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

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: Increased VE/VCO2 slope was associated with more severe disease and higher PVR and was independently associated with increased mortality in patients with HFpEF. (J Cardiac Fail 2017;23:777-782) Key Words: VE/VCO2 slope, heart failure with preserved ejection fraction, cardiopulmonary exercise test.

Heart Failure With Preserved Ejection Fraction vs. Reduced Ejection Fraction ― Mechanisms of Ventilatory Inefficiency During Exercise in Heart Failure ―

“…5,24,25 In HFpEF, increased mean pulmonary artery pressure and pulmonary vascular resistance at rest were reported to be associated with elevated V E/V CO2 slope. 26 Consistent in part with the previous observations, we found that CO during exercise was associated with the lowest V E/V CO2 ratio independently of other clinical factors in HFrEF. However, E/e', a parameter of LV filling pressure, was not a significant indicator of this in the current HFrEF population, which is in contrast to the study by Ponikowski et al 27 Because the present HFrEF patients had more advanced HF signs, manifesting as severely reduced LVEF of 28% on average and worse HF symptoms (NYHA class III in 58%), LV relaxation could have been highly impaired and elevated LV filling pressure could frequently be present even at rest and, as a result, the impact of LV relaxation reserve and of exercise-induced lung congestion might have higher in CPX than in exercise-stress echocardiography, which might have weakened the relationships between the parameters of these examinations.…”

Diastolic dysfunction is associated with exercise impairment in patients with sickle cell anemia

“…[10][11][12] The ventilation-to-carbon dioxide production slope at maximum exercise (VE/VCO 2 slope) is another important exercise measure that assesses ventilation efficiency and has been shown to correlate with left ventricular filling pressures and mortality in patients with DD. 9,10,13,14 The VE/VCO 2 slope has also been reported to be abnormal in patients with SCA. 10 Several factors could lead to the exercise abnormalities seen in patients with SCA, but the effects of cardiac disease in SCA on exercise capacity using CPET have not been elucidated.…”

“…Peak VO 2 is decreased in a significant proportion of children and young adults with SCA compared to normal controls even after controlling for anemia . The ventilation‐to‐carbon dioxide production slope at maximum exercise (VE/VCO 2 slope) is another important exercise measure that assesses ventilation efficiency and has been shown to correlate with left ventricular filling pressures and mortality in patients with DD . The VE/VCO 2 slope has also been reported to be abnormal in patients with SCA …”

Abnormal submaximal cardiopulmonary exercise parameters predict impaired peak exercise performance in sickle cell anemia patients

“…In addition to evaluating PFT at rest, the CPET is helpful in assessing the ventilatory efficiency by utilizing the VE/VCO 2 slope. The VE/VCO 2 slope has previously been used as a measure in heart failure and pulmonary hypertension patients with higher slopes (> 32), indicating heightened ventilation associated with reduced cardiac output and poor pulmonary perfusion . The VE/VCO 2 slope is often calculated as a maximal effort result with values from rest to peak exercise as opposed to reporting as a submaximal measure (calculating from rest to AT).…”

“…The VE/VCO 2 slope has previously been used as a measure in heart failure and pulmonary hypertension patients with higher slopes (> 32), indicating heightened ventilation associated with reduced cardiac output and poor pulmonary perfusion. 24,25 The VE/VCO 2 slope is often calculated as a maximal effort result with values from rest to peak exercise as opposed to reporting as a submaximal measure (calculating from rest to AT). In the heart failure population, the VE/VCO 2 slope at maximum exercise has been shown to be higher than VE/VCO 2 at AT, with both values showing prognostic significance.…”