The current use of vasoactive agents in cardiogenic shock related to myocardial infarction and acute decompensated heart failure

Abstract

Cardiogenic shock (CS) is a heterogeneous condition associated with exceptionally high mortality rates, despite significant advances in the field of cardiology. The primary causes of CS are myocardial infarction-related CS (AMI-CS) and acute decompensated heart failure-related CS (ADHF-CS). Management of CS is inherently complex, with the initial focus-irrespective of the underlying etiology-centered on preserving end-organ perfusion. Parenteral vasopressors and inotropes are the cornerstone of therapy to achieve this objective. However, data on the comparative efficacy of different vasoactive agents in CS remain limited, and no single agent has demonstrated clear superiority. Recent progress in the staging and phenotyping of CS has provided a framework for more tailored therapeutic approaches. This review offers a comprehensive and updated summary of current evidence on the use of vasopressors and inotropes in AMI-CS and ADHF-CS, including a discussion of specific scenarios, such as right ventricular CS (RV-CS).

Keywords: Acute decompensated heart failure cardiogenic shock (ADHF-CS); Acute myocardial infarction cardiogenic shock (AMI-CS); Cardiogenic shock; Inotropes; Vasopressors.

Fig. 1

Society for Cardiovascular Angiography and Interventions (SCAI) SHOCK stages [Adapted from SCAI updated consensus 2021]. After the first publication of this staging system, several trials have validated this classification and have demonstrated the clinical utility in diagnosis and prognosis. Moreover, serial evaluation of the patient with cardiogenic shock helps define the pathways to deterioration and/or recovery, showing the importance of this classification in monitoring and defining course as well as assisting medical decision making. CS, Cardiogenic shock; ADHF, acute decompensated heart failure, BNP, B-natriuretic peptide; AKI, acute kidney injury; CPR, cardiopulmonary resuscitation; JVD, jugular vein distention; LFTs, liver function tests. *Defined as creatinine increase to 1.5 x baseline (or 0.3 mg/dL) or > 50 % drop in glomerular filtration rate (GFR). † Intervention (pharmacological or mechanical) beyond volume resuscitation. ‡ CPR is A-modifier.

Fig. 2

Simplified pathophysiology of cardiogenic shock (CS). Several intertwined mechanisms participate in the development of CS after an acute drop in myocardial contractility of any etiology that causes low cardiac output (CO), hypotension and congestion. There is a severe imbalance in the oxygen needs and consumption that stimulates neurohormonal mechanisms resulting in vasoconstriction. This increase in vascular tone continues to worsen the myocardial dysfunction in a vicious cycle. Additionally, there is reactive inflammatory response that causes significant hypotension, aggravating the cycle and perpetuating the pathologic neurohormonal response.

Fig. 3

Mechanisms of action of catecholamines, milrinone and levosimendan in cardiomyocytes. Through different mechanisms, catecholamines and milrinone cause increased levels of cytosolic calcium (thus considered calcitropes), resulting in increased actin-myosin interaction and enhanced contractility and relaxation. Levosimendan does not affect the levels of calcium but increases the myofilaments sensitivity to calcium by binding to troponin C, promoting the actin-myosin interaction, which improves myocardial contractility and relaxation. AMP indicates adenosine monophosphate; ADP, adenosine diphosphate; ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; Ca²⁺, calcium ion; RyR, ryanodine receptor; SERCA, sarcoplasmic reticulum Ca^{2 +}ATPase.

Fig. 4

Mechanisms of action of catecholamines, milrinone, levosimendan and vasopressin in vascular smooth muscle cells. By interacting with the β2-receptors, catecholamines induce phospholamban-mediated uptake of calcium by the sarcoplasmic reticulum via adenylyl cyclase. Milrinone inhibits the phosphodiesterase-3, which increases cAMP, promoting calcium uptake by the sarcoplasmic reticulum with resultant vasodilation. Levosimendan interacts with the ATP-dependent potassium channel, also resulting in vasodilation. Vasoconstriction is caused by the interaction of catecholamines with the α1-adrenergic receptors that activates the phospholipase C cascade. Vasopressin stimulates the V1-receptors causing activation of phospholipase C and subsequent vasoconstriction. AMP indicates adenosine monophosphate; ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; Ca²⁺, calcium ion; DAG, diacylglycerol; IP₃, inositol 1, 4, 5-triphosphate; and K⁺, potassium ion.