BACKGROUND:Strain parameters are sensitive indicators of myocardial performance, but the optimal combination for prognostic prediction in pulmonary arterial hypertension remains unclear. METHODS:Patients diagnosed with pulmonary arterial hypertension between June 2013 and June 2024 were prospectively recruited. Strain parameters, including left ventricular global longitudinal strain, right ventricular GLS, right ventricular free-wall longitudinal strain, and right atrial phasic strain, were analyzed. Feature selection used elastic net Cox regression and stepwise Cox regression with the Akaike information criterion. Survival analyses were performed for all-cause mortality and a composite end point (mortality and heart failure rehospitalization). RESULTS:A total of 269 patients with pulmonary arterial hypertension (mean age, 42±15 years) were included. During a median follow-up of 39.3 months, 68 patients reached the primary end point, and 91 reached the secondary end point. The combination of left ventricular global longitudinal strain and right atrial reservoir strain had the strongest prognostic value. Both left ventricular global longitudinal strain (hazard ratio, 1.46, per 5% increase [95% CI, 1.07-2.00]; P=0.02) and right atrial reservoir strain (hazard ratio, 0.77, per 5% increase [95% CI, 0.62-0.95]; P=0.02) remained independent predictors of all-cause mortality. Their combination outperformed conventional cardiac magnetic resonance and clinical models, as evidenced by higher C-index values (all P≤0.05), and stratified patients into low-, intermediate-, and high-risk groups with distinct 1-year mortality rates (2.8%, 6.2%, 21.0%, respectively; P<0.001). Landmark analysis confirmed their long-term prognostic relevance. CONCLUSIONS:The combined assessment of left ventricular global longitudinal strain and right atrial reservoir strain yields the strongest prognostic utility among the strain parameters in pulmonary arterial hypertension, significantly improves risk stratification beyond several established cardiac magnetic resonance and clinical predictors, and holds promise as a practical tool for guiding management strategies.
BACKGROUND:Obesity is a major risk factor for atrial fibrillation and heart failure. We aimed to characterize left atrial (LA) structural and functional changes across body mass index (BMI) strata in patients with atrial fibrillation referred for catheter ablation. METHODS:We studied 1040 consecutive patients (67% male; mean age, 62 years; 71% in sinus rhythm). Participants were stratified by BMI (<25.0, 25-29.9, 30-34.9, and ≥35 kg/m2). Comprehensive echocardiographic assessment of LA structure and function was integrated with invasive LA pressure measurements obtained via transseptal access during the ablation procedure. Associations across BMI strata were evaluated using regression analyses. RESULTS:Patients with higher BMI had larger estimated total blood and plasma volumes along with higher LA volumes and pressures, greater cyclic wall stress, and a rightward shift of the estimated LA pressure-volume relationship. Conversely, estimated operant LA stiffness did not differ across BMI strata. BMI-related differences in LA volume were attenuated by body surface area indexing but preserved with height-based indexing. Conventional volumetric indices of LA phasic function were similar across BMI strata, whereas available LA strain indices (n=107) were lower with greater adiposity, consistent with worse LA phasic function. Compared with patients without heart failure, those with heart failure exhibited more pronounced structural, functional, and hemodynamic atrial remodeling, consistent with a more advanced atrial myopathy phenotype. CONCLUSIONS:In patients undergoing atrial fibrillation ablation, higher BMI is associated with a predominantly load-related pattern of LA remodeling, characterized by larger LA volume and pressures, greater cyclic wall stress, and a rightward shift of the estimated pressure-volume relationship. BMI-associated early atrial remodeling may precede overt atrial dysfunction, potentially contributing to the link between excess adiposity, atrial fibrillation, and heart failure with preserved ejection fraction.
