Effect of iron chelation on myocardial infarct size and oxidative stress in ST-elevation-myocardial infarction.

BACKGROUND: Experimental studies suggest that deferoxamine (DFO) limits the generation of reactive oxygen species by chelating redox-active iron and thereby may reduce ischemia-reperfusion injury and myocardial infarct (MI) size. We investigated whether DFO administered before reperfusion by primary percutaneous coronary intervention (PPCI) would ameliorate oxidative stress and MI size. METHODS AND RESULTS: We randomly assigned 60 patients with ST-elevation-MI to receive an intravenous bolus of DFO (500 mg) immediately before PPCI followed by a 12-hour infusion (50 mg/kg of body weight) (n=28) or normal saline bolus and infusion (placebo group, n=32). MI size was measured by contrast-enhanced cardiac MRI (CMRI; day 3±1), creatine kinase and troponin I area-under-the-curve, and severity of wall motion abnormality on echocardiography. Clinical follow-up including repeat CMRI and echocardiography were performed at 3 months (100±17 days). Oxidative stress was assessed by plasma F(2)-isoprostane levels. DFO and placebo groups were well balanced with respect to baseline characteristics, symptom- and door-to-balloon times, pre-PPCI coronary patency, and infarct-related artery location. Serum iron levels were decreased with DFO treatment after PPCI compared with placebo (3.0±2.5 versus 12.6±5.5 µmol/L, P<0.0001), which persisted until the end of the infusion. In DFO-treated patients, there was a significant reduction in plasma F(2)-isoprostane levels immediately after PPCI (2878±1461 versus 2213±579 pmol/L, P=0.04). However, there was no difference in CMRI-determined infarct size (DFO, 17.4±10.8%, versus placebo, 18.6±10.2%; P=0.73), myocardial salvage index at 3 days or at 3 months, or the area-under-the-curve for creatine kinase or troponin I. CONCLUSIONS: Adjunctive DFO treatment after the onset of ischemia and continued periprocedurally ameliorates oxidative stress without limiting infarct size. CLINICAL TRIAL REGISTRATION: URL: http://www.anzctr.org.au/. Unique identifier: ACTRN12608000308392.

Myocardial fibrosis predicts appropriate device therapy in patients with implantable cardioverter-defibrillators for primary prevention of sudden cardiac death.

OBJECTIVES: The purpose of this study was to evaluate the association between regional myocardial fibrosis and ventricular arrhythmias in patients with cardiomyopathy. BACKGROUND: Patients with heart failure are at risk of sudden cardiac death (SCD). Current guidelines recommend implantable cardioverter-defibrillator (ICD) devices for a subgroup based on impaired left ventricular function. A significant proportion of devices never discharge, hence a more accurate method for targeting those at risk is desirable. METHODS: We prospectively enrolled 103 patients meeting criteria for ICD implantation for primary prevention of SCD. Cardiac magnetic resonance imaging was performed before device implantation. Regional fibrosis was identified with late gadolinium enhancement (LGE). RESULTS: Median follow-up was 573 days (interquartile range: 379 to 863 days). The LGE identified regional fibrosis in 31 of 61 (51%) patients with nonischemic cardiomyopathy (NICM) and in all 42 patients with ischemic cardiomyopathy (ICM). There was a 29% (9 of 31) discharge rate in the NICM group with LGE compared with a 14% (6 of 42) discharge rate in the ICM group (p = NS). There were no ICD discharges in the NICM group without LGE, which was significantly lower than the rate observed in both the ICM patients (p = 0.04) and the NICM patients with LGE (p < 0.01). Left ventricular ejection fraction was similar in patients with and without device therapy (24 ± 12% vs. 26 ± 8%, p = NS) and those with or without LGE (25 ± 9% vs. 26 ± 9%, p = NS). CONCLUSIONS: Patients with advanced cardiomyopathy and myocardial fibrosis demonstrated by LGE on cardiac magnetic resonance imaging have a high likelihood of appropriate ICD therapy. Correspondingly, absence of LGE may indicate a lower risk for malignant ventricular arrhythmias.