Recent Heart Failure Hospitalization Research Articles

Ferric derisomaltose versus usual care in patients with heart failure, reduced ejection fraction, and iron deficiency: a short-term UK cost-utility analysis based on the IRONMAN RCT

Abstract Background In the IRONMAN trial, patients with heart failure (HF), a reduced ejection fraction and iron deficiency who were randomly assigned to ferric derisomaltose (FDI), rather than usual care, had a lower rate of the composite of hospitalization for heart failure (HHF) and cardiovascular (CV) death (rate ratio, RR, 0.82; 95% CI 0.66 to 1.02; p=0.07). A COVID-19 sensitivity analysis, censoring data at 1 year of follow-up showed a greater magnitude of treatment effect (RR 0.66; 95% CI 0.48 to 0.91; p=0.011). Purpose Patient-level data from IRONMAN were used to evaluate the effectiveness and cost-utility of FDI compared to usual care for patients with a current or recent HHF, or raised plasma natriuretic peptide concentrations, from a UK National Health Service (NHS) perspective. Methods A cost-utility analysis (CUA) was conducted covering the first year after randomization. Numbers-needed-to-treat (NNTs) were calculated for the primary endpoint censored at 1 year. In the CUA model, patient survival and rates of (re)hospitalization due to HF, other CV events, infections, respiratory conditions, and other non-CV events were modeled based directly on data from the IRONMAN RCT. UK-specific costs were obtained from the national schedule of NHS costs. Quality of life was estimated based on EQ-5D-5L data collected from patients included in the IRONMAN RCT. Results were undiscounted and reported as absolute and incremental costs in 2023 pounds sterling, and quality-adjusted life expectancy in quality-adjusted life years (QALYs). A willingness-to-pay threshold of £20,000 per QALY was adopted to allow calculation of a net monetary benefit (NMB), a summary measure of the overall value of FDI in monetary terms, capturing changes in both cost and QALY outcomes. Results The NNT analysis showed that 9 patients would need to be treated with FDI to avoid one composite primary endpoint event (CV death and HHF) over 1 year. Relative to usual care, FDI was associated with an improvement of 0.01 QALYs per patient over 1 year (0.58 versus 0.57 QALYs). Total average costs per-patient were £1,672 for FDI, versus £1,975 for usual care, leading to a saving of £302 per patient with FDI. The cost of iron procurement was more than offset by reductions in costs of (re)hospitalizations (Figure). FDI was therefore dominant over usual care, yielding an NMB of £483 over 1 year. Conclusions This short-term, within-trial CUA suggests that FDI both improves QALYs and reduces healthcare expenditure versus usual care when administered to patients with HF and iron deficiency in the UK. Iron repletion with FDI may be a prudent allocation of healthcare resources in this patient population.Breakdown of costs

Projecting the benefit of vericiguat in PARADIGM-HF and DAPA-HF populations: Insights from the VICTORIA trial.

The VICTORIA trial demonstrated a significant reduction in the primary composite outcome of heart failure (HF) hospitalization or cardiovascular death with vericiguat relative to placebo in high-risk HF. This study aimed to contextualize treatment effects of vericiguat in populations with varying risk profiles simulated from the PARADIGM-HF and DAPA-HF trials. Subgroups of VICTORIA participants (n=5050) were generated to simulate PARADIGM-HF and DAPA-HF trial populations. The PARADIGM-HF-eligible population excluded participants not meeting left ventricular ejection fraction (LVEF), estimated glomerular filtration rate (eGFR), and minimal dose criteria and those with high predicted probability of run-in failure. The DAPA-HF-eligible population excluded those not meeting LVEF and eGFR criteria or with recent (<30days) HF hospitalization. The time-to-first-event analysis was performed using an unadjusted Cox proportional hazards model. A total of 1982 (39.2%) and 2543 (50.4%) VICTORIA participants were respectively deemed eligible for PARADIGM-HF and DAPA-HF. Vericiguat was associated with numerically larger reductions in the primary outcome of HF hospitalization or cardiovascular death in populations simulated from PARADIGM-HF [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.72-0.99] and DAPA-HF (HR 0.82, 95% CI 0.71-0.94) compared with the overall VICTORIA trial (HR 0.90). Significant reduction in HF hospitalization with vericiguat was also observed in the DAPA-HF-eligible population (HR 0.83, 95%CI 0.73-0.95) and with a nominal reduction in the PARADIGM-HF-eligible population (HR 0.86, 95% CI 0.74-1.01). A trend towards enhanced efficacy of vericiguat in populations simulated from PARADIGM-HF and DAPA-HF was observed. These findings support further exploration of vericiguat in lower-risk HF populations as is being investigated in the ongoing VICTOR (a study of vericiguat in participants with chronic heart failure with reduced ejection fraction) trial.

