Search

IntroductionIn recent years, high-density microelectrode arrays (HD-MEAs) have emerged as a valuable tool in preclinical research for characterizing the electrophysiology of human induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs). HD-MEAs enable the capturing of both extracellular and intracellular signals on a large scale, while minimizing potential damage to the cell. However, despite technological advancements of HD-MEAs, there is a lack of effective data-analysis platforms that are capable of processing and analyzing the data, particularly in the context of cardiac arrhythmias and drug testing.MethodsTo address this need, we introduce CardioMEA, a comprehensive data-analysis platform designed specifically for HD-MEA data that have been obtained from iPSCCMs. CardioMEA features scalable data processing pipelines and an interactive web-based dashboard for advanced visualization and analysis. In addition to its core functionalities, CardioMEA incorporates modules designed to discern crucial electrophysiological features between diseased and healthy iPSC-CMs. Notably, CardioMEA has the unique capability to analyze both extracellular and intracellular signals, thereby facilitating customized analyses for specific research tasks.Results and discussionWe demonstrate the practical application of CardioMEA by analyzing electrophysiological signals from iPSC-CM cultures exposed to seven antiarrhythmic drugs. CardioMEA holds great potential as an intuitive, userfriendly platform for studying cardiac diseases and assessing drug effects.

ABSTRACT Much effort has been made to uncover the cellular heterogeneities of human hearts by single-nucleus RNA sequencing. However, the cardiac transcriptional regulation networks have not been systematically described because of the limitations in detecting transcription factors. In this study, we optimized a pipeline for isolating nuclei and conducting single-nucleus RNA sequencing targeted to detect a higher number of cell signal genes and an optimal number of transcription factors. With this unbiased protocol, we characterized the cellular composition of healthy human hearts and investigated the transcriptional regulation networks involved in determining the cellular identities and functions of the main cardiac cell subtypes. Particularly in fibroblasts, a novel regulator, PKNOX2, was identified as being associated with physiological fibroblast activation in healthy hearts. To validate the roles of these transcription factors in maintaining homeostasis, we used single-nucleus RNA-sequencing analysis of transplanted failing hearts focusing on fibroblast remodelling. The trajectory analysis suggested that PKNOX2 was abnormally decreased from fibroblast activation to pathological myofibroblast formation. Both gain- and loss-of-function in vitro experiments demonstrated the inhibitory role of PKNOX2 in pathological fibrosis remodelling. Moreover, fibroblast-specific overexpression and knockout of PKNOX2 in a heart failure mouse model induced by transverse aortic constriction surgery significantly improved and aggravated myocardial fibrosis, respectively. In summary, this study established a high-quality pipeline for single-nucleus RNA-sequencing analysis of heart muscle. With this optimized protocol, we described the transcriptional regulation networks of the main cardiac cell subtypes and identified PKNOX2 as a novel regulator in suppressing fibrosis and a potential therapeutic target for future translational studies.

BackgroundData on the use of the wearable cardioverter defibrillator in patients suffering from inherited and congenital heart disease are limited. Consequently, evidence for guideline recommendations in this patient population is lacking.MethodsIn total 1,675 patients were included in a multicenter registry of eight European centers. In the present cohort, we included 18 patients suffering from congenital and inherited heart disease.ResultsNine patients (50%) were male with a mean age of 41.3 ± 16.4 years. Four patients suffered from hypertrophic cardiomyopathy (HCM), four patients suffered from non-compaction cardiomyopathy (NCCM), two patients were diagnosed with arrhythmogenic right ventricular cardiomyopathy (ARVC) and one patient suffered from muscular dystrophy of the limb-girdle type with cardiac involvement, secondary cardiomyopathy. Three patients presented with Brugada syndrome (BrS). One patient suffered from long-QT syndrome type 1 (LQTS1). Furthermore, two patients had congenital heart defects and one patient suffered from cardiac sarcoidosis (CS). There were no appropriate/inappropriate shocks with the WCD in this cohort. One patient had recurrent self-limiting sustained ventricular tachycardia during the wear time, but actively inhibited a shock and was hospitalized. The compliance rate in this cohort was 77.8% with a mean wear time of 45.3 ± 26.9 days with a mean follow-up time of 570 ± 734 days. 55.6% (10/18) of the patients received an ICD after WCD wear time.ConclusionsThis retrospective study of patients with inherited and congenital heart disease shows that WCD use is not beneficial in the majority of patients with inherited and congenital heart disease.

