The effect of Aliskiren on exercise capacity in older patients with heart failure and preserved ejection fraction: A randomized, placebo-controlled, double-blind trial.
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ABSTRACT:
SUBMITTER: Upadhya B
PROVIDER: S-EPMC7707854 | biostudies-literature | 2018 Jul
REPOSITORIES: biostudies-literature
Publications
The effect of Aliskiren on exercise capacity in older patients with heart failure and preserved ejection fraction: A randomized, placebo-controlled, double-blind trial.
Upadhya Bharathi B Brubaker Peter H PH Morgan Timothy M TM Eggebeen Joel D JD Jao Geoffrey T GT Stewart Kathryn P KP Kitzman Dalane W DW
American heart journal 20180404
In older patients (70 ± 7 years) with chronic well-compensated heart failure with preserved ejection and controlled blood pressure, 6 months treatment with aliskiren (direct renin inhibitor) showed non-significant trends for modest improvements in peak exercise oxygen consumption (14.9 ± 0.2 mL kg<sup>-1</sup> min<sup>-1</sup> versus 14.4 ± 0.2 mL kg<sup>-1</sup> min<sup>-1</sup>; P = .10, trend) and ventilatory anaerobic threshold (888 ± 19 mL/min versus 841 ± 18 mL/min; P = .08). ...[more]
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Project description:Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by impaired exercise capacity due to shortness of breath and/or fatigue. Assessment of diastolic dysfunction at rest and with exercise may provide insight into the pathophysiology of exercise intolerance in HFpEF.To measure echocardio-Doppler-derived parameters of diastolic function as they relate to various indices of aerobic exercise capacity in HFpEF.We selected 16 subjects with clinically stable HFpEF, no evidence of volume overload, but impaired functional capacity by cardiopulmonary exercise testing [peak oxygen consumption (VO2 )]. We measured the transmitral E and A flow velocities, E/A ratio, and E deceleration time (DT) and tissue Doppler E' velocity. We also indexed the E' to the DT, as additional measure of impaired relaxation (E'DT ), and calculated the diastolic functional reserve index (DFRI), as the product of E' at rest and change in E' with exercise.E' velocity, at rest and peak exercise, as well as the DFRI positively correlated with peak VO2 , whereas DT, E'DT , and E/E' with exercise inversely correlated with peak VO2 . Of note, the E'DT at rest also significantly predicted E' velocity at peak exercise (R = +0.81, P < 0.001). Exercise E' was the only independent predictor of peak VO2 at multivariable analysis (R = +0.67, P = 0.005).The E' velocity at peak exercise is a strong and independent predictor of aerobic exercise capacity as measured by peak VO2 in patients with HFpEF, providing the link between abnormal myocardial relaxation with exercise and impaired aerobic exercise capacity in HFpEF.
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Project description:BackgroundHeart failure with preserved ejection fraction (HFpEF) is characterized by left ventricular hypertrophy and decreased exercise capacity. Fibroblast growth factor 23 (FGF23), a hormone involved in phosphate, vitamin D, and iron homeostasis, is linked to left ventricular hypertrophy and HF. We measured c-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels and examined their associations with exercise capacity in patients with HFpEF.Methods and resultsUsing multivariable linear regression and linear mixed models, we studied the associations of cFGF23 and iFGF23 with baseline and mean weekly change over 24 weeks in peak oxygen consumption and 6-minute walk distance in individuals enrolled in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF trial. Our study population included 172 individuals with available plasma for cFGF23 and iFGF23 measurements. Median (25th-75th percentile) baseline cFGF23 and iFGF23 levels were 208.7 RU/mL (132.1-379.5 RU/mL) and 90.3 pg/mL (68.6-128.5 pg/mL), respectively. After adjustment for cardiovascular disease and hematologic and kidney parameters, higher cFGF23 was independently associated with a lower peak oxygen consumption at baseline. Higher iFGF23 was independently associated with shorter 6-minute walk distance at baseline. No significant associations were appreciated with the longitudinal outcomes.ConclusionsIn patients with HFpEF, higher FGF23 levels are independently associated with decreased exercise capacity at baseline.