Differential impacts of self-care behavior on clinical outcomes in patients with and without recent heart failure hospitalization

BackgroundAlthough clinical guidelines recommend self-care assessment for patients with chronic heart failure (CHF), its prognostic significance remains controversial. This study aimed to compare the prognostic significance of self-care behavior on mortality between patients with and without a history of recent hospitalization for heart failure (HF). MethodsWe analyzed consecutive 1907 CHF patients from a Japanese multicenter registry (January 2020–June 2023) using the 9-item European Heart Failure Self-care Behavior Scale (EHFScBS-9) at enrolment. Suboptimal self-care behavior was defined as a score < 70 on the EHFScBS-9. Patients were divided into recent (within 30 days post-discharge, n = 664) and no recent hospitalization for HF groups (n = 1263), respectively. The primary outcome was a composite of all-cause death and rehospitalization for HF. ResultsDuring a median follow-up period of 427 (interquartile range 273–630) days, the primary outcome occurred in 100 patients. Patients with suboptimal self-care behavior exhibited a higher incidence of the primary outcome in the recent hospitalization for HF group (p = 0.020) but not in the no recent hospitalization for HF group (P = 0.16). Multivariable regressions showed suboptimal self-care behavior was independently associated with the primary outcome in the recent hospitalization for HF group with a significant interaction (P = 0.029). ConclusionIn patients recently hospitalized for HF, but not in those without a recent hospitalization history for HF, suboptimal self-care behavior was associated with adverse events. This indicates the importance of self-care education for these patients.

Seated Pulmonary Artery Pressure Monitoring in Patients With Heart Failure: Results of the PROACTIVE-HF Trial

BackgroundMonitoring supine pulmonary artery pressures to guide heart failure (HF) management has reduced HF hospitalizations in select patients. ObjectivesThe purpose of this study was to evaluate the effect of managing seated mean pulmonary artery pressure (mPAP) with the Cordella Pulmonary Artery sensor on outcomes in patients with HF. MethodsFollowing GUIDE-HF (Hemodynamic-GUIDEd Management of Heart Failure Trial), with U.S. Food and Drug Administration input, PROACTIVE-HF (A Prospective, Multi-Center, Open Label, Single Arm Clinical Trial Evaluating the Safety and Efficacy of the Cordella Pulmonary Artery Sensor System in NYHA Class III Heart Failure Patients trial) was changed from a randomized to a single-arm, open label trial, conducted at 75 centers in the USA and Europe. Eligible patients had chronic HF with NYHA functional class III symptoms, irrespective of the ejection fraction, and recent HF hospitalization and/or elevated natriuretic peptides. The primary effectiveness endpoint at 6 months required the HF hospitalization or all-cause mortality rate to be lower than a performance goal of 0.43 events/patient, established from previous hemodynamic monitoring trials. Primary safety endpoints at 6 months were freedom from device- or system-related complications or pressure sensor failure. ResultsBetween February 7, 2020, and March 31, 2023, 456 patients were successfully implanted in modified intent-to-treat cohort. The 6-month event rate was 0.15 (95% CI: 0.12-0.20) which was significantly lower than performance goal (0.15 vs 0.43; P < 0.0001). Freedom from device- or system-related complications was 99.2% and freedom from sensor failure was 99.8% through 6 months. ConclusionsRemote management of seated mPAP is safe and results in a low rate of HF hospitalizations and mortality. These results support the use of seated mPAP monitoring and extend the growing body of evidence that pulmonary artery pressure–guided management improves outcomes in heart failure. (Multi-Center, Open Label, Single Arm Clinical Trial Evaluating the Safety and Efficacy of the Cordella Pulmonary Artery Sensor System in NYHA Class III Heart Failure Patients trial [PROACTIVE-HF]; NCT04089059)

Hospitalization of Symptomatic Patients With HeartFailure and Moderate to Severe Functional Mitral Regurgitation Treated With MitraClip: Insights From RESHAPE-HF2.

For patients with functional mitral regurgitation (FMR) and symptomatic heart failure (HF), randomized trials of mitral transcatheter edge-to-edge repair (M-TEER) have produced conflicting results. This study sought to assess the impact of M-TEER on hospitalization rates, and explore the effects of M-TEER on patients who did or did not have a history of recent HF hospitalizations before undergoing M-TEER. RESHAPE-HF2 (Randomized Investigation of the MitraClip Device in HeartFailure: 2nd Trial in Patients with Clinically Significant Functional Mitral Regurgitation) included patients with symptomatic HF and moderate to severe FMR (mean effective regurgitant orifice area 0.25cm2; 14% >0.40cm2, 23%<0.20cm2) and showed that M-TEER reduced recurrent HF hospitalizations with and without the addition of cardiovascular (CV) death and improved quality of life. We now report the results of prespecified analyses on hospitalization rates and for the subgroup of patients (n=333) with a HF hospitalization in the 12months before randomization. At 24months, the time to first event of CV death or HF hospitalization (HR: 0.65; 95%CI: 0.49-0.85; P=0.002), the rate of recurrent CV hospitalizations (rate ratio [RR]: 0.75; 95%CI: 0.57-0.99; P=0.046), the composite rate of recurrent CV hospitalizations and all-cause mortality (RR: 0.74; 95%CI: 0.57-0.95; P=0.017), and of recurrent CV death and CV hospitalizations (RR: 0.76; 95%CI: 0.58-0.99; P=0.040), were all lower in the M-TEER group. The RR of recurrent hospitalizations for any cause was 0.82 (95%CI: 0.63-1.07; P=0.15) for patients in the M-TEER group vs control group patients. Patients randomized to M-TEER lost fewer days due to death or HF hospitalization (13.9% [95%CI: 13.0%-14.8%] vs 17.4% [95% CI: 16.4%-18.4%] of follow-up time; P< 0.0001, and 1,067 vs 1,776 total days lost; P< 0.0001). Patients randomized to M-TEER also had better NYHA functional class at 30days and at 6, 12, and 24months of follow-up (P< 0.0001). A history of HF hospitalizations before randomization was associated with worse outcomes and greater benefit with M-TEER on the rate of the composite of recurrent HF hospitalizations and CV death (Pinteraction=0.03) and of recurrent HF hospitalizations within 24months (Pinteraction=0.06). These results indicate that a broader application of M-TEER in addition to optimal guideline-directed medical therapy should be considered among patients with symptomatic HF and moderate to severe FMR, particularly in those with a history of a recent hospitalization for HF.

