Henry, Timothy D

Background: Coronary microvascular dysfunction results in angina and adverse outcomes in patients with evidence of ischemia and nonobstructive coronary artery disease; however, no specific therapy exists. CD34+ cell therapy increases microvasculature in preclinical models and improves symptoms, exercise tolerance, and mortality in refractory angina patients with obstructive coronary artery disease. The objective of this research was to evaluate the safety, tolerability, and efficacy of intracoronary CD34+ cell therapy in patients with coronary microvascular dysfunction. Methods: We conducted a 2-center, 20-participant trial of autologous CD34+ cell therapy (protocol CLBS16-P01; NCT03508609) in patients with ischemia and nonobstructive coronary artery disease with persistent angina and coronary flow reserve ≤2.5. Efficacy measures included coronary flow reserve, angina frequency, Canadian Cardiovascular Society angina class, Seattle Angina Questionnaire, SF-36, and modified Bruce exercise treadmill test obtained at baseline and 6 months after treatment. Autologous CD34+ cells (CLBS16) were mobilized by administration of granulocyte-colony stimulating factor 5µg/kg/day for 5 days and collected by leukapheresis. Participants received a single intracoronary left anterior descending infusion of isolated CD34+ cells in medium that enhances cell function. Results: Coronary flow reserve improved from 2.08±0.32 at baseline to 2.68±0.79 at 6 months after treatment ( P <0.005). Angina frequency decreased ( P <0.004), Canadian Cardiovascular Society class improved ( P <0.001), and quality of life improved as assessed by the Seattle Angina Questionnaire ( P ≤0.03, all scales) and SF-36 ( P ≤0.04, all scales). There were no cell-related serious adverse events. Conclusions: In this pilot clinical trial of microvascular angina, patients with ischemia and nonobstructive coronary artery disease receiving intracoronary infusion of CD34+ cell therapy had higher coronary flow reserve, less severe angina, and better quality of life at 6 months. The current study supports a potential therapeutic role for CD34+ cells in patients with microvascular angina. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03508609.

AbstractBackgroundRandomized studies of intra‐aortic balloon pump (IABP) in cardiogenic shock (CS) have only included on patients with acute coronary syndromes (ACS) without stratification according to shock severity. We examined the association between IABP and mortality in CS patients across the Society for Cardiovascular Angiography and Intervention (SCAI) shock stages.MethodsWe included cardiac intensive care unit patients admitted from 2007 to 2015 with CS from any etiology. In‐hospital mortality associated with IABP was examined in each SCAI shock stage. Multivariable logistic regression was performed using inverse probability of treatment weighting (IPTW) to determine the association between IABP and in‐hospital mortality.ResultsWe included 934 patients, with a mean age of 68 ± 14 years; 60% had ACS. The distribution of SCAI shock stages was: B, 41%; C, 13%; D, 38%; E, 8%. In‐hospital mortality was lower in the 39% of patients who received IABP (27% vs. 43%, adjusted OR with IABP after IPTW 0.53, 95% CI 0.40–0.72, p < .0001). IABP use was associated with lower crude in‐hospital mortality in each SCAI shock stage (all p < .05, except p = .08 in SCAI shock stage E). We did not observe any significant heterogeneity in the association between IABP use and in‐hospital mortality as a function of SCAI shock stage.ConclusionsPatients with CS who were selected to receive an IABP had lower in‐hospital mortality, without differences in this effect across the SCAI shock stages. Future studies should account for the severity and etiology of shock when evaluating the efficacy of IABP for CS.

AbstractBackgroundAmong 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.MethodsWe 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.ResultsA 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%.ConclusionsIn 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.