The effect of time of eating on cardiometabolic risk in primary and secondary prevention of cardiovascular disease.

Continuous energy restriction is currently considered the first-line dietary therapy for weight loss in individuals with obesity. Recently, interventions which alter the eating window and time of eating occasions have been explored as means to achieve weight loss and other cardiometabolic improvements such as a reduction in blood pressure, glycaemia, lipids and inflammation. It is unknown, however, whether these changes result from unintentional energy restriction or from other mechanisms such as the alignment of nutrient intake with the internal circadian clock. Even less is known regarding the safety and efficacy of these interventions in individuals with established chronic noncommunicable disease states, such as cardiovascular disease. This review examines the effects of interventions which alter both eating window and time of eating occasions on weight and other cardiometabolic risk factors in both healthy participants and those with established cardiovascular disease. We then summarise the state of existing knowledge and explore future directions of study.

Time of eating and mortality in U.S. adults with heart failure: Analyses of the National Health and Nutrition Examination Survey 2003-2018.

BACKGROUND AND AIMS: Promising associations have been demonstrated between delayed last eating occasion and cardiorespiratory fitness in adults with heart failure (HF), however, it is unknown if time of eating is associated with clinical endpoints such as mortality. This study aimed to examine associations between time of eating variables and all-cause and cardiovascular mortality in the National Health and Nutrition Examination Survey (NHANES). METHODS AND RESULTS: Participants self-disclosed HF diagnosis. Two dietary recalls were obtained and categorical variables were created based on mean time of first eating occasion (8:31 AM), last eating occasion (7:33 PM) and eating window (11.02 h). Mortality was obtained through linkage to the National Death Index. Covariate-adjusted Cox proportional hazard regression models were created examining the association between time of eating and mortality. Participants (n = 991) were 68 (95 % CI 67-69) years of age, 52.6 (95 % CI 49.0-56.3)% men and had a body mass index of 32.5 (95 % CI 31.8-33.2) kg/m2 with follow up time of 68.9 (95 % CI 64.8-72.9) person-months. When models were adjusted for time of eating variables and all other covariates, extending the eating window beyond 11.02 h was associated with decreased risk of cardiovascular (HR 0.36 [95 % CI 0.16-0.81]), but not all-cause mortality. Time of first and last eating occasions were not associated with mortality. CONCLUSIONS: In adults with HF, an extended eating window is associated with reduced risk for cardiovascular mortality. Randomized controlled trials should examine if extending the eating window can improve prognostic indicators such as cardiorespiratory fitness in this population.

Nutritional Aspects to Cardiovascular Diseases and Type 2 Diabetes Mellitus.

PURPOSE OF REVIEW: In this narrative review, we discuss the current evidence related to the role of dietary interventions to prevent and treat type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). We also propose alternative therapeutic strategies other than weight loss in this population, namely, improvements in cardiorespiratory fitness and its determinants. RECENT FINDINGS: While weight loss has been consistently associated with the prevention of T2DM and improvements in glycemic control in those with established diseases, its role in preventing and treating CVD is less clear. In fact, in this setting, improvements in diet quality have provided greater benefits, suggesting that this might represent an alternative, or an even more effective strategy than energy-restriction. Improvements in diet quality, with and without caloric restriction have been shown to improve CVD risk and to prevent the development of T2DM in individuals at risk; however, with regard to glycemic control in patients with T2DM, any dietary intervention resulting in significant weight loss may produce clinically meaningful benefits. Finally, dietary interventions with and without energy restriction that can improve cardiorespiratory fitness, even in absence of weight loss in patients with obesity, should be encouraged.

Effect of Canagliflozin Compared With Sitagliptin on Serum Lipids in Patients with Type 2 Diabetes Mellitus and Heart Failure with Reduced Ejection Fraction: A Post-Hoc Analysis of the CANA-HF Study.