Abstract Background Stereotactic arrhythmia radioablation (STAR) is delivered with a planning target volume (PTV) prescription dose of 25 Gy, mostly to the surrounding 75–85% isodose line. This means that the average and maximum dose received by the target is less than 35 Gy, which is the minimum threshold required to create a homogenous transmural fibrosis. Similar to catheter ablation, the primary objective of STAR should be transmural fibrosis to prevent heterogenous intracardiac conduction velocities and the occurrence of sustained ventricular arrhythmias (sVA) caused by reentry. We hypothesize that the current dose prescription used in STAR is inadequate for the long-term prevention of sVA and that a significant increase in dose is necessary to induce transmural scar formation. Objective A single arm, multi-center, phase II, dose escalation prospective clinical trial employing the i3 + 3 design is being conducted to examine the safety of a radiation dose-escalation strategy aimed at inducing transmural scar formation. The ultimate objective of this trial is to decrease the likelihood of sVA recurrence in patients at risk. Methods Patients with ischemic or non-ischemic cardiomyopathy and recurrent sVA, with an ICD and history of ≥ 1 catheter ablation for sVA will be included. This is a prospective, multicenter, one-arm, dose-escalation trial utilizing the i3 + 3 design, a modified 3 + 3 specifically created to overcome limitations in traditional dose-finding studies. A total of 15 patients will be recruited. The trial aims to escalate the ITV dose from 27.0 Gy to an ITV prescription dose-equivalent level of maximum 35.1 Gy by keeping the PTV prescription dose constant at 25 Gy while increasing the dose to the target (i.e. the VT substrate without PTV margin) by step-wise reduction of the prescribing isodose line (85% down to 65%). The primary outcome of this trial is safety measured by registered radiation associated adverse events (AE) up to 90 days after study intervention including radiation associated serious adverse events graded as at least 4 or 5 according to CTCAE v5, radiation pneumonitis or pericarditis requiring hospitalization and decrease in LVEF ≥ 10% as assessed by echocardiography or cardiac MRI at 90 days after STAR. The sample size was determined assuming an acceptable primary outcome event rate of 20%. Secondary outcomes include sVA burden at 6 months after STAR, time to first sVA recurrence, reduction in appropriate ICD therapies, the need for escalation of antiarrhythmic drugs, non-radiation associated safety and patient reported outcome measures such as SF-36 and EQ5D. Discussion DEFT-STAR is an innovative prospective phase II trial that aims to evaluate the optimal radiation dose for STAR in patients with therapy-refractory sVA. The trial has obtained IRB approval and focuses on determining the safe and effective radiation dose to be employed in the STAR procedure. Trial registration NCT05594368.

Introduction Patients suffering from arrhythmogenic right ventricular cardiomyopathy (ARVC) should avoid intense endurance exercise to reduce the risk of adverse cardiac events and disease progression. On the other hand, an active lifestyle might be preferable to a sedentary one, which also brings a host of complications. Evidence for safe levels of physical activity in ARVC, however, is scarce. This is study aimed to describe the ventricular arrhythmia burden - estimated as the prevalence of premature ventricular contractions (PVC) - of different exercise modalities and intensities on ARVC patients. Methods The pilot analysis includes four (1F, 33 ± 12 yrs, BMI 24 ± 4 kg/m2) ARVC patients harboring a pathogenic plakophilin-2 variant and carrying an implantable cardioverter-defibrillator performed different exercises while monitored via 12-lead ECG. The order of modalities was randomized and participants instructed to stop when surpassing perceived exertion of 15 on the Borg 6-20 scale. Resistance exercises included two-legged squats and single arm biceps curls (each with 20 repetitions and 2 min duration) while endurance exercise included 5 min of treadmill walking, 3 min cycling bouts at heart rate (HR) of 80, 100 and 120 bpm as well as cycling at 120 bpm with 2 additional min of active cool down. Blood lactate concentration was assessed at the end of the cycling bouts. Results No adverse cardiac event were noted and no exercise was terminated for medical reasons. During walking HR was 76 ± 8 bpm, whereas PVC burden was 11 ± 6% (range 4-18%). Cycling at 82 ± 4 bpm induced a PVC burden of 7 ± 5% (range 3- 14%), which increased to 13 ± 8% (range 3- 21%) at 93 ± 2 bpm and further to 16 ± 16% (range 7-37%) at 105 ± 3 bpm. In all three modalities the PVC burden was higher in the first 3 min of recovery than during the activity itself. Adding a 2 min active cool down increased the PVC burden to 25 ± 16% (range 6-45%). 2-legged squats performed at 101 ± 15 bpm had a PVC burden of 9 ± 12%, which increased to 19 ± 14% at recovery. One arm biceps curls at 75 ± 13 bpm had a PVC burden of 4 ± 3% during the activity and 9 ± 5% during recovery. Perception of effort varied widely when cycling at 80 bpm (range 6-12) or 100 bpm (range 8-14), but less so at 120 bpm (range 13-15). Blood lactate concentration when cycling at 120 bpm ranged between 2.2 and 3.5 mmol/L, typically associated with exercise in the “heavy” intensity domain. Discussion/Conclusion ARVC patients present a high, intensity-dependent PVC burden during exercise and short-term recovery. However, we observed widely different PVC burdens and perceived exertion at a given HR during different exercise modalities, which calls for personalized recommendations on physical activity. Exercises with small muscle mass seem to minimize the PVC burden and training the different muscles separately could be an interesting avenue to maintain physical fitness in ARVC patients.

