Impact of baseline kidney dysfunction on oral diuretic efficacy following hospitalization for heart failure - insights from TRANSFORM-HF.

AIM: Among patients discharged after hospitalization for heart failure (HF), a strategy of torsemide versus furosemide showed no difference in all-cause mortality or hospitalization. Clinicians have traditionally favoured torsemide in the setting of kidney dysfunction due to better oral bioavailability and longer half-life, but direct supportive evidence is lacking. METHODS AND RESULTS: The TRANSFORM-HF trial randomized patients hospitalized for HF to a long-term strategy of torsemide versus furosemide, and enrolled patients across the spectrum of renal function (without dialysis). In this post-hoc analysis, baseline renal function during the index hospitalization was assessed as categories of estimated glomerular filtration rate (eGFR; <30, 30-<60, ≥60 ml/min/1.73 m2). The interaction between baseline renal function and treatment effect of torsemide versus furosemide was assessed with respect to mortality and hospitalization outcomes, and the change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS). Of 2859 patients randomized, 336 (11.8%) had eGFR <30 ml/min/1.73 m2, 1138 (39.8%) had eGFR 30-<60 ml/min/1.73 m2, and 1385 (48.4%) had eGFR ≥60 ml/min/1.73 m2. Baseline eGFR did not modify treatment effects of torsemide versus furosemide on all adverse clinical outcomes including individual components or composites of all-cause mortality and all-cause (re)-hospitalizations, both when assessing eGFR categorically or continuously (p-value for interaction all >0.108). Similarly, no treatment effect modification by eGFR was found for the change in KCCQ-CSS (p-value for interaction all >0.052) when assessing eGFR categorically or continuously. CONCLUSION: Among patients discharged after hospitalization for HF, there was no significant difference in clinical and patient-reported outcomes between torsemide and furosemide, irrespective of renal function.

Genitourinary Tract Infections in Patients Taking SGLT2 Inhibitors: JACC Review Topic of the Week.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to reduce adverse cardiovascular events in patients with type 2 diabetes mellitus, all-cause mortality, and heart failure hospitalization in patients with heart failure, as well as adverse renal outcomes. However, concerns regarding the heightened risk of genitourinary (GU) infections, particularly urinary tract infections, remain a significant barrier to their wider adoption. Addressing these misconceptions using existing evidence is needed to ensure proper risk-benefit assessment and optimal utilization of this efficacious therapy. This review aims to provide a balanced perspective on the evidence-based cardiovascular and renal benefits of SGLT2is and the associated risk of GU infections. We also summarize and propose clinical practice considerations for SGLT2i-associated GU infections focusing on patients with cardiovascular disease.

Dietary sodium and fluid intake in heart failure. A clinical consensus statement of the Heart Failure Association of the ESC.

Sodium and fluid restriction has traditionally been advocated in patients with heart failure (HF) due to their sodium and water avid state. However, most evidence regarding the altered sodium handling, fluid homeostasis and congestion-related signs and symptoms in patients with HF originates from untreated patient cohorts and physiological investigations. Recent data challenge the beneficial role of dietary sodium and fluid restriction in HF. Consequently, the European Society of Cardiology HF guidelines have gradually downgraded these recommendations over time, now advising for the limitation of salt intake to no more than 5 g/day in patients with HF, while contemplating fluid restriction of 1.5-2 L/day only in selected patients. Therefore, the objective of this clinical consensus statement is to provide advice on fluid and sodium intake in patients with acute and chronic HF, based on contemporary evidence and expert opinion.

Sacubitril/Valsartan in Patients Hospitalized With Decompensated Heart Failure.

