Sex-Related Differences in Dynamic Right Ventricular-Pulmonary Vascular Coupling in Heart Failure With Preserved Ejection Fraction.

Right ventricular (RV) dysfunction is associated with poorer outcomes in heart failure with preserved ejection fraction (HFpEF). Although female subjects are more likely to have HFpEF, male subjects have worse prognosis and resting RV function. The contribution of dynamic RV-pulmonary arterial (RV-PA) coupling between sex and its impact on peak exercise capacity (VO2) in HFpEF is not known. The goal of this study was to investigate the differential effects of sex on RV-PA coupling during maximum incremental exercise in patients with HFpEF. This study examined rest and exercise invasive pulmonary hemodynamics in 22 male patients with HFpEF and 27 female patients with HFpEF. To further investigate the discrepancy in RV-PA response between sex, 26 age-matched control subjects (11 male subjects and 15 female subjects) were included. Single beat analysis of RV pressure waveforms was used to determine the end-systolic elastance (Ees) and pulmonary arterial elastance. RV-PA coupling was determined as the ratio of end-systolic elastance/PA elastance. Both HFpEF groups experienced decreased peak VO2 (% predicted). However, male patients with HFpEF experienced a greater decrement in peak VO2 compared with female patients (58 ± 16% vs 70 ± 15%; P < .05). Male patients with HFpEF had a more pronounced increase in RV afterload, Ea (1.8 ± 0.6 mm Hg/mL/m2 vs 1.3 ± 0.4 mm Hg/mL/m2; P < .05) and failed to increase RV contractility during exercise, resulting in dynamic RV-PA uncoupling (0.9 ± 0.4 vs 1.2 ± 0.4; P < .05) and subsequent reduced stroke volume index augmentation. In contrast, female patients with HFpEF were able to augment RV contractility in the face of increasing afterload, preserving RV-PA coupling during exercise. Male patients with HFpEF were more compromised regarding dynamic RV-PA uncoupling and reduced peak VO2 compared with female patients. This finding was driven by both RV contractile impairment and afterload mismatch. In contrast, female patients with HFpEF had preserved RV-PA coupling during exercise and better peak exercise VO2 compared with male patients with HFpEF.

Singh I ，Oliveira RKF ，Heerdt PM ，Pari R ，Systrom DM ，Waxman AB ... -  《-》

Right Ventricular-Arterial Uncoupling During Exercise in Heart Failure With Preserved Ejection Fraction: Role of Pulmonary Vascular Dysfunction.

Right ventricular (RV) dysfunction is associated with shortened life expectancy in heart failure with preserved ejection fraction (HFpEF). The contribution of pulmonary vascular dysfunction to RV dysfunction in HFpEF is not well understood. We investigated rest and exercise invasive pulmonary hemodynamics, ventilation, and gas exchange in 67 patients with HFpEF (of whom 28 had an abnormal pulmonary vascular response during exercise referred to as HFpEF+PVR group and 39 had a normal pulmonary vascular response during exercise referred to as HFpEF group) and in 21 matched control subjects. Both groups of patients with HFpEF had a markedly decreased peak oxygen consumption (Vo2), decreased oxygen delivery, and impaired chronotropic response. Single beat analysis of RV pressure waveforms was used to compute the end-systolic elastance (Ees) and pulmonary arterial elastance (Ea). Right ventricular-pulmonary artery (RV-PA) coupling was measured as the ratio of Ees/Ea. Exercise was associated with a preserved Ees response but a decreased Ees/Ea in patients with HFpEF with a normal PVR response, indicating partially preserved RV contractile reserve. In HFpEF+PVR, exercise-induced increase in Ees was markedly reduced, resulting in decreased Ees/Ea and RV-PA uncoupling. Patients with HFpEF+PVR with an exercise-induced decrease in Ees/Ea had lower pulmonary artery compliance, lower peak Vo2, and lower stroke volume than patients with HFpEF. We conclude that RV-PA uncoupling is common in HFpEF and is caused by both intrinsic RV contractile impairment and afterload mismatch. Resting and dynamic RV-PA uncoupling in HFpEF is driven by an increase in RV pulsatile rather than resistive afterload. However, with the additive effects of increased RV resistive afterload, RV-PA uncoupling worsens dynamically during exercise.

Singh I ，Rahaghi FN ，Naeije R ，Oliveira RKF ，Systrom DM ，Waxman AB ... -  《-》

Dapagliflozin and Right Ventricular-Pulmonary Vascular Interaction in Heart Failure With Preserved Ejection Fraction: A Secondary Analysis of a Randomized Clinical Trial.

