The Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure with Preserved Ejection Fraction (SPIRRIT-HFpEF): Rationale and design.

AIMS: Benefits of mineralocorticoid receptor antagonists (MRAs) in heart failure with preserved and mildly reduced ejection fraction (HFpEF/HFmrEF) have not been established. Conventional randomized controlled trials are complex and expensive. The Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure with Preserved Ejection Fraction (SPIRRIT-HFpEF) is a unique pragmatic registry-based randomized controlled trial. METHODS: SPIRRIT-HFpEF is a multicentre, prospective, randomized, open-label, blinded endpoint trial conducted on platforms in the Swedish Heart Failure Registry (SwedeHF) and the United States (US) Trial Innovation Network. Patients with HFpEF/HFmrEF are randomized 1:1 to spironolactone (or eplerenone) in addition to usual care, versus usual care alone. The primary outcome is total number of cardiovascular deaths and hospitalizations for heart failure. Outcomes are collected from Swedish administrative complete coverage registries and a US call centre and subsequently adjudicated. Simple eligibility criteria were based on data available in SwedeHF: heart failure as outpatient or at discharge from hospital, left ventricular ejection fraction ≥40%, N-terminal pro-B-type natriuretic peptide >300 ng/L (in sinus rhythm) or >750 ng/L (in atrial fibrillation), with pre-specified adjustment for elevated body mass index, and chronic loop diuretic use. Power and sample size assessments were based on an event-driven design allowing enrolment over approximately 6 years, and application of hazard ratios from the TOPCAT trial, Americas subset. The final sample size is expected to be approximately 2400 patients. CONCLUSION: SPIRRIT-HFpEF will be informative on the effectiveness of generic MRAs in HFpEF and HFmrEF, and on the feasibility of conducting pragmatic and registry-based trials in heart failure and other chronic conditions.

Late Follow-up for a Randomized Trial of Surgical Treatment of Tricuspid Valve Regurgitation in Patients Undergoing Left Ventricular Assist Device Implantation.

OBJECTIVES: We previously reported that concurrent tricuspid valve surgery (TVS) was not associated with a lower incidence of early RHF among patients undergoing durable LVAD implantation. This is a follow-up analysis to further define the clinical impact of concurrent TVS within 12-months of follow-up. METHODS: Patients with moderate or severe TR on pre-operative echocardiography (n=71) were randomized to either LVAD implantation alone (No TVS, n=34) or with concurrent TVS (TVS, n=37). Randomization was stratified by pre-operative right ventricular dysfunction. Patients were followed for at least 12-months after surgery. The incidence of RHF was determined using INTERMACS criteria by an adjudication committee. Functional studies and repeat echocardiography were performed at 12-months. RESULTS: Demographics were similar between the two arms. At 12-months, the rate of moderate or severe RHF was 50.0% (No TVS) versus 51.4% (TVS). No patients developed RHF between 6- and 12-months following the procedure. Death from RHF was 5.4% (TVS) versus 8.8% (No TVS). At 12-months, there was no significant difference in TR severity between the two arms due to improvement in TR severity in the No TVS arm. On cardiopulmonary exercise testing at 12+ months, there was no significant difference in peak oxygen consumption. CONCLUSIONS: In patients with significant pre-implant TR, the severity of TR improved over time in the LVAD implantation alone arm. By 12-months, there is no significant difference in TR severity between the two arms. This may account for the lack of difference in late clinical or functional parameters.

Surveillance and Alert-Based Multiparameter Monitoring to reduce Worsening Heart Failure Events: Results from SCALE-HF 1.

