Clinical Characterization of Arrhythmia-Induced Cardiomyopathy in Patients With Tachyarrhythmia and Idiopathic Heart Failure.

BACKGROUND: Arrhythmia-induced cardiomyopathy (AIC) is a known entity, but prospective evidence for its characterization is limited. OBJECTIVES: This study aimed to: 1) determine the relative frequency of the pure form of AIC in the clinically relevant cohort of patients with newly diagnosed, otherwise unexplained left ventricular systolic dysfunction (LVSD) and tachyarrhythmia; 2) assess the time to recovery from LVSD; and 3) identify parameters for an early diagnosis of AIC. METHODS: Patients were prospectively included, underwent effective rhythm restoration, and were followed-up at 2, 4, and 6 months to evaluate clinical characteristics, biomarkers, and cardiac imaging including cardiac magnetic resonance imaging. Patients with recurred arrhythmia were excluded from analysis. RESULTS: 41 of 50 patients were diagnosed with AIC 6 months after rhythm restoration. Left ventricular (LV) ejection fraction increased 2 months after rhythm restoration from 35.4% ± 8.2% to 52.7% ± 8.0% in AIC patients vs 37.0% ± 9.5% to 43.3% ± 7.0% in non-AIC patients. From month 2 to 6, LV ejection fraction continued to increase in AIC patients (57.2% ± 6.1%; P < 0.001) but remained stable in non-AIC patients (44.0% ± 7.8%; P = 0.628). Multivariable logistic regression analysis revealed that lower LV end-diastolic diameter at baseline could be used for early diagnosis of AIC, whereas biomarkers and other morphological or functional parameters, including late LV gadolinium enhancement, did not show suitability for early diagnosis. CONCLUSIONS: We observed a high prevalence of AIC in patients with otherwise unexplained LVSD and concomitant tachyarrhythmia, suggesting that this condition may be underdiagnosed in clinical practice. Most patients recovered fast, within months, from LVSD. A low initial LV end-diastolic diameter may constitute an early marker for diagnosis of AIC.

[Chest pain and cardiovascular diseases in women : Diagnostics and treatment]. / Brustschmerz und kardiovaskuläre Erkrankungen bei Frauen : Diagnostik und Therapie.

Cardiovascular diseases (CVD) are the leading cause of global mortality not only in men but also in women. The incidence of CVD significantly increases in women, especially after the menopause. Sex and gender differences in the incidence, prevalence and mortality of CVD are due to hormonal, anatomical, and sociocultural differences. As part of the primary and secondary prevention of coronary heart disease (CHD), risk factors specific for women, such as autoimmune diseases and pregnancy-associated diseases (e.g., gestational diabetes and pre-eclampsia) should also be taken into account in addition to the classical cardiovascular risk factors. Furthermore, in women with angina pectoris it should be considered that women in particular frequently suffer from ischemia with nonobstructive coronary arteries (INOCA) that can be caused, for example, by coronary microvascular dysfunction (CMD) or coronary spasms. Based on this, the diagnostics should not be terminated in symptomatic women after coronary angiography with normal epicardial vessels. A targeted diagnostics for CMD and coronary spasms should be carried out at an early stage.

A multilocus genetic risk score for obesity: Association with BMI and metabolic alterations in a cohort with severe obesity.

Genome wide association studies have identified numerous single nucleotide polymorphisms (SNPs) associated with obesity, yet effect sizes of individual SNPs are small. Therefore, the aim of our study was to investigate whether a genetic risk score (GRS) comprising risk alleles of SNPs identified in the GIANT consortium meta-analyses shows association with body mass index (BMI) and other BMI related metabolic alterations in a cohort with an extreme phenotype. Genotyping of 93 SNPs was performed in 314 obese individuals (mean BMI 40.5 ± 7.8 kg/m², aged 45 ± 12 years), participating in a standardized weight reduction program, and in 74 lean controls (mean BMI 24.6 ± 3.3 kg/m², aged 41.7 ± 13.4 years). Allele numbers of all 93 SNPs were added to a GRS. Anthropometric parameters, parameters of glucose/insulin and lipid metabolism were assessed standardized after a 12 hours fast. GRS was significantly different between controls and obese individuals (unweighted GRS: 86.6 vs 89.0, P = .002; weighted GRS: 84.9 vs 88.3, P = .005). Furthermore, linear regression analysis showed significant associations of GRS with BMI ( P < .0001), weight ( P = .0005), waist circumference ( P = .0039), fat mass ( P < .0001) and epicardial fat thickness ( P = .0032), yet with small effect sizes ( r ² < 0.06). In conclusion, in our study GRS could differentiate between extreme obese and lean individuals, and was associated with BMI and its related traits, yet with small effect sizes.

