Obesity and Weight Loss Strategies for Patients With Heart Failure.

Obesity is a common comorbidity among patients with heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF), with the strongest pathophysiologic link of obesity being seen for HFpEF. Lifestyle measures are the cornerstone of weight loss management, but sustainability is a challenge, and there are limited efficacy data in the heart failure (HF) population. Bariatric surgery has moderate efficacy and safety data for patients with preoperative HF or left ventricular dysfunction and has been associated with reductions in HF hospitalizations and medium-term mortality. Antiobesity medications historically carried concerns for cardiovascular adverse effects, but the safety and weight loss efficacy seen in general population trials of glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide/GLP-1 agonists are highly encouraging. Although there are safety concerns regarding GLP-1 agonists in advanced HFrEF, trials of the GLP-1 agonist semaglutide for treatment of obesity have confirmed safety and efficacy in patients with HFpEF.

Anti-Obesity Medications in Patients With Heart Failure: Current Evidence and Practical Guidance.

Obesity is a significant risk factor for heart failure (HF) development, particularly HF with preserved ejection fraction and as a result, many patients with HF also have obesity. There is growing clinical interest in optimizing strategies for the management of obesity in patients with HF across the spectrums of both ejection fraction and disease severity. The emergence of anti-obesity medications with cardiovascular outcomes benefits, principally glucagon-like peptide-1 receptor agonists, has made it possible to study the impact of anti-obesity medications for patients with baseline cardiovascular conditions, including HF. However, clinical trials data supporting the safety and efficacy of treating obesity in patients with HF is currently limited to patients with HF with preserved ejection fraction, but do confirm safety and weight loss efficacy in this patient population as well as improvements in HF functional status, biomarkers of inflammation and HF stability. Here, we review the current data available surrounding the management of obesity for patients with HF, including the limitations of this evidence and ongoing areas for investigation, summarize the next phase of emerging anti-obesity medications and provide practical clinical advice for the multidisciplinary management of patients with both HF and obesity.

Obesity, Challenges, and Weight-Loss Strategies for Patients With Ventricular Assist Devices.

For adults with advanced heart failure, class II/III obesity (body mass index ≥35 kg/m2) represents major challenges, and it is even considered a contraindication for heart transplantation (HT) at many centers. This has led to growing interest in preventing and treating obesity to help patients with advanced heart failure become HT candidates. Among all weight-loss strategies, bariatric surgery (BSx) has the greatest weight loss efficacy and has shown value in enabling select patients with left ventricular assist devices (LVADs) and obesity to lose sufficient weight to access HT. Nevertheless, both BSx and antiobesity medications warrant caution in the LVAD population. In this review, the authors describe and interpret the available published reports on the impact of obesity and weight-loss strategies for patients with LVADs from general and HT candidacy standpoints. The authors also provide an overview of the journey of LVAD recipients who undergo BSx and review major aspects of perioperative protocols.

Controversies and Conundrums in Cardiac Cachexia: Key Questions About Wasting in Patients With HFrEF.

Cardiac cachexia is characterized by unintentional catabolic weight loss, decreased appetite, and inflammation and is common in patients with stage D (advanced) heart failure with reduced ejection fraction (HFrEF). Cardiac cachexia and related muscle-wasting syndromes are markers of, and a consequence of, the heart failure (HF) syndrome. Although many potential modalities for identifying cardiac cachexia exist, the optimal definition, diagnostic tools, and treatment options for cardiac cachexia remain unclear. Furthermore, it remains unclear whether attempts to reverse muscle wasting prior to advanced HF surgeries, such as left ventricular assist devices and heart transplantation, can improve outcomes. It is important that HF clinicians and dietitians are aware of the pathophysiology and mechanisms of muscle-wasting syndromes in patients with HF, to aid in the recognition and risk stratification of advanced HFrEF. Although the opportunities and rationale for attempting to address cardiac cachexia prior to advanced HF surgeries are uncertain, recent publications suggest that control of the neurohumoral syndrome of advanced HF may be important to permit the recovery of skeletal muscle mass.

