Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is characterized by fibrofatty infiltration of the myocardium and ventricular arrhythmias that may lead to sudden cardiac death. It ...has been observed that male patients develop the disease earlier and present with more severe phenotypes as compared to females. Thus, we hypothesized that serum levels of sex hormones may contribute to major arrhythmic cardiovascular events (MACE) in patients with ARVC/D.
The serum levels of five sex hormones, sex hormone-binding globulin, high sensitivity troponin T, pro-brain natriuretic peptide, cholesterol, triglycerides, insulin, and glucose were measured in 54 ARVC/D patients (72% male). Twenty-six patients (48%) experienced MACE. Total and free testosterone levels were significantly increased in males with MACE as compared to males with a favourable outcome, whereas estradiol was significantly lower in females with MACE as compared to females with a favourable outcome. Increased testosterone levels remained independently associated with MACE in males after adjusting for age, body mass index, Task Force criteria, ventricular function, and desmosomal mutation status. Furthermore, an induced pluripotent stem cell-derived ARVC/D cardiomyocyte model was used to investigate the effects of sex hormones. In this model, testosterone worsened and estradiol improved ARVC/D-related pathologies such as cardiomyocyte apoptosis and lipogenesis, strongly supporting our clinical findings.
Elevated serum testosterone levels in males and decreased estradiol levels in females are independently associated with MACE in ARVC/D, and directly influence disease pathology. Therefore, determining the levels of sex hormones may be useful for risk stratification and may open a new window for preventive interventions.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease, which is characterized by fibro-fatty replacement of predominantly the right ventricle (RV). The disease ...can result in ventricular tachyarrhythmias and sudden cardiac death. Our understanding of the pathophysiology and clinical expressivity of ARVC has been continuously evolving. The diagnosis can be challenging due to its variable expressivity, incomplete penetrance and the lack of specific diagnostic criteria. Idiopathic RV outflow tract tachycardia, Brugada Syndrome, athlete's heart, dilated cardiomyopathy, myocarditis, cardiac sarcoidosis, congenital aneurysms and diverticula may mimic clinical phenotypes of ARVC. This review aims to provide an update on the differential diagnosis of ARVC.
An aortic aneurysm is defined as a balloon-shaped bulging of all three histologic components of the aortic vessel walls (intima, media and adventitia). This dilation results from vessel weakening ...owing to remodeling, i.e. due to cystic degeneration of the Tunica media (Marfan), progression of atherosclerosis or presence of a bicuspid aortic valve. The growth rate of the aortic diameter varies from patient to patient and may progress until the aneurysm ultimately ruptures. The role of hemodynamics, i.e. blood flow patterns, and shear stresses that are supposed to intensify during aneurysm growth are not yet fully understood, but thought to play a key role in the enlargement process. The aim of this study is to characterize the aortic blood flow in a silicone model of a pathological aorta with ascending aneurysm, to analyze the differences in the blood flow pattern compared to a healthy aortic model, and to single out possible blood flow characteristics measurable using phase contrast magnetic resonance imaging (MRI) that could serve as indicators for aneurysm severity. MRI simulations were performed under physiological, pulsatile flow conditions using data obtained from optical three dimensional particle tracking measurements. In comparison to the healthy geometry, elevated turbulence intensity and pressure loss are measured in the diseased aorta, which we propose as a complimentary indicator for assessing the aneurysmal severity. Our results shed a light on the interplay between the blood flow dynamics and their contribution to the pathophysiology and possible role for future risk assessment of ascending aortic aneurysms.
Cardiac injury is a common complication of the coronavirus disease 2019 (COVID-19), and is associated with adverse clinical outcomes. In this study, we aimed to reveal the association of cardiac ...injury with coagulation dysfunction. We enrolled 181 consecutive patients who were hospitalized with COVID-19, and studied the clinical characteristics and outcome of these patients. Cardiac biomarkers high-sensitivity troponin I (hs-cTnI), myohemoglobin and creatine kinase-myocardial band (CK-MB) were assessed in all patients. The clinical outcomes were defined as hospital discharge or death. The median age of the study cohort was 55 (IQR, 46-65) years, and 102 (56.4%) were males. Forty-two of the 181 patients (23.2%) had cardiac injury. Old age, high leukocyte count, and high levels of aspartate transaminase (AST), D-dimer and serum ferritin were significantly associated with cardiac injury. Multivariate regression analysis revealed old age and elevated D-dimer levels as being strong risk predictors of in-hospital mortality. Interleukin 6 (IL6) levels were comparable in patients with or without cardiac injury. Serial observations of coagulation parameters demonstrated highly synchronous alterations of D-dimer along with progression to cardiac injury. Cardiac injury is a common complication of COVID-19 and is an independent risk factor for in-hospital mortality. Old age, high leukocyte count, and high levels of AST, D-dimer and serum ferritin are significantly associated with cardiac injury, whereas IL6 are not. Therefore, the pathogenesis of cardiac injury in COVID-19 may be primarily due to coagulation dysfunction along with microvascular injury.
