Variability in reporting of key outcome predictors in acute myocardial infarction cardiogenic shock trials

Abstract

Background: Among acute myocardial infarction patients with cardiogenic shock (AMICS), a number of key variables predict mortality, including cardiac arrest (CA) and shock classification as proposed by Society for Cardiovascular Angiography and Intervention (SCAI). Given this prognostic importance, we examined the frequency of reporting of high risk variables in published randomized controlled trials (RCTs) of AMICS patients.Methods: We identified 15 RCTs enrolling 2,500 AMICS patients and then reviewed rates of CA, baseline neurologic status, right heart catheterization data, lactate levels, inotrope and vasopressor requirement, hypothermia, mechanical ventilation, left ventricular ejection fraction (LVEF), mechanical circulatory support, and specific cause of death based on the primary manuscript and Data in S1.Results: A total of 2,500 AMICS patients have been enrolled in 15 clinical trials over 21 years with only four trials enrolling >80 patients. The reporting frequency and range for key prognostic factors was: neurologic status (0% reported), hypothermia (28% reported, prevalence 33-75%), specific cause of death (33% reported), cardiac index and wedge pressure (47% reported, range 1.6-2.3 L min −1 m −2 and 15-24 mmHg), lactate (60% reported, range 4-7.7 mmol/L), LVEF (73% reported, range 25-45%), CA (80% reported, prevalence 0-92%), MCS (80% reported, prevalence 13-100%), and mechanical ventilation (93% reported, prevalence 35-100%). This variability was reflected in the 30-day mortality which ranged from 20-73%.Conclusions: In a comprehensive review of seminal RCTs in AMICS, important predictors of outcome were frequently not reported. Future efforts to standardize CS trial data collection and reporting may allow for better assessment of novel therapies for AMICS.

Validation of cardiogenic shock phenotypes in a mixed cardiac intensive care unit population

“…have not been demonstrated to improve survival in clinical trials. 1,20 We observed some differences in the association between the use of temporary MCS (particularly the IABP) and in-hospital mortality across the clusters, which could suggest heterogeneity of MCS benefit by phenotyope; we have previously observed better outcomes with IABP use in this CS cohort. 15 If it is true that MCS devices might have greater efficacy in one of the phenotypic clusters we identified, then the inclusion of a mix of phenotypes in a clinical trial population might mask this benefit.…”

“…If the individual phenotypes have different treatment responses, then the relative prevalence of each phenotype within a theoretical clinical trial population could directly influence the magnitude and direction of the observed treatment effect 8 . It is imperative that we gain similar insights into CS populations, in whom commonly employed treatments such as temporary MCS devices have clear hemodynamic efficacy yet have not been demonstrated to improve survival in clinical trials 1,20 . We observed some differences in the association between the use of temporary MCS (particularly the IABP) and in‐hospital mortality across the clusters, which could suggest heterogeneity of MCS benefit by phenotyope; we have previously observed better outcomes with IABP use in this CS cohort 15 .…”

“…Cardiogenic shock (CS) remains associated with high mortality, with no incremental improvements in survival demonstrated by clinical trials in the past 20 years 1–4 . CS is a heterogeneous syndrome regarding its causative etiologies, disease severity, associated complications, and underlying pathophysiologic processes 3,4 .…”

A deceptively simple problem: the case of cardiogenic shock

“…21 The other key variable is the presence of cardiac arrest, as many patients die of neurological injury and not cardiac dysfunction. 22 However, such a trial would require large numbers of patients, and would not be neatly defined like the described trials with ACS CS.…”

“…The way forward is to conduct trials involving an ‘all‐comers’ population, and stratify by severity of shock (perhaps by prospectively assigning Society for Cardiac Angiography and Intervention Shock Stage, SCAI) 21 . The other key variable is the presence of cardiac arrest, as many patients die of neurological injury and not cardiac dysfunction 22 . However, such a trial would require large numbers of patients, and would not be neatly defined like the described trials with ACS CS.…”