Right Ventricular Failure
Accurate and rapid assessment of right ventricular failure (RVF) is challenging. The thin-walled right ventricle (RV), which serves as a conduit to the typically high-flow low-pressure pulmonary circulation, is less tolerant of increases in afterload and wall stress. Right ventricular hemodynamic compromise can occur as a result of a variety of clinical insults and can benefit from an equally diverse group of therapies. This chapter presents the clinical approach to the evaluation of the failing right heart, while providing evidence-based strategies for effective therapeutic intervention.
CLASSIFICATION AND EPIDEMIOLOGY
RVF is a complex clinical process defined by the inability to provide adequate blood flow through the pulmonary circulation at a normal central venous pressure (CVP).1,2 Although heart failure is often ascribed to either the left or the right ventricle, the interdependence of these structures renders this division somewhat artificial. Isolated left ventricular failure can create an unhealthy milieu for an otherwise well-functioning RV, just as a struggling RV can hinder the performance of a normal LV. In the latter case, RV distension and diminished contractility may lead to paradoxical interventricular septal motion, producing an acute deficit in LV filling and therefore decreased cardiac output and oxygen delivery.
RV dysfunction or failure occurs as the result of one or more of three pathophysiologic processes: RV pressure overload, volume overload, or reduced contractility (see Fig. 15.1). RV pressure overload may occur in conditions such as pulmonary embolism (PE), pulmonary arterial hypertension (PAH) (with or without associated lung disease), and positive pressure ventilation. RV volume overload occurs in the setting of valvular (tricuspid or pulmonic) regurgitation and has particularly deleterious effects on LV systolic function. Finally, depressed RV contractility may manifest as a result of myocardial ischemia, arrhythmia, or sepsis.
FIGURE 15.1 Pathophysiologic contributors in acute right heart failure. (RVMI, right ventricular myocardial infarction; PAH, pulmonary arterial hypertension; PE, pulmonary embolism; CHD, congenital heart disease; PR, pulmonic regurgitation; TR, tricuspid regurgitation). Adapted from Piazza G, Goldhaber SZ. The acutely decompensated right ventricle, pathways for diagnosis and management. Chest. 2005;128:1836–1852.3 Reproduced with permission from Stanford University School of Medicine.
Specific etiologies of RV dysfunction include intrinsic pulmonary or pulmonary vascular conditions (also termed cor pulmonale) or cardiac disease. Data regarding the incidence and associated morbidity and mortality of various causes are presented in Table 15.1. Patients requiring ICU admission for RV failure frequently experience high mortality rates and require prolonged medical intensive care.31,32 Other conditions not mentioned in Table 15.1 that can result in RV failure include adult congenital heart disease, sleep-disordered breathing, any disorder associated with pulmonary hypertension (PH)—including chronic thromboembolic disease—and connective tissue disorders such as scleroderma (Table 15.2).
TABLE 15.1 Epidemiology and Associated Morbidity and Mortality of RV Dysfunction
aNo uniform criteria exists to assess the presence of right ventricular dysfunction. In the majority of studies included in this meta-analysis, right ventricular dysfunction was defined as right ventricular hypokinesis as assessed by a qualitative evaluation of the right ventricular wall motion.
bCirculatory collapse defined as loss of consciousness or systolic blood pressure ≤80 mm Hg.
cTechnetium-99m pyrophosphate scintigraphy and a dynamic flow study performed to detect right ventricular involvement.
dAcute cor pulmonale defined as RV dilation (a right ventricular end-diastolic area to left ventricular end-diastolic area ratio >0.6 on long-axis view) associated with septal dyskinesia on the short-axis view.
ePresence of RHF with no demonstrable cause other than COPD.
fRV dysfunction defined as a right ventricular ejection fraction (RVEF) <45% as determined by radionuclide ventriculography.
gDefined as a mean pulmonary artery pressure of >25 mm Hg on cardiac catheterization.
hRV function evaluated with a multimodal approach (lateral tricuspid annulus peak systolic velocity was used in association with the relative RV to LV size, motion of the RV wall, and expert evaluation).