The German CaRe high registry for familial hypercholesterolemia - Sex differences, treatment strategies, and target value attainment.

Background and aims: Familial hypercholesterolemia (FH) is among the most common genetic disorders in primary care. However, only 15% or less of patients are diagnosed, and few achieve the goals for low-density lipoprotein cholesterol (LDL-C). In this analysis of the German Cascade Screening and Registry for High Cholesterol (CaRe High), we examined the status of lipid management, treatment strategies, and LDL-C goal attainment according to the ESC/EAS dyslipidemia guidelines. Methods: We evaluated consolidated datasets from 1501 FH patients diagnosed clinically and seen either by lipid specialists or general practitioners and internists. We conducted a questionnaire survey of both the recruiting physicians and patients. Results: Among the 1501 patients, 86% regularly received lipid-lowering drugs. LDL-C goals were achieved by 26% and 10% of patients with atherosclerotic cardiovascular disease (ASCVD) according to the 2016 and 2019 ESC/EAS dyslipidemia guidelines, respectively. High intensity lipid-lowering was administered more often in men than in women, in patients with ASCVD, at higher LDL-C and in patients with a genetic diagnosis of FH. Conclusions: FH is under-treated in Germany compared to guideline recommendations. Male gender, genetic proof of FH, treatment by a specialist, and presence of ASCVD appear to be associated with increased treatment intensity. Achieving the LDL-C goals of the 2019 ESC/EAS dyslipidemia guidelines remains challenging if pre-treatment LDL-C is very high.

Improvement of obstructive sleep apnea does not rescue left atrial enlargement in obese participants of a multimodal weight reduction program.

The aim of our study was to investigate the effect of obstructive sleep apnea (OSA) and its weight loss related improvement on left atrial (LA) area in individuals with severe obesity participating in a multimodal weight reduction (WR) program. Participants with obesity (body mass index, BMI, 40.2 ± 7.3 kg/m2) underwent a 1-year WR program. Phenotyping was performed at baseline and after 12 months. Individuals were categorized according to their baseline apnea-hypopnea-index (AHI) into "no OSA" (AHI < 5) and "OSA" (AHI ≥ 5). From a total of 84 study participants, 69 completed the program. Average WR was 19.0 ± 15.7 kg after 12 months. Participants with obesity and OSA had a larger LA area at baseline as compared to participants with obesity but without OSA (22.4 ± 5.6 vs 18.8 ± 3.8 cm2; P = .008). Linear regression showed significant associations of AHI and BMI with LA area. In contrast, despite a significant decrease of AHI in participants with OSA as compared to those without OSA at 1 year follow up (ΔAHI was -12 ± 14) ΔLA area did not significantly differ between groups. Multivariable linear regression showed no significant association of ΔAHI or ΔBMI with ΔLA. In conclusion, the presence of obstructive sleep apnea contributes to LA enlargement on top of obesity in our study cohort. Yet, successful WR with subsequently improved OSA was not associated with an improvement of LA area.

Prevalences of cardiometabolic risk and lifestyle factors in young parents: evidence from a German birth cohort study.