Baseline characteristics of patients with heart failure with mildly reduced or preserved ejection fraction: The FINEARTS-HF trial.

To describe the baseline characteristics of participants in the FINEARTS-HF trial, contextualized with prior trials including patients with heart failure (HF) with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF). The FINEARTS-HF trial is comparing the effects of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo in reducing cardiovascular death and total worsening HF events in patients with HFmrEF/HFpEF. Patients with symptomatic HF, left ventricular ejection fraction (LVEF) ≥40%, estimated glomerular filtration rate ≥ 25 ml/min/1.73 m2, elevated natriuretic peptide levels and evidence of structural heart disease were enrolled and randomized to finerenone titrated to a maximum of 40 mg once daily or matching placebo. We validly randomized 6001 patients to finerenone or placebo (mean age 72 ± 10 years, 46% women). The majority were New York Heart Association functional class II (69%). The baseline mean LVEF was 53 ± 8% (range 34-84%); 36% of participants had a LVEF <50% and 64% had a LVEF ≥50%. The median N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 1041 (interquartile range 449-1946) pg/ml. A total of 1219 (20%) patients were enrolled during or within 7 days of a worsening HF event, and 3247 (54%) patients were enrolled within 3 months of a worsening HF event. Compared with prior large-scale HFmrEF/HFpEF trials, FINEARTS-HF participants were more likely to have recent (within 6 months) HF hospitalization and greater symptoms and functional limitations. Further, concomitant medications included a larger percentage of sodium-glucose cotransporter 2 inhibitors and angiotensin receptor-neprilysin inhibitors than previous trials. FINEARTS-HF has enrolled a broad range of high-risk patients with HFmrEF and HFpEF. The trial will determine the safety and efficacy of finerenone in this population.

Dapagliflozin and Timing of Prior Heart Failure Hospitalization: A Patient-Level Meta-Analysis of DAPA-HF and DELIVER

BackgroundPatients recently hospitalized for heart failure (HF) are at a higher risk of adverse clinical outcomes, but they may experience a greater absolute and relative benefit from effective therapies than individuals who are considered more “stable.” ObjectivesThe authors examined the effects of dapagliflozin according to the timing of prior HF hospitalization in a patient-level pooled analysis of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure). MethodsA total of 11,007 patients were randomized in DAPA-HF and DELIVER. The primary outcome was the composite of worsening HF or cardiovascular death. ResultsIn total, 12.4% were hospitalized for HF within 3 months of randomization, 14.2% between 3 and 12 months, and 16.8% more than 1 year before randomization, whereas 56.5% had not been hospitalized. The risk of the primary endpoint was inversely associated with time from prior HF hospitalization, and patients with a recent HF hospitalization had the highest risk. Compared with placebo, dapagliflozin reduced the risk of the primary outcome across HF hospitalization category (0-3 months, HR: 0.66 [95% CI: 0.55-0.81]; 3-12 months, HR: 0.73 [95% CI: 0.59-0.90]; >1 year, HR: 0.91 [95% CI: 0.74-1.12]; and no prior hospitalization, HR: 0.83 [95% CI: 0.73-0.94]; Pinteraction = 0.09). The number of patients needed to treat with dapagliflozin to prevent 1 event over the median follow-up of 22 months was 13, 20, 23, and 28, respectively. The beneficial effect was consistent across the range of LVEF regardless of HF hospitalization category. ConclusionsThe relative benefits of dapagliflozin were consistent across the range of LVEF regardless of the timing of the most recent HF hospitalization with a greater absolute benefit in patients with recent hospitalization.

Use of remote patient monitoring kits to reduce hospitalization and mortality rates for patients with heart failure.

Patients with heart failure (HF) are at an increased risk of volume overload, which can lead to hospital admission. Use of noninvasive remote patient monitoring (RPM) devices utilizing biometric sensors and weighing scales to track vital signs and body weight has uncertain benefits. At the Baptist Health Louisville (BHLOU) HF Clinic, high-risk patients were given RPM kits. The purpose of this study was to determine whether RPM led to reductions in HF hospitalizations and mortality. This single-center, retrospective chart review evaluated adult patients presenting to the BHLOU HF Clinic after a recent hospitalization for HF or need for intravenous diuretics within the past 60 days. The study evaluated patients before and after implementation of RPM kits. The primary endpoints were differences in the rates of 30-day HF hospitalization and 30-day mortality. Secondary endpoints included differences in the number of interventions in 90 days, the 90-day rate of HF hospitalization, and the 90-day rate of mortality. The final analysis included 58 patients in the preimplementation group and 34 patients in the postimplementation group. The rate of 30-day HF hospitalization was 10.3% in the preimplementation group and 0% in the postimplementation group. The rate of 30-day mortality was 3.4% in the preimplementation group and 0% in the postimplementation group. For the secondary endpoints, the number of interventions in 90 days was 3 vs 4, the 90-day rate of HF hospitalization was 22.4% vs 11.8%, and the rate of 90-day mortality was 6.9% vs 5.9% in the preimplementation vs postimplementation group, respectively. Implementation of RPM in patients with acutely decompensated HF led to numerically lower 30-day and 90-day rates of HF hospitalization.