ABSTRACT: The sodium glucose co-transporter 2 inhibitors have demonstrated favorable effects on cardiovascular and renal disease; however, they may also increase low-density lipoprotein cholesterol (LDL-C). There are limited data directly comparing the effects of sodium glucose co-transporter 2inhibitors on serum lipids to other antihyperglycemic therapies. In this post-hoc analysis of the CANA-HF trial, we sought to compare the effects of canagliflozin to sitagliptin in patients with type 2 diabetes mellitus (T2DM) and heart failure and reduced ejection fraction (HFrEF). The CANA-HF trial was a prospective, randomized controlled study that compared the effects of canagliflozin 100 mg daily to sitagliptin 100 mg daily on cardiorespiratory fitness in patients with HFrEF and T2DM. Of the 36 patients enrolled in CANA-HF, 35 patients had both baseline and 12-weeks serum lipids obtained via venipuncture. The change in LDL-C from baseline to 12 weeks was 5 (-12.5 to 19.5) mg/dL versus -8 (-19 to -1) mg/dL (P = 0.82) and triglyceride levels was -4 (-26 to 9) mg/dL and -10.5 (-50 to 29.3) mg/dL (P = 0.52) for canagliflozin and sitagliptin, respectively. No significant differences were found between canagliflozin and sitagliptin for total cholesterol, high-density lipoprotein cholesterol or non-HDL-C (P > 0.5 for all). These data suggest that compared with sitagliptin, canagliflozin may not increase LDL-C in patients with T2DM and HFrEF.

Time of eating and cardiorespiratory fitness in patients with heart failure with preserved ejection fraction and obesity.

BACKGROUND AND AIMS: Our objective was to examine the impact of caloric intake before or after the mean time of evening meal on cardiorespiratory fitness (CRF) in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. METHODS AND RESULTS: Twelve patients with HFpEF and obesity completed a cardiorespiratory exercise test to measure CRF, defined as peak oxygen consumption (VO2). Three five-pass 24-h dietary recalls were performed for each participant and mean evening meal time was determined for each participant individually as well as the group. Participants were divided into those who ate before (Group I) and after (Group II) the mean time of evening meal, 7:25 PM. Peak VO2 and exercise time were significantly greater in Group II compared to Group I, moreover, delaying time of evening meal was associated with greater peak VO2. CONCLUSION: Caloric intake after the mean time of evening meal was associated with better CRF in patients with HFpEF and concomitant obesity. Later nutrient intake may help prevent fasting related stress associated with cardiac metabolic disturbances present in HFpEF. Based on these findings, prospective trials aimed at examining the effects of later evening meal times in patients with HFpEF and obesity are warranted.

The effects of canagliflozin compared to sitagliptin on cardiorespiratory fitness in type 2 diabetes mellitus and heart failure with reduced ejection fraction: The CANA-HF study.

BACKGROUND: Canagliflozin reduces hospitalizations for heart failure (HF) in type 2 diabetes mellitus (T2DM). Its effect on cardiorespiratory fitness and cardiac function in patients with established HF with reduced ejection fraction (HFrEF) is unknown. METHODS: We conducted a double-blind randomized controlled trial of canagliflozin 100 mg or sitagliptin 100 mg daily for 12 weeks in 88 patients, and measured peak oxygen consumption (VO2 ) and minute ventilation/carbon dioxide production (VE/VCO2 ) slope (co-primary endpoints for repeated measure ANOVA time_x_group interaction), lean peak VO2 , ventilatory anaerobic threshold (VAT), cardiac function and quality of life (ie, Minnesota Living with Heart Failure Questionnaire [MLHFQ]), at baseline and 12-week follow-up. RESULTS: The study was terminated early due to the new guidelines recommending canagliflozin over sitagliptin in HF: 17 patients were assigned to canagliflozin and 19 to sitagliptin, total of 36 patients. There were no significant changes in peak VO2 and VE/VCO2 slope between the two groups (P = .083 and P = .98, respectively). Canagliflozin improved lean peak VO2 (+2.4 mL kgLM-1 min-1 , P = .036), VAT (+1.5 mL kg-1 min-1 , P = .012) and VO2 matched for respiratory exchange ratio (+2.4 mL Kg-1 min-1 , P = .002) compared to sitagliptin. Canagliflozin also reduced MLHFQ score (-12.1, P = .018). CONCLUSIONS: In this small and short-term study of patients with T2DM and HFrEF, interrupted early after only 36 patients, canagliflozin did not improve the primary endpoints of peak VO2 or VE/VCO2 slope compared to sitagliptin, while showing favourable trends observed on several additional surrogate endpoints such as lean peak VO2 , VAT and quality of life.

