BackgroundRecent 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.ObjectivesTo investigate whether Opa1 (protein involved in mitochondrial inner-membrane fusion) deficiency affects I/R injuries.Methods and ResultsWe 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.ConclusionOpa1 deficiency was associated with increased sensitivity to I/R, imbalance in dynamic mitochondrial Ca2+ uptake, and subsequent increase in NCX activity.

AIMTo assess the arrhythmic determinants and prognosis of patients presenting with myocardial infarction and non-obstructive coronary arteries (MINOCA) with normal ejection fraction (EF).METHODSThis 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.RESULTSVentricular 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.CONCLUSIONMINOCA 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.

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