Initiation, titration, and discontinuation - utilization of heart failure medicines in England (EVOLUTION HF UK)

Abstract Background Guidelines advise early initiation and optimisation of several guideline-recommended pharmacological therapies (GRPTs) for managing heart failure (HF) with reduced ejection fraction. Recent guidelines have expanded this list to include two new classes of agents: sodium-glucose cotransporter 2 (SGLT2) inhibitors and angiotensin receptor neprilysin inhibitor (ARNI). Auditing real-world GRPT use is critical in closing the evidence-practice gap. Purpose To generate insights into utilization patterns of novel and established GRPTs after a recent hospitalization for HF (hHF) in England using administrative healthcare records. Methods New users of GRPTs within 12 months of a hHF discharge were identified using linked national electronic health records (Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics mortality data) between January 2021 — May 2022. Time to initiation of dapagliflozin (the only SGLT2 inhibitor approved for HF in January 2021), sacubitril/valsartan, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) were considered separately. Titration and discontinuation of the most frequently used drug for each pharmacological class was identified and analysed as representative of the entire class. Doses and discontinuation were assessed in the 12 months following initiation. If a new package isn't collected after the previous one ends, discontinuation is assumed until a new package is collected. Target dose was defined as ≥100% of the guideline-recommended dose. Results Overall, 16,090 new users of GRPTs were identified. Mean times from hHF to GRPT initiation were longer for novel agents (dapagliflozin or sacubitril/valsartan) than for established agents: 195 and 137 vs 48 to 73 days. Similarly, the cumulative percentage of patients initiating a GRPT within 100 days of hHF discharge were lower for novel agents (Figure 1). In the following 12 months, the average target dose achieved was higher for novel agents: 61.8% (dapagliflozin), 32.4% (sacubitril/valsartan), 8.5% (ACE inhibitor: ramipril), 5.9% (ARB: candesartan), 7.6% (beta-blocker: bisoprolol), and 6.6% (MRA: spironolactone). Corresponding discontinuation rates were 32.0%, 24.3%, 36.3%, 38.2%, 23.4%, and 50.1%, respectively (Figure 1 and 2). Conclusion In the UK, early initiation of novel GRPTs after recent hHF in routine clinical practice remains a challenge. For GRPTs requiring uptitration, few patients received the target dose in the 12 months after initiation, and many discontinued treatments. Conversely, dapagliflozin was associated with relatively higher rates of target dose achievement, perhaps because only a single fixed dose is recommended. Our data highlight the need for increased access to appropriate, timely and sustained HF therapeutic optimization.

An electronic consultation programme impacts on heart failure patients prognosis: implications for heart failure care

Abstract Background Multidisciplinary care plans that comprise professionals from different levels of care optimize the diagnosis and treatment of patients with heart failure (HF). Purpose Our objective was to analyse the clinical characteristics, 1 year prognosis and the prognostic determinants of patients with a previous diagnosis of HF, categorized by their previous HF-related hospitalization status (&amp;lt;1year or &amp;gt;1 year before or never hospitalized), referred by general practitioners (GPs) to a cardiology department (CD) by an e-consultation. Methods Data were obtained from 4851 HF patients referred by GPs to the cardiology department for an e-consultation from 2013 to 2020. We analysed the clinical characteristics of HF patient. We studied the whole cohort, and then subdivided it into three groups of diagnosis: patients who had never been hospitalized due to HF, patients with a recent HF-related hospitalization (&amp;lt;1 year), and patients with a remote HF-related hospitalization (≥1 year). To assess 1 year prognosis after e-consultation, we analysed the following health outcomes: HF-related hospitalizations, cardiovascular hospitalizations, HF-related mortality, cardiovascular mortality and all-cause mortality (Fig. 1). Qualitative variables are expressed as percentages (%), and quantitative continuous variables as means (standard deviation), or medians (interquartile range) if the distribution was asymmetric. To verify differences between groups, χ2 was used for quantitative variables, and ANOVA for qualitative variables. Results The delay of time to e-consults were solved was 8.6 + 8.6 days with 84.3% solved in &amp;lt;14 days. For the 1 year prognosis evaluation after the e-consult were assessed the cardiovascular hospitalizations, HF-related hospitalizations, HF-related mortality, cardiovascular mortality, and all-cause mortality. Compared with the group without a previous hospitalization, patients with recent and remote HF hospitalization were at higher risk of a new HF-related hospitalization (OR: 19.41 [95% CI: 12.95–29.11]; OR: 8.44 [95% CI: 5.14–13.87], respectively) (Fig 2), HF-related mortality (OR: 2.47 [95% CI: 1.43–4.27]; OR: 1.25 [95% CI: 0.51–3.06], respectively), as well as cardiovascular hospitalizations and mortality and all-cause mortality. Reduction in the time elapsed because e-consultation was solved was associated with lower risk of HF-related mortality (OR: 0.94 [95% CI: 0.89–0.99]), cardiovascular mortality (OR: 0.96 [95% CI: 0.93–0.98]), and all-cause mortality (OR: 0.98 [95% CI: 0.97–1.00]). Conclusions A clinician-to-clinician e-consultation programme between GPs and cardiologists in patients with HF allows to solve the demand of care in around 25% e-consults without an in-person consultation; the patients with a previous history of HF-related hospitalization showed a worse 1 year outcome. A reduction in the time elapsed because e-consultation was solved was associated with a mortality reduction.