Abstract The pathophysiological mechanisms underlying the development of the athlete’s heart are still poorly understood. To characterize the intracavitary blood flows in the right ventricle (RV) and right-ventricular outflow tract (RVOT) in 2 healthy probands, patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and 2 endurance athletes, we performed 4D-MRI flow measurements to assess differences in kinetic energy and shear stresses. Time evolution of velocity magnitude, mean kinetic energy (MKE), turbulent kinetic energy (TKE) and viscous shear stress (VSS) were measured both along the whole RV and in the RVOT. RVOT regions had higher kinetic energy values and higher shear stresses levels compared to the global averaging over RV among all subjects. Endurance athletes had relatively lower kinetic energy and shear stresses in the RVOT regions compared to both healthy probands and ARVC patients. The athlete’s heart is characterized by lower kinetic energy and shear stresses in the RVOT, which might be explained by a higher diastolic compliance of the RV.

Background Data on the use of the wearable cardioverter‐defibrillator (WCD) among patients with myocarditis remain sparse. Consequently, evidence for guideline recommendations in this patient population is lacking. Methods and Results In total, 1596 consecutive patients were included in a multicenter registry from 8 European centers, with 124 patients (8%) having received the WCD due to myocarditis and reduced left ventricular ejection fraction or prior ventricular tachyarrhythmia. The mean age was 51.6±16.3 years, with 74% being male. Patients were discharged after index hospitalization on heart failure medication: Angiotensin‐converting enzyme inhibitors (62.5%), angiotensin‐receptor‐neprilysin inhibitor (22.9%), aldosterone‐antagonists (51%), or beta blockers (91.4%). The initial median left ventricular ejection fraction was 30% (22%–45%) and increased to 48% (39%–55%) over long‐term follow‐up (P

Background Data on the incidence of arrhythmias, associated cardiac interventions, and outcome in patients with dextro‐transposition of the great arteries and atrial switch are scarce. Methods and Results In this multicenter analysis, we included adult patients with dextro‐transposition of the great arteries and atrial switch regularly followed up at 3 Swiss tertiary care hospitals. The primary outcome was a composite of left ventricular assist device, heart transplantation, and death. The secondary outcome was occurrence of ventricular tachycardia, ventricular fibrillation, or sudden cardiac death. We identified 207 patients (34% women; median age at last follow‐up, 35 years) with dextro‐transposition of the great arteries and atrial switch. Arrhythmias occurred in 97 patients (47%) at a median age of 22 years. A pacemaker or an implantable cardioverter‐defibrillator was implanted in 39 (19%) and 13 (6%) patients, respectively, and 33 (16%) patients underwent a total of 51 ablation procedures to target 60 intra‐atrial re‐entry tachycardias, 4 atrioventricular nodal re‐entry tachycardias, and 1 atrial fibrillation. The primary outcome occurred in 21 patients (10%), and the secondary outcome occurred in 18 patients (9%); both were more common in patients with concomitant ventricular septum defect than in those without (hazard ratio [HR], 3.06 [95% CI, 1.29–7.27], P=0.011; and HR, 3.62 [95% CI, 1.43–9.18], P=0.007, respectively). Conclusions In patients with dextro‐transposition of the great arteries and atrial switch reaching adulthood, arrhythmias occur in almost half of patients, and associated rhythm interventions are frequent. One‐tenth of those patients do not survive until the age of 35 years free from left ventricular assist device or heart transplantation, and the outcome is worse in patients with concomitant ventricular septum defect.

AimTo investigate the clinical significance of right atrial mapping prior to cavotricuspid isthmus (CTI) ablation in patients with typical atrial flutter (AFL).MethodsClinical and ablation parameters were retrospectively assessed and compared in patients undergoing CTI ablation with or without a first-step right atrial mapping (FRAM) by using the CARTO 3D mapping system.ResultsCTI block by radiofrequency ablation (RFA) was achieved in all 143 patients. In the FRAM group there was a shorter ablation duration and fluoroscopy exposure compared with the non-FRAM group. CHA2DS2-VASc score was associated with higher ablation durations, more ablation applications and increased fluoroscopy exposure. Body mass index (BMI) was associated with longer ablation duration and more ablation applications. Furthermore, patients with reduced left ventricular ejection fraction (LVEF) had longer ablation durations and more fluoroscopy exposure. One patient in the non-FRAM group developed cardiac effusion after ablation. None of the patients had recurrence after 6 months of follow-up.ConclusionsPatients with high BMI, high CHA2DS2-VASc score and reduced LVEF may benefit from the FRAM approach by reducing ablation duration, number of ablation applications and fluoroscopy exposure.