BACKGROUND: The efficacy and safety of sacubitril/valsartan in patients hospitalized with heart failure (HF) across the spectrum of left ventricular ejection fraction (EF) has not been described. OBJECTIVES: Data from randomized trials of sacubitril/valsartan in HF patients with EF ≤40% (PIONEER-HF [Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode] trial) and >40% (PARAGLIDE-HF [Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF] trial) following recent worsening heart failure (WHF) were pooled to examine treatment effect across the EF spectrum. METHODS: The PIONEER-HF and PARAGLIDE-HF trials were double-blind, randomized trials of sacubitril/valsartan vs control therapy (enalapril or valsartan, respectively). All participants in the PIONEER-HF trial and 69.5% in the PARAGLIDE-HF trial were enrolled during hospitalization for HF after stabilization. The remainder in the PARAGLIDE-HF trial were enrolled ≤30 days after a WHF event. The primary endpoint of both trials was time-averaged proportional change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline through weeks 4 and 8. Adjudicated clinical endpoints were analyzed through the end of follow-up, adjusting for trial. RESULTS: The pooled analysis included 1,347 patients (881 from PIONEER-HF, 466 from PARAGLIDE-HF). Baseline characteristics included median age 66 years, 36% women, 31% Black, 34% de novo HF, and median EF 30%. The reduction in NT-proBNP was 24% greater with sacubitril/valsartan vs control therapy (n = 1,130; ratio of change = 0.76; 95% CI: 0.69-0.83; P < 0.0001). Cardiovascular death or hospitalization for HF was reduced by 30% with sacubitril/valsartan vs control therapy (HR: 0.70; 95% CI: 0.54-0.91; P = 0.0077). This effect was consistent across the spectrum of EF ≤60%. Sacubitril/valsartan increased symptomatic hypotension (risk ratio: 1.35; 95% CI: 1.05-1.72). CONCLUSIONS: In patients stabilized after WHF, sacubitril/valsartan led to a greater reduction in plasma NT-proBNP and improved clinical outcome compared with control therapy, in particular across the spectrum of EF ≤60%. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890; Changes in NT-proBNP, Safety, and Tolerability in HFpEF Patients With a WHF Event [HFpEF Decompensation] Who Have Been Stabilized and Initiated at the Time of or Within 30 Days Post-decompensation [PARAGLIDE-HF]; NCT03988634).

Sacubitril/Valsartan-Related Hypotension in Patients with Heart Failure and Preserved or Mildly Reduced Ejection Fraction.

BACKGROUND: Hypotension is a potential adverse effect of sacubitril/valsartan, but there are limited data regarding the predictors and implications of treatment-related hypotension in HFmrEF and HFpEF. OBJECTIVES: We investigated predictors of treatment-associated hypotension, clinical outcomes after hypotension, and the relationship between LVEF and incidence of hypotension in the PARAGON-HF trial. METHODS: PARAGON-HF randomized patients with chronic HF (≥45%) to sacubitril/valsartan or valsartan. Following randomization, hypotension was defined as investigator-reported hypotension with a SBP <100 mmHg. Predictors of hypotension were assessed using multivariable Cox models. Associations between hypotension and clinical outcomes were evaluated in time-updated Cox models. The relationship between treatment, LVEF, and incident rates of hypotension and clinical outcomes was estimated using Poisson regression models. RESULTS: Of 4,796 patients in PARAGON-HF, 637 (13%) experienced hypotension, more frequently in the sacubitril/valsartan arm (p<0.001). Following documented hypotension, patients had higher risk of CV death and total HF hospitalizations (adjusted RR 1.63; CI 1.27-2.09; p<0.001) and all-cause death (adjusted HR 1.62; CI 1.28-2.05; p<0.001). LVEF modified the association between sacubitril/valsartan and risk of hypotension (Pinteraction=0.019) such that patients with LVEF≥60% experienced substantially higher treatment-related risks of hypotension. CONCLUSIONS: In PARAGON-HF, a higher LVEF was associated with an increased risk of hypotension in patients treated with sacubitril/valsartan compared with valsartan. Since these subjects are also less likely to derive clinical benefit from sacubitril/valsartan, our data reinforce that the benefit/risk ratio favors the use of sacubitril/valsartan in patients with LVEF below normal, but not at higher LVEF.

Torsemide Versus Furosemide After Discharge in Patients Hospitalized With Heart Failure Across the Spectrum of Ejection Fraction: Findings From TRANSFORM-HF.