BACKGROUND: There is a need for better noninvasive remote monitoring solutions that prevent hospitalizations through the early prediction and management of heart failure (HF). SCALE-HF 1 evaluated the performance of a novel Congestion Index that alerts to fluid accumulation preceding HF events. METHODS: SCALE-HF 1 was a multicenter, prospective, observational study investigating HF event prediction using data from the Cardiac Scale. Participants with HF took measurements at home by standing barefoot on the scale for approximately 20 seconds each day. The Congestion Index was applied retrospectively, and an alert was generated when the index exceeded a fixed threshold established in prior studies. HF events, defined as unplanned administration of IV diuretics or admissions with a primary diagnosis of HF. Sensitivity was defined as the ratio of correctly identified HF events to the total number of HF events. RESULTS: 329 participants were enrolled (mean age 64±14 years; 43% women; 32% black; 56% with reduced ejection fraction) across 8 sites with 238 participant-years of follow-up and 69 usable HF events. The Congestion Index predicted 48 of the 69 HF events (70%) at 2.58 alerts per participant-year. In contrast, the standard weight rule (weight gain exceeds 3lb in 1 day or 5lb in 7 days) predicted only 24 of the 69 HF events (35%) at 4.18 alerts per participant-year. The Congestion Index alerts had a significantly higher sensitivity (p<0.01) at a lower alert rate than the standard weight rule. CONCLUSIONS: The Congestion Index alerts demonstrated sensitive prediction of HF events at a low alert rate, significantly exceeding the performance of weight-based monitoring. GOV IDENTIFIER: NCT04882449.

Feasibility of a Multidomain Resiliency Assessment in Patients with Advanced Heart Failure Requiring Surgery: A Pilot Study.

OBJECTIVE: The resiliency of patients who have advanced heart failure (HF) and undergo a physical stressor such as heart transplantation or left ventricular assist device implantation has yet to be studied in the physical, cognitive, and psychosocial domains. The primary aim of this pilot study was to assess the feasibility of a multidomain resiliency assessment in patients who have advanced HF and require surgery. METHODS: A battery of assessments in each of the domains was completed at baseline before surgical intervention, after intensive care discharge, and 3 and 6 months after surgery. Feasibility was assessed through completion rates, time required to complete the assessments, and qualitative feedback from assessors. RESULTS: Although various completion rates were noted at different time points, high completion rates were seen for grip strength, the modified Fried frailty phenotype, and the Montreal Cognitive Assessment. Additionally, when controlled for patients who were medically restricted from physical function, the Short Physical Performance Battery, gait speed, and the 30-second chair stand test also had high completion rates. A trend toward return to baseline status or an improvement in baseline status was observed in all physical and cognitive assessments and most psychosocial assessments at 3 and 6 months. Minimal change was noted in the Brief Resilience Scale questionnaire. CONCLUSION: This pilot study demonstrates that a multidomain assessment of resiliency is feasible in patients with advanced HF. Future studies are needed to help determine specific assessments or patient factors that would help predict positive postsurgical outcomes in this population. IMPACT: This study has implications for clinical practice on the most feasible assessments in multiple domains for patients who have advanced HF and are being evaluated for heart transplantation or left ventricular assist device.

Early U.S. Heart Transplant Experience With Normothermic Regional Perfusion Following Donation After Circulatory Death.

BACKGROUND: Heart transplantation following donation after circulatory death (DCD HT) has short-term survival outcomes comparable to donation after brain death and has led to a significant increase in transplantation volume. The U.S. experience with the normothermic regional perfusion (NRP) DCD HT procurement method has not been evaluated. OBJECTIVES: The aim of this study was to examine short-term outcomes associated with NRP vs direct procurement and perfusion (DPP) methods used during DCD HT in the United States. METHODS: The UNOS (United Network for Organ Sharing) registry was queried for all adult (age ≥18 years) heart recipients and corresponding donors of controlled DCD HT from January 2019-December 2023. Transplantations were stratified by NRP or DPP reperfusion methods. The primary outcome was overall survival. RESULTS: A total of 918 heart donors and recipients met inclusion criteria, including 622 (68%) DPP and 296 (32%) NRP transplantations. Unadjusted Kaplan-Meier survival analysis demonstrated improved short-term survival associated with NRP (log-rank P = 0.005). After adjustment, DCD HT with NRP was independently associated with improved survival (HR: 0.39 [95% CI: 0.22-0.70]; P = 0.002). A propensity-matched analysis similarly demonstrated a cumulative survival benefit to NRP (log-rank P = 0.006). CONCLUSIONS: In this largest national series of DCD HT procurement perfusion strategies, NRP is associated with improved short-term survival as compared with DPP. This study evaluates the U.S. early experience with DCD HT, and longer-term follow-up data are needed to further assess the impact of DPP and NRP methods on post-heart transplantation outcomes.