Experimentally Induced Peripheral Venous Congestion Exacerbates Inflammation, Oxidative Stress, and Neurohormonal and Endothelial Cell Activation in Patients With Systolic Heart Failure

Venous congestion (VC) is a hallmark of symptomatic heart failure (HF) requiring hospitalization; however, its role in the pathogenesis of HF progression remains unclear. We investigated whether peripheral VC exacerbates inflammation, oxidative stress and neurohormonal and endothelial cell (EC) activation in patients with HF with reduced ejection fraction (HFrEF). Two matched groups of patients with HFrEF and with no peripheral VC vs without recent HF hospitalization were studied. We modeled peripheral VC by inflating a cuff around the dominant arm, targeting ∼ 30 mmHg increase in venous pressure (venous stress test [VST]). Blood and ECs were sampled before and after 90 minutes of VST. We studied 44 patients (age 53 ± 12 years, 32% female). Circulating endothelin-1, tumor necrosis factor-α, interleukin-6, isoprostane, angiotensin II (ang-2), angiopoietin-2, vascular cell adhesion molecule-1, and CD146 significantly increased after the VST. Enhanced endothelin-1 and angiopoietin-2 responses to the VST were present in patients with vs without recent hospitalization and were prospectively associated with incident HF-related events; 6698 messenger ribonucleic acid (mRNA probe sets were differentially expressed in ECs after VST. Experimental VC exacerbates inflammation, oxidative stress, neurohormonal and EC activation and promotes unfavorable transcriptome remodeling in ECs of patients with HFrEF. A distinct biological sensitivity to VC appears to be associated with high risk for HF progression.

Real-world use of sodium-glucose co-transporter 2 inhibitors in patients with heart failure and reduced ejection fraction: Data from the Swedish Heart Failure Registry.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) reduce mortality/morbidity in heart failure (HF). We explored the implementation of SGLT2i over time, and patient characteristics associated with their use, in a large, nationwide population with HF with reduced ejection fraction (HFrEF). Patients with HFrEF (EF < 40%), no type1 diabetes, estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73m2 and/or on dialysis, registered in the Swedish HF Registry between 1-November-2020 and 5-August-2022 were included. Independent predictors of use were investigated by multivariable logistic regressions. Of 8192 patients, 37% received SGLT2i. Use increased overall from 20.5% to 59.0% over time, from 46.2% and 12.5% to 69.8% and 55.4% in patients with and without type 2 diabetes (T2DM), from 14.7% and 22.3% to 58.0% and 59.8% in eGFR<60 vs. ≥60 mL/min/1.73m2 , from 21.6% and 18.9% to 61.6% and 52.0% in males vs. females, from 24.2% and 18.0% to 60.8% and 57.7% in patients with vs. without recent HF hospitalization, from 26.1% and 19.8% to 54.7% and 59.6% in in- vs. out-patient, and from 20.2% and 21.2% to 59.2% and 58.7% in those with HF duration < vs ≥6 months, respectively. Important characteristics associated with SGLT2i use were male sex, recent HF hospitalization, specialized HF follow-up, lower EF, T2DM, higher education level, use of other HF/cardiovascular interventions. Older age, higher blood pressure, atrial fibrillation and anemia were associated with less use. Discontinuation rate at 6 and 12 months was 13.1% and 20.0%, respectively. Use of SGLT2i increased 3-fold over 2 years. Although this indicates a more rapid translation of trials results and guidelines into clinical practice compared to previous HF drugs, further efforts are advocated to complete the implementation process while avoiding inequities across different patients' subgroups and discontinuations. This article is protected by copyright. All rights reserved.

Renal and blood pressure effects of dapagliflozin in recently hospitalized patients with heart failure with mildly reduced or preserved ejection fraction: Insights from the DELIVER trial.

Patients recently hospitalized for heart failure (HF) often have unstable haemodynamics and experience worsening renal failure, and are at elevated risk for recurrent HF events. In DELIVER, dapagliflozin reduced HF events or cardiovascular death including among patients who were hospitalized or recently hospitalized. We examined the effects of dapagliflozin versus placebo on estimated glomerular filtration rate (eGFR) slope (acute and chronic), 1-month change in systolic blood pressure, and the occurrence of serious hypovolaemic or renal adverse events in patients with and without HF hospitalization within 30 days of randomization. The 654 (90 randomized during hospitalization, 147 1-7 days post-discharge and 417 8-30 days post-discharge) recently hospitalized patients had lower baseline eGFR compared with those without recent HF hospitalization (median [interquartile range] 55 [43, 71] vs. 60 [47, 75] ml/min/1.73 m2 ). Dapagliflozin consistently reduced the risk of all-cause (pinteraction = 0.20), cardiac-related (pinteraction = 0.75), and HF-specific (pinteraction = 0.90) hospitalizations, irrespective of recent HF hospitalization. In those recently hospitalized, acute placebo-corrected eGFR reductions with dapagliflozin were modest and similar to patients without recent hospitalization (-2.0 [-4.1, +0.1] vs. -3.4 [-3.9, -2.9] ml/min/1.73 m2 , pinteraction = 0.12). Dapagliflozin's effect to slow chronic eGFR decline was similar regardless of recent hospitalization (pinteraction = 0.57). Dapagliflozin had a minimal effect on 1-month systolic blood pressure and to a similar degree in patients with and without recent hospitalization (-1.3 vs.-1.8 mmHg, pinteraction = 0.64). There was no treatment-related excess in renal or hypovolaemic serious adverse events, irrespective of recent HF hospitalization. In patients recently hospitalized with HF, initiation of dapagliflozin had minimal effects on blood pressure and did not increase renal or hypovolaemic serious adverse events, yet afforded long-term cardiovascular and kidney protective effects. These data suggest that the benefit to risk ratio favours initiation of dapagliflozin among stabilized patients hospitalized or recently hospitalized for HF. ClinicalTrials.gov NCT03619213.

