Septic Cardiomyopathy: Difficult Definition, Challenging Diagnosis, Unclear Treatment

Abstract

Sepsis is a systemic inflammatory response syndrome of suspected or confirmed infectious origin, which frequently culminates in multiorgan failure, including cardiac involvement. Septic cardiomyopathy (SCM) remains a poorly defined clinical entity, lacking a formal or consensus definition and representing a significant knowledge gap in critical care medicine. It is an often-underdiagnosed complication of sepsis. The only widely accepted aspect of its definition is that SCM is a transient myocardial dysfunction occurring in patients with sepsis, which cannot be attributed to ischemia or pre-existing cardiac disease. The pathogenesis of SCM appears to be multifactorial, involving inflammatory cytokines, overproduction of nitric oxide, mitochondrial dysfunction, calcium homeostasis dysregulation, autonomic imbalance, and myocardial edema. Diagnosis primarily relies on echocardiography, with advanced tools such as tissue Doppler imaging (TDI) and global longitudinal strain (GLS) providing greater sensitivity for detecting subclinical dysfunction and guiding therapeutic decisions. Traditional echocardiographic findings, such as left ventricular ejection fraction measured by 2D echocardiography, often reflect systemic vasoplegia rather than intrinsic myocardial dysfunction, complicating accurate diagnosis. Right ventricular (RV) dysfunction, identified as a critical component of SCM in many studies, has multifactorial pathophysiology. Factors including septic cardiomyopathy itself, mechanical ventilation, hypoxemia, and hypercapnia-particularly in cases complicated by acute respiratory distress syndrome (ARDS)-increase RV afterload and exacerbate RV dysfunction. The prognostic value of cardiac biomarkers, such as troponins and natriuretic peptides, remains uncertain, as these markers primarily reflect illness severity rather than being specific to SCM. Treatment focuses on the early recognition of sepsis, hemodynamic optimization, and etiological interventions, as no targeted therapies currently exist. Emerging therapies, such as levosimendan and VA-ECMO, show potential in severe SCM cases, though further validation is needed. The lack of standardized diagnostic criteria, combined with the heterogeneity of sepsis presentations, poses significant challenges to the effective management of SCM. Future research should focus on developing cluster-based classification systems for septic shock patients by integrating biomarkers, echocardiographic findings, and clinical parameters. These advancements could clarify the underlying pathophysiology and enable tailored therapeutic strategies to improve outcomes for SCM patients.

Keywords: B-type natriuretic peptide; biomarkers; cardiac MRI; diastolic function; echocardiography; global longitudinal strain; levosimendan; mitochondrial dysfunction; myocardial dysfunction; myocardium-depressing factors; sepsis; sepsis phenotypes; sepsis-induced myocardial dysfunction; septic cardiomyopathy; troponin; venoarterial extracorporeal membrane oxygenation (VA-ECMO).

Figure 1

Echocardiographic markers of left ventricular systolic and diastolic function. (A,B): Left ventricular ejection fraction (EF) estimation through the Simpson’s method in a patients with SCM. LVEF was 27%. (C): Tissue Doppler imaging evaluating the systolic velocity of the lateral mitral annulus (S’) which was very low in the present patient (0.04 m/s) (red arrows). (D,E): Mitral Annular Plane Systolic Excursion (MAPSE) at the septal and lateral mitral annulus which was 0.8 and 1.3 mm, respectively, indicating severe LV systolic dysfunction. (F,G): transmitral flow and tissue Doppler imaging at the mitral annulus to evaluate diastolic LV function. E/e’ was 16.35, severely increased, indicating diastolic dysfunction in a patient with urinary sepsis and previously normal cardiac function. E’ was 0.04 cm/s also indicating severe diastolic dysfunction.

Figure 2

(A). Speckle-tracking analysis of a patient with normal systolic left ventricular (LV) function. Two-dimensional image showing speckles within the LV being tracked by the ultrasound Machine Software (EchoPAC Software version 203). Graphical representation of the movement of speckles throughout the cardiac cycle (x-axis, longitudinal strain; y-axis, time in msec), with each line representing a different segment of the LV; large negative values represent movement of speckles towards one another during contraction representing normal function. (B). Bullseye map showing global longitudinal strain values throughout the LV. (C). Speckle-tracking analysis of a patient with sepsis and severely reduced left ventricular (LV) systolic function. A 2D image showing speckles within the LV being tracked by the ultrasound machine software. Graphical representation of movement of speckles throughout the cardiac cycle (x-axis, longitudinal strain; y-axis, time in msec) with each line representing a different segment of the LV; note smaller negative values with variable time to peak strain representing reduced LV function with mechanical dyssynchrony. Bullseye map showing global longitudinal strain values throughout the LV; blue zones represent areas of the LV where there is lengthening of the segments during systole rather than shortening (D).

Figure 3

Speckle-tracking analysis in patients with SCM. (A). A patient with severely decreased LV EF (18%) measured with the Simpson’s method and the (B). corresponding GLS with STE which was also found severely decreased. (C). A patient with septic shock and mildly reduced LVEF (47%). The corresponding GLS (D) was found severely decreased, better depicting the depressed cardiac contractility which was probably masked due to the decreased peripheral vascular resistances. (E,F) present GLS examinations in patients with SCM. Interesting is the difference in the distribution of the affected myocardial regions presenting altered contractility.

Figure 4

Indices of RV function. (A). Assessment of RV size through the evaluation of RV end diastolic area) (RVEDA) to LVEDA. (B) RV outflow tract velocity Time Integral (RVOT VTI). The ascending part of the RVOT VTI envelop presents a midsystolic notch which is indicative of increased pulmonary vascular resistances (PVRs). (C). D shape of the LV at the parasternal short axis indicating Acute Core Pulmonale (ACP) due to increased RV pressures. In order to conclude that ACP is due to sepsis (SCM) it is essential to exclude all other features that result to RV dusfunction. (D). Tricuspid annular Plane Systolic Excursion (TAPSE) which is borderline. (E). Fractional Area Change quantification through the equation [RVED area − RVESA)/RVESA]. (F). Estimation of RV Systolic pressure through the velocity of the envelope of tricuspid regurgitation. Using the Bernouli equation. Using the above measurements, TAPSE/PASP, a derived variable indicating right ventriculoarterial; coupling, can be evaluated. Moreover, PASP/VTI RVOT can indicate the value of PVRs.

Figure 5

(A,C): Superior vena cava collapsibility index measured with transesophageal echocardiography. The reported threshold to identify fluid responsiveness varies in the literature between 18 and 36%. Patient (A) is probably not a fluid responder. On the contrary, patient (C) will respond to fluid administration. (B): IVC distensibility index in a fully sedated patient under controlled mechanical ventilation. The value of 31% indicates fluid responsiveness (D): IVC collapsibility index in a spontaneously breathing patient. The value of 100% indicates fluid responsiveness, although it should be considered with caution in a patient with rigorous respiratory efforts.