Pulmonary Hypertension

Introduction

Historically, the pulmonary circulation and right ventricle (RV) have not been given the same degree of attention as the left heart circulation. The increasing attention devoted to researching pulmonary hypertension (PH) and right heart failure have led to a profound increase in our understanding of pulmonary vasculature and right heart physiology. Together with advances in echocardiography, these efforts have enabled us to better characterize PH and right heart failure. This chapter will focus on the anatomy of the RV, the pathophysiology of PH, and the echocardiographic evaluation of the pulmonary hypertensive patient.

Pulmonary Hypertension and Right Heart Failure

PH is a disorder where flow to the pulmonary arterial circulation is restricted related to increased pulmonary vascular resistance (PVR), ultimately leading to right heart failure. The pulmonary circulation is normally a low-pressure, low-resistance circulation. Mild PH is generally defined as a mean pulmonary artery pressure (mPAP) above 25 mmHg at rest and PVR greater than 300 dynes·sec·cm⁻⁵ (>3.75 Wood units), whereas severe PH constitutes mPAP above 50 mmHg and PVR greater than 600 dynes·sec·cm⁻⁵ (>7.5 Wood units). ¹

At the recent 4th World Conference on Pulmonary Hypertension held by the World Health Organization, PH was classified into five groups:

1. Idiopathic pulmonary arterial hypertension (IPH), familial pulmonary hypertension (FPH), and PH associated with conditions such as connective tissue disorders, portal hypertension, pulmonary veno-occlusive disease, HIV, and anorexigens

2. PH with left heart disease

3. PH with lung diseases and/or hypoxemia

4. PH due to chronic thromboembolic disease

5. Miscellaneous ²

Regardless of the primary pathologic mechanisms, once PH exists, the effects on the right heart and pulmonary arteries are similar.

Pathophysiology

PH is a panvasculopathy, mostly affecting small and medium-sized arterial vessels with a wide range of abnormalities, including intimal hyperplasia, medial hypertrophy, adventitial proliferation, and plexiform arteriopathy. Multiple pathogenic pathways have been implicated in the development of PH. There is a vasoconstriction phase, starting with altered vascular endothelial and smooth muscle function, leading to vasoconstriction and localized thrombosis. With progression of the disease, vascular remodeling, proliferation, and formation of plexiform lesions ³ result in increased PVR and end with right heart failure and death. The plexiform lesion, a histologic hallmark of FPH and IPH, is a result of monoclonal proliferation of endothelial cells and migration and proliferation of smooth muscle cells. ⁴ The basis for current medical therapies is that endothelial dysfunction leads to an imbalance between vasoconstrictors (endothelin 1, thromboxane A₂) and vasodilators (prostacyclin, nitric oxide). ⁵

The endothelium releases thromboxane A₂, which is a potent vasoconstrictor, cell proliferator, and powerful platelet activator, in addition to prostacyclin, a potent vasodilator and inhibitor of platelet aggregation. ⁶ This mediator imbalance results in pulmonary vasoconstriction, disordered endothelial cell proliferation, and proliferation of intimal cells, leading to the characteristic plexiform lesions.

Clinical Manifestations

The most common presenting symptom in PH is dyspnea. Other symptoms may include angina, fatigue, weakness, and syncope. The first step in diagnosing PH is recognizing patients at high risk. Insidious and nonspecific onset of shortness of breath often results in delayed diagnosis. Symptoms of the disease are first noted when the RV is unable to increase contractility sufficiently to augment left ventricular (LV) preload and cardiac output during exercise.

Physical examination focuses on signs of both PH and right heart failure. Accentuation of the pulmonic component of the second heart sound and an early systolic murmur reflecting tricuspid regurgitation (that enhances with spontaneous inspiration) might be the only findings on physical exam. Jugular venous distention, hepatojugular reflux, peripheral edema, hepatomegaly, and ascites are signs of advanced PH.7,8 Correct evaluation is essential for appropriate management, and echocardiography is the most appropriate next step. Findings such as RV hypertrophy and/or dilation, LV filling impairment, or paradoxical interventricular septal motion are indicative of right heart failure. To confirm the diagnosis, a right heart catheterization (RHC) assessment of PVR, right atrial (RA) and RV pressures, and LV pressures is required.

Right Ventricle and Pathophysiology of Right Heart Failure

The RV is a unique and complex structure. Its primary function is to pump the venous return into the pulmonary arteries. When ventricular function and loading conditions are normal, the RV is triangular in shape when viewed from the side in the midesophageal four-chamber view and crescent shaped when viewed in cross-section; the LV is ellipsoid in shape. The RV is divided into three portions: (1) the inflow, consisting of the tricuspid valve (TV), chordae tendineae, and papillary muscles; (2) the trabeculated apical myocardium; and (3) the outflow, corresponding to the smooth myocardial infundibulum and ending with the pulmonic valve (PV).

