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 ... -  《-》

Physiological dead space and arterial carbon dioxide contributions to exercise ventilatory inefficiency in patients with reduced or preserved ejection fraction heart failure.

Patients with heart failure (HF) with reduced (HFrEF) or preserved (HFpEF) ejection fraction demonstrate an increased ventilatory equivalent for carbon dioxide (V̇E /V̇CO2 ) slope. The physiological correlates of the V̇E /V̇CO2 slope remain unclear in the two HF phenotypes. We hypothesized that changes in the physiological dead space to tidal volume ratio (VD /VT ) and arterial CO2 tension (PaCO2 ) differentially contribute to the V̇E /V̇CO2 slope in HFrEF vs. HFpEF. Adults with HFrEF (n = 32) and HFpEF (n = 27) [mean ± standard deviation (SD) left ventricular ejection fraction: 22 ± 7% and 61 ± 9%, respectively; mean ± SD body mass index: 28 ± 4 kg/m2 and 33 ± 6 kg/m2 , respectively; P < 0.01] performed cardiopulmonary exercise testing with breath-by-breath ventilation and gas exchange measurements. PaCO2 was measured via radial arterial catheterization. We calculated the V̇E /V̇CO2 slope via linear regression, and VD /VT  = 1 - [(863 × V̇CO2 )/(V̇E  × PaCO2 )]. Resting VD /VT (0.48 ± 0.08 vs. 0.41 ± 0.11; P = 0.04), but not PaCO2 (38 ± 5 mmHg vs. 40 ± 3 mmHg; P = 0.21) differed between HFrEF and HFpEF. Peak exercise VD /VT (0.39 ± 0.08 vs. 0.32 ± 0.12; P = 0.02) and PaCO2 (33 ± 6 mmHg vs. 38 ± 4 mmHg; P < 0.01) differed between HFrEF and HFpEF. The V̇E /V̇CO2 slope was higher in HFrEF compared with HFpEF (44 ± 11 vs. 35 ± 8; P < 0.01). Variance associated with the V̇E /V̇CO2 slope in HFrEF and HFpEF was explained by peak exercise VD /VT (R2  = 0.30 and R2  = 0.50, respectively) and PaCO2 (R2  = 0.64 and R2  = 0.28, respectively), but the relative contributions of each differed (all P < 0.01). Relationships between the V̇E /V̇CO2 slope and both VD /VT and PaCO2 are robust, but differ between HFpEF and HFrEF. Increasing V̇E /V̇CO2 slope appears to be strongly explained by mechanisms influential in regulating PaCO2 in HFrEF, which contrasts with the strong role of increased VD /VT in HFpEF.

Van Iterson EH ，Johnson BD ，Borlaug BA ，Olson TP ... -  《-》

Prognostic Value of Cardiopulmonary Exercise Testing in Heart Failure With Reduced, Midrange, and Preserved Ejection Fraction.

This study aimed to compare the independent and incremental prognostic value of peak oxygen consumption (VO2) and minute ventilation/carbon dioxide production (VE/VCO2) in heart failure (HF) with preserved (HFpEF), midrange (HFmEF), and reduced (HFrEF) ejection fraction (LVEF). In 195 HFpEF (LVEF ≥50%), 144 HFmEF (LVEF 40-49%), and 630 HFrEF (LVEF <40%) patients, we assessed the association of cardiopulmonary exercise testing variables with the composite outcome of death, left ventricular assist device implantation, or heart transplantation (256 events; median follow-up of 4.2 years), and 2-year incident HF hospitalization (244 events). In multivariable Cox regression analysis, greater association with outcomes in HFpEF than HFrEF were noted with peak VO2 (HR [95% confidence interval]: 0.76 [0.67-0.87] versus 0.87 [0.83-0.90] for the composite outcome, Pinteraction=0.052; 0.77 [0.69-0.86] versus 0.92 [0.88-0.95], respectively for HF hospitalization, Pinteraction=0.003) and VE/VCO2 slope (1.11 [1.06-1.17] versus 1.04 [1.03-1.06], respectively for the composite outcome, Pinteraction=0.012; 1.10 [1.05-1.15] versus 1.04 [1.03-1.06], respectively for HF hospitalization, Pinteraction=0.019). In HFmEF, peak VO2 and VE/VCO2 slope were associated with the composite outcome (0.79 [0.70-0.90] and 1.12 [1.05-1.19], respectively), while only peak VO2 was related to HF hospitalization (0.81 [0.72-0.92]). In HFpEF and HFrEF, peak VO2 and VE/VCO2 slope provided incremental prognostic value beyond clinical variables based on the C-statistic, net reclassification improvement, and integrated diagnostic improvement, with models containing both measures demonstrating the greatest incremental value. Both peak VO2 and VE/VCO2 slope provided incremental value beyond clinical characteristics and LVEF for predicting outcomes in HFpEF. Cardiopulmonary exercise testing variables provided greater risk discrimination in HFpEF than HFrEF.

Nadruz W Jr ，West E ，Sengeløv M ，Santos M ，Groarke JD ，Forman DE ，Claggett B ，Skali H ，Shah AM ... -  《Journal of the American Heart Association》

Cardiopulmonary exercise testing reflects similar pathophysiology and disease severity in heart failure patients with reduced and preserved ejection fraction.

We are unaware of any previous investigation that has compared the relationship of key cardiopulmonary exercise testing (CPX) variables to various measures of pathophysiology between heart failure-reduced ejection fraction (HFrEF) and HF-preserved ejection fraction (HFpEF) cohorts that are well matched with respect to baseline characteristics and their exercise response, which is the purpose of the present study. Thirty-four patients with HFpEF were randomly matched to 34 subjects with HFrEF according to age and sex as well as peak oxygen consumption (VO2), ventilatory efficiency (VE/VCO2 slope), and exercise oscillatory ventilation (EOV). In addition to CPX, patients also underwent echocardiography with tissue Doppler imaging (TDI) and assessment of N-terminal pro-B-type natriuretic peptide (NT-proBNP). When matched for age, sex, and CPX variables, the HFrEF and HFpEF cohorts had similar echocardiography with TDI and NT-proBNP values, indicating comparable disease severity. In addition, the correlations between key CPX measures (peak VO2 and VE/VCO2 slope) and echocardiography with TDI and NT-proBNP measures were similar between HFrEF and HFpEF groups. Of note, the correlation between the VE/VCO2 slope and pulmonary artery systolic pressure and NT-proBNP was highly significant in both groups (r ≥ 0.65, p < 0.01). Moreover, subjects with EOV in both groups had a significantly higher PASP (∼47 vs. ∼35 mmHg, p < 0.05). The results of the current study indicate CPX equally represents disease severity in HFrEF and HFpEF patients. This is a novel finding supporting the key role of CPX in the clinical follow-up of HF patients irrespective of LVEF and cardiac phenotype.

Guazzi M ，Labate V ，Cahalin LP ，Arena R ... -  《-》

Exercise VE/VCO2 Slope: An Endurance Marker of Prognosis Also in Patients with HFpEF and Pulmonary Hypertension, at Least!

Guazzi M 《-》