The effect of Aliskiren on exercise capacity in older patients with heart failure and preserved ejection fraction: A randomized, placebo-controlled, double-blind trial.
Ontology highlight
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]
Similar Datasets
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.
| S-EPMC7914143 | biostudies-literature
Project description:BackgroundInorganic nitrate (NO3(-)), abundant in certain vegetables, is converted to nitrite by bacteria in the oral cavity. Nitrite can be converted to nitric oxide in the setting of hypoxia. We tested the hypothesis that NO3(-) supplementation improves exercise capacity in heart failure with preserved ejection fraction via specific adaptations to exercise.Methods and resultsSeventeen subjects participated in this randomized, double-blind, crossover study comparing a single dose of NO3-rich beetroot juice (NO3(-), 12.9 mmol) with an identical nitrate-depleted placebo. Subjects performed supine-cycle maximal-effort cardiopulmonary exercise tests, with measurements of cardiac output and skeletal muscle oxygenation. We also assessed skeletal muscle oxidative function. Study end points included exercise efficiency (total work/total oxygen consumed), peak VO2, total work performed, vasodilatory reserve, forearm mitochondrial oxidative function, and augmentation index (a marker of arterial wave reflections, measured via radial arterial tonometry). Supplementation increased plasma nitric oxide metabolites (median, 326 versus 10 μmol/L; P=0.0003), peak VO2 (12.6±3.7 versus 11.6±3.1 mL O2·min(-1)·kg(-1); P=0.005), and total work performed (55.6±35.3 versus 49.2±28.9 kJ; P=0.04). However, efficiency was unchanged. NO3(-) led to greater reductions in systemic vascular resistance (-42.4±16.6% versus -31.8±20.3%; P=0.03) and increases in cardiac output (121.2±59.9% versus 88.7±53.3%; P=0.006) with exercise. NO3(-) reduced aortic augmentation index (132.2±16.7% versus 141.4±21.9%; P=0.03) and tended to improve mitochondrial oxidative function.ConclusionsNO3(-) increased exercise capacity in heart failure with preserved ejection fraction by targeting peripheral abnormalities. Efficiency did not change as a result of parallel increases in total work and VO2. NO3(-) increased exercise vasodilatory and cardiac output reserves. NO3(-) also reduced arterial wave reflections, which are linked to left ventricular diastolic dysfunction and remodeling.Clinical trial registration urlwww.clinicaltrials.gov. Unique identifier: NCT01919177.
| S-EPMC5823250 | biostudies-literature
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.
| S-EPMC5542717 | biostudies-other
Project description:There is a lack of evidence-based therapies for the treatment of heart failure (HF) with preserved ejection fraction (HFpEF). Beta blockers may provide some benefit in HFpEF due to their proven role in HF with reduced ejection fraction.The main objective of the present study was to evaluate the efficacy of controlled-release metoprolol (metoprolol succinate) in HFpEF.This was an investigator-initiated, randomized, double-blind, placebo-controlled, 14-week pilot study with metoprolol succinate as a study drug. Dose titration protocol was used with optional upward titration of doses ranging from 25 to 100 mg. The end points included clinical, echocardiographic, biochemical (N-terminal pro-B-type natriuretic peptide and serum carboxy-terminal propeptide of procollagen type I), and quality of life (QoL) (SF-36) parameters.Twenty patients were enrolled in each of the treatment arms. An improvement in New York Heart Association class and exercise capacity was seen in both treatment arms. The mean change in various echocardiographic and biochemical parameters between the two groups was statistically insignificant. A significant improvement in some QoL parameters was observed in both the groups. No serious adverse events were seen.Hence, this pilot study showed that metoprolol succinate possibly has some beneficial role in HFpEF as reflected by improvement in some parameters. The findings highlight the need of a larger study with longer follow-up to provide a definitive answer.
