Inotrope versus placebo therapy in cardiogenic shock: Rationale and study design of the CAPITAL DOREMI2 trial.

BACKGROUND: Cardiogenic shock (CS) is a state of end-organ hypoperfusion related to cardiac dysfunction. Current guidelines recommend consideration of inotrope therapy in patients with CS, however no robust data support their use. The purpose of the CAPITAL DOREMI2 trial is to examine the efficacy and safety of inotrope therapy against placebo in the initial resuscitation of patients with CS. METHODS AND DESIGN: This is a multi-center, double-blind, randomized, placebo-controlled trial comparing single-agent inotrope therapy to placebo in patients with CS. A total of 346 participants with Society for Cardiovascular Angiography and Interventions class C or D CS will be randomized in a 1:1 fashion to inotrope or placebo therapy, which will be administered over a 12-hour period. After this period, participants will continue open-label therapies at the discretion of the treating team. The primary outcome is a composite of all-cause in-hospital death, and, as measured during the 12-hour intervention period, any of: sustained hypotension or high dose vasopressor requirements, lactate greater than 3.5 mmol/L at 6 hours or thereafter, need for mechanical circulatory support, arrhythmia leading to emergent electrical cardioversion, and resuscitated cardiac arrest. All participants will be followed for the duration of their hospitalization, and secondary outcomes will be assessed at the time of discharge. IMPLICATION: This trial will be the first to establish the safety and efficacy of inotrope therapy against placebo in a population of patients with CS and has the potential to alter the standard care provided to this group of patients.

Prognostic Factors Associated with Mortality in Cardiogenic Shock - A Systematic Review and Meta-Analysis.

BACKGROUND: Cardiogenic shock remains highly associated with early mortality, with mortality often exceeding 50%. We sought to determine the association between prognostic factors and in-hospital and 30-day mortality in cardiogenic shock. METHODS: We performed a systematic review and meta-analysis of prognostic factors in cardiogenic shock, searching MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for records up to June 5, 2023. English-language studies that investigated prognostic factors and in-hospital and/or 30-day mortality in cardiogenic shock were included. Studies were excluded if they evaluated the pediatric population, were postmortem studies, or included fewer than 100 patients. The primary aim was to identify modifiable and non-modifiable prognostic factors associated with in-hospital and 30-day mortality in cardiogenic shock. RESULTS: We identified 160 studies, including 2,459,703 patients with a median in-hospital mortality of 41.4% (interquartile range, 33.6% to 49.2%). The majority were retrospective cohort studies. Patient factors potentially associated with an increase in early mortality included an age greater than or equal to 75 years of age, peripheral arterial disease, chronic kidney disease, and female sex. Procedural and presentation factors potentially associated with increased mortality included out-of-hospital cardiac arrest, left main culprit artery, left ventricular ejection fraction less than 30%, dialysis, and need for mechanical circulatory support. Revascularization in the form of coronary artery bypass graft and percutaneous coronary intervention were potentially associated with reduced in-hospital mortality. CONCLUSIONS: This analysis quantifies the association between patient, presentation, and treatment-related factors and early mortality in cardiogenic shock. Increased certainty in the association of these prognostic factors with cardiogenic shock outcomes can aid in clinical risk assessment, development of risk tools, and analysis of clinical trials.

Inhaled anaesthesia compared with conventional sedation in post cardiac arrest patients undergoing temperature control: A systematic review and meta-analysis.

INTRODUCTION: Patients admitted with return of spontaneous circulation (ROSC) following out of hospital cardiac arrest (OHCA) are often sedated to facilitate care. Volatile anaesthetics have been proposed as alternative sedatives because of their rapid offset. We performed a systematic review and meta-analysis comparing the use of volatile anaesthetics to conventional sedation in this population. MATERIALS: We searched four databases (MEDLINE, Embase, CENTRAL, and Scopus) from inception to January 6, 2022. We included randomized trials and observational studies evaluating patients admitted following ROSC. We pooled data and reported summary estimates using odds ratio (OR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, both with 95% confidence intervals (CIs). We assessed risk of bias using the Newcastle Ottawa Scale and certainty of evidence using GRADE methodology. RESULTS: Of 1,973 citations, we included three observational studies (n = 604 patients). Compared to conventional sedation, volatile agents had an uncertain effect on delirium (OR 0.96, 95% CI 0.68-1.37), survival to discharge (OR 0.66, 95% CI 0.17-2.61), and ICU length of stay (MD 1.59 days fewer, 95% CI 1.17-4.36, all very low certainty). Patients who received volatile anaesthetic underwent a shorter duration of mechanical ventilation (MD 37.32 hours shorter, 95% CI 7.74-66.90), however this was based on low-certainty evidence. No harms were described with use of volatile anesthetics. CONCLUSION: Volatile anaesthetics may be associated with a decreased duration of mechanical ventilation in patients admitted with ROSC however this is based on low-certainty evidence. Further data are needed to assess their role in this population.

Significant Valvular Dysfunction and Outcomes in Cardiogenic Shock: Insights From the Randomized DOREMI Trial.

BACKGROUND: Patients with cardiogenic shock (CS) suffer high rates of in-hospital mortality, with little evidence guiding management. The impact of valvular heart disease in patients with CS remains unclear. We therefore conducted a post hoc analysis of the randomized Dobutamine Compared to Milrinone (DOREMI) trial to determine the impact of valvular disease on outcomes in patients with CS. METHODS: We defined significant valvular disease as moderate to severe or greater valvular stenosis or regurgitation and divided participants into a group of those with significant valvular disease and those without. Our primary outcome was all-cause in-hospital mortality. Secondary endpoints included resuscitated cardiac arrest; cardiac transplantation or mechanical circulatory support; nonfatal myocardial infarction; stroke; initiation of renal replacement therapy; as well as changes in renal function, perfusion, and hemodynamics over time. RESULTS: One hundred eighty-nine (98.4%) participants from the DOREMI trial were included in our analysis, and 74 (39.2%) had significant valvular dysfunction. Thirty-six (48.7%) patients with valvular disease died in hospital, compared with 37 (32.2%) in the comparator group (relative risk, 1.5; 95% confidence interval 1.06-2.15; P = 0.02). Patients with aortic stenosis (2.42, 1.56-3.75; P < 0.01) and patients with mitral regurgitation (1.63, 1.1-2.43; P = 0.02) also had increased incidence of in-hospital mortality. There was no significant difference in any secondary outcomes among groups, apart from variances in mean arterial pressure observed in patients with valvular disease (P < 0.01). CONCLUSIONS: Significant valvular dysfunction is associated with increased in-hospital mortality in patients with CS. Randomized clinical trial data are needed to further elucidate the role of transcatheter valvular interventions as a therapeutic target in this population.