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Background: Dietary interventions have potential to improve symptoms and outcomes in patients with heart failure (HF), but there are barriers to eating nutrient-dense diets. One strategy to address challenges is to provide medically tailored meals (MTMs), fully prepared meals that align with an individual's nutritional needs. In this systematic review, we examined clinical outcomes of studies that provided MTMs to patients with HF., Methods and Results: We searched CINAH, EBSCO/MEDLINE, EMBASE, PUBMED and the Cochrane Central Register of Controlled Trials to identify MTM interventions published between 2013 and 2023. We included six studies. Five studies involved sodium restriction. Four of these were randomized control trials and one was a matched cohort study. Sample sizes ranged from 31 to 641. Patient populations included individuals who had heart failure, acute decompensated heart failure and heart failure with preserved ejection fraction. One study involved energy restriction in patients with heart failure with preserved ejection fraction and obesity. This was a randomized controlled study with a sample size of 100. Sodium-restriction interventions, when aligned with Dietary Approaches to Stop Hypertension goals, reduced 90-day HF readmissions in one study and trended towards improving 30-day and 12-week HF readmissions in another. The energy-restriction intervention reduced diastolic blood pressure, weight, and inflammatory biomarkers, and improved quality of life (QoL) and cardiorespiratory fitness. Neither intervention had an impact on mortality., Conclusions: Provision of sodium-restricted MTMs to patients with HF may reduce the risk of rehospitalization. Provision of energy-restricted MTMs to patients with HF and obesity can improve symptoms, weight loss, QoL, and cardiorespiratory fitness. Adequately powered randomized controlled trials are needed to confirm these effects and investigate underlying mechanisms., (Published by Elsevier Inc.)

Objective: Splanchnic vasoconstriction augments transfer of blood volume from the abdomen into the thorax, which may increase filling pressures and hemodynamic congestion in patients with noncompliant hearts. Therapeutic interruption of splanchnic nerve activity holds promise to reduce hemodynamic congestion in patients with heart failure with preserved ejection fraction (HFpEF). Here we describe (1) the rationale and design of the first sham-controlled, randomized clinical trial of splanchnic nerve ablation for HFpEF and (2) the 12-month results of the lead-in (open-label) trial's participants., Methods: REBALANCE-HF is a prospective, multicenter, randomized, double-blinded, sham-controlled clinical trial of endovascular, transcatheter, right-sided greater splanchnic nerve ablation for volume management (SAVM) in patients with HFpEF. The primary objectives are to evaluate the safety and efficacy of SAVM and identify responder characteristics to inform future studies. The trial consists of an open-label lead-in phase followed by the randomized, sham-controlled phase. The primary efficacy endpoint is the reduction in pulmonary capillary wedge pressure (PCWP) at 1-month follow-up compared to baseline during passive leg raise and 20W exercise. Secondary and exploratory endpoints include health status (Kansas City Cardiomyopathy Questionnaire), 6-minute walk test distance, New York Heart Association class, and NTproBNP levels at 3, 6 and 12 months. The primary safety endpoint is device- or procedure-related serious adverse events at the 1-month follow-up., Results: The lead-in phase of the study, which enrolled 26 patients with HFpEF who underwent SAVM, demonstrated favorable safety outcomes and reduction in exercise PCWP at 1 month post-procedure and improvements in all secondary endpoints at 6 and 12 months of follow-up. The randomized phase of the trial (n = 44 SAVM; n = 46 sham) has completed enrollment, and follow-up is ongoing., Conclusion: REBALANCE-HF is the first sham-controlled randomized clinical trial of greater splanchnic nerve ablation in HFpEF. Initial 12-month open-label results are promising, and the results of the randomized portion of the trial will inform the design of a future pivotal clinical trial. SAVM may offer a promising therapeutic