Septic cardiomyopathy

Reviewed and revised 11 November 2016

OVERVIEW

• Septic cardiomyopathy is a common feature of severe sepsis syndromes and results in impaired intrinsic cardiac contractility
• First described by Parker et al in 1984
• Incidence varies in studies, most report 20-60% incidence in the first few days of ICU admission

MECHANISMS

Proposed mechanisms include

• cardiac depression due to catecholamine-induced cardiomyocyte toxic effects following excessive sympathetic activation
• cytokine-mediated impaired contractility (e.g. TNF-alpha, IL1beta)
• increased cGMP and NO intracellular second messengers
• sepsis-induced mitochondrial dysfunction
• increased troponin I phosphorylation resulting in decreased calcium sensitivity
• release of histones into the circulation

Not due to coronary occlusion! (however, septic cardiomyopathy may be aggravated by co-existent ischaemia)

CHARACTERISTICS

Characteristic features (Vieillard-Baron, 2011; Sato and Nasu, 2014)

• rapid onset
• reversible and leads to full recovery in survivors, usually over 7-10 days
• left ventricular dilatation with normal or low filling pressure (due to increased LV compliance and EDV and coexistent RV dysfunction)
• global ventricular dysfunction with decreased ejection fraction (due to ventricular dilatation despite preserved stroke volume)
• absence of regional dysfunction (distinct from Takotsubo cardiomyopathy and myocardial ischaemia)

Note that

• cardiac index may not be reduced in vasoplegic patients even if there is significant ventricular dysfunction
  • e.g. the “hyperkinetic profile”: tachycardia, supra-normal LV EF, small LV cavity size and supra-normal cardiac index
• noradrenaline may unmask septic cardiomyopathy by increasing systemic vascular resistance, causing decreased cardiac output

INVESTIGATIONS

• echocardiography is diagnostic
• exclude other causes of cardiomyopathy (e.g. ischaemic cardiomyopathy, sepsis-induced takotsubo cardiomyopathy)
• biomarkers
  • troponin
    • correlates with mortality in sepsis, but is not diagnostic of septic cardiomyopathy (Landesberg et al, 2014)
  • BNP
    • likely correlates with critical illness rather than septic cardiomyopathy per se
• septic screen for the underlying cause
• low filling pressures and low SVR means PAC is often insensitive for detecting septic cardiomyopathy

MANAGEMENT

• resuscitation, addressing immediate life threats (e.g. septic shock)
• seek and treat underlying cause of sepsis (antibiotics and source control)
• fluid resuscitation if fluid responsive and clinically indicated (avoid fluid overload)
  • positive fluid balance and raised CVP are associated with worse mortality in sepsis (Boyd et al, 2011)
• vasoactive agents
  • inotropes e.g. dobutamine or adrenaline, if evidence of persistent shock (e.g. hyperlactaemia, oliguria)
  • noradrenaline
    • improves preload and driving pressures for end-organ perfusion (Hamzaoui et al, 2010)
    • vasopressin may be used if unresponsive to noradrenaline
  • levosimendan may avoid catecholamine-related cardiotoxicity (Zangrillo et al, 2015)
  • the benefit of vasoactive agents in terms of patient-orientated outcomes is uncertain
• negative chronotropic agents (Rudiger and Singer, 2013)
  • Heart rate reduction with ivabradine and beta-blockers have been proposed as beneficial therapies for septic cardiomyopathy
  • They should be viewed as experimental
  • They may myocardial oxygen expenditure and ameliorates diastolic dysfunction. Beta-blockers may additionally reduce local and systemic inflammation and catecholamin toxicity.
• severe cases may require circulatory support devices (e.g. VA ECMO)
• seek and treat other complications of sepsis
• supportive care and monitoring

PROGNOSIS

• Septic cardiomyopathy usually resolves within 7-10 days in survivors
• The significance of septic cardiomyopathy as an independent prognostic indicator is uncertain (Huang et al, 2013)
• the hyperkinetic state in particular is associated with high mortality in one study, but this was not confirmed in a meta-analysis (Huang et al, 2013)
• impaired intrinsic contractility may be masked by profound vasoplegia, leading to preserved or supra-normal cardiac output
• dobutamine response (increased cardiac index and oxygen delivery) predicts improved prognosis in septic shock (Kumar et al, 2008)

References and Links

LITFL

• CCC — Sepsis Definitions
• CCC — Catecholamine excess, Beta Blockade and Critical Illness

Journal articles

• Boyd JH, Forbes J, Nakada TA, Walley KR, Russell JA. Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Critical care medicine. 39(2):259-65. 2011. [pubmed]
• Flynn A, Chokkalingam Mani B, Mather PJ. Sepsis-induced cardiomyopathy: a review of pathophysiologic mechanisms. Heart failure reviews. 15(6):605-11. 2010. [pubmed]
• Hamzaoui O, Georger JF, Monnet X. Early administration of norepinephrine increases cardiac preload and cardiac output in septic patients with life-threatening hypotension. Critical care (London, England). 14(4):R142. 2010. [pubmed]
• Huang SJ, Nalos M, McLean AS. Is early ventricular dysfunction or dilatation associated with lower mortality rate in adult severe sepsis and septic shock? A meta-analysis. Critical care (London, England). 17(3):R96. 2013. [pubmed] [free full text]
• Kumar A, Schupp E, Bunnell E, Ali A, Milcarek B, Parrillo JE. Cardiovascular response to dobutamine stress predicts outcome in severe sepsis and septic shock. Critical Care. 12(2):R35. 2008. [pubmed] [free full text]
• Landesberg G, Jaffe AS, Gilon D. Troponin elevation in severe sepsis and septic shock: the role of left ventricular diastolic dysfunction and right ventricular dilatation*. Critical care medicine. 42(4):790-800. 2014. [pubmed]
• Merx MW, Weber C. Sepsis and the heart. Circulation. 116(7):793-802. 2007. [pubmed] [free full text]
• Muller-Werdan U, Buerke M, Ebelt H. Septic cardiomyopathy – A not yet discovered cardiomyopathy? Experimental and clinical cardiology. 11(3):226-36. 2006. [pubmed] [free full text]
• Parker MM, Shelhamer JH, Bacharach SL. Profound but reversible myocardial depression in patients with septic shock. Annals of internal medicine. 100(4):483-90. 1984. [pubmed]
• Rudiger A, Singer M. The heart in sepsis: from basic mechanisms to clinical management. Current vascular pharmacology. 11(2):187-95. 2013. [pubmed]
• Sato R, Nasu M. A review of sepsis-induced cardiomyopathy. Journal of intensive care. 3:48. 2015. [pubmed] [free full text]
• Sevilla Berrios RA, O’Horo JC, Velagapudi V, Pulido JN. Correlation of left ventricular systolic dysfunction determined by low ejection fraction and 30-day mortality in patients with severe sepsis and septic shock: a systematic review and meta-analysis. Journal of critical care. 29(4):495-9. 2014. [pubmed]
• Vieillard-Baron A. Septic cardiomyopathy. Annals of intensive care. 1(1):6. 2011. [pubmed] [free full text]
• Zangrillo A, Putzu A, Monaco F. Levosimendan reduces mortality in patients with severe sepsis and septic shock: A meta-analysis of randomized trials. Journal of critical care. 2015. [pubmed]