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Sodium-glucose cotransporter-2 inhibitor therapy is well suited for initiation during the heart failure hospitalization, owing to clinical benefits that accrue rapidly within days to weeks, a strong safety and tolerability profile, minimal to no effects on blood pressure, and no excess risk of adverse kidney events. There is no evidence to suggest that deferring initiation to the outpatient setting accomplishes anything beneficial. Instead, there is compelling evidence that deferring in-hospital initiation exposes patients to excess risk of early postdischarge clinical worsening and death. Lessons from other heart failure with reduced ejection fraction therapies highlight that deferring initiation of guideline-recommended medications to the U.S. outpatient setting carries a >75% chance they will not be initiated within the next year. Recognizing that 1 in 4 patients hospitalized for worsening heart failure die or are readmitted within 30 days, clinicians should embrace the in-hospital period as an optimal time to initiate sodium-glucose cotransporter-2 inhibitor therapy and treat this population with the urgency it deserves.

AimsImproving the health status (symptoms, function, and quality of life) of patients with heart failure with reduced ejection fraction (HFrEF) is a primary treatment goal. Angiotensin receptor neprilysin inhibitors (ARNI) improve short-term health status in clinical practice, but the sustainability of these improvements is unknown.Methods and resultsIn CHAMP-HF, a multicentre observational study of outpatients with HFrEF, patients initiated on ARNI were propensity score matched 1:2 to patients not using ARNI with Cox regression modelling time to ARNI initiation, adjusted for sociodemographic and clinical variables, medical history, medications, and baseline Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. Repeated measures models for the overall KCCQ score and each domain compared the health status trajectories of patients initiated on ARNI vs. not. Among 3930 participants, 746 (19.0%) began ARNI, of whom 576 were matched to 1152 non-ARNI patients. Prior to matching, participants initiated on ARNI were younger, non-Hispanic, had lower EFs, more commonly had a history of ventricular arrhythmia, were less likely to be taking an ACEI/ARB, and more likely to be treated with beta-blockers and mineralocorticoid receptor antagonists. There were no differences after matching. In the matched cohort, participants initiated on ARNI experienced improved health status by 3 months that persisted through 12 months [KCCQ Overall Summary Score (OSS) = 73.4 vs. 70.8; P

AimsThe aim of our study was to investigate heterogeneity of health status treatment response of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF).Methods and resultsWe leveraged data from CHAMP-HF, an observational registry of 140 US clinics and 5026 outpatients with chronic HFrEF, where health status was serially assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 Overall Summary Scale (range from 0 to 100; ≥20-point improvement is a very large improvement). In 334 patients newly initiated on sacubitril/valsartan, we used hierarchical multivariable logistic regression (13 patient-level characteristics as well as baseline KCCQ-12 score) to calculate the odds ratio (OR) of any characteristic being associated with a very large health status improvement. A total of 104/334 (31.1%) of patients achieved the primary endpoint, where only worse baseline health status [KCCQ-12 score of 0-60 points had an OR = 0.86/5-point higher score (CI 0.79, 0.93)], and those with a KCCQ-12 score of 60-80 points had an OR = 0.61/5-point higher score (0.45-0.82), which was associated with a very large benefit. No other patient characteristic was associated with a very large health status improvement (P > 0.05).ConclusionsWe found that, after initiation of sacubitril/valsartan, only worse baseline health status was associated with very large health status improvement. Accordingly, a trial of therapy-particularly in those with worse symptoms, function, and quality of life-and assessing treatment response are likely to be the best prospective strategy.

ObjectivesThis study sought to describe the short-term health status benefits of angiotensin-neprilysin inhibitor (ARNI) therapy in patients with heart failure and reduced ejection fraction (HFrEF).BackgroundAlthough therapy with sacubitril/valsartan, a neprilysin inhibitor, improved patients' health status (compared with enalapril) at 8 months in the PARADIGM-HF (Prospective Comparison of ARNI with ACE inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) study, the early impact of ARNI on patients' symptoms, functions, and quality of life is unknown.MethodsHealth status was assessed by using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ) in 3,918 outpatients with HFrEF and left ventricular ejection fraction ≤40% across 140 U.S. centers in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry. ARNI therapy was initiated in 508 patients who were matched 1:2 to 1,016 patients who were not initiated on ARNI (no-ARNI), using a nonparsimonious time-dependent propensity score (6 sociodemographic factors, 23 clinical characteristics), prior KCCQ overall summary (KCCQ-OS) score, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker status.ResultsMultivariate linear regression demonstrated a greater mean improvement in KCCQ-OS in patients initiated on ARNI therapy (5.3 ± 19 vs. 2.5 ± 17.4, respectively; p

