Acute myocardial infarction reparation/regeneration strategy using Wharton's jelly multipotent stem cells as an 'unlimited' therapeutic agent: 3-year outcomes in a pilot cohort of the CIRCULATE-AMI trial.

Introduction: CIRCULATE-AMI (NCT03404063), a cardiac magnetic resonance imaging (cMRI) infarct size-reduction-powered double-blind randomized controlled trial (RCT) of standardized Wharton jelly multipotent stem cells (WJMSCs, CardioCell Investigational Medical Product) vs. placebo (2 : 1) transcoronary transfer on acute myocardial infarction (AMI) day ~5-7, is preceded by safety and feasibility evaluation in a pilot study cohort (CIRCULATE-AMI PSC). Aim: To evaluate WJMSC transplantation safety and evolution of left ventricular (LV) remodeling in CIRCULATE-AMI PSC. Material and methods: In 10 consecutive patients (32-65 years, peak CK-MB 533 ±89 U/l, cMRI-LVEF 40.3 ±2.7%, cMRI-infarct size 20.1 ±2.8%), 30 × 106 WJMSCs were administered using a novel cell delivery-dedicated, coronary-non-occlusive method (CIRCULATE catheter). Other treatment was guideline-based. Results: WJMSC transfer was safe and occurred in the absence of coronary (TIMI-3 in all) or myocardial (corrected TIMI frame count (cTFC) 45 ±8 vs. 44 ±9, p = 0.51) flow deterioration or troponin elevation. By 3 years, 1 patient died from a new, non-index territory AMI; there were no other major adverse cardiovascular and cerebrovascular events (MACCE) and no adverse events that might be related to WJMSCs. cMRI infarct size was reduced from 33.2 ±7.6 g to 25.5 ±6.4 g at 1 year and 23.1 ±5.6 g at 3 years (p = 0.03 vs. baseline). cMRI, SPECT, and echo showed a consistent, statistically significant increase in LVEF at 6-12 months (41.9 ±2.6% vs. 51.0 ±3.3%, 36.0 ±3.9% vs. 44.9 ±5.0%, and 38.4 ±2.5% vs. 48.0 ±2.1% respectively, p < 0.01 for all); the effect was sustained at 3 years. Conclusions: CIRCULATE-AMI PSC data suggest that WJMSC transcoronary application ~5-7 days after large AMI in humans is feasible and safe and it may be associated with a durable LVEF improvement. CIRCULATE-AMI RCT will quantify the magnitude of LV adverse remodeling attenuation with CardioCell/placebo administration.

Myocardial perfusion in hypertensive patients with normal coronary angiograms.

BACKGROUND: Pressure-induced left ventricular hypertrophy is one of the mechanisms responsible for an impaired coronary vasodilating capacity leading to myocardial ischemia and angina. The aim of the study was to investigate myocardial perfusion using cardiovascular magnetic resonance in patients with arterial hypertension and a history of chest pain and normal coronary angiography, and to estimate the influence of left ventricular hypertrophy on the parameters of myocardial perfusion. METHODS: The study included 102 patients (mean age 55.4 +/- 7.7 years) with well controlled hypertension and 12 healthy volunteers. In 96 patients, myocardial first-pass perfusion cardiovascular magnetic resonance both at rest and during an infusion of adenosine 140 microg/kg/min was performed. Semiquantitative perfusion analysis was performed by using the upslope of myocardial signal enhancement to derive the myocardial perfusion index and the myocardial perfusion reserve index. The study group was divided according to the presence of left ventricular hypertrophy in the cardiovascular magnetic resonance examination: group with left ventricular hypertrophy (n = 40) and without left ventricular hypertrophy (n = 56). RESULTS: Independent of the presence of left ventricular hypertrophy, there were significant differences in baseline myocardial perfusion index between hypertensive patients and controls (0.13 +/- 0.07 vs. 0.04 +/- 0.01; P < 0.001), and in stress myocardial perfusion index (hypertensive patients 0.21 +/- 0.10 vs. controls 0.09 +/- 0.03; P < 0.001). In hypertensive patients, the myocardial perfusion reserve index was reduced in the mid and apical portions of the left ventricle (1.71 +/- 1.1 vs. 2.52 +/- 0.83; P < 0.02). There was no significant correlation of myocardial perfusion reserve index with left ventricular mass or hypertrophy. CONCLUSION: In patients with mild or moderate hypertension and a history of chest pain with normal coronary angiography, there is regional myocardial perfusion reserve impairment that is independent of the presence of left ventricular hypertrophy and may be a reason for angina.

Magnetic resonance imaging and clinical outcome in patients with symptomatic carotid artery stenosis after carotid artery revascularization.

INTRODUCTION: About 30% of patients with carotid artery stenosis (CAS) develop dementia after a cerebral ischemic event (CIE), and 20-50% suffer from CIE recurrence during 6 months. Carotid artery revascularization (CAR) may prevent CIE recurrence, at the cost of new microembolic lesions (MES). The impact of CAR on cognitive function is debatable. AIM: To assess functional and cognitive outcome, cerebral flow on transcranial Doppler (TCD) and brain magnetic resonance imaging (MRI) in patients with symptomatic CAS referred for CAR. MATERIAL AND METHODS: Twenty-two patients (aged 69.0 ±7.2 y.o., 15 male) with recent CIE (21.9 ±20.9 days to CAR) related to CAS of mean 89.8 ±3.9% lumen reduction were prospectively evaluated with TCD, diffusion and perfusion MRI, Montreal Cognitive Assessment (MoCA), Mini Mental State Examination (MMSE), modified Rankin Scale (mRS) and the National Institutes of Health Stroke Scale (NIHSS) 24 h before, at 24-48 h and 1 month following CAR. RESULTS: New MES were found in 11 (50%) subjects following CAR. CAR resulted in a significant increase of cerebral flow velocity in the middle and anterior cerebral arteries (p < 0.002 and p = 0.003; respectively) and cerebral perfusion measured by time to peak (TTP) and mean transit time (MTT) (p = 0.0009 and p = 0.0002; respectively). Neurologic tests showed improvement in NIHSS (2.4 ±1.6 to 1.5 ±1.2, p = 0.003), mRS (from 1.3 ±0.9 to 0.7 ±0.9, p = 0.005), and MMSE (26.7 ±2.2 to 27.6 ±2.3, p = 0.019) at 1 month, while similar MoCA scores were observed before and 1 month after CAR (23.4 ±3.3 vs. 24.1 ±3.7, p = 0.136). CONCLUSIONS: Improvement of cerebral flow and perfusion and functional outcome, as well as at least no cognitive decline, is observed after CAR for symptomatic CAS.