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Aging and obesity both contribute to the onset of metabolic disorders and cardiovascular disease. Whether aging worsens high-fat diet (HFD)-induced obesity cardiac alterations in a murine model is not yet demonstrated. Furthermore, the beneficial effect of a weight loss induced by switch diet (SD), from HFD to control diet (CD) has been demonstrated on cardiac remodelling and function in young mice but not in aged mice. Our aim was first to assess the impact of HFD in old mice and to evaluate the reversibility of HFD-induced cardiac alterations by SD in young and aged mice. We performed a study in young (5-month-old) and old (12-month-old) mice, fed with HFD (60% fat + 5% sucrose) for 20 weeks or switched to CD for 8 weeks (SD group) after 12 weeks of HFD. We performed metabolic tests (GTT, ITT) and echocardiography [cardiac function assessed by left ventricular ejection fraction (LVEF) and systolic strain rate (SR)]. The comparison between young and old mice in CD groups shows that aging increases the body weight, adiposity index and cardiac hypertrophy and impairs myocardial function (SR but not LVEF). HFD regimen increases similarly body weight and adiposity index in both young and old mice, whilst cardiac function is impaired with a similar decrease of systolic SR in young and old mice. SD induces a similar weight loss and decrease of the adiposity index in young and old mice. However, SD improves systolic function assessed by SR in young but not aged mice. Interestingly, this improvement in SR was associated with an amelioration of glucose tolerance in young mice. Our data demonstrate that HFD-induced obesity and SD-induced weight loss modulate cardiac function differently with aging. Thus, the improvement of cardiac function by SD in young mice is not found in old mice. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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Obstructive sleep apnea is a growing health problem effecting almost 1 billion world population presently. The landmark feature of OSA is a chronic intermittent hypoxia (CIH) responsible for multiple organ damages including heart diseases. CIH profoundly alters both visceral white adipose tissue (vWAT) and heart structures and functions, but little is known regarding their interactions in the context of CIH. We recently showed that vWAT senescence drives myocardial alterations through the release of profibrotic factors in aged mice. We aim at demonstrating that CIH induces a premature vWAT senescent phenotype, responsible for subsequent heart dysfunction In a first experiment, ten-weeks old C57BL6 male mice (n = 10/group) were exposed to 14 days CIH protocol (8 hours daily, 5–21% cyclic inspired oxygen fraction, 60 seconds per cycle). In a second series, mice were submitted to either vWAT surgical lipectomy or sham-surgery. Finally, we used p53 KO mice or littermates, also exposed to the same CIH protocol. vWAT and hearts were assessed for fibrosis, hypertrophy, DNA damage, oxidative stress, markers of senescence (p16, p21, p53) and inflammation by histology, RT-qPCR and western blot. CIH induced a "senescent-like" phenotype in vWAT, characterized by increased fibrosis, oxidative stress, DNA damage and inflammation (macrophage infiltration and inflammatory markers expression). This was associated with CIH-induced myocardial interstitial fibrosis and upregulation of profibrotic gene expression in myocardium. Interestingly, CIH did not induce vWAT remodeling in p53KO mice and CIH-induced myocardial interstitial fibrosis was prevented by both vWAT resection and p53 deletion. Short-term exposure to CIH is sufficient to induce vWAT premature senescence and cardiac interstitial fibrosis that was prevented by vWAT lipectomy and deletion of p53 senescence pathway. This strongly suggest a causal crosstalk between CIH-induced vWAT senescence and cardiac remodelling. [ABSTRACT FROM AUTHOR]