Cardiovascular disease remains a major cause of morbidity and mortality, with heart failure representing the common and often irreversible end stage, for which current therapies are largely palliative rather than restorative. Cardiac microcurrent therapy delivers a low-intensity, nondepolarizing direct current across the myocardium and has been proposed to modulate fibrosis, inflammation, and remodeling in heart failure with reduced ejection fraction. In Cardiac Microcurrent I (New York Heart Association III nonischemic heart failure with reduced ejection fraction), left ventricular ejection fraction increased by 12.6% at 6 months, 6-minute walk distance improved by 191 m, and 8 of 10 patients improved to New York Heart Association I within 2 weeks. In the randomized Cardiac Microcurrent II trial, patients showed further improvements, including a 5.1% increase in left ventricular ejection fraction, a reduction in New York Heart Association class (up to 69%), and a 38 m increase in 6-minute walk distance. However, NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels did not show a consistent corresponding reduction. In vitro, microcurrent altered the myofibroblast phenotype and reduced the expression of transforming growth factor-β1, collagen, α-smooth muscle actin, and fibronectin. Transcriptomics revealed downregulation of inflammatory and immune pathways, while cardiomyocytes from spontaneously hypertensive rats exhibited enhanced survival and stress resistance. This review combines early clinical observations and preclinical findings to examine potential mechanisms of action and bioelectrical effects of cardiac microcurrent therapy. Given the limited clinical evidence and largely in vitro nature of the data, the current mechanistic findings should be considered preliminary. We highlight key knowledge gaps and propose future studies to define molecular mechanisms, discover biomarkers, analyze key signaling pathways, and evaluate clinical outcomes in adequately powered, sham-controlled trials, which could further validate this therapeutic approach.
Heart failure remains a major cause of global morbidity and mortality despite advances in guideline-directed medical therapy. Nanoparticle-based approaches have gained attention as strategies to enhance therapeutic delivery; however, their clinical relevance depends on addressing true pharmacological barriers rather than repackaging existing agents. In this review, we present a conceptual framework to define when nanomedicine provides meaningful therapeutic value in heart failure. We argue that nanotechnology should not be viewed as a replacement for guideline-directed medical therapy, but as an enabling platform for the targeted delivery of potent therapies limited by pharmacokinetic and biodistribution constraints. We summarize the principal nanoparticle platforms used in cardiovascular applications, including lipid-based and polymeric systems, and contextualize their use across key pathophysiological domains in heart failure: TGF-β (transforming growth factor-beta)-mediated fibrosis, IL-1β (interleukin-1 beta) and TNF-α (tumor necrosis factor-alpha)-driven inflammation, reactive oxygen species-mediated injury, regenerative strategies, and gene- and mRNA-based therapies. We propose 3 criteria for translational relevance: (1) a targetable myocardial microenvironment, (2) a therapeutic agent limited by conventional delivery, and (3) a formulation that confers a demonstrable clinical advantage. Although these conditions are met in selected preclinical models, clinical translation remains limited. The field is therefore shifting from an emphasis on delivery feasibility to therapeutic necessity. Nanomedicine is best positioned as a precision adjunct to heart failure therapy-enabling the right therapy to reach the right myocardium at the right time.
BACKGROUND:Although diabetes is a known driver of heart failure with preserved ejection fraction, whether antecedent hyperinsulinemia drives preclinical diastolic dysfunction (DD) progression before overt hyperglycemia remains unknown. Therefore, we investigated whether elevated endogenous insulin and insulin resistance independently predict longitudinal DD progression and adverse cardiovascular outcomes. METHODS:In a community-based cohort study, we evaluated 1191 participants from the Olmsted County Heart Function Study (median age, 58.7 [interquartile range, 52.4-66.6 years]) who underwent echocardiography at baseline and after 4 years. Fasting insulin and homeostatic model assessment of insulin resistance were assessed. The primary end point was DD progression. Secondary outcomes (mortality, heart failure) were assessed in 2030 participants followed for a median of 10.97 (95% CI, 10.90-11.05) years for heart failure and a median of 18.1 (95% CI, 18.0-18.2) years for mortality. RESULTS:DD progression occurred in 7.5% of participants. Baseline fasting insulin and homeostatic model assessment of insulin resistance strongly predicted progression (P<0.001). In multivariable analysis, every 1-SD increase in log-transformed insulin was associated with 65% increased odds of progression (odds ratio, 1.65 [95% CI, 1.33-2.07]; P<0.001), adjusting for age, creatinine, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Similar results were observed for homeostatic model assessment of insulin resistance (odds ratio, 1.66 [95% CI, 1.34-2.08]; P<0.001). In secondary analyses, elevated insulin independently predicted all-cause (hazard ratio, 1.11 per 1-SD [95% CI, 1.02-1.21]) and cardiovascular mortality (hazard ratio, 1.16 [95% CI, 1.02-1.33]). Homeostatic model assessment of insulin resistance was similarly predictive of all-cause (hazard ratio, 1.11 [95% CI, 1.03-1.20]) and cardiovascular mortality (hazard ratio, 1.16 [95% CI, 1.02-1.32]). CONCLUSIONS:Elevated endogenous insulin and insulin resistance are predictors of progressive DD and long-term mortality, even after accounting for body mass index. Metabolic dysregulation may drive myocardial stiffening before diabetes onset, identifying a potential early therapeutic window for heart failure with preserved ejection fraction prevention.
