Potential Pathophysiological Mechanisms in Septic Cardiomyopathy: an Overview

Septic cardiomyopathy can be classified as a secondary form of cardiomyopathy, the heart being involved in the systemic disease “sepsis”. The pathophysiology of septic cardiomyopathy is much more complex than the pathophysiology of most of the textbook heart diseases. This complexity is the consequence of the impact of numerous toxins and sepsis mediators on the heart in the course of the disease. Main trigger substances of septic pump failure are endotoxin, TNF-α, IL-1 and NO, which interfere with receptors, inotropic signal transduction pathways, Ca2+ transients and the contractile apparatus of the cardiomyocyte. These inflammatory mediators also impair mitochondrial function of cardiac cells, with the consequence of cytopathic hypoxia and energy depletion, but also increased production of reactive oxygen species and induction of apoptosis in the organ. Cardiac dysfunction is characterized by systolic as well as diastolic dysfunction of the left and the right ventricle and – typically – by reversible dilation of the heart; diastolic dysfunction of the left ventricle seems to be the prognostically most relevant alteration. For compensation of the sepsis-induced vasoplegia resulting in a fall in blood pressure, the diseased heart has to pump even more, to furnish the demands of circulation, which further stresses the organ. Thus “afterload-related cardiac performance” (ACP) characterizes the cardiac pump failure in sepsis much better than isolated measures of systolic or diastolic dysfunction. Septic cardiomyopathy is not a primary ischemic disease: Coronary macrocirculation seems not impaired, while coronary microcirculation probably is. Drastic alterations are seen in cardiac metabolism, with a strong reduction of free fatty acids fuelling, with cytopathic hypoxia and some form of myocardial hibernation. Also chronotropic and bathmotropic dysregulation characterizes septic cardiomyopathy: resting heart rate is high and heart rate variability is reduced. This is the result of cardiac autonomic dysfunction with a strongly depressed vagal as well as sympathetic regulation in sepsis. Moreover, endotoxin interacts with the HCN channels of the pacemaker current in sinus node, thereby contributing to the intrinsic impairment of heart rate regulation. The pathophysiology of septic cardiomyopathy is complex, the cardiac alterations can be reversible and the impairments of heart function contribute to the unfavorable prognosis of septic patients.