Sex-specific patterns of donor-derived cell-free DNA in heart transplant rejection: An analysis from the Genomic Research Alliance for Transplantation (GRAfT).

BACKGROUND: Noninvasive methods for surveillance of acute rejection are increasingly used in heart transplantation (HT), including donor-derived cell-free DNA (dd-cfDNA). As other cardiac biomarkers differ by sex, we hypothesized that there may be sex-specific differences in the performance of dd-cfDNA for the detection of acute rejection. The purpose of the current study was to examine patterns of dd-cfDNA seen in quiescence and acute rejection in male and female transplant recipients. METHODS: Patients enrolled in the Genomic Research Alliance for Transplantation who were ≥18 years at the time of HT were included. Rejection was defined by endomyocardial biopsy with acute cellular rejection (ACR) grade ≥2R and/or antibody-mediated rejection ≥ pAMR 1. dd-cfDNA was quantitated using shotgun sequencing. Median dd-cfDNA levels were compared between sexes during quiescence and rejection. The performance of dd-cfDNA by sex was assessed using area under the receiver operator characteristic (AUROC) curve. Allograft injury was defined as dd-cfDNA ≥0.25%. RESULTS: One hundred fifty-one unique patients (49 female, 32%) were included in the analysis with 1,119 available dd-cfDNA measurements. Baseline characteristics including demographics and comorbidities were not significantly different between sexes. During quiescence, there were no significant sex differences in median dd-cfDNA level (0.04% [IQR 0.00, 0.16] in females vs 0.03% [IQR 0.00, 0.12] in males, p = 0.22). There were no significant sex differences in median dd-cfDNA for ACR (0.33% [0.21, 0.36] in females vs 0.32% [0.21, 1.10] in males, p = 0.57). Overall, median dd-cfDNA levels were higher in antibody-mediated rejection (AMR) than ACR but did not significantly differ by sex (0.50% [IQR 0.18, 0.82] in females vs 0.63% [IQR 0.32, 1.95] in males, p = 0.51). Elevated dd-cfDNA detected ACR/AMR with an AUROC of 0.83 in females and 0.89 in males, p-value for comparison = 0.16. CONCLUSIONS: There were no significant sex differences in dd-cfDNA levels during quiescence and rejection. Performance characteristics were similar, suggesting similar diagnostic thresholds can be used in men and women for rejection surveillance.

The Cardiac Amyloidosis Registry Study (CARS): Rationale, Design and Methodology.

BACKGROUND: CARS (Cardiac Amyloidosis Registry Study) is a multicenter registry established in 2019 that includes patients with transthyretin (ATTR, wild-type and variant) and light chain (AL) cardiac amyloidosis (CA) evaluated at major amyloidosis centers between 1997 and 2025. CARS aims to describe the natural history of CA with attention to clinical and diagnostic variables at the time of diagnosis, real-world treatment patterns, and associated outcomes of patients in a diverse cohort that is more representative of the at-risk population than that described in CA clinical trials. METHODS AND RESULTS: This article describes the design and methodology of CARS, including procedures for data collection and preliminary results. As of February 2023, 20 centers in the United States enrolled 1415 patients, including 1155 (82%) with ATTR and 260 (18%) with AL CA. Among those with ATTR, wild-type is the most common ATTR (71%), and most of the 305 patients with variant ATTR have the p.V142I mutation (68%). A quarter of the total population identifies as Black. More individuals with AL are female (39%) compared to those with ATTR (13%). CONCLUSIONS: CARS will answer crucial clinical questions about CA natural history and permit comparison of different therapeutics not possible through current clinical trials. Future international collaboration will further strengthen the validity of observations of this increasingly recognized condition.

Cardiac Cachexia in Left Ventricular Assist Device Recipients and the Implications of Weight Gain Early After Implantation.