BACKGROUND:Frequent transthoracic echocardiograms (TTEs) are required to monitor for left ventricular systolic dysfunction (LVSD) in patients with obstructive hypertrophic cardiomyopathy receiving myosin inhibitors. This requirement may be cumbersome and limit access in underserved and rural areas. The objective of this study was to evaluate the performance of an artificial intelligence (AI)-enabled ECG tool in predicting LVSD in hypertrophic cardiomyopathy patients on mavacamten. METHODS:At Morristown Medical Center/Atlantic Health, 147 patients initiated on mavacamten between June 2022 and June 2025 underwent ECGs and TTEs at baseline and clinically available follow-up visits. A validated AI-enabled ECG algorithm predicted the probability of LVSD. Sensitivity, specificity, negative predictive value, positive predictive value, and area under the curve were calculated for left ventricular ejection fraction <50%, with CIs accounting for repeated paired ECG-TTE observations within patients. RESULTS:In 147 patients, mean age was 65±14 years; 44% were male. Among 453 paired ECG-TTE observations, 8 LVSD event observations occurred. At an AI probability threshold of 20%, sensitivity was 100% (95% CI, 68%-100%), specificity was 75% (95% CI, 69%-82%), positive predictive value was 7% (95% CI, 3%-11%), and negative predictive value was 100% (95% CI, 99%-100%). The area under the curve was 0.94 (95% CI, 0.90-0.98). Patient-level classifications between AI-enabled ECG and echo-confirmed LVSD were concordant in 127 of 147 patients (86%), inconclusive in 17 of 147 (12%), and discordant in 3 of 147 (2%). CONCLUSIONS:In this single-center exploratory cohort of patients with obstructive hypertrophic cardiomyopathy receiving mavacamten, ECG-Vision left ventricular demonstrated high observed sensitivity and negative predictive value for TTE-defined LVSD, although estimates were imprecise because LVSD events were infrequent. These findings support prospective multicenter validation of AI-enabled ECG as a potential adjunctive triage tool.
BACKGROUND:There are concerns that renin-angiotensin system inhibitors are less effective in Black patients than non-Black patients with heart failure (HF). We examined the efficacy and safety of mineralocorticoid-receptor antagonists (MRAs), compared with placebo, in patients with HF with reduced ejection fraction or HF with mildly reduced/preserved ejection fraction, according to self-reported race (Black or non-Black). METHODS:This was a post hoc individual participant data meta-analysis of the 4 large placebo-controlled trials comparing MRAs to placebo in patients with HF with reduced ejection fraction (RALES [Randomized Aldactone Evaluation Study], EMPHASIS-HF [Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure]) and HF with mildly reduced/preserved ejection fraction (TOPCAT [Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist], FINEARTS-HF [Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure]). The primary outcome was a composite of cardiovascular death or first HF hospitalization. RESULTS:Of the 13 846 patients randomized in the 4 trials, 577 (4.2%) identified as Black. Despite being younger (64 versus 70 years), rates of HF hospitalizations and death were higher in Black than non-Black patients. The hazard ratio for MRA versus placebo for the primary composite outcome was 0.87 (95% CI, 0.66-1.15) in Black patients and 0.77 (95% CI, 0.72-0.82) in non-Black patients (Pinteraction=0.34), with 3.9 and 2.7 fewer events per 100 person-years of treatment, respectively. For first HF hospitalization, the hazard ratios were 0.86 (95% CI, 0.63-1.17) and 0.73 (95% CI, 0.68-0.80) for Black and non-Black patients, respectively (Pinteraction=0.36). The corresponding hazard ratios for cardiovascular death were 0.75 (95% CI, 0.48-1.17) and 0.81 (95% CI, 0.74-0.90), respectively (Pinteraction=0.80). Adverse events with MRAs, compared with placebo, were not modified by race. The effects of MRAs in patients with HF with reduced ejection fraction and HF with preserved ejection fraction, individually, were not modified by race. CONCLUSIONS:There was no statistically significant evidence of heterogeneity in the absolute or relative effects of MRAs on clinical outcomes between Black and non-Black patients with HF, regardless of HF phenotype.
