Effectiveness of a Smartphone App-Based Intervention With Bluetooth-Connected Monitoring Devices and a Feedback System in Heart Failure (SMART-HF Trial): Randomized Controlled Trial.

BACKGROUND: Current heart failure (HF) guidelines recommend a multidisciplinary approach, discharge education, and self-management for HF. However, the recommendations are challenging to implement in real-world clinical settings. OBJECTIVE: We developed a mobile health (mHealth) platform for HF self-care to evaluate whether a smartphone app-based intervention with Bluetooth-connected monitoring devices and a feedback system can help improve HF symptoms. METHODS: In this prospective, randomized, multicenter study, we enrolled patients 20 years of age and older, hospitalized for acute HF, and who could use a smartphone from 7 tertiary hospitals in South Korea. In the intervention group (n=39), the apps were automatically paired with Bluetooth-connected monitoring devices. The patients could enter information on vital signs, HF symptoms, diet, medications, and exercise regimen into the app daily and receive feedback or alerts on their input. In the control group (n=38), patients could only enter their blood pressure, heart rate, and weight using conventional, non-Bluetooth devices and could not receive any feedback or alerts from the app. The primary end point was the change in dyspnea symptom scores from baseline to 4 weeks, assessed using a questionnaire. RESULTS: At 4 weeks, the change in dyspnea symptom score from baseline was significantly greater in the intervention group than in the control group (mean -1.3, SD 2.1 vs mean -0.3, SD 2.3; P=.048). A significant reduction was found in body water composition from baseline to the final measurement in the intervention group (baseline level mean 7.4, SD 2.5 vs final level mean 6.6, SD 2.5; P=.003). App adherence, which was assessed based on log-in or the percentage of days when symptoms were first observed, was higher in the intervention group than in the control group. Composite end points, including death, rehospitalization, and urgent HF visits, were not significantly different between the 2 groups. CONCLUSIONS: The mobile-based health platform with Bluetooth-connected monitoring devices and a feedback system demonstrated improvement in dyspnea symptoms in patients with HF. This study provides evidence and rationale for implementing mobile app-based self-care strategies and feedback for patients with HF. TRIAL REGISTRATION: ClinicalTrials.gov NCT05668000; https://clinicaltrials.gov/study/NCT05668000.

Real-World Eligibility and Cost-Effectiveness Analysis of Empagliflozin for Heart Failure in Korea.

BACKGROUND: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. METHODS: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). RESULTS: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). CONCLUSION: There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01389843.

The effect of sustained-release CARvedilol in patients with hypErtension and heart failure with preserved ejection fraction: a study protocol for a pilot randomized controlled trial (CARE-preserved HF).

Background: Although beta-blockers improve clinical outcomes in heart failure with reduced ejection fraction, the benefit of beta-blockers in heart failure with preserved ejection fraction (HFpEF) is uncertain. Global longitudinal strain (GLS) is a robust predictor of heart failure outcomes, and recent studies have shown that beta-blockers are associated with improved survival in those with low GLS (GLS <14%) but not in those with GLS ≥14% among patients with LVEF ≥40%. Therefore, the objective of this trial is to evaluate the effect of sustained-release carvedilol (carvedilol-SR) on the outcome [N-terminal pro-B-natriuretic peptide (NT-proBNP) concentration] in patients with hypertension and HFpEF and will assess the differential effects of these drugs on the outcome, according to the GLS categories. Methods: This prospective randomized double-blind multicenter trial (CARE-preserved HF) will include 100 patients with HFpEF from three tertiary hospitals in South Korea. Patients with HFpEF and hypertension aged ≥20 years who have evidence of functional and structural heart disease on echocardiography and elevated natriuretic peptide will be enrolled. Eligible participants will be randomized 1:1 to either the carvedilol-SR group (n = 50) or the placebo group (n = 50). Patients in the carvedilol-SR group will receive 8, 16, 32, or 64 mg carvedilol-SR once daily for 6 months, and the dose of carvedilol will be up-titrated at the discretion of the treating physicians. The primary efficacy outcome was the time-averaged proportional change in N-terminal pro-B-natriuretic peptide concentration from baseline to months 3 and 6. We will also evaluate the differential effects of carvedilol-SR on primary outcomes according to GLS, using a cut-off of 14% or the median value. Discussion: This randomized controlled trial will investigate the efficacy and safety of carvedilol-SR in patients with HFpEF and hypertension. Clinical Trial Registration: ClinicalTrial.gov, identifier NCT05553314.

Differences in the Effects of Beta-Blockers Depending on Heart Rate at Discharge in Patients With Heart Failure With Preserved Ejection Fraction and Atrial Fibrillation.

Background and Objectives: Beta-blockers (BBs) improve prognosis in heart failure (HF), which is mediated by lowering heart rate (HR). However, HR has no prognostic implication in atrial fibrillation (AF) and also BBs have not been shown to improve prognosis in heart failure with preserved ejection fraction (HFpEF) with AF. This study assessed the prognostic implication of BB in HFpEF with AF according to discharge HR. Methods: From the Korean Acute Heart Failure Registry, 687 patients with HFpEF and AF were selected. Study subjects were divided into 4 groups based on 75 beats per minute (bpm) of HR at discharge and whether or not they were treated with BB at discharge. Results: Of the 687 patients with HFpEF and AF, 128 (36.1%) were in low HR group and 121 (36.4%) were in high HR group among those treated with BB at discharge. In high HR group, HR at discharge was significantly faster in BB non-users (85.5±9.1 bpm vs. 89.2±12.5 bpm, p=0.005). In the Cox model, BB did not improve 60-day rehospitalization (hazard ratio, 0.93; 95% confidence interval [95% CI], 0.35-2.47) or mortality (hazard ratio, 0.77; 95% CI, 0.22-2.74) in low HR group. However, in high HR group, BB treatment at discharge was associated with 82% reduced 60-day HF rehospitalization (hazard ratio, 0.18; 95% CI, 0.04-0.81), but not with mortality (hazard ratio, 0.77; 95% CI, 0.20-2.98). Conclusions: In HFpEF with AF, in patients with HR over 75 bpm at discharge, BB treatment at discharge was associated with a reduced 60-day rehospitalization rate.

