Clinical phenotypes and outcomes of pulmonary hypertension due to left heart disease: Role of the pre-capillary component

Abstract

Background: In pulmonary hypertension (PH), both wedge pressure elevation (PAWP) and a precapillary component may affect right ventricular (RV) afterload. These changes may contribute to RV failure and prognosis. We aimed at describing the different haemodynamic phenotypes of patients with PH due to left heart disease (LHD) and at characterizing the impact of pulmonary haemodynamics on RV function and outcome PH-LHD.

Methods: Patients with PH-LHD were compared with treatment-naïve idiopathic/heritable pulmonary arterial hypertension (PAH, n = 35). PH-LHD patients were subdivided in Isolated post-capillary PH (IpcPH: diastolic pressure gradient, DPG<7 mmHg and pulmonary vascular resistance, PVR≤3 WU, n = 37), Combined post- and pre-capillary PH (CpcPH: DPG≥7 mmHg and PVR>3 WU, n = 27), and "intermediate" PH-LHD (either DPG <7 mmHg or PVR ≤3 WU, n = 29).

Results: Despite similar PAWP and cardiac index, haemodynamic severity and prevalence of RV dysfunction increased from IpcPH, to "intermediate" and CpcPH. PVR and DPG (but not compliance, Ca) were linearly correlated with RV dysfunction. CpcPH had worse prognosis (p<0.05) than IpcPH and PAH, but similar to "intermediate" patients. Only NTproBNP and Ca independently predicted survival in PH-LHD.

Conclusions: In PH-LHD, haemodynamic characterization according to DPG and PVR provides important information on disease severity, predisposition to RV failure and prognosis. Patients presenting the CpcPH phenotype appear to have haemodynamic profile closer to PAH but with worse prognosis. In PH-LHD, Ca and NTproBNP were independent predictors of survival.

Fig 1. Effects of varying the diastolic pressure gradient and pulmonary artery wedge pressure on the compliance-resistance relationship in patients with pulmonary hypertension.

Panel a): pulmonary arterial compliance as a function of pulmonary vascular resistance, both logarithmically transformed. Panel b): resistance-compliance product as a function of pulmonary artery wedge pressure. Ca = pulmonary arterial compliance; DPG = diastolic pressure gradient; PAH = pulmonary arterial hypertension; PH-LHD = pulmonary hypertension due to left heart disease; PVR = pulmonary vascular resistance; RC-time = pulmonary vascular resistance-compliance product.

Fig 2

Prevalence of echocardiographic signs of right ventricular dysfunction in the four groups of patients as a function of pulmonary haemodynamics: pulmonary vascular resistance (panel a), diastolic pressure gradient (panel b), and pulmonary arterial compliance (panel c). Ca = pulmonary arterial compliance; CpcPH = combined post- and pre-capillary pulmonary hypertension; DPG = diastolic pressure gradient; Interm = intermediate; IpcPH = isolated post-capillary pulmonary hypertension; PAH = pulmonary arterial hypertension; PVR = pulmonary vascular resistance; RV = right ventricle.

Fig 3. Kaplan-Meier curves of survival for patients with pulmonary arterial hypertension and patients with pulmonary hypertension due to left heart disease.

In the panel a) patients with pulmonary hypertension due to left heart disease are all pooled together, while in the panel b) they are subdivided in three groups according to the diastolic pressure gradient and pulmonary vascular resistance. CpcPH = combined post- and pre-capillary pulmonary hypertension; Interm = intermediate PH-LHD; IpcPH = isolated post-capillary pulmonary hypertension; PAH = pulmonary arterial hypertension; PH-LHD = pulmonary hypertension due to left heart disease.