BACKGROUND: The TRANSFORM-HF trial (Torsemide Comparison With Furosemide for Management of Heart Failure) found no significant difference in all-cause mortality or hospitalization among patients randomized to a strategy of torsemide versus furosemide following a heart failure (HF) hospitalization. However, outcomes and responses to some therapies differ by left ventricular ejection fraction (LVEF). Thus, we sought to explore the effect of torsemide versus furosemide by baseline LVEF and to assess outcomes across LVEF groups. METHODS: We compared baseline patient characteristics and randomized treatment effects for various end points in TRANSFORM-HF stratified by LVEF: HF with reduced LVEF, ≤40% versus HF with mildly reduced LVEF, 41% to 49% versus HF with preserved LVEF, ≥50%. We also evaluated associations between LVEF and clinical outcomes. Study end points were all-cause mortality or hospitalization at 30 days and 12 months, total hospitalizations at 12 months, and change from baseline in Kansas City Cardiomyopathy Questionnaire clinical summary score. RESULTS: Overall, 2635 patients (median 64 years, 36% female, 34% Black) had LVEF data. Compared with HF with reduced LVEF, patients with HF with mildly reduced LVEF and HF with preserved LVEF had a higher prevalence of comorbidities. After adjusting for covariates, there was no significant difference in risk of clinical outcomes across the LVEF groups (adjusted hazard ratio for 12-month all-cause mortality, 0.91 [95% CI, 0.59-1.39] for HF with mildly reduced LVEF versus HF with reduced LVEF and 0.91 [95% CI, 0.70-1.17] for HF with preserved LVEF versus HF with reduced LVEF; P=0.73). In addition, there was no significant difference between torsemide and furosemide (1) for mortality and hospitalization outcomes, irrespective of LVEF group and (2) in changes in Kansas City Cardiomyopathy Questionnaire clinical summary score in any LVEF subgroup. CONCLUSIONS: Despite baseline demographic and clinical differences between LVEF cohorts in TRANSFORM-HF, there were no significant differences in the clinical end points with torsemide versus furosemide across the LVEF spectrum. There was a substantial risk for all-cause mortality and subsequent hospitalization independent of baseline LVEF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03296813.

Patient Risk-Benefit Preferences for Transcatheter Versus Surgical Mitral Valve Repair.

BACKGROUND: Transcatheter edge-to-edge repair (TEER) of mitral regurgitation is less invasive than surgery but has greater 5-year mortality and reintervention risks, and leads to smaller improvements in physical functioning. The study objective was to quantify patient preferences for risk-benefit trade-offs associated with TEER and surgery. METHODS AND RESULTS: A discrete choice experiment survey was administered to patients with mitral regurgitation. Attributes included procedure type; 30-day mortality risk; 5-year mortality risk and physical functioning for 5 years; number of hospitalizations in the next 5 years; and risk of additional surgery in the next 5 years. A mixed-logit regression model was fit to estimate preference weights. Two hundred one individuals completed the survey: 63% were female and mean age was 74 years. On average, respondents preferred TEER over surgery. To undergo a less invasive procedure (ie, TEER), respondents would accept up to a 13.3% (95% CI, 8.7%-18.5%) increase in reintervention risk above a baseline of 10%, 4.6 (95% CI, 3.1-6.2) more hospitalizations above a baseline of 1, a 10.7% (95% CI, 6.5%-14.5%) increase in 5-year mortality risk above a baseline of 20%, or more limited physical functioning representing nearly 1 New York Heart Association class (0.7 [95% CI, 0.4-1.1]) over 5 years. CONCLUSIONS: Patients in general preferred TEER over surgery. When holding constant all other factors, a functional improvement from New York Heart Association class III to class I maintained over 5 years would be needed, on average, for patients to prefer surgery over TEER.

Diuretic use and outcomes in patients with heart failure with reduced ejection fraction: Insights from the VICTORIA trial.

AIMS: In VICTORIA, vericiguat compared with placebo reduced the risk of cardiovascular death (CVD) and heart failure hospitalization (HFH) in patients enrolled after a worsening heart failure (WHF) event. We examined clinical outcomes and efficacy of vericiguat as it relates to background use of loop diuretics in patients with WHF. METHODS AND RESULTS: We calculated the total daily loop diuretic dose equivalent to furosemide dosing at randomization and categorized these as: no loop diuretic, 1-39, 41-80, 40, and >80 mg total daily dose (TDD). The primary composite outcome of CVD/HFH and its components were evaluated based on TDD loop diuretic and expressed as adjusted hazard ratios with 95% confidence intervals. Post-randomization rates of change in TDD were also examined. Of 4974 patients (98% of the trial) with diuretic dose information available at randomization, 540 (10.8%) were on no loop diuretic, 647 (13.0%) were on 1-39, 1633 (32.8%) were on 40, 1185 (23.8%) were on 41-80, and 969 (19.4%) were on >80 mg TDD. Patients with higher TDD had a higher rate of primary and secondary clinical outcomes. There were no significant interactions with TDD at randomization and efficacy of vericiguat versus placebo for any outcome (all pinteraction > 0.5). Post-randomization diuretic dose changes for vericiguat and placebo showed similar rates of up-titration (19.6 and 20.2/100 person-years), down-titration (16.8 and 18.1/100 person-years), and stopping diuretics (22.9 and 24.2/100 person-years). CONCLUSIONS: Loop diuretic TDD at randomization was independently associated with worse outcomes in this high-risk population. The efficacy of vericiguat was consistent across the range of diuretic doses.

