No abstract

O besity and type 2 diabetes mellitus (DM) have reached epidemic levels worldwide. These 2 metabolic disorders are independent risk factors for the development of heart failure. [1][2][3] Epidemiological and clinical studies strongly support the existence of obesity and diabetic cardiomyopathies unrelated to coronary artery disease, hypertension, and other comorbidities. 4,5 Clinical Perspective on p 564Studies in rodent models of obesity and DM have identified intrinsic cardiomyocyte dysfunctions secondary to alterations in energy substrate utilization, mitochondrial dysfunction, increased oxidative stress, and intracellular accumulation of lipotoxic byproducts. Similarly, human studies have shown that dysregulation of the energy conversion process is one of the major characteristics of the failing heart of subjects with cardiomyopathy related to DM or obesity. 6,7Background-Obesity and diabetes mellitus are independently associated with the development of heart failure. In this study, we determined the respective effects of obesity, insulin resistance, and diabetes mellitus on the intrinsic contraction and mitochondrial function of the human myocardium before the onset of cardiomyopathy. Methods and Results-Right atrial myocardium was obtained from 141 consecutive patients presenting no sign of cardiomyopathy. We investigated ex vivo isometric contraction, mitochondrial respiration and calcium retention capacity, and respiratory chain complex activities and oxidative stress status. Diabetes mellitus was associated with a pronounced impairment of intrinsic contraction, mitochondrial dysfunction, and increased myocardial oxidative stress, regardless of weight status. In contrast, obesity was associated with less pronounced contractile dysfunction without any significant perturbation of mitochondrial function or oxidative stress status. Tested as continuous variables, glycated hemoglobin A 1C , but neither body mass index nor the insulin resistance index (homeostasis model assessment-insulin resistance), was independently associated with cardiac mitochondrial function. Furthermore, diabetes mellitus was associated with cardiac mitochondrial network fragmentation and significantly decreased expression of the mitochondrial fusion related protein MFN1. Myocardial MFN1 content was inversely proportional to hemoglobin A 1C . Conclusion-Worsening

The FRANCE TAVI registry provided reassuring data regarding trends in TAVR performance in an all-comers population on a national scale. Nonetheless, given that TAVR indications are likely to expand to patients at lower surgical risk, concerns remain regarding potentially life-threatening complications and pacemaker implantation. (Registry of Aortic Valve Bioprostheses Established by Catheter [FRANCE TAVI]; NCT01777828).

Our prospective study identifies an association between pre-operative mitochondrial dysfunction of the atrial myocardium and AF occurrence after cardiac surgery in patients with metabolic disease, providing novel insights into the link between mitochondria and arrhythmias in patients.