ObjectivesThe aim of this study was to use a multicenter, observational outpatient registry of patients with heart failure with reduced ejection fraction (HFrEF) to describe the association between changes in patients' medications with changes in health status.BackgroundAlleviating symptoms and improving function and quality of life for patients with HFrEF are primary treatment goals and potential indicators of quality. Whether titrating medications in routine clinical care improves patients' health status is unknown.MethodsThe association of any change in HFrEF medications with 3-month change in health status, as measured using the 12-item Kansas City Cardiomyopathy Questionnaire Overall Summary Scale, was determined in unadjusted and multivariate-adjusted (25 clinical characteristics, baseline health status) models using hierarchical linear regression.ResultsAmong 3,313 outpatients with HFrEF from 140 centers, 21.9% had medication changes. Three months later, 23.7% and 46.4% had clinically meaningfully worse (≥5-point decrease) and improved (≥5-point increase) Kansas City Cardiomyopathy Questionnaire Overall Summary Scale scores. The 3-month median change in Kansas City Cardiomyopathy Questionnaire Overall Summary Scale score for patients whose HFrEF medications were changed was significantly larger (7.3 points; interquartile range: -3.1 to 20.8 points) than in patients whose medications were not changed (3.1 points; interquartile range: -4.7 to 12.5 points) (adjusted difference 3.0 points; 95% confidence interval: 1.4 to 4.6 points; p

ObjectivesThis study sought to describe the health status of outpatients with heart failure and reduced ejection fraction (HFrEF) by sex, race/ethnicity, and socioeconomic status (SES).BackgroundAlthough a primary goal in treating patients with HFrEF is to optimize health status, whether disparities by sex, race/ethnicity, and SES exist is unknown.MethodsIn the CHAMP-HF (Change the Management of Patients with Heart Failure) registry, the associations among sex, race, and SES and health status, as measured by the Kansas City Cardiomyopathy Questionnaire-overall summary (KCCQ-os) score (range 0 to 100; higher scores indicate better health status) was compared among 3,494 patients from 140 U.S. clinics. SES was categorized by total household income. Hierarchical multivariate linear regression estimated differences in KCCQ-os score after adjusting for 31 patient characteristics and 10 medications.ResultsOverall mean KCCQ-os scores were 64.2 ± 24.0 but lower for women (29% of sample; 60.3 ± 24.0 vs. 65.9 ± 24.0, respectively; p < 0.001), for blacks (60.5 ± 25.0 vs. 64.9 ± 23.0, respectively; p < 0.001), for Hispanics (59.1 ± 21.0 vs. 64.9 ± 23.0, respectively; p < 0.001), and for those with the lowest income (

BACKGROUND:Although a key treatment goal for patients with heart failure with reduced ejection fraction is to optimize their health status (their symptoms, function, and quality of life), the variability across outpatient practices in achieving this goal is unknown. METHODS AND RESULTS:In the CHAMP-HF (Change the Management of Patients With Heart Failure) registry, associations between baseline practice characteristics and Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary (OS) and Symptom Frequency (SF) scores were assessed in 3494 patients across 140 US practices using hierarchical regression after accounting for 23 patient and 11 treatment characteristics. We then calculated an adjusted median odds ratio to quantify the average difference in likelihood that a patient would have excellent (KCCQ-OS, ≥75) health status or minimal (monthly or fewer) symptoms (KCCQ-SF, ≥75) when treated at one practice versus another, at random. The mean (±SD) KCCQ-OS and KCCQ-SF were 64.2±24 and 68.9±25.6, with 40% (n=1380) and 50% (n=1760) having KCCQ scores ≥75, respectively. The adjusted median odds ratio across practices, for KCCQ-OS ≥75, was 1.70 (95% confidence interval, 1.54-1.99; P

Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3-9.2, P = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0-9.6, P = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7-10.0, P = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6-34.7, P = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1-7.8, P = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05-2.85, P = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01-1.42, P = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF. In a multicenter, randomized trial, the SGLT2 inhibitor dapagliflozin improved the health status and exercise function of patients with heart failure with preserved ejection fraction (HFpEF), a condition for which effective treatments are lacking., Author(s): Michael E. Nassif [sup.1] [sup.2] , Sheryl L. Windsor [sup.1] , Barry A. Borlaug [sup.3] , Dalane W. Kitzman [sup.4] , Sanjiv J. Shah [sup.5] , Fengming Tang [sup.1] [...]