Phase 1B, Randomized, Double-Blinded, Dose Escalation, Single-Center, Repeat Dose Safety and Pharmacodynamics Study of the Oral NLRP3 Inhibitor Dapansutrile in Subjects With NYHA II-III Systolic Heart Failure.

ABSTRACT: The NLRP3 inflammasome has been implicated in the development and progression of heart failure. The aim of this study was to determine the safety of an oral inhibitor of the NLRP3 inflammasome, dapansutrile (OLT1177), in patients with heart failure and reduced ejection fraction (HFrEF). This was a phase 1B, randomized, double-blind, dose escalation, single-center, repeat dose safety and pharmacodynamics study of dapansutrile in stable patients with HFrEF (New York Heart Association Class II-III). Subjects were randomized to treatment with dapansutrile for up to 14 days at a ratio of 4:1 into 1 of 3 sequential ascending dose cohorts (500, 1000, or 2000 mg) each including 10 patients. Subjects underwent clinical assessment, biomarker determination, transthoracic echocardiogram, and maximal cardiopulmonary exercise testing at baseline, day 14, and day 28 to ascertain changes in clinical status. Placebo cases (N = 2 per cohort) were used as a decoy to reduce bias and not for statistical comparisons. Thirty participants (20 men) were treated for 13 (12-14) days. No serious adverse events during the study were recorded. All clinical or laboratory parameters at day 14 compared with baseline suggested clinical stability without significant within-group differences in the dapansutrile-pooled group or the 3 dapansutrile cohorts. Improvements in left ventricular EF [from 31.5% (27.5-39) to 36.5% (27.5-45), P = 0.039] and in exercise time [from 570 (399.5-627) to 616 (446.5-688) seconds, P = 0.039] were seen in the dapansutrile 2000 mg cohort. Treatment with dapansutrile for 14 days was safe and well tolerated in patients with stable HFrEF.

Effects of empagliflozin on cardiorespiratory fitness and significant interaction of loop diuretics.

The effects of empagliflozin on cardiorespiratory fitness in patients with type 2 diabetes mellitus (T2DM) and heart failure with reduced ejection fraction (HFrEF) are unknown. In this pilot study we determined the effects of empagliflozin 10 mg/d for 4 weeks on peak oxygen consumption (VO2 ) in 15 patients with T2DM and HFrEF. As an exploratory analysis, we assessed whether there was an interaction of the effects of empagliflozin on peak VO2 of loop diuretics. Empagliflozin reduced body weight (-1.7 kg; P = .031), but did not change peak VO2 (from 14.5 mL kg-1 min-1 [12.6-17.8] to 15.8 [12.5-17.4] mL kg-1 min-1 ; P = .95). However, patients using loop diuretics (N = 9) demonstrated an improvement, whereas those without loop diuretics (N = 6) experienced a decrease in peak VO2 (+0.9 [0.1-1.4] vs -0.9 [-2.1 to -0.3] mL kg-1 min-1 ; P = .001), and peak VO2 changes correlated with the baseline daily dose of diuretics (R = +0.83; P < .001). Empagliflozin did not improve peak VO2 in patients with T2DM and HFrEF. However, as a result of exploratory analysis, patients concomitantly treated with loop diuretics experienced a significant improvement in peak VO2 .

Skeletal muscle quality, measured via phase angle, and cardiorespiratory fitness in patients with obesity and heart failure with preserved ejection fraction.