BACKGROUND: Studies show that parents significantly impact their children's health through their cardiometabolic risk profile and health behavior. There is only little information about the prevalence of cardiometabolic risk factors and lifestyle factors among new parents yet. The aims of this study are therefore to evaluate the prevalences of cardiometabolic risk factors in parents of infants in Germany and to examine their lifestyle and health behavior. METHODS: In the KUNO-Kids health study, an ongoing birth cohort, parents (n = 930 mothers and 769 fathers) were asked about cardiometabolic risk factors (obesity/hypertension/type 2 diabetes mellitus) and lifestyle factors (dietary/sports/smoking habits/alcohol consumption) during the first year after the birth of their children via questionnaires. Chi-square as well as fisher exact tests were conducted to analyse associations between lifestyle factors and cardiometabolic risk factors. RESULTS: 34.2% of mothers and 58.5% of fathers were overweight or obese. In 11.8% of the families, at least one parent suffered from hypertension, in 2.4% from type 2 diabetes mellitus. One year after delivery, 8.5% of mothers were smoking, 6.9% showed a risky alcohol consumption (> 10 g/d). 16.0% of fathers were smoking 4 weeks after childbirth, 10.7% showed risky alcohol consumption (> 20 g/d). 21.6% of mothers carried out sports activity for more than 2 h a week then. Parental hypertension was linked to a higher prevalence of risky alcohol consumption, obesity to a lower prevalence of daily fruits consumption. CONCLUSIONS: Cardiometabolic risk factors were widespread among new parents with obesity and overweight having the highest prevalences. A considerable number of parents also practiced an unhealthy lifestyle showing that there is potential for improvement to promote the healthy development of their children.

Electroconvulsive therapy in a patient with hypertrophic cardiomyopathy: A case report.

The use of electroconvulsive therapy (ECT) in patients with underlying cardiac disease like hypertrophic cardiomyopathy (HCM) remains without satisfactory clinical guidelines. We provide a case report of successful application of ECT in a 43-year-old patient with bipolar disorder and comorbid HCM, including detailed diagnostic information and outlining key clinical considerations.

Usage of the wearable cardioverter-defibrillator during pregnancy.

Background: Pregnancy can trigger or aggravate the risk for life-threating arrhythmias in cardiac diseases. Pregnancy is associated with reluctance for implantable cardioverter-defibrillators (ICD) due to concerns about radiation. Thus, the wearable cardioverter-defibrillator (WCD) might be an option during pregnancy. Aim of the study was to collect experiences about the use of WCD in pregnancy. Methods and results: This study retrospectively included eight women who received a WCD during pregnancy. They suffered from ventricular tachycardia (VT) without known cardiac disease (n = 3), Brugada syndrome (n = 1), hypertrophic cardiomyopathy (n = 1), dilated cardiomyopathy (n = 1), non-compaction (n = 1), and survived sudden cardiac arrest during a preceding pregnancy (n = 1). WCD usage was started between 13 and 28 weeks of gestation. WCD wearing period ranged from 3 days to 30.9 weeks, WCD wearing time ranged from 13.0 to 23.7 h per day. Two women (25%) abandoned WCD already during pregnancy. Neither appropriate nor inappropriate WCD shocks were recorded. Antiarrhythmic management included beta-blockers (n = 5) and flecainide (n = 2). After delivery, ICD were implanted (n = 4), refused (n = 2) and estimated not necessary after successful catheter ablation (n = 2). Conclusion: Uneventful pregnancy is possible in women at risk for sudden cardiac death by interdisciplinary monitoring and diligent pharmacotherapy protected by the WCD. Since no WCD shocks were recorded, the effectiveness of WCD during pregnancy is still unclear. However, arrhythmia detection by WCD was very good despite the changed anatomy in pregnancy. Nevertheless, further studies are necessary to assess effectiveness of WCD in pregnant women. Furthermore, efforts should be made to increase the wearing adherence of WCD during pregnancy.

[Novel options to maximize oral lipid lowering treatment : Role of bempedoic acid in combination treatment]. / Neue Optionen zur Intensivierung der lipidsenkenden Therapie : Rolle von Bempedoinsäure in der Kombinationstherapie.

