SD] 16.3) years, and 52.2% were female. The primary outcome occurred in 99 (17.3%) HaH patients and 114 (19.8%) B&M patients (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.63–1.14, p = .28), meeting the non‐inferiority criterion. Thirty‐day unplanned readmission occurred in 84 (14.7%) HaH patients and 101 (17.5%) B&M patients (OR 0.81, 95% CI 0.59–1.11, p = .19). Thirty‐day all‐cause mortality occurred in 25 (4.4%) HaH patients and 19 (3.3%) B&M patients (OR 1.34, 95% CI 0.73–2.46, p = .35). No HaH patients died while receiving their hospital care at home. HaH program was associated with a higher likelihood of patients reporting feeling extremely comfortable or very comfortable (84.4% HaH; 60.9% B&M, p = .001). Conclusion A hybrid HaH model is a safe and comfortable alternative to traditional B&M hospital care.

Background Heart failure self‐care can contribute to a high daily workload and treatment burden. The goal of this cohort study was to assess the characteristics and outcomes associated with burden of treatment (BoT). Methods Surveys comprising validated instruments to measure BoT and other constructs were mailed to patients with heart failure in Southeastern Minnesota. Participants were divided into tertiles by BoT scores. Associations of clinical variables with BoT were examined using multinomial logistic regression. Associations of BoT with mortality and hospitalizations were examined using Cox proportional hazard regression and Andersen–Gill models, respectively. Results A total of 609 participants (mean age 76.3 years, 60.3% men, 55.2% urban, 64.3% preserved ejection fraction) completed surveys. Higher BoT was associated with worse health status, more depressive symptoms, lower resilience, less social support, lower medication adherence, and worse health literacy. Mean±SD follow‐up was 14.4 (4.1) months. Estimated 1‐year mortality (8.3% [95% CI, 4.3%–12.1%], 11.0% [95% CI, 6.5%–15.2%], 16.0% [95% CI, 10.8%–21.0%]) and 1‐year mean cumulative hospitalizations (0.57 [95% CI, 0.45–0.72], 0.83 [95% CI, 0.66–1.05], 1.15 [95% CI, 0.93–1.42]) increased across patients reporting low, medium, and high BoT, respectively. Adjustment for health status eliminated any significant association of BoT with risks of death and hospitalization (adjusted hazard ratio [HR], 1.10 [95% CI, 0.58–2.07] and 1.09 [95% CI, 0.74–1.61], respectively, highest versus lowest BoT tertile). Conclusions BoT in heart failure varies by clinical and psychosocial factors. Higher BoT identifies patients at increased risk of adverse health outcomes due to their worse health status. These findings can serve as a foundation for interventions to minimize workload and improve quality of life.

ImportanceThe advanced ambulatory heart failure (HF) population comprises patients who have progressed beyond the pillars of recommended stage C HF therapies but can still find meaningful life-years ahead. Although these patients are commonly encountered in practice, national databases selectively capture the small groups accepted for heart transplant listing or left ventricular assist devices. The epidemiology, trajectories, and therapies for other ambulatory patients with advanced HF are poorly understood.ObservationsIn December 2022, the National Heart, Lung and Blood Institute convened a team of experts to identify knowledge gaps and research priorities for the ambulatory population with limiting daily symptoms and transition toward refractory end-stage D HF, designated as stage C2D. This article summarizes the findings from that 3-day workshop. Workshop participants surveyed the initial challenges and knowledge gaps for (1) recognition of ambulatory C2D HF, (2) estimation of the magnitude of the affected population and identifiable subpopulations, and (3) physiologic phenotypes, such as low cardiac output, right HF, cardiorenal syndromes, congestive hepatopathy and frailty, which offer distinct targets for existing and emerging therapies. Social drivers of HF and patient preferences for quality/length of survival were highlighted as essential modifiers for personalization of therapies.Conclusions and RelevanceTen key points summarized workshop findings, with target cohorts for study proposed as a crucial next step. This workshop summary is intended as a call for action to address knowledge gaps and develop new strategies to improve outcomes in the large ambulatory population with C2D HF.