Search

BACKGROUND: The impact of routine clinic use of patient-reported outcome (PRO) measures on clinical outcomes in patients with heart failure (HF) has not been well-characterized. We tested if clinic-based use of a disease-specific PRO improves patient-reported quality of life at 1 year. METHODS: The PRO-HF trial (Patient-Reported Outcome Measurement in Heart Failure Clinic) was an open-label, parallel, patient-level randomized clinical trial of routine PRO assessment or usual care at an academic HF clinic between August 30, 2021, and June 30, 2022, with 1 year of follow-up. In the PRO assessment arm, participants completed the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) at each HF clinic visit, and results were shared with their treating clinician. The usual care arm completed the KCCQ-12 at randomization and 1 year later, which was not shared with the treating clinician. The primary outcome was the KCCQ-12 overall summary score (OSS) between 12 and 15 months after randomization. Secondary outcomes included domains of the KCCQ-12, hospitalization and emergency department visit rates, HF medication therapy, clinic visit frequency, and testing rates. RESULTS: Across 17 clinicians, 1248 participants were enrolled and randomized to PRO assessment (n=624) or usual care (n=624). The median age was 63.9 years (interquartile range [IQR], 51.8--72.8), 38.9% were women, and the median baseline KCCQ-12 OSS was 82.3 (IQR, 58.3--94.8). Final KCCQ-12 (available in 87.9% of the PRO arm and 85.1% in usual care; P=0.16) median OSS were 87.5 (IQR, 68.8--96.9) in the PRO arm and 87.6 (IQR, 69.7--96.9) in the usual care arm with a baseline-adjusted mean difference of 0.2 ([95% CI, -1.7 to 2.0]; P=0.85). The results were consistent across prespecified subgroups. A post hoc analysis demonstrated a significant interaction with greater benefit among participants with a baseline KCCQ-12 OSS of 60 to 80 but not in less or more symptomatic participants. No significant differences were found in 1-year mortality, hospitalizations, emergency department visits, medication therapy, clinic follow-up, or testing rates between arms. CONCLUSIONS: Routine PRO assessment in HF clinic visits did not impact patient-reported quality of life or other clinical outcomes. Alternate strategies and settings for embedding PROs into routine clinical care should be tested. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04164004. [ABSTRACT FROM AUTHOR]

Conventional time-to-first-event analyses cannot incorporate recurrent hospitalizations and patient well-being in a single outcome. To overcome this limitation, we tested an integrated measure that includes days lost from death and hospitalization, and additional days of full health lost through diminished well-being. The effect of dapagliflozin on this integrated measure was assessed in the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial, which examined the efficacy of dapagliflozin, compared with placebo, in patients with NYHA functional class II to IV heart failure and a left ventricular ejection fraction ≤40%. Over 360 days, patients in the dapagliflozin group (n = 2,127) lost 10.6 ± 1.0 (2.9%) of potential follow-up days through cardiovascular death and heart failure hospitalization, compared with 14.4 ± 1.0 days (4.0%) in the placebo group (n = 2,108), and this component of all measures of days lost accounted for the greatest between-treatment difference (−3.8 days [95% CI: −6.6 to −1.0 days]). Patients receiving dapagliflozin also had fewer days lost to death and hospitalization from all causes vs placebo (15.5 ± 1.1 days [4.3%] vs 20.3 ± 1.1 days [5.6%]). When additional days of full health lost (ie, adjusted for Kansas City Cardiomyopathy Questionnaire–overall summary score) were added, total days lost were 110.6 ± 1.6 days (30.7%) with dapagliflozin vs 116.9 ± 1.6 days (32.5%) with placebo. The difference in all measures between the 2 groups increased over time (ie, days lost by death and hospitalization −0.9 days [−0.7%] at 120 days, −2.3 days [−1.0%] at 240 days, and −4.8 days [−1.3%] at 360 days). Dapagliflozin reduced the total days of potential full health lost due to death, hospitalizations, and impaired well-being, and this benefit increased over time during the first year. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure; NCT03036124) [Display omitted] [ABSTRACT FROM AUTHOR]

BACKGROUND Obesity and type 2 diabetes are prevalent in patients with heart failure with preserved ejection fraction and are characterized by a high symptom burden. No approved therapies specifically target obesity-related heart failure with preserved ejection fraction in persons with type 2 diabetes. METHODS We randomly assigned patients who had heart failure with preserved ejection fraction, a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or more, and type 2 diabetes to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. The primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary end points included the change in 6-minute walk distance; a hierarchical composite end point that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level. RESULTS A total of 616 participants underwent randomization. The mean change in the KCCQ-CSS was 13.7 points with semaglutide and 6.4 points with placebo (estimated difference, 7.3 points; 95% confidence interval [CI], 4.1 to 10.4; P<0.001), and the mean percentage change in body weight was -9.8% with semaglutide and -3.4% with placebo (estimated difference, -6.4 percentage points; 95% CI, -7.6 to -5.2; PcO.OOl). The results for the confirmatory secondary end points favored semaglutide over placebo (estimated between-group difference in change in 6-minute walk distance, 14.3 m [95% CI, 3.7 to 24.9; P=0.008]; win ratio for hierarchical composite end point, 1.58 [95% CI, 1.29 to 1.94; P<0.001]; and estimated treatment ratio for change in CRP level, 0.67 [95% CI, 0.55 to 0.80; P<0.001]). Serious adverse events were reported in 55 participants (17.7%) in the semaglutide group and 88 (28.8%) in the placebo group. CONCLUSIONS Among patients with obesity-related heart failure with preserved ejection fraction and type 2 diabetes, semaglutide led to larger reductions in heart failure-related symptoms and physical limitations and greater weight loss than placebo at 1 year. [ABSTRACT FROM AUTHOR]

Aims: Patients with heart failure and mildly reduced or preserved ejection fraction have limited therapeutic options. The ALT‐FLOW Early Feasibility Study evaluated safety, haemodynamics and outcomes for the APTURE transcatheter shunt system, a novel left atrium to coronary sinus shunt in these patients. Methods and results: Safety and shunt implantation success was evaluated for all 116 enrolled patients. An analysis population of implanted patients with a left ventricular ejection fraction (LVEF) >40% (n = 95) was chosen to assess efficacy via paired comparison between baseline and follow‐up haemodynamic (3 and 6 months), and echocardiographic, clinical and functional outcomes (6 months and 1 year). Health status and quality of life outcomes were assessed using the Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ‐OSS). The primary safety endpoint, major adverse cardiac, cerebral, and renal events, and reintervention through 30 days, occurred in 3/116 patients (2.6%). All implanted shunts were patent at 1 year. In patients with LVEF >40%, the mean (95% confidence interval) reduction in exercise pulmonary capillary wedge pressure (PCWP) at 20 W was −5.7 (−8.6, −2.9) mmHg at 6 months (p < 0.001). At baseline, 8% had New York Heart Association class I–II status and improved to 68% at 1 year (p < 0.001). KCCQ‐OSS at baseline was 39 (35, 43) and improved at 6 months and 1 year by 25 (20–30) and 27 (22–32) points, respectively (both p < 0.0001). No adverse changes in haemodynamic and echocardiographic indices of right heart function were observed at 1 year. Overall, the reduction in PCWP at 20 W and improvement in KCCQ‐OSS in multiple subgroups were consistent with those observed for the entire population. Conclusions: In patients with heart failure and LVEF >40%, the APTURE shunt demonstrated an acceptable safety profile with significant sustained improvements in haemodynamic and patient‐centred outcomes, underscoring the need for further evaluation of the APTURE shunt in a randomized trial. [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]

Aim: To assess the cost‐effectiveness of dapagliflozin in addition to usual care, compared with usual care alone, in a large population of patients with heart failure (HF), spanning the full range of left ventricular ejection fraction (LVEF). Methods and results: Patient‐level data were pooled from HF trials (DAPA‐HF, DELIVER) to generate a population including HF with reduced, mildly reduced and preserved LVEF, to increase statistical power and enable exploration of interactions among LVEF, renal function and N‐terminal pro‐B‐type natriuretic peptide levels, as they are relevant determinants of health status in this population. Survival and HF recurrent event risk equations were derived and applied to a lifetime horizon Markov model with health states defined by Kansas City Cardiomyopathy Questionnaire total symptom score quartiles; costs and utilities were in the UK setting. The base case incremental cost‐effectiveness ratio (ICER) was £6470 per quality‐adjusted life year (QALY) gained, well below the UK willingness‐to‐pay (WTP) threshold of £20 000/QALY gained. In interaction sensitivity analyses, the highest ICER was observed for elderly patients with preserved LVEF (£16 624/QALY gained), and ranged to a region of dominance (increased QALYs, decreased costs) for patients with poorer renal function and reduced/mildly reduced LVEF. Results across the patient characteristic interaction plane were mostly between £5000 and £10 000/QALY gained. Conclusions: Dapagliflozin plus usual care, versus usual care alone, yielded results well below the WTP threshold for the UK across a heterogeneous population of patients with HF including the full spectrum of LVEF, and is likely a cost‐effective intervention. [ABSTRACT FROM AUTHOR]