Epidemiological, randomized, controlled, clinical and genetic studies confirm that low-density lipoprotein cholesterol (LDL-C) is a causative factor for atherosclerotic diseases. The current European Society of Cardiology and European Atherosclerosis Society (ESC/EAS) guidelines on the management of dyslipidemia recommend a target LDL-C < 55 mg/dl and at least a 50% reduction in baseline LDL­C for high-risk patients; however, these target values are often not achieved in routine clinical practice, as shown by recent cross-sectional data from EUROASPIRE or DaVinci. Therefore, combination treatment is recommended, which, as with treatment of blood pressure, can improve the success of treatment. Bempedoic acid is a new substance, which is suitable for combination treatment and represents an alternative particularly for patients with statin-associated muscular symptoms. Bempedoic acid reduces LDL­C by approximately 25% in statin-naïve patients and by some 18% in addition to statins. In a fixed doses combination with ezetimibe, bempedoic acid can lower LDL­C by up to 45% in statin-naïve patients and by 38% (placebo-corrected) in addition to statins. Bempedoic acid is generally very well tolerated: however, it can lead to a reversible increase in uric acid. Occasionally, a slight decrease in hemoglobin has been documented. Therefore, it is recommended that not only changes in lipid levels but also uric acid and hematological parameters should be monitored in the first 3 months.

Gender differences in cardiometabolic health and disease in a cross-sectional observational obesity study.

BACKGROUND: Beyond the degree of adiposity, the pattern of fat distribution has a profound influence on cardiometabolic risk. It is unclear if sex differences in body fat distribution can potentially explain any sex differences in the prevalence of the metabolic syndrome (MetS) and in individual cardiometabolic risk factors among obese men and women. METHODS: In this cross-sectional analysis, 432 persons from the ongoing Obesity Weight Reduction Study (n = 356 obese, ØBMI 41 ± 8 kg/m2, and 76 non-obese, ØBMI 25 ± 3 kg/m2), were included. The relations of sex to MetS prevalence and selected cardiometabolic risk factors were assessed using univariate and multivariate adjusted regression models. RESULTS: In crude analyses, %fat mass and the fat mass/lean mass ratio were significantly higher in women than in men, regardless of increasing obesity categories, from normal weight to grade-3-obesity. In contrast, markers of abdominal obesity, such as waist circumference and waist-to-hip ratio were higher in men than in women, despite similar BMI. The prevalence of the MetS was higher in obese men than in women (67.6 vs. 45.0%, p < 0.0001), particularly in younger individuals < 40 years (72.5 vs. 36.8%, p < 0.0001), but "metabolically healthy obesity" (BMI ≥ 30, no other NCEP ATPIII MetS component) was more common in women than in men (15.6 vs. 4.1%, p < 0.0001). After adjusting for age, %body fat and height, sex differences were observed for HDL-cholesterol (p < 0.001), triglycerides (p < 0.001), fasting glucose (p = 0.002), insulin and HOMA-IR levels (p < 0.001), ALAT (p < 0.001), adiponectin (p < 0.001), and sE-selectin (p = 0.005). In contrast, crude sex differences in other variables, such as leptin levels (68 ± 4 in obese women vs. 33 ± 2 µg/L in men, p < 0.0001), disappeared after accounting for differences in %body fat (least-squares means of leptin: 52 ± 4 vs. 55 ± 6 µg /L, p = 0.740). A logistic regression model adjusting for age and lifestyle factors revealed a lower risk of having MetS for women as compared to men (OR = 0.38[0.22-0.60]). That risk estimate did not materially alter after adding BMI to the model. In contrast, no statistically significant association between sex and MetS prevalence was observed after adding waist circumference and adiponectin to the model (OR = 1.41[0.59-3.36]). CONCLUSIONS: Different body fat distribution patterns, particularly abdominal adiposity, adiponectin, and related biomarkers, may contribute to sex differences in cardiometabolic risk factors and to the prevalence of the MetS.

Successful weight loss reduces endothelial activation in individuals with severe obesity participating in a multimodal weight loss program.

