Cardiogenic shock

  • Cardiogenic shock is a high risk condition with a in-hospital mortality of 40%
  • Mortality is only slightly improved despite hemodynamics optimisation

Definition of cardiogenic shock

  • presence of sustained hypotension (systolic blood pressure <90 mmHg for ≥30 minutes) and low cardiac output (cardiac index <2.2 L/min/m2) with normal or elevated pulmonary capillary wedge pressure (>15 mmHg)
  • evidence of end-organ hypoperfusion (cold extremities, agitation, oliguria, lactic acidosis)

Signs of hypoperfusion: mixed venous oxygen saturation <60%, arterial lactates >2 mmol/L, oliguria <0.5 ml/Kg/h.

Neurohumoral and inflammatory response

  • Early mortality is largely related to severe circulatory failure but death is also strongly influenced by activation of a neurohumoral and inflammatory response leading to multiorgan failure
  • Inflammatory mediators, including interleukin-6 (IL-6) and tumor necrosis factor-alpha, are frequently elevated and contribute to cardiac dysfunction through their negative inotropic effect
  • cytokines increase nitric oxide production, which may result in a state of inappropriate vasodilation and perturbation of endothelial function
  • angiopoietins (Ang) might contribute to organ oedema and inflammation as they are involved in endothelial permeability:
    • Ang-2 is associated with fluid overload, organ dysfunction, and mortality in human septic shock and in ACS-CS
    • Ang-2 is increased in acute HF and elevated levels at discharge is associated with six-months mortality
  • elevated plasma concentrations of markers reflecting perturbation of the endothelial glycocalix have been found associated to poor outcome in a variety of severe acute diseases including haemorrhagic shock, sepsis, and cardiac arrest
    • Syndecan-1 has been associated to the development of CS in STEMI patients
    • glycosaminoglycan heparan sulfate (HS) showed a delayed increase with respect to Syndecan-1 both in post-STEMI CS and post-cardiac arrest syndrome, in the absence of predictive value for outcome
  • altered biochemical pathways have been suggested in HF, in particular in relation to fatty acid, glucose and amino acid metabolism

Ischemic cardiogenic shock vs. non-ischemic cardiogenic shock

ADHF- and ACS-related cardiogenic shock differ substantially in terms of hemodynamic conditions and neurohormonal activation and with regard to age, gender, ventricular function and dimensions

ACS-CS

  • ACS-CS is mainly due to an acute loss of myocardial tissue and ventricular stunning, often triggering systemic responses with inflammation and endothelial activation
  • on ventricular pressure/volume (PV) diagram, this is represented by a sharp shift downward and rightward of the end-systolic pressure-volume relationship (ESPVR)

ADHF-related CS

  • ADHF-related CS has usually a substrate of chronic compensatory mechanisms including ventricular adaptation to increased end- diastolic pressure and reduced contractility, the upregulation of the renin-angiotensin-aldosterone axis and increased circulating catecholamine, leading to a different CS phenotype characterized by a less pronounced shift of the ESPVR

IABP

  • IABP remains the most commonly used mechanical circulatory support in cardiogenic shock patients
  • 2017 ESC STEMI guidelines give a III/B recommendations for the routine use of IABP in cardiogenic shock and suggests to consider IABP only in patients with mechanical complications (IIa/C) or requiring transfer to Hub centres
  • scarse evidence supporting its use in acute decopensated heart failure complicated by cardiogenic shock (ADHF-CS)
  • some registry studies have suggested that IABP could lead to clinical stabilization and improved tissue perfusion in severe to refractory ADHF and serve as a bridge to durable LVAD implantation or HTx
  • the IABP has demonstrated, by an in vivo left PV loops, an acute decrease in left ventricular end-systolic volume by 6%, a decrease in left ventricular end-systolic pressure by 18%, and an increase in stroke volume by 14%, leading to a reduction in left ventricular stroke work, a rise in mean perfusion pressure and a passive increase in cardiac output
  • in studies comparing the effect of IABP between ACS- and non-ACS-CS described a further hemodynamic improvement by IABP in the latter
    • underlying mechanism is unclear, the hypothesised mechanism is not the acute decreased contractility BUT the different contractile reserve and the IABP benefit (afterload reduction and increased end-organ perfusion pressure) in patients with high-volume status
  • compared to vasoactive agents, IABP can decrease arrhythmia, improve vascular elastance and ventricular-arterial coupling, leading to stabilization without the risk of more advanced MCS (vascular access complications and haemolysis for Impella, biological cost and haematological derangements related to prolonged ECMO assistance)
  • successfully bridge the patients to durable heart replacement therapies (HRT) or heart transplantation, mostly in cases of preserved right ventricle (RV) function.
  • IABP reduces afterload and may allow more forward flow in the setting of higher filling pressures but requires an intrinsic pulsatility to be effective
  • recently published RCT on ADHF patients with low output state has shown a considerable improvement in organ perfusion with IABP compared to inotropes (with 44% of crossover from drugs to IABP) (only 16 for arm providing only hypothesis-generating results)
  • in a chronic situation with even a mild functional reserve it is important to manage the compensatory mechanisms of HF: modulate afterload through pharmacological means or mechanical support
    • arterial elastance (Ea) is a major determinant of ventriculo-arterial coupling (VAC), its reduction may contribute to restore cardiovascular function and prevent organ hypoperfusion
    • IABP implantation could improve VAC, in particular Ea, on top of a selective and conservative use of inotropes/vasoconstrictors