Peak Exercise Oxygen Uptake Predicts Recurrent Admissions in Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent syndrome with an elevated risk of morbidity and mortality. To date, there is scarce evidence on the role of peak exercise oxygen uptake (peak VO2) for predicting the morbidity burden in HFpEF. We sought to evaluate the association between peak VO2 and the risk of recurrent hospitalizations in patients with HFpEF. A total of 74 stable symptomatic patients with HFpEF underwent a cardiopulmonary exercise test between June 2012 and May 2016. A negative binomial regression method was used to determine the association between the percentage of predicted peak VO2 (pp-peak VO2) and recurrent hospitalizations. Risk estimates are reported as incidence rate ratios. The mean age was 72.5 ± 9.1 years, 53% were women, and all patients were in New York Heart Association functional class II to III. Mean peak VO2 and median pp-peak VO2 were 10 ± 2.8mL/min/kg and 60% (range, 47-67), respectively. During a median follow-up of 276 days [interquartile range, 153-1231], 84 all-cause hospitalizations in 31 patients (41.9%) were registered. A total of 15 (20.3%) deaths were also recorded. On multivariate analysis, accounting for mortality as a terminal event, pp-peak VO2 was independently and linearly associated with the risk of recurrent admission. Thus, and modeled as continuous, a 10% decrease of pp-peak VO2 increased the risk of recurrent hospitalizations by 32% (IRR, 1.32; 95%CI, 1.03-1.68; P = .028). In symptomatic elderly patients with HFpEF, pp-peak VO2 predicts all-cause recurrent admission.

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

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 ... -  《-》

Mechanisms of exercise intolerance in heart failure with preserved ejection fraction: the role of abnormal peripheral oxygen extraction.

Exercise capacity as measured by peak oxygen uptake (Vo2) is similarly impaired in patients with heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). However, characterization of how each component of Vo2 changes in response to incremental exercise in HFpEF versus HFrEF has not been previously defined. We hypothesized that abnormally low peripheral o2 extraction (arterio-mixed venous o2 content difference, [C(a-v)o2]) during exercise significantly contributes to impaired exercise capacity in HFpEF. We performed maximum incremental cardiopulmonary exercise testing with invasive hemodynamic monitoring on 104 patients with symptomatic NYHA II to IV heart failure (HFpEF, n=48, peak Vo2=13.9±0.5 mL kg(-1) min(-1), mean±SEM, and HFrEF, n=56, peak Vo2=12.1±0.5 mL kg(-1) min(-1)) and 24 control subjects (peak Vo2 27.0±1.7 mL kg(-1) min(-1)). Peak exercise C(a-v)o2 was lower in HFpEF compared with HFrEF (11.5±0.27 versus 13.5±0.34 mL/dL, respectively, P<0.0001), despite no differences in age, hemoglobin level, peak respiratory exchange ratio, Cao2, or cardiac filling pressures. Peak C(a-v)o2 and peak heart rate emerged as the leading predictors of peak Vo2 in HFpEF. Impaired peripheral o2 extraction was the predominant limiting factor to exercise capacity in 40% of patients with HFpEF and was closely related to elevated systemic blood pressure during exercise (r=0.49, P=0.0005). In the first study to directly measure C(a-v)o2 throughout exercise in HFpEF, HFrEF, and normals, we found that peak C(a-v)o2 was a major determinant of exercise capacity in HFpEF. The important functional limitation imposed by impaired o2 extraction may reflect intrinsic abnormalities in skeletal muscle or peripheral microvascular function, and represents a potential target for therapeutic intervention.

Dhakal BP ，Malhotra R ，Murphy RM ，Pappagianopoulos PP ，Baggish AL ，Weiner RB ，Houstis NE ，Eisman AS ，Hough SS ，Lewis GD ... -  《-》

Preserved right ventricular ejection fraction predicts exercise capacity and survival in advanced heart failure.

Di Salvo TG ，Mathier M ，Semigran MJ ，Dec GW ... -  《JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY》

Clinical and Hemodynamic Correlates and Prognostic Value of VE/VCO(2) Slope in Patients With Heart Failure With Preserved Ejection Fraction and Pulmonary Hypertension.

Impaired exercise capacity is one of the hallmarks of heart failure with preserved ejection fraction (HFpEF), but the clinical and hemodynamic correlates and prognostic value of exercise testing in patients with HFpEF is unknown. Patients with HFpEF (left ventricular ejection fraction [LVEF] ≥45%) and pulmonary hypertension underwent cardiopulmonary exercise test (CPX) to measure maximal (peak VO2) and submaximal (ventilatory equivalent for carbon dioxide [VE/VCO2] slope) exercise capacity. In addition, right heart catheterization was performed. Patients were grouped in tertiles based on the VE/VCO2 slope. Univariate and multivariate regression analyses were performed. A Cox regression analysis was performed to determine the mortality during follow-up. We studied 88 patients: mean age 73 ± 9 years, 67% female, mean LVEF 58%, median N-terminal pro-B-type natriuretic peptide (NT-proBNP) 840 (interquartile range 411-1938) ng/L. Patients in the highest VE/VCO2 tertile had the most severe HF, as reflected in higher New York Heart Association functional class and higher NT-proBNP plasma levels (all P < .05 for trend), whereas LVEF was similar between the groups. Multivariable regression analysis with backward elimination on invasive hemodynamic measurements showed that VE/VCO2 slope was independently associated with pulmonary vascular resistance (PVR). Cox regression analysis showed that increased VE/VCO2 slope (but not peak VO2) was independently associated with increased mortality. Increased VE/VCO2 slope was associated with more severe disease and higher PVR and was independently associated with increased mortality in patients with HFpEF.

Klaassen SHC ，Liu LCY ，Hummel YM ，Damman K ，van der Meer P ，Voors AA ，Hoendermis ES ，van Veldhuisen DJ ... -  《-》