INTRODUCTION: Endothelial dysfunction is a very common finding in obesity and metabolic syndrome. The aim of our study was to investigate if longterm weight reduction (WR) success may reverse endothelial activation in individuals with severe obesity participating in a multimodal WR program. METHODS: Participants with obesity (øBMI 40.3 ±7.5 kg/m2) underwent a standardized non-surgical 1-year WR program. Carotid artery studies and determination of endothelial function biomarkers were performed at baseline and after 1 year. Individuals were dichotomized in "successful WR" (% WR≥10% of initial body weight) and "failed WR" (% WR<10% of initial body weight). RESULTS: From 191 people with obesity, 115 achieved successful WR. Compared to controls without obesity (n=44) participants with obesity had higher carotid intima media thickness as well as higher sICAM-1, sE-selectin, MMP-9, hsCRP and IL-6 levels. After 12 months follow up delta values of inflammation and endothelial adhesion markers were significantly different between participants with obesity and successful WR and participants with obesity and failed WR, in favour of the successful WR group (mean ± standard deviation): ΔhsCRP (-5.2 mg/L ±7.8 vs. 1.1 mg/L ±5.1, P<0.001; Padj=0.009), ΔIL-6 (-1.0 pg/mL ±3.4 vs. 0.5 pg/mL ±2.6, P<0.001; Padj=0.057), ΔsE-selectin (-19.0 ng/mL ±24.4 vs. 39.2 ng/mL ±20.3, P<0.001; Padj<0.001), ΔsICAM-1 (-26.4 ng/mL ±68.8 vs. 10.6 ng/mL ±73.9, P=0.004; Padj=0.805) and ΔoxLDL (-4 mg/dL ±30 vs. 5 mg/dL ±25, P=0.004; Padj=0.473). In linear regression analysis reduction of BMI was significantly associated with improvement of several endothelial dysfunction biomarkers with the strongest effects for ΔsE-selectin and ΔhsCRP. CONCLUSION: Our data corroborate the finding that obesity leads to endothelial dysfunction. Furthermore, successful non-surgical WR may at least partially reverse endothelial activation implicating cardiovascular health benefits of WR in people with severe obesity.

Association between Single Nucleotide Polymorphisms and Weight Reduction in Behavioural Interventions-A Pooled Analysis.

Knowledge of the association between single nucleotide polymorphisms (SNPs) and weight loss is limited. The aim was to analyse whether selected obesity-associated SNPs within the fat mass and obesity-associated (FTO), transmembrane protein 18 (TMEM18), melanocortin-4 receptor (MC4R), SEC16 homolog B (SEC16B), and brain-derived neurotrophic factor (BDNF) gene are associated with anthropometric changes during behavioural intervention for weight loss. genetic and anthropometric data from 576 individuals with overweight and obesity from four lifestyle interventions were obtained. A genetic predisposition score (GPS) was calculated. Our results show that study participants had a mean age of 48.2 ± 12.6 years and a mean baseline body mass index of 33.9 ± 6.4 kg/m2. Mean weight reduction after 12 months was -7.7 ± 10.9 kg. After 12 months of intervention, the MC4R SNPs rs571312 and rs17782313 were significantly associated with a greater decrease in body weight and BMI (p = 0.012, p = 0.011, respectively). The investigated SNPs within the other four genetic loci showed no statistically significant association with changes in anthropometric parameters. The GPS showed no statistically significant association with weight reduction. In conclusion there was no consistent evidence for statistically significant associations of SNPs with anthropometric changes during a behavioural intervention. It seems that other factors play a more significant in weight management than the investigated SNPs.

SNP dependent modulation of circulating miRNAs from the miR25/93/106 cluster in patients undergoing weight loss.