Reproduced with the permission of Stanford University School of Medicine.
TABLE 15.2 World Health Organization Classification of PH
Adapted from Simonneau G, Robbins IM, Beghetti M, et al. Updated clinical classifications of pulmonary hypertension. J Am Coll Cardiol. 2009;54:S43.33
HISTORY AND PHYSICAL EXAM
In patients with mild to moderate chronic right heart disease, reports of dyspnea, fatigue, lethargy, light-headedness, angina, and exertional syncope or presyncope will predominate.3 Patients with a more severe disease may initially present with lower extremity edema or ascites, prompting complaints of abdominal pain or fullness due to hepatic congestion.
In a patient with established RV dysfunction, a careful review of medications is an essential part of the initial patient history, as any missed doses or lapses in compliance can result in a dramatic clinical decline. Patients with chronic PH treated with vasodilatory agents—or patients with chronic lung diseases treated with daily inhalers or immunomodulators—may develop advanced symptoms, despite seemingly minimal changes in their prescribed routine. Likewise, recreational or illicit drug use may trigger new, or exacerbate chronic, RV dysfunction. In particular, amphetamines, cocaine, and dietary supplements containing fenfluramine constitute a common cohort of agents known to cause PH and subsequent cor pulmonale.34,46
The initial physical exam centers on a determination of CVP and signs of low cardiac output or hemodynamic compromise. In the absence of significant tricuspid valve stenosis, CVP provides a reasonable estimate of the filling pressure of the RV, in much the same way that the pulmonary capillary wedge pressure can estimate LV diastolic pressure.1 Jugular venous pressure (JVP) is a surrogate for CVP, but it can be measured by direct visualization of the internal jugular vein. To perform the exam, position the patient at a 45-degree angle and measure at the vertical height of the jugular vein, just above the sternal angle (or angle of Louis).36 Calculate the JVP by adding 5 cm to this height (the distance from the middle of the right atrium to the sternal angle). CVP can also be estimated using ultrasound and examining the inferior vena cava (IVC) diameter (see Echocardiography below). A JVP >8 cm is suggestive of elevated right-sided filling pressures.
Additional physical exam signs suggestive of RV failure include an increase in intensity of the pulmonic component of S2, a narrowly split S2, a holosystolic murmur at the left lower sternal border (usually compatible with tricuspid regurgitation), a prominence of the “A” wave in the jugular venous pulse (corresponding to atrial contraction), and either a left parasternal heave or a downward subxiphoid thrust. In the patient presenting with severe decompensated disease, systemic signs of cardiogenic shock may manifest as cool extremities, diminished peripheral pulses, and decreased urine output.37
Identifying conditions that mimic RV failure requires consideration of disease processes that cause either a real or perceived elevation in CVP. For example, constrictive pericarditis produces elevated right-sided filling pressures with elevations in CVP as well as signs and symptoms of acute heart failure. Superior vena cava syndrome, as might be seen in patients with a history of central venous catheters, device placement, or known malignancies, can present with an increase in jugular venous distension, or height, without a true elevation in right atrial pressure.
Because lower extremity edema, abdominal ascites, and even hepatic engorgement can result from RVF, other syndromes marked by anasarca—or total body fluid excess—must also be excluded. Cirrhosis, nephrotic syndrome, or disorders disruptive of the hepatic circulation (such as Budd-Chiari or hepatic venoocclusive disease) may produce a pattern of edema identical to that found in states of RVF.
