Dataset Information

Effect of Caloric Restriction or Aerobic Exercise Training on Peak Oxygen Consumption and Quality of Life in Obese Older Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial.

ABSTRACT:

Importance

More than 80% of patients with heart failure with preserved ejection fraction (HFPEF), the most common form of heart failure among older persons, are overweight or obese. Exercise intolerance is the primary symptom of chronic HFPEF and a major determinant of reduced quality of life (QOL).

Objective

To determine whether caloric restriction (diet) or aerobic exercise training (exercise) improves exercise capacity and QOL in obese older patients with HFPEF.

Design, setting, and participants

Randomized, attention-controlled, 2?×?2 factorial trial conducted from February 2009 through November 2014 in an urban academic medical center. Of 577 initially screened participants, 100 older obese participants (mean [SD]: age, 67 years [5]; body mass index, 39.3 [5.6]) with chronic, stable HFPEF were enrolled (366 excluded by inclusion and exclusion criteria, 31 for other reasons, and 80 declined participation).

Interventions

Twenty weeks of diet, exercise, or both; attention control consisted of telephone calls every 2 weeks.

Main outcomes and measures

Exercise capacity measured as peak oxygen consumption (V?O2, mL/kg/min; co-primary outcome) and QOL measured by the Minnesota Living with Heart Failure (MLHF) Questionnaire (score range: 0-105, higher scores indicate worse heart failure-related QOL; co-primary outcome).

Results

Of the 100 enrolled participants, 26 participants were randomized to exercise; 24 to diet; 25 to exercise?+?diet; 25 to control. Of these, 92 participants completed the trial. Exercise attendance was 84% (SD, 14%) and diet adherence was 99% (SD, 1%). By main effects analysis, peak V?O2 was increased significantly by both interventions: exercise, 1.2 mL/kg body mass/min (95% CI, 0.7 to 1.7), P?Conclusions and relevanceAmong obese older patients with clinically stable HFPEF, caloric restriction or aerobic exercise training increased peak V?O2, and the effects may be additive. Neither intervention had a significant effect on quality of life as measured by the MLHF Questionnaire.

Trial registration

clinicaltrials.gov Identifier: NCT00959660.

SUBMITTER: Kitzman DW

PROVIDER: S-EPMC4787295 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of Caloric Restriction or Aerobic Exercise Training on Peak Oxygen Consumption and Quality of Life in Obese Older Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial.

Kitzman Dalane W DW Brubaker Peter P Morgan Timothy T Haykowsky Mark M Hundley Gregory G Kraus William E WE Eggebeen Joel J Nicklas Barbara J BJ

JAMA 20160101 1

<h4>Importance</h4>More than 80% of patients with heart failure with preserved ejection fraction (HFPEF), the most common form of heart failure among older persons, are overweight or obese. Exercise intolerance is the primary symptom of chronic HFPEF and a major determinant of reduced quality of life (QOL).<h4>Objective</h4>To determine whether caloric restriction (diet) or aerobic exercise training (exercise) improves exercise capacity and QOL in obese older patients with HFPEF.<h4>Design, sett ...[more]

PMID: 26746456

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Project description:ImportanceHeart failure with preserved ejection fraction (HFpEF) is often characterized by nitric oxide deficiency.ObjectiveTo evaluate the efficacy and adverse effects of praliciguat, an oral soluble guanylate cyclase stimulator, in patients with HFpEF.Design, setting, and participantsCAPACITY HFpEF was a randomized, double-blind, placebo-controlled, phase 2 trial. Fifty-nine sites enrolled 196 patients with heart failure and an ejection fraction of at least 40%, impaired peak rate of oxygen consumption (peak V̇o2), and at least 2 conditions associated with nitric oxide deficiency (diabetes, hypertension, obesity, or advanced age). The trial randomized patients to 1 of 3 praliciguat dose groups or a placebo group, but was refocused early to a comparison of the 40-mg praliciguat dose vs placebo. Participants were enrolled from November 15, 2017, to April 30, 2019, with final follow-up on August 19, 2019.InterventionsPatients were randomized to receive 12 weeks of treatment with 40 mg of praliciguat daily (n = 91) or placebo (n = 90).Main outcomes and measuresThe primary efficacy end point was the change from baseline in peak V̇o2 in patients who completed at least 8 weeks of assigned dosing. Secondary end points included the change from baseline in 6-minute walk test distance and in ventilatory efficiency (ventilation/carbon dioxide production slope). The primary adverse event end point was the incidence of treatment-emergent adverse events (TEAEs).ResultsAmong 181 patients (mean [SD] age, 70 [9] years; 75 [41%] women), 155 (86%) completed the trial. In the placebo (n = 78) and praliciguat (n = 65) groups, changes in peak V̇o2 were 0.04 mL/kg/min (95% CI, -0.49 to 0.56) and -0.26 mL/kg/min (95% CI, -0.83 to 0.31), respectively; the placebo-adjusted least-squares between-group difference in mean change from baseline was -0.30 mL/kg/min ([95% CI, -0.95 to 0.35]; P = .37). None of the 3 prespecified secondary end points were statistically significant. In the placebo and praliciguat groups, changes in 6-minute walk test distance were 58.1 m (95% CI, 26.1-90.1) and 41.4 m (95% CI, 8.2-74.5), respectively; the placebo-adjusted least-squares between-group difference in mean change from baseline was -16.7 m (95% CI, -47.4 to 13.9). In the placebo and praliciguat groups, the placebo-adjusted least-squares between-group difference in mean change in ventilation/carbon dioxide production slope was -0.3 (95% CI, -1.6 to 1.0). There were more dizziness (9.9% vs 1.1%), hypotension (8.8% vs 0%), and headache (11% vs 6.7%) TEAEs with praliciguat compared with placebo. The frequency of serious TEAEs was similar between the groups (10% in the praliciguat group and 11% in the placebo group).Conclusions and relevanceAmong patients with HFpEF, the soluble guanylate cyclase stimulator praliciguat, compared with placebo, did not significantly improve peak V̇o2 from baseline to week 12. These findings do not support the use of praliciguat in patients with HFpEF.Trial registrationClinicalTrials.gov Identifier: NCT03254485.

