Right ventriculo–arterial uncoupling and impaired contractile reserve in obese patients with unexplained exercise intolerance

Abstract

BackgroundRight ventricular (RV) dysfunction and heart failure with preserved ejection fraction may contribute to exercise intolerance in obesity. To further define RV exercise responses, we investigated RV–arterial coupling in obesity with and without development of exercise pulmonary venous hypertension (ePVH).MethodsRV–arterial coupling defined as RV end-systolic elastance/pulmonary artery elastance (Ees/Ea) was calculated from invasive cardiopulmonary exercise test data in 6 controls, 8 obese patients without ePVH (Obese−ePVH) and 8 obese patients with ePVH (Obese+ePVH) within a larger series. ePVH was defined as a resting pulmonary arterial wedge pressure < 15 mmHg but ≥ 20 mmHg on exercise. Exercise haemodynamics were further evaluated in 18 controls, 20 Obese−ePVH and 17 Obese+ePVH patients.ResultsBoth Obese−ePVH and Obese+ePVH groups developed exercise RV–arterial uncoupling (peak Ees/Ea = 1.45 ± 0.26 vs 0.67 ± 0.18 vs 0.56 ± 0.11, p < 0.001, controls vs Obese−ePVH vs Obese+ePVH respectively) with higher peak afterload (peak Ea = 0.31 ± 0.07 vs 0.75 ± 0.32 vs 0.88 ± 0.62 mL/mmHg, p = 0.043) and similar peak contractility (peak Ees = 0.50 ± 0.16 vs 0.45 ± 0.22 vs 0.48 ± 0.17 mL/mmHg, p = 0.89). RV contractile reserve was highest in controls (ΔEes = 224 ± 80 vs 154 ± 39 vs 141 ± 34% of baseline respectively, p < 0.001). Peak Ees/Ea correlated with peak pulmonary vascular compliance (PVC, r = 0.53, p = 0.02) but not peak pulmonary vascular resistance (PVR, r = − 0.20, p = 0.46). In the larger cohort, Obese+ePVH patients on exercise demonstrated higher right atrial pressure, lower cardiac output and steeper pressure-flow responses. BMI correlated with peak PVC (r = − 0.35, p = 0.04) but not with peak PVR (r = 0.24, p = 0.25).ConclusionsExercise RV–arterial uncoupling and reduced RV contractile reserve further characterise obesity-related exercise intolerance. RV dysfunction in obesity may develop independent of exercise LV filling pressures.

Right ventricular-pulmonary arterial coupling impairment and exercise capacity in obese adults

“…The absence of a significant exercise-induced increase in E/e' is in keeping with previous echocardiographic studies in healthy subjects (12,13,15). However, invasively measured pulmonary artery wedge pressure to estimate LAP has been reported in patients with obesity complaining of exercise dyspnea (9). Insufficient accuracy of LAP estimation from E/e' or insufficient maximal Q levels may account for the lack of a more sustained increase in LAP at exercise.…”

“…Previous echocardiographic and magnetic resonance imaging studies have shown that obesity is associated with increased RV dimensions and hypertrophy, and depressed indices of systolic function (6)(7)(8). This was confirmed by an invasive study, which reported on a decreased RV/PA coupling assessed by gold standard Ees/Ea that was correlated to a decreased exercise capacity and decreased PA compliance (9). In the present study, RV-PA coupling was estimated by the TAPSE/sPAP ratio.…”

“…An invasive cardiopulmonary exercise test (CPET) study recently reported on RV-pulmonary arterial (PA) uncoupling measured by gold standard ratio of end-systolic to arterial elastances (Ees/Ea) as a cause of obesity-related exercise intolerance (9). However, quantification of cardiorespiratory fitness in obese subjects is difficult because of variety of prediction equations and body mass corrections (10).…”

Right ventricular oxygen delivery as a determinant of right ventricular functional reserve during exercise in juvenile swine with chronic pulmonary hypertension

“…In addition, the increased work and afterload of the RV in PH were not accompanied by an equivalent increase in RV contractile function, particularly during exercise. The observation that maximal RV contractility in PH during exercise was not higher than in control is consistent with a recent observation in obese patients with exercise-induced PH and reduced exercise tolerance (30). Together with data showing E a is a robust and independent predictor of mortality in patients with WHO group 2 PH, and correlates strongly with RV dysfunction (16,43), it appears that the reduced RV contractile reserve, which results in a decrease in RV PA coupling during exercise, is an important limiting factor in exercise tolerance in PH patients.…”

Exercise haemodynamics in heart failure with preserved ejection fraction: a systematic review and meta‐analysis

“…35 In four of the six studies evaluating patients exercising in the upright position, a peak PAWP > 20 mmHg or a PAWP/CO slope > 2 mmHg/L/min was considered as a pathological threshold to define HFpEF. 3,4,24,28 Notably, six studies focused on specific HFpEF subpopulations, such as those with obesity, recent myocardial infarction, non-obstructive coronary artery disease, or patients included in an interventional trial. 20,24,29,32,34,36 Only in four studies the left ventricular ejection fraction to define HFpEF was >40% or >45%, rather than the currently adopted cut-off of ≥50%.…”