Effect of cardiosphere-derived cells on segmental myocardial function after myocardial infarction: ALLSTAR randomised clinical trial.

BACKGROUND: Most cell therapy trials failed to show an improvement in global left ventricular (LV) function measures after myocardial infarction (MI). Myocardial segments are heterogeneously impacted by MI. Global LV function indices are not able to detect the small treatment effects on segmental myocardial function which may have prognostic implications for cardiac events. We aimed to test the efficacy of allogeneic cardiosphere-derived cells (CDCs) for improving regional myocardial function and contractility. METHODS: In this exploratory analysis of a randomised clinical trial, 142 patients with post-MI with LVEF <45% and 15% or greater LV scar size were randomised in 2:1 ratio to receive intracoronary infusion of allogenic CDCs or placebo, respectively. Change in segmental myocardial circumferential strain (Ecc) by MRI from baseline to 6 months was compared between CDCs and placebo groups. RESULTS: In total, 124 patients completed the 6-month follow-up (mean (SD) age 54.3 (10.8) and 108 (87.1%) men). Segmental Ecc improvement was significantly greater in patients receiving CDC (-0.5% (4.0)) compared with placebo (0.2% (3.7), p=0.05). The greatest benefit for improvement in segmental Ecc was observed in segments containing scar tissue (change in segmental Ecc of -0.7% (3.5) in patients receiving CDC vs 0.04% (3.7) in the placebo group, p=0.04). CONCLUSIONS: In patients with post-MI LV dysfunction, CDC administration resulted in improved segmental myocardial function. Our findings highlight the importance of segmental myocardial function indices as an endpoint in future clinical trials of patients with post-MI. TRIAL REGISTRATION NUMBER: NCT01458405.

Achieving sustainable first door-to-balloon times of 90 minutes for regional transfer ST-segment elevation myocardial infarction.

OBJECTIVES: A network approach to transfer ST-segment elevation myocardial infarction (STEMI) patients can achieve durable first door-to-balloon times (1st D2B) for percutaneous coronary intervention (PCI) within 90 min. BACKGROUND: Nationally, a minority of STEMI patients from referral centers obtain 1st D2B in <2 h and even fewer in <90 min. METHODS: Included were transfer STEMI patients from 9 network hospitals treated in 2007 compared with 2008 to 2011 after installing the following initiatives: 1) established hospital referral system; 2) goal-oriented performance protocols; 3) expedited transport by ground or air; 4) first hospital activation of the PCI hospital catheterization laboratory; and 5) outreach coordinator and patient-level web-based feedback to the referring hospital. RESULTS: A total of 101 STEMI patients transported in 2007 were compared with 442 STEMI patients transferred after starting these initiatives for STEMI from 2008 to 2011, with the median door-in to door-out time decreased from 44 to 35 min (p < 0.0001), the median 1st D2B decreasing from 109.5 to 88.0 min (p < 0.0001), and the percentage under 90 min increased from 22.8% to 55.9% (p < 0.0001). Overall, throughout the study period (2007 to 2011), the transport times remained consistent (median 36.5 vs. 36.0 min, p = 0.98), whereas the PCI hospital D2B decreased from 20.0 to 16.0 min (p < 0.0001). Length of stay and in-hospital mortality remained low at 3.0 days and under 4%, respectively. CONCLUSIONS: A system-wide network program can achieve sustained (over 4 years) 1st D2B times of <90 min.

AngioJet experience from the multi-center STENT Registry.

OBJECTIVE: To explore the utilization and clinical outcomes of AngioJet Rheolytic thrombectomy from the Strategic Transcatheter Evaluation of New Therapies (STENT) multi-center prospective registry from May 2003 through December 2005. METHODS: Prospective consent was sought for all consecutive percutaneous coronary intervention (PCI) patients at all institutions and achieved in 84% of all patients. Of these, clinical follow-up at 9 months was achieved in 94% of eligible patients at all institutions. RESULTS: Of a total of 9,707 patients, AngioJet was utilized in 3-4% of all procedures, including 12-14% of all procedures with thrombolysis in myocardial infarction (TIMI) grade 3 thrombus or greater and 10-12% of acute evolving MI patients. Nine-month clinical outcomes showed similar mortality rates for patients treated with AngioJet (5.0%) versus those with no thrombectomy (6.5%) for patients with thrombus grade 3 or greater, despite the higher clinical risk profile of the AngioJet patient population due to a higher percentage of cardiogenic shock and larger thrombus. CONCLUSION: The results of this larger, multi-center registry indicate that AngioJet thrombectomy, when selected in general clinical practice for high risk patients with thrombus, results in non-significant numerically lower rate of mortality with no indication of safety issues.