Design and Baseline Characteristics of STEP-HFpEF Program Evaluating Semaglutide in Patients With Obesity HFpEF Phenotype

BackgroundThe majority of patients with heart failure with preserved ejection fraction (HFpEF) have the obesity phenotype, but no therapies specifically targeting obesity in HFpEF exist. ObjectivesThe aim of this study was to describe the design and baseline characteristics of 2 trials of semaglutide, a glucagon-like peptide-1 receptor agonist, in patients with the obesity HFpEF phenotype: STEP-HFpEF (Semaglutide Treatment Effect in People with obesity and HFpEF; NCT04788511) and STEP-HFpEF DM (Semaglutide Treatment Effect in People with obesity and HFpEF and type 2 diabetes; NCT04916470). MethodsBoth STEP-HFpEF and STEP-HFpEF DM are international multicenter, double-blind, placebo-controlled trials that randomized adults with HFpEF and a body mass index ≥30 kg/m2 to once-weekly semaglutide at a dose of 2.4 mg or placebo. Participants were eligible if they had a left ventricular ejection fraction (LVEF) ≥45%; NYHA functional class II to IV; a Kansas City Cardiomyopathy Questionnaire (KCCQ)–Clinical Summary Score (CSS) <90 points; and ≥1 of the following: elevated filling pressures, elevated natriuretic peptides plus structural echocardiographic abnormalities, recent heart failure hospitalization plus ongoing diuretic use, and/or structural abnormalities. The dual primary endpoints are the 52-week change in the KCCQ-CSS and body weight. ResultsIn STEP-HFpEF and STEP-HFpEF DM (N = 529 and N = 617, respectively), nearly half were women, and most had severe obesity (median body mass index of 37 kg/m2) with typical features of HFpEF (median LVEF of 57%, frequent comorbidities, and elevated natriuretic peptides). Most participants received diuretic agents and renin-angiotensin blockers at baseline, and approximately one-third were on mineralocorticoid receptor antagonists. Sodium-glucose cotransporter-2 inhibitor use was rare in STEP-HFpEF but not in STEP HFpEF DM (32%). Patients in both trials had marked symptomatic and functional impairments (KCCQ-CSS ∼59 points, 6-minute walking distance ∼300 m). ConclusionsIn total, STEP-HFpEF program randomized 1,146 participants with the obesity phenotype of HFpEF and will determine whether semaglutide improves symptoms, physical limitations, and exercise function in addition to weight loss in this vulnerable group.

MP-453086-7 ATRIOVENTRICULAR JUNCTION ABLATION AND CARDIAC RESYNCHRONIZATION THERAPY IN PATIENTS WITH NONOBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY AND PERMANENT ATRIAL FIBRILLATION

Atrial fibrillation (AF) is the most common arrhythmia encountered with hypertrophic cardiomyopathy (HCM) and is associated with adverse cardiovascular outcomes. The outcomes of ablate-and-pace strategy for the management of refractory AF in HCM patients are unclear. The objective of this retrospective study was to investigate the incremental benefit and safety of atrioventricular junction (AVJ) ablation and biventricular pacing (CRT) in patients with nonobstructive (NO) HCM and symptomatic permanent AF. Between January 2016 and December 2021, 20 patients with NO-HCM underwent AVJ ablation + CRT for uncontrolled permanent AF. The control group included 86 NO-HCM patients with permanent AF treated by the best medical rate-control therapy. A 1:1 propensity score (PS) matching analysis weighted on clinical (age, gender, hypertension, diabetes, recent hospitalization for heart failure [HF], cerebrovascular accident, chronic kidney disease, NYHA class) and imaging characteristics (left ventricle [LV] ejection fraction [EF], left atrial dimension, estimated pulmonary hypertension, maximal wall thickness, late gadolinium enhancement extension) was performed to compare outcomes between groups. The primary endpoint was a composite of all-cause mortality and hospitalization due to HF during follow-up. PS matching yielded 40 patients, 20 patients with AVN ablation + CRT (Group 1), and 20 patients in best medical rate-control therapy (Group 2). CRT was achieved in all patients (100% CRT-D). No acute procedure-related complications were noted. The mean paced QRS duration was 119±12 ms. Within the matched cohort, mean age was 64±7 years, the median time since AF diagnosis was 2 years (IQR 0.8-2.3 years), the mean LV EF was 53%±5%. During a median follow-up period of 23 months (IQR 19-27 months), patients in Group 1 had a lower risk of primary outcomes (HR 0.7; 95% CI 0.47-0.92; p=0.04), mainly driven by a significantly lower risk of HF hospitalization (HR 0.4; 95% CI 0.23–0.75; p=0.02). Compared to Group 2, Group 1 experienced a significant improvement in LV EF (55%±5% [Group 1] vs 48%±6% [Group 2], p=0.03) and improvement in NYHA class. No long-term device-related complications were noted. Ablation of AVJ + CRT was safe and superior to medical therapy in reducing HF hospitalization in patients with NO-HCM and permanent AF.