Project description:BackgroundComorbidity-driven microvascular inflammation is posited as a unifying pathophysiologic mechanism for heart failure with preserved ejection fraction (HFpEF). Obesity is proinflammatory and common in HFpEF. We hypothesized that unique obesity-inflammation HFpEF phenotypes exist and are associated with differences in clinical features, fibrosis biomarkers, and functional performance.MethodsPatients (n=301) from 3 HFpEF clinical trials were studied. Unsupervised machine learning (hierarchical clustering) with obese status and 13 inflammatory biomarkers as input variables was performed. Associations of clusters with HFpEF severity and fibrosis biomarkers (PIIINP [procollagen III N-terminal peptide], CITP [C-telopeptide for type I collagen], IGFBP7 [insulin-like growth factor-binding protein-7], and GAL-3 [galectin-3]) were assessed.ResultsHierarchical clustering revealed 3 phenotypes: pan-inflammatory (n=129; 64% obese), noninflammatory (n=83; 55% obese), and obese high CRP (C-reactive protein; n=89; 98% obese). The pan-inflammatory phenotype had more comorbidities and heart failure hospitalizations; higher left atrial volume, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and fibrosis biomarkers; and lower glomerular filtration rate, peak oxygen consumption, 6-minute walk distance, and active hours/day (P<0.05 for all). The noninflammatory phenotype had the most favorable values for all measures. The obese high CRP phenotype resembled the noninflammatory phenotype except for isolated elevation of CRP and lower functional performance. Hierarchical cluster assignment was independent of CRP genotype combinations that alter CRP levels and more biologically plausible than other clustering approaches. Multiple traditional analytic techniques confirmed and extended the hierarchical clustering findings.ConclusionsUnique obesity-inflammation phenotypes exist in HFpEF and are associated with differences in comorbidity burden, HFpEF severity, and fibrosis. These data support comorbidity-driven microvascular inflammation as a pathophysiologic mechanism for many but not all HFpEF patients.