BACKGROUND: Diet induced weight loss represents an intervention for obesity to prevent associated diseases. However there is considerable inter-individual variation. Single nucleotide polymorphisms (SNPs) and plasma miRNA might be contributing factors. We therefore hypothesized that changes in the miRNA pattern during weight loss depend on the SNP genotype. METHODS: Plasma miRNA profiles from 12 patients were determined before and after a three month weight loss intervention by Illumina sequencing. 46 further patients were analyzed by qPCR. SNP genotypes were determined on the Sequenom iPLEX platform. RESULTS: Samples before and after weight loss were analyzed by miRNA-seq and delta miRNA levels ranked according to p-value. Levels of miRNAs 25, 93 and 106 that are expressed from a common genomic cluster were reduced after weight loss. Those results were substantiated in a qPCR analysis of 46 additional patients. This is in accordance with mouse data showing a functional involvement of this cluster in obesity. Correlation of the changes in miRNA abundance with SNP genotypes revealed a statistical association of all three miRNAs with known obesity susceptibility SNPs. CONCLUSION: Diet induced weight loss leads to SNP dependent modulation of miRNAs from the miR 25/93/106 gene cluster in humans.

Design of the SILICOFCM study: Effect of sacubitril/valsartan vs lifestyle intervention on functional capacity in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease with a broad spectrum of disease severity. HCM ranges from a benign course to a progressive disorder characterized by angina, heart failure, malignant arrhythmia, syncope, or sudden cardiac death. So far, no medical treatment has reliably shown to halt or reverse progression of HCM or to alleviate its symptoms. While the angiotensin receptor neprilysin inhibitor sacubitril/valsartan has shown to reduce mortality and hospitalization in heart failure with reduced ejection fraction, data on its effect on HCM are sparse. HYPOTHESIS: A 4-month pharmacological (sacubitril/valsartan) or lifestyle intervention will significantly improve exercise tolerance (ie, peak oxygen consumption) in patients with nonobstructive HCM compared to the optimal standard therapy (control group). METHODS: SILICOFCM is a prospective, multicenter, open-label, randomized, controlled, three-arm clinical trial (NCT03832660) that will recruit 240 adult patients with a confirmed diagnosis of nonobstructive HCM. Eligible patients are randomized to sacubitril/valsartan, lifestyle intervention (physical activity and dietary supplementation with inorganic nitrate), or optimal standard therapy alone (control group). The primary endpoint is the change in functional capacity (ie, peak oxygen consumption). Secondary endpoints include: (a) Change in cardiac structure and function as assessed by transthoracic echocardiography and cardiac magnetic resonance (MRI imaging), (b) change in biomarkers (ie, CK, CKMB, and NT-proBNP), (c) physical activity, and (d) quality of life. RESULTS: Until December 2019, a total of 41 patients were recruited into the ongoing SILICOFCM study and were allocated to the study groups and the control group. There was no significant difference in key baseline characteristics between the three groups. CONCLUSION: The SILICOFCM study will provide novel evidence about the effect of sacubitril/valsartan or lifestyle intervention on functional capacity, clinical phenotype, injury and stretch activation markers, physical activity, and quality of life in patients with nonobstructive HCM.

The adipo-fibrokine activin A is associated with metabolic abnormalities and left ventricular diastolic dysfunction in obese patients.

AIMS: Left ventricular diastolic dysfunction (LVDD) is common in obese subjects, and a relationship between epicardial adipose tissue (EAT), increased adipocytokines, and cardiovascular diseases has been reported. This study sought to examine as to whether the adipo-fibrokine activin A is a link between increased EAT, the metabolic syndrome (MetS), and LVDD in severely obese subjects. METHODS AND RESULTS: In 236 obese subjects (ø body mass index 39.8 ± 7.9 kg/m2 ) with a variable degree of the MetS and in 60 healthy non-obese controls (ø body mass index 24.8 ± 3.4 kg/m2 ), serum activin A levels were measured and correlated with parameters of the MetS, epicardial fat thickness (EFT), and echocardiographic parameters of LVDD. Activin A levels were higher in obese than in non-obese subjects (362 ± 124 vs. 301 ± 94 pg/mL, P = 0.0004), increased with the number of MetS components (from 285 ± 82 with no MetS component, 323 ± 94 with one or two MetS components, to 403 ± 131 pg/mL with ≥3 MetS components, P < 0.0001) and correlated with EFT (r = 0.41, P < 0.001). Furthermore, activin A levels were related to several parameters of LVDD [e.g. left atrial size (382 ± 117 vs. 352 125 pg/mL, P = 0.024), E/e' (394 ± 108 vs. 356 ± 127 pg/mL, P = 0.005)]. LVDD was highest in MetS obese subjects with high EFT (44.3%) compared with MetS obese subjects with low EFT (27.0%), non-MetS obese subjects with high EFT (24.2%), and non-MetS obese subjects with low EFT (10.6%, P < 0.0001). CONCLUSIONS: In severe obesity, activin A was significantly related to EFT, MetS, and LVDD, implicating MetS-related alterations in the secretory profile of EAT in the pathogenesis of obesity-related heart disease.