Reddy YNV ，Carter RE ，Sorimachi H ，Omar M ，Popovic D ，Alogna A ，Jensen MD ，Borlaug BA ... -  《-》

Ventricular-Arterial Coupling and Exercise-Induced Pulmonary Hypertension During Low-Level Exercise in Heart Failure With Preserved or Reduced Ejection Fraction.

Exercise-induced pulmonary hypertension (EIPH) may develop even at low workloads in heart failure (HF) patients. Ventricular-arterial stiffening plays an important role in the pathophysiology of HF with preserved ejection fraction (HFpEF). This study aimed to compare the response of ventricular-arterial coupling and PH during low-level exercise between HFpEF and HF with reduced EF (HFrEF). Echocardiography was performed at rest and during 10 W of bicycle exercise in HFpEF (n = 37) and HFrEF (n = 43). Load-independent contractility (end-systolic elastance [Ees], preload recruitable stroke work [PRSW], and peak power index [PWRI]), arterial afterload (arterial elastance [Ea]), and ventricular-arterial interaction (Ea/Ees) were measured with the use of a noninvasive single-beat technique. EIPH was defined as an estimated pulmonary arterial systolic pressure (PASP) of ≥50 mm Hg at 10 W of exercise. PASP was significantly increased during 10 W of exercise in both HF types, and ~50% of HFpEF patients developed EIPH. Arterial afterload was increased significantly during exercise in both groups. HFrEF and HFpEF patients showed a significant increase in LV contractility assessed by Ees, PRSW, and PWRI during exercise. Although Ea/Ees ratio decreased significantly in HFrEF, reduction in Ea/Ees was attenuated because of blunted Ees increases in patients with HFpEF compared with HFrEF. Even at low-level exercise, ~50% of HFpEF patients developed EIPH. Reduction in Ea/Ees was attenuated owing to less Ees increase in HFpEF compared with HFrEF. Further studies are needed to elucidate the association between ventricular-arterial coupling and EIPH in HFpEF.

Obokata M ，Nagata Y ，Kado Y ，Kurabayashi M ，Otsuji Y ，Takeuchi M ... -  《-》

RV Contractile Function and its Coupling to Pulmonary Circulation in Heart Failure With Preserved Ejection Fraction: Stratification of Clinical Phenotypes and Outcomes.

This study sought to investigate how right ventricular (RV) contractile function and its coupling with pulmonary circulation (PC) stratify clinical phenotypes and outcome in heart failure preserved ejection fraction (HFpEF) patients. Pulmonary hypertension and RV dysfunction are key hemodynamic abnormalities in HFpEF. Three hundred eighty seven HFpEF patients (mean age 64 ± 12 years, 59% females, left ventricular ejection fraction 59 ± 7%) underwent RV and pulmonary hemodynamic evaluation by echocardiography (entire population) and right heart catheterization (219 patients). Patients were investigated by tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) relationship and stratified according to TAPSE/PASP ratio tertiles (1: <0.35; 2: 0.35 to 0.57; 3: >0.57). Specifically, TAPSE/PASP ratio was taken as a noninvasive index of RV to PC coupling based on the correlation with invasively evaluated RV systolic elastance/arterial elastance (r = 0.35; p < 0.0001). Groups had similar prevalence of comorbidities except for a higher prevalence of atrial fibrillation and kidney dysfunction in tertile 1. Progressively increasing levels of natriuretic peptides, worse systemic and pulmonary hemodynamics, abnormal exercise aerobic capacity and ventilatory inefficiency were observed from the highest to lowest TAPSE/PASP tertile. TASPE/PASP correlated with pulmonary artery compliance (r = 0.69; p < 0.0001). Remarkably, the tertile 1 group distributed along the worse portion of the curve at lower pulmonary artery compliance and higher pulmonary vascular resistances. In addition, the TAPSE/PASP ratio emerged as an independent predictor of worse outcomes. A thorough assessment of RV-PC coupling and RV contractile function stratify HFpEF phenotypes at different level of risk. These observations shift the interest toward therapeutic strategies that may benefit the right heart as primary unmet need in the complex pathophysiology of the HFpEF syndrome.

Guazzi M ，Dixon D ，Labate V ，Beussink-Nelson L ，Bandera F ，Cuttica MJ ，Shah SJ ... -  《-》