Project description:ImportanceEndurance exercise is effective in improving peak oxygen consumption (peak V̇o2) in patients with heart failure with preserved ejection fraction (HFpEF). However, it remains unknown whether differing modes of exercise have different effects.ObjectiveTo determine whether high-intensity interval training, moderate continuous training, and guideline-based advice on physical activity have different effects on change in peak V̇o2 in patients with HFpEF.Design, setting, and participantsRandomized clinical trial at 5 sites (Berlin, Leipzig, and Munich, Germany; Antwerp, Belgium; and Trondheim, Norway) from July 2014 to September 2018. From 532 screened patients, 180 sedentary patients with chronic, stable HFpEF were enrolled. Outcomes were analyzed by core laboratories blinded to treatment groups; however, the patients and staff conducting the evaluations were not blinded.InterventionsPatients were randomly assigned (1:1:1; n = 60 per group) to high-intensity interval training (3 × 38 minutes/week), moderate continuous training (5 × 40 minutes/week), or guideline control (1-time advice on physical activity according to guidelines) for 12 months (3 months in clinic followed by 9 months telemedically supervised home-based exercise).Main outcomes and measuresPrimary end point was change in peak V̇o2 after 3 months, with the minimal clinically important difference set at 2.5 mL/kg/min. Secondary end points included changes in metrics of cardiorespiratory fitness, diastolic function, and natriuretic peptides after 3 and 12 months.ResultsAmong 180 patients who were randomized (mean age, 70 years; 120 women [67%]), 166 (92%) and 154 (86%) completed evaluation at 3 and 12 months, respectively. Change in peak V̇o2 over 3 months for high-intensity interval training vs guideline control was 1.1 vs -0.6 mL/kg/min (difference, 1.5 [95% CI, 0.4 to 2.7]); for moderate continuous training vs guideline control, 1.6 vs -0.6 mL/kg/min (difference, 2.0 [95% CI, 0.9 to 3.1]); and for high-intensity interval training vs moderate continuous training, 1.1 vs 1.6 mL/kg/min (difference, -0.4 [95% CI, -1.4 to 0.6]). No comparisons were statistically significant after 12 months. There were no significant changes in diastolic function or natriuretic peptides. Acute coronary syndrome was recorded in 4 high-intensity interval training patients (7%), 3 moderate continuous training patients (5%), and 5 guideline control patients (8%).Conclusions and relevanceAmong patients with HFpEF, there was no statistically significant difference in change in peak V̇o2 at 3 months between those assigned to high-intensity interval vs moderate continuous training, and neither group met the prespecified minimal clinically important difference compared with the guideline control. These findings do not support either high-intensity interval training or moderate continuous training compared with guideline-based physical activity for patients with HFpEF.Trial registrationClinicalTrials.gov Identifier: NCT02078947.

Project description:BACKGROUND:Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. Phenotyping patients into pathophysiologically homogeneous groups may enable better targeting of treatment. Obesity is common in HFpEF and has many cardiovascular effects, suggesting that it may be a viable candidate for phenotyping. We compared cardiovascular structure, function, and reserve capacity in subjects with obese HFpEF, those with nonobese HFpEF, and control subjects. METHODS:Subjects with obese HFpEF (body mass index ?35 kg/m2; n=99), nonobese HFpEF (body mass index <30 kg/m2; n=96), and nonobese control subjects free of HF (n=71) underwent detailed clinical assessment, echocardiography, and invasive hemodynamic exercise testing. RESULTS:Compared with both subjects with nonobese HFpEF and control subjects, subjects with obese HFpEF displayed increased plasma volume (3907 mL [3563-4333 mL] versus 2772 mL [2555-3133 mL], and 2680 mL [2380-3006 mL]; P<0.0001), more concentric left ventricular remodeling, greater right ventricular dilatation (base, 34±7 versus 31±6 and 30±6 mm, P=0.0005; length, 66±7 versus 61±7 and 61±7 mm, P<0.0001), more right ventricular dysfunction, increased epicardial fat thickness (10±2 versus 7±2 and 6±2 mm; P<0.0001), and greater total epicardial heart volume (945 mL [831-1105 mL] versus 797 mL [643-979 mL] and 632 mL [517-768 mL]; P<0.0001), despite lower N-terminal pro-B-type natriuretic peptide levels. Pulmonary capillary wedge pressure was correlated with body mass and plasma volume in obese HFpEF (r=0.22 and 0.27, both P<0.05) but not in nonobese HFpEF (P?0.3). The increase in heart volumes in obese HFpEF was associated with greater pericardial restraint and heightened ventricular interdependence, reflected by increased ratio of right- to left-sided heart filling pressures (0.64±0.17 versus 0.56±0.19 and 0.53±0.20; P=0.0004), higher pulmonary venous pressure relative to left ventricular transmural pressure, and greater left ventricular eccentricity index (1.10±0.19 versus 0.99±0.06 and 0.97±0.12; P<0.0001). Interdependence was enhanced as pulmonary artery pressure load increased (P for interaction <0.05). Compared with those with nonobese HFpEF and control subjects, obese patients with HFpEF displayed worse exercise capacity (peak oxygen consumption, 7.7±2.3 versus 10.0±3.4 and12.9±4.0 mL/min·kg; P<0.0001), higher biventricular filling pressures with exercise, and depressed pulmonary artery vasodilator reserve. CONCLUSIONS:Obesity-related HFpEF is a genuine form of cardiac failure and a clinically relevant phenotype that may require specific treatments.

Dataset Information

Effect of Caloric Restriction or Aerobic Exercise Training on Peak Oxygen Consumption and Quality of Life in Obese Older Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial.

Importance

Objective

Design, setting, and participants

Interventions

Main outcomes and measures

Results

Trial registration

Publications

Effect of Caloric Restriction or Aerobic Exercise Training on Peak Oxygen Consumption and Quality of Life in Obese Older Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial.

Similar Datasets

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