The initial evaluation of a patient with suspected RV dysfunction should begin with an assessment using simple and noninvasive diagnostic modalities. An electrocardiogram (ECG) can offer significant insight into the presence or absence of RV strain. Significant ECG findings include an S1Q3T3 pattern, right axis deviation, or signs of RV hypertrophy such as a dominant R wave in V1 and V2 with a prominent S wave in V5 and V6.38 A low threshold for performing a right-sided ECG (providing the additional leads of V3R to V6R) can improve the detection of RV infarction and inferior wall ischemia.8 In a prospective study of patients with acute inferior myocardial infarction (MI) complicated by RV involvement (evidenced by ST-segment elevation in V4R), in-hospital mortality rate was significantly higher when compared to those with inferior MI in the absence of RV ischemia (31% vs. 6%, respectively).39 Posterior MI, especially in patients with a right dominant coronary circulation, represents another potential insult to RV perfusion. This can manifest with subtle ECG findings, including prominent R wave amplitude and ST depressions in V1 to V3. However, more demonstrative ST-segment elevations can become evident with the use of posterior or the so-called esophageal ECG leads (V7 to V9).40
FIGURE 15.2 Signs of right ventricular hypertrophy/pulmonary hypertension. A: Enlarged pulmonary arteries and (B) loss of retrosternal airspace in a patient with chronic PAH.
Appreciating signs of RV enlargement on a single- or two-view chest x-ray (CXR) requires close attention to subtle findings. PH and RV hypertrophy may produce enlargement of the proximal pulmonary arteries or a reduction in retrosternal air space (Fig. 15.2). Classic CXR findings in PE include Westermark sign (focal oligemia) and Hampton hump (peripheral area of opacification representing pulmonary infarction); note that these findings lack in sensitivity and specificity.41 The absence of pulmonary edema in the setting of elevated JVP is considered to be the most specific sign for isolated RVF.1,2 Once conventional imaging studies such as CXR and computed tomography demonstrate evidence for RV dysfunction, however, the disease process is likely already advanced.
Bedside portable ultrasound and echocardiography has gained widespread popularity and can provide direct assessment of cardiac function. Findings indicative of RV dysfunction include tricuspid regurgitation, RV hypokinesis or dilatation (Fig. 15.3), right atrial enlargement, and paradoxical septal motion.12,37 CVP can be evaluated echocardiographically by measurement of the degree of IVC collapse with inspiration.42 RV failure due to acute PE—or occasionally MI—may present with diffuse hypokinesis of the RV free wall sparing the apex (McConnell sign).3 Echocardiographic findings in RV failure are discussed in further detail in Chapter 6.
FIGURE 15.3 Bedside echocardiogram in short-axis view demonstrating sizeable RV dilatation in a patient with PH. (RV, right ventricle; LV, Left ventricle.)
Poor end-organ perfusion as a result of diminished right heart function may be suggested by elevations in serum lactate or evidenced by markers of organ-specific injury such as serum creatinine (kidney) or hepatic function tests and bilirubin (liver).37 Troponin and brain natriuretic peptide (BNP)—two biomarkers of cardiac injury—also have predictive value in the setting of RV dysfunction due to PE or acute exacerbations of PH. In acute PE, an elevated troponin T was found to be associated with in-hospital and 30-day mortality, prolonged hypotension, cardiogenic shock, and need for resuscitation.43,44 BNP has also been shown to have significant predictive value for outcomes in PE. In one study of 79 patients with acute PE, those who had an uncomplicated clinical course (16.5%) all had normal BNP values, whereas all in-hospital deaths and serious events occurred in the group with elevated measures. BNP also serves as a reliable marker of RV strain and correlates well with echocardiographic measurements of RV/LV ratio and IVC dimension.45 In patients with PAH requiring hospitalization for ICU management of acute right heart failure, elevations in admission BNP, C-reactive protein, and creatinine were found to negatively correlate with survival.20
MONITORING AND SUPPORTIVE CARE
Initial treatment of RVF requires the basic supportive care necessary for all critically ill patients. Monitoring of blood pressure, heart rate, and pulse oximetry—whether performed noninvasively or with the assistance of an intra-arterial catheter—is essential. Central venous access, in addition to enabling complex pharmacotherapy, offers the additional benefit of regular CVP measurement and central venous oxygen saturation (ScvO2), data that can assist in the assessment of response to vasoactive medications and fluid therapy.