Background Severe cardiac cachexia or malnutrition are commonly considered relative contraindications to left ventricular assist device (LVAD) implantation, but post-LVAD prognosis for patients with cachexia is uncertain. Methods and Results Intermacs (Interagency Registry for Mechanically Assisted Circulatory Support) 2006 to 2017 was queried for the preimplantation variable cachexia/malnutrition. Cox proportional hazards modeling examined the relationship between cachexia and LVAD outcomes. Of 20 332 primary LVAD recipients with available data, 516 (2.54%) were reported to have baseline cachexia and had higher risk baseline characteristics. Cachexia was associated with higher mortality during LVAD support (unadjusted hazard ratio [HR], 1.36 [95% CI, 1.18-1.56]; P<0.0001), persisting after adjustment for baseline characteristics (adjusted HR, 1.23 [95% CI, 1.0-1.42]; P=0.005). Mean weight change at 12 months was +3.9±9.4 kg. Across the cohort, weight gain ≥5% during the first 3 months of LVAD support was associated with lower mortality (unadjusted HR, 0.90 [95% CI, 0.84-0.98]; P=0.012; adjusted HR, 0.89 [95% CI, 0.82-0.97]; P=0.006). Conclusions The proportion of LVAD recipients recognized to have cachexia preimplantation was low at 2.5%. Recognized cachexia was independently associated with higher mortality during LVAD support. Early weight gain ≥5% was independently associated with lower mortality during subsequent LVAD support.

Long-Term Changes in Estimated Glomerular Filtration Rate in Left Ventricular Assist Device Recipients: A Longitudinal Joint Model Analysis.

Background Advanced kidney disease is often a relative contraindication to left ventricular assist device (LVAD) implantation because of concerns for poor outcomes including worsening kidney disease. Data are lacking on long-term changes and sex-based differences in estimated glomerular filtration rate (eGFR), with published data limited by potential bias introduced by the competing risks of death and heart transplantation. Methods and Results We conducted a longitudinal analysis of 288 adults receiving durable continuous-flow LVADs from January 2010 to December 2017 at a single center. A joint model was constructed to evaluate change in eGFR over 2 years, the prespecified primary outcome, adjusted for the competing risks of death and heart transplantation. Median baseline eGFR was 60 mL/min per 1.73 m2 (interquartile range 42-78). At 2 years, 74 patients died and 104 received a heart transplant. In unadjusted analysis, LVAD recipients had a modest initial increase in eGFR of ≈2 mL/min per 1.73 m2 within the first 6 months after implantation, followed by a decrease in eGFR below baseline values at 1 and 2 years. Men experienced an eGFR decline of 5 to 10 mL/min per 1.73 m2 over the first year which then stabilized, while women had an ≈5 mL/min per 1.73 m2 increase in eGFR within the first 6 months followed by decline towards baseline eGFR levels (interaction P=0.005). Conclusions Estimated GFR remains relatively stable in most patients following LVAD implantation. Larger studies are needed to investigate sex-based differences in eGFR and to evaluate eGFR trajectory and mortality in LVAD recipients with lower eGFR.

The effect of tablet computer-based telemonitoring added to an established telephone disease management program on heart failure hospitalizations: The Specialized Primary and Networked Care in Heart Failure (SPAN-CHF) III Randomized Controlled Trial.

BACKGROUND: Mobile health applications are becoming increasingly common. Prior work has demonstrated reduced heart failure (HF) hospitalizations with HF disease management programs; however, few of these programs have used tablet computer-based technology. METHODS: Participants with a diagnosis of HF and at least 1 high risk feature for hospitalization were randomized to either an established telephone-based disease management program or the same disease management program with the addition of remote monitoring of weight, blood pressure, heart rate and symptoms via a tablet computer for 90 days. The primary endpoint was the number of days hospitalized for HF assessed at 90 days. RESULTS: From August 2014 to April 2019, 212 participants from 3 hospitals in Massachusetts were randomized 3:1 to telemonitoring-based HF disease management (n = 159) or telephone-based HF disease management (n = 53) with 98% of individuals in both study groups completing the 90 days of follow-up. There was no significant difference in the number of days hospitalized for HF between the telemonitoring disease management group (0.88 ± 3.28 days per patient-90 days) and the telephone-based disease management group (1.00 ± 2.97 days per patient-90 days); incidence rate ratio 0.82 (95% confidence interval, 0.43-1.58; P = .442). CONCLUSIONS: The addition of tablet-based telemonitoring to an established HF telephone-based disease management program did not reduce HF hospitalizations; however, study power was limited.

