Septic Cardiomyopathy: From Pathophysiology to the Clinical Setting

Abstract

The onset of cardiomyopathy is a common feature in sepsis, with relevant effects on its pathophysiology and clinical care. Septic cardiomyopathy is characterized by reduced left ventricular (LV) contractility eventually associated with LV dilatation with or without right ventricle failure. Unfortunately, such a wide range of ultrasonographic findings does not reflect a deep comprehension of sepsis-induced cardiomyopathy, but rather a lack of consensus about its definition. Several echocardiographic parameters intrinsically depend on loading conditions (both preload and afterload) so that it may be challenging to discriminate which is primitive and which is induced by hemodynamic perturbances. Here, we explore the state of the art in sepsis-related cardiomyopathy. We focus on the shortcomings in its definition and point out how cardiac performance dynamically changes in response to different hemodynamic clusters. A special attention is also given to update the knowledge about molecular mechanisms leading to myocardial dysfunction and that recall those of myocardial hibernation. Ultimately, the aim of this review is to highlight the unsolved issue in the field of sepsis-induced cardiomyopathy as their implementation would lead to improve risk stratification and clinical care.

Keywords: cardiomyopathy; inflammation; sepsis; septic shock.

Figure 1

Diagnostic challenges in septic cardiomyopathy are a consequence of its complex pathophysiology. Recent advances in cardiac imaging paradoxically increased the uncertainty on how to define sepsis-induced cardiomyopathy. Underlying myocardial dysfunction, heart rate and the need of acute interventions (i.e., fluid challenge and inotrope use) add further layer of complexity. These issues highlight the importance of a dynamic assessment of cardiac performance over time, not limited to echocardiographic findings but also considering the cardiac performance.

Figure 2

Hemodynamic stress and systemic inflammation exert a synergistic effect on myocardial function impairment during sepsis. Systemic response to sepsis triggers and sustains myocardial dysfunction through several pathways: by impairing the compensatory reaction of sympathetic system with consequent microvascular dysfunction and—In parallel—through theimmune system activation and microvascular dysfunction (black arrows). Those mechanisms deeply impair myocardial tissue through a cascade involving damage- and pathogen-associated molecular pattern (DAMPs and PAMPs, respectively), Toll-like receptors (TLRs), complement and release of cytokines and reactive oxygen species.