BACKGROUND:With evolving therapy for heart failure with reduced ejection fraction, the benefits of adding a defibrillator in patients undergoing cardiac resynchronization therapy (CRT) remain unclear, particularly for nonischemic cardiomyopathy (NICM). This study evaluates long-term survival among patients with NICM treated with CRT defibrillator (CRT-D) versus CRT pacemaker (CRT-P). METHODS:DECIDE-CRT (Cardiac Resynchronization With or Without Defibrillator in Non-Ischemic Cardiomyopathy) is a multicenter cohort study across 170 US Veterans Affairs hospitals. We identified patients with NICM receiving primary-prevention CRT-P or CRT-D between January 1, 2006, and December 31, 2020. Using a propensity score approach, we applied inverse probability of treatment weighting to balance baseline characteristics between the CRT-P and CRT-D groups. An inverse probability of treatment weighting-weighted Cox model estimated hazards for all-cause mortality. Secondary outcomes included generator replacement, device-related infections, hospitalization for heart failure, and ventricular arrhythmias. RESULTS:Of 16 609 CRT recipients, 3965 met NICM primary-prevention criteria (CRT-D=3158; CRT-P=807). At baseline, patients with NICM receiving CRT-P were much older, with more cardiovascular and noncardiovascular comorbidities compared with the CRT-D group. During the median follow-up of 5.2 years, the mortality rate for CRT-P versus CRT-D was 9.46 versus 9.21 per 100 person-years (RR, 0.97 [95% CI, 0.71-1.13]; P=0.66). The adjusted hazard ratio for all-cause mortality using the inverse probability of treatment weighting-Cox model was 0.90 (95% CI, 0.71-1.13; P=0.34). There was no difference in adjusted hazard for heart failure hospitalization (hazard ratio, 1.27 [95% CI, 0.86-1.87]), while the CRT-D group had higher rates of generator replacement and device-related infections. CONCLUSIONS:This nationwide observational study from the Veterans Affairs Health system did not demonstrate a clear survival advantage with the addition of a defibrillator among patients with NICM receiving CRT although residual confounding cannot be excluded. Given the uncertainty surrounding the incremental benefit of the defibrillator in this setting, a randomized trial is needed to test the incremental value of CRT-D over CRT-P in NICM.
BACKGROUND: Fetal cardiomyopathy is a rare condition, often with an unknown cause and associated with high perinatal mortality. Recent years have seen improvement in fetal cardiac screening, genetic testing, and management. We sought to investigate genetic associations and clinical outcomes of fetal cardiomyopathy in the contemporary era. METHODS: A single-arm (descriptive) retrospective cohort study of fetal cardiomyopathy cases diagnosed from January 2017 to December 2021 at 26 North American centers in the Fetal Heart Society Research Collaborative was undertaken. Cases attributable to maternal diabetes, extra-cardiac conditions, structural heart disease, or arrhythmias were excluded. Genetic testing results, extra-cardiac structural anomalies, and outcomes were collected. Logistic regression was performed to determine prenatal risk factors for death or cardiac transplantation by 1-year of age. Descriptive competing-risk analyses (cumulative incidence functions) and Kaplan-Meier survival estimates were used to describe outcomes. Multivariable logistic regression with 5 prespecified covariates was performed to identify prenatal factors associated with death or cardiac transplantation by 1-year of age. RESULTS: In 148 cases of fetal cardiomyopathy, 6.7% (10/148) opted for pregnancy termination, 8.6% (12/138) of continuing pregnancies experienced fetal death, and 1.4% (2/138) were lost to follow-up. Among continuing pregnancies, overall 1-year survival was 61.5% (85/138) with 1-year transplant-free survival of 50.0% (69/138). Of live births, 8.8% (11/124) received palliative care from the outset, and 21.2% (24/113) of those with intention to treat were listed for cardiac transplant, of whom 75.0% (18/24) received transplantation by age 1-year. Genetic etiologies were found in 34.0% (50/147) of the cohort, with variants of uncertain significance detected in an additional 27.2% (40/147). Fetal hydrops at the time of prenatal diagnosis ( P =0.001) and a prenatal diagnosis of extracardiac structural anomalies ( P ≤0.001) were significantly associated with death or transplant by 1-year of age. CONCLUSIONS: Fetal cardiomyopathy outcomes have improved in the current era, although only half achieve 1-year cardiac transplant-free survival. Genetic testing identifies a cause in one-third of cases. Hydrops at the time of fetal cardiomyopathy diagnosis and a prenatal diagnosis of extra-cardiac structural anomalies remain important risk factors for mortality.