BACKGROUND: Patients with heart failure (HF) with preserved ejection fraction (HFpEF) and obesity experience a high burden of symptoms and functional impairment, and a poor quality of life. In the STEP-HFpEF trial (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity), once-weekly semaglutide 2.4 mg improved symptoms, physical limitations, and exercise function, and reduced inflammation and body weight. This prespecified analysis investigated the effects of semaglutide on the primary and confirmatory secondary end points across the range of the Kansas City Cardiomyopathy Questionnaire (KCCQ) scores at baseline and on all key summary and individual KCCQ domains. METHODS: STEP-HFpEF randomly assigned 529 participants with symptomatic HF, an ejection fraction of ≥45%, and a body mass index of ≥30 kg/m2 to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. Dual primary end points change in KCCQ-Clinical Summary Score (CSS) and body weight. Confirmatory secondary end points included change in 6-minute walk distance, a hierarchical composite end point (death, HF events, and change in KCCQ-CSS and 6-minute walk distance) and change in C-reactive protein. Patients were stratified by KCCQ-CSS tertiles at baseline. Semaglutide effects on the primary, confirmatory secondary, and select exploratory end points (N-terminal pro-brain natriuretic peptide) were examined across these subgroups. Semaglutide effects on additional KCCQ domains (Total Symptom Score [including symptom burden and frequency], Physical Limitations Score, Social Limitations Score, Quality of Life Score, and Overall Summary Score) were also evaluated. RESULTS: Baseline median KCCQ-CSS across tertiles was 37, 59, and 77 points, respectively. Semaglutide consistently improved primary end points across KCCQ tertiles 1 to 3 (estimated treatment differences [95% CI]: for KCCQ-CSS, 10.7 [5.4 to 16.1], 8.1 [2.7 to 13.4], and 4.6 [-0.6 to 9.9] points; for body weight, -11 [-13.2 to -8.8], -9.4 [-11.5 to -7.2], and -11.8 [-14.0 to -9.6], respectively; Pinteraction=0.28 and 0.29, respectively); the same was observed for confirmatory secondary and exploratory end points (Pinteraction>0.1 for all). Semaglutide-treated patients experienced improvements in all key KCCQ domains (estimated treatment differences, 6.7-9.6 points across domains; P≤0.001 for all). Greater proportion of semaglutide-treated versus placebo-treated patients experienced at least 5-, 10-, 15-, and 20-point improvements in all KCCQ domains (odds ratios, 1.6-2.9 across domains; P<0.05 for all). CONCLUSIONS: In patients with HFpEF and obesity, semaglutide produced large improvements in HF-related symptoms, physical limitations, exercise function, inflammation, body weight, and N-terminal pro-brain natriuretic peptide, regardless of baseline health status. The benefits of semaglutide extended to all key KCCQ domains. [ABSTRACT FROM AUTHOR]

Acute decompensated heart failure involves a high rate of mortality and complications. Management typically involves a multi-day hospital admission. However, patients often lose part of their function with each successive admission, and are at a high risk for hospital-associated complications such as nosocomial infection. This study aims to determine the safety and efficacy of the management of patients presenting with acute decompensated heart failure to clinic-based therapy vs usual inpatient care using a reproducible management pathway. An investigator-initiated, prospective, non-inferiority, 1:1 randomised-controlled trial, stratified by left ventricular ejection fraction including 460 patients with a minimum follow-up of 7 days. This is a multi-centre study to be performed in centres across Victoria, Australia. Participants will be patients with either heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF), admitted for acute decompensation of heart failure. Intervention: Early discharge to an outpatient-based Heart Failure Rapid Access Clinical Review (RACER) in addition to frequent medical/nursing at-home review for patients admitted with decompensated heart failure. The primary endpoint will be a non-inferiority assessment of re-hospitalisation at 30 days. Secondary outcomes include superiority assessment of hospitalisation at 30 days, a composite clinical endpoint of major adverse cardiac and cerebrovascular event (MACCE), hospital re-admission or mortality at 3 months, achievement of guideline-directed medical therapy, patient assessment of symptoms (visual-analogue scale quantified as area under curve and Kansas City Cardiomyopathy Questionnaire-12 [KCCQ-12]), attendance at 3-month outpatient follow-up, number of bed stays/clinics attended, proportion of patients free from congestion, change in serum creatinine level, treatment for electrolyte disturbances, time to transition from intravenous to oral diuretics, and health economics analysis (cost-benefit analysis, cost-utility analysis, incremental cost-effectiveness ratio). The Early Discharge to Clinic-Based Therapy of Patients Presenting with Decompensated Heart Failure (EDICT-HF) trial will help determine whether earlier discharge to out-of-hospital care is non-inferior to the usual practice of inpatient care, in patients with heart failure admitted to hospital for acute decompensation, as an alternative model of care. [ABSTRACT FROM AUTHOR]

Aims: Small studies and observations suggested that exercise training may improve peak oxygen consumption (peakVO2) in patients with advanced heart failure and left ventricular assist device (LVAD). We investigated whether in this patient group a supervised exercise training can improve exercise capacity. Methods and results: In this multicentre, prospective, randomized, controlled trial, patients with stable heart failure and LVAD were randomly assigned (2:1) to 12 weeks of supervised exercise training or usual care, with 12 weeks of follow‐up. The primary endpoint was the change in peakVO2 after 12 weeks (51 patients provided a power of 90% with an expected group difference in peakVO2 of 3 ml/kg/min). Secondary endpoints included changes in submaximal exercise capacity and quality of life. Among 64 patients enrolled (97% male, mean age 56 years), 54 were included in the analysis. Mean difference in the change of peakVO2 after 12 weeks was 0.826 ml/min/kg (95% confidence interval [CI] −0.37, 2.03; p = 0.183). There was a positive effect of exercise training on 6‐min walk distance with a mean increase in the intervention group by 43.4 m (95% CI 16.9, 69.9; p = 0.0024), and on the Kansas City Cardiomyopathy Questionnaire physical domain score (mean 14.3, 95% CI 3.7, 24.9; p = 0.0124), both after 12 weeks. The overall adherence was high (71%), and there were no differences in adverse events between groups. Conclusion: In patients with advanced heart failure and LVAD, 12 weeks of exercise training did not improve peakVO2 but demonstrated positive effects on submaximal exercise capacity and physical quality of life. [ABSTRACT FROM AUTHOR]

Many therapies for heart failure (HF) have shown differential impact across the spectrum of left ventricular ejection fraction (LVEF). In this prespecified analysis, the authors assessed the effects of semaglutide across the baseline LVEF strata in patients with the obesity phenotype of HF with preserved ejection fraction (HFpEF) in the STEP-HFpEF (Semaglutide Treatment Effect in People with obesity and HFpEF) trial. STEP-HFpEF randomized 529 patients (263 semaglutide; 266 placebo). For this prespecified analysis, patients were categorized into 3 groups based on LVEF: 45% to 49% (n = 85), 50% to 59% (n = 215), and ≥60% (n = 229). At 52 weeks, semaglutide improved the dual primary endpoints of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (estimated treatment difference: EF [ejection fraction] 45%-49%: 5.0 points [95% CI: −2.7 to 12.8 points], EF 50%-59%: 9.8 points [95% CI: 5.0 to 14.6 points], and EF ≥60%: 7.4 points [95% CI: 2.8 to 12.0 points]; P interaction = 0.56) and body weight (EF: 45%-49%: −7.6 [95% CI: −10.7 to −4.4], EF 50%-59%: −10.6 [95% CI: −12.6 to −8.6] and EF ≥60%: −11.9 [95% CI: −13.8 to −9.9]; P interaction = 0.08), to a similar extent across LVEF categories. Likewise, LVEF did not influence the benefit of semaglutide on confirmatory secondary endpoints: 6-minute walk distance (P interaction = 0.19), hierarchal composite endpoint (P interaction = 0.43), and high-sensitivity C-reactive protein (P interaction = 0.26); or exploratory endpoint of N-terminal pro-brain natriuretic peptide (P interaction = 0.96). Semaglutide was well-tolerated across LVEF categories. In patients with HFpEF and obesity, semaglutide 2.4 mg improved symptoms, physical limitations, and exercise function, and reduced inflammation and body weight to a similar extent across LVEF categories. These data support treatment with semaglutide in patients with the obesity phenotype of HFpEF regardless of LVEF. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF]; NCT04788511) [Display omitted] [ABSTRACT FROM AUTHOR]

Real-world applicability of the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) randomized controlled trial (RCT) has been debated because of careful patient selection and the contrasting results of the MITRA-FR (Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients with Severe Secondary Mitral Regurgitation) RCT. The COAPT-PAS (COAPT Post-Approval Study) was initiated to assess the safety and effectiveness of the MitraClip in patients with secondary mitral regurgitation (SMR). COAPT-PAS is a prospective, single-arm, observational study of 5,000 consecutive patients with SMR treated with the MitraClip at 406 U.S. centers participating in the TVT (Transcatheter Valve Therapy) registry from 2019 to 2020. The 1-year outcomes from the COAPT-PAS full cohort and the COAPT-like and MITRA-FR–like subgroups who met RCT inclusion/exclusion criteria are reported. Patients in the COAPT-PAS had more comorbidities, more severe HF and functional limitations, and less guideline-directed medical therapy than those in the COAPT or MITRA-FR RCTs. Patients in the COAPT-PAS full cohort and the COAPT-like (n = 991) and MITRA-FR–like (n = 917) subgroups achieved a 97.7% MitraClip implant rate, a similar and durable reduction of mitral regurgitation to ≤2+ at 1 year (90.7%, 89.7%, and 86.6%, respectively), a large improvement in quality of life at 1 year (Kansas City Cardiomyopathy Questionnaire +29 COAPT-PAS, +27 COAPT-like, and +33 MITRA-FR–like), faster procedure times, similar or lower clinical event rates compared with the RCTs' MitraClip arms, and lower clinical event rates than the RCTs' guideline-directed medical therapy only arms. One-year heart failure hospitalizations was 18.9% in COAPT-PAS, 19.7% in COAPT-like compared with 24.9% in COAPT-RCT, and 28.7% in COAPT-PAS-MITRA-FR–like compared with 47.4% in MITRA-FR-RCT. This large, contemporary, real-world study reinforces the safety and effectiveness of the MitraClip System in patients with SMR, including those who met the COAPT or MITRA-FR RCT inclusion/exclusion criteria and patients excluded from the RCTs. [Display omitted] [ABSTRACT FROM AUTHOR]