Regional variation in cause of death in patients with type 2 diabetes: Insights from EXSCEL.

AIMS: Type 2 diabetes (T2D) is a risk factor for cardiovascular and non-cardiovascular mortality. However, global distribution of cause-specific deaths in T2D is poorly understood. We characterized cause-specific deaths by geographic region among individuals with T2D at risk for cardiovascular disease (CVD). METHODS AND RESULTS: The international EXSCEL trial included 14,752 participants with T2D (73% with established CVD). We identified the proportion of deaths over 5-year follow-up attributed to cardiovascular and non-cardiovascular causes, and associated risk factors. During median 3.2-year follow-up, 1,091 (7.4%) participants died. Adjudicated causes of death were 723 cardiovascular (66.3% of deaths), including 252 unknown, and 368 non-cardiovascular (33.7%). Most deaths occurred in North America (N = 356/9.6% across region) and Eastern Europe (N = 326/8.1%), with fewest in Asia/Pacific (N = 68/4.4%). The highest proportional cause-specific deaths by region were sudden cardiac in Asia/Pacific (23/34% of regional deaths) and North America (86/24%); unknown in Eastern Europe (90/28%) and Western Europe (39/21%); and non-malignant non-cardiovascular in Latin America (48/31%). Cox proportional hazards model for adjudicated causes of death showed prognostic risk factors (hazard ratio [95% CI]) for cardiovascular and non-cardiovascular deaths, respectively: heart failure 2.04 (1.72-2.42) and 1.86 (1.46-2.39); peripheral artery disease 1.83 (1.54-2.18) and 1.78 (1.40-2.26); and current smoking status 1.61 (1.29-2.01) and 1.77 (1.31-2.40). CONCLUSIONS: In a contemporary T2D trial population, with and without established CVD, leading causes of death varied by geographic region. Underlying mechanisms leading to variability in cause of death across geographic regions and its impact on clinical trial endpoints warrant future research.

Recurrent Hospitalizations and Response to Vericiguat in Heart Failure and Reduced Ejection Fraction.

BACKGROUND: In VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction), vericiguat compared with placebo reduced cardiovascular death or heart failure (HF) hospitalization in patients with HF with reduced ejection fraction. OBJECTIVES: This study explored the association between vericiguat and recurrent hospitalizations and subsequent mortality after HF hospitalization. METHODS: The treatment effect of vericiguat on the burden of HF hospitalizations was evaluated by assessing total HF hospitalization and cardiovascular death in the overall trial and based on baseline N-terminal pro-B-type natriuretic peptide levels with and without adjustment for VICTORIA model covariates (ie, baseline variables associated with the primary endpoint) assessed via the Andersen-Gill method. Associations between vericiguat and recurrent hospitalization and mortality adjusted for VICTORIA model covariates are reported. RESULTS: There were 1,222 total HF hospitalizations and cardiovascular deaths among 2,526 patients in the vericiguat group and 1,336 total events among 2,524 patients in the placebo group (unadjusted HR: 0.89 [95% CI: 0.81-0.97] and adjusted HR: 0.92 [95% CI: 0.84-1.01]). In the subgroup with N-terminal pro-B-type natriuretic peptide levels ≤2,816 pg/mL (ie, Q1 and Q2; median or below), there was a suggestion of a benefit with vericiguat (adjusted HRs of 0.80 [95% CI: 0.64-1.01] and 0.77 [95% CI: 0.62-0.94], respectively) compared with those above this value (adjusted HRs of 1.12 [95% CI: 0.93-1.34] and 0.87 [95% CI: 0.74-1.04] for Q3 and Q4). There was no significant difference in treatment effect between patients with vs without an HF hospitalization. After HF hospitalization, the all-cause mortality rate (events per 100 patient-years) was 48.6 for vericiguat and 44.1 for placebo. CONCLUSIONS: Additional investigation of the association between vericiguat and cardiovascular death and total HF hospitalizations by recurrent event analysis did not show a statistically significant reduction in events. Mortality was high after HF hospitalization, emphasizing the need for further therapies to reduce morbidity and mortality. (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction [VICTORIA]; NCT02861534).

Hierarchical End Points in Prior Heart Failure Trials and the HEART-FID Trial.

