Mechanical circulatory support in refractory cardiogenic shock due to influenza virus-related myocarditis

Abstract

Background: There is scarce evidence for mechanical circulatory support (MCS) in patients with influenza-related myocarditis complicated by refractory cardiogenic shock (rCS). We sought to investigate the impact of MCS using combined veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and micro-axial flow pumps (the ECMELLA concept) in influenza-related myocarditis complicated by rCS.

Methods: This is a prospective, observational analysis from the single centre HAnnover Cardiac Unloading REgistry (HACURE) from two recent epidemic influenza seasons. We analysed patients with verified influenza-associated myocarditis complicated by rCS who were admitted to our intensive care unit (ICU) on MCS. Subsequently, we performed a propensity score (PS) matched analysis to patients with acute myocardial infarction (AMI) complicated by rCS and non-ischaemic cardiomyopathy (DCM) related rCS.

Results: We describe a series of seven patients with rCS-complicated influenza-related myocarditis (mean age 56±10 years, 58% male, influenza A (n=2)/influenza B (n=5)). No patient had been vaccinated prior to the influenza season. MCS was provided using combined VA-ECMO and Impella micro-axial flow pump. In two patients with out-of-hospital cardiac arrest, VA-ECMO had been implanted for extracorporeal cardiopulmonary resuscitation. All patients died within 18 days of hospital admission. By PS-based comparison to patients with AMI- or DCM-related rCS and combined MCS, 30-day mortality was significantly higher in influenza-related rCS.

Conclusion: Despite initial stabilisation with combined MCS in patients with rCS-complicated influenza-related myocarditis, the detrimental course of shock could not be stopped and all patients died. Influenza virus infection potentially critically affects other organs besides the heart, leading to irreversible end-organ damage that MCS cannot compensate for and, therefore, results in a devastating outcome.

FIGURE 1

Flow diagram of study enrolment. AMI: acute myocardial infarction; DCM: non-ischaemic cardiomyopathy; rCS: refractory cardiogenic shock; AMI-rCS: AMI-related rCS; influenza-rCS: influenza-related rCS; DCM-rCS: DCM-related rCS; MCS: mechanical circulatory support; VA-ECMO: veno-arterial extracorporeal membrane oxygenation; ECMELLA: MCS with combined VA-ECMO and Impella micro-axial flow pump; PS: propensity score; OHCA: out-of-hospital cardiac arrest.

FIGURE 2

Time course of treatment in patients with refractory cardiogenic shock (rCS)-complicated myocarditis induced by influenza virus infection. ARDS: acute respiratory distress syndrome; CAG: coronary angiography; CS: cardiogenic shock; PE: pericardial effusion; PCI: percutaneous coronary intervention; ABD: anoxic brain damage; CPR: cardio-pulmonary resuscitation; VA-ECMO: veno-arterial extracorporeal membrane oxygenation; VAV-ECMO: veno-arterial venous extracorporeal membrane oxygenation; MHH: Hannover Medical School; ICU: intensive care unit.

FIGURE 3

Endomyocardial biopsies of patients supported by percutaneous mechanical circulatory support (MCS) with refractory cardiogenic shock (rCS)-complicated non-ischaemic cardiomyopathy (DCM) and influenza-related myocarditis. (a–c) Controls: cardiac left-ventricular biopsies of patients with rCS-complicated DCM with percutaneous MCS. In these endomyocardial biopsies cardiomyocytes show signs of irregular hypertrophy with varying hyperchromasia of the corresponding nuclei. Also present are unevenly dispersed, mildly eosinophilic contraction bands, as well as a mild intracellular and extracellular oedema. While there is some sparse interstitial inflammatory infiltration, the criteria of an active myocarditis (according to the Dallas classification) are not met. By definition, the histological changes in dilated cardiomyopathy are nonspecific, rendering the histopathological diagnosis one of exclusion. Signs of specific disorders, such as granulomatous inflammation, myocardial inclusions or siderosis are absent. (d–f) Influenza-associated myocarditis: endomyocardial biopsies of patients with rCS-complicated influenza-related active myocarditis. There is a pronounced if unevenly distributed interstitial inflammatory infiltrate, for the most part made up of activated T-lymphocytes. All biopsies show evidence of myocyte damage, which ranges from prominent contraction bands to hyper-eosinophilic (early) stages of necrosis. Adjacent capillaries are dilated, packed with erythrocytes and their endothelial nuclei are activated. Cardiomyocytes as well as the cardiac interstitium show accompanying oedematous changes. As in (a–c), signs of specific disorders such as granulomatous inflammation, myocardial inclusions or siderosis are absent. Scale bars=50 µm.

FIGURE 4

Haemodynamic effects of mechanical circulatory support (MCS) in patients with refractory cardiogenic shock (rCS)-complicated myocarditis induced by influenza virus infection (where a) systolic blood pressure (SBP); b) heart rate (HR); c) inotropic equivalent level; d) lactate level). Despite stabilisation of haemodynamic parameters (with consequent decrease of the inotropic equivalent level) and counteracting of rCS status (with consequent decrease of the lactate level), based on percutaneous MCS, patients died within 18 days of admission to the intensive care unit (ICU) and cardiac arrest centre of Hannover Medical School (MHH). Catecholamine dose was evaluated by the inotrope equivalent method (where [ug·kg⁻¹·min⁻¹]=dopamine+dobutamine+100·epinephrine+100·norepinephrine+100·isoproterenol+15·milrinone) [15]. *: p<0.05 versus baseline.

FIGURE 5

30-Day survival of propensity score (PS) matched cohorts. a) Matching of influenza-rCS and AMI-rCS. b) Matching of influenza-rCS and DCM-rCS. CI: confidence interval; AMI: acute myocardial infarction; DCM: non-ischaemic cardiomyopathy; rCS: refractory cardiogenic shock; AMI-rCS: AMI-related rCS; DCM-rCS: DCM-related rCS; influenza-rCS: influenza-related rCS.