An encircling muscular band separates the RV into the inflow portion, the sinus, and the outflow portion (or conus). This muscular band is referred to as the crista supraventricularis and is made up of the infundibular septum and the parietal band. Two other muscular bands are present in the RV: the septal and moderator bands. The moderator band is an important landmark of the RV that is well visualized by echocardiography. It is attached to the right ventricular outflow tract (RVOT) and runs from the septum to the anterior RV wall.9,10

The RV contracts in a fashion resembling peristalsis, beginning with contraction of the inlet portion, followed by the apex, and ending with contraction of the infundibulum. It pumps on average the same stroke volume as the LV but generates only about 25% of the stroke work, owing to the low-pressure, low-resistance, and high-compliance nature of the pulmonary circulation. ¹¹ As a result, the normal RV’s wall thickness is half that of the LV and accordingly more compliant. Because of the RV’s reduced contractile reserve compared to the LV’s, it is much more sensitive to increases in afterload. Functionally and anatomically, the RV is adapted for generation of sustained low-pressure perfusion. ¹² The dissimilarity in ventricular afterload is responsible for the difference in ventricular pressure-volume loops between the two ventricles. The LV has a square-shaped pressure-volume loop, whereas the RV pressure-volume loop is triangular. The triangular shape depicts the shorter pre-ejection period that is due to the RV systolic pressure, which rapidly exceeds pulmonary artery diastolic pressure. This means the normal RV has a longer period of ejection and shorter periods of isovolumic contraction and relaxation. ¹³ The RV pressure-volume loop becomes more square shaped with increases in RV afterload. In addition, the orientation of the interventricular septum (IVS) and geometry of the ventricles change with any increase in RV volume or pressure overload. ¹⁴

Ventricular interdependence results from the close anatomic association between the LV and RV; they share the IVS and are enclosed within the same pericardial sac. The IVS contributes to both LV and RV function 15,16 and is responsible for approximately one third of the RV stroke work under normal conditions; it is a major determinant of overall RV performance. ¹⁷ Ventricular interdependence is mediated mainly through the IVS and plays an essential part in the pathophysiology of RV dysfunction. In the setting of RV infarction and loss of RV free wall contractility, it is the septum that continues to generate RV systolic pressure. RV ejection fraction (RVEF) is very sensitive to increases in RV afterload (i.e., pulmonary artery pressures); high afterload leads to increased RV wall tension and oxygen demand and RV ischemia. As the RV enlarges to accommodate the increase in pressure, this results in dilation of the tricuspid annulus and creates tricuspid regurgitation (TR). Eventually this results in a rise in RV end-diastolic and RA pressures, with associated clinical signs of RV failure. ¹⁸ Whereas the RV is normally perfused during both diastole and systole, the systolic component becomes compromised with raised chamber pressures. ¹⁹ Thus, maintaining perfusion pressure is essential, especially when RV systolic pressure is elevated. Vlahakes et al. examined the mechanism of RV failure in dogs under anesthesia and the importance of maintaining perfusion pressure. After producing RV failure with increasing PA pressures, infusion of phenylephrine raised aortic pressure, thereby increasing myocardial perfusion pressure and reversing RV failure, as shown by the increase in cardiac output. ²⁰

Normally the IVS is shifted toward the RV free wall during systole and diastole, which contributes to RV ejection. However, in conditions with increased RV pressure or volume overload, the IVS paradoxically shifts toward the LV. The shifted septum alters LV geometry, leading to decreased LV preload, increased LV end-diastolic pressure, low cardiac output, and a diminished contribution to RV ejection. ²¹ As noted earlier, systemic vasoconstrictors and maintenance of perfusion pressure can be used to restore RV ejection and blood supply.^22,23

Echocardiography is extremely valuable in the diagnosis, assessment, and perioperative management of the pulmonary hypertensive patient.

Echocardiographic Examination of the Pulmonary Hypertensive Patient

Echocardiographic evaluation of patients with PH includes a complete exam with particular focus on the right side of the heart. This includes examining the anatomy and function of the RA and RV (including their influence on left heart function), the TV and PV, and connecting vascular structures (superior and inferior venae cavae [SVC, IVC], pulmonary artery [PA]). The following is a brief description of the standard echocardiographic views required for evaluation of the right heart, as well as detailed descriptions of evaluating these structures in patients with PH. In addition, Kasper et al. have described five additional views of the right heart, of which three specifically increase visualization of the RV myocardium and evaluation of the PV. ²⁴ Use of echocardiography in estimating right heart hemodynamics will also be discussed.

Right Ventricular Hypertrophy

In response to chronically elevated RV afterload, the RV myocardium hypertrophies. This may be demonstrated on echocardiography as RV free wall thickness greater than 5 mm at end-diastole ( Fig. 25-3). Long-standing severe chronic PH may result in RV hypertrophy exceeding 10 mm. This measurement may be obtained in the ME four-chamber view, the ME RV inflow-outflow view, or the TG mid-papillary view, often aided by the use of M-mode echocardiography. Hypertrophy of the RV includes the encircling bands, yielding an often easily identified hypertrophied moderator band near the RV apex ( Fig. 25-4 and Video 25-2 ).