Therapy

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Summary

Therapy

The management for cardiogenic shock due to STEMI centres on early revascularisation and the provision of pharmacological and mechanical haemodynamic support. Re-establishing coronary perfusion can reverse the ischaemic injury to cardiac myocytes and potentially recover ventricular function. Therefore, revascularisation via percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) should be attempted on an urgent basis. Early presentation and early intervention are associated with significantly lower mortality rates at six months and 12 months as seen in the SHOCK trial.^14,21 It is the widespread adoption of early revascularisation that has led to the steady improvement in survival for cardiogenic shock over the last two decades, which previously was almost always fatal.^1,21 Revascularisation should be attempted even for delayed presentations of cardiogenic shock. Survival benefit has been demonstrated for PCI performed within 48 hours of STEMI onset and 18 hours after onset of shock.²²

In settings where PCI and CABG are unavailable, fibrinolysis should be performed, although the mortality benefit conferred is modest and inferior to PCI or CABG.^23,24 If fibrinolysis does not achieve reperfusion, often considered “primary failure” of thrombolytic therapy, then rescue PCI should be undertaken as soon as possible, ideally within 12 hours of initial chest pain.^25–27 Among patients for whom fibrinolysis initially appears successful, a substantial proportion will develop recurrent ischaemia caused by threatened reocclusion of their coronary artery.²⁸ These patients, similarly to those who undergo rescue PCI, also derive survival benefit from early revascularisation with PCI.^29,30 A comparison of outcomes between PCI and CABG in the setting of cardiogenic shock found no difference in survival at 30 days and one year. Notably, the patients in the CABG group were more likely to have three-vessel disease or left main disease.³¹ Overall for patients in cardiogenic shock due to STEMI, PCI is performed much more commonly than CABG, particularly if a culprit lesion is found. Rarely, in cases involving multi-vessel or left main disease, PCI may be necessary to stabilise patients prior to CABG.

In addition to revascularisation, patients should be started on antithrombotic therapy including aspirin, heparin, P2Y12 inhibitors, and potentially glycoprotein IIb/IIIa inhibitors whereas beta blockers and other drugs with negative inotropic effects should be withheld. Although aspirin and heparin have not been specifically studied in cardiogenic shock, they should be continued given their established benefit in acute coronary syndromes and lack of obvious contraindication.^32,33 Antiplatelet therapy with P2Y12 inhibitors like clopidogrel, ticagrelor, or prasugrel are also indicated.^34–36 Glycoprotein IIb/IIIa inhibitors have been shown to independently reduce the 30-day mortality rate for patients in cardiogenic shock and should be considered particularly when P2Y12 inhibitors are not used.³⁷ In combination with antithrombotic therapy, the risk of major periprocedural bleeding is nontrivial and should be weighed carefully. For PCI, the risk has been reported as high as 5 %, although the increasing use of radial access has lowered the rate of vascular and bleeding complications.^38–42 Beta blockers and calcium channel blockers should be avoided given their negative inotropic effects and potential to prolong or worsen cardiogenic shock.⁴³ While revascularisation is the definitive therapy for cardiogenic shock in STEMI, inotropic and vasopressor support is critical to maintain perfusion of vital organs. The ideal choice of first-line agent is not well-established, likely reflecting the complex physiology of cardiogenic shock. PACs are useful for tailoring vasopressor and inotropic therapy given the often uncertain and dynamic haemodynamic parameters in these settings. For patients who are severely hypotensive, norepinephrine is a reasonable first choice that exerts both inotropic and vasopressor activity. Dopamine at doses >10 mcg/kg/min is similar in effect, although it is associated with more arrhythmias and possibly higher mortality compared to norepinephrine.⁴⁴ However, the increased systemic vascular resistance brought on by both norepinephrine and dopamine raises afterload so that the heart must work harder to maintain cardiac output. For patients whose hypotension is less severe, inotropes such as dobutamine and milrinone should be considered. The vasodilation caused by both of these inotropes may be prohibitive in the severely hypotensive patient. In patients with milder cardiogenic shock, however, the vasodilatory effect and reduction in afterload may improve cardiac output such that on balance blood pressure may not actually decrease. The minimum required dose should be used for all of these agents as escalating doses increase the chance of arrhythmia and impose increased demand on an already struggling heart.

In addition to determining the optimal choice of inotropic or vasopressor support, a PAC can also guide fluid management.²⁰ The overall goal of fluid management is to maximise cardiac output and minimise ventricular filling pressures. The optimal filling pressures are often a moving target and must be individualised to each patient in cardiogenic shock. Some patients in cardiogenic shock may be hypovolaemic with relatively low PCWP shown on PAC and these patients may benefit from a small volume challenge. Other patients present with pulmonary oedema with evidence of high filling pressures on PAC and require intravenous diuresis. Typically the goal PCWP ranges from 18–25 mmHg.¹⁰

Placement of an intra-aortic balloon pump (IABP) should also be considered to provide mechanical support of cardiac function, particularly for severe cardiogenic shock. The balloon pump is inserted into the proximal aorta and inflates during diastole to augment coronary perfusion and deflates in systole to reduce afterload by a vacuum effect. In the IABP SHOCK II trial, patients in cardiogenic shock from acute MI were randomised to either undergo IABP placement or not. There was no mortality difference between the two groups both at 30 days and at one year.^45,46 Nonetheless, the study authors acknowledge that their patient population represented primarily mild to moderately severe cardiogenic shock. IABP may provide mortality benefit for patients in rapidly decompensating and severe cardiogenic shock.

Early experience with other forms of mechanical support such as the percutaneous or surgically implanted left ventricular assist device (LVAD) has been relatively inconclusive thus far. The ventricular assist devices appear to result in more rapid haemodynamic improvement than IABPs but have not been shown to provide additional mortality benefit and yet are more invasive and associated with more complications.^47,48

Patients with predominantly right ventricular dysfunction also derive benefit from early revascularisation and haemodynamic support but there are distinctive aspects to their management. These patients are highly preload dependent and often require large volume fluid resuscitation.^49,50 Fluids should be administered until the jugular venous pressure is greater than 15 mmHg and there is no longer improvement in blood pressure.⁵¹ Nitrates and diuretics should generally be avoided as they both reduce preload of the right ventricle. If inotropic support is needed, dopamine and dobutamine are first-line agents.⁵² Both agents also provide chronotropic support that is often necessary given the high frequency of bradycardia associated with right ventricular STEMIs. As low heart rates in this setting may substantially impair cardiac output, atropine or placement of a temporary pacemaker may also be required.^53,54