Managing Right Ventricular Failure in PAH: An Algorithmic Approach

Abstract

Pulmonary arterial hypertension (PAH) is a disorder characterized by progressive elevation of pulmonary artery pressure (PAP) and vascular resistance in the absence of left-sided cardiac disease , pulmonary vein compression, respiratory disorders, or thromboembolic disease. It is defined by a mean PAP over 25 mmHg at rest or over 30 mmHg with exercise and a pulmonary artery occlusion pressure (PAOP) of less than 15 mmHg. PAH is associated with a poor prognosis. The estimated median survival from diagnosis is 2.8 years and the 1-year and 5-year survival rates are only 68% and 34%, respectively. 1,2 More than 70% of PAH patients will die as a result of right ventricular failure and most of the remainder from dysrhythmia. Predictors of a poor prognosis in PAH are related to the development of right ventricular failure. 1,3,4 The objectives of this review are to examine the pathophysiologic mechanisms leading to the development of right ventricular failure due to PAH, the diagnostic features of right ventricular failure, and the management of chronic right ventricular failure with emphasis on acute decom-pensation in this setting. Pathophysiology Clinical Manifestations and Hemodynamic Derangements The normal right ventricle is a thin-walled (less than 0.6 cm), trabeculated, roughly triangular structure that weighs less than 65 g in men and less than 50 g in women. 5,6 It is designed to empty its volume into a low-impedance, high-capacitance, pulmonary circulation by contracting sequentially from inflow to outflow. The pulmonary circulation can tolerate three-to fourfold increases in right-sided cardiac output without significant increases in PAP. In healthy individuals , pulmonary vascular resistance (PVR) decreases as the cardiac output rises with exercise. 7 In the setting of PAH, PVR does not sufficiently decrease with exercise, resulting in dyspnea and poor exercise capacity. Progressive PAH presents a pressure overload state to the right ventricle, increasing right ventricular workload leading to concentric hypertrophy (Figure 1). The right ventricle compensates: the walls hypertrophy while maintaining a normal or smaller chamber size, resulting in normal or reduced right ventricular wall stress. During this compensated phase of adaptive hypertrophy and normal to reduced wall stress, the ventricle is able to eject blood against the high PVR while maintaining an adequate right-sided cardiac output and normal right atrial pressure. During this phase patients exhibit few symptoms. The right ventricle can compensate only so long, initiating the symptomatic/declining phase (Figure 1). During this phase, with marked, maladaptive right ventricular hypertro-phy and variable degrees of interstitial fibrosis, diastolic function may be impaired, altering the right ventricular dias-tolic pressure-volume relationship and leading to increases in right ventricular end-diastolic and right atrial pressures. With persistent pressure overload, the right ventricle undergoes a remodeling process eventually leading to right ven-tricular failure. The right ventricular chamber dilates and the concentric hypertrophy transitions to eccentric hypertrophy, resulting in increased wall stress and systolic dysfunction. Increased heart rate and right ventricular wall stress lead to significant increases in right ventricular myocardial oxygen consumption. This, in combination with reduced right ven-tricular endomyocardial coronary perfusion (due to reduced right coronary artery pressure, rising right ventricular end-diastolic pressure, and increased right ventricular mass), leads to right ventricular ischemia and worsening right ven-tricular diastolic and systolic function. The right ventricular ischemia may be clinically manifest as chest pain. As the right ventricle and the tricuspid valve annulus dilate, functional tricuspid regurgitation progressively worsens. Tricuspid regurgitation further compromises right ventricular forward output, and ultimately, left ventricular filling. During this phase of right ventricular remodeling, cardiac output does not meet peripheral demands and right atrial pressure rises further as reflected clinically by exercise intolerance, progressive dyspnea, elevated jugular venous pressure, and fluid retention with edema (the hallmarks of right ventricu-lar failure). These clinical signs reflect both a low cardiac output and the detrimental activation of neurohormones and other mediators. 2,8,9 Natriuretic peptide levels become significantly elevated in patients with right heart failure even in the absence of left ventricular dysfunction. B-type natriuret