BACKGROUND:Heart failure (HF) involves complex metabolic and lipid-related disturbances. While prior studies have shown that static lipid and metabolic profiles are associated with poor prognosis in chronic stable HF, it remains unclear whether serially measured lipid and metabolic biomarkers are associated with adverse outcomes. METHODS:We analyzed longitudinal data from 2 independent HF cohorts with serial blood sampling (Bio-SHiFT and TRIUMPH [Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure]), using nuclear magnetic resonance spectroscopy to quantify 45 circulating metabolic biomarkers. Joint models, combining linear mixed-effects models for repeated biomarker measurements with Cox proportional hazards models for time-to-event outcomes, were used to assess associations between current levels of serially measured biomarkers and the cohort-specific primary end point, defined as a composite of HF hospitalization, advanced HF therapy, or cardiovascular death. Models were adjusted for relevant clinical covariates. RESULTS:The Bio-SHiFT cohort (n=382; mean age, 63±13 years; 73% men; 72% New York Heart Association class I-II) contributed 2956 serial nuclear magnetic resonance measurements, while the TRIUMPH cohort (n=233; mean age 69±13 years; 69% men; 21% New York Heart Association class I-II) contributed 666. Multiple lipid-related biomarkers, including lipoprotein particle concentration, size, and standard lipid components, were associated with the primary end point. Findings were consistent between the 2 cohorts. Among high-density lipoprotein-related measures, higher current levels of S-high-density lipoprotein particle (hazard ratio [95% CI] for Bio-SHiFT per Z score of natural log-transformed biomarker, 0.59 [0.45-0.78]), high-density lipoprotein subclass 2 particle (0.57[0.42-0.80]), and total high-density lipoprotein particle (0.54 [0.41-0.70]) were consistently associated with lower risk, whereas greater mean high-density lipoprotein particle size (1.52 [1.23-1.87]) was associated with higher risk. In addition, higher current levels of medium-triglyceride-rich lipoprotein particle, total triglycerides, triglyceride-rich lipoprotein cholesterol, triglyceride-rich lipoprotein total triglycerides, and ApoA-I (apolipoprotein AI) were associated with lower risk. Beyond lipid-related biomarkers, higher current levels of the inflammation and metabolic dysregulation markers inflammation vulnerability index (3.11 [2.07-4.88]), metabolic malnutrition index (1.98 [1.38-2.96]), and metabolic vulnerability index (3.79 [2.43-5.98]) were associated with higher risk. CONCLUSIONS:Serially measured nuclear magnetic resonance-derived lipoprotein and metabolic biomarkers were associated with the primary end point in chronic stable HF. These findings support further evaluation of serial metabolic profiling as a complementary approach to risk assessment in HF.
BACKGROUND:Static cold storage of cardiac allografts at 4-8 °C or 10 °C has yielded promising heart transplant outcomes compared with ice storage. However, direct comparisons between these 2 preservation temperatures are lacking. This dual-center study is the first to compare adult heart transplant outcomes using allografts preserved at 10 °C versus 4-8 °C static cold storage. METHODS:All single-organ, donation-after-brain-death adult heart transplants performed at 2 high-volume centers between January 2020 and April 2025 were retrospectively analyzed. Multiorgan, adult congenital, and donation-after-circulatory-death cases were excluded. A 3:1 nearest-neighbor propensity score matching was applied using a standardized mean difference <20% to create balanced cohorts. Firth logistic regression and quantile regression were used to evaluate categorical and continuous outcomes in unmatched and matched cohorts. RESULTS:Among 365 recipients, 113 received allografts preserved at 10 °C and 252 at 4-8 °C. The 10 °C group had higher donor and recipient risk profiles, including older donors (37 [28-43] versus 31 [24-39] years; P=0.004), greater donor-recipient sex mismatch, and more frequent donor undersizing by predicted heart mass ratio. Recipients in this cohort were older and had more re-sternotomies and higher serum creatinine levels at transplant. Patients in the 4-8 °C group were more often listed as Status 2. After matching, 10 °C preservation was associated with less primary graft dysfunction (2 [2.9%] versus 19 [14.6%]; P=0.008), less left and right ventricular dysfunction, reduced new intraaortic balloon pump use, and improved 1-year survival (95.7% versus 86.2%; P=0.02). Other outcomes, including cardiac indices and posttransplant length of stay, were not significantly different between groups. CONCLUSIONS:Preservation of cardiac allografts at 10 °C may yield superior early graft function compared with 4-8 °C static cold storage. However, further prospective studies are required to delineate the optimal donor heart preservation temperature.