BACKGROUND: It is not known whether the benefits of sodium-glucose cotransporter 2 inhibitors in heart failure persist after years of therapy. METHODS: In the EMPEROR-Reduced (Empagliflozin Outcome Trials in Chronic Heart Failure With Reduced Ejection Fraction) and EMPEROR-Preserved (Empagliflozin Outcome Trials in Chronic Heart Failure With Preserved Ejection Fraction) trials, patients with heart failure were randomly assigned (double-blind) to placebo or empagliflozin 10 mg/day for a median of 16 and 26 months, respectively. At the end of the trials, 6799 patients (placebo 3381, empagliflozin 3418) were prospectively withdrawn from treatment in a blinded manner, and, of these, 3981 patients (placebo 2020, empagliflozin 1961) underwent prespecified in-person assessments after ≈30 days off treatment. RESULTS: From 90 days from the start of closeout to the end of double-blind treatment, the annualized risk of cardiovascular death or hospitalization for heart failure was lower in empagliflozin-treated patients than in placebo-treated patients (10.7 [95% CI, 9.0-12.6] versus 13.5 [95% CI, 11.5-15.6] events per 100 patient-years, respectively; hazard ratio 0.76 [95% CI, 0.60-0.96]). When the study drugs were withdrawn for ≈30 days, the annualized risk of cardiovascular death or hospitalization for heart failure increased in patients withdrawn from empagliflozin but not in those withdrawn from placebo (17.0 [95% CI, 12.6-22.1] versus 14.1 [95% CI, 10.1-18.8] events per 100 patient-years for empagliflozin and placebo, respectively). The hazard ratio for the change in risk in the patients withdrawn from empagliflozin was 1.75 (95% CI, 1.20-2.54), P=0.0034, whereas the change in the risk in patients withdrawn from placebo was not significant (hazard ratio 1.12 [95% CI, 0.76-1.66]); time period-by-treatment interaction, P=0.068. After withdrawal, the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score declined by 1.6±0.4 in patients withdrawn from empagliflozin versus placebo (P<0.0001). Furthermore, withdrawal of empagliflozin was accompanied by increases in fasting glucose, body weight, systolic blood pressure, estimated glomerular filtration rate, N-terminal pro-hormone B-type natriuretic peptide, uric acid, and serum bicarbonate and decreases in hemoglobin and hematocrit (all P<0.01). These physiological and laboratory changes were the inverse of the effects of the drug seen at the start of the trials during the initiation of treatment (≈1-3 years earlier) in the same cohort of patients. CONCLUSIONS: These observations demonstrate a persistent effect of empagliflozin in patients with heart failure even after years of treatment, which dissipated rapidly after withdrawal of the drug. [ABSTRACT FROM AUTHOR]

BACKGROUND: Heart failure with preserved ejection fraction is increasing in prevalence and is associated with a high symptom burden and functional impairment, especially in persons with obesity. No therapies have been approved to target obesity-related heart failure with preserved ejection fraction. METHODS: We randomly assigned 529 patients who had heart failure with preserved ejection fraction and a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or higher to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. The dual primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary end points included the change in the 6-minute walk distance; a hierarchical composite end point that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level. RESULTS: The mean change in the KCCQ-CSS was 16.6 points with semaglutide and 8.7 points with placebo (estimated difference, 7.8 points; 95% confidence interval [CI], 4.8 to 10.9; PcO.001), and the mean percentage change in body weight was -13.3% with semaglutide and -2.6% with placebo (estimated difference, -10.7 percentage points; 95% CI, -11.9 to -9.4; P<0.001). The mean change in the 6-minute walk distance was 21.5 m with semaglutide and 1.2 m with placebo (estimated difference, 20.3 m; 95% CI, 8.6 to 32.1; P<0.001). In the analysis of the hierarchical composite end point, semaglutide produced more wins than placebo (win ratio, 1.72; 95% CI, 1.37 to 2.15; PcO.001). The mean percentage change in the CRP level was -43.5% with semaglutide and -7.3% with placebo (estimated treatment ratio, 0. 61; 95% CI, 0.51 to 0.72; PcO.001). Serious adverse events were reported in 35 participants (13.3%) in the semaglutide group and 71 (26.7%) in the placebo group. CONCLUSIONS: In patients with heart failure with preserved ejection fraction and obesity, treatment with semaglutide (2.4 mg) led to larger reductions in symptoms and physical limitations, greater improvements in exercise function, and greater weight loss than placebo. [ABSTRACT FROM AUTHOR]

Aim: Patients with heart failure (HF) often suffer from a range of comorbidities, which may affect their health status. The aim of this study was to assess the impact of different comorbidities on health status in patients with HF and reduced (HFrEF) and preserved ejection fraction (HFpEF). Methods and results: Using individual patient data from HFrEF (ATMOSPHERE, PARADIGM‐HF, DAPA‐HF) and HFpEF (TOPCAT, PARAGON‐HF) trials, we examined the Kansas City Cardiomyopathy Questionnaire (KCCQ) domain scores and overall summary score (KCCQ‐OSS) across a range of cardiorespiratory (angina, atrial fibrillation [AF], stroke, chronic obstructive pulmonary disease [COPD]) and other comorbidities (obesity, diabetes, chronic kidney disease [CKD], anaemia). Of patients with HFrEF (n = 20 159), 36.2% had AF, 33.9% CKD, 33.9% diabetes, 31.4% obesity, 25.5% angina, 12.2% COPD, 8.4% stroke, and 4.4% anaemia; the corresponding proportions in HFpEF (n = 6563) were: 54.0% AF, 48.7% CKD, 43.4% diabetes, 53.3% obesity, 28.6% angina, 14.7% COPD, 10.2% stroke, and 6.5% anaemia. HFpEF patients had lower KCCQ domain scores and KCCQ‐OSS (67.8 vs. 71.3) than HFrEF patients. Physical limitations, social limitations and quality of life domains were reduced more than symptom frequency and symptom burden domains. In both HFrEF and HFpEF, COPD, angina, anaemia, and obesity were associated with the lowest scores. An increasing number of comorbidities was associated with decreasing scores (e.g. KCCQ‐OSS 0 vs. ≥4 comorbidities: HFrEF 76.8 vs. 66.4; HFpEF 73.7 vs. 65.2). Conclusions: Cardiac and non‐cardiac comorbidities are common in both HFrEF and HFpEF patients and most are associated with reductions in health status although the impact varied among comorbidities, by the number of comorbidities, and by HF phenotype. Treating/correcting comorbidity is a therapeutic approach that may improve the health status of patients with HF. [ABSTRACT FROM AUTHOR]

Background: In AFFIRM-AHF, treatment of iron deficiency with intravenous ferric carboxymaltose (FCM) reduced the risk of heart failure (HF) hospitalization and improved quality of life (QoL) vs placebo in patients stabilized following an acute HF (AHF) episode, with no effect on cardiovascular (CV) death. Diabetes and iron deficiency frequently accompany AHF. This post hoc analysis explored the effects of diabetes on outcomes in AFFIRM-AHF patients. Methods: Patients were stratified by diabetes yes/no at baseline. The effects of FCM vs placebo on primary (total HF hospitalizations and CV death) and secondary (total CV hospitalizations and CV death; CV death; total HF hospitalizations; time to first HF hospitalization or CV death; and days lost due to HF hospitalizations or CV death) endpoints at Week 52 and change vs baseline in disease-specific QoL (12-item Kansas City Cardiomyopathy Questionnaire [KCCQ-12]) at Week 24 were assessed by subgroup. For each endpoint, the interaction between diabetes status and treatment outcome was explored. Results: Of 1108 AFFIRM-AHF patients, 475 (FCM: 231; placebo: 244) had diabetes and 633 (FCM: 327; placebo: 306) did not have diabetes. Patients with diabetes were more commonly male (61.5% vs 50.9%), with a higher frequency of ischemic HF etiology (57.9% vs 39.0%), prior HF history (77.7% vs 66.5%), and comorbidities (including previous myocardial infarction [49.3% vs 32.9%] and chronic kidney disease [51.4% vs 32.4%]) than those without diabetes. The annualized event rate/100 patient-years with FCM vs placebo for the primary endpoint was 66.9 vs 80.9 in patients with diabetes (rate ratio [RR]: 0.83, 95% CI 0.58–1.81) and 51.3 vs 66.9 in patients without diabetes (RR: 0.77, 95% CI 0.55–1.07), with no significant interaction between diabetes status and treatment effect (pinteraction = 0.76). Similar findings were observed for secondary outcomes. Change from baseline in KCCQ-12 overall summary score was numerically greater with FCM vs placebo at almost all time points in both subgroups, with no interaction between diabetes and treatment effect at Week 24. Conclusions: The clinical and QoL benefits observed with intravenous FCM in patients with iron deficiency following stabilization from an AHF episode are independent of diabetes status. Trial registration Clinicaltrials.gov, NCT02937454 (registered 10.18.2016). [ABSTRACT FROM AUTHOR]

Aims: Adrenomedullin is a vasodilatory peptide with a role in microcirculatory and endothelial homeostasis. Adrenomedullin is a substrate for neprilysin and may therefore play a role in beneficial effects of sacubitril/valsartan (Sac/Val) treatment. Methods and results: Mid‐regional pro‐adrenomedullin (MR‐proADM) was measured in 156 patients with heart failure with reduced ejection fraction (HFrEF) treated with Sac/Val and 264 patients with heart failure with preserved ejection fraction (HFpEF) randomized to treatment with Sac/Val or valsartan. Echocardiography and Kansas City Cardiomyopathy Questionnaire results were collected at baseline and after 6 and 12 months in the HFrEF cohort. Median (Q1–Q3) baseline MR‐proADM concentrations were 0.80 (0.59–0.99) nmol/L in HFrEF and 0.88 (0.68–1.20) nmol/L in HFpEF. After 12 weeks of treatment with Sac/Val, MR‐proADM increased by median 49% in HFrEF and 60% in HFpEF, while there were no significant changes in valsartan‐treated patients (median 2%). Greater increases in MR‐proADM were associated with higher Sac/Val doses. Changes in MR‐proADM correlated weakly with changes in N‐terminal pro‐B‐type natriuretic peptide, cardiac troponin T and urinary cyclic guanosine monophosphate. Increases in MR‐proADM were associated with decreases in blood pressure, but not significantly associated with changes in echocardiographic parameters or health status. Conclusions: MR‐proAD concentrations rise substantially following treatment with Sac/Val, in contrast to no change from valsartan. Change in MR‐proADM from neprilysin inhibition did not correlate with improvements in cardiac structure and function or health status. More data are needed regarding the role of adrenomedullin and its related peptides in the treatment of heart failure. Clinical Trial Registration: PROVE‐HF ClinicalTrials.gov Identifier: NCT02887183, PARAMOUNT ClinicalTrials.gov Identifier: NCT00887588. [ABSTRACT FROM AUTHOR]

