Early coronary angiography is associated with improved functional outcome among resuscitated patients with and without STEMI. Resuscitated patients with a presumed cardiac etiology appear to benefit from immediate coronary angiography.
Background: In ST-segment–elevation myocardial infarction (STEMI), infarct size correlates directly with heart failure and mortality. Preclinical testing has shown that, in comparison with reperfusion alone, mechanically unloading the left ventricle (LV) before reperfusion reduces infarct size and that 30 minutes of unloading activates a cardioprotective program that limits reperfusion injury. The DTU-STEMI pilot trial (Door-To-Unload in STEMI Pilot Trial) represents the first exploratory study testing whether LV unloading and delayed reperfusion in patients with STEMI without cardiogenic shock is safe and feasible. Methods: In a multicenter, prospective, randomized exploratory safety and feasibility trial, we assigned 50 patients with anterior STEMI to LV unloading by using the Impella CP followed by immediate reperfusion (U-IR) versus delayed reperfusion after 30 minutes of unloading (U-DR). The primary safety outcome was a composite of major adverse cardiovascular and cerebrovascular events at 30 days. Efficacy parameters included the assessment of infarct size by using cardiac magnetic resonance imaging. Results: All patients completed the U-IR (n=25) or U-DR (n=25) protocols with respective mean door-to-balloon times of 72 versus 97 minutes. Major adverse cardiovascular and cerebrovascular event rates were not statistically different between the U-IR versus U-DR groups (8% versus 12%, respectively, P =0.99). In comparison with the U-IR group, delaying reperfusion in the U-DR group did not affect 30-day mean infarct size measured as a percentage of LV mass (15±12% versus 13±11%, U-IR versus U-DR, P =0.53). Conclusions: We report that LV unloading using the Impella CP device with a 30-minute delay before reperfusion is feasible within a relatively short time period in anterior STEMI. The DTU-STEMI pilot trial did not identify prohibitive safety signals that would preclude proceeding to a larger pivotal study of LV unloading before reperfusion. An appropriately powered pivotal trial comparing LV unloading before reperfusion to the current standard of care is required. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03000270.
Background: The benefit of emergent coronary angiography after resuscitation from out-of-hospital cardiac arrest (OHCA) is uncertain for patients without ST-segment elevation (STE). The aim of this randomized trial was to evaluate the efficacy and safety of early coronary angiography and to determine the prevalence of acute coronary occlusion in resuscitated OHCA patients without STE. Methods: Adult (>18 years) comatose survivors without STE after resuscitation from OHCA were prospectively randomized in a 1:1 fashion under exception to informed consent regulations to early coronary angiography versus no early coronary angiography in this multi-center study. Early angiography was defined as ≤ 120 minutes from arrival at the percutaneous coronary intervention capable facility. The primary endpoint was a composite of efficacy and safety measures, including efficacy parameters of survival to discharge, favorable neurological status at discharge (Cerebral Performance Category ≤ 2), echocardiographic measures of left ventricular ejection fraction >50% and a normal regional wall motion score of 16 within 24 hours of admission. Adverse events included re-arrest, pulmonary edema on chest x-ray, acute renal dysfunction, bleeding requiring transfusion or intervention, hypotension (systolic arterial pressure ≤90 mmHg), and pneumonia. Secondary endpoints included the incidence of culprit vessels with acute occlusion. Results: The study was prematurely terminated before enrolling the target number of patients. A total of 99 patients were enrolled from 2015-2018, including 75 with initially shockable rhythms. Forty-nine patients were randomized to early coronary angiography. The primary endpoint of efficacy and safety was not different between the two groups (55.1% vs 46.0%; p=0.64). Early coronary angiography was not associated with any significant increase in survival (55.1% vs 48.0%; p=0.55 or adverse events (26.5% vs 26.0%; p=1.00). Early coronary angiography revealed a culprit vessel in 47%, with a total of 14% of patients undergoing early coronary angiography having an acutely occluded culprit coronary artery. Conclusions: This underpowered study, when considered together with previous clinical trials, does not support early coronary angiography for comatose survivors of cardiac arrest without ST elevation. Whether early detection of occluded potential culprit arteries leads to interventions that improve outcomes requires additional study. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02387398
We tested the hypothesis that early vascularization of the embryonic heart is enhanced after bolus injections of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) into the vitelline vein before the onset of myocardial vasculogenesis (3.5 days, stage 21). Electron and light microscopy were utilized to obtain morphometric data. At stages 29 and 31, myocardial vessel volume or numerical density were higher in embryos injected with 50 ng bFGF than in the saline-injected controls. A VEGF injection increased vascular volume density at stage 29 and both volume and numerical density at stage 31. bFGF, but not VEGF, was associated with an enhancement of the sinusoidal system (spongy layer of the ventricle) at stage 29. This effect disappeared by stage 31. In conclusion, 1) enhancement of bFGF or VEGF before myocardial vascularization increases vascular growth, but the initial effect of bFGF is greater; 2) the effects of these growth factors on vascular volume and numerical density are temporally dependent; and 3) bFGF, in addition to its effects on the coronary vasculature, influences ventricular modeling by apparently acting on myocytes as well as endothelial cells.
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