The Third Nationwide Korean Heart Failure III Registry (KorHF III): The Study Design Paper.

With advancements in both pharmacologic and non-pharmacologic treatments, significant changes have occurred in heart failure (HF) management. The previous Korean HF registries, namely the Korea Heart Failure Registry (KorHF-registry) and Korean Acute Heart Failure Registry (KorAHF-registry), no longer accurately reflect contemporary acute heart failure (AHF) patients. Our objective is to assess contemporary AHF patients through a nationwide registry encompassing various aspects, such as clinical characteristics, management approaches, hospital course, and long-term outcomes of individuals hospitalized for AHF in Korea. This prospective observational multicenter cohort study (KorHF III) is organized by the Korean Society of Heart Failure. We aim to prospectively enroll 7,000 or more patients hospitalized for AHF at 47 tertiary hospitals in Korea starting from March 2018. Eligible patients exhibit signs and symptoms of HF and demonstrate either lung congestion or objective evidence of structural or functional cardiac abnormalities in echocardiography, or isolated right-sided HF. Patients will be followed up for up to 5 years after enrollment in the registry to evaluate long-term clinical outcomes. KorHF III represents the nationwide AHF registry that will elucidate the clinical characteristics, management strategies, and outcomes of contemporary AHF patients in Korea. Trial Registration: ClinicalTrials.gov Identifier: NCT04329234.

Metformin treatment is associated with improved survival in diabetic patients hospitalized with acute heart failure: A prospective observational study using the Korean acute heart failure registry data.

AIMS: Although the hypothesis that metformin is beneficial for patients with diabetes and heart failure (HF) has been steadily raised, there is limited data on metformin use in patients with acute HF. We analyzed the association of metformin on all-cause mortality in hospitalized patients with type 2 diabetes and acute HF. METHODS: The Korean Acute Heart Failure registry prospectively enrolled patients hospitalized for acute HF from 2011 to 2014. Among this cohort, we analyzed patients with diabetes with baseline estimated glomerular filtration rate (eGFR) of 30 ml/min/1.73 m2 or more. We analyzed the all-cause mortality and re-hospitalization for HF within 1 year after discharge. Inverse probability treatment weighting method was used to adjust baseline differences on metformin treatment. RESULTS: The study analyzed data from 1,309 patients with HF and diabetes (mean age 69 years, 56 % male). Among them, 613 (47 %) patients were on metformin at admission. During the median follow-up period of 11 months, 132 (19 %) and 74 (12 %) patients not receiving and receiving metformin treatment died, respectively. The mortality rate was lower in metformin users than in non-users (hazard ratio 0.616 [0.464-0.819] P<0.001). After adjustment, metformin was significantly associated with a lower risk for the mortality (hazard ratio 0.677 [0.495-0.928] P=0.015). In subgroup analyses, this association remains significant irrespective of baseline kidney function (eGFR <60 or ≥60 ml/min/1.73 m2, P-for-interaction=0.176) or left ventricular ejection fraction (<40 %, 40-49 %, or ≥50 %, P-for-interaction=0.224). CONCLUSIONS: Metformin treatment at the time of admission was associated with a lower risk for 1-year mortality in patients with diabetes, hospitalized for acute HF.

Eligibility and Cost-Utility Analysis of Dapagliflozin in Patients with Heart Failure Across the Whole Spectrum of Ejection Fraction in South Korea.

BACKGROUND: The DAPA-HF and DELIVER trials demonstrated the clinical benefits of dapagliflozin in heart failure (HF) patients across the entire ejection fraction (EF) spectrum. However, further investigation is needed for the real-world application of dapagliflozin in HF patients. This study examines the proportion of real-world HF patients eligible for dapagliflozin and evaluates the cost-effectiveness of adding dapagliflozin to current HF therapy. METHODS: Data from the nationwide prospective registry, the Korean Acute Heart Failure (KorAHF) registry, were used to determine dapagliflozin eligibility based on the enrollment criteria of the DAPA-HF/DELIVER trials. A cost-utility analysis was conducted using a Markov model to assess the cost-effectiveness of dapagliflozin by comparing it to the standard of care. RESULTS: Out of 5178 KorAHF patients, 48.7% met the enrollment criteria of the DAPA-HF/DELIVER trials, while 89.5% met the label criteria (US Food and Drug Administration, European Medicines Agency, and Korean Ministry of Food and Drug Safety). Eligibility was highest among HF patients with preserved EF (55.3% vs. HF with mildly reduced EF and HF with reduced EF 46.4%). Dapagliflozin proved to be cost-effective, with an incremental cost-effectiveness ratio (ICER) of 4557 US dollar (US$) per quality-adjusted life year, which falls below the US$18,182 willingness-to-pay threshold. The cost-effectiveness benefit was more pronounced in patients with a left ventricular EF (LVEF) ≤ 40% (ICER US$3279 for LVEF ≤ 40% vs. US$8383 for LVEF > 40%). CONCLUSIONS: Discrepancies in dapagliflozin eligibility were observed between real-world data and clinical trial results. The addition of dapagliflozin to HF therapy proved to be highly cost-effective across the entire EF spectrum.