BACKGROUND: Health status outcomes, including symptoms, function, and quality of life, are worse for Black compared with White patients with heart failure. Sodium–glucose cotransporter 2 inhibitors (SGLT2is) reduce cardiovascular mortality and improve health status in patients with heart failure, but whether the health status benefit of SGLT2is is similar across races is not established. The objective of this study was to compare the treatment effect of SGLT2is (versus placebo) on health status for Black compared with White patients with heart failure. METHODS: We combined patient-level data from 3 randomized clinical trials of SGLT2is: DEFINE-HF (Dapagliflozin Effect on Symptoms and Biomarkers in Patients With Heart Failure; n=263), PRESERVED-HF (Dapagliflozin in Preserved Ejection Fraction Heart Failure; n=324), and CHIEF-HF (A Study on Impact of Canagliflozin on Health Status, Quality of Life, and Functional Status in Heart Failure; n=448). These 3 United States–based trials enrolled a substantial proportion of Black patients, and each used the Kansas City Cardiomyopathy Questionnaire (KCCQ) to measure health status at baseline and after 12 weeks of treatment. Among 1035 total participants, selecting self-identified Black and White patients with complete information yielded a final analytic cohort of 935 patients. The primary endpoint was KCCQ Clinical Summary score. Twelve-week change in KCCQ with SGLT2is versus placebo was compared between Black and White patients by testing the interaction between race and treatment using multivariable linear regression models adjusted for trial, baseline KCCQ (as a restricted cubic spline), race, and treatment. The data that support the findings of this study are available from the corresponding author upon reasonable request. RESULTS: Among 935 participants, 236 (25%) self-identified as Black, and 469 (50.2%) were treated with an SGLT2i. Treatment with an SGLT2i, compared with placebo, resulted in KCCQ Clinical Summary score improvements at 12 weeks of +4.0 points (95% CI, 1.7–6.3; P =0.0007) in White patients and +4.7 points (95% CI, 0.7–8.7; P =0.02) in Black patients, with no significant interaction by race and treatment (P =0.76). Other KCCQ scales showed similar results. CONCLUSIONS: Treatment with an SGLT2i resulted in consistent and significant improvements in health status for both Black and White patients with heart failure. [ABSTRACT FROM AUTHOR]

Aims: Patients with heart failure experience a high burden of symptoms and physical limitations, and poor quality of life. Dapagliflozin reduces heart failure hospitalization and cardiovascular death in patients with reduced, mildly reduced, and preserved ejection fractions. We examined the effects of dapagliflozin on health status, measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), across the full spectrum of left ventricular ejection fraction (LVEF). Methods and results: Participant‐level data were pooled from the DAPA‐HF and DELIVER trials. Both trials were randomized, global, double‐blind, placebo‐controlled trials of patients with symptomatic heart failure and elevated natriuretic peptides. DAPA‐HF and DELIVER included patients with LVEF ≤40% and LVEF >40%, respectively. KCCQ was evaluated at randomization and at 4 and 8 months post‐randomization; the effect of dapagliflozin versus placebo on KCCQ total symptom score (TSS) was a pre‐specified secondary outcome in both trials. Interaction testing was performed to assess potential heterogeneity in the effects of dapagliflozin versus placebo on KCCQ‐TSS, clinical summary score (CSS), overall summary score (OSS), and physical limitation score (PLS), by continuous LVEF using restricted cubic splines. Responder analyses examining the proportion of patients with meaningful deterioration (≥5 point decline) and meaningful improvements (≥5 point increase) in KCCQ‐TSS was assessed across LVEF categories. Of 11 007 randomized participants, 10 238 (93%) had full data on KCCQ‐TSS at randomization. Benefits of dapagliflozin versus placebo on KCCQ‐TSS, ‐CSS, ‐OSS, ‐PLS, at 8 months were consistent across the full range of LVEF (pinteraction = 0.19, 0.10, 0.12, 0.10, respectively). In responder analyses, fewer dapagliflozin‐ versus placebo‐treated patients had clinically meaningful deteriorations in KCCQ‐TSS (overall: 21% vs. 23%; LVEF ≤40%: 21% vs. 29%; LVEF 41–60%: 21% vs. 26%; LVEF >60%: 22% vs. 27%). A greater proportion of patients randomized to dapagliflozin experienced at least small improvements in KCCQ‐TSS (overall: 50% vs. 45%; LVEF ≤40%: 48% vs. 41%; LVEF 41–60%: 51% vs. 49%; LVEF >60%: 53% vs. 45%). The effects of dapagliflozin versus placebo on clinically meaningful deteriorations and improvements in health status by KCCQ‐TSS were consistent across the full spectrum of LVEF assessed continuously (pinteraction = 0.20 and 0.64, respectively). Across the LVEF spectrum, the number needed to treat to affect ≥5 point improvement in health status assessed by KCCQ‐TSS was 20. Health status declines preceding a HF hospitalization by ∼10 points were observed in both trials, evident up to 3 months prior to hospitalization. Conclusions: In participant‐level pooled analyses of DAPA‐HF and DELIVER, dapagliflozin improved all key domains of health status across the full range of LVEF. Clinically meaningful improvements in health status were also observed consistently across LVEF, including in those with LVEF >60%. Clinical Trial Registration: NCT03036124 and NCT03619213. [ABSTRACT FROM AUTHOR]

Objective: To examine the impact of administering low-dose sacubitril-valsartan on the quality of health in individuals suffering from heart failure and reduced ejection fraction. Methodology: It is a prospective, cohort study comprising n=77 heart failure patients from a Tertiary Care Hospital with low ejection fraction. An FDA-approved KCCQ questionnaire was used for data collection at admission and after a 6-week follow-up. Descriptive statistics were reported in terms of percentage and mean± Std. dev. For mean comparison paired t-test was used. P value <0.05 was considered statistically significant. Results: Out of 77 patients, 28 (36.4%) were women and 49 (63.6%) were men. The study included participants with an average age of 60.05±11.80 years. Among the participants, 68.8% had hypertension and 51.9% had diabetes. 29.9% of the patients included had an EF of 30%, 49.3% had it between 31-39%, and 20.8% had an EF of 40%. Regarding classification by New York Heart Association (NYHA), before initiating Sacubitril/Valsartan, around 84.4% of patients were categorized as class 3, while 15.6% as class 4. Six weeks after therapy 79.2% of patients improved to functional class 2 and 20.8% to class 3. Statistical analysis revealed a significant difference in Kansas City Cardiomyopathy Questionnaire (KCCQ) scores of heart failure patients when comparing scores prior to and after receiving treatment of sacubitril/valsartan, 24/26mg BID. Conclusion: The study showed that patients with heart failure having a low ejection fraction experienced an improvement in quality of life as judged by KCCQ scores even while using sacubitril-valsartan at a low dose. [ABSTRACT FROM AUTHOR]

The effect of haemodynamic monitoring of pulmonary artery pressure has predominantly been studied in the USA. There is a clear need for randomised trial data from patients treated with contemporary guideline-directed-medical-therapy with long-term follow-up in a different health-care system. MONITOR-HF was an open-label, randomised trial, done in 25 centres in the Netherlands. Eligible patients had chronic heart failure of New York Heart Association class III and a previous heart failure hospitalisation, irrespective of ejection fraction. Patients were randomly assigned (1:1) to haemodynamic monitoring (CardioMEMS-HF system, Abbott Laboratories, Abbott Park, IL, USA) or standard care. All patients were scheduled to be seen by their clinician at 3 months and 6 months, and every 6 months thereafter, up to 48 months. The primary endpoint was the mean difference in the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score at 12 months. All analyses were by intention-to-treat. This trial was prospectively registered under the clinical trial registration number NTR7673 (NL7430) on the International Clinical Trials Registry Platform. Between April 1, 2019, and Jan 14, 2022, we randomly assigned 348 patients to either the CardioMEMS-HF group (n=176 [51%]) or the control group (n=172 [49%]). The median age was 69 years (IQR 61–75) and median ejection fraction was 30% (23–40). The difference in mean change in KCCQ overall summary score at 12 months was 7·13 (95% CI 1·51–12·75; p=0·013) between groups (+7·05 in the CardioMEMS group, p=0·0014, and –0·08 in the standard care group, p=0·97). In the responder analysis, the odds ratio (OR) of an improvement of at least 5 points in KCCQ overall summary score was OR 1·69 (95% CI 1·01–2·83; p=0·046) and the OR of a deterioration of at least 5 points was 0·45 (0·26–0·77; p=0·0035) in the CardioMEMS-HF group compared with in the standard care group. The freedom of device-related or system-related complications and sensor failure were 97·7% and 98·8%, respectively. Haemodynamic monitoring substantially improved quality of life and reduced heart failure hospitalisations in patients with moderate-to-severe heart failure treated according to contemporary guidelines. These findings contribute to the aggregate evidence for this technology and might have implications for guideline recommendations and implementation of remote pulmonary artery pressure monitoring. The Dutch Ministry of Health, Health Care Institute (Zorginstituut), and Abbott Laboratories. [ABSTRACT FROM AUTHOR]

