Induction and Deduction in Sepsis-Induced Cardiomyopathy: Five Typical Categories

Sepsis-induced cardiomyopathy (SIC) represents a complex and life-threatening complication of sepsis, characterized by heterogeneous cardiac dysfunction patterns. This review synthesizes current evidence to categorize SIC into five distinct phenotypes, each with unique pathophysiological mechanisms, clinical presentations, and therapeutic implications.

Left Ventricular Systolic Dysfunction: A Stress-Induced Phenomenon

Left ventricular systolic dysfunction (LVSD) is historically recognized as a hallmark of SIC. Studies report LVSD incidence ranging from 12% to 60% in sepsis patients. Early landmark studies by Parker et al. (1984) demonstrated reversible left ventricular dilation and reduced contractility in 50% of sepsis patients, with recovery within 7–10 days. Contemporary research identifies LVSD as more prevalent in younger patients and women, paralleling features of Takotsubo syndrome (TTS), a stress-induced cardiomyopathy. Shared mechanisms include excessive catecholamine release, β-adrenergic receptor desensitization, and myocardial inflammation.

Echocardiographic findings in LVSD include reduced left ventricular ejection fraction (LVEF) and transient segmental wall motion abnormalities. Despite its dramatic presentation, LVSD does not consistently correlate with increased mortality. Meta-analyses indicate no significant survival disadvantage, emphasizing the transient and reversible nature of this dysfunction. Treatment focuses on optimizing cardiac output through judicious fluid resuscitation and inotropic support (e.g., milrinone, levosimendan), avoiding catecholamines that may exacerbate stress-mediated injury.

Left Ventricular Diastolic Dysfunction: The Role of Comorbidities

Left ventricular diastolic dysfunction (LVDD) affects 20%–79% of sepsis patients, with higher prevalence in elderly populations and those with pre-existing hypertension, diabetes, or ischemic heart disease. Diastolic impairment arises from increased myocardial stiffness, prolonged relaxation, and elevated filling pressures. Echocardiographic criteria include reduced mitral annular tissue Doppler velocities (e’ 14), and left atrial enlargement.

Sepsis exacerbates LVDD through tachycardia-induced shortened diastolic filling time and systemic inflammation impairing calcium handling. Mortality rates increase significantly in LVDD patients, as diastolic dysfunction limits cardiac reserve during stress. Management strategies emphasize heart rate control (e.g., β-blockers), fluid balance optimization, and treatment of underlying comorbidities.

Right Ventricular Dysfunction: The Afterload Challenge

Right ventricular dysfunction (RVD) occurs in 30%–55% of sepsis cases, often associated with increased right ventricular afterload from acute respiratory distress syndrome (ARDS), pulmonary hypertension, or mechanical ventilation. Echocardiography reveals right ventricular dilation, reduced tricuspid annular plane systolic excursion (TAPSE <17 mm), and elevated pulmonary artery systolic pressure.

RVD carries a poor prognosis, with 1-year mortality reaching 57% in severe cases. Pathophysiology involves direct myocardial depression from inflammatory mediators combined with increased right ventricular workload. Treatment focuses on reducing pulmonary vascular resistance through lung-protective ventilation, prone positioning in ARDS, and cautious fluid management to avoid volume overload.

Diffuse Cardiac Dysfunction: The Classic Presentation

Diffuse biventricular dysfunction represents the traditional model of SIC, characterized by global hypokinesis and ventricular dilation. This pattern reflects direct myocardial injury from endotoxins, reactive oxygen species, and mitochondrial dysfunction. Histopathological studies show cardiomyocyte apoptosis, interstitial edema, and inflammatory infiltrates. While diffuse dysfunction is reversible in survivors, persistent myocardial damage correlates with long-term cardiovascular morbidity.

Coexisting Dysfunction: The Clinical Reality

Mixed cardiac dysfunction—combining elements of LVSD, LVDD, and RVD—is the most common clinical presentation. Patient-specific factors such as age, comorbidities, and infection site determine the predominant phenotype. For example, younger patients with septic shock may develop LVSD resembling TTS, while elderly patients with hypertension exhibit LVDD. Echocardiography plays a critical role in phenotyping and guiding tailored hemodynamic management.

Pathophysiological Insights and Therapeutic Directions

Emerging evidence highlights the interplay between inflammatory cascades, autonomic dysregulation, and metabolic derangements in SIC. Key mechanisms include:

1. Cytokine Storm: Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) impair calcium homeostasis and reduce contractility.
2. Mitochondrial Dysfunction: Sepsis disrupts oxidative phosphorylation, leading to ATP depletion and myocardial stunning.
3. Autonomic Imbalance: Excessive sympathetic activation causes β-receptor downregulation and microvascular dysfunction.

Advanced imaging techniques like speckle-tracking echocardiography (STE) detect subclinical myocardial strain abnormalities, enabling early intervention. Future therapies may target mitochondrial repair, inflammatory modulation, and β-adrenergic receptor resensitization.

Conclusion

Sepsis-induced cardiomyopathy encompasses five distinct phenotypes with overlapping mechanisms and clinical manifestations. LVSD mirrors stress cardiomyopathy, LVDD reflects age-related and comorbid vulnerabilities, RVD arises from pulmonary-vascular interactions, diffuse dysfunction represents classic myocardial injury, and mixed patterns dominate clinical practice. Echocardiography remains indispensable for diagnosis, phenotyping, and guiding precision therapy. A deeper understanding of molecular pathways and individualized hemodynamic management are essential to improving outcomes in this heterogeneous condition.

doi.org/10.1097/CM9.0000000000000929

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