Pharmacologic support of cardiac failure

Pathophysiology

The pathophysiologic mechanisms leading to ADHF, as well as the goals of pharmacologic treatment, must be identified in order to successfully treat patients with ADHF. Understanding the complex nature of each specific disease process and its physiologic response is crucial for improving function and outcome. Cardiac failure is usually a result of derangement in any number of physiologic factors, including preload, afterload, contractility, heart rate, and heart rhythm.

Increased preload is common in ADHF and is usually secondary to volume overload but can also occur with myocardial ischemia and valvular dysfunction. The body’s natural compensatory response is to increase filling pressures to improve myocardial contractility by increasing wall stress on the ventricle (moving up on the Frank-Starling curve). Heart failure generally causes a decrease in renal blood flow and subsequently activates the renin-angiotensin-aldosterone axis (RAAA). The end results of these compensatory mechanisms are vasoconstriction by angiotensin II with increased renal blood flow; release of aldosterone, which increases sodium absorption in exchange for potassium; and promotion of ventricular hypertrophy, fibrosis, and remodeling that ultimately leads to increased ventricular stiffness.

Increased cardiac afterload is common in the perioperative setting and is due to multiple causes such as preexisting hypertension, catecholamine surge, postoperative hypertension, and release of cytokines and inflammatory mediators. Moreover, pulmonary artery hypertension is increased owing to similar causes, but can be exacerbated as well by relative hypoxic vasoconstriction and acidosis. In the failing heart, the sympathetic nervous system (SNS) is stimulated as the body acts to increase systemic vascular resistance (SVR) to maintain normal perfusion to vital organs. The failing heart is further strained as it attempts to increase cardiac output against higher outflow pressures. The increased sympathetic tone also stimulates the release of renin, further activating the RAAA and its inherent problems in heart failure. Subsequently, there is an increase in myocardial oxygen demand, worsening sodium and water retention, and a heightened potential to exacerbate lethal cardiac arrhythmias. Furthermore, higher plasma levels of circulating catecholamine have been correlated with worse prognosis.

Myocardial contractility is largely affected by stimulation of the SNS. Adrenergic agents increase intracellular cyclic adenosine monophosphate (cAMP), which in turn, increases calcium influx and strengthens the contraction. However, with chronically increased sympathetic tone, the failing heart becomes less responsive to circulating catecholamines, seemingly protecting the myocytes from the excessive catecholamines and their resulting inotropic and chronotropic drive. This dampened response is due to decreased sensitivity and downregulation of the β-receptors from the chronically elevated catecholamine levels that persist in congestive heart failure. Contractility becomes impaired and is less responsive to physiologic needs as well as to pharmacologic agents that act at the β-adrenergic receptors. In addition, the failing heart responds inadequately to volume overload. The Frank-Starling mechanism is blunted, and significant increases in preload are poorly tolerated, further exacerbating congestive symptoms.

Right ventricle (RV) failure is becoming increasingly recognized as a significant cause of morbidity and fatality in the ICU. The RV is thin walled and compliant relative to the left ventricle (LV) and is designed to function in a low-pressure, low-resistance environment. Contraction occurs in three stages: (1) papillary muscle contraction, (2) RV movement toward the interventricular septum, and (3) LV contraction with twisting of the RV. There is minimal time spent in isovolumic contraction and relaxation, resulting in almost continuous flow to the lungs. The RV is perfused primarily from the right coronary artery (RCA), with perfusion occurring in systole and diastole as long as the low-pressure system remains intact. The RV is vulnerable to elevation in pulmonary vascular resistance, which will increase the time spent in isovolumic contraction and relaxation, decreasing overall forward blood flow. Both ventricles are dependent on movement of the interventricular septum, which can shift toward either the RV or LV, both of which can impair adequate filling and increase end-diastolic pressures.

Following cardiac surgery, ventricular function is transiently impaired even in patients with normal preoperative ventricular function. This is due to several factors, including aortic cross-clamping, inadequate myocardial protection, hypothermia and cardioplegia, and reperfusion injury, as well as excessive levels of inotropes in the perioperative setting. There is a biphasic pattern, with initial recovery following weaning from cardiopulmonary bypass (CPB), a nadir at about 3 to 6 hours, and then full recovery at 8 to 24 hours. This pattern can obviously be delayed by poor preoperative ventricular function. Pharmacologic support is frequently necessary until adequate function returns.

Treatment

The general pharmacologic goals of supporting the acutely decompensated heart are to ameliorate afterload, optimize preload and myocardial performance while modulating myocardial oxygen consumption, and minimize further activation of the neurohormonal cascade. Additional support is often needed to maintain an adequate mean arterial blood pressure to ensure sufficient coronary blood flow.