Coronary Artery Ectasia Are Frequently Observed in Patients With Bicuspid Aortic Valves With and Without Dilatation of the Ascending Aorta.

BACKGROUND: The presence of coronary artery ectasia (CAE) is influenced by genetic factors and related to the presence of aneurysms in other vascular beds. Bicuspid aortic valve (BAV) disease is frequently accompanied by ascending aortic aneurysm. Because the aortic valve and the proximal parts of the coronary arteries share a common embryonic origin, we hypothesized that CAE is associated with BAV disease. METHODS AND RESULTS: One hundred seventy-seven patients with suspected aortic valve disease (n=94 BAV, n=83 tricuspid aortic valve) underwent both cardiac magnetic resonance imaging and coronary angiography. To confirm the association of CAE with BAV, the frequency of CAE was evaluated in an in-house BAV registry (n=600, n=231 with available coronary angiogram) and compared with the frequency of CAE in the German Myocardial Infarction (MI) Family Study, in which the heritability of CAE was formerly established (n=899). Furthermore, the frequency of CAE was investigated in an observational registry of real-life patients undergoing coronary angiography for clinically indicated reasons (n=3.097) and in a subgroup of the KORA MI study (Cooperative Health Research in the Region of Augsburg), which is a population-based MI registry (n=403).Compared with tricuspid aortic valve disease, CAE occurred more than twice as frequently in cardiac magnetic resonance-confirmed BAV disease (17% versus 44%; P<0.0001) and CAE was observed similarly often in subjects with BAV with (37%) and without (54%, P=0.11) ascending aortic pathology. The common appearance of CAE in patients with BAV could be independently confirmed in the BAV registry (frequency 37%), whereas CAE was found less frequently in family history of positive MI patients (21%), sporadic MI without familial disposition (10%), and rarely in unrelated real-life catheterization patients (6%). CONCLUSIONS: To our knowledge, our data show for the first time that ectatic coronary artery disease is a common appearance of BAV disease with and without ascending aortic ectasia.

Relation Between Obesity, Metabolic Syndrome, Successful Long-Term Weight Reduction, and Right Ventricular Function.

This study sought to examine the relationships between right ventricular (RV) function and geometry, morbid obesity with and without the metabolic syndrome, and the effect of long-term weight loss. Obese (n = 153, BMI 41.2 ± 8.7 kg/m(2)) and healthy non-obese control subjects (n = 38, BMI 25.5 ± 3.3 kg/m(2)) of similar age and gender distribution were prospectively studied during the course of a 1-year weight reduction program with echocardiography at baseline and after one year of follow up. Function and geometry of the right heart were evaluated by tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (TDI S'), RV myocardial performance index (TEI), RV end-diastolic (RVEDD) and end-systolic diameter (RVESD), area of the right atrium (RAA), and systolic pulmonary artery pressure (PAP). Whereas parameters of systolic and diastolic LV function were significantly worse in the obese subjects than those in the non-obese subjects (EF 66 ± 6 versus 69 ± 6%, P = 0.004; E/E' 7.4 ± 2.5 versus 6.3 ± 2.6, P = 0.010), parameters of RV function (TAPSE 25.6 ± 4.5 versus 25.1 ± 3.5 mm, P = 0.528; TDI S' 13.5 ± 2.9 versus 13.8 ± 2.9 mm/second, P = 0.553; TEI 0.25 ± 0.13 versus 0.28 ± 0.09, P = 0.283) as well as geometry measurements were comparable between the obese and non-obese participants and also in obese subjects with full blown metabolic syndrome. Additionally, successful weight reduction did not alter the RV parameters. Nevertheless, in the few obese subjects with RV dysfunction (n = 7), metabolic syndrome parameters were more pronounced than in obese with normal RV function.Morbid obesity with and without the metabolic syndrome is accompanied by an impaired LV systolic and diastolic function. In contrast, RV function appears to be less affected by obesity independent of the presence of the metabolic syndrome.