Aim S.AGES is a multicenter prospective cohort study of non-institutionalized patients aged 65 and over with atrial fibrillation, type 2 diabetes or chronic pain. Its objective is to describe the medical management in primary care. This article presents the baseline characteristics of subjects in the diabetes subcohort and compares the results to those from cohorts of older diabetic patients. Methods From April 2009 to June 2011, 983 patients were included in the diabetes subcohort by 213 primary care providers. Demographic data, geriatric parameters and the history, characteristics and treatment of the diabetes were recorded at baseline. Results The mean age was 76.7 ± 5.9 years. Most patients were living independently, with no cognitive impairment and in relatively good health. The duration of diabetes was 11.3 ± 8.7 years with average HbA1c of 6.9 ± 1.0%. 20% of patients had macrovascular disease, 33% renal failure, 14.6% ocular complication and 7.1% neuropathy. The first-line antidiabetic treatment was metformin (61.2%) and 18% of patients had used insulin. Treatment intensified with the worsening of diabetic symptoms. When compared to those from French and North American cohorts, the results showed increased complications and use of insulin with age, disease duration and severity. Conclusion Due to the method of recruitment, S.AGES patients were generally healthy with well-controlled diabetes. However, the results were consistent with those from other cohorts. Three-year follow-up is expected to study the management of diabetic patients aged 65 and over in primary care. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Mechanistic target of rapamycin (mTOR) is a central regulator of cell growth, proliferation, survival and metabolism. mTOR inhibition is increasingly used in antitumoral therapies and mTOR inhibition with rapamycin was shown to be cardioprotective during aging and cardiac stress. Studies in genetic mice models have shown that mTOR is essential for heart development and cardiac function in adult. However, mTOR functions during postnatal cardiac development are not fully elucidated. We have therefore generated a cardiac-specific mTOR knockout mouse using α-MHC-Cre mice leading to mTOR inactivation in early postnatal mouse myocardium. The mutant mice develop a severe lethal dilated cardiomyopathy due to defects in cardiomyocyte growth, survival and subsequent fibrosis. In contrast to adult myocardium, both mTORC1 and mTORC2 activities are impaired in juvenile heart, as shown by hypophosphorylation of the translation inhibitor 4E-BP1 and loss of the cardioprotective AKTS473 phosphorylation. We find that translation initiation defects and altered ribosome biogenesis both contribute to impaired cardiomyocyte growth. In addition, we show that increased apoptosis is associated with activation of JNK kinase and p53 accumulation. Moreover mTORcmKO hearts display a strong decreased expression of the primary oxygen carrier, myoglobin, and HIF1α accumulation suggesting hypoxia. However, mTORcmKO hearts do not display HIF1 hypoxic response consistently with mTOR being essential for HIF1-dependant trancriptionnal activity. These observations indicate that hypoxia-induced apoptosis likely contribute to DCM in mTORcmKO mice. Altogether, our results demonstrate that mTOR is a key regulator of cardiomyocyte growth, viability and oxygen supply in early postnatal myocardium. Our findings highlight potential cardiotoxicity of new mTOR inhibitors and the importance to set up optimal treatments in cardiology to both target mTOR hypertrophic functions and maintain adequate oxygen supply. [ABSTRACT FROM AUTHOR]

The article presents an abstract on a paper titled "Cine Displacement Encoding Imaging With Stimulated Echoes (cine-DENSE) Confirms Systolic Myocardial Dysfunction in Asymptomatic Patients With Type 2 Diabetes Mellitus: Comparison With MR-Tagging," presented at the 2011 Society for Cardiovascular Magnetic Resonance (CMR)/Euro CMR Joint Scientific Sessions held in France.

An abstract of the paper "Myocardial T1-Mapping for Early Detection of Left Ventricular Myocardial Fibrosis in Systemic Sclerosis," by Franck Thuny and colleagues is presented.

Objective: This study examined the effect of cyclosporine A used at the time of reperfusion, on LV remodeling and function by cardiac magnetic resonance (CMR) in the early days and several months after AMI. Background: In a human study, administration of cyclosporine A at the time of acute myocardial infarction (AMI) reperfusion was associated with a smaller infarct size. However, experimental data suggest that cyclosporine A has a detrimental effect on left ventricular remodeling. Methods: 28 patients of the original cyclosporine A study had an acute (day 5) and a follow-up (6 months) CMR study. Cine imaging was used to determine LV volumes, mass, ejection fraction and myocardial wall thickness in infarcted and remote non-infarcted myocardium, and late gadolinium imaging was used to determine infarct size. Results: There was a persistent reduction of the absolute infarct size at 6 months in the cyclosporine A group compared with the control group of patients (29±15 grams VS 38±14 grams; P=0.04). There was a significant reduction of LV end-systolic volume (and a trend for LV end-diastolic volume; P=0.07) in the cyclosporine A group, compared with the control group, both at day 5 and at 6 months after infarction. There was no significant difference between the two groups in either global LV mass or regional wall thickness of the remote non-infarcted myocardium at day 5 or at 6 months. Attenuation of LV dilatation and improvement of LV ejection fraction by cyclosporine A at 6 months were correlated with infarct size reduction. Conclusion: Cyclosporine A used at the moment of AMI reperfusion persistently reduces infarct size and does not have a detrimental effect on LV remodeling [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine whether post-conditioning at the time of percutaneous coronary intervention could reduce reperfusion-induced myocardial edema in patients with acute ST-segment elevation myocardial infarction (STEMI). Background: Myocardial edema is a reperfusion injury with potentially severe consequences. Post-conditioning is a cardioprotective therapy that reduces infarct size after reperfusion, but no previous studies have analyzed the impact of this strategy on reperfusion-induced myocardial edema in humans. Methods: Fifty patients with STEMI were randomly assigned to either a control or post-conditioned group. Cardiac magnetic resonance imaging was performed within 48 to 72 h after admission. Myocardial edema was measured by T2-weighted sequences, and infarct size was determined by late gadolinium enhancement sequences and creatine kinase release. Results: The post-conditioned and control groups were similar with respect to ischemia time, the size of the area at risk, and the ejection fraction before percutaneous coronary intervention. As expected, post-conditioning was associated with smaller infarct size (13 ± 7 g/m2 vs. 21 ± 14 g/m2; p = 0.01) and creatine kinase peak serum level (median [interquartile range]: 1,695 [1,118 to 3,692] IU/l vs. 3,505 [2,307 to 4,929] IU/l; p = 0.003). At reperfusion, the extent of myocardial edema was significantly reduced in the post-conditioned group as compared with the control group (23 ± 16 g/m2 vs. 34 ± 18 g/m2; p = 0.03); the relative increase in T2W signal intensity was also significantly lower (p = 0.02). This protective effect was confirmed after adjustment for the size of the area at risk. Conclusions: This randomized study demonstrated that post-conditioning reduced infarct size and edema in patients with reperfused STEMI. (Post Cond No Reflow; NCT01208727) [ABSTRACT FROM AUTHOR]