Optimal Medical Therapy and Outcomes Among Patients With Chronic Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Optimal medical therapy (OMT) scoring may stratify clinical risk in real-world chronic heart failure with reduced ejection fraction (HFrEF) by integrating use and dosing of guideline-directed medical therapy (GDMT) for HFrEF. OBJECTIVES: The purpose of this study was to characterize patients and associated long-term clinical outcomes by OMT score-derived treatment groups. METHODS: CHAMP-HF (Change the Management of Patients with Heart Failure) included U.S. outpatients with chronic HFrEF receiving ≥1 GDMT. OMT subgroups were defined as suboptimal (score <3), acceptable (score = 3), and optimal (score ≥4) by baseline use and dose of GDMT, as proposed by the HF Collaboratory consortium. Cox proportional hazard analyses were used to assess for all-cause and cardiovascular death across subgroups, after adjusting for demographic and clinical covariates. RESULTS: The authors studied 4,582 participants enrolled in CHAMP-HF with available 2-year follow-up. Median age was 68 years, 1,327 (29%) were women, and 2,842 (62%) were White, non-Hispanic. Median OMT score across the population was 4 (Q1-Q3: 2-5), and 1,628 (35%) had suboptimal, 665 (14%) had acceptable, and 2,289 (50%) had optimal therapy. Participants with optimal treatment were younger, had higher annual household income, and were enrolled from practices with dedicated HF clinics (all P < 0.001) than participants with acceptable or suboptimal treatment. Participants with optimal treatment had lower all-cause death (adjusted HR: 0.77; 95% CI: 0.64-0.92) and cardiovascular death (adjusted HR: 0.79; 95% CI: 0.65-0.96) than those with suboptimal treatment. CONCLUSIONS: Across a large cohort of chronic ambulatory HFrEF, OMT scores stratified risk of all-cause and cardiovascular death.

Association of Medication Adherence and Health Status in Heart Failure With Reduced Ejection Fraction: Insights From the CHAMP-HF Registry.

BACKGROUND: The foundation for managing heart failure with reduced ejection fraction (HFrEF) is adherence to guideline-directed medical therapy. Finding an association between medication adherence and patients' health status (their symptoms, function, and quality of life) can be used to underscore its importance to patients. METHODS: The association of self-reported medication adherence in US outpatients with HFrEF enrolled in the Change the Management of Patients with Heart Failure registry from 2015 to 2017 was compared with their health status at baseline and 12 months later. A secondary analysis of changes in adherence between baseline and 6 months with 6-month health status was also performed. Medication adherence was assessed with the self-reported 4-item Morisky-Green-Levine Medication Adherence Scale, with scores ≥1 classified as nonadherent. The primary health status outcome was the disease-specific 12-item Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS; range, 0-100; higher is better). Robust linear regression models adjusted for confounders were used. RESULTS: After excluding those who died (n=316) or did not provide 12-month KCCQ (n=1285), 3495 outpatients with HFrEF were included, of whom 1108 (31.7%) reported being nonadherent. Nonadherent participants were younger, had significantly worse baseline health status (-5.83-point difference; P<0.001), and showed less improvement at 12 months (-1.7-point difference in mean change; P=0.017) than adherent participants. Among nonadherent patients at baseline, those whose adherence improved trended toward greater 6-month health status improvements than those remaining nonadherent (fully adjusted difference of 2.52 points; P=0.054). CONCLUSIONS: In HFrEF, medication nonadherence was associated with worse health status and less improvement over the following year. Improvements in adherence were associated with better health status than remaining nonadherent, underscoring the importance of supporting adherence with guideline-directed medical therapy in patients with HFrEF.