Pulse pressure and coronary atherosclerosis progression in postmenopausal women.

Pulse pressure, an index of large artery stiffness, has been associated with coronary events. However, mechanisms for this association remain unclear. In this study, we examined the relationship between pulse pressure and the progression of coronary atherosclerosis and the effects of hormone replacement therapy (HRT) on pulse pressure in postmenopausal women with angiographically confirmed coronary disease followed for 3.2 years in the Estrogen Replacement in Atherosclerosis (ERA) trial. In the ERA trial, 309 postmenopausal women (mean age 66+/-7 years) with coronary disease were randomized to estrogen, estrogen plus progestin, or placebo, and followed for 3.2 years. Ten standardized epicardial segments were measured for minimal diameter values at baseline and follow-up using quantitative coronary angiography. For this study, mixed-model analysis of covariance was used to: (1) test the association between pulse pressure and change in mean minimum diameter (MMD) adjusted for baseline MMD and (2) the effect of HRT on follow-up pulse pressure. After adjustment for potential confounders, there was a significant graded increase in progression of coronary stenosis with increasing quartiles of baseline pulse pressure (P test for trend=0.0001). The progression rate in women with the highest quartile of baseline pulse pressure was 5-fold higher than in women in the lowest quartile (P<0.01). In postmenopausal women with coronary disease, increased levels of baseline pulse pressure are associated with subsequent progression of coronary atherosclerosis in postmenopausal women. HRT had no detectable effect on pulse pressure.

Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial.

CONTEXT: Contrast-induced nephropathy remains a common complication of radiographic procedures. Pretreatment with sodium bicarbonate is more protective than sodium chloride in animal models of acute ischemic renal failure. Acute renal failure from both ischemia and contrast are postulated to occur from free-radical injury. However, no studies in humans or animals have evaluated the efficacy of sodium bicarbonate for prophylaxis against contrast-induced nephropathy. OBJECTIVE: To examine the efficacy of sodium bicarbonate compared with sodium chloride for preventive hydration before and after radiographic contrast. DESIGN, SETTING, AND PATIENTS: A prospective, single-center, randomized trial conducted from September 16, 2002, to June 17, 2003, of 119 patients with stable serum creatinine levels of at least 1.1 mg/dL (> or =97.2 micromol/L) who were randomized to receive a 154-mEq/L infusion of either sodium chloride (n = 59) or sodium bicarbonate (n = 60) before and after iopamidol administration (370 mg iodine/mL). Serum creatinine levels were measured at baseline and 1 and 2 days after contrast. INTERVENTIONS: Patients received 154 mEq/L of either sodium chloride or sodium bicarbonate, as a bolus of 3 mL/kg per hour for 1 hour before iopamidol contrast, followed by an infusion of 1 mL/kg per hour for 6 hours after the procedure. MAIN OUTCOME MEASURE: Contrast-induced nephropathy, defined as an increase of 25% or more in serum creatinine within 2 days of contrast. RESULTS: There were no significant group differences in age, sex, incidence of diabetes mellitus, ethnicity, or contrast volume. Baseline serum creatinine was slightly higher but not statistically different in patients receiving sodium bicarbonate treatment (mean [SD], 1.71 [0.42] mg/dL [151.2 [37.1] micromol/L] for sodium chloride and 1.89 [0.69] mg/dL [167.1 [61.0] micromol/L] for sodium bicarbonate; P =.09). The primary end point of contrast-induced nephropathy occurred in 8 patients (13.6%) infused with sodium chloride but in only 1 (1.7%) of those receiving sodium bicarbonate (mean difference, 11.9%; 95% confidence interval [CI], 2.6%-21.2%; P =.02). A follow-up registry of 191 consecutive patients receiving prophylactic sodium bicarbonate and meeting the same inclusion criteria as the study resulted in 3 cases of contrast-induced nephropathy (1.6%; 95% CI, 0%-3.4%). CONCLUSION: Hydration with sodium bicarbonate before contrast exposure is more effective than hydration with sodium chloride for prophylaxis of contrast-induced renal failure.