Hemodynamic-Guided Heart Failure Management in Patients With Either Prior HF Hospitalization or Elevated Natriuretic Peptides

BackgroundIn patients with symptomatic heart failure (HF) and previous heart failure hospitalization (HFH), hemodynamic-guided HF management using a wireless pulmonary artery pressure (PAP) sensor reduces HFH, but it is unclear whether these benefits extend to patients who have not been recently hospitalized but remain at risk because of elevated natriuretic peptides (NPs). ObjectivesThis study assessed the efficacy and safety of hemodynamic-guided HF management in patients with elevated NPs but no recent HFH. MethodsIn the GUIDE-HF (Hemodynamic-Guided Management of Heart Failure) trial, 1,000 patients with New York Heart Association (NYHA) functional class II to IV HF and either previous HFH or elevated NP levels were randomly assigned to hemodynamic-guided HF management or usual care. The authors evaluated the primary study composite of all-cause mortality and total HF events at 12 months according to treatment assignment and enrollment stratum (HFH vs elevated NPs) by using Cox proportional hazards models. ResultsOf 999 evaluable patients, 557 were enrolled on the basis of a previous HFH and 442 on the basis of elevated NPs alone. Those patients enrolled by NP criteria were older and more commonly White persons with lower body mass index, lower NYHA class, less diabetes, more atrial fibrillation, and lower baseline PAP. Event rates were lower among those patients in the NP group for both the full follow-up (40.9 per 100 patient-years vs 82.0 per 100 patient-years) and the pre–COVID-19 analysis (43.6 per 100 patient-years vs 88.0 per 100 patient-years). The effects of hemodynamic monitoring were consistent across enrollment strata for the primary endpoint over the full study duration (interaction P = 0.71) and the pre–COVID-19 analysis (interaction P = 0.58). ConclusionsConsistent effects of hemodynamic-guided HF management across enrollment strata in GUIDE-HF support consideration of hemodynamic monitoring in the expanded group of patients with chronic HF and elevated NPs without recent HFH. (Hemodynamic-Guided Management of Heart Failure [GUIDE-HF]; NCT03387813)

Recency of Heart Failure Hospitalization, Outcomes, and the Effect of Empagliflozin: An EMPEROR-Pooled Analysis

BackgroundPatients with a recent heart failure (HF) hospitalization have a high risk of rehospitalization and mortality. Early treatment may have a substantial impact on patient outcomes. ObjectivesThis study sought to study the outcomes and effect of empagliflozin according to timing of prior HF hospitalization. MethodsEMPEROR-Pooled (EMPEROR-Reduced [EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction] and EMPEROR-Preserved [EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction] combined) included 9,718 HF patients who were grouped according to the recency of HF hospitalization (none, <3 months, 3-6 months, 6-12 months, >12 months). The primary outcome was a composite of time to first of HF hospitalization or cardiovascular death, over a median follow-up of 21 months. ResultsThe primary outcome event rates (per 100 person-years) in the placebo group were 26.7, 18.1, 13.7, and 2.8 for patients hospitalized within 3 months, 3-6 months, 6-12 months, and >12 months, respectively. The relative risk reduction of primary outcome events with empagliflozin was similar across HF hospitalization categories (P interaction = 0.67). The primary outcome absolute risk reduction was more pronounced among patients with a recent HF hospitalization but without statistical heterogeneity of treatment effect: −6.9, −5.5, −0.8, and −0.6 events prevented per 100 person-years for patients hospitalized within <3 months, 3-6 months, 6-12 months, and >12 months, respectively, and −2.4 events prevented per 100 person-years of follow-up in those without a prior HF hospitalization (P interaction = 0.64). Empagliflozin was safe irrespective of HF hospitalization recency. ConclusionsPatients with a recent HF hospitalization have a high risk of events. Empagliflozin reduced HF events regardless of HF hospitalization recency.

Effects of Remote Patient Management on Self-Care Behaviour in Heart Failure Patients: Results from the randomised TIM-HF2 Trial.

Remote patient management (RPM) in heart failure (HF) patients has beneficial clinical effects. This analysis investigates the effects of RPM used in the Telemedical Interventional Management in Heart Failure II trial on HF-specific self-care. From 2013 to 2017 1,538 HF outpatients (age 70.3±10.5years, 70% men, 52%/47% NYHA II/III, 65% LVEF ≤45%) with a recent HF hospitalisation were included to the study and randomised to Usual Care (UC) plus RPM (n=796) or UC only (n=775), with a 12-month follow-up. Self-reported self-care behaviour at baseline and at end of study was assessed with the 9-item European Heart Failure Self-care Behaviour Scale (EHFScBS-9), obtaining 1,321 patients with valid baseline and follow-up questionnaires for the analysis.EHFScBS-9 sum scores increased in the RPM group (n=667) from 78.7±17 to 84.5±14 and in the UC group (n=654) from 79.0±17 to 80.0±16 from baseline to 12 months (difference in means [MD] 4.58 [3.02, 6.14]; p<0.001) with highest improvement (8.66 [3.52; 13.81]) in patients living alone and having an inadequate (<70) baseline EHFScBS-9. There were differences between both groups in item "I weight myself every day" (MD -1.13 [-1.24, -1.02]; p<0.001), and item "I take my medication as prescribed" (MD -0.06 [-0.10, -0.01]; p=0.014). No correlation was found between the EHFScBS-9 score and the efficacy of RPM on the TIM-HF2 primary endpoint of percentage of days lost due to unplanned cardiovascular hospitalisation or death of any cause. RPM improves HF-specific self-care behaviour by achieving a better adherence to recommended HF regimen.

