Early detection of myocardial fibrosis in type II diabetic patients using MR T1-mapping

ORAL PRESENTATIONInternational audienc

Echocardiographic Evidence for Valvular Toxicity of Benfluorex: A Double-Blind Randomised Trial in Patients with Type 2 Diabetes Mellitus

OBJECTIVES: REGULATE trial was designed to compare the efficacy and safety of benfluorex versus pioglitazone in type 2 diabetes mellitus (DM) patients. METHODS: Double-blind, parallel-group, international, randomised, non-inferiority trial. More than half of the 196 participating centres were primary care centres. Patients eligible had type 2 DM uncontrolled on sulfonylurea. 846 were randomised. They received study treatment for 1 year. 423 patients were allocated to benfluorex (150 to 450 mg/day) and 423 were allocated to pioglitazone (30 to 45 mg/day). Primary efficacy criterion was HbA(1c). Safety assessment included blinded echocardiographic evaluation of cardiac and valvular status. RESULTS: At baseline, patients were 59.1 ± 10.5 years old with HbA1c 8.3 ± 0.8%, and DM duration 7.1 ± 6.0 years. During the study, mean HbA1c significantly decreased in both groups (benfluorex: from 8.30 ± 0.80 to 7.77 ± 1.31 versus pioglitazone: from 8.30 ± 0.80 to 7.45 ± 1.30%). The last HbA1c value was significantly lower with pioglitazone than with benfluorex (p<0.001) and non-inferiority of benfluorex was not confirmed (p = 0.19). Among the 615 patients with assessable paired echocardiography (310 benfluorex, 305 pioglitazone), 314 (51%) had at least one morphological valvular abnormality and 515 (84%) at least one functional valvular abnormality at baseline. Emergent morphological abnormalities occurred in 8 patients with benfluorex versus 4 with pioglitazone (OR 1.99), 95% CI (0.59 to 6.69). Emergent regurgitation (new or increased by one grade or more) occurred more frequently with benfluorex (82 patients, 27%) than with pioglitazone (33 patients, 11%) (OR 2.97), 95% CI (1.91 to 4.63) and were mainly rated grade 1; grade 2 (mild) was detected in 2 patients with benfluorex and 3 with pioglitazone. There was no moderate or severe regurgitation. CONCLUSION: After 1 year of exposure, our results show a 2.97 fold increase in the incidence of valvular regurgitation with benfluorex and provide evidence for the valvular toxicity of this drug

Impact of cardiac resynchronization therapy optimization inside a heart failure programme : a real‐world experience

Aims: This study sought to describe and evaluate the impact of a routine in‐hospital cardiac resynchronization therapy (CRT) programme, including comprehensive heart failure (HF) evaluation and systematic echo‐guided CRT optimization. Methods and results: CRT implanted patients were referred for optimization programme at 3 to 12 months from implantation. The program included clinical and biological status, standardized screening for potential cause of CRT non‐response and systematic echo‐guided atrioventricular and interventricular delays (AVd and VVd) optimization. Initial CRT‐response and improvement at 6 months post‐optimization were assessed with a clinical composite score (CCS). Major HF events were tracked during 1 year after optimization. A total of 227 patients were referred for CRT optimization and enrolled (71 ± 11 years old, 77% male, LVEF 30.6 ± 7.9%), of whom 111 (48.9%) were classified as initial non‐responders. Left ventricular lead dislodgement was noted in 4 patients (1.8%), and loss or ≤90% biventricular capture in 22 (9.7%), mostly due to arrhythmias. Of the 196 patients (86%) who could undergo echo‐guided CRT optimization, 71 (36.2%) required VVd modification and 50/144 (34.7%) AVd modification. At 6 months post‐optimization, 34.3% of the initial non‐responders were improved according to the CCS, but neither AVd nor VVd echo‐guided modification was significantly associated with CCS‐improvement. After one‐year follow‐up, initial non‐responders maintained a higher rate of major HF events than initial responders, with no significant difference between AVd/VVd modified or not. Conclusions: Our study supports the necessity of a close, comprehensive and multidisciplinary follow‐up of CRT patients, without arguing for routine use of echo‐guided CRT optimization

Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy

Brown adipose tissue (BAT) has well recognized thermogenic properties mediated by uncoupling protein 1 (UCP1); more recently, BAT has been demonstrated to modulate cardiovascular risk factors. To investigate whether BAT also affects myocardial injury and remodeling, UCP1-deficient (UCP1−/−) mice, which have dysfunctional BAT, were subjected to catecholamine-induced cardiomyopathy. At baseline, there were no differences in echocardiographic parameters, plasma cardiac troponin I (cTnI) or myocardial fibrosis between wild-type (WT) and UCP1−/− mice. Isoproterenol infusion increased cTnI and myocardial fibrosis and induced left ventricular (LV) hypertrophy in both WT and UCP1−/− mice. UCP1−/− mice also demonstrated exaggerated myocardial injury, fibrosis, and adverse remodeling, as well as decreased survival. Transplantation of WT BAT to UCP1−/− mice prevented the isoproterenol-induced cTnI increase and improved survival, whereas UCP1−/− BAT transplanted to either UCP1−/− or WT mice had no effect on cTnI release. After 3 days of isoproterenol treatment, phosphorylated AKT and ERK were lower in the LV's of UCP1−/− mice than in those of WT mice. Activation of BAT was also noted in a model of chronic ischemic cardiomyopathy, and was correlated to LV dysfunction. Deficiency in UCP1, and accompanying BAT dysfunction, increases cardiomyocyte injury and adverse LV remodeling, and decreases survival in a mouse model of catecholamine-induced cardiomyopathy. Myocardial injury and decreased survival are rescued by transplantation of functional BAT to UCP1−/− mice, suggesting a systemic cardioprotective role of functional BAT. BAT is also activated in chronic ischemic cardiomyopathy

Apport de la TEMP couplée à l'ECG au Tc-99m-sestamibi sous perfusion de dobutamine dans la prediction du remodelage du ventricule gauche chez des patients traités par angioplastie à la phase aiguë d'un primo-infarctus du myocarde

Le remodelage ventriculaire gauche après infarctus du myocarde est fréquent et entraîne une augmentation du risque d'insuffisance cardiaque et de la mortalité. Sa détection précoce permettait d'adapter le traitement et la surveillance des patients à risque. Le but de cette étude prospective était d'évaluer la capacité de la TEMP couplée à l'ECG au Tc-99m-sestamibi, à l'état basal et sous faible dose de dobutamine, réalisée au 6e jour après infarctus du myocarde, à détecter une évolution vers le remodelage ventriculaire au 6e mois. Notre travail a mis en évidence que l'analyse combinée de la fixation moyenne du traceur dans le territoire de l'artère responsable de l'infarctus et de l'épaississement pariétal systolique de ce même territoire, à l'état basal, permet de prédire un remodelage ventriculaire gauche au 6e mois avec une sensibilité de 70%, une spécificité de 86,7%, une exactitude de 90%, une VPP de 63,7% et une VPN de 89,7%. L'analyse de ces mêmes paramètres sous dobutamine, en démasquant une viabilité myocardique résiduelle, permet d'augmenter la sensibilité à 90%, la spécificité à 96,7%, l'exactitude du test à 95%, la VPP à 90,9% et la VPN à 96%.CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Diabète de type 2 et réentraînement à l'effort (effet sur la réserve contractile myocardique ?)

Le diabète de type 2 est associé à une augmentation du risque de la survenue d'une insuffisance cardiaque par le biais de l'atteinte ischémique mais aussi par une atteinte spécifique de la fonction myocardique appelée cardiomyopathie diabétique. A un stade préclinique, des anomalies de la fonction systolique et diastolique ainsi qu'une diminution de la réserve contractile myocardique ont été démontrées chez des patients diabétiques supposés indemnes de cardiomyopathie. Par ailleurs, des effets bénéfiques du réentraînement à l'effort chez les diabétiques ont été démontrés, en particulier sur l'équilibre glycémique et la diminution des facteurs de risques cardiovasculaires. L'objectif de cette étude pilote, prospective, était d'étudier les effets du réentraînement à l'effort durant 4 mois sur la fonction myocardique de repos et la réserve contractile myocardique chez des patients diabétiques de type 2 sans cardiopathie connue. Vingt patients répartis en 2 groupes, l'un participant à un programme de réentraînement à l'effort, supervisé pendant 4 mois et l'autre ne bénéficiant pas du réentraînement, ont été étudiés en réalisant une échocardiographie de repos et d'effort avant et après réentraînement. Ce travail a montré la faisabilité de cette étude. Il n'a pas été démontré d'amélioration significative de réserve contractile dans le groupe réentraîné par rapport au groupe témoin. Cependant, il existait une tendance à une amélioration des pressions de remplissage du ventricule gauche au repos après réentraînement. Enfin, cette étude a confirmé l'effet bénéfique du réentraînement à l'effort sur les facteurs de risque cardiovasculaire associé au diabète.CLERMONT FD-BCIU-Santé (631132104) / SudocSudocFranceF