BACKGROUND: Clinical trials in heart failure (HF) traditionally use time-to-event analyses focusing on death and hospitalization for HF. These time-to-first event analyses may have more limited abilities to assess the probability of benefiting from a therapy, especially if that benefit manifests as improved functional status rather than reduced risk of death or HF hospitalization. Hierarchical end points including clinical outcomes and patient status measures allow for ranked evaluation of outcomes in 1 metric assessing whether patients randomized to intervention or control are more likely to derive an overall benefit while also allowing more patients to contribute to the primary outcome. METHODS: We review the rationale for using hierarchical end points in HF trials, provide examples of HF trials that used this type of end point, and discuss its use in the HEART-FID trial (Randomized Placebo-Controlled Trial of Ferric Carboxymaltose as Treatment for Heart Failure With Iron Deficiency), the largest HF trial to date implementing a hierarchical end point analysis for the primary outcome. RESULTS: Using a hierarchical end point as the primary outcome allows for the inclusion of different types of outcomes in 1 ranked end point, making it possible to more holistically assess the potential utility of a new therapy on patient well-being and outcomes. CONCLUSIONS: Hierarchical end points assess the potential utility of a new therapy on patient well-being and outcome more holistically than time-to-first event analysis. Trials that would not have been feasible due to decreasing rates of death and hospitalization in the HF population can use hierarchical end points to successfully power studies to identify promising HF therapies. The HEART-FID trial used hierarchical end points to better determine the role of intravenous ferric carboxymaltose in patients with HF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03037931.

Torsemide vs Furosemide Among Patients With New-Onset vs Worsening Chronic Heart Failure: A Substudy of the TRANSFORM-HF Randomized Clinical Trial.

Importance: Differences in clinical profiles, outcomes, and diuretic treatment effects may exist between patients with de novo heart failure (HF) and worsening chronic HF (WHF). Objectives: To compare clinical characteristics and treatment outcomes of torsemide vs furosemide in patients hospitalized with de novo HF vs WHF. Design, Setting, and Participants: All patients with a documented ejection fraction who were randomized in the Torsemide Comparison With Furosemide for Management of Heart Failure (TRANSFORM-HF) trial, conducted from June 18 through March 2022, were included in this post hoc analysis. Study data were analyzed March to May 2023. Exposure: Patients were categorized by HF type and further divided by loop diuretic strategy. Main Outcomes and Measures: End points included all-cause mortality and hospitalization outcomes over 12 months, as well as change from baseline in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). Results: Among 2858 patients (mean [SD] age, 64.5 [14.0] years; 1803 male [63.1%]), 838 patients (29.3%) had de novo HF, and 2020 patients (70.7%) had WHF. Patients with de novo HF were younger (mean [SD] age, 60.6 [14.5] years vs 66.1 [13.5] years), had a higher glomerular filtration rate (mean [SD], 68.6 [24.9] vs 57.0 [24.0]), lower levels of natriuretic peptides (median [IQR], brain-type natriuretic peptide, 855.0 [423.0-1555.0] pg/mL vs 1022.0 [500.0-1927.0] pg/mL), and tended to be discharged on lower doses of loop diuretic (mean [SD], 50.3 [46.2] mg vs 63.8 [52.4] mg). De novo HF was associated with lower all-cause mortality at 12 months (de novo, 65 of 838 [9.1%] vs WHF, 408 of 2020 [25.4%]; adjusted hazard ratio [aHR], 0.50; 95% CI, 0.38-0.66; P < .001). Similarly, lower all-cause first rehospitalization at 12 months and greater improvement from baseline in KCCQ-CSS at 12 months were noted among patients with de novo HF (median [IQR]: de novo, 29.94 [27.35-32.54] vs WHF, 23.68 [21.62-25.74]; adjusted estimated difference in means: 6.26; 95% CI, 3.72-8.81; P < .001). There was no significant difference in mortality with torsemide vs furosemide in either de novo (No. of events [rate per 100 patient-years]: torsemide, 27 [7.4%] vs furosemide, 38 [10.9%]; aHR, 0.70; 95% CI, 0.40-1.14; P = .15) or WHF (torsemide 212 [26.8%] vs furosemide, 196 [24.0%]; aHR, 1.08; 95% CI, 0.89-1.32; P = .42; P for interaction = .10), In addition, no significant differences in hospitalizations, first all-cause hospitalization, or total hospitalizations at 12 months were noted with a strategy of torsemide vs furosemide in either de novo HF or WHF. Conclusions and Relevance: Among patients discharged after hospitalization for HF, de novo HF was associated with better clinical and patient-reported outcomes when compared with WHF. Regardless of HF type, there was no significant difference between torsemide and furosemide with respect to 12-month clinical or patient-reported outcomes.