option for patients with HFpEF., Trial Registration: NCT04592445., Competing Interests: DISCLOSURES MF was supported by the NIH (1OT2HL156812-01) and Doris Duke, and he consults for or owns equity in Abbott, Ajax, Alio Health, Alleviant, Artha, Audicor, AxonTherapies, Bayer, Bodyguide, Bodyport, Boston Scientific, Broadview, Cadence, Cardioflow, Cardionomics, Coridea, CVRx, Daxor, Deerfield Catalyst, Edwards LifeSciences, Echosens, EKO, Feldschuh Foundation, Fire1, FutureCardia, Galvani, Gradient, Hatteras, HemodynamiQ, Impulse Dynamics, Intershunt, Medtronic, Merck, NIMedical, NovoNordisk, NucleusRx, NXT Biomedical, Orchestra, Pharmacosmos, PreHealth, Presidio, Procyreon, ReCor, Rockley, SCPharma, Shifamed, Splendo, Summacor, SyMap, Verily, Vironix, Viscardia, Zoll. SL reports research support from Axon, Corvia, V Wave, Astra Zeneca, Eli Lilly, and Rivus and has consulting relationships with Axon, Corvia, Eli Lilly, and Rivus. BAB receives research support from the National Institutes of Health and the United States Department of Defense as well as research grant funding from AstraZeneca, Axon, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, and Tenax Therapeutics and has served as a consultant for Actelion, Amgen, Aria, BD, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Eli Lilly, Janssen, Merck, and Novo Nordisk. BAB and SJA are named inventors (U.S. Patent no. 10,307,179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure. RCM consults for Alleviant, Corvia and HemodynamiQ. MJP reports consulting honoraria, speaker's fees and proctoring fees from Abbott Vascular and Boston Scientific, consulting honoraria from W.L. Gore, Biotronik, and Philips Medical, consulting honoraria and speaker's fees from Medtronic, consulting honoraria from Shockwave and Innovheart and equity in InterShunt. PG has grant support from the NIH (K76AG064428, R21AG077092, R24AG064025), has received consulting fees from Sensorum Health and Axon Therapies and has received personal fees for expert testimony related to heart failure. RVP reports consulting fees from ICA. VYR reports serving as a consultant to and receiving stock options from Axon Therapies and, unrelated to this manuscript, VYR also serves as a consultant for and has equity in Ablacon, Acutus Medical, Affera-Medtronic, Apama Medical-Boston Scientific, Anumana, APN Health, Aquaheart, Atacor, Autonomix, Backbeat, BioSig, CardiaCare, CardioNXT/AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD-Philips, EP Frontiers, Epix Therapeutics-Medtronic, EpiEP, Eximo, Farapulse-Boston Scientific, Field Medical, Focused Therapeutics, HRT, Intershunt, Javelin, Kardium, Keystone Heart, LuxMed, Medlumics, Middlepeak, Neutrace, Nuvera-Biosense Webster, Oracle Health, Restore Medical, Sirona Medical, SoundCath, Valcare; and, unrelated to this work, has served as a consultant for Abbott, AtriAN, Biosense-Webster, BioTel Heart, Biotronik, Boston Scientific, Cairdac, Cardiofocus, Cardionomic, CoreMap, Fire1, Gore & Associates, Impulse Dynamics, Medtronic, Novartis, Philips, Pulse Biosciences and has equity in DRS Vascular, Manual Surgical Sciences, Newpace, Nyra Medical, Surecor, and Vizaramed. DB reports consulting fees and grant support from Axon Therapies. MRP is a consultant to Axon Therapies. SIS is an employee of Axon Therapies. SJS reports support from research grants from the National Institutes of Health (U54 HL160273, R01 HL107577, R01 HL127028, R01 HL140731, and R01 HL149423), Pfizer and AstraZeneca and consulting fees from Abbott, AstraZeneca, Amgen, Aria CV, Axon Therapies, Bayer, Boehringer-Ingelheim, Boston Scientific, Bristol Myers Squibb, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, Imara, Impulse Dynamics, Intellia, Ionis, Lilly, Merck, Metabolic Flux, MyoKardia, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Pfizer, Prothena, Regeneron, Rivus, Sardocor, Shifamed, Tenax, Tenaya, and United Therapeutics. All other authors have nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures SLH has previously received research funding from PurFoods. His effort is supported by VA CSR&D Merit Award RDC-2017-1066, and NIH grants R01-AG062582 and R61-HL155498, and research funding from PurFoods. His efforts are supported by VA CSR&D Merit AwardRDC-2017-1066 and NIH grants R01-AG062582 and R61-HL155498.

