Diastolic but not systolic dysfunction is associated with troponin and N-terminal pro-brain natriuretic peptide elevation in sepsis

Abstract

Introduction: Cardiac dysfunction is one of the key features in sepsis and septic shock, yet its mechanism is poorly understood. We aimed to investigate the pathophysiology of cardiac dysfunction in sepsis by integrating echocardiographic with biochemical and inflammatory markers. Methods: Over 14 months, 127 consecutive, septic/systemic inflammatory response syndrome (SIRS) patients in our ICU were collected. All patients underwent transthoracic echocardiography with measurements of systolic and diastolic function, and blood samples were collected and serum separated for measurements of biomarkers. All clinical parameters were collected from the ICU charts during the days of echocardiography studies and blood sampling. Outcome measures were ICU, inhospital survival and survival up to 2 years. Patients with segmental wall motion abnormality - indicating myocardial infarction or regional ischemia and/or significant mitral or aortic disease - were excluded from the analyses. Results: Out of 86 patients without regional myocardial dysfunction and/or significant valvular disease, 36 (42%) died during follow-up, almost all of them within the first 6 months. Thirty-one (36%) patients had positive blood cultures and they were more tachycardic and hypotensive and had shorter E-wave deceleration time than SIRS (negative culture) patients (P = 0.024). The echocardiographic measurements most predictive of mortality by Cox survival analysis were E-wave/Em ratio (Exp(beta) = 1.12, P = 0.006) and pressure gradient over the tricuspid valve (Exp(beta) = 1.04, P <0.0001). Among the biomarkers, N-terminal pro-brain natriuretic peptide (NT-proBNP), and IL-18 were the strongest predictors of mortality (P = 0.004 and P <0.001). Troponin and NT-proBNP best correlated with higher E-wave/Em ratio, and lower Em and Sm waves and with the cytokines TNFalpha and IL-8. The left ventricular end-diastolic volume, left ventricular endsystolic volume or left ventricular ejection fraction did not predict survival and did not correlate with troponin or NT-proBNP elevation. Conclusions: After exclusion of all patients with coronary artery disease and/or significant valvular dysfunction, there is still a significant incidence of troponin and NT-proBNP elevation in septic/SIRS patients. Echocardiographic features most significantly associated with troponin and NT-proBNP elevation were measures of diastolic dysfunction (high E-wave/Em ratio, low Sm and Em). Measures of systolic dysfunction did not correlate with troponin or NT-proBNP elevation.