OBJECTIVES: Cardiorespiratory fitness (CRF) is influenced by body composition quantity and quality in heart failure with preserved ejection fraction (HFpEF) and obesity. Bioelectrical impedance analysis (BIA) provides a noninvasive quantitative and qualitative body composition assessment. The aim of this study was to determine the role of phase angle (PhA), a BIA-measure of skeletal muscle quality and body cell mass, on CRF in patients with obesity and HFpEF. METHODS: Fifty-nine consecutive outpatients with HFpEF underwent cardiopulmonary exercise testing to measure CRF. Single-frequency segmental BIA was used to measure PhA and body composition quantity. Resting Doppler echocardiography and biomarkers were measured to assess cardiac function and systemic inflammation. RESULTS: Compared with patients with lower PhA, patients with higher PhA (above mean 5.8°) presented a greater absolute peak oxygen consumption (VO2; 1.83 [1.3-2.1] versus 1.39 [1.1-1.6] L/min, P = 0.003), VO2 peak adjusted for body weight (17.5 [12.3-18.1] versus 13.3 [12.7-15.2] mL/kg/min, P = 0.040), and a lower edema index (48.7 [2.9] versus 51.4% [2.7], P < 0.001) and N-terminal pro-B-type natriuretic peptide (NT-proBNP; 64 [50-121] versus 183 [68-343.5] pg/dL, P < 0.001). In the overall sample, PhA was correlated with absolute VO2 peak (r = 0.468, P < 0.001), VO2 peak adjusted for body weight (r = 0.368, P = 0.004), VO2 peak adjusted for fat-free mass (r = 0.315, P = 0.015), edema index (r = -0.508, P < 0.001), and NT-proBNP (r = -0.579, P < 0.001). PhA remained a significant predictor for CRF even after adjustment for potential confounders and HFpEF severity. CONCLUSION: In patients with obesity and HFpEF, a greater PhA is an independent predictor for favorable CRF.

Contribution of hemoglobin concentration to cardiorespiratory fitness in black African American patients with recently decompensated heart failure and reduced ejection fraction.

BACKGROUND: Previous studies have shown that patients with heart failure with reduced ejection fraction (HFrEF) and anemia have reduced peak oxygen consumption (VO2). Black or African American (B-AA) patients have a higher prevalence of anemia and are underrepresented in clinical studies of HFrEF. The aim of this study was to determine the contribution of hemoglobin to peak VO2 in B-AA patients recently hospitalized for acute decompensated HFrEF. METHODS: We analyzed cardiopulmonary exercise testing (CPX) data measured within two weeks of discharge for acute decompensated HF in B-AA patients with HFrEF (left ventricular ejection fraction [LVEF] ≤40%) without severe anemia (Hb<8 g/dL). Blood samples were collected prior to CPX. Data are reported as median [interquartile range] and compared between groups with the Mann-Whitney, Chi-Square, and Spearman's rank tests. RESULTS: We included 81 patients; 27 (33%) women, 57 [27-79] years of age, Body Mass Index of 33 [15-55] kg/m2 and LVEF of 30 [23-36] %. Hemoglobin ranged between 9.1 to 18.1 g/dL (median= 13.3 [11.9-14.5] g/dL); 26 (32%) were considered to have anemia based on a Hb concentration of males <13 g/dL and females <12 g/dL. Peak VO2 was lower in patients with anemia (11.8 [10.0-14.2] vs. 14.1 [10.6-17.0] mL·kg-1·min-1; P=0.010) with a significant correlation between peak VO2 and hemoglobin concentration (R=+0.455; P<0.001). CONCLUSIONS: Anemia is prevalent among B-AA patients with recently decompensated HFrEF and appears to be a significant contributor to reductions in peak VO2.

Change in Eosinophil Count in Patients with Heart Failure Treated with Anakinra.

BACKGROUND: Interleukin-1 blockade with anakinra leads to a transient increase in eosinophil blood count (eosinophils) in patients with acute myocardial infarction. We aimed to investigate the effect of anakinra on changes in eosinophils in patients with heart failure (HF) and their correlation with cardiorespiratory fitness (CRF). METHODS: We measured eosinophils in 64 patients with HF (50% females), 55 (51-63) years of age, before and after treatment, and, in a subset of 41 patients, also after treatment cessation. We also evaluated CRF, measuring peak oxygen consumption (VO2) with a treadmill test. RESULTS: Treatment with anakinra significantly and transiently increased eosinophils, from 0.2 [0.1-0.3] to 0.3 [0.1-0.4] × 103 cells/µL (p < 0.001) and from 0.3 [0.2-0.5] to 0.2 [0.1-0.3] × 103 cells/µL, with suspension (p < 0.001). Changes in eosinophils correlated with the changes in peak VO2 (Spearman's Rho = +0.228, p = 0.020). Eosinophils were higher in patients with injection site reactions (ISR) (n = 8, 13%; 0.5 [0.4-0.6] vs. 0.2 [0.1-0.4] × 103 cells/µL, p = 0.023), who also showed a greater increase in peak VO2 (3.0 [0.9-4.3] vs. 0.3 [-0.6-1.8] mLO2·kg-1·min-1, p = 0.015). CONCLUSION: Patients with HF treated with anakinra experience a transient increase in eosinophils, which is associated with ISR and a greater improvement in peak VO2.