Background: The Dietary Approaches to Stop Hypertension (DASH) diet pattern has shown some promise for preventing heart failure (HF), but studies have been conflicting., Objective: To determine whether the DASH diet pattern was associated with incident HF in a large biracial and geographically diverse population., Methods and Results: Among participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study of adults aged ≥45 years who were free of suspected HF at baseline in 2003-2007, the DASH diet score was derived from the baseline food frequency questionnaire. The main outcome was incident HF defined as the first adjudicated HF hospitalization or HF death through December 31, 2016. We estimated hazard ratios for the associations of DASH diet score quartiles with incident HF, and incident HF with reduced ejection fraction and HF with preserved ejection fraction using the Lunn-McNeil extension to the Cox model. We tested for several prespecified interactions, including with age. Compared with the lowest quartile, individuals in the second to fourth DASH diet score quartiles had a lower risk for incident HF after adjustment for sociodemographic and health characteristics: quartile 2 hazard ratio, 0.69 (95% confidence interval [CI], 0.56-0.85); quartile 3 hazard ratio, 0.71 (95% CI, 0.58-0.87); and quartile 4 hazard ratio, 0.73 (95% CI, 0.58-0.92). When stratifying results by age, quartiles 2-4 had a lower hazard for incident HF among those age <65 years, quartiles 3-4 had a lower hazard among those age 65-74, and the quartiles had similar hazard among those age ≥75 years (P interaction  = .003). We did not find a difference in the association of DASH diet with incident HF with reduced ejection fraction vs HF with preserved ejection fraction (P = .11)., Conclusions: DASH diet adherence was inversely associated with incident HF, specifically among individuals <75 years old., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Dietary sodium excess and malnutrition have been associated with poor outcomes in heart failure (HF). Few previous studies have examined the barriers to following a low-sodium, nutritionally robust diet in hospitalized patients with HF., Methods and Results: As part of a dietary intervention pilot study, 76 inpatients with HF (age 71 ± 8 years, 30% female, 30% black, 36% Hispanic/Latino) completed 2 questionnaires, the Dietary Sodium Restriction Questionnaire (DSRQ) and the Brief Dietary Psychosocial Scale (BDPS), to assess challenges in following a low-sodium, nutritionally complete diet. We assessed the factor structure of the DSRQ and BDPS with confirmatory and exploratory factor analysis (CFA and EFA). CFA did not support the established 3-factor solution for the DSRQ; instead, EFA indicated that a 2-factor solution (subjective norms/attitudes and perceived behavioral control) provided the best fit for the data. EFA supported 4 separate factors for the BDPS, as in its original derivation. Cronbach's alphas supported internal consistency reliability for both scales (DSRQ: 0.85-0.94; BDPS: 0.72-0.95)., Conclusions: In a mixed-ethnicity group of hospitalized older patients with HF, the DSRQ and BDPS have reasonable psychometric properties. These questionnaires may help identify barriers to healthy dietary practices and facilitate nutritional interventions in this high-risk population., (Published by Elsevier Inc.)

Background: Frailty reflects decreased resilience to physiological stressors; its prevalence and prognosis are not fully defined in heart failure with preserved ejection fraction (HFpEF)., Methods: The Short Physical Performance Battery (SPPB) was prospectively obtained in 114 outpatients with HFpEF. The SPPB tests gait speed, tandem balance, and timed chair rises, each scored from 0 to 4 points. Severe and mild frailty were respectively defined as an SPPB score ≤6 and 7-9 points. We used risk-adjusted logistic, Poisson, and negative binominal regression, respectively, to assess the relationship between SPPB score and risk of death or all-cause hospitalization, number of hospitalizations, and days hospitalized or dead longer than 6 months., Results: Patients were similar to other HFpEF cohorts (age 68 ± 13 years, 58% female, body mass index 36 ± 8 kg/m 2 , multiple comorbidities). Mean SPPB score was 6.9 ± 3.2, and 80% of patients were at least mildly frail. Over a 6-month period, the SPPB score independently predicted death or all-cause hospitalization (odds ratio 0.81 per point, 95% confidence interval [CI] 0.69-0.94, P = .006), number of hospitalizations (incidence rate ratio 0.92 per point, 95% CI 0.86-0.97, P = .006), and days hospitalized or dead (incidence rate ratio 0.85 per point, 95% CI 0.73-0.99, P = .04)., Conclusions: Lower extremity function, as measured by the SPPB, independently predicts hospitalization burden in outpatients with HFpEF. Additional studies are warranted to explore shared mechanisms and treatment implications of frailty in HFpEF., (Published by Elsevier Inc.)

