Pulmonary Venous Hypertension- An On Going Quest for Treatment: Is PDE5 Inhibition the Right Solution?

Abstract

Pulmonary venous hypertension is pulmonary hypertension resulting from elevated left sided filling pressures. This may result from chronic elevation of left atrial pressures from heart failure; either heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) or from valvular heart disease. This is classified as Group 2 pulmonary hypertension in the Dana point classification [1]. Pulmonary hypertension due to left heart disease is defined as mean pulmonary arterial pressure (mPAP) greater than or equal to 25 mm Hg, pulmonary capillary wedge pressure (PCWP) of greater than or equal to 15 mm Hg and pulmonary vascular resistance (PVR) greater than 3WU. Chronic elevation of left ventricular end diastolic pressures will result in increased left atrial pressures, initially causing passive congestion and rise in pulmonary venous pressures and resulting pulmonary arterial hypertension. This usually reverses readily with diuresis and lowering the left atrial pressures. Transpulmonary gradient (TPG = mPAP – PCWP) is normal at this stage. Continued elevation in PCWP may result in pulmonary vasoconstriction and reactive pulmonary hypertension where the TPG is greater than 12 mm HG and pulmonary vascular resistance (PVR) is greater than 3WU. This reactive pulmonary hypertension responds to diuresis and pulmonary vasodilation with agents such as nipride, nesiritide, inhaled nitric oxide or milrinone. Over time, the passive congestion and vasocontiction causes pulmonary vascular remodeling resulting in abnormalities of elastic fibres, smooth muscle proliferation and endothelial proliferation causing pulmonary arterial remodeling and resulting obliterative arteriopathy which is in part mediated by endothelin and is histologically indistinguishable from pulmonary arterial hypertension [2] Table 1. Epidemiology