Sepsis-induced Cardiomyopathy

Sepsis is a dysregulated immune response due to infection, leading to life-threatening organ dysfunction affecting respiratory, renal, immunological, digestive, neurological, and cardiovascular organs. The prevalence of cardiovascular dysfunction caused by sepsis may reach up to 50%, and the symptoms may comprise vasodilatory shock, myocardial injury, arrhythmia, and sepsis-induced cardiomyopathy. (1) Sepsis-induced cardiomyopathy occurs frequently in critically ill patients, but the clinical features and prognostic impact of sepsis-induced cardiomyopathy on sepsis outcome remain controversial. Cardiac troponins I and T are regulatory proteins that control the calcium-mediated interaction of actin and myosin, producing myocardial contraction. Since troponins do not occur in extracellular space, their appearance in serum is sensitive and specific marker of myocardium damage. They have been established as the gold standard biochemical markers for myocardial necrosis . Elevated cardiac troponins levels have been detected in critically ill children with congenital heart disease before and after cardiac surgery.(2) Echocardiography is the cornerstone for the diagnosis of septic cardiomyopathy. There is consensus and expert opinion that every hemodynamically unstable patient should receive critical care echocardiography.(3) Improved understanding of sepsis induced myocardial injury is important for multiple reasons. First, cardiac function is crucial for maintaining hemodynamic stability in patients with septic shock. Second, by understanding the clinical features and predictors of sepsis induced myocardial injury, the investigators can discriminate sepsis-induced cardiomyopathy from other cardiac diseases and avoid unnecessary invasive procedures, such as coronary angiography, a risky procedure in critically ill patients. Thus, the investigators aimed to define clinical predictors of sepsis-induced cardiomyopathy and assess the clinical course and outcome of sepsis-induced cardiomyopathy in patients with sepsis.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and is associated with a high mortality rate in the ICU. Sepsis induced cardiomyopathy (SICM) is a multi-factorial process that appears in approximately 50% of patients with sepsis/septic shock and is associated with increased mortality. It is suggested that ketone bodies are more efficient substrates of energy metabolism than glucose, with a lower oxygen consumption per ATP-molecule produced and that the failing human heart increases the capacity to metabolize ketones. Previous studies have found acute beneficial hemodynamic effects of ketone esters in patients with chronic heart failure and cardiogenic shock, respectively. Improved hemodynamics and reduced systemic oxygen consumption as an effect of ketone esters might be of great benefit in patients admitted to the ICU. Thus, the investigators aim to investigate the hemodynamic effects of ketone esters in patients with sepsis induced cardiomyopathy in this randomized, placebo-controlled, double-blinded, cross-over, acute intervention study. .

As infection control improves and circulation stabilizes, treatment de-escalation of septic shock begins, accompanied by fluid redistribution from interstitial spaces to the vasculature, increasing cardiac volume load. Synthetic recombinant human BNP (rh-BNP) plays a role in inducing vasodilation, particularly in the venous system, alleviating cardiac congestion, and enhancing natriuresis and diuresis. Thus the investigators designed a single-center, prospective physiological study to evaluate the efficacy of standard rh-BNP infusion in reducing venous return and enhancing fluid removal, with a secondary objective of assessing the maintenance of perfusion pressure and tissue perfusion.

Takotsubo syndrome (TTS) is an acute and reversible form of myocardial injury often preceded by a physical or emotional trigger. Although TTS was generally considered a benign disease for its reversible nature, it is now clear that hemodynamic and electrical instability during the acute phase exposes patients to frequent serious adverse in-hospital complications. However, the pathophysiology of TTS is far from being completely understood. Consistent evidence demonstrated that the environmental events experienced by most of these patients and perceived as stressful (both physical or emotional) induce a brain activation and a stress-related response, with increasing bioavailability of local and circulating stress mediators, such as catecholamine and cortisol, which showed to play a major role in the etiology of to the "neurogenic stunning myocardium" responsible for this clinical condition. Primary and secondary TTS showed an important clinical heterogeneity identifying two different subtypes of patients with different outcomes and risk profiles. the invastigators hypothesize that a different activation of the brain structures involved in acute stress response, as well as a different exposure to chronic stress, may subtend the different clinical and risk profiles observed in primary vs. secondary TTS patients. Moreover, the invastigators hypothesize that distinct signatures of circulating biomarkers may be associated with these two categories of TTS patients. Therefore, identifying these specific signatures may help in the diagnosis of these patients and pave the way for the identification of specific pathophysiologic pathways and the development of future therapies.