BACKGROUND: Among 508 patients randomized to interatrial shunt implantation versus a placebo procedure in the RELIEVE-HF trial (Reducing Lung Congestion Symptoms Using the V-Wave Shunt in Advanced Heart Failure), 2-year clinical outcomes were improved in heart failure with reduced ejection fraction (HFrEF, n=206) and worsened in heart failure with preserved ejection fraction (HFpEF, n=302). However, randomized trials typically include therapeutic responders and nonresponders. We sought to determine the independent predictors of outcomes and model individual patient risk after atrial shunt implantation in HFrEF and HFpEF. METHODS: The primary outcome included all-cause death, cardiac transplantation or left ventricular assist device implantation, heart failure hospitalizations, and outpatient worsening heart failure events. From 37 baseline clinical, laboratory, echocardiographic, and hemodynamic covariates, the cumulative mean function of recurrent events during follow-up was modeled by the Lin-Wei-Yang-Ying method. RESULTS: Among control patients with HFrEF, independent baseline predictors of outcomes were atrial fibrillation, elevated troponin, lower left ventricular ejection fraction, and greater right atrial pressure. In contrast, independent predictors of outcomes in shunt-treated patients with HFrEF were lower systolic blood pressure and elevated right ventricular end-diastolic area index, pulmonary artery pressure, and pulmonary vascular resistance. Among control patients with HFpEF, independent predictors of outcomes were diabetes, higher heart rate and left ventricular end-systolic volume, and lower right ventricular fractional area change. Conversely, independent predictors in shunt-treated patients with HFpEF were hypertension, smoking, lower 6-minute walk distance, reduced estimated glomerular filtration rate, elevated troponin, and moderate or greater tricuspid regurgitation. Risk modeling estimated that 67.2% of patients with HFrEF might benefit from shunt placement compared with 21.4% of patients with HFpEF. CONCLUSIONS: In RELIEVE-HF, distinct baseline risk factors influenced cardiovascular outcomes before and after atrial shunt treatment in HFrEF and HFpEF. Despite markedly different group responses to atrial shunt treatment in the randomized HFrEF and HFpEF strata, given individual differences in patient risk factor profiles, most but not all patients with HFrEF may benefit, and some patients with HFpEF may also improve after shunt treatment. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03499236.
BACKGROUND:Despite strong evidence, adoption of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction remains suboptimal. The Get With The Guidelines-Heart Failure (GWTG-HF) program was designed to close gaps in care. We evaluated whether hospital participation in GWTG-HF was associated with greater GDMT intensity and improved outcomes. METHODS:We conducted a retrospective analysis (2013-2021) of Medicare beneficiaries with part A and part D hospitalized with heart failure with reduced ejection fraction. Using a multiple baseline time series design, we compared changes in GDMT and outcomes before and after GWTG-HF enrollment with hospitals that never participated. Coprimary outcomes were a 90-day postdischarge GDMT score under a parallel and nonparallel slopes model. Secondary outcomes included class-specific medication fills, achievement of ≥50% target doses, and 30-day, 90-day, and 1-year all-cause and HF readmission and mortality. Mortality and first HF readmission were also evaluated using Cox proportional hazards models. We adjusted for baseline hospital performance, patient characteristics, and temporal trends. RESULTS:Among 1274 863 Medicare beneficiaries hospitalized for heart failure with reduced ejection fraction, 53.5% were treated at hospitals that never participated in GWTG-HF and 9.6% at GWTG-HF hospitals. Unadjusted median GDMT scores increased from 3.0 in both groups to 4.0 in nonparticipating hospitals and 4.5 in GWTG-HF hospitals at 90 days (P<0.001). Hospital enrollment was associated with a higher 90-day GDMT score (+0.15 points [95% CI, 0.12-0.20]; P<0.001) and greater use of β-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists but not angiotensin receptor-neprilysin inhibitors. GWTG-HF participation was associated with lower all-cause mortality at 30 days (odds ratio, 0.95 [95% CI, 0.92-0.98]) and 1 year (0.97 [95% CI, 0.95-0.1.00]; both P<0.05). Mortality differences were attenuated and no longer significant in the nonparallel slopes model. CONCLUSIONS:Hospital participation in GWTG-HF was associated with modest but significant improvements in postdischarge GDMT intensity, supporting the value of quality improvement initiatives to address persistent treatment gaps in heart failure with reduced ejection fraction.