Patients with heart failure (HF) often have multiple chronic conditions and are at increased risk for severe disease and mortality when infected by SARS-CoV-2, the virus that causes COVID-19. Furthermore, disparities in outcomes with COVID-19 have been associated with both racial/ethnic identity but also social determinants of health. Among older, urban-dwelling, minority patients with HF, we sought to characterize medical and non-medical factors associated with SARS-CoV-2 infection. Patients with HF living in Boston and New York City over 60 years of age participating in the Screening for Cardiac Amyloidosis with Nuclear Imaging (SCAN-MP) study between 12/1/2019 and 10/15/2021 (n = 180) were tested for nucleocapsid antibodies to SARS-CoV-2 and queried for symptomatic infection with PCR verification. Baseline testing included the Kansas City Cardiomyopathy Questionnaire (KCCQ), assessment of health literacy, biochemical, functional capacity, echocardiography, and a novel survey tool that determined living conditions, perceived risk of infection, and attitudes towards COVID-19 mitigation. The association of infection with prevalent socio-economic conditions was assessed by the area deprivation index (ADI). There were 50 overall cases of SARS-CoV-2 infection (28%) including 40 demonstrating antibodies to SARS-CoV-2 (indicative of prior infection) and 10 positive PCR tests. There was no overlap between these groups. The first documented case from New York City indicated infection prior to January 17, 2020. Among active smokers, none tested positive for prior SARS-CoV-2 infection (0 (0%) vs. 20 (15%), p = 0.004) vs. non-smokers. Cases were more likely to be taking ACE-inhibitors/ARBs compared to non-cases (78% vs 62%, p = 0.04). Over a mean follow-up of 9.6 months, there were 6 total deaths (3.3%) all unrelated to COVID-19. Death and hospitalizations (n = 84) were not associated with incident (PCR tested) or prior (antibody) SARS-CoV-2 infection. There was no difference in age, co-morbidities, living conditions, attitudes toward mitigation, health literacy, or ADI between those with and without infection. SARS-CoV-2 infection was common among older, minority patients with HF living in New York City and Boston, with evidence of infection documented in early January 2020. Health literacy and ADI were not associated with infection, and there was no increased mortality or hospitalizations among those infected with SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as a key pharmacotherapy in heart failure (HF) with both reduced and preserved ejection fraction. The benefit of other HF therapies may be modified by sex, but whether sex modifies the treatment effect and safety profile of SGLT2 inhibitors remains unclear. Our analyses aim to assess the impact of sex on the efficacy and safety of dapagliflozin.Methods: In a pre-specified patient-level pooled analysis of DAPA-HF and DELIVER, clinical outcomes were compared by sex (including the composite of cardiovascular [CV] death or worsening HF events; CV death; all-cause death, total events (first and recurrent HF hospitalization and CV death), and Kansas City Cardiomyopathy Questionnaire [KCCQ] scores) across the spectrum of left ventricular ejection fraction (EF).Results: Of a total of 11,007 randomized patients, 3856 (35%) were women. Women with HF were older, had higher body mass index, but were less likely to have a history of diabetes and myocardial infarction/stroke; and more likely to have hypertension and atrial fibrillation, compared to men. At baseline, women had higher EF but worse KCCQ scores than men. After adjusting for baseline differences, women were less likely than men to experience CV death (adjusted hazard ratio [aHR] 0.69, 95% CI 0.60-0.79), all-cause death (aHR 0.69, 95% 0.62-0.78), HF hospitalizations (aHR 0.82, 95% CI 0.72-0.94), and total events (adjusted rate ratio 0.77, 95% CI 0.71-0.84). Dapagliflozin reduced the primary endpoint in both men and women similarly (p-interaction=0.77) with no sex-related differences in secondary outcomes (all p-interactions > 0.35) or safety events. The benefit of dapagliflozin was observed across the entire EF spectrum and was not modified by sex (p-interaction > 0.40). There were no sex-related differences in serious adverse events, adverse events, or drug discontinuation due to adverse events.Conclusions: In DAPA-HF and DELIVER, the response to dapagliflozin was similar between men and women. Sex did not modify the treatment effect of dapagliflozin across the range of ejection fraction. [ABSTRACT FROM AUTHOR]

Aims: This pilot study aimed to assess the potential benefits of cardiac contractility modulation (CCM) in patients with heart failure with preserved ejection fraction (HFpEF). Methods and results: This was a prospective, multicentre, single‐arm, pilot study of CCM therapy in patients with HFpEF and New York Heart Association (NYHA) class II or III. Echocardiographic parameters were measured by an echo core laboratory to determine study eligibility. After CCM device implantation, patients were followed for 24 weeks. Overall, 47 patients (mean age 74.3 ± 4.4 years, 70.2% female) were enrolled, with left ventricular ejection fraction of 59 ± 4.4%, 63.8% with hypertension, 46.8% with atrial fibrillation, 40.4% with diabetes, 31.9% with at least one heart failure hospitalization in the prior year, 61.7% in NYHA class III, and Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score of 48.9 ± 21.7. The primary efficacy endpoint (mean change in the KCCQ overall summary score) improved by 18.0 ± 16.6 points (p < 0.001) and there was an event‐free rate of 93.6% for the primary safety endpoint (device‐ and procedure‐related complications), as adjudicated by an independent physician committee. Conclusion: This pilot study demonstrates that the benefits of CCM may extend to the HFpEF patient population. The significant improvement in health status observed, with no obvious impact on safety, suggests that utilization of CCM for patients with HFpEF could prove to be promising. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that sodium-glucose cotransporter-2 inhibitors (SGLT2i) can achieve significant improvement in blood pressure in people with diabetes. Furthermore, randomized controlled trials (RCTs) have established that SGLT2i have a cardioprotective effect in adults with heart failure (HF). Therefore, we performed this systematic review an meta-analysis to determine the effect of SGLT2i on blood pressure in patients with HF. Methods: We used the Medline, Cochrane Library, Embase, and PubMed databases to identify RCTs (published through to April 29, 2022) that evaluated the effect of SGLT2i on HF. The primary endpoint was defined as change in blood pressure. Secondary composite outcomes were heart rate, hematocrit, body weight, and glycated hemoglobin. The N-terminal pro-brain natriuretic peptide level, Kansas City Cardiomyopathy Questionnaire scores, and estimated glomerular filtration rate were also evaluated. Results: After a literature search and detailed evaluation, 16 RCTs were included in the quantitative analysis. Pooled analyses showed that SGLT2i were associated with a statistically significant reduction in systolic blood pressure of 1.68 mmHg (95% confidence interval [CI] − 2.7, − 0.66; P = 0.001; I2 = 45%) but not diastolic blood pressure (mean difference [MD] −1.06 mmHg; 95% CI −3.20, 1.08; P = 0.33; I2 = 43%) in comparison with controls. Furthermore, SGLT2i decreased body weight (MD − 1.36 kg, 95% CI − 1.68, − 1.03; P < 0.001; I2 = 61%) and the glycated hemoglobin level (MD − 0.16%, 95% CI − 0.28, −0.04, P = 0.007; I2 = 91%) but increased hematocrit (MD 1.63%, 95% CI 0.63, 2.62, P = 0.001; I2 = 100%). There was no significant between-group difference in heart rate (MD − 0.35; 95% CI − 2.05, 1.35, P = 0.69; I2 = 0). Conclusions: SGLT2i decreased systolic blood pressure in patients with HF but had no effect on diastolic blood pressure. These inhibitors may have numerous potentially beneficial clinical effects in patients with HF. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study is to explore the application of semistructured interview based on doctor-patient perspective in constructing a palliative care regimen for patients with advanced heart failure. Methods. 112 patients with advanced heart failure who were admitted to the hospital were selected between December 2019 and December 2020, and they were randomly divided into an interview group and a routine group, with 56 cases in each group. The routine group was given routine nursing for advanced heart failure while the interview group developed a palliative care regimen based on a semistructured interview from the doctor-patient perspective. The psychological states (Depression-Anxiety-Stress Scale (DASS-21)), symptoms (Memorial Symptom Assessment Scale-Heart Failure (MSAS-HF)), quality of life (Kansas City Cardiomyopathy Questionnaire (KCCQ)), and prognosis (readmission rate, mortality rate) were compared between the two groups before and after intervention. Results. Compared with before intervention, there were no significant differences in the scores of DASS-21, MSAS-HF, and KCCQ in the routine group after intervention (P > 0.05), and the scores of DASS-21 and MSAS-HF in the interview group were decreased while KCCQ scores were increased (P < 0.05). Scores of DASS-21 and MSAS-HF and readmission rate were lower while the KCCQ scores were higher in the interview group compared with those in the routine group (P < 0.05). There was no significant difference in the mortality rate between the two groups (P > 0.05). Conclusion. The application of a semistructured interview based on the doctor-patient perspective to construct the palliative care regimen for patients with advanced heart failure can eliminate the negative emotions, improve the psychological states, relieve the clinical symptoms, enhance the quality of life, and reduce the risk of readmission. [ABSTRACT FROM AUTHOR]

Background: There is uncertainty and limited data regarding initiation of sodium-glucose cotransporter 2 (SGLT2) inhibitors among patients hospitalized with acute heart failure (AHF). This systematic review and meta-analysis aim to establish the efficacy and safety of SGLT2 inhibitors initiated in patients hospitalized for AHF. Methods: PubMed/Medline, Embase, and Cochrane library were searched using the following terms: ("sglt2" and "acute heart failure") and ("sglt2" and "worsening heart failure") from inception till November 15th, 2021 for randomized controlled trials (RCTs) comparing the efficacy and safety of initiating an SGLT2 inhibitor compared with placebo in patients with AHF. Major cardiovascular and diabetes scientific meetings in 2021 were also searched for relevant studies. Prespecified efficacy outcomes were all-cause mortality, rehospitalization for heart failure, and improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ) scale score. Prespecified safety outcomes were acute kidney injury (AKI), hypotension, and hypoglycemia. Random effects odds ratio (OR) and mean difference with 95% confidence intervals (CIs) were calculated. Results: Three RCTs with a total of 1831 patients were included. Initiation of SGLT2 inhibitors in patients with AHF reduced the risk of rehospitalization for heart failure (OR 0.52; 95% CI [0.42, 0.65]) and improved Kansas City Cardiomyopathy Questionnaire scores (mean difference 4.12; 95% CI [0.1.89, 6.53]). There was no statistically significant effect for initiation of SGLT2 inhibitors in patients with AHF on all-cause mortality (OR 0.70; 95% CI [0.46, 1.08]). Initiation of SGLT2 inhibitors in patients with AHF did not increase the acute kidney injury (OR 0.76; 95% CI [0.50, 1.16]), hypotension (OR 1.17; 95% CI [0.80, 1.71]), or hypoglycemia (OR 1.51; 95% CI [0.86, 2.65]). Conclusion: Initiation of SGLT2 inhibitors in patients hospitalized for AHF during hospitalization or early post-discharge (within 3 days) reduces the risk of rehospitalization for heart failure and improves patient-reported outcomes with no excess risk of adverse effects. [ABSTRACT FROM AUTHOR]

