David Montaigne

Myocardial Contractile Dysfunction Is Associated With Impaired Mitochondrial Function and Dynamics in Type 2 Diabetic but Not in Obese Patients

Background— 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 A1C, 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 A1C. Conclusion— Worsening of intrinsic myocardial contraction in the transition from obesity to diabetes mellitus is likely related to worsening of cardiac mitochondrial function because impaired mitochondrial function and dynamics and contractile dysfunction are observed in diabetic patients but not in “metabolically healthy” obese patients at early stage in insulin resistance.

The SGLT2 Inhibitor Dapagliflozin Prevents Cardiomyopathy in a Diabetic Lipodystrophic Mouse Model

Type 2 diabetes mellitus (T2DM) is a well-recognized independent risk factor for heart failure. T2DM is associated with altered cardiac energy metabolism, leading to ectopic lipid accumulation and glucose overload, the exact contribution of these two parameters remaining unclear. To provide new insight into the mechanism driving the development of diabetic cardiomyopathy, we studied a unique model of T2DM: lipodystrophic Bscl2−/− (seipin knockout [SKO]) mice. Echocardiography and cardiac magnetic resonance imaging revealed hypertrophic cardiomyopathy with left ventricular dysfunction in SKO mice, and these two abnormalities were strongly correlated with hyperglycemia. Surprisingly, neither intramyocardial lipid accumulation nor lipotoxic hallmarks were detected in SKO mice. [18F]Fludeoxyglucose positron emission tomography showed increased myocardial glucose uptake. Consistently, the O-GlcNAcylated protein levels were markedly increased in an SKO heart, suggesting a glucose overload. To test this hypothesis, we treated SKO mice with the hypoglycemic sodium–glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin and the insulin sensitizer pioglitazone. Both treatments reduced the O-GlcNAcylated protein levels in SKO mice, and dapagliflozin successfully prevented the development of hypertrophic cardiomyopathy. Our data demonstrate that glucotoxicity by itself can trigger cardiac dysfunction and that a glucose-lowering agent can correct it. This result will contribute to better understanding of the potential cardiovascular benefits of SGLT2 inhibitors.

Mitochondrial Cardiomyopathy and Related Arrhythmias

Mitochondrial dysfunction has been shown to be involved in the pathophysiology of arrhythmia, not only in inherited cardiomyopathy due to specific mutations in the mitochondrial DNA but also in acquired cardiomyopathy such as ischemic or diabetic cardiomyopathy. This article briefly discusses the basics of mitochondrial physiology and details the mechanisms generating arrhythmias due to mitochondrial dysfunction. The clinical spectrum of inherited and acquired cardiomyopathies associated with mitochondrial dysfunction is discussed followed by general aspects of the management of mitochondrial cardiomyopathy and related arrhythmia.

Comment on Patel et al. ACE2 Deficiency Worsens Epicardial Adipose Tissue Inflammation and Cardiac Dysfunction in Response to Diet-Induced Obesity. Diabetes 2016;65:85-95.

We read with interest, but concern, the recently published article by Patel et al. (1) in Diabetes , which focused on potential links between angiotensin-converting enzyme 2 (ACE2) deficiency, epicardial adipose tissue (EAT) inflammation, and cardiac dysfunction in a high-fat diet mouse model.nnThe human heart is coated by fat whose function is becoming a hot topic in cardiovascular research. Indeed, EAT, i.e., the fat depot beneath the visceral pericardium and in direct contact with the epicardium, is a source …

Modified David Operation: A New Simple Method Using a Single Inflow Suture Line

The reimplantation technique for valve sparing aortic root replacement is increasingly used to treat aortic root enlargement. The systematic approach described by El Khoury in 2009 and modified in 2011 using the valsava graft (Gelweave valsalva, Sultzer, Vaskutek, renfrewshire, Scotland) is simple and reproducible. However, in-conduit suturing of the aortic valve annulus and small rim of sinus remnant to the graft sinuses is time consuming and may lead to bleeding, or distorsion of the native valve in the prosthetic root. We describe a simple technique to facilitate the native valve reimplantation. A reproducible, easy to achieve single inflow suture line is used allowing avoiding the continuous suture of the native valve used in all valve sparing surgical techniques.

2D-speckle tracking right ventricular strain to assess right ventricular systolic function in systolic heart failure. Analysis of the right ventricular free and posterolateral walls

BACKGROUNDnRight ventricular (RV) systolic function is a powerful prognostic factor in patients with systolic heart failure. The accurate estimation of RV function remains difficult. The aim of the study was to determine the diagnostic accuracy of 2D-speckle tracking RV strain in patients with systolic heart failure, analyzing both free and posterolateral walls.nnnMETHODSnSeventy-six patients with dilated cardiopathy (left ventricular end-diastolic volume≥75ml/m2) and left ventricular ejection fraction≤45% had an analysis of the RV strain. Feasibility, reproducibility and diagnostic accuracy of RV strain were analyzed and compared to other echocardiographic parameters of RV function. RV dysfunction was defined as a RV ejection fraction≤40% measured by radionuclide angiography.nnnRESULTSnRV strain feasibility was 93.9% for the free-wall and 79.8% for the posterolateral wall. RV strain reproducibility was good (intra-observer and inter-observer bias and limits of agreement of 0.16±1.2% [-2.2-2.5] and 0.84±2.4 [-5.5-3.8], respectively). Patients with left heart failure have a RV systolic dysfunction that can be unmasked by advanced echocardiographic imaging: mean RV strain was -21±5.7% in patients without RV dysfunction and -15.8±5.1% in patients with RV dysfunction (p=0.0001). Mean RV strain showed the highest diagnostic accuracy to predict depressed RVEF (area under the curve (AUC) 0.75) with moderate sensitivity (60.5%) but high specificity (87.5%) using a cutoff value of -16%.nnnCONCLUSIONSnRV strain seems to be a promising and more efficient measure than previous RV echocardiographic parameters for the diagnosis of RV systolic dysfunction.

Maladies cardiovasculaires: anomalies des canaux calciques

La meilleure comprehension de la physiologie cardiaque liee aux mouvements et aux changements de concentration intracellulaire des ions Ca++ a permis de mieux comprendre les consequences des anomalies de fonctionnement des canaux calciques, « canalopathies » dans un grand nombre de pathologies cardiovasculaires acquises et congenitales. Ces connaissances devraient permettre de developper des outils therapeutiques ciblant des aspects specifiques de la physiopathologie de l’insuffisance cardiaque ou de la fibrillation auriculaire, des problemes importants de sante publique.