Objectives: This study examined the effect of a single dose of cyclosporine administered at the time of reperfusion on left ventricular (LV) remodeling and function by cardiac magnetic resonance 5 days and 6 months after myocardial infarction. Background: In a human study, administration of cyclosporine at the time of acute reperfusion was associated with a smaller infarct size. Methods: Twenty-eight patients of the original cyclosporine study had an acute (at 5 days) and a follow-up (at 6 months) cardiac magnetic resonance study to determine LV volumes, mass, ejection fraction, myocardial wall thickness in infarcted and remote noninfarcted myocardium, and infarct size. Results: There was a persistent reduction in infarct size at 6 months in the cyclosporine group compared with the control group of patients (29 ± 15 g vs. 38 ± 14 g; p = 0.04). There was a significant reduction of LV end-systolic volume (and a trend for LV end-diastolic volume; p = 0.07) in the cyclosporine group compared with the control group, both at 5 days and 6 months after infarction. There was no significant difference between the 2 groups in either global LV mass or regional wall thickness of the remote noninfarcted myocardium at 5 days or 6 months. Attenuation of LV dilation and improvement of LV ejection fraction by cyclosporine at 6 months were correlated with infarct size reduction. Conclusions: Cyclosporine used at the moment of acute myocardial infarction reperfusion persistently reduces infarct size and does not have a detrimental effect on LV remodeling. These results are preliminary and must be supported by further studies. (Ciclosporin A and Acute Myocardial Infarction; NCT00403728) [Copyright &y& Elsevier]

Objectives: To compare the incidence of diastolic and systolic asynchrony, assessed by tissue Doppler imaging (TDI), in patients with congestive heart failure (CHF) and severe left ventricular (LV) dysfunction, and to assess TDI changes induced by cardiac resynchronization therapy (CRT). Background: Thirty percent of CRT candidates are nonresponders. Besides QRS width, the presence of echographic systolic asynchrony has been used to identify future responders. Little is known about diastolic asynchrony and its change after CRT. Methods: Tissue Doppler imaging was performed in 116 CHF patients (LV ejection fraction 26 ± 8%). Systolic and diastolic asynchrony was calculated using TDI recordings of right ventricular and LV walls. Results: The CHF group consisted of 116 patients. Diastolic asynchrony was more frequent than systolic, concerning both intraventricular (58% vs. 47%; p = 0.0004) and interventricular (72 vs. 45%; p < 0.0001) asynchrony. Systolic and diastolic asynchrony were both present in 41% patients, but one-third had isolated diastolic asynchrony. Although diastolic delays increased with QRS duration, 42% patients with narrow QRS presented with diastolic asynchrony. Conversely, 27% patients with large QRS had no diastolic asynchrony. Forty-two patients underwent CRT. Incidence of systolic intraventricular asynchrony decreased from 71% to 33% after CRT (p < 0.0001), but diastolic asynchrony decreased only from 81% to 55% (p < 0.0002). Cardiac resynchronization therapy induced new diastolic asynchrony in eight patients. Conclusions: Diastolic asynchrony is weakly correlated with QRS duration, is more frequent than systolic asynchrony, and may be observed alone. Diastolic asynchrony is less improved by CRT than systolic. Persistent diastolic asynchrony may explain some cases of lack of improvement after CRT despite good systolic resynchronization. [Copyright &y& Elsevier]