0324: Prognostic value of epicardial-endocardial gradient measured by echocardiography to predict Cardiac Resynchronization Therapy (CRT) response

BackgroundAs right ventricular lead is positioned endocardialy and left ventricular lead epicardialy, we hypothesized that baseline epi-endo gradient could predict CRT response.Method and resultsWe studied 46 patients referred for CRT. Transthoracic echocardiography (TTE) was performed for all patients before and one year after implantation. Offline analysis with speckle tracking imaging (STI) analysis of LV endocardial and epicardial wall was performed. Specifically, epi-endo gradient delay (GD) and gradient contraction (GC) measurements were performed on the septal and lateral LV wall before and one year after implantation. CRT response was defined as a reduction>15% of LV end systolic volume one year after CRT.ResultsMean age was 62±11 year-old and mean EF was 26±7%. Twenty-two patients were classified as responders. Baseline characteristics of patients with or without CRT response were similar, except for QRS duration. Before implantation, septal (10±31ms vs. 20±133ms, p=0.67) and lateral GD (1±25ms vs. 4±26ms, p=0.76) were low and similar in both groups. However lateral GC was higher in CRT responders (–4.05±2.29% vs. –2.38±2.82%, p=0.009). After multivariate analysis, lateral GC was the best predictor of CRT response (p=0.013). One year after implantation, septal GD and GC were comparable in CRT responders or not. However lateral GC significantly decreased in CRT responders (–4.05±2.29% at baseline vs. –1.86±2.2%, p<0.01) whereas no changes were observed for non-responders. Finally lateral GD was significantly increased at one year in CRT non responders 4±26ms at baseline vs. 18±43ms, p<0.01). Conclusion: At baseline no significant LV epicardial-endocardial delay gradient was observed in patients with CRT response or not. However lateral epi-endo gradient contraction is highly independently associated with CRT response. Finally this gradient was homo-genezing one year after CRT for responders

The role of hyperglycaemia in the development of diabetic cardiomyopathy

International audienceAbstract The cardiovascular system is significantly affected in coronavirus disease-19 (COVID-19). Microvascular injury, endothelial dysfunction, and thrombosis resulting from viral infection or indirectly related to the intense systemic inflammatory and immune responses are characteristic features of severe COVID-19. Pre-existing cardiovascular disease and viral load are linked to myocardial injury and worse outcomes. The vascular response to cytokine production and the interaction between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and angiotensin-converting enzyme 2 receptor may lead to a significant reduction in cardiac contractility and subsequent myocardial dysfunction. In addition, a considerable proportion of patients who have been infected with SARS-CoV-2 do not fully recover and continue to experience a large number of symptoms and post-acute complications in the absence of a detectable viral infection. This conditions often referred to as ‘post-acute COVID-19’ may have multiple causes. Viral reservoirs or lingering fragments of viral RNA or proteins contribute to the condition. Systemic inflammatory response to COVID-19 has the potential to increase myocardial fibrosis which in turn may impair cardiac remodelling. Here, we summarize the current knowledge of cardiovascular injury and post-acute sequelae of COVID-19. As the pandemic continues and new variants emerge, we can advance our knowledge of the underlying mechanisms only by integrating our understanding of the pathophysiology with the corresponding clinical findings. Identification of new biomarkers of cardiovascular complications, and development of effective treatments for COVID-19 infection are of crucial importance