Background: Patients with heart failure with preserved ejection fraction have significant impairment in health-related quality of life. In the EMPEROR-Preserved trial (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction), we evaluated the efficacy of empagliflozin on health-related quality of life in patients with heart failure with preserved ejection fraction and whether the clinical benefit observed with empagliflozin varies according to baseline health status.Methods: Health-related quality of life was measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and 12, 32, and 52 weeks. Patients were divided by baseline KCCQ Clinical Summary Score (CSS) tertiles, and the effect of empagliflozin on outcomes was examined. The effect of empagliflozin on KCCQ-CSS, Total Symptom Score, and Overall Summary Score was evaluated. Responder analyses were performed to compare the odds of improvement and deterioration in KCCQ related to treatment with empagliflozin.Results: The effect of empagliflozin on reducing the risk of time to cardiovascular death or heart failure hospitalization was consistent across baseline KCCQ-CSS tertiles (hazard ratio, 0.83 [95% CI, 0.69-1.00], 0.70 [95% CI, 0.55-0.88], and 0.82 [95% CI, 0.62-1.08] for scores <62.5, 62.5-83.3, and ≥83.3, respectively; P trend=0.77). Similar results were seen for total heart failure hospitalizations. Patients treated with empagliflozin had significant improvement in KCCQ-CSS versus placebo (+1.03, +1.24, and +1.50 at 12, 32, and 52 weeks, respectively; P<0.01); similar results were seen for Total Symptom Score and Overall Summary Score. At 12 weeks, patients on empagliflozin had higher odds of improvement ≥5 points (odds ratio, 1.23 [95% CI, 1.10-1.37]), ≥10 points (odds ratio, 1.15 [95% CI, 1.03-1.27]), and ≥15 points (odds ratio, 1.13 [95% CI, 1.02-1.26]) and lower odds of deterioration ≥5 points in KCCQ-CSS (odds ratio, 0.85 [95% CI, 0.75-0.97]). A similar pattern was seen at 32 and 52 weeks, and results were consistent for Total Symptom Score and Overall Summary Score.Conclusions: In patients with heart failure with preserved ejection fraction, empagliflozin reduced the risk for major heart failure outcomes across the range of baseline KCCQ scores. Empagliflozin improved health-related quality of life, an effect that appeared early and was sustained for at least 1 year. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057951. [ABSTRACT FROM AUTHOR]

Improving health-related quality of life (HRQoL) and exercise capacity is an important goal of treatment in heart failure (HF). However, evidence for the effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on the improvement of HRQoL and exercise capacity seems to be conflicted. We performed a systematic review and meta-analysis to evaluate the effects of SGLT-2 inhibitors on HRQL and exercise capacity in patients with heart failure and reduced ejection fraction (HFrEF). All studies (up to March 20, 2021) evaluating the effects of SGLT-2 inhibitors on HRQoL and exercise capacity in patients with HFrEF were initially searched from four electronic search engines: PubMed, Web of Science, Cochrane Library, and SinoMed. All statistical analyses were performed with RevMan 5.4. We included 9 articles describing 7 trials with 9428 patients. SGLT-2 inhibitors group exhibited significant improvement in HRQoL assessed by Kansas City Cardiomyopathy Questionnaires (KCCQ) (MD: 2.13, 95% CI: 1.11 to 3.14, p < 0.001) and the rate of KCCQ-overall summary score improvement≥5 points (RR 1.15, 95%CI 1.08 to 1.21, P < 0.001) compared with placebo. No significant difference was observed in exercise capacity assessed by 6-min walk test distance between SGLT-2 inhibitors and placebo (MD 24.45, 95%CI -22.82 to 71.72, P = 0.31). Our meta-analysis demonstrates that SGLT-2 inhibitors significantly improve HRQoL, and supports the concept that SGLT-2 inhibitors do not significantly improve exercise capacity in patients with HFrEF. Studies with larger sample sizes and longer follow-up duration are needed to determine whether the treatment with SGLT-2 inhibitors may improve exercise ability. PROSPERO: CRD42021248346. • Despite successful therapies that improve morbidity and mortality, most patients with HF have troublesome symptoms. • Evidence for the effects of SGLT-2 inhibitors on the improvement of HRQoL and exercise capacity seems to be conflicted. • SGLT-2 inhibitors significantly improve HRQoL as measured by KCCQ in patients with HFrEF. • SGLT-2 inhibitors do not significantly improve exercise capacity as measured by 6MWTD and accelerometry. [ABSTRACT FROM AUTHOR]

Purpose: Anxiety, depression, poor sleep quality and lower quality of life (QOL) are associated with worse outcomes in heart failure (HF) patients. Motivational interview (MI) has been effective in different patient populations to promote self-care. However, its effect on anxiety, depression, sleep quality and QOL in HF patients is unknown. The aim of this study was to evaluate the effect of MI on anxiety, depression, sleep quality and QOL over 12 months from the intervention. Methods: This was a planned, secondary outcome analysis of the MOTIVATE-HF study, a three-arm randomized controlled trial (1:1:1) evaluating the effect of MI in improving self-care in HF patients. In Arm 1, the patient received MI, while in Arm 2, the patient and the caregiver received MI. Arm 3, the control group, received standard treatment. Endpoints were evaluated with the Hospital Anxiety and Depression Scale (HADS), the Pittsburgh Sleep Quality Index (PSQI), the 12-Item Short-Form Health Survey (SF-12) and the Kansas City Cardiomyopathy Questionnaire (KCCQ) every three months for one year. Results: We enrolled and randomized 510 HF patient and caregiver dyads (155 dyads in Arm 1, 177 dyads in Arm 2, and 178 dyads in Arm 3). A total of 238 HF patients and 235 caregivers completed the 12-month trial. No significant changes were seen in anxiety, depression and sleep quality over time among the three study arms, but disease-specific QOL improved in the intervention groups, especially in Arm 2. Conclusion: Clinicians may want to include both patients and caregivers when providing MI interventions. Further research is needed to investigate the required intensity of MI to be effective on sleep quality, anxiety and depression (ClinicalTrials.gov Identifier: NCT02894502). [ABSTRACT FROM AUTHOR]

Aims: Attenuating exercise‐induced elevated left atrial pressure with an atrial shunt device is under clinical investigation for treatment of symptomatic heart failure (HF). Methods and results: PRELIEVE was a prospective, non‐randomised, multicentre, first‐in‐man study in symptomatic HF patients with reduced (HFrEF) or preserved (HFpEF) ejection fraction and pulmonary capillary wedge pressure (PCWP) ≥15 mmHg at rest or ≥25 mmHg during exercise. Here, we provide follow‐up data up to 1 year after implantation of the Atrial Flow Regulator (AFR) device. The AFR was successfully implanted in 53 patients (HFrEF n = 24 and HFpEF n = 29). Two patients were not enrolled due to an unsuccessful transseptal puncture. There was one device embolisation into the left atrium, which required surgical removal. One patient experienced a serious procedure‐related adverse event (post‐procedural bleeding and syncope). All patients with sufficient echocardiography readout confirmed device patency with left–right shunt both at 3 (n = 47/51, 92%) and 12 (n = 45/49, 92%) months. At 3 months, rest PCWP decreased by 5 (−12, 0) mmHg (P = 0.0003, median Q1, Q3). No patient developed a stroke, worsening of right heart function or significant increase of pulmonary artery pressure. Six (6/53, 11%) patients were hospitalised for worsening of HF and three (3/53, 6%) patients died. We observed improvements in New York Heart Association functional class, 6‐min walking distance and quality of life (Kansas City Cardiomyopathy Questionnaire) in certain patients. Conclusions: Implantation of the AFR device in HF patients was feasible. No shunt occlusion, stroke or new right HF was observed during the 1‐year follow‐up, with clinical improvements in certain patients. [ABSTRACT FROM AUTHOR]

Background: Large clinical trials established the benefits of sodium-glucose cotransporter 2 inhibitors in patients with diabetes and with heart failure with reduced ejection fraction (HFrEF). The early and significant improvement in clinical outcomes is likely explained by effects beyond a reduction in hyperglycemia.Objectives: The purpose of this study was to assess the effect of empagliflozin on left ventricular (LV) function and volumes, functional capacity, and quality of life (QoL) in nondiabetic HFrEF patients.Methods: In this double-blind, placebo-controlled trial, nondiabetic HFrEF patients (n = 84) were randomized to empagliflozin 10 mg daily or placebo for 6 months. The primary endpoint was change in LV end-diastolic and -systolic volume assessed by cardiac magnetic resonance. Secondary endpoints included changes in LV mass, LV ejection fraction, peak oxygen consumption in the cardiopulmonary exercise test, 6-min walk test, and quality of life.Results: Empagliflozin was associated with a significant reduction of LV end-diastolic volume (-25.1 ± 26.0 ml vs. -1.5 ± 25.4 ml for empagliflozin vs. placebo, respectively; p < 0.001) and LV end-systolic volume (-26.6 ± 20.5 ml vs. -0.5 ± 21.9 ml for empagliflozin vs. placebo; p < 0.001). Empagliflozin was associated with reductions in LV mass (-17.8 ± 31.9 g vs. 4.1 ± 13.4 g, for empagliflozin vs. placebo, respectively; p < 0.001) and LV sphericity, and improvements in LV ejection fraction (6.0 ± 4.2 vs. -0.1 ± 3.9; p < 0.001). Patients who received empagliflozin had significant improvements in peak O2 consumption (1.1 ± 2.6 ml/min/kg vs. -0.5 ± 1.9 ml/min/kg for empagliflozin vs. placebo, respectively; p = 0.017), oxygen uptake efficiency slope (111 ± 267 vs. -145 ± 318; p < 0.001), as well as in 6-min walk test (81 ± 64 m vs. -35 ± 68 m; p < 0.001) and quality of life (Kansas City Cardiomyopathy Questionnaire-12: 21 ± 18 vs. 2 ± 15; p < 0.001).Conclusions: Empagliflozin administration to nondiabetic HFrEF patients significantly improves LV volumes, LV mass, LV systolic function, functional capacity, and quality of life when compared with placebo. Our observations strongly support a role for sodium-glucose cotransporter 2 inhibitors in the treatment of HFrEF patients independently of their glycemic status. (Are the "Cardiac Benefits" of Empagliflozin Independent of Its Hypoglycemic Activity? [ATRU-4] [EMPA-TROPISM]; NCT03485222). [ABSTRACT FROM AUTHOR]

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P=0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016-002299-28.). [ABSTRACT FROM AUTHOR]

