Risk of ventricular arrhythmia in patients with myocardial infarction and non-obstructive coronary arteries and normal ejection fraction.

AIM: To assess the arrhythmic determinants and prognosis of patients presenting with myocardial infarction and non-obstructive coronary arteries (MINOCA) with normal ejection fraction (EF). METHODS: This is an observational analysis of 131 MINOCA patients with normal EF. Three cardiac magnetic resonance (CMR) diagnosis classes were recognized according to the late gadolinium enhancement (LGE) pattern: Myocardial infarction (MI) (n = 34), myocarditis (n = 47), and "no LGE" (n = 50). Ventricular events occurring during hospitalization were recorded and the entire population was followed-up at 1 year. RESULTS: Ventricular arrhythmia was observed in 18 (13.8%) patients during hospitalization. The "no LGE" patients experienced fewer ventricular events than the MI and myocarditis patients [4.0% vs 26.5% and 14.9%, respectively (P = 0.013)]. There was no significant difference between the MI and myocarditis groups. On multivariate analysis, LGE transmural extent [OR = 1.52 (1.08-2.15), P = 0.017] and ST-segment elevation [OR = 4.65 (1.61-13.40), P = 0.004] were independent predictors of ventricular arrhythmic events, irrespective of the diagnosis class. Finally, no patient experienced sudden cardiac death or ventricular arrhythmia recurrence at 1-year. CONCLUSION: MINOCA patients with normal EF presented no 1-year cardiovascular events, irrespective of the CMR diagnosis class. LGE transmural extent and ST segment elevation at admission are risk markers of ventricular arrhythmia during hospitalization.

Increase in Cardiac Ischemia-Reperfusion Injuries in Opa1+/- Mouse Model.

BACKGROUND: Recent data suggests the involvement of mitochondrial dynamics in cardiac ischemia/reperfusion (I/R) injuries. Whilst excessive mitochondrial fission has been described as detrimental, the role of fusion proteins in this context remains uncertain. OBJECTIVES: To investigate whether Opa1 (protein involved in mitochondrial inner-membrane fusion) deficiency affects I/R injuries. METHODS AND RESULTS: We examined mice exhibiting Opa1delTTAG mutations (Opa1+/-), showing 70% Opa1 protein expression in the myocardium as compared to their wild-type (WT) littermates. Cardiac left-ventricular systolic function assessed by means of echocardiography was observed to be similar in 3-month-old WT and Opa1+/- mice. After subjection to I/R, infarct size was significantly greater in Opa1+/- than in WTs both in vivo (43.2±4.1% vs. 28.4±3.5%, respectively; p<0.01) and ex vivo (71.1±3.2% vs. 59.6±8.5%, respectively; p<0.05). No difference was observed in the expression of other main fission/fusion protein, oxidative phosphorylation, apoptotic markers, or mitochondrial permeability transition pore (mPTP) function. Analysis of calcium transients in isolated ventricular cardiomyocytes demonstrated a lower sarcoplasmic reticulum Ca2+ uptake, whereas cytosolic Ca2+ removal from the Na+/Ca2+ exchanger (NCX) was increased, whilst SERCA2a, phospholamban, and NCX protein expression levels were unaffected in Opa1+/- compared to WT mice. Simultaneous whole-cell patch-clamp recordings of mitochondrial Ca2+ movements and ventricular action potential (AP) showed impairment of dynamic mitochondrial Ca2+ uptake and a marked increase in the AP late repolarization phase in conjunction with greater occurrence of arrhythmia in Opa1+/- mice. CONCLUSION: Opa1 deficiency was associated with increased sensitivity to I/R, imbalance in dynamic mitochondrial Ca2+ uptake, and subsequent increase in NCX activity.