Implications of trial eligibility in patients with heart failure with mildly reduced or preserved ejection fraction.

AIMS: Clinical trials in heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) commonly have detailed eligibility criteria. This may contribute to challenges with efficient enrolment and questions regarding the generalizability of trial findings. METHODS AND RESULTS: Patients with HFmrEF/HFpEF from a large US healthcare system were identified through a computable phenotype applied in linked imaging and electronic health record databases. We evaluated shared eligibility criteria from five recent/ongoing HFmrEF/HFpEF trials (PARAGON-HF, EMPEROR-Preserved, DELIVER, FINE-ARTS, and SPIRRIT-HFpEF) and compared clinical and echocardiographic features as well as outcomes between trial-eligible and trial-ineligible patients. Among 5552 patients with HFpEF/HFmrEF, 792 (14%) were eligible for trial consideration, having met all criteria assessed. Causes of ineligibility included lack of recent loop diuretics (37%), significant pulmonary disease (24%), reduced estimated glomerular filtration rate (17%), recent stroke/transient ischaemic attack (13%), or low natriuretic peptides (12%); 53% of ineligible patients had >1 reason for exclusion. Compared with eligible patients, ineligible patients were younger (age 71 vs. 75 years, P < 0.001) with higher rates of coronary artery disease (66% vs. 59%, P < 0.001) and peripheral vascular disease (40% vs. 33%, P < 0.001), but less mitral regurgitation, lower E/e' ratio, and smaller left atrial sizes. Both eligible and ineligible patients demonstrated high rates of structural heart disease consistent with HFpEF [elevated left atrial size or left ventricular (LV) hypertrophy/increased LV mass], although this was slightly higher among eligible patients (95% vs. 92%, P = 0.001). The two cohorts demonstrated similar LV global longitudinal strain along with a similar prevalence of atrial fibrillation/flutter, hypertension, and obesity. Ineligible patients had similar all-cause mortality (33% vs. 33% at 3 years) to those eligible but lower rates of heart failure hospitalization (20% vs. 28% at 3 years, P < 0.001). CONCLUSIONS: Among patients with HFmrEF/HFpEF from a large health system, approximately one in seven were eligible for major trials based on key criteria applied through a clinical computable phenotype. These findings highlight the large proportion of patients with HFmrEF/HFpEF ineligible for contemporary trials for whom the generalizability of trial findings may be questioned and further investigation would be beneficial.

Generalizable Approach to Quantifying Guideline-Directed Medical Therapy.

BACKGROUND: Quantifying guideline-directed medical therapy (GDMT) intensity is foundational for improving heart failure (HF) care. Existing measures discount dose intensity or use inconsistent weighting. METHODS: The Kansas City Medical Optimization (KCMO) score is the average of total daily to target dose percentages for eligible GDMT, reflecting the percentage of optimal GDMT prescribed (range, 0-100). In Change the Management of Patients With HF, we computed KCMO, HF collaboratory (0-7), and modified HF Collaboratory (0-100) scores for each patient at baseline and for 1-year change in established GDMT at the time (mineralocorticoid receptor antagonist, ß-blocker, ACE [angiotensin-converting enzyme] inhibitor/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitor). We compared baseline and 1-year change distributions and the coefficient of variation (SD/mean) across scores. RESULTS: Among 4532 patients at baseline, mean KCMO, HF collaboratory, and modified HF Collaboratory scores were 38.8 (SD, 25.7), 3.4 (1.7), and 42.2 (22.2), respectively. The mean 1-year change (n=4061) for KCMO was -1.94 (17.8); HF collaborator, -0.11 (1.32); and modified HF Collaboratory, -1.35 (19.8). KCMO had the highest coefficient of variation (0.66), indicating greater variability around the mean than the HF collaboratory (0.49) and modified HF Collaboratory (0.53) scores, reflecting higher resolution of the variability in GDMT intensity across patients. CONCLUSIONS: KCMO measures GDMT intensity by incorporating dosing and treatment eligibility, provides more granularity than existing methods, is easily interpretable (percentage of ideal GDMT), and can be adapted as performance measures evolve. Further study of its association with outcomes and its usefulness for quality assessment and improvement is needed.