| S-EPMC5543763 | biostudies-other
Project description:AimsWhether and how iron deficiency (ID) impacts patients with heart failure (HF) with preserved ejection fraction (HFpEF) remain unclear. The aim of our study was to investigate the impact of ID on functional status, exercise capacity, and prognosis in HFpEF.Methods and resultsThe study population consisted of 300 HFpEF patients. ID was defined as serum ferritin <100 μg/L or 100-300 μg/L and transferrin-saturation <20%. Baseline functional status, quality of life (HADS score and EQ 5D index), 6 min walking test, echocardiography, and outcome (all-cause mortality and combined all cause-mortality and HF hospitalization) were evaluated. ID was found in 159 (53%) patients. Patients with ID had a worse prognosis with a higher combined endpoint of all-cause mortality and HF hospitalization after 4 years of follow-up (log rank = 0.008). Pulmonary hypertension, depression, and thyroid disease were more prevalent in the ID group. Multivariable analysis showed that ID was independently associated with body mass index (P = 0.003), pulmonary hypertension (P = 0.008), and thyroid disease (P = 0.01). Although patients with ID had a lower exercise capacity compared with patients without ID (393 m [294-455] vs. 344 m [260-441], P = 0.008), there was no significant correlation after multivariable correction for age, BMI, NT-proBNP, DM, and depression.ConclusionsHeart failure with preserved ejection fraction patients with ID have a worse prognosis and impaired exercise capacity compared with those without ID. However, although a trend was observed, after multivariable correction ID was no longer significantly associated with a reduced exercise capacity. This reflects that impaired exercise capacity in HFpEF is complex and seems multifactorial. Interestingly, pulmonary hypertension was an independent predictor of both ID and exercise capacity.
| S-EPMC8006701 | biostudies-literature
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.
| S-EPMC7395858 | 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
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 [? 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:ImportanceThere are few effective treatments for heart failure with preserved ejection fraction (HFpEF). Short-term administration of inorganic nitrite or nitrate preparations has been shown to enhance nitric oxide signaling, which may improve aerobic capacity in HFpEF.ObjectiveTo determine the effect of 4 weeks' administration of inhaled, nebulized inorganic nitrite on exercise capacity in HFpEF.Design, setting, and participantsMulticenter, double-blind, placebo-controlled, 2-treatment, crossover trial of 105 patients with HFpEF. Participants were enrolled from July 22, 2016, to September 12, 2017, at 17 US sites, with final date of follow-up of January 2, 2018.InterventionsInorganic nitrite or placebo administered via micronebulizer device. During each 6-week phase of the crossover study, participants received no study drug for 2 weeks (baseline/washout) followed by study drug (nitrite or placebo) at 46 mg 3 times a day for 1 week followed by 80 mg 3 times a day for 3 weeks.Main outcomes and measuresThe primary end point was peak oxygen consumption (mL/kg/min). Secondary end points included daily activity levels assessed by accelerometry, health status as assessed by the Kansas City Cardiomyopathy Questionnaire (score range, 0-100, with higher scores reflecting better quality of life), functional class, cardiac filling pressures assessed by echocardiography, N-terminal fragment of the prohormone brain natriuretic peptide levels, other exercise indices, adverse events, and tolerability. Outcomes were assessed after treatment for 4 weeks.ResultsAmong 105 patients who were randomized (median age, 68 years; 56% women), 98 (93%) completed the trial. During the nitrite phase, there was no significant difference in mean peak oxygen consumption as compared with the placebo phase (13.5 vs 13.7 mL/kg/min; difference, -0.20 [95% CI, -0.56 to 0.16]; P = .27). There were no significant between-treatment phase differences in daily activity levels (5497 vs 5503 accelerometry units; difference, -15 [95% CI, -264 to 234]; P = .91), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (62.6 vs 61.9; difference, 1.1 [95% CI, -1.4 to 3.5]; P = .39), functional class (2.5 vs 2.5; difference, 0.1 [95% CI, -0.1 to 0.2]; P = .43), echocardiographic E/e' ratio (16.4 vs 16.6; difference, 0.1 [95% CI, -1.2 to 1.3]; P = .93), or N-terminal fragment of the prohormone brain natriuretic peptide levels (520 vs 533 pg/mL; difference, 11 [95% CI, -53 to 75]; P = .74). Worsening heart failure occurred in 3 participants (2.9%) during the nitrite phase and 8 (7.6%) during the placebo phase.Conclusions and relevanceAmong patients with HFpEF, administration of inhaled inorganic nitrite for 4 weeks, compared with placebo, did not result in significant improvement in exercise capacity.Trial registrationClinicalTrials.gov Identifier: NCT02742129.
| S-EPMC6248105 | biostudies-literature