Management of Severe Pulmonary Arterial Hypertension
Management of Severe Pulmonary Arterial Hypertension
The RV is embryologically, morphologically, and functionally distinct from the left ventricular (LV). The metabolic and genetic profile in response to an increase in afterload also differ. Before the birth the RV is the dominant ventricle and is well suited to eject blood into the systemic circulation via a patent ductus arteriosis. After birth and following normal lung inflation it rapidly assumes the adult phenotype of a relatively thin-walled, oddly crescent-shaped structure (Fig. 1). Despite these changes it is highly efficient and well adapted to eject into the pulmonary circulation; a circuit that is able to accommodate large increases in blood flow with little change in pressure owing to high vascular reserve, high compliance, and low impedance. The RV and LV are mechanically interrelated by the shared interventricular septum and pericardium. Although, RV contraction contributes to pulmonary blood flow, ejection of the RV is significantly augmented by LV contraction. Though the RV is highly efficient, it is ill adapted to sudden increases in afterload. When presented with an acute increase in afterload, cardiac output is likely preserved through an increase in RV end-diastolic volumes via a Frank-Starling mechanism as well as a homeometric mechanism that is characterized by an increase in work and more rapid development of pressure at a given end-diastolic volume. However, a severe and sudden increase in RV afterload may overwhelm the contractile capability of the RV and lead to hemodynamic collapse. In patients with chronic pulmonary vascular disease, manifested by a more gradual increase in RV afterload, there is a change in the mechanical characteristics of the RV as it starts to assume a similar pattern of ejection to that of the left ventricle with an increase in RV elastance and a reduction in diastolic compliance. However, in the face of a progressive or sudden worsening in RV afterload these compensatory mechanisms are overwhelmed. In addition to the rate of progression in RV afterload, differences in the ability of the RV to compensate for an increase in afterload likely relate to age of the patient (or age at onset of the RV pressure load). Early in life the fetal RV is well adapted to high afterload making it well suited to situations where it may assume the role as the systemic ventricle. Additionally, there may be differences in RV adaptation in the setting of proximal (pulmonary artery [PA] banding or pulmonic stenosis) as opposed to more distal pulmonary vascular occlusion (PAH). Finally, the chronically dilated or volume overloaded RV may adapt differently and may be less capable of compensating for an increase in RV afterload.
(Enlarge Image)
Figure 1.
Cross-sectional view of the normal heart contrasting the differences in the shape of the right and left ventricles. The right ventricle is thin walled, crescented in shape, and shares the muscular intraventricular septum. Image courtesy of Dr. Jagdish Butany.
Physiologically, RV failure represents the point at which there is dissociation between ventriculoarterial coupling. This coupling is a major determinant of RV function as it relates RV end-systolic elastance (a load-independent measure of contractility) relative to pulmonary arterial elastance (difference in end-systolic and end-diastolic RV pressure relative to stroke volume). Normal coupling represents a point at which there is adequate output at the lowest energy cost. In addition to the reduction in RV output, an increase in RV wall tension with resultant imbalance in myocardial oxygen consumption and delivery as well as adverse RV-LV interdependence may also contribute to the spiraling decrease in cardiac function and must be emphasized as important therapeutic targets in treating patients with RV failure (vide infra).
The clinical sequelae of RV failure is more familiar, and characterized by a reduction in cardiac output with resultant increase in venous pressure and signs/symptoms of venous congestion such as jugular venous distention, hepatomegaly, peripheral edema, and ascities. A reduction in a reduced cardiac output (i.e., cardiac index < 2.5 L/min/m) will eventually lead to an impairment of systemic oxygen delivery to tissues. Indeed the development of systemic hypotension and renal insufficiency are ominous prognostic signs.
Pathophysiology of Right Ventricular Failure
The RV is embryologically, morphologically, and functionally distinct from the left ventricular (LV). The metabolic and genetic profile in response to an increase in afterload also differ. Before the birth the RV is the dominant ventricle and is well suited to eject blood into the systemic circulation via a patent ductus arteriosis. After birth and following normal lung inflation it rapidly assumes the adult phenotype of a relatively thin-walled, oddly crescent-shaped structure (Fig. 1). Despite these changes it is highly efficient and well adapted to eject into the pulmonary circulation; a circuit that is able to accommodate large increases in blood flow with little change in pressure owing to high vascular reserve, high compliance, and low impedance. The RV and LV are mechanically interrelated by the shared interventricular septum and pericardium. Although, RV contraction contributes to pulmonary blood flow, ejection of the RV is significantly augmented by LV contraction. Though the RV is highly efficient, it is ill adapted to sudden increases in afterload. When presented with an acute increase in afterload, cardiac output is likely preserved through an increase in RV end-diastolic volumes via a Frank-Starling mechanism as well as a homeometric mechanism that is characterized by an increase in work and more rapid development of pressure at a given end-diastolic volume. However, a severe and sudden increase in RV afterload may overwhelm the contractile capability of the RV and lead to hemodynamic collapse. In patients with chronic pulmonary vascular disease, manifested by a more gradual increase in RV afterload, there is a change in the mechanical characteristics of the RV as it starts to assume a similar pattern of ejection to that of the left ventricle with an increase in RV elastance and a reduction in diastolic compliance. However, in the face of a progressive or sudden worsening in RV afterload these compensatory mechanisms are overwhelmed. In addition to the rate of progression in RV afterload, differences in the ability of the RV to compensate for an increase in afterload likely relate to age of the patient (or age at onset of the RV pressure load). Early in life the fetal RV is well adapted to high afterload making it well suited to situations where it may assume the role as the systemic ventricle. Additionally, there may be differences in RV adaptation in the setting of proximal (pulmonary artery [PA] banding or pulmonic stenosis) as opposed to more distal pulmonary vascular occlusion (PAH). Finally, the chronically dilated or volume overloaded RV may adapt differently and may be less capable of compensating for an increase in RV afterload.
(Enlarge Image)
Figure 1.
Cross-sectional view of the normal heart contrasting the differences in the shape of the right and left ventricles. The right ventricle is thin walled, crescented in shape, and shares the muscular intraventricular septum. Image courtesy of Dr. Jagdish Butany.
Physiologically, RV failure represents the point at which there is dissociation between ventriculoarterial coupling. This coupling is a major determinant of RV function as it relates RV end-systolic elastance (a load-independent measure of contractility) relative to pulmonary arterial elastance (difference in end-systolic and end-diastolic RV pressure relative to stroke volume). Normal coupling represents a point at which there is adequate output at the lowest energy cost. In addition to the reduction in RV output, an increase in RV wall tension with resultant imbalance in myocardial oxygen consumption and delivery as well as adverse RV-LV interdependence may also contribute to the spiraling decrease in cardiac function and must be emphasized as important therapeutic targets in treating patients with RV failure (vide infra).
The clinical sequelae of RV failure is more familiar, and characterized by a reduction in cardiac output with resultant increase in venous pressure and signs/symptoms of venous congestion such as jugular venous distention, hepatomegaly, peripheral edema, and ascities. A reduction in a reduced cardiac output (i.e., cardiac index < 2.5 L/min/m) will eventually lead to an impairment of systemic oxygen delivery to tissues. Indeed the development of systemic hypotension and renal insufficiency are ominous prognostic signs.