Currently, available evidence on the use of the Impella device in cardiogenic shock is limited to observational studies and one small randomized trial [22–24]. In the ISAR‐SHOCK (efficacy study of LV assist device to treat patients with cardiogenic shock) trials, 26 patients with advanced/established cardiogenic shock were randomized to IABP or Impella [22]. In this small study the cardiac index after 30 minutes of support was significantly higher in the Impella group compared with the IABP group (delta 0.49±0.46 l/min/m2 vs 0.11±0.31 l/min/m2, p = 0.02). Overall, 30‐day mortality was similar in both groups. Recent retrospective database studies using the American College of Cardiology’s National Cardiovascular Data Registry [25] and the Premier Healthcare Database [26] reported an association between higher mortality and use of Impella during PCI for CS as compared to either IABP or no Impella use. Given the retrospective nature of these data it is not possible to distinguish whether Impella is a marker for unknown confounders (sicker patients) or Impella leads to worse outcomes in CS. Randomized data is currently scarce, the 48‐patient IMPRESS‐in‐Severe‐SHOCK trial randomized intubated and ventilated patients with CS to Impella CP or IABP [27]. This underpowered study failed to show a benefit in terms of 30‐day mortality with Impella. The ongoing Danish‐German Cardiogenic Shock Trial (DanGer) is investigating whether mechanical support with Impella can improve survival in CS patients [28].
Tandemheart
In 2 small randomized clinical trials enrolling about 40 patients each, the Tandemheart was associated with significant improvements in hemodynamic parameters when compared with the IABP [29, 30]. However, without direct left ventricular unloading the Tandemheart increases left ventricular afterload which partially offsets the potential cardiac workload benefits. Other concerns with the TandemHeart are the complications (bleeding and limb ischaemia) and the complex trans‐septal insertion procedure, which have limited its uptake in clinical practice.
ECMO
The use of ECMO for cardiogenic shock has evolved significant during the past decade. Compared with other support devices, ECMO is able to provide higher blood flow rates, oxygenation and ability to support both the left‐ as well as the right ventricle. Important advances include a compact ECMO device (Cardiohelp®, Maquet, Rastatt, Germany) allowing for out‐of‐hospital or bedside ECMO insertion. French physicians have pioneered pre‐hospital extracorporeal cardiopulmonary resuscitation with encouraging survival rates (ECPR) [31]. Several randomized controlled trials investigating ECMO in cardiogenic shock are currently ongoing including the ECMO‐CS (Extra Corporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock) [32], ANCHOR (assessment of ECMO in Acute Myocardial Infarction Cardiogenic Shock, NCT 04184635), ECLS‐SHOCK (Extracorporeal Life Support in Cardiogenic Shock, NCT 03637205) and EURO‐SHOCK (Testing the Value of Novel Strategy and its Cost Efficacy in Order to Improve the Poor Outcomes in Cardiogenic Shock, CT 03813134) trials.
Guideline recommendations for the IABP and left ventricular assist devices
The 2018 ESC/EACTS guidelines for myocardial revascularization no longer recommend the use of IABP in patients with cardiogenic shock (class III recommendation, level of evidence A) [33]. These guidelines state a class IIb, level of evidence C recommendation for the use of left ventricular assist devices “short‐term mechanical circulatory support in ACS patients with cardiogenic shock may be considered”. The 2013 ACC/AHA guidelines state a class IIa level of evidence B recommendation for the use of the IABP “The use of intra‐aortic balloon pump (IABP) counterpulsation can be useful for patients with cardiogenic shock after STEMI who do not quickly stabilize with pharmacological therapy” [14]. The ACC/AHA recommendation for left ventricular assist devices is class IIb, level of evidence C “Alternative LV assist devices for circulatory support may be considered in patients with refractory cardiogenic shock”.
Vasopressors and inotropes
Rapid treatment of hypoperfusion and hypotension is essential when dealing with cardiogenic shock. Inotropes can be used to increase cardiac output and vasopressors to increase blood pressure. However, inotropes and vasopressors increase myocardial oxygen consumption and current guidelines suggest their use should be assessed on an individual basis [14]. Sympathomimetic agents are most commonly used in the setting of cardiogenic shock, but phosphodiesterase inhibitors and calcium sensitizers are also sometimes used.
Sympathomimetic agents
Norephinephrine has a high affinity for the alpha‐adrenergic receptor and has minor beta‐agonistic effects. Therefore, norepinephrine is a potent vasopressor with limited inotropic effects. Dopamine has a variety of effects depending on the dosage. At low doses (1–2 μg/kg/min) it increases urine output by augmenting renal blood flow and natriuresis [34, 35]. At intermediate doses (5–10 μg/kg/min) dopamine stimulates beta‐1 adrenergic receptors, allowing for an increased stroke volume and an increased heart rate, increasing cardiac output. At high‐doses (>10 μg/kg/min) dopamine predominantly stimulates alpha‐adrenergic receptors, causing vaso‐constriction. A randomized study of 1679 patients with shock (septic, hypovolemic, and cardiogenic) assigned to dopamine or norepinephrine as the first‐line vasopressor showed more arrhythmic events in the dopamine group (24.1% vs 12.4%, p<0.001). A subgroup analysis of patients with cardiogenic shock showed that dopamine was associated with increased 28‐day mortality compared with norepinephrine [36]. An alternative is dobutamine, which is a synthetic catecholamine with strong beta‐1 and beta‐2 receptor affinity. The beta‐2 affinity of dobutamine may cause vasodilation and can cause hypotension.
Phosphodiesterase inhibitors and calcium sensitizers
Agents such as milrinone and enoximone increase the intracellular concentration of cyclic adenosine mono phosphate (cAMP) by inhibiting the action of phosphodiesterase 3 [37]. Phosphodiesterase 3 is an enzyme found in the sarcoplasmic reticulum of cardiac myocytes and vascular smooth muscle cells which breaks down cAMP into AMP. The increased intracellular concentration of cAMP increases myocardial contractility, improves diastolic relaxation, and causes vasodilation. Milrinone, the most widely used phophodiesterase inhibitor has a relatively long half‐life of 2 to 4 hours. The calcium‐sensitizer levosimendan sensitizes troponin C to calcium, thereby increasing the effects of calcium on cardiac myofilaments which increases cardiac contractility at low energy costs. Levosi‐mendan also causes vasodilatation by opening ATP‐dependent potassium channels [38, 39]. Both milrinone and levosimendan have not been tested in the setting of cardiogenic shock complicating myocardial infarction and experience with these agents in this setting is limited.
Treatment pathways for cardiogenic shock complicating myocardial infarction
A patient with CS complicating AMI should ideally be started on inotropes and vasopressors as soon as possible and be transferred to a catheterization laboratory for emergent invasive angiography. In order to better understand the etiology of CS immediate echocardiography should be performed ideally without delaying emergency angiography. A rapid bedside echo in the catheterization laboratory during preparation of the patient may suffice to evaluate left and right ventricular function and possible mechanical complications such as a ventricular septal rupture, papillary muscle rupture, or a free wall rupture. In the absence of mechanical complications, one should proceed to emergency PCI (preferably of the culprit‐lesion only) or emergency CABG if the lesions are not deemed amenable to PCI. In case of mechanical complications, surgical intervention is warranted. Short‐term percutaneous mechanical support may be considered before performing PCI as observational studies have suggested improved outcomes with early‐ rather than late initiation of mechanical support [40]. Before, throughout and after the procedure the respiratory status, blood pressure, and urine output
