Effects of inspiratory muscle training in patients with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is remarkably common in elderly people with highly prevalent comorbid conditions. Despite its increasing in prevalence, there is no evidence-based effective therapy for HFpEF. We sought to evaluate whether inspiratory muscle training (IMT) improves exercise capacity, as well as left ventricular diastolic function, biomarker profile and quality of life (QoL) in patients with advanced HFpEF and nonreduced maximal inspiratory pressure (MIP). A total of 26 patients with HFpEF (median (interquartile range) age, peak exercise oxygen uptake (peak VO2) and left ventricular ejection fraction of 73 years (66-76), 10 ml/min/kg (7.6-10.5) and 72% (65-77), respectively) were randomized to receive a 12-week programme of IMT plus standard care vs. standard care alone. The primary endpoint of the study was evaluated by positive changes in cardiopulmonary exercise parameters and distance walked in 6 minutes (6MWT). Secondary endpoints were changes in QoL, echocardiogram parameters of diastolic function, and prognostic biomarkers. The IMT group improved significantly their MIP (p < 0.001), peak VO2 (p < 0.001), exercise oxygen uptake at anaerobic threshold (p = 0.001), ventilatory efficiency (p = 0.007), metabolic equivalents (p < 0,001), 6MWT (p < 0.001), and QoL (p = 0.037) as compared to the control group. No changes on diastolic function parameters or biomarkers levels were observed between both groups. In HFpEF patients with low aerobic capacity and non-reduced MIP, IMT was associated with marked improvement in exercise capacity and QoL.

Palau P ，Domínguez E ，Núñez E ，Schmid JP ，Vergara P ，Ramón JM ，Mascarell B ，Sanchis J ，Chorro FJ ，Núñez J ... -  《-》

Inspiratory Muscle Training and Functional Electrical Stimulation for Treatment of Heart Failure With Preserved Ejection Fraction: Rationale and Study Design of a Prospective Randomized Controlled Trial.

Heart failure with preserved ejection fraction (HFpEF) has become the most prevalent form of heart failure in developed countries. Regrettably, there is no evidence-based effective therapy for HFpEF. We seek to evaluate whether inspiratory muscle training, functional electrical stimulation, or a combination of both can improve exercise capacity as well as left ventricular diastolic function, biomarker profile, quality of life (QoL), and prognosis in patients with HFpEF. A total of 60 stable symptomatic patients with HFpEF (New York Heart Association class II-III/IV) will be randomized (1:1:1:1) to receive a 12-week program of inspiratory muscle training, functional electrical stimulation, a combination of both, or standard care alone. The primary endpoint of the study is change in peak exercise oxygen uptake; secondary endpoints are changes in QoL, echocardiogram parameters, and prognostic biomarkers. As of March 21, 2016, thirty patients have been enrolled. Searching for novel therapies that improve QoL and autonomy in the elderly with HFpEF has become a health care priority. We believe that this study will add important knowledge about the potential utility of 2 simple and feasible physical interventions for the treatment of advanced HFpEF.

Palau P ，Domínguez E ，López L ，Heredia R ，González J ，Ramón JM ，Serra P ，Santas E ，Bodi V ，Sanchis J ，Chorro FJ ，Núñez J ... -  《-》

Inspiratory Muscle Training and Functional Electrical Stimulation for Treatment of Heart Failure With Preserved Ejection Fraction: The TRAINING-HF Trial.

Despite the prevalence of heart failure with preserved ejection fraction (HFpEF), there is currently no evidence-based effective therapy for this disease. This study sought to evaluate whether inspiratory muscle training (IMT), functional electrical stimulation (FES), or a combination of both (IMT + FES) improves 12- and 24-week exercise capacity as well as left ventricular diastolic function, biomarker profile, and quality of life in HFpEF. A total of 61 stable symptomatic patients (New York Heart Association II-III) with HFpEF were randomized (1:1:1:1) to receive a 12-week program of IMT, FES, or IMT + FES vs usual care. The primary endpoint of the study was to evaluate change in peak exercise oxygen uptake at 12 and 24 weeks. Secondary endpoints were changes in quality of life, echocardiogram parameters, and prognostic biomarkers. We used a mixed-effects model for repeated-measures to compare endpoints changes. Mean age and peak exercise oxygen uptake were 74 ± 9 years and 9.9 ± 2.5mL/min/kg, respectively. The proportion of women was 58%. At 12 weeks, the mean increase in peak exercise oxygen uptake (mL/kg/min) compared with usual care was 2.98, 2.93, and 2.47 for IMT, FES, and IMT + FES, respectively (P < .001) and this beneficial effect persisted after 6 months (1.95, 2.08, and 1.56; P < .001). Significant increases in quality of life scores were found at 12 weeks (P < .001). No other changes were found. In HFpEF patients with low aerobic capacity, IMT and FES were associated with a significant improvement in exercise capacity and quality of life. This trial was registered at ClinicalTrials.gov (Identifier: NCT02638961)..