Aims: The aim of this study was to report safety and efficacy of aficamten in patients with non‐obstructive hypertrophic cardiomyopathy (nHCM) over 36 weeks in the ongoing FOREST‐HCM trial. Methods and results: Patients were started on aficamten 5 mg daily, with doses adjusted in 5‐mg increments (5–20 mg) at ≥2‐week intervals according to site‐read left ventricular ejection fraction (LVEF). Aficamten dose was increased if LVEF ≥55%, maintained if LVEF 50–54%, decreased if LVEF 40–<50%, and temporarily interrupted if LVEF <40%. Safety and efficacy were assessed over 36 weeks. Overall, 34 patients were enrolled (mean age 57.2 ± 15.3 years, 62% female, 41% in New York Heart Association [NYHA] class III). Over 36 weeks, 82.3% achieved 15–20 mg daily dose and there was a modest reduction in LVEF by −4.3% ± 5.2 from 70% ± 6.1 (p < 0.0001). At Week 36, NYHA class improved by ≥1 class in 27 (79.4%) patients. Mean Kansas City Cardiomyopathy Questionnaire clinical summary score improved by 13.8 ± 12.5 points relative to baseline. Median (interquartile range) levels of N‐terminal pro‐B‐type natriuretic peptide were significantly improved from baseline (−665.5 pg/ml [−1244.0, −232.0]; p < 0.0001), while high‐sensitivity cardiac troponin I was unchanged (−2.7 ng/L [−11.3, 1.6]; p = 0.25). There were no drug discontinuations due to adverse events. LVEF <50% occurred in 2 (5.9%) patients, one following pulmonary vein isolation and one associated with atrial fibrillation. Conclusions: Over 36 weeks, aficamten appeared safe and effective in the studied patients with nHCM. [ABSTRACT FROM AUTHOR]

Aims: Patients hospitalized for acute heart failure (HF) could be enrolled in EMPULSE (NCT04157751) upon haemodynamic stabilization and between 24 h and 5 days after hospital admission. The timing of treatment initiation may influence the efficacy and safety of drugs such as empagliflozin. The aim of this study was to evaluate patient characteristics, clinical events, and treatment effects according to time from admission to randomization. Methods and results: The EMPULSE population was dichotomized by median time from hospital admission to randomization (1–2 days vs. 3–5 days). The primary outcome was a hierarchical composite endpoint of time to all‐cause death, number of HF events, time to first HF event, and a ≥5‐point difference in Kansas City Cardiomyopathy Questionnaire total symptom score change from baseline after 90 days, analysed using the win ratio (WR) method. Patients randomized later (3–5 days, average time 3.9 days; n = 312) had a higher risk of experiencing clinical events than patients randomized earlier (1–2 days, average time 1.7 days; n = 215). The treatment effect favoured empagliflozin versus placebo in patients randomized later (3–5 days: WR 1.69, 95% confidence interval [CI] 1.26–2.25) but was attenuated in patients randomized earlier (1–2 days: WR 1.04, 95% CI 0.74–1.44) (interaction p = 0.029). A similar pattern was observed for the composite of HF hospitalization or cardiovascular death and all‐cause hospitalizations (interaction p < 0.1 for both). The reduction of N‐terminal pro‐B‐type natriuretic peptide levels was more pronounced with empagliflozin among patients randomized later than in patients randomized earlier (interaction p = 0.004). Conclusions: Among patients hospitalized for acute HF enrolled in EMPULSE, those randomized later after hospital admission (3–5 days) experienced greater clinical benefit with empagliflozin than those randomized earlier (1–2 days). These findings should be confirmed in future studies before clinical application. [ABSTRACT FROM AUTHOR]

Aim: The EMPULSE (EMPagliflozin in patients hospitalised with acUte heart faiLure who have been StabilizEd) trial showed that, compared to placebo, the sodium–glucose cotransporter 2 inhibitor empagliflozin (10 mg/day) improved clinical outcomes of patients hospitalized for acute heart failure (HF). We investigated whether efficacy and safety of empagliflozin were consistent across the spectrum of left ventricular ejection fraction (LVEF). Methods and results: A total of 530 patients hospitalized for acute de novo or decompensated HF were included irrespective of LVEF. For the present analysis, patients were classified as HF with reduced (HFrEF, LVEF ≤40%), mildly reduced (HFmrEF, LVEF 41–49%) or preserved (HFpEF, LVEF ≥50%) ejection fraction at baseline. The primary endpoint was a hierarchical outcome of death, worsening HF events (HFE) and quality of life over 90 days, assessed by the win ratio. Secondary endpoints included individual components of the primary endpoint and safety. Out of 523 patients with baseline data, 354 (67.7%) had HFrEF, 54 (10.3%) had HFmrEF and 115 (22.0%) had HFpEF. The clinical benefit (hierarchical composite of all‐cause death, HFE and Kansas City Cardiomyopathy Questionnaire total symptom score) of empagliflozin at 90 days compared to placebo was consistent across LVEF categories (≤40%: win ratio 1.35 [95% confidence interval 1.04, 1.75]; 41–49%: win ratio 1.25 [0.66, 2.37)] and ≥50%: win ratio 1.40 [0.87, 2.23], pinteraction = 0.96) with a favourable safety profile. Results were consistent across individual components of the hierarchical primary endpoint. Conclusion: The clinical benefit of empagliflozin proved consistent across LVEF categories in the EMPULSE trial. These results support early in‐hospital initiation of empagliflozin regardless of LVEF. [ABSTRACT FROM AUTHOR]