Background: Heart failure is a worldwide health problem that significantly affects patients' physical function and health state. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a disease-specific patient-reported outcome measure commonly used for the assessment of health states of patients with heart failure. This study aimed to evaluate the psychometric properties of the Japanese version of the KCCQ.Methods: Using pooled data of 141 Japanese patients with chronic heart failure from three clinical trials, the Japanese version of the KCCQ was evaluated for validity and reliability, with a focus on the clinical summary score (CSS) and its component domains. For construct validity, the associations of baseline KCCQ scores with New York Heart Association (NYHA) class and the EuroQol five-dimension, three-level (EQ-5D-3L) scores at baseline were analyzed. For reliability, internal consistency was assessed using Cronbach's α, and test-retest reliability (reproducibility) was assessed among stable patients. Responsiveness to changes in patients' clinical status was assessed by analyzing score changes between two timepoints among patients whose health states improved.Results: Among 141 patients (mean age, 73.7 ± 10.9 years), 76.6% were NYHA class II at baseline. For CSS and its component domains (physical limitations, symptom frequency, and symptom severity), baseline scores were all significantly lower in patients with a higher NYHA class (p <  0.001 for all, Jonckheere-Terpstra test). The physical limitations domain and CSS showed a moderate correlation (Spearman's ρ = - 0.40 to - 0.54) with three functional status-related EQ-5D dimensions (mobility, self-care, and usual activities). The Cronbach's standardized α was high (> 0.70) for all KCCQ domain/summary scores. In the test-retest analysis among 58 stable patients, all domain/summary scores minimally changed by 0.3-4.2 points with intraclass correlation coefficients of 0.65-0.84, demonstrating moderate to good reproducibility, except for the symptom stability domain. Among 44 patients with improved health states, all domain/summary scores except for the symptom stability and self-efficacy domains substantially improved from baseline with a medium to large effect size of 0.62-0.88.Conclusions: The Japanese version of the KCCQ was demonstrated to be a valid and reliable tool for the assessment of symptoms and physical function of Japanese patients with chronic heart failure. [ABSTRACT FROM AUTHOR]

Current challenges for using the Kansas City Cardiomyopathy Questionnaire to obtain a standardized patient-reported health status outcome In April 2020, the U.S. Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) approved the use of the Kansas City Cardiomyopathy Questionnaire (KCCQ) as a primary endpoint in drug trials for patients with heart failure (HF).1 Noted in the FDA approval is a recommendation to establish thresholds for clinically meaningful within-patient change on KCCQ subscales.1 This approval represents an important step forward for using a patient-reported outcome measure to evaluate clinical services. The patient's Kansas City Cardiomyopathy Questionnaire starting point Guidelines for categorizing qualitative differences in a patient's KCCQ score have yet to be established. [Extracted from the article]

Aims: Heart failure (HF) is associated with considerable symptom burden and impairment in physical functioning and quality of life. The sodium-glucose co-transporter 2 inhibitor empagliflozin reduced the risk of HF hospitalisation and cardiovascular death in patients with type 2 diabetes and established cardiovascular disease in the EMPA-REG OUTCOME trial, and could potentially improve congestion symptoms and exercise capacity in patients with HF. We describe the designs of the EMPERIAL-Preserved and EMPERIAL-Reduced trials of empagliflozin in patients with chronic stable HF, with or without type 2 diabetes.Methods: EMPERIAL-Preserved and EMPERIAL-Reduced are randomised, placebo-controlled trials designed to investigate the effects of empagliflozin on exercise capacity and patient-reported outcomes in patients with chronic stable HF with preserved ejection fraction [HFpEF; left ventricular ejection fraction (LVEF) > 40%] and HF with reduced ejection fraction (HFrEF; LVEF ≤ 40%), respectively. In each trial, approximately 300 patients will be randomised 1:1 to receive empagliflozin 10 mg or placebo once daily for 12 weeks. In both trials, the primary endpoint is the change from baseline in 6-min walk test distance at week 12. Key secondary endpoints are the change from baseline in Kansas City Cardiomyopathy Questionnaire total symptom score and change from baseline in dyspnoea score of the Chronic Heart Failure Questionnaire at week 12.Conclusion: The EMPERIAL-Preserved and EMPERIAL-Reduced trials will determine the effects of empagliflozin on exercise capacity and patient-reported outcomes in patients with HFpEF and HFrEF, respectively, and provide insight into the potential of empagliflozin in the treatment of patients with HF.Clinical Trial Registration: ClinicalTrials.gov ID: NCT03448406 (EMPERIAL-Preserved), NCT03448419 (EMPERIAL-Reduced). [ABSTRACT FROM AUTHOR]

Guidelines for heart failure management commonly focus on mortality, hospitalization, or surrogate measures such as change in ejection fraction as outcome parameter. Reducing symptoms and increasing functional capacity and quality of life are commonly articulated goals, but there is no consensus on how best to achieve these outcomes. We aimed to evaluate the feasibility of routinely measurement of a defined standard pragmatic patient-reported outcome set. We assessed a panel of PROM assessment tools proposed by the International Consortium for Health Outcomes Measurement (ICHOM) in patients with advanced heart failure three months after discharge from Heart failure unit. Patients completed the Kansas City Cardiomyopathy Questionnaire (KCCQ-12), PROMIS Physical Function Short Form 4a as (PROMIS-4a) well as EQ 5D and Patient Health Questionnaire-2 (PHQ-2). We included n=99 patients (33% female; mean age 64 years ±16 SD) into the study. Three months later, n=79 (80%) participated in PROM assessment. Eight patient died, ten patients were lost to follow-up and two patient were still at the ward. Nearly all patients (97%) suffered from systolic heart failure and two thirds had a reduced right ventricular function. Patients reported a mean KCCQ-12 overall score of 29.7 points (±12.0 SD). PHQ-2 score ≥3 points was found in 20 patients (25%). Further, patients reported a mean PROMIS-4a sum score of 12.6 (±4.8 SD) and a mean EQ-5D VAS of 56.8 points (±21.1 SD). In all questionnaires, we found <10% missing values. A vast majority of patients (73%) agreed that their responses provided good insight into their health state and limitations due to heart failure. 71% of patients would approve adjusting heart failure treatment based on their responses. We measured relatively low mean scores of all PROM assessment tools, underpinning the burden of disease in advanced heart failure. Low percentage of missing data hallmarks the feasibility of PROM assessment. We conclude that routinely PROM assessment and standardization might improve heart failure care, monitor quality of life and therefore permit comparison across several therapeutic strategies. [ABSTRACT FROM AUTHOR]

Introduction: The present study aimed to determine the relationship between New York Heart Association (NYHA) classification and disease characteristics on the quality of life scores and the distribution of the scores at different stages of Heart Failure (HF). Materials and Methods: A total of 150 patients with HF participated in this cross-sectional study. The method of data collection was interview based on NYHA classification and using the validated Persian version of the Kansas City Cardiomyopathy Questionnaire (PKCCQ). Results: According to NYHA classification, 10% of patients were classified as mild HF, 16% as moderate HF, 63% as severe HF, and 11% as very severe HF. Significant differences were observed for total score and the component scores of PKCCQ among four stages of the disease (P<0.001). By comparing the PKCCQ total score and three domains in male and female groups, it was revealed that sex cannot affect quality of life based on PKCCQ total score and its functional areas (P=0.18). Conclusion: Distribution of the quality of life scores in patients with different stages of HF showed that quality of life scores overlap in the severe and very severe stages. Classifying the disease using NYHA classification cannot distinct patients with HF according to impairments in their health status between severe and very severe stages. In addition, the degree of education is the factor that may affect the quality of life. [ABSTRACT FROM AUTHOR]

Background—Oxidative stress may contribute to heart failure (HF) progression. Inhibiting xanthine oxidase in hyperuricemic HF patients may improve outcomes. Methods and Results—We randomly assigned 253 patients with symptomatic HF, left ventricular ejection fraction =40%, and serum uric acid levels ≥9.5 mg/dL to receive allopurinol (target dose, 600 mg daily) or placebo in a double-blind, multicenter trial. The primary composite end point at 24 weeks was based on survival, worsening HF, and patient global assessment. Secondary end points included change in quality of life, submaximal exercise capacity, and left ventricular ejection fraction. Uric acid levels were significantly reduced with allopurinol in comparison with placebo (treatment difference, -4.2 [-4.9, -3.5] mg/dL and -3.5 [-4.2, -2.7] mg/dL at 12 and 24 weeks, respectively, both P<0.0001). At 24 weeks, there was no significant difference in clinical status between the allopurinol- and placebo-treated patients (worsened 45% versus 46%, unchanged 42% versus 34%, improved 13% versus 19%, respectively; P=0.68). At 12 and 24 weeks, there was no significant difference in change in Kansas City Cardiomyopathy Questionnaire scores or 6-minute walk distances between the 2 groups. At 24 weeks, left ventricular ejection fraction did not change in either group or between groups. Rash occurred more frequently with allopurinol (10% versus 2%, P=0.01), but there was no difference in serious adverse event rates between the groups (20% versus 15%, P=0.36). Conclusions—In high-risk HF patients with reduced ejection fraction and elevated uric acid levels, xanthine oxidase inhibition with allopurinol failed to improve clinical status, exercise capacity, quality of life, or left ventricular ejection fraction at 24 weeks. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00987415. [ABSTRACT FROM AUTHOR]

The health benefits of physical activity have been widely recognized, yet there is limited information on associations between accelerometer-related parameters and established patient-reported health status. This study investigated the association between the waist-worn accelerometer measurements, cardiopulmonary exercise testing (CPX), and results of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in heart failure (HF) patients hospitalized for acute decompensation. A total of 31 patients were enrolled and wore a validated three-axis accelerometer for 2 weeks and completed the short version of the KCCQ after removing the device. Daily step counts, exercise time (metabolic equivalents × hours), and %sedentary time (sedentary time/device-equipped time) were measured. Among the measured parameters, the best correlation was observed between %sedentary time and the KCCQ overall and clinical summary scores (r = −0.65 and −0.65, each p < 0.001). All of the individual domains of the KCCQ (physical limitation, symptom frequency, and quality of life), with the exception of the social limitation domain, showed moderate correlations with %sedentary time. Finally, oxygen consumption assessed by CPX demonstrated only weak associations with the accelerometer-measured parameters. An accelerometer could complement the KCCQ results in accurately assessing the physical activity in HF patients immediately after hospitalization, albeit its correlation with CPX was at most moderate. [ABSTRACT FROM AUTHOR]