Supplemental oxygen administration to maintain oxygen saturation >92% can reverse one of the more injurious influences on RV afterload, namely, hypoxic vasoconstriction (see below). Basic lab work, including a complete blood count, coagulation studies, and a comprehensive metabolic panel, permits identification of easily correctable disorders such as anemia, electrolyte or acid/base abnormalities, as well as renal or hepatic dysfunction.
Once advanced monitoring is in place, and initial diagnostic studies performed, targeted interventions should be implemented to relieve RV strain. Prior to initiating medical therapy, however, consideration of the following unique characteristics of RV failure can help avoid unintentional exacerbation of cardiopulmonary function.
Administration of RV afterload-reducing agents such as inhaled nitric oxide can precipitate acute pulmonary edema if the RV failure is secondary to a left-sided cardiac process (e.g., LV systolic or diastolic failure, mitral stenosis). This occurs as a result of decreased pulmonary vascular resistance in the face of a relatively fixed left-sided obstruction or defect.46
In the case of RV failure presenting with systemic hypotension, initiation of certain vasopressor therapies may become necessary. There is no evidence to suggest that one inotrope or vasopressor has greater success than another at maintaining circulatory support in RVF. However, careful consideration should precede the use of strong alpha-1 agonists as they can increase pulmonary vascular tone and further impinge on RV function.
Although a trial of intravenous volume administration may be appropriate in hypotensive patients without an increased CVP or evidence of pulmonary edema (as in the case of right ventricular MI), signs of RV volume overload including a CVP of >12 to 15 mm Hg should preclude this therapy. In these instances, initiation of vasopressors or inotropes may be preferable; if uncertainty exists, aggressive fluid therapy should be avoided. A trial bolus of 500 cc of crystalloid, with careful monitoring of clinical response, should be used instead.3,47
Hypoxic pulmonary vasoconstriction—although normally a protective physiologic response against V/Q mismatching when pO2 levels drop below 50 to 60 mm Hg—requires a reversal in instances of life-threatening RV failure. Application of supplemental oxygen via nasal cannula, Venturi mask, simple face mask, nonrebreathing face mask, or other device depending on the degree of hypoxia can reduce pulmonary vascular resistance.48 Additionally, systemic acidosis, if present, can worsen hypoxic vasoconstriction and should be corrected.49
Available in the inhaled form (iNO), nitric oxide can diffuse rapidly across the alveolocapillary membrane into adjacent smooth muscle of pulmonary vessels to increase cyclic guanosine monophosphate, leading to vasodilatation. In right heart failure (RHF), iNO is an attractive therapeutic option given its ability to preferentially improve perfusion to well-ventilated pulmonary segments while avoiding unwanted systemic hypotension (prevented by the scavenging of NO by native hemoglobin). Initial dosing begins at 20 parts per million or less; higher concentrations provide little additional hemodynamic benefit.50 Disadvantages of iNO include the risk of developing methemoglobinemia as well as rebound PH upon discontinuation.51,52
Vasopressors and Inotropes
Improvement of a poorly contractile RV requires augmentation of ventricular perfusion, RV ejection fraction, and ultimately stroke volume. Various agents have been employed for this purpose, and each agent comes with different risks and benefits depending on the underlying etiology of the dysfunction (Table 15.3). Definitive evidence to guide choice of vasopressor or inotrope in patients with acute RHF is lacking. Experimental studies suggest that dobutamine may be more beneficial than norepinephrine.47,54 A recent extensive literature review gave weak evidence-based recommendations for the use of norepinephrine, vasopressin, dobutamine, and levosimendan. Strong recommendations were made for the use of PDE3 inhibitors (e.g., milrinone) for improvement in RV performance and reduction in pulmonary vascular resistance (PVR). A strong recommendation advised against the use of dopamine in cardiogenic shock secondary to an increase in tachyarrhythmias.55
TABLE 15.3 Common Agents Used in the Treatment of RV Failure
Adapted from Overgaard CB, Dzavík V. Inotropes and vasopressors: review of physiology and clinical use in cardiovascular disease. Circulation. 2008;118(10):1047–1056.53