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Background: Type 2 diabetes (T2D) is a frequent comorbidity encountered in patients with severe aortic stenosis (AS), leading to an adverse left ventricular (LV) remodeling and dysfunction. Metabolic alterations have been suggested as contributors of the deleterious effect of T2D on LV remodeling and function in patients with severe AS, but so far, the underlying mechanisms remain unclear. Mitochondria play a central role in the regulation of cardiac energy metabolism., Objectives: We aimed to explore the mitochondrial alterations associated with the deleterious effect of T2D on LV remodeling and function in patients with AS, preserved ejection fraction, and no additional heart disease., Methods: We combined an in-depth clinical, biological and echocardiography phenotype of patients with severe AS, with (n = 34) or without (n = 50) T2D, referred for a valve replacement, with transcriptomic and histological analyses of an intra-operative myocardial LV biopsy., Results: T2D patients had similar AS severity but displayed worse cardiac remodeling, systolic and diastolic function than non-diabetics. RNAseq analysis identified 1029 significantly differentially expressed genes. Functional enrichment analysis revealed several T2D-specific upregulated pathways despite comorbidity adjustment, gathering regulation of inflammation, extracellular matrix organization, endothelial function/angiogenesis, and adaptation to cardiac hypertrophy. Downregulated gene sets independently associated with T2D were related to mitochondrial respiratory chain organization/function and mitochondrial organization. Generation of causal networks suggested a reduced Ca 2+ signaling up to the mitochondria, with the measured gene remodeling of the mitochondrial Ca 2+ uniporter in favor of enhanced uptake. Histological analyses supported a greater cardiomyocyte hypertrophy and a decreased proximity between the mitochondrial VDAC porin and the reticular IP3-receptor in T2D., Conclusions: Our data support a crucial role for mitochondrial Ca 2+ signaling in T2D-induced cardiac dysfunction in severe AS patients, from a structural reticulum-mitochondria Ca 2+ uncoupling to a mitochondrial gene remodeling. Thus, our findings open a new therapeutic avenue to be tested in animal models and further human cardiac biopsies in order to propose new treatments for T2D patients suffering from AS., Trial Registration: URL: https://www., Clinicaltrials: gov ; Unique Identifier: NCT01862237., (© 2024. The Author(s).)

Aims: Diastolic dysfunction is frequent in patients with type 2 diabetes mellitus (DM2) and associated with a poor prognosis. This study aimed to describe diastolic function changes over time in DM2 patients and to identify predictive factors of diastolic function deterioration., Methods and Results: Diastolic function was assessed by echocardiography according to the EACVI/ASE recommendations at baseline and 3-year follow-up in a prospective cohort of 310 DM2 patients without overt heart disease. Predictors of diastolic function deterioration were identified using logistic regression analysis. During the 3-year follow-up, prevalence of diastolic dysfunction increased from 49% to 67% (P = 0.001). Only 32% of the patients had a normal diastolic function both at baseline and 3 years and 27% of the patients presented diastolic function deterioration. At multivariable analysis, age (OR = 1.05 [1.01-1.09], P < 0.01), retinopathy (OR = 2.00 [1.10-3.63], P = 0.02), and increase in systolic blood pressure during follow-up (OR = 1.03 [1.01-1.04], P < 0.01) were predictive of diastolic function deterioration., Conclusion: Age, retinopathy, and increase in blood pressure over time are associated with an increased risk of diastolic function deterioration in DM2 patients. The presence of these co-factors might help to early identify patients at risk of heart failure., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Background: Type 2 diabetes mellitus (T2DM) may alter cardiac structure and function, but obesity, hypertension (HTN), or aging can induce similar abnormalities., Objectives: This study sought to link cardiac phenotypes in T2DM patients with clinical profiles and outcomes using cluster analysis., Methods: Baseline echocardiography and a composite endpoint (cardiovascular mortality and hospitalization) were evaluated in 842 T2DM patients from 2 prospective cohorts. A cluster analysis was performed on echocardiographic variables, and the association between clusters and clinical profiles and outcomes was assessed., Results: Three clusters were identified. Cluster 1 patients had the lowest left ventricular (LV) mass index and ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e') ratio, had the highest left ventricular ejection fraction (LVEF), and were predominantly male with the lowest rate of obesity or HTN. Cluster 2 patients had the highest strain and highest E/e' ratio, were the oldest, were predominantly female, and had the lowest rate of isolated T2DM (without HTN or obesity). Cluster 3 patients had the highest LV mass index and volumes and the lowest LVEF and strain, were predominantly male, and shared similar age and rate of obesity and HTN as cluster 1 patients. After follow-up of 67 months (interquartile range: 40 to 87), the composite endpoint occurred in 56 of 521 patients (10.8%). Clusters 2 (hazard ratio: 2.37; 95% confidence interval: 1.15 to 4.88) and 3 (hazard ratio: 2.19; 95% confidence interval: 1.00 to 4.82) had a similar outcome, which was worse than cluster 1., Conclusions: Cluster analysis of echocardiographic variables identified 3 different echocardiographic phenotypes of T2DM patients that were associated with distinct clinical profiles and highlighted the prognostic value of LV remodeling and subclinical dysfunction., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In normal subjects, left ventricular (LV) dimensions have been shown to decrease over time, while wall thickness is increasing. The aim of this study was to investigate LV remodeling in a cohort of patients with type 2 diabetes mellitus during a 3-year follow-up period and its potential association with decreased longitudinal systolic strain (εL)., Methods: One hundred seventy-two patients with type 2 diabetes without overt heart disease were