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| S-EPMC5823250 | biostudies-literature
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| S-EPMC5543763 | biostudies-other
Project description:BackgroundHeart failure with preserved ejection fraction (HFpEF) is common in elderly people and is increasing in prevalence. No specific treatment for this condition exists. Coenzyme Q10 (CoQ10) is an essential cofactor for energy production, with reduced levels being noted in HF. Previous studies have suggested a possible role for CoQ10 in the treatment of HF. This study examined the effect of CoQ10 supplementation on diastolic function in HFpEF patients.MethodsWe conducted a prospective, randomized, double-blind, placebo-controlled trial including patients aged > 55 years presenting with New York Heart Association class II-IV heart failure symptoms and left ventricular ejection fraction > 50%, with impaired diastolic function. Echocardiography and levels of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) were performed at baseline and following 4 months of CoQ10 or placebo supplementation.ResultsA total of 39 patients were enrolled-19 in the CoQ10 group and 20 in the placebo group. Baseline clinical characteristics were similar between groups, while compliance was high and also similar between the CoQ10 and placebo groups. There was no significant effect of treatment on indices of diastolic function (difference in the lateral E/e' ratio: -0.86 ± 6.57 in the CoQ10 group, +0.18 ± 3.76 in the placebo group; p = 0.561) or on serum NT-proBNP levels (- 72 pg/mL vs. - 42 pg/mL; p = 0.195).ConclusionsIn this pilot trial in elderly patients with HFpEF, treatment with CoQ10 did not significantly affect echocardiographic indices of diastolic function and serum NT-proBNP levels.Trial registrationThis trial was registered in the US National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT02779634).
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Project description:Exercise intolerance is a principal feature of heart failure with preserved ejection fraction (HFpEF), whether or not there is evidence of congestion at rest. The degree of functional limitation observed in HFpEF is comparable to patients with advanced heart failure and reduced ejection fraction. Exercise intolerance in HFpEF is characterized by impairments in the physiological reserve capacity of multiple organ systems, but the relative cardiac and extracardiac deficits vary among individuals. Detailed measurements made during exercise are necessary to identify and rank-order the multiorgan system limitations in reserve capacity that culminate in exertional intolerance in a given person. We use a case-based approach to comprehensively review mechanisms of exercise intolerance and optimal approaches to evaluate exercise capacity in HFpEF. We also summarize recent and ongoing trials of novel devices, drugs, and behavioral interventions that aim to improve specific exercise measures such as peak oxygen uptake, 6-min walk distance, heart rate, and hemodynamic profiles in HFpEF. Evaluation during the clinically relevant physiological perturbation of exercise holds promise to improve the precision with which HFpEF is defined and therapeutically targeted.
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Project description:AimsExercise intolerance is the leading manifestation of heart failure with preserved or mid-range ejection fraction (HFpEF or HFmrEF), and left atrial (LA) function might contribute to modulating left ventricular filling and pulmonary venous pressures. We aim to assess the association between LA function and maximal exercise capacity in patients with HFpEF or HFmrEF.Methods and resultsSixty-five patients, prospectively enrolled in the German HFpEF Registry, were analysed. Inclusion criteria were New York Heart Association functional class ≥ II, left ventricular ejection fraction > 40%, structural heart disease or diastolic dysfunction, and elevated levels of N terminal pro brain natriuretic peptide (NT-proBNP). LA function was evaluated through speckle-tracking echocardiography by central reading in the Charité Academic Echocardiography core lab. All patients underwent maximal cardiopulmonary exercise test and were classified according to a peak VO2 cut-off of prognostic value (14 mL/kg/min). NT-pro-BNP was measured. Twenty-nine patients (45%) reached a peak VO2 < 14 mL/kg/min (mean value 12.4 ± 1.5) and 36 patients (55%) peak VO2 ≥ 14 mL/kg/min (mean value 19.4 ± 3.9). There was no significant difference in left ventricular ejection fraction (60 ± 9 vs. 59 ± 8%), left ventricular mass (109 ± 23 vs. 112 ± 32 g/m2 ), LA volume index (45 ± 17 vs. 47 ± 22 mL/m2 ), or E/e´ (13.1 ± 4.7 vs. 13.0 ± 6.0) between these groups. In contrast, all LA strain measures were impaired in patients with lower peak VO2 (reservoir strain 14 ± 5 vs. 21 ± 9%, P = 0.002; conduit strain 9 ± 2 vs. 13 ± 4%, P = 0.001; contractile strain 7 ± 4 vs. 11 ± 6%, P = 0.02; reported lower limits of normality for LA reservoir, conduit and contractile strains: 26.1%, 12.0%, and 7.7%). In linear regression analysis, lower values of LA reservoir strain were associated with impaired peak VO2 after adjustment for age, sex, body mass index, heart rhythm (sinus/AFib), and log-NTproBNP [β 0.29, 95% confidence interval (CI) 0.02-0.30, P = 0.02], with an odds ratio 1.22 (95% CI 1.05-1.42, P = 0.01) for peak VO2 < 14 mL/kg/min for LA reservoir strain decrease after adjustment for these five covariates. Adding left ventricular ejection fraction, it did not influence the results. On the other hand, the addition of LA strain to the adjustment parameters alone described above provided a significant increase of the predictive value for lower peak VO2 values (R2 0.50 vs. 0.45, P = 0.02). With receiver operating characteristic curve analysis, we identified LA reservoir strain < 22% to have 93% sensitivity and 49% specificity in predicting peak VO2 < 14 mL/kg/min. Using this cut-off, LA reservoir strain < 22% was associated with peak VO2 < 14 mL/kg/min in logistic regression analysis after comprehensive adjustment for age, sex, body mass index, heart rhythm, and log-NTproBNP [odds ratio 95% CI 10.4 (1.4-74), P = 0.02].ConclusionsIn this HFpEF and HFmrEF cohort, a reduction in LA reservoir strain was a sensible marker of decreased peak exercise capacity. Therefore, LA reservoir strain might be of clinical value in predicting exercise capacity in patients with HFpEF or HFmrEF.
