Dataset Information

Exercise unmasks distinct pathophysiologic features in heart failure with preserved ejection fraction and pulmonary vascular disease.

ABSTRACT:

Aims

Pulmonary hypertension (PH) and pulmonary vascular disease (PVD) are common and associated with adverse outcomes in heart failure with preserved ejection fraction (HFpEF). Little is known about the impact of PVD on the pathophysiology of exercise intolerance.

Methods and results

Heart failure with preserved ejection fraction patients (n = 161) with elevated pulmonary capillary wedge pressure (≥15 mmHg) at rest were classified into three groups: non-PH-HFpEF (n = 21); PH but no PVD (isolated post-capillary PH, IpcPH; n = 95); and PH with PVD (combined post- and pre-capillary PH, CpcPH; n = 45). At rest, CpcPH-HFpEF patients had more right ventricular (RV) dysfunction and lower pulmonary arterial (PA) compliance compared to all other groups. While right atrial pressure (RAP) and left ventricular transmural pressure (LVTMP) were similar in HFpEF with and without PH or PVD at rest, CpcPH-HFpEF patients demonstrated greater increase in RAP, enhanced ventricular interdependence, and paradoxical reduction in LVTMP during exercise, differing from all other groups (P < 0.05). Lower PA compliance was correlated with greater increase in RAP with exercise. During exercise, CpcPH-HFpEF patients displayed an inability to enhance cardiac output, reduction in forward stroke volume, and blunted augmentation in RV systolic performance, changes that were coupled with marked limitation in aerobic capacity.

Conclusion

Heart failure with preserved ejection fraction patients with PVD demonstrate unique haemodynamic limitations during exercise that constrain aerobic capacity, including impaired recruitment of LV preload due to excessive right heart congestion and blunted RV systolic reserve. Interventions targeted to this distinct pathophysiology require testing in patients with HFpEF and PVD.

SUBMITTER: Gorter TM

PROVIDER: S-EPMC6093469 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundHeart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome associated with multiple pathophysiologic abnormalities, including left ventricular (LV) diastolic dysfunction, longitudinal LV systolic dysfunction, abnormal ventricular-arterial coupling, pulmonary hypertension, and right ventricular (RV) remodeling/dysfunction. However, the relative prognostic significance of each of these pathophysiologic abnormalities in HFpEF is unknown.Methods and resultsWe prospectively studied 419 patients with HFpEF using echocardiography and sphygmomanometry to assess HFpEF pathophysiologic markers. Cox proportional hazards analyses were used to determine the associations between pathophysiologic markers and outcomes. Mean age was 65±12 years; 62% were women; 39% were black; comorbidities were common; and study participants met published criteria for HFpEF. RV abnormalities were frequent: 28% had abnormal tricuspid annular plane systolic excursion, 15% had reduced RV fractional area change, and 34% had RV hypertrophy. During a median follow-up time of 18 months, 102 (24%) were hospitalized for HF and 175 (42%) experienced the composite end point of cardiovascular hospitalization or death. Decreased LV compliance, measured as reduced LV end-diastolic volume at an idealized LV end-diastolic pressure of 20 mm Hg (EDV20), and RV remodeling, as indicated by increased RV wall thickness, were the 2 pathophysiologic markers most predictive of worse outcomes: adjusted hazard ratio per 1 SD decrease in EDV20=1.39 (95% confidence interval [CI], 1.10-1.75; P=0.006), and hazard ratio per 1 SD increase in RV wall thickness=1.37 (95% CI, 1.16-1.61; P<0.001). These associations persisted after additional adjustment for markers of HF severity. By contrast, markers of LV relaxation, longitudinal LV systolic dysfunction, and ventricular-arterial coupling were not significantly associated with adverse outcomes.ConclusionsIn patients with HFpEF, reduced LV compliance and RV remodeling are the strongest pathophysiologic predictors of adverse outcomes.

Project description:BackgroundMany patients with heart failure and preserved ejection fraction have no overt volume overload and normal resting left atrial (LA) pressure.ObjectivesThis study sought to characterize patients with normal resting LA pressure (pulmonary capillary wedge pressure [PCWP] <15 mm Hg) but exercise-induced left atrial hypertension (EILAH).MethodsThe REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trial randomized 626 patients with ejection fraction ≥40% and exercise PCWP ≥25 mm Hg to atrial shunt or sham procedure. The primary trial outcome, a hierarchical composite of death, heart failure hospitalization, intensification of diuretics, and change in health status was compared between patients with EILAH and those with heart failure and resting left atrial hypertension (RELAH).ResultsPatients with EILAH (29%) had similar symptom severity, but lower natriuretic peptide levels, higher 6-minute walk distance, less atrial fibrillation, lower left ventricular mass, smaller LA volumes, lower E/e', and better LA strain. PCWP was lower at rest, but had a larger increase with exercise in EILAH. Neither group as a whole had a significant effect from shunt therapy vs sham. Patients with EILAH were more likely to have characteristics associated with atrial shunt responsiveness (peak exercise pulmonary vascular resistance <1.74 WU) and no pacemaker (63% vs 46%; P < 0.001). The win ratio for the primary outcome was 1.56 (P = 0.08) in patients with EILAH and 1.51 (P = 0.04) in those with RELAH when responder characteristics were present.ConclusionsPatients with EILAH had similar symptom severity but less advanced myocardial and pulmonary vascular disease. This important subgroup may be difficult to diagnose without invasive exercise hemodynamics, but it has characteristics associated with favorable response to atrial shunt therapy. (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure [REDUCE LAP-HF TRIAL II]; NCT03088033).

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