prospectively enrolled and underwent echocardiography with speckle-tracking imaging to assess global LV εL at baseline and at 3 years. The associations between alteration in εL (defined as |εL| < 18%), LV geometry at baseline, and LV remodeling over time were evaluated., Results: Among the 172 enrolled patients, 154 completed 3-year follow-up. At baseline, patients with εL alteration had higher LV end-systolic volumes (28 ± 11 vs 23 ± 9 mL, P < .001) and relative wall thicknesses (RWT; 0.44 ± 0.06 vs 0.40 ± 0.07, P = .008) compared with those with normal εL. At 3-year follow-up, RWTs remained stable in both groups. LV volumes significantly decreased in patients with normal εL but not in patients with εL alteration. Multivariate analysis showed that εL alteration was independently associated with LV end-systolic volume (β = 5.0, P = .006) and RWT (β = 0.03, P = .03) at baseline and with changes in both LV end-diastolic volume (β = 19.1, P = .001) and LV end-systolic volume (β = 2.6, P = .047) over 3 years., Conclusions: In patients with type 2 diabetes, εL alteration was associated with higher RWT and LV volumes and with the absence of decreases in LV volumes over time, which might be an early sign of adverse LV remodeling., (Copyright © 2014 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Purpose: To determine if cine displacement encoding with stimulated echoes (DENSE) can help to identify and determine the patterns of subclinical myocardial systolic dysfunction in patients with type 2 diabetes mellitus (DM) when compared with cine DENSE in control patients., Materials and Methods: After obtaining approval from the institutional ethics committee and written informed consent from the patients, 37 patients with type 2 DM without overt heart disease and 23 age-matched control patients were prospectively included in the study. The patients underwent standard cine magnetic resonance (MR) imaging with two-dimensional cine DENSE acquisitions. Circumferential (Ecc) and radial (Err) systolic strains were measured on short-axis views at basal, mid, and apical left ventricular levels. Longitudinal strain (Ell) was measured on four- and two-chamber views. Statistical testing included the intraclass correlation coefficient and multiple linear regression analysis., Results: The intraobserver intraclass correlation coefficient values were 0.85, 0.95, and 0.90, and the interobserver intraclass correlation coefficient values were 0.79, 0.91 and 0.80 for Ecc, Err, and Ell, respectively. The left ventricular ejection fraction was in the reference range and similar between the groups, and the patients with DM showed a decrease in Ecc (-14.4%±1.6 vs -17.0%±1.6, P<.001), Err (36.2%±10.9 vs 44.4%±9.9, P=.006) and Ell (-12.9%±2.1 vs -15.5%±1.6, P<.001) compared with the control patients. Finally, DM was independently associated with Ecc (P<.001), Err (P=.05) and Ell (P=.01) after adjustment for age, sex, hypertension, body mass index, and left ventricular mass., Conclusion: Cine DENSE, a motion-encoding MR imaging technique for myocardial strain assessment with high spatial resolution, appears to be useful in the identification of subclinical myocardial dysfunction in patients with DM., (© RSNA, 2012)

Background: Diastolic dysfunction is considered the first marker of diabetic cardiomyopathy. However, preclinical systolic alteration was also recently described by strain, but its association with diastolic dysfunction has never been investigated., Methods: One hundred fourteen patients with type 2 diabetes mellitus (DM) with controlled blood pressure and without overt heart disease were prospectively enrolled and compared with 88 age-matched controls. All subjects underwent comprehensive echocardiography, including diastolic evaluation according to current recommendations and speckle-tracking imaging. The prevalence of diastolic dysfunction, the determinants of diastolic parameters, and the association between preclinical systolic and diastolic dysfunctions were studied., Results: Diastolic parameters were altered in patients compared with controls, with lower E/A ratios, longer mitral deceleration and isovolumic relaxation times, and higher E/e' ratio. Diastolic dysfunction occurred in 47% of patients with DM (33% and 14% with grade I and II diastolic dysfunction, respectively) and systolic alteration (longitudinal strain ≥ -18%) in 32% of patients. Whereas longitudinal systolic strain was independently associated with DM and gender, diastolic parameters were influenced by many factors, including age, rate-pressure product, history of hypertension, and body mass index. Systolic alteration occurred in 28% of patients with DM with normal diastolic function and in 35% with diastolic dysfunction., Conclusions: Diastolic dysfunction diagnosed according to current recommendations is frequent in patients with DM but is also influenced by other factors. Systolic strain alteration may exist despite normal diastolic function, indicating that diastolic dysfunction should not be considered the first marker of a preclinical form of diabetic cardiomyopathy., (Copyright © 2011 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Background: Diabetic cardiomyopathy has been characterized by an early impairment of left ventricular (LV) longitudinal function as opposed to preserved LV radial function., Methods: Conventional echocardiography and longitudinal (ε(L)) and radial (ε(R)) systolic strain assessed by speckle-tracking imaging were obtained in 114 type 2 diabetic patients and 88 age-matched controls., Results: LV ejection fraction was similar in diabetic patients and controls. The presence of subclinical LV systolic dysfunction in diabetic patients was demonstrated by lower values of midwall fractional shortening (18% ± 3% vs 20% ± 3%, P = .006), ε(L) (-19% ± 3% vs -22% ± 2%, P < .001), and ε(R) (50% ± 16% vs 56% ± 12%, P = .003) compared with controls. On multivariate analysis, factors predicting strain values were diabetes (P = .001) and gender (P = .001) for ε(L) and diabetes (P = .003) for ε(R)., Conclusion: Diabetic patients without overt heart disease display subclinical alteration of both radial and longitudinal LV systolic function even after adjustment for blood pressure, age, and body mass index., (Copyright © 2010 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)