Nonpharmacological Strategies in Heart Failure with Preserved Ejection Fraction.

Patients with heart failure with preserved ejection fraction (HFpEF) suffer from a high rate of cardiometabolic comorbidities with limited pharmaceutical therapies proven to improve clinical outcomes and cardiorespiratory fitness (CRF). Nonpharmacologic therapies, such as exercise training and dietary interventions, are promising strategies for this population. The aim of this narrative review is to present a summary of the literature published to date and future directions related to the efficacy of nonpharmacologic, lifestyle-related therapies in HFpEF, with a focus on exercise training and dietary interventions.

Effects of Replacing Sedentary Time With Physical Activity on Mortality Among Patients With Heart Failure: National Health and Nutrition Examination Survey Follow-Up Study.

A sedentary lifestyle is prevalent among patients with heart failure (HF) and is associated with poor prognosis and survival, possibly owing to the displacement of health-enhancing behaviors, such as physical activity (PA). However, there is limited evidence examining the displacement effects of reducing duration of sedentary time (ST) on clinical outcomes in patients with HF. The current study examined the theoretical effects of relocating ST with PA on all-cause and cardiovascular disease (CVD)-specific mortality risks in patients with HF. We analyzed 265 patients with HF who participated in the National Health and Nutrition Examination Survey from 2003 to 2006. Cox proportional hazards regression model was fitted to estimate mortality risks based on objectively measured ST well as time spent in light-intensity PA (LPA) and moderate- and vigorous-intensity PA (MVPA). The theoretical changes in the hazard ratio (HR) by replacing ST with LPA or MVPA were examined using isotemporal substitutional modeling. On average, patients with HF spent 70% of waking hours per day in ST (9.01 hours), followed by LPA (29%; 3.75 hours) and MVPA (1%; 0.13 hours). Ten-minute substitution of ST with LPA was associated with significantly lower all-cause and CVD-specific mortality risks (hazard ratio [HR]=0.93 for both). The mortality risks progressively decreased as more ST was relocated to LPA. The relocation effects of ST with MVPA were not statistically significant, possibly because of limited MVPA accrued in this clinical population. The current study provides empirical evidence about the potential health benefits of replacing a modest amount of ST with LPA among patients with HF.

Midpoint of energy intake, non-fasting time and cardiorespiratory fitness in heart failure with preserved ejection fraction and obesity.

BACKGROUND: Delayed time of evening meal is associated with favorable cardiorespiratory fitness (CRF) in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. It is unknown, however, if increasing daily non-fasting time or delaying the midpoint of energy intake may also be associated with CRF. OBJECTIVE: Our aim was to examine whether a longer non-fasting time, delayed midpoint of energy intake, or both, are associated with greater CRF in patients with HFpEF and obesity. METHODS: We measured peak oxygen consumption (VO2), a measure of CRF, in 32 patients with HFpEF and obesity with cardiopulmonary exercise testing, and dietary intake using a five-pass 24-h dietary recall. Participants were divided into groups by having lesser (<11.6) or greater (≥11.6) periods of non-fasting time than the median and similarly, with earlier (<2:15 PM) or later (≥2:15 PM) than median midpoint of energy intake. RESULTS: Median non-fasting time was 11.6 [10.6-12.9] hours and midpoint of energy intake was 2:15 [1:04-3:00] PM. There were no differences in CRF between those with a shorter (<11.6) or longer (≥11.6) non-fasting time. Participants with a delayed midpoint of energy intake (≥2:15 PM) had greater peak VO2 and exercise time. Midpoint of energy intake (r = 0.444, P = 0.011) and time of last meal (r = 0.550, P = 0.001) displayed a positive association with peak VO2, but not non-fasting time nor time of first meal. CONCLUSIONS: Delaying the midpoint of energy intake by postponing last meal is associated with better peak VO2 and exercise time in patients with HFpEF and obesity.

