An Integrated Approach of Subclinical Myocardial Dysfunction in Patients With Hepatic Cirrhosis: Echocardiography, Specific Biomarkers, and Vascular Assessment

Scientific context and motivation:

Cirrhosis is the end stage of chronic damage to the liver. The prevalence is estimated to be very high in Romania, more than 1000/100.000 inhabitants, with 10-year mortality of 34-66%. Upward trends of mortality are observed in a few countries, including Romania, which had extremely high mortality rates. The cost in terms of hospital costs and lost productivity is high. Therefore, hepatic cirrhosis represents a major public health in Romania.

It is known that hepatic cirrhosis is associated with cardiovascular abnormalities. These abnormalities have been suggested to induce/aggravate several complications of cirrhosis, and also to increase postoperative mortality after major surgery or liver transplantation. Few studies documented the existence of a hyperdynamic circulation, with increased cardiac output and reduced systemic vascular resistance. Despite this hyperkinetic circulation, some patients have abnormal ventricular function unmasked by physiologic/pharmacologic stress.

There are few studies of cardiac function in cirrhosis, although contractile function disorders found in nonalcoholic cirrhosis in animal models suggested that this is independent from alcohol intake. These issues are complicated by the fact that, alcohol use represents one of the commonest causes of both cirrhosis and cardiomyopathy. There are reasons to believe that cirrhosis per se may be associated with subtle contractile dysfunction. First, hyperkinetic circulatory changes may induce a high-output cardiac failure resembling a chronic volume overload of the heart. Second, cirrhosis is associated with high serum catecholamine levels, and long-term exposure to elevated catecholamines results in cardiomyopathy. Third, necropsy series of patients with alcoholic/nonalcoholic cirrhosis show similar cardiac pathologic findings: diffuse fibrosis, subendocardial edema, nuclear and cytoplasmic vacuolation.

Despite the increased cardiac output, ventricular inotropic and chronotropic responses to stimuli are blunted, a condition known as "cirrhotic cardiomyopathy". These include systolic and diastolic dysfunction, electrophysiological changes, and structural changes. There are no clear consensus definition for this condition. Cardiac function was evaluated by classic echocardiography, 2D and color/spectral Doppler: cardiac dimensions, left ventricular ejection fraction (LVEF), systolic and diastolic timings. All of these changes are dependent on load conditions, and cirrhosis has major variability of preload conditions. However, these conventional measurements allow only the late diagnosis of cardiac dysfunction, which might be already irreversible.