The HFSA Advanced Heart Failure and Transplant Cardiology Fellowship Consensus Conference.

There is waning interest among cardiology trainees in pursuing an Advanced Heart Failure/Transplant Cardiology (AHFTC) fellowship as evidenced by fewer applicants in the National Resident Matching Program match to this specialty. This trend has generated considerable attention across the heart failure community. In response, the Heart Failure Society of America convened the AHFTC Fellowship Task Force with a charge to develop strategies to increase the value proposition of an AHFTC fellowship. Subsequently, the HFSA sponsored the AHFTC Fellowship Consensus Conference April 26-27, 2023. Before the conference, interviews of 44 expert stakeholders diverse across geography, site of practice (traditional academic medical center or other centers), specialty/area of expertise, sex, and stage of career were conducted virtually. Based on these interviews, potential solutions to address the declining interest in AHFTC fellowship were categorized into five themes: (1) alternative training pathways, (2) regulatory and compensation, (3) educational improvements, (4) exposure and marketing for pipeline development, and (5) quality of life and mental health. These themes provided structure to the deliberations of the AHFTC Fellowship Consensus Conference. The recommendations from the Consensus Conference were subsequently presented to the HFSA Board of Directors to inform strategic plans and interventions. The HFSA Board of Directors later reviewed and approved submission of this document. The purpose of this communication is to provide the HF community with an update summarizing the processes used and concepts that emerged from the work of the HFSA AHFTC Fellowship Task Force and Consensus Conference.

Standardized Definitions for Evaluation of Acute Decompensated Heart Failure Therapies: HF-ARC Expert Panel Paper.

Acute decompensated heart failure (ADHF) is one of the most common reasons for hospitalizations or urgent care and is associated with poor outcomes. Therapies shown to improve outcomes are limited, however, and innovation in pharmacologic and device-based therapeutics are therefore actively being sought. Standardizing definitions for ADHF and its trajectory is complex, limiting the generalizability and translation of clinical trials to effect clinical care and policy change. The Heart Failure Collaboratory is a multistakeholder organization comprising clinical investigators, clinicians, patients, government representatives (including U.S. Food and Drug Administration and National Institutes of Health participants), payors, and industry collaborators. The following expert consensus document is the product of the Heart Failure Collaboratory convening with the Academic Research Consortium, including members from academia, the U.S. Food and Drug Administration, and industry, for the purposes of proposing standardized definitions for ADHF and highlighting important endpoint considerations to inform the design and conduct of clinical trials for drugs and devices in this clinical arena.

Costs of care and financial hardship among patients with heart failure.

With the implementation of new therapies, more patients are living with heart failure (HF) as a chronic condition. Alongside these advances, out-of-pocket (OOP) medical costs have increased, and patients experience significant financial burden. Despite increasing interest in understanding and mitigating financial burdens, there is a relative paucity of data specific to HF. Here, we explore financial hardship in HF from the patient perspective, including estimated OOP costs for guideline-directed medical therapy for HF with reduced ejection fraction, hospitalizations, and total direct medical costs, as well as the consequences of high OOP costs. Studies estimate that high OOP costs are common in HF, and a large proportion are related to prescription drugs. Subsequently, the effects on patients can lead to worsening adherence, delayed care, and poor outcomes, leading to a financial toxicity spiral. Further, we summarize patients' cost preferences and outline future research that is needed to develop evidence-based solutions to reduce costs in HF.

Improving Guideline-Directed Medical Therapy for Patients With Heart Failure With Reduced Ejection Fraction: A Review of Implementation Strategies.

Despite recent advances in the use of guideline-directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF), achievement of target GDMT use and up-titration to goal dosages continue to be modest. In recent years, a number of interventional approaches to improve the usage of GDMT have been published, but many are limited by single-center experiences with small sample sizes. However, strategies including the use of multidisciplinary teams, dedicated GDMT titration algorithms and clinician audits with feedback have shown promise. There remains a critical need for large, rigorous trials to assess the utility of differing interventions to improve the use and titration of GDMT in HFrEF. Here, we review existing literature in GDMT implementation for those with HFrEF and discuss future directions and considerations in the field.