Sarcopenic Obesity Is Associated With Reduced Cardiorespiratory Fitness Compared With Nonsarcopenic Obesity in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Sarcopenia impairs cardiorespiratory fitness (CRF) in patients with heart failure with reduced ejection fraction (HFrEF). Obesity has also been shown to impair CRF; however, the effects of sarcopenia on CRF in patients with obesity and HFrEF are unknown. The aim of this analysis was to examine differences in CRF between patients with sarcopenic obesity (SO) and non-SO (NSO) with HFrEF. We also assessed associations between skeletal muscle mass index (SMMI) and CRF. METHODS: Forty patients with HFrEF and obesity underwent cardiopulmonary exercise testing to collect measures of CRF including peak oxygen consumption (VO2), circulatory power, oxygen uptake efficiency slope, O2 pulse, and exercise time. Body composition was performed in all patients using bioelectrical impedance analysis to quantify fat mass index and divide patients into SO and NSO based on SMMI cutoffs. Results are presented as mean (SD) or median [interquartile range] as appropriate. RESULTS: Nearly half (43% [n=17]) of patients had SO. Patients with SO had a lower SMMI than those with NSO, and no differences in fat mass index were observed between groups. Those with SO achieved a lower absolute peak VO2 (NSO, 1.62±0.53 L·min-1 versus SO, 1.27±0.44 L·min-1, P=0.035), oxygen uptake efficiency slope (NSO, 1.92±0.59 versus SO, 1.54±0.48, P=0.036), and exercise time (NSO, 549±198 seconds versus SO, 413±140 seconds, P=0.021) compared to those with NSO. On multivariate analysis, SMMI remained a significant predictor of absolute peak VO2 when adjusted for age, sex, adiposity, and HF severity. CONCLUSIONS: In patients with HFrEF and obesity, sarcopenia, defined as low SMMI, is associated with a clinically significant reduction in CRF, independent of adiposity.

Left ventricular concentric remodeling and impaired cardiorespiratory fitness in patients with heart failure and preserved ejection fraction.

BACKGROUND: Left ventricular (LV) concentric remodeling refers to a process by which increased LV relative wall thickness alters myocardial geometry, resulting in reduced LV end-diastolic volume (LVEDV) and stroke volume (SV). While the degree of concentric remodeling is a negative prognostic factor in heart failure with preserved ejection fraction (HFpEF), it is not known how it contributes to cardiorespiratory fitness (CRF). METHODS: We performed a retrospective analysis of patients with HFpEF who underwent treadmill single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) and cardiopulmonary exercise testing (CPX). From exercise SPECT-MPI, we recorded postexercise LVEDVi, LVESVi, SVi, LVEF, the presence and extent of perfusion defects, and perfusion reversibility. Peak oxygen consumption (VO2), the oxygen uptake efficiency slope (OUES), oxygen (O2) pulse, ventilatory efficiency (VE/VCO2 slope), ventilatory anaerobic threshold, respiratory exchange ratio, exercise time, and maximum heart rate were obtained from CPX. Data are expressed as mean (±standard deviation). Univariate and multivariate linear regression was performed. RESULTS: We identified 23 subjects who had completed both an exercise SPECT-MPI and a CPX. Patients were more commonly women (83%), black (65%), middle age (50 [±7.3] years), and obese (Body Mass Index [BMI] 39.7 [±6.0] kg/m2). Greater LVEDVi and LVESVi correlated positively with peak VO2 (R=+0.648, P=0.001; R=+0.601, P=0.002), O2 pulse (R=+0.686, P<0.001; R=+0.625, P=0.001) and OUES (R=+0.882, P<0.001; R=+0.779, P<0.001). The LVEF correlated inversely with peak VO2 and OUES (R=-0.450, P=0.031; R=-0.485, P=0.035). Perfusion defect area, grade of severity, and presence of reversibility were not associated with CRF variables. CONCLUSIONS: Postexercise reduced LV volumes correlate with measures of impaired CRF in patients with HFpEF, thus supporting a pathophysiologic role of concentric remodeling in impaired CRF in HFpEF.

The role of diet and nutrition in heart failure: A state-of-the-art narrative review.

Heart Failure (HF) incidence is increasing steadily worldwide, while prognosis remains poor. Though nutrition is a lifestyle factor implicated in prevention of HF, little is known about the effects of macro- and micronutrients as well as dietary patterns on the progression and treatment of HF. This is reflected in a lack of nutrition recommendations in all major HF scientific guidelines. In this state-of-the-art review, we examine and discuss the implications of evidence contained in existing randomized control trials as well as observational studies covering the topics of sodium restriction, dietary patterns and caloric restriction as well as supplementation of dietary fats and fatty acids, protein and amino acids and micronutrients in the setting of pre-existing HF. Finally, we explore future directions and discuss knowledge gaps regarding nutrition therapies for the treatment of HF.