Background: The cardiac system is a combination of a complex structure, various cells, and versatile specified functions and sophisticated regulatory mechanisms. Moreover, cardiac diseases that ...encompass a wide range of endogenous conditions, remain a serious health burden worldwide. Recent genome-wide profiling techniques have taken the lead in uncovering a new realm of cell types and molecular programs driving physiological and pathological processes in various organs and diseases. In particular, the emerging technique single-cell RNA sequencing dominates a breakthrough in decoding the cell heterogeneity, phenotype transition, and developmental dynamics in cardiovascular science.
Conclusion: Herein, we review recent advances in single cellular studies of cardiovascular system and summarize new insights provided by single-cell RNA sequencing in heart developmental sciences, stem-cell researches as well as normal or disease-related working mechanisms.
Abstract
Cardiovascular diseases are the main cause of sudden cardiac death (SCD) in developed and developing countries. Inherited cardiac channelopathies are linked to 5–10% of SCDs, mainly in the ...young. Short QT syndrome (SQTS) is a rare inherited channelopathy, which leads to both atrial and ventricular tachyarrhythmias, syncope, and even SCD. International European Society of Cardiology guidelines include as diagnostic criteria: (i) QTc ≤ 340 ms on electrocardiogram, (ii) QTc ≤ 360 ms plus one of the follwing, an affected short QT syndrome pathogenic gene mutation, or family history of SQTS, or aborted cardiac arrest, or family history of cardiac arrest in the young. However, further evaluation of the QTc ranges seems to be required, which might be possible by assembling large short QT cohorts and considering genetic screening of the newly described pathogenic mutations. Since the mechanisms underlying the arrhythmogenesis of SQTS is unclear, optimal therapy for SQTS is still lacking. The disease is rare, unclear genotype–phenotype correlations exist in a bevy of cases and the absence of an international short QT registry limit studies on the pathophysiological mechanisms of arrhythmogenesis and therapy of SQTS. This leads to the necessity of experimental models or platforms for studying SQTS. Here, we focus on reviewing preclinical SQTS models and platforms such as animal models, heterologous expression systems, human-induced pluripotent stem cell-derived cardiomyocyte models and computer models as well as three-dimensional engineered heart tissues. We discuss their usefulness for SQTS studies to examine genotype–phenotype associations, uncover disease mechanisms and test drugs. These models might be helpful for providing novel insights into the exact pathophysiological mechanisms of this channelopathy and may offer opportunities to improve the diagnosis and treatment of patients with SQT syndrome.
Arrhythmogenic cardiomyopathy (ACM) is a rare inherited cardiomyopathy characterized as fibro-fatty replacement, and a common cause for sudden cardiac death in young athletes. Development of heart ...failure (HF) has been an under-recognized complication of ACM for a long time. The current clinical management guidelines for HF in ACM progression have nowadays been updated. Thus, a comprehensive review for this great achievement in our understanding of HF in ACM is necessary. In this review, we aim to describe the research progress on epidemiology, clinical characteristics, risk stratification and therapeutics of HF in ACM.
Background: The wearable cardioverter–defibrillator (WCD) has a built-in accelerometer, which allows tracking of patients’ physical activity by remote monitoring. It is unclear whether WCD-measured ...physical activity, step count, and heart rate correlate with established tools for the assessment of cardiopulmonary fitness such as the 6-min walk test (6MWT). Objective: To correlate measurements of patient physical activity through the WCD with a supervised 6MWT during in-patient cardiac rehabilitation (CR) and to allow their use as surrogate parameters of cardiopulmonary fitness in an out-patient setting. Methods: Consecutive patients with a history of WCD use treated at our center and an in-patient CR following an index hospitalization were included. Baseline characteristics, measurements of WCD accelerometer (median daily step count, median daily activity level), median daily heart rate, and clinically supervised 6MWT at admission and discharge of CR were obtained. Results: Forty-one patients with a mean age of 55.5 (±11.5) years were included. Thirty-five patients (85.4%) were male and 28 patients (68%) had a primary prophylactic WCD-indication. The most common underlying heart diseases were ischemic heart disease (24 patients 58.6%) and dilated cardiomyopathy (13 patients, 31.7%). Median CR duration was 20 (IQR 19.75–26.25) days. 6MWT distance increased from a mean of 329 m (±107) to 470 m (±116) during CR (p < 0.0001). The median daily step count and activity level increased significantly, from 5542 steps (IQR 3718–7055) to 8778 (IQR 6229–12,920, p < 0.0001) and median 117 × 106 (IQR 96 × 106–142 × 106) threshold value exceedance (TVE) to 146 × 106 TVE (IQR 110 × 106–169 × 106, p < 0.0001), respectively. The median heart rate was 74.9 bpm (IQR 65.8–84.5) and 70.2 (IQR 64.1–77.3, p = 0.09) at admission and discharge, respectively. Of all three parameters, median daily step count showed the best correlation to the results of the 6MWT at admission and discharge (r = 0.32, p = 0.04 and 0.37, p = 0.02, respectively). Conclusions: Remote monitoring of median daily step count as assessed by the WCD’s accelerometer showed positive correlation with the 6MWT and could serve as a surrogate for cardiopulmonary exercise capacity. Assessment of daily step count and activity level measured remotely by the WCD could help to tailor optimal exercise instruction for patients not attending CR.