Kidney Outcomes Among Medicare Beneficiaries After Hospitalization for Heart Failure.

Importance: Kidney health has received increasing focus as part of comprehensive heart failure (HF) treatment efforts. However, the occurrence of clinically relevant kidney outcomes in contemporary populations with HF has not been well studied. Objective: To examine rates of incident dialysis and acute kidney injury (AKI) among Medicare beneficiaries after HF hospitalization. Design, Setting, and Participants: This retrospective cohort study evaluated adults aged 65 years or older who were hospitalized for HF across 372 sites in the Get With The Guidelines-Heart Failure registry in the US between January 1, 2014, and December 31, 2018. Patients younger than 65 years or requiring dialysis either during or prior to hospitalization were excluded. Data were analyzed from May 4, 2021, to March 8, 2024. Main Outcomes and Measures: The primary outcome was inpatient dialysis initiation in the year after HF hospitalization and was ascertained via linkage with Medicare claims data. Other all-cause and cause-specific hospitalizations were also evaluated. The covariate-adjusted association between discharge estimated glomerular filtration rate (eGFR) and 1-year postdischarge outcomes was examined using Cox proportional hazards regression models. Results: Overall, among 85 298 patients included in the analysis (mean [SD] age, 80 [9] years; 53% women) mean (SD) left ventricular ejection fraction was 47% (16%) and mean (SD) eGFR was 53 (29) mL/min per 1.73 m2; 54 010 (63%) had an eGFR less than 60 mL/min per 1.73 m2. By 1 year after HF hospitalization, 6% had progressed to dialysis, 7% had progressed to dialysis or end-stage kidney disease, and 7% had been readmitted for AKI. Incident dialysis increased steeply with lower discharge eGFR category: compared with patients with an eGFR of 60 mL/min per 1.73 m2 or more, individuals with an eGFR of 45 to less than 60 and of less than 30 mL/min per 1.73 m2 had higher rates of dialysis readmission (45 to <60: adjusted hazard ratio [AHR], 2.16 [95% CI, 1.86-2.51]; <30: AHR, 28.46 [95% CI, 25.25-32.08]). Lower discharge eGFR (per 10 mL/min per 1.73 m2 decrease) was independently associated with a higher rate of readmission for dialysis (AHR, 2.23; 95% CI, 2.14-2.32), dialysis or end-stage kidney disease (AHR, 2.34; 95% CI, 2.24-2.44), and AKI (AHR, 1.25; 95% CI, 1.23-1.27), with similar findings for all-cause mortality, all-cause readmission, and HF readmission. Baseline left ventricular ejection fraction did not modify the covariate-adjusted association between lower discharge eGFR and kidney outcomes. Conclusions and Relevance: In this study, older adults with HF had substantial risk of kidney complications, with an estimated 6% progressing to dialysis in the year after HF hospitalization. These findings emphasize the need for health care approaches prioritizing kidney health in this high-risk population.

Cause-Specific Health Care Costs Following Hospitalization for Heart Failure and Cost Offset With SGLT2i Therapy.