Telemonitoring in heart failure patients: Systematic review and meta-analysis of randomized controlled trials.

Home telemonitoring has been used as a modality to prevent readmission and improve outcomes for patients with heart failure. However, studies have produced conflicting outcomes over the years. To determine the aggregate effect of telemonitoring on all-cause mortality, heart failure-related mortality, all-cause hospitalization, and heart failure-related hospitalization in heart failure patients. We conducted a systematic review and meta-analysis of 38 home telemonitoring randomized controlled trials involving 14993 patients. We also conducted a sensitivity analysis to examine the effect of telemonitoring duration, recent heart failure hospitalization, and age on telemonitoring outcomes. Our study demonstrated that home telemonitoring in heart failure patients was associated with reduced all-cause [relative risk (RR) = 0.83, 95% confidence interval (CI): 0.75-0.92, P = 0.001] and cardiovascular mortality (RR = 0.66, 95%CI: 0.54-0.81, P < 0.001). Additionally, telemonitoring decreased the all-cause hospitalization (RR = 0.87, 95%CI: 0.80-0.94, P = 0.002) but did not decrease heart failure-related hospitalization (RR = 0.88, 95%CI: 0.77-1.01, P = 0.066). However, prolonged home telemonitoring (12 mo or more) was associated with both decreased all-cause and heart failure hospitalization, unlike shorter duration (6 mo or less) telemonitoring. Home telemonitoring using digital/broadband/satellite/wireless or blue-tooth transmission of physiological data reduces all-cause and cardiovascular mortality in heart failure patients. In addition, prolonged telemonitoring (≥ 12 mo) reduces all-cause and heart failure-related hospitalization. The implication for practice is that hospitals considering telemonitoring to reduce heart failure readmission rates may need to plan for prolonged telemonitoring to see the effect they are looking for.

826 NEW THERAPEUTIC PERSPECTIVES IN CARDIAC AMYLOIDOSIS

Abstract Man, 72 years old, smoker, hypertensive and dyslipidemic, came to our clinic suspected of heart disease with a hypertrophic phenotype. In anamnesis there was a recent hospitalization for heart failure in the course of undated atrial fibrillation. During hospitalization because of the presence of antero-septal and lateral QS complexes, a coronary disease was excluded by coronary angiography while the echocardiogram showed a left ventricle with moderate concentric wall thickening, LVEF 38% with a restrictive transmitral pattern. The patient was discharged on therapy with ramipril, bisoprolol, canrenone, furosemide and rivaroxaban with an electrical cardioversion program which had been subsequently ineffective. At the time of the first evaluation the patient was symptomatic of dyspnea in functional class NYHA III, he also reported in anamnesis a progressive reduction of exercise tolerance for about two years and a previous surgery for bilateral carpal tunnel syndrome 5 years earlier. The echocardiogram showed concentric parietal thickening in the presence of granular sparkling, apical sparing, thickening of the valvular apparatus and reduced GLS (- 12%) which led to a suspect of cardiac amyloidosis. To complete the diagnosis, the patient underwent: total-body bone scan with 99-Tc-DPD (Perugini score = 2); assay of serum kappa and lambda light chains (negative), serum and urinary immunofixation (negative), NT-proBNP (980 pg / mL) and a determination of troponin I (32 ng / L) which showed a picture of transthyretin cardiac amyloidosis. The genetic sampling confirmed the presence of the Ile68Leu transthyretin mutation and a neurological evaluation with electromyography ruled out a peripheral polyneuropathy. During follow-up the patient presented a worsening of clinical and instrumental pattern despite the progressive uptitration of diuretic therapy and the addition of metolazone with a simultaneous deterioration of left ventricular dysfunction (LVEF 30%) at echocardiogram. Therefore, the patient's case and possible therapeutic strategies were discussed collectively as it was not possible to access conventional therapies for cardiac amyloidosis with Tafamidis, Inotersen and Patisiran due to the contextual functional class NYHA&amp;gt; II and the absence of polyneuropathy, not it was possible to undertake biventricular resynchronization in the absence of intraventricular block or to implement therapy for heart failure with reduced ejection fraction due to intolerance. As a last option, implantation of a cardiac contractility modulation device (CCM) was proposed and performed via right subclavicular. At the successive follow-up after implantation, the patient showed a slight clinical and instrumental improvement and it was possible to reduce the diuretic dose, discontinuing metolazone. The echocardiogram also showed a slight increase in LVEF (35%). The long-term outpatient evaluation of the patient is currently underway with the aim of undertaking specific therapy with Tafamidis if the prescription criteria are met. Family screening has started. Conclusion the present clinical case represents an example of the application of alternative and potentially effective therapeutic strategies in patients with cardiac amyloidosis not susceptible to conventional pharmacological treatments.