Palau P ，Domínguez E ，López L ，Ramón JM ，Heredia R ，González J ，Santas E ，Bodí V ，Miñana G ，Valero E ，Mollar A ，Bertomeu González V ，Chorro FJ ，Sanchis J ，Lupón J ，Bayés-Genís A ，Núñez J ... -  《-》

Functional iron deficiency and diastolic function in heart failure with preserved ejection fraction.

Functional iron deficiency (FID) is an independent risk factor for poor outcome in advanced heart failure with reduced EF, but its role in heart failure with preserved EF (HFPEF) remains unclear. We aimed to investigate the impact of FID on cardiac performance determined by pressure-volume loop analysis in HFPEF. 26 HFPEF patients who showed an increase in LV stiffness by pressure-volume (PV) loop analysis obtained by conductance-catheterization, performed exercise testing, echocardiographic examination including tissue Doppler and determination of iron metabolism: serum iron, ferritin and transferrin saturation. HFPEF patients who provided ferritin <100 μg/l or ferritin of 100-299 μg/l in combination with transferrin saturation <20% were defined as having FID. In 14 patients the expression of transferrin receptor was determined from available endomyocardial biopsies. Fifteen out of 26 HFPEF patients showed FID without anemia. Compared to control subjects and HFPEF patients without FID, HFPEF patients with FID showed an up-regulation of the myocardial transferrin receptor expression (p<0.05). No differences between HFPEF patients with and without iron deficiency were found in heart dimensions, systolic and diastolic function obtained by PV-loop and echocardiography analysis. According to the linear regression analysis, LV stiffness was correlated with peak oxygen uptake (r=-0.636, p<0.001) but not with the ferritin level or transferrin saturation. No relation was found between FID and exercise capacity. The association of LV stiffness with exercise performance was independent from the level of iron deficiency. In non-anemic HFPEF patients, cardiac dysfunction and impaired exercise capacity occur independently of FID.

Kasner M ，Aleksandrov AS ，Westermann D ，Lassner D ，Gross M ，von Haehling S ，Anker SD ，Schultheiss HP ，Tschöpe C ... -  《-》

Inspiratory Muscle Function and Exercise Capacity in Patients With Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by impaired exercise capacity resulting from dyspnea and fatigue. The pathophysiological mechanisms underlying the exercise intolerance in HFpEF are not well established. We sought to evaluate the effects of inspiratory muscle function on exercise tolerance in symptomatic patients with HFpEF. A total of 74 stable symptomatic patients with HFpEF and New York Heart Association class II-III underwent a cardiopulmonary exercise test between June 2012 and May 2016. Inspiratory muscle weakness was defined as maximum inspiratory pressure (MIP)  <70% of normal predicted values. Pearson correlation coefficient and multivariate linear regression analysis were used to assess the association between percent of predicted MIP (pp-MIP) and maximal exercise capacity [measured by peak oxygen uptake (peak VO2) and percent of predicted peak VO2 (pp-peak VO2)]. Thirty-one patients (42%) displayed inspiratory muscle weakness. Mean (standard deviation) age was 72.5 ± 9.1 years, 53% were women, and 35.1% displayed New York Heart Association class III. Mean peak VO2 and pp-peak VO2 were 10 ± 2.8 mL•min•kg and 57.3 ± 13.8%, respectively. The median (interquartile range) of pp-MIP was 72% (58%-90%). pp-MIP was not correlated with peak VO2 (r = -0.047, P = .689) nor pp-peak VO2 (r = -0.078, P = .509). Furthermore, in multivariable analysis, pp-MIP showed no association with peak VO2 (β coefficient = 0.01, 95% confidence interval -0.01 to 0.03, P = .241) and pp-peak VO2 (β coefficient = -0.00, 95% confidence interval -0.10 to 0.10, P = .975). In symptomatic elderly patients with HFpEF, we found that pp-MIP was not associated with either peak VO2 or pp-peak VO2.

Palau P ，Domínguez E ，Núñez E ，Ramón JM ，López L ，Melero J ，Bellver A ，Chorro FJ ，Bodí V ，Bayés-Genis A ，Sanchis J ，Núñez J ... -  《-》