| S-EPMC7835603 | biostudies-literature
Project description:ImportanceSex differences in heart failure with preserved ejection fraction (HFpEF) have been established, but insights into the mechanistic drivers of these differences are limited.ObjectiveTo examine sex differences in cardiometabolic profiles and exercise hemodynamic profiles among individuals with HFpEF.Design, setting, and participantsThis cross-sectional study was conducted at a single-center tertiary care referral hospital from December 2006 to June 2017 and included 295 participants who met hemodynamic criteria for HFpEF based on invasive cardiopulmonary exercise testing results. We examined sex differences in distinct components of oxygen transport and utilization during exercise using linear and logistic regression models. The data were analyzed from June 2018 to May 2019.Main outcomes and measuresResting and exercise gas exchange and hemodynamic parameters obtained during cardiopulmonary exercise testing.ResultsOf 295 participants, 121 (41.0%) were men (mean [SD] age, 64 [12] years) and 174 (59.0%) were women (mean [SD] age, 61 [13] years). Compared with men, women with HFpEF in this tertiary referral cohort had fewer comorbidities, including diabetes, insulin resistance, and hypertension, and a more favorable adipokine profile. Exercise capacity was similar in men and women (percent predicted peak oxygen [O2] consumption: 66% in women vs 68% in men; P = .38), but women had distinct deficits in components of the O2 pathway, including worse biventricular systolic reserve (multivariable-adjusted analyses: ΔLVEF β = -1.70; SE, 0.86; P < .05; ΔRVEF β = -2.39, SE=0.80; P = .003), diastolic reserve (PCWP/CO: β = 0.63; SE, 0.31; P = .04), and peripheral O2 extraction (C(a-v)O2 β=-0.90, SE=0.22; P < .001)).Conclusions and relevanceDespite a lower burden of cardiometabolic disease and a similar percent predicted exercise capacity, women with HFpEF demonstrated greater cardiac and extracardiac deficits, including systolic reserve, diastolic reserve, and peripheral O2 extraction. These sex differences in cardiac and skeletal muscle responses to exercise may illuminate the pathophysiology underlying the development of HFpEF and should be investigated further.
| S-EPMC6822160 | biostudies-literature
Project description:AimsThis study aimed to assess plasma fibroblast growth factor 23 (FGF23) in patients with heart failure with preserved ejection fraction (HFpEF) and its relation to inflammation, renal function, clinical and imaging characteristics, exercise capacity, and prognosis.Methods and resultsWe performed a prospective, observational study of 172 age-matched and sex-matched subjects (HFpEF n = 130; controls n = 42, age 73 ± 9, female 50%) who underwent plasma biomarker sampling, echocardiography, cardiac magnetic resonance imaging, and 6 min walk testing (6MWT). The primary endpoint was the composite of all-cause death or HF hospitalization. FGF23 was higher in HFpEF compared with controls (62 [42-105] vs. 34 [22-41] pg/mL, P < 0.0001). In HFpEF, FGF23 correlated with greater symptom burden (New York Heart Association class: r = 0.308), poorer exercise capacity (6MWT distance: r = -0.345), and plasma biomarkers reflecting inflammation (highly sensitive C-reactive protein: r = 0.207, myeloperoxidase: r = 0.311), bone metabolism (osteoprotegerin: r = 0.446), renal dysfunction (urea: r = 0.267, creatinine: r = 0.351, estimated glomerular filtration rate: r = -0.367), and echocardiographic E/e' (r = 0.298); P < 0.05. Following multivariable linear regression modelling, FGF23 remained independently associated with shorter 6MWT distance (P = 0.012) in addition to age, body mass index, and lower haemoglobin. During follow-up (median 1428 days), there were 61 composite events (21 deaths, 40 HF hospitalizations) in patients with HFpEF. In multivariable Cox regression analysis, FGF23 [adjusted hazard ratio (HR) 1.665; 95% confidence interval (CI) (1.284-2.160; P < 0.0001)], B-type natriuretic peptide (HR 1.433; CI 1.053-1.951; P = 0.022), and prior HF hospitalization (HR 2.058; CI 1.074-3.942; P = 0.030) were independent predictors of the composite endpoint.ConclusionsPlasma FGF23 is higher in HFpEF compared with age-matched and sex-matched controls and is strongly associated with exercise incapacity and prognosis. FGF23 correlates with plasma markers of inflammation and renal impairment.
| S-EPMC7755022 | biostudies-literature