The End of Endomyocardial Biopsy?: A Practical Guide for Noninvasive Heart Transplant Rejection Surveillance.

Noninvasive heart transplant rejection surveillance using gene expression profiling (GEP) to monitor immune activation is widely used among heart transplant programs. With the new development of donor-derived cell-free DNA (dd-cfDNA) assays, more programs are transitioning to a predominantly noninvasive rejection surveillance protocol with a reduced frequency of endomyocardial biopsies. As a result, many practical questions arise that potentially delay implementation of these valuable new tools. The purpose of this review is to provide practical guidance for clinicians transitioning toward a less invasive acute rejection monitoring protocol after heart transplantation, and to answer 10 common questions about the GEP and dd-cfDNA assays. Evidence supporting GEP and dd-cfDNA testing is reviewed, as well as guidance on test interpretation and future directions.

Taking Care of Us© (TCU) study protocol: feasibility and acceptability of a dyadic intervention for couples living with heart failure.

BACKGROUND: There are more than 1 million hospital admissions and 3 million emergency visits for heart failure in the USA annually. Although spouse/partners make substantial contributions to the management of heart failure and experience poor health and high levels of care strain, they are rarely the focus of heart failure interventions. This protocol describes a pilot randomized controlled trial that tests the feasibility, acceptability, and preliminary change in outcomes of a seven-session couple-based intervention called Taking Care of Us© (TCU). The TCU© intervention is grounded in the theory of dyadic illness management and was developed to promote collaborative illness management and better physical and mental health of adults with heart failure and their partners. METHODS: A two-arm randomized controlled trial will be conducted. Eligible adults with heart failure and their co-residing spouse/partner will be recruited from a clinical site in the USA and community/social media outreach and randomized to either the TCU© intervention or to a control condition (SUPPORT©) that offers education around heart failure management. The target sample is 60 couples (30 per arm). TCU© couples will receive seven sessions over 2 months via Zoom; SUPPORT© couples will receive three sessions over 2 months via Zoom. All participants will complete self-report measures at baseline (T1), post-treatment (T2), and 3 months post-treatment (T3). Acceptability and feasibility of the intervention will be examined using both closed-ended and open-ended questions as well as enrollment, retention, completion, and satisfaction metrics. Preliminary exploration of change in outcomes of TCU© on dyadic health, dyadic appraisal, and collaborative management will also be conducted. DISCUSSION: Theoretically driven, evidence-based dyadic interventions are needed to optimize the health of both members of the couple living with heart failure. Results from this study will provide important information about recruitment and retention and benefits and drawbacks of the TCU© program to directly inform any needed refinements of the program and decision to move to a main trial. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04737759) registered on 27 January 2021.

Impella 5.5 Support Beyond 50 Days as Bridge to Heart Transplant in End-Stage Heart Failure Patients.

Prolonged mechanical circulatory support (MCS) for severe left ventricular dysfunction in cardiogenic shock as a bridge to heart transplantation (HTx) generally requires a surgical procedure. Typically, a surgically implanted temporary extracorporeal left ventricular assist device (LVAD) is chosen because of superior flow and durability compared with a percutaneously delivered endovascular LVAD (pVAD). However, compared with its predecessors, the Impella 5.5 trans-valvular pVAD provides higher hemodynamic support and features improved durability. Here, we present four successful cases with prolonged Impella 5.5 support as a bridge to HTx, with a mean support duration of 70 days (maximum 83 days). These cases highlight several potential benefits of Impella 5.5. The minimally invasive implantation procedure of the device reduces bleeding, decreases the postoperative recovery period, and enables early patient ambulation to reduce physical deconditioning before HTx surgery. Furthermore, Impella 5.5 adequately unloads the left ventricle and provides hemodynamic support to maintain end-organ function to further optimize hemodynamics before HTx. The evolution of Impella 5.5 technology may provide an alternative bridging strategy to traditional surgically implanted temporary MCS in select cases.