Introduction: Coronary microvascular dysfunction (MVD) may contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Using myocardial flow reserve (MFR) measured by positron emission tomography (PET) as an assessment of microvascular function, we hypothesized that abnormal MFR is associated with LV diastolic dysfunction (DD) and reduced LV and LA strain in patients with risk factors for HFpEF and normal epicardial perfusion on cardiac PET., Methods and Results: Retrospective study of patients without heart failure who underwent cardiac rubidium-82 PET and echocardiography. Global MFR was calculated as the ratio of global stress to rest myocardial blood flow. Echocardiographic measures of diastolic function were recorded. Global longitudinal LA and LV strain were measured with a 2-dimensional speckle-tracking technique. Relationships among MFR and echocardiographic measures were assessed with linear regression, analysis of variance, and test for trend. Seventy-three patients (age 64 ± 11 years, 52% male) were identified with no epicardial perfusion defect on cardiac PET and an ejection fraction ≥50%. Decreased MFR was associated with LV DD (P = .02) and increased E/e', an estimation of LV filling pressure (low E/e' [<8] vs. high E/e' [>15], P < .001). MFR was associated with LA strain independent of age, gender, and common comorbidities (adjusted β = 2.6% per unit MFR, P = 0.046); however, MFR was only marginally related to LV strain., Conclusions: In patients with risk factors for HFpEF, MVD assessed with MFR was associated with DD, increased estimated LV filling pressure, and abnormal LA strain., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Heart failure (HF) disproportionately affects older adults. Dietary sodium indiscretion is frequently implicated in HF decompensation. The affinity for and ability to taste salt in this process is unexplored. We sought to evaluate differences in salt taste by age and HF diagnosis and to map changes after hospitalization for acute decompensated heart failure (ADHF)., Methods: Seventy-two subjects underwent initial salt-taste testing during hospitalization for ADHF. Follow-up taste testing occurred at discharge and 1, 4, and 12 weeks after hospitalization. Three different groups were included as control subjects and underwent 1-time salt-taste testing: 10 patients with stable HF, 10 healthy older adults, and 10 healthy younger adults. Salt-taste testing was completed with the use of commercially available and validated Salsave test strips with increasing concentrations of NaCl (0.6-1.6 mg/cm 2 ) to identify salt taste recognition threshold. Respectively, 2-sample t tests, multiple regression, and linear mixed-effects modeling were used for intergroup comparisons, to adjust for confounders, and to assess the effect of time after discharge from ADHF hospitalization., Results: The baseline salt taste recognition threshold was lowest in the young healthy control group (0.62 [SD 0.05] mg/cm 2 NaCl) compared with the healthy older control subjects (0.92 [SD 0.29] mg/cm 2 NaCl), stable HF outpatients, (1.06 [SD 0.22] mg/cm 2 NaCl), and ADHF subjects on admission (1.06 [SD 0.48] mg/cm 2 NaCl). There was a strong trend toward higher recognition threshold in HF patients (P = .051) that was independent from age and other potential confounders. Serial salt-taste testing in the ADHF group demonstrated a decrease in recognition threshold that persisted over the 12 weeks after discharge (1.04 [SD 0.44] to 0.76 [SD 0.22] mg/cm 2 NaCl; P = .003)., Discussion: When compared with young healthy control subjects, HF patients have impaired recognition of salt taste. The salt taste recognition threshold decreases after hospitalization for ADHF. This change demonstrates the first evidence of the phenomenon known as the "hedonic shift" in HF, in which the threshold to recognize salt taste decreases after prescribed sodium restriction., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Distinct monocyte subsets predict cardiovascular risk and contribute to heart failure progression in murine models, but they have not been examined in clinical acute decompensated heart failure (ADHF)., Methods and Results: Blood samples were obtained from 11 healthy control subjects (HCs) and at admission and discharge from 19 ADHF