This randomized controlled trial aims to determine the feasibility and preliminary efficacy of a patient-centered, mobile health technology intervention (iCardia4HF) in patients with chronic Heart Failure (HF). Participants (n = 92) are recruited and randomized 1:1 to the intervention or control group. The intervention group receives a commercial HF self-care app (Heart Failure Storylines), three connected health devices that interface with the app (Withings weight scale and blood pressure monitor, and Fitbit activity tracker), and a program of individually tailored text-messages targeting health beliefs, self-care self-efficacy, HF-knowledge, and physical activity. The control group receives the same connected health devices, but without the HF self-care app and text messages. Follow-up assessments occur at 30 days and 12 weeks. The main outcome of interest is adherence to HF self-care assessed objectively through time-stamped data from the electronic devices and also via patient self-reports. Primary measures of HF self-care include medication adherence and adherence to daily weight monitoring. Secondary measures of HF self-care include adherence to daily self-monitoring of HF symptoms and blood pressure, adherence to low-sodium diet, and engagement in physical activity. Self-reported HF self-care and health-related quality of life are assessed with the Self-care Heart Failure Index and the Kansas City Cardiomyopathy Questionnaire, respectively. Hospitalizations and emergency room visits are tracked in both groups over 12 weeks as part of our safety protocol. This study represents an important step in testing a scalable mHealth solution that has the potential to bring about a new paradigm in self-management of HF. [ABSTRACT FROM AUTHOR]

Patients are the best source of information about how they feel and how care affects them. Patient-reported outcome measures (PROMs) are standardized, validated questionnaires completed by patients to measure their perception of their well-being and health status. Aim : To create a cost-effective, valid, and sensitive PROMs data capture process for patients with Advanced Heart Failure (AHF) to understand to what extent a Heart Transplant (HT) affects their quality of life A prospective data collection model has been designed for AHF patients eligible for HT based on the Outcomes Management and Evaluation (OME) system developed by Cleveland Clinic. Two types of data will be collected: 1) Patient condition-specific PROMs; 2) OME for HT and potential Bridge to Transplant Therapies (BTT). Patient condition-specific PROMs will be measured using the Kansas City Cardiomyopathy Questionnaire and social determinants of health (e.g., smoking habits and drug abuse). The OME data for BTT include: A)Pre-BTT details (e.g., UNOS status),B)Post-BTT details (e.g., post-transplant mechanical support). The OME data for HT include:A)Pre-transplant details (e.g., UNOS status),B)Donor characteristics (e.g., ischemic trigger greater than 4 hours),C)Post-transplant details (e.g., post-transplant mechanical support). The process for collecting PROMs is divided into 5 phases (see fig). Data will start to be collected approximately in November 2020 until June 2021, aiming to have the first results analyzed by July 2021 This is one of the first PROMs processes implemented in an AHF program to the best of our knowledge. Our goal is to imbed PROMs into our workflow and create an umbrella of PROMs across the entire Heart and Vascular Institute to measure the quality of care from our patients' perspective to improve the clinical decision-making process. [ABSTRACT FROM AUTHOR]

Previous studies have shown that heart failure is associated with worse health-related quality of life (HRQoL). The existence of differences according to gender remains controversial. We studied 1028 consecutive outpatients with heart failure and reduced ejection fraction (HFrEF) from a multicentre cross-sectional descriptive study across Spain that assessed HRQoL using two questionnaires (KCCQ, Kansas City Cardiomyopathy Questionnaire; and EQ-5D, EuroQoL 5 dimensions). The primary objective of the study was to describe differences in HRQoL between men and women in global scores and domains of health status of patients and explore gender differences and its interactions with heart failure related factors. In adjusted analysis women had lower scores in KCCQ overall summary scores when compared to men denoting worse HRQoL (54.7 ± 1.3 vs. 62.7 ± 0.8, p < 0.0001), and specifically got lower score in domains of symptom frequency, symptoms burden, physical limitation, quality of life and social limitation. No differences were found in domains of symptom stability and self-efficacy. Women also had lower scores on all items of EQ-5D (EQ-5D index 0.58 ± 0.01 vs. 0.67 ± 0.01, p < 0.0001). Finally, we analyzed interaction between gender and different clinical determinants regarding the presence of limitations in the 5Q-5D and overall summary score of KCCQ. Interestingly, there was no statistical significance for interaction for any variable. In conclusion, women with HFrEF have worse HRQoL compared to men. These differences do not appear to be mediated by clinical or biological factors classically associated with HRQoL nor with heart failure severity. [ABSTRACT FROM AUTHOR]

Introduction: The hallmark of chronic stable heart failure with preserved ejection fraction (HFpEFT) is exercise intolerance, objectively measured by reduced peak exercise capacity (peak VO2). The relationship between the degree of right ventricular dysfunction, exercise performance, and quality of life (QOL) in HFpEF is unknown. Hypothesis: RV dysfunction is associated with reduced peak VO2 and QOL. Methods: Analysis of RV structure and function from CMR images from a completed trial of diet and exercise in elderly, obese chronic HFpEF patients vs. age-matched healthy controls (HC). Relationships between RV structure/function (ejection fraction-EF; end-diastolic volume-EDV; stroke volume-SV; and mass); exercise performance (peak VO2; 6-minute walk distance-6MWD); QOL (Kansas City Cardiomyopathy Questionnaire); and inflammation biomarkers (IL-6 and hsCRP) were determined with Spearman's correlation coefficients. Multivariate regression was performed to determine independent predictors of peak VO2. Results: There were 127 patients; 74 HFpEF and 53 HC. HFpEF patients had markedly reduced peak VO2 (15.3 ± 0.5 vs 24.6 ± 0.6 ml/kg/min, p<0.001) and 6MWD (434.7 ± 8.3 vs 547.3 ± 10.5 m, p<0.001) compared to HC. RV EF (49.9 ± 1.2 vs 55.0 ± 1.5%, p=0.026), EDV (112.4 ± 3.2 vs 128.5 ± 4.0 ml, p=0.008), SV (56.8 ± 2.4 vs 70.4 ± 3.1 ml, p0.003), and mass (23.7 ± 0.7 vs 27.2 ± 0.9 g, p=0.006) were significantly lower among HFpEF vs. HC. All of the above RV parameters were also significantly associated with lower peak VO2 and 6MWD (Table) but not with QOL. In multivariate analyses, RVEF was independently associated with lower peak VO2 (partial R=0.265, p=0.003) and shorter 6MWD (partial R=0.361, p<0.001). Conclusions: Compared to HC, chronic stable HFpEF patients have reduced RV EF, EDV, SV, and mass by CMR. RVEF is independently associated with worse peak VO2 and 6MWD but not QOL. This suggests RV dysfunction as a potential target for improving exercise intolerance in HFpEF. [ABSTRACT FROM AUTHOR]

Introduction: Sarcopenia is the age-related deterioration in skeletal muscle mass and function, which can be accelerated by chronic comorbidities. The prevalence in advanced systolic heart failure (HF) and impact on HF health status are currently uncertain. Sarcopenia diagnostic criteria from the Foundation for the National Institutes of Health (FNIH) and European Working Group on Sarcopenia in Older People (EWGSOP) have not been applied to HF cohorts. Hypothesis: We hypothesized that at the time of left ventricular assist device (LVAD) implantation systolic HF patients have prevalent sarcopenia, and that sarcopenia is associated with poorer nutritional and HF health status. Methods: We recruited 18 adults with systolic HF ±21 days from LVAD implantation. All underwent whole-body dual X-ray absorptiometry (DXA) to calculate appendicular lean mass (ALM). Subjects also underwent a 3-day food recall, Simplified Nutritional Appetite Questionnaire (SNAQ), Kansas City Cardiomyopathy Questionnaire (KCCQ) for HF health status, handgrip strength and blood testing. Sarcopenia was defined by 2 ALM criteria: FNIH – males <19.75kg, females <15.02kg; EWGSOP – males <7.26kg/m2, females <5.5kg/m2. Linear regression determined relationships between appendicular lean mass and age, weight, handgrip strength, KCCQ summary score, SNAQ score, 24-hour protein intake, and key blood variables, without/with adjustment for sex and height. Results: Sarcopenia was diagnosed in 5 subjects (28%) by FNIH criteria and an additional 5 (10 total, 56%) by EWGSOP criteria (Figure). There were unadjusted associations between lower appendicular lean mass and lower handgrip strength; higher SNAQ score (higher malnutrition risk); lower sodium; and lower hemoglobin. After adjustment for sex and height, lower lean mass remained associated with lower hemoglobin. Lower appendicular lean mass was also independently associated with higher (more favorable) KCCQ scores. Conclusions: As many as half of advanced systolic HF patients meet standard DXA criteria for sarcopenia. Lower appendicular lean mass is independently associated with lower hemoglobin but does not appear to be associated with poorer HF status. [ABSTRACT FROM AUTHOR]

Introduction: Among patients with heart failure, health status is hampered by heavy symptom burden. Symptom monitoring is crucial for optimal health status, and yet patients struggle with this aspect of self-care symptom management. To help patients with heart failure report symptoms to better communicate with their healthcare providers, we developed a mHealth application, mi.Symptoms. The purpose of this study was to identify patient symptoms and predictors of health status in patients with heart failure. Methods: A patient's symptom reporting in this study was conducted using mi.Symptoms that measures acute physical symptoms with the 18-item Heart Failure Somatic Perception Scale v.3 (HFSPS) and the Patient Reported Outcomes Measurement Information system (PROMIS®) that measures non-cardiac symptoms. The primary outcome of the study was health status, measured with the 23-item Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, using Qualtrics survey software. Data were analyzed using descriptive statistics, Pearson correlations, and generalized linear regression model analysis. Results: The sample (n=168) had a mean age of 58.7 (±12.54) years, 37% were female, 32% were White (n=51), 36% were Black (n=58), 44% of participants reported not having enough income to make ends meet (n=73), and the majority (48%) was symptomatic with class III HF (n=81). Overall 37% identified as Latino (n=60) and 19% completed the study in Spanish (n=33). After adjusting for demographic characteristics (age, gender, race, financial status), psychological (anxiety, depression, anger) and physical symptoms (fatigue, sleep, cognitive impairment, pain, dyspnea), the predictors of health status were NYHA Class IV (β = -11.7, p = 0.005), PROMIS physical function scores (β = 0.89, p = 0.001), dyspnea measured by the HFSPS Dyspnea subscale (β = -0.77, p < 0.001), and social limitations measured by the PROMIS social limitations score (β = 0.58, p = 0.002). Conclusions: This study demonstrates that both cardiac and non-cardiac symptoms are associated with health status. Interventions that optimize patient's physical function and social interaction with others and reduce dyspnea may improve the health status of patients with heart failure. [ABSTRACT FROM AUTHOR]