BACKGROUND: Little is known regarding differences in cause-specific costs between heart failure (HF) with ejection fraction (EF) ≤40% vs >40%, and potential cost implications of sodium glucose co-transporter 2 inhibitor (SGLT2i) therapy. OBJECTIVES: This study sought to compare cause-specific health care costs following hospitalization for HF with EF ≤40% vs >40% and estimate the cost offset with implementation of SGLT2i therapy. METHODS: This study examined Medicare beneficiaries hospitalized for HF in the Get With The Guidelines-Heart Failure registry from 2016 to 2020. Mean per-patient total (excluding drug costs) and cause-specific costs from discharge through 1-year follow-up were calculated and compared between EF ≤40% vs >40%. Next, risk reductions on total all-cause and HF hospitalizations were estimated in a trial-level meta-analysis of 5 pivotal trials of SGLT2is in HF. Finally, these relative treatment effects were applied to Medicare beneficiaries eligible for SGLT2i therapy to estimate the projected cost offset with implementation of SGLT2i, excluding drug costs. RESULTS: Among 146,003 patients, 50,598 (34.7%) had EF ≤40% and 95,405 (65.3%) had EF >40%. Mean total cost through 1 year was $40,557. Total costs were similar between EF groups overall but were higher for EF ≤40% among patients surviving the 1-year follow-up period. Patients with EF >40% had higher costs caused by non-HF and noncardiovascular hospitalizations, and skilled nursing facilities (all P < 0.001). Trial-level meta-analysis of the 5 SGLT2i clinical trials estimated 11% (rate ratio: 0.89; 95% CI: 0.84-0.93; P < 0.001) and 29% (rate ratio: 0.71; 95% CI: 0.66-0.76; P < 0.001) relative reductions in rates of total all-cause and HF hospitalizations, respectively, regardless of EF. Reductions in all-cause and HF hospitalizations were projected to reduce annual costs of readmission by $2,451 to $2,668 per patient with EF ≤40% and $1,439 to $2,410 per patient with EF >40%. CONCLUSIONS: In this large cohort of older U.S. adults hospitalized for HF, cause-specific costs of care differed among patients with EF ≤40% vs >40%. SGLT2i significantly reduced the rate of HF and all-cause hospitalizations irrespective of EF in clinical trials, and implementation of SGLT2i therapy in clinical practice is projected to reduce costs by $1,439 to $2,668 per patient over the 1 year post-discharge, excluding drug costs.

Remote Follow-up in a Heart Failure Pragmatic Trial: Insights From the CONNECT-HF.

BACKGROUND: Randomized controlled trials typically require study-specific visits, which can burden participants and sites. Remote follow-up, such as centralized call centers for participant-reported or site-reported, holds promise for reducing costs and enhancing the pragmatism of trials. In this secondary analysis of the CONNECT-HF (Care Optimization Through Patient and Hospital Engagement For HF) trial, we aimed to evaluate the completeness and validity of the remote follow-up process. METHODS AND RESULTS: The CONNECT-HF trial evaluated the effect of a post-discharge quality-improvement intervention for heart failure compared to usual care for up to 1 year. Suspected events were reported either by participants or by health care proxies through a centralized call center or by sites through medical-record queries. When potential hospitalization events were suspected, additional medical records were collected and adjudicated. Among 5942 potential hospitalizations, 18% were only participant-reported, 28% were reported by both participants and sites, and 50% were only site-reported. Concordance rates between the participant/site reports and adjudication for hospitalization were high: 87% participant-reported, 86% both, and 86% site-reported. Rates of adjudicated heart failure hospitalization events among adjudicated all-cause hospitalization were lower but also consistent: 45% participant-reported, 50% both, and 50% site-reported. CONCLUSIONS: Participant-only and site-only reports missed a substantial number of hospitalization events. We observed similar concordance between participant/site reports and adjudication for hospitalizations. Combining participant-reported and site-reported outcomes data is important to capture and validate hospitalizations effectively in pragmatic heart failure trials.

Early Outcomes in Patients With LVAD Undergoing Heart Transplant via Use of the SherpaPak Cardiac Transport System.