Sarcopenic Obesity in Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a public health epidemic that is projected to double over the next two decades. Despite the high prevalence of HFpEF, there are currently no FDA approved therapies for health-related outcomes in this clinical syndrome making it one the greatest unmet needs in cardiovascular medicine. Aging and obesity are hallmarks of HFpEF and therefore there is a high incidence of sarcopenic obesity (SO) associated with this syndrome. The presence of SO in HFpEF patients is noteworthy as it is associated with co-morbidities, worsened cardiovascular health, hospitalizations, quality of life, and mortality. Furthermore, SO plays a central role in exercise intolerance, the most commonly reported clinical symptom of this condition. The aim of this review is to provide insights into the current knowledge pertaining to the contributing pathophysiological mechanisms and clinical outcomes associated with HFpEF-related SO. Current and prospective therapies to address SO in HFpEF, including lifestyle and pharmaceutical approaches, are discussed. The urgent need for future research aimed at better understanding the multifaceted physiological contributions to SO in HFpEF and implementing interventional strategies to specifically target SO is highlighted.

Lean Mass Abnormalities in Heart Failure: The Role of Sarcopenia, Sarcopenic Obesity, and Cachexia.

The role of body composition in patients with heart failure (HF) has been receiving much attention in the last few years. Particularly, reduced lean mass (LM), the best surrogate for skeletal muscle mass, is independently associated with abnormal cardiorespiratory fitness (CRF) and muscle strength, ultimately leading to reduced quality of life and worse prognosis. While in the past, reduced CRF in patients with HF was thought to result exclusively from cardiac dysfunction leading to reduced cardiac output at peak exercise, current evidence supports the concept that abnormalities in LM may also play a critical role. Abnormalities in the LM body composition compartment are associated with the development of sarcopenia, sarcopenic obesity, and cachexia. Such conditions have been implicated in the pathophysiology and progression of HF. However, identification of such conditions remains challenging, as universal definitions for sarcopenia, sarcopenic obesity, and cachexia are lacking. In this review article, we describe the most common body composition abnormalities related to the LM compartment, including skeletal and respiratory muscle mass abnormalities, and the consequences of such anomalies on CRF and muscle strength in patients with HF. Finally, we discuss the potential nonpharmacologic therapeutic strategies such as exercise training (ie, aerobic exercise and resistance exercise) and dietary interventions (ie, dietary supplementation and dietary patterns) that have been implemented to target body composition, with a focus on HF.

Obesity paradox in cardiovascular disease: where do we stand?

Obesity is associated with an increased risk of developing cardiovascular disease (CVD), particularly heart failure (HF) and coronary heart disease (CHD). The mechanisms through which obesity increases CVD risk involve changes in body composition that can affect hemodynamics and alters heart structure. Pro-inflammatory cytokines produced by the adipose tissue itself which can induce cardiac dysfunction and can promote the formation of atherosclerotic plaques. When obesity and HF or CHD coexist, individuals with class I obesity present a more favorable prognosis compared to individuals who are normal or underweight. This phenomenon has been termed the "obesity paradox." Obesity is defined as an excess fat mass (FM), but individuals with obesity typically also present with an increased amount of lean mass (LM). The increase in LM may explain part of the obesity paradox as it is associated with improved cardiorespiratory fitness (CRF), a major determinant of clinical outcomes in the general population, but particularly in those with CVD, including HF. While increased LM is a stronger prognosticator in HF compared to FM, in patients with CHD excess FM can exert protective effects particularly when not associated with increased systemic inflammation. In the present review, we discuss the mechanisms through which obesity may increase the risk for CVD, and how it may exert protective effects in the setting of established CVD, with a focus on body composition. We also highlight the importance of measuring or estimating CRF, including body composition-adjusted measures of CRF (ie, lean peak oxygen consumption) for an improved risk status stratification in patients with CVD and finally, we discuss the potential non-pharmacologic therapeutics, such as exercise training and dietary interventions, aimed at improving CRF and perhaps clinical outcomes.