patients. Serologic markers of inflammation were assessed at admission and discharge. Monocyte populations were defined with the use of flow cytometry for cell-surface expression of CD14 and CD16: CD14++CD16- (classic), CD14++CD16+ (intermediate), and CD14+CD16++ (nonclassic). In ADHF patients, C-reactive protein (CRP) and interleukin-6 (IL-6) were higher compared with HCs (both P < .001) and decreased from admission to discharge (CRP: 12.1 ± 10.1 to 8.6 ± 8.4 mg/L [P = .005]; IL-6: 19.8 ± 34.5 to 7.1 ± 4.7 pg/mL [P = .08]). In ADHF patients, the admission proportion of CD14++CD16- monocytes was lower (68% vs 85%; P < .001) and that of CD14++CD16+ (15% vs 8%; P = .002) and CD14+CD16++ (17% vs 7%, P = .07) monocytes higher compared with HCs. Additionally, the proportion of CD14++CD16- monocytes increased (68% to 79%, P = .04) and the CD14+CD16++ monocytes decreased (17% to 7%, P = .049) between admission and discharge., Conclusions: Following standard treatment of ADHF, the monocyte profile and circulating inflammatory markers shifts to more closely resemble those of HC, suggesting a resolution of the acute inflammatory state. Functional studies are warranted to understand how specific monocyte subsets and systemic inflammation may contribute to ADHF pathophysiology., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized as a distinct entity with unique pathophysiology. In the Dietary Approaches to Stop Hypertension in Diastolic Heart Failure (DASH-DHF) study, the sodium-restricted Dietary Approaches to Stop Hypertension diet (DASH/SRD) was associated with improved blood pressure and cardiovascular function in 13 hypertensive patients with HFpEF. With the use of targeted metabolomics, we explored metabolite changes and their relationship with energy-dependent measures of cardiac function in DASH-DHF., Methods and Results: With the use of chromatography and mass spectrometry, 152 metabolites including amino acids, free fatty acids, phospholipids, diglycerides, triglycerides, cholesterol esters, and acyl carnitines were measured. Comparison of baseline and post-DASH/SRD samples revealed increases in short-chain acetyl, butryl, and propionyl carnitines (P values .02, .03, .03, respectively). Increases in propionyl carnitine correlated with ventricular-arterial coupling ratio (Ees:Ea; r = 0.78; P = .005) and ventricular contractility (maximum rate of change of pressure-normalized stress [dσ*/dtmax]; r = 0.66; P = .03). Changes in L-carnitine also correlated with Ees:Ea (r = 0.62; P = .04) and dσ*/dtmax (r = 0.60; P = .05) and inversely with ventricular stiffness (r = -0.63; P = .03)., Conclusions: Metabolite profile changes of patients with HFpEF during dietary modification with the use of DASH/SRD suggest improved energy substrate utilization. Additional studies are needed to clarify connections between diet, metabolic changes, and myocardial function in HFpEF., (Published by Elsevier Inc.)

Background: Prolonged electrocardiogram (ECG) QRS duration (>or=120 ms) is a risk factor for death in systolic heart failure, but its effects in heart failure with preserved systolic function (HFPSF) have not been extensively studied. We hypothesized that prolonged ECG QRS duration would independently predict long-term mortality in hospitalized HFPSF patients., Methods and Results: We analyzed 872 HFPSF patients (defined as left ventricular ejection fraction >or=50%) admitted to Michigan community hospitals between 2002 and 2004 and followed for a median of 660 days. We used Cox proportional hazards models to assess mortality hazard for prolonged QRS duration (>or=120 ms) on the last available predischarge ECG, first on a univariable basis and then after multivariable adjustment for other known risk factors. Prolonged QRS duration increased univariable all-cause mortality (HR 1.71; 95% CI 1.33-2.19, P < .001) and after multivariable adjustment (HR 1.31; 95% CI 1.01-1.71, P=.04). The univariable effect size was larger in younger patients. In multivariable models, there was no significant interaction between prolonged QRS and age, hypertension, or coronary artery disease status., Conclusions: Prolonged QRS duration (>or=120 ms) on a predischarge ECG is an independent and consistent predictor of long-term mortality in hospitalized HFPSF patients.