BACKGROUND: Heart transplant (HT) in recipients with left ventricular assist devices (LVADs) is associated with poor early post-HT outcomes, including primary graft dysfunction (PGD). As complicated heart explants in recipients with LVADs may produce longer ischemic times, innovations in donor heart preservation may yield improved post-HT outcomes. The SherpaPak Cardiac Transport System is an organ preservation technology that maintains donor heart temperatures between 4 °C and 8 °C, which may minimize ischemic and cold-induced graft injuries. This analysis sought to identify whether the use of SherpaPak versus traditional cold storage was associated with differential outcomes among patients with durable LVAD undergoing HT. METHODS: Global Utilization and Registry Database for Improved Heart Preservation-Heart (NCT04141605) is a multicenter registry assessing post-HT outcomes comparing 2 methods of donor heart preservation: SherpaPak versus traditional cold storage. A retrospective review of all patients with durable LVAD who underwent HT was performed. Outcomes assessed included rates of PGD, post-HT mechanical circulatory support use, and 30-day and 1-year survival. RESULTS: SherpaPak (n=149) and traditional cold storage (n=178) patients had similar baseline characteristics. SherpaPak use was associated with reduced PGD (adjusted odds ratio, 0.56 [95% CI, 0.32-0.99]; P=0.045) and severe PGD (adjusted odds ratio, 0.31 [95% CI, 0.13-0.75]; P=0.009), despite an increased total ischemic time in the SherpaPak group. Propensity matched analysis also noted a trend toward reduced intensive care unit (SherpaPak 7.5±6.4 days versus traditional cold storage 11.3±18.8 days; P=0.09) and hospital (SherpaPak 20.5±11.9 days versus traditional cold storage 28.7±37.0 days; P=0.06) lengths of stay. The 30-day and 1-year survival was similar between groups. CONCLUSIONS: SherpaPak use was associated with improved early post-HT outcomes among patients with LVAD undergoing HT. This innovation in preservation technology may be an option for HT candidates at increased risk for PGD. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04141605.

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).

Role of telemedicine in the management of obesity: State-of-the-art review.

Obesity is a worsening public health epidemic that remains challenging to manage. Obesity substantially increases the risk of cardiovascular diseases and presents a significant financial burden on the healthcare system. Digital health interventions, specifically telemedicine, may offer an attractive and viable solution for managing obesity. During the COVID-19 pandemic, the need for a safer alternative to in-person visits led to the increased popularity of telemedicine. Multiple studies have tested the efficacy of telemedicine modalities, including digital coaching via videoconferencing sessions, e-health monitoring using wearable devices, and asynchronous forms of communication such as online chatrooms with counselors. In this review, we discuss the available evidence for telemedicine interventions in managing obesity, review current challenges and barriers to using telemedicine, and outline future directions to optimize the management of patients with obesity using telemedicine.

Previous heart failure hospitalization, spironolactone, and outcomes in heart failure with preserved ejection fraction - a secondary analysis of TOPCAT.

BACKGROUND: Hospitalization for heart failure (HHF) is associated with poor postdischarge outcomes but the role of time since most recent HHF and potential treatment interactions are unknown. We aimed to assess history of and time since previous HHF, associations with composite of cardiovascular (CV) death and total HHF, first HHF and interactions with randomization to spironolactone, in heart failure with preserved ejection fraction. METHODS AND RESULTS: We assessed these objectives using uni- and multivariable regressions and spline analyses in TOPCAT-Americas. Among 1,765 patients, 66% had a previous HHF. Over a median of 2.9 years, 1,064 composite events of CV death or total HHFs occurred. Previous HHF was associated with more severe HF, and was independently associated with the composite outcome (HR 1.26, 95%CI 1.05-1.52, P = .014), and all secondary outcomes. A shorter time since most recent HHF appeared to be associated with subsequent first HHF, but not the composite of CV death or total HHF. Spironolactone had a significant interaction with previous HHF (interaction-P .046). Patients without a previous HHF had a larger effect of spironolactone on the composite outcome (HR 0.63, 95%CI 0.46-0.87, P = .005) than patients with a previous HHF (HR 0.91, 95%CI 0.78-1.06, P = .224). CONCLUSION: In TOPCAT-Americas, previous HHF was associated with CV death and first and total HHF. Duration since most recent HHF seemed to be associated with time to first HHF only. Spironolactone was associated with better outcomes in patients without a previous HHF. This interaction is hypothesis-generating and requires validation in future trials.