Patients at high risk for sudden cardiac death (SCD) may benefit from wearable cardioverter defibrillators (WCD) by avoiding immediate implantable cardioverter defibrillator (ICD) implantation. ...Different factors play an important role including patient selection, compliance and optimal drug treatment. We aimed to present real world data from 4 centers from Germany and Switzerland. Between 04/2012 and 03/2019, 708 patients were included in this registry. Patients were followed up over a mean time of 28 ± 35.5 months. Outcome data including gender differences and different etiologies of cardiomyopathy were analyzed. Out of 708 patients (81.8% males, mean age 61.0 ± 14.6), 44.6% of patients had non-ischemic cardiomyopathy, 39.8% ischemic cardiomyopathy, 7.9% myocarditis, 5.4% prior need for ICD explantation and 2.1% channelopathy. The mean wear time of WCD was 21.2 ± 4.3 h per day. In 46% of patients, left ventricular ejection fraction (LVEF) was > 35% during follow-up. The younger the patient was, the higher the LVEF and the lower the wear hours per day were. The total shock rate during follow-up was 2.7%. Whereas an appropriate WCD shock was documented in 16 patients (2.2%), 3 patients received an inappropriate ICD shock (0.5%). During follow-up, implantation of a cardiac implantable electronic device was carried out in 34.5% of patients. When comparing German patients (n = 516) to Swiss patients (n = 192), Swiss patients presented with longer wear days (70.72 ± 49.47 days versus 58.06 ± 40.45 days; p = 0.001) and a higher ICD implantation rate compared to German patients (48.4% versus 29.3%; p = 0.001), although LVEF at follow-up was similar between both groups. Young age is a negative independent predictor for the compliance in this large registry. The most common indication for WCD was non-ischemic cardiomyopathy followed by ischemic cardiomyopathy. The compliance rate was generally high with a decrease of wear hours per day at younger age. Slight differences were found between Swiss and German patients, which might be related to differences in mentality for ICD implantation.
Background
ECG criteria differentiating Takotsubo cardiomyopathy (TTC) from mainly anterior myocardial infarction (MI) have been suggested; however, this was in small patient populations.
Methods and ...Results
Twelve‐lead admission ECGs of consecutive 200 TTC and 200 MI patients were compared in dichotomized groups based on the presence or absence of ST‐elevation MI (STEMI versus STE‐TTC and non‐ST elevation MI versus non ST‐elevation‐TTC). When comparing STEMI and STE‐TTC, ST‐elevation in –aVR was characteristic of STE‐TTC with a sensitivity/specificity of 43% and 95%, positive predictive value (PPV) 91%, and a negative predictive value (NPV) 62% (P<0.001); when ST‐elevation in –aVR is accompanied by ST‐elevation in inferior leads, sensitivity/specificity were 14% and 98% (PPV was 89% and NPV 52%) (P=0.001), and 12% and 100% when associated with ST‐elevation in anteroseptal leads (PPV 100%, NPV 52%) (P<0.001). On the other hand, STEMI was characterized by ST‐elevation in aVR (sensitivity/specificity of 31% and 95% P<0.001, PPV 85% and NPV 59%) and ST‐depression in V2‐V3‐V4 (sensitivity/specificity of 24% and 100% P<0.001, PPV 100% and NPV 76%). When comparing non‐ST elevation MI and non ST‐elevation‐TTC, T‐inversion in leads I‐aVL‐V5‐V6 had a sensitivity/specificity of 17% and 97% for non ST‐elevation‐TTC (PPV 83% and NPV 55%) (P<0.001), and ST‐elevation in –aVR with T‐inversion in any lead was also specific for non ST‐elevation‐TTC (sensitivity/specificity of 8% and 100%, PPV 100% and NPV 53%) (P=0.006). In non‐ST elevation MI patients, the presence of ST‐depression in V2‐V3 was specific (sensitivity/specificity of 11% and 99%, PPV 91% and NPV 51%) (P=0.01).
Conclusions
ECG on admission can differentiate between TTC and acute MI, with high specificity and positive predictive value.
Clinical Trial Registration
URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01947621.
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