Generation of highly purified human cardiomyocytes from peripheral blood mononuclear cell-derived induced pluripotent stem cells.

Induced pluripotent stem (iPS) cells have an enormous potential for physiological studies. A novel protocol was developed combining the derivation of iPS from peripheral blood with an optimized directed differentiation to cardiomyocytes and a subsequent metabolic selection. The human iPS cells were retrovirally dedifferentiated from activated T cells. The subsequent optimized directed differentiation protocol yielded 30-45% cardiomyocytes at day 16 of differentiation. The derived cardiomyocytes expressed appropriate structural markers like cardiac troponin T, α-actinin and myosin light chain 2 (MLC2V). In a subsequent metabolic selection with lactate, the cardiomyocytes content could be increased to more than 90%. Loss of cardiomyocytes during metabolic selection were less than 50%, whereas alternative surface antibody-based selection procedures resulted in loss of up to 80% of cardiomyocytes. Electrophysiological characterization confirmed the typical cardiac features and the presence of ventricular, atrial and nodal-like action potentials within the derived cardiomyocyte population. Our combined and optimized protocol is highly robust and applicable for scalable cardiac differentiation. It provides a simple and cost-efficient method without expensive equipment for generating large numbers of highly purified, functional cardiomyocytes. It will further enhance the applicability of iPS cell-derived cardiomyocytes for disease modeling, drug discovery, and regenerative medicine.

Successful weight reduction improves left ventricular diastolic function and physical performance in severe obesity.

Obesity and the metabolic syndrome (MetS) are risk factors for left ventricular diastolic dysfunction (LVDD). However, little is known about the impact of successful weight reduction (WR) on diastolic function and physical performance.Obese subjects (øBMI 40.2 ± 8.6 kg/m(2)) underwent a 1-year WR program comprising diet and lifestyle components. Echocardiography and exercise capacity (6-minute walk) were performed at baseline and after 1 year. The distribution of weight reduction was split at the sample median and subjects were dichotomized in "successful WR" (% WR ≥ median, corresponding to a weight loss of 8%) and "failed-WR" (% WR < median).From a total of 188 obese subjects, 71 had LVDD at baseline. Obese patients with successful WR improved their MetS alterations, including fasting glucose, insulin, lipids, adipokines, blood pressure levels, and epicardial fat thickness. The same was not true for obesity with failed WR. Subjects with successful WR demonstrated significant improvement in echocardiographic LVDD parameters (median [interquartile range]): Δe' (2,5 [-1.0, 4.7], P < 0.01), Δe'/a' (0.34 [0.07, 079], P < 0.01), ΔE/e' (-1.14 [-2.72, -0.54], P < 0.05), ΔE/A (0.08 [-0.04, 0.26], P < 0.05), ΔArd-Ad (-28 [-54, -4], P < 0.01), and 6-minute walk distance (65 [19, 135], P < 0.01). Improvement of ≥ 2 LVDD criteria was accomplished in 30% of subjects with WR versus 10% without (P = 0.009). Using multivariable regression analysis, reduction of epicardial fat thickness was particularly predictive for the improvement of diastolic function.In summary, in severe obesity, successful long-term WR was associated with improved LV diastolic function and exercise capacity.