Patient reported outcomes measures are infrequently used in clinical studies of heart transplant recipients.

BACKGROUND: Clinical trials in heart transplantation (HT) recipients have largely focused on objective outcomes such as survival; however, there is a paucity of data regarding the use of patient-reported outcome measures (PROMs) in these studies. We aimed to characterize the use of PROMs in registered clinical studies of HT recipients. METHODS: All clinical studies of adult HT recipients were queried from ClinicalTrials.gov and stratified by inclusion of PROMs. Studies reporting PROMs were identified via specific search terms using the "outcomes measures" field. Summary statistics compared characteristics of studies with and without PROMs. RESULTS: Between November 1999 and August 2022, 227 studies of HT recipients were registered on ClinicalTrials.gov. PROMs were included in 11% (n = 24/227) of studies. Studies reporting PROMs were more likely to be conducted outside of the United States (91.7% vs 54.2%, p < 0.001) and report a greater number of primary/secondary outcomes (PROMs: median 7 [interquartile ranges (IQR): 4, 9] vs no PROMs: median 3 [IQR: 2, 6]; p < 0.001). The majority of studies reporting PROMs (58.3%) were initiated after 2020. Twenty-one distinct PROM tools/domains were reported as outcome measures, with the Short Form Health Survey 36 being most frequently used (n = 10/24). Thirteen of the 21 PROMs included questions assessing mental health, whereas only 3 PROM tools were cardiac-specific. CONCLUSIONS: About 1 in 10 registered clinical trials of HT recipients includes PROMs, and mental health is the most commonly assessed PROM domain. Development and validation of PROM tools is needed to fully assess health-related quality of life in HT recipients.

Association between postoperative hemodynamic metrics of pulmonary hypertension and right ventricular dysfunction and clinical outcomes after left ventricular assist device implantation.

BACKGROUND: While preoperative hemodynamic risk factors associated with early right heart failure (RHF) following left ventricular assist device (LVAD) surgery are well-established, the relationship between postoperative hemodynamic status and subsequent outcomes remains poorly defined. METHODS: We analyzed adult CF-LVAD patients from the STS-INTERMACS registry surviving at least 3 months without evidence of early RHF and with hemodynamic data available at 3 months after LVAD implant. The association between metrics of RV afterload and function and the subsequent risk of death, right heart failure (RHF), gastrointestinal bleeding (GIB), or stroke were assessed using multivariable Cox proportional hazards modeling. RESULTS: Among 1,050 patients with available 3-month hemodynamics, pulmonary hypertension was common, with 585 (55.7%) having mPAP ≥ 20 mm Hg and 164 (15.6%) having PVR ≥ 3 WU. Pulmonary artery pulsatility index (PAPi, HR 0.62 per log-increase for values < 3, 95% CI 0.43-0.89) and PVR (HR 1.19 per 1 WU-increase for values > 1.5 WU, 95% CI 1.03-1.38) were independently associated with the composite of death or RHF. Postoperative RAP (HR 1.18 per 5 mm Hg increase, 95% CI 1.04-1.33), RAP:PCWP (HR 1.46 per log-increase, 95% CI 1.12-1.91), and PAPi (HR 0.76 per log-increase, 95% CI 0.61-0.95) were each associated with GIB risk. Postoperative hemodynamics was not associated with stroke risk. CONCLUSIONS: Hemodynamic metrics of postoperative RV dysfunction and elevated RV afterload are independently associated with RHF, mortality and GIB. Whether strategies targeting postoperative optimization of RV function and afterload can reduce the burden of these adverse events requires prospective study.