Introduction: In recent years, high-density microelectrode arrays (HD-MEAs) have emerged as a valuable tool in preclinical research for characterizing the electrophysiology of human induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs). HD-MEAs enable the capturing of both extracellular and intracellular signals on a large scale, while minimizing potential damage to the cell. However, despite technological advancements of HD-MEAs, there is a lack of effective data-analysis platforms that are capable of processing and analyzing the data, particularly in the context of cardiac arrhythmias and drug testing. Methods: To address this need, we introduce CardioMEA, a comprehensive data-analysis platform designed specifically for HD-MEA data that have been obtained from iPSCCMs. CardioMEA features scalable data processing pipelines and an interactive web-based dashboard for advanced visualization and analysis. In addition to its core functionalities, CardioMEA incorporates modules designed to discern crucial electrophysiological features between diseased and healthy iPSC-CMs. Notably, CardioMEA has the unique capability to analyze both extracellular and intracellular signals, thereby facilitating customized analyses for specific research tasks. Results and discussion: We demonstrate the practical application of CardioMEA by analyzing electrophysiological signals from iPSC-CM cultures exposed to seven antiarrhythmic drugs. CardioMEA holds great potential as an intuitive, userfriendly platform for studying cardiac diseases and assessing drug effects. [ABSTRACT FROM AUTHOR]

Abstract 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 Patients with arrhythmogenic right ventricular cardiomyopathy are at risk for life‐threatening ventricular tachyarrhythmias, but progressive heart failure (HF) may occur in later stages of disease. This study aimed to characterize potential risk predictors and develop a model for individualized assessment of adverse HF outcomes in arrhythmogenic right ventricular cardiomyopathy. Methods and Results Longitudinal and observational cohorts with 290 patients with arrhythmogenic right ventricular cardiomyopathy from the Fuwai Hospital in Beijing, China, and 99 patients from the University Heart Center in Zurich, Switzerland, with follow‐up data were studied. The primary end point of the study was heart transplantation or death attributable to HF. The model was developed by Cox regression analysis for predicting risk and was internally validated. During 4.92±3.03 years of follow‐up, 48 patients reached the primary end point. The determinants of the risk prediction model were left ventricular ejection fraction, serum creatinine levels, moderate‐to‐severe tricuspid regurgitation, and atrial fibrillation. Implantable cardioverter‐defibrillators did not reduce the occurrence of adverse HF outcomes. Conclusions A novel risk prediction model for arrhythmogenic right ventricular cardiomyopathy has been developed using 2 large and well‐established cohorts, incorporating common clinical parameters such as left ventricular ejection fraction, serum creatinine levels, tricuspid regurgitation, and atrial fibrillation, which can identify patients who are at risk for terminal HF events, and may guide physicians to assess individualized HF risk and to optimize management strategies.

Background and Aims Pathogenic desmoplakin (DSP) gene variants are associated with the development of a distinct form of arrhythmogenic cardiomyopathy known as DSP cardiomyopathy. Patients harbouring these variants are at high risk for sustained ventricular arrhythmia (VA), but existing tools for individualized arrhythmic risk assessment have proven unreliable in this population. Methods Patients from the multi-national DSP-ERADOS (Desmoplakin SPecific Effort for a RAre Disease Outcome Study) Network patient registry who had pathogenic or likely pathogenic DSP variants and no sustained VA prior to enrolment were followed longitudinally for the development of first sustained VA event. Clinically guided, step-wise Cox regression analysis was used to develop a novel clinical tool predicting the development of incident VA. Model performance was assessed by c -statistic in both the model development cohort (n = 385) and in an external validation cohort (n = 86). Results In total, 471 DSP patients [mean age 37.8 years, 65.6% women, 38.6% probands, 26% with left ventricular ejection fraction (LVEF) < 50%] were followed for a median of 4.0 (interquartile range: 1.6–7.3) years; 71 experienced first sustained VA events {2.6% [95% confidence interval (CI): 2.0, 3.5] events/year}. Within the development cohort, five readily available clinical parameters were identified as independent predictors of VA and included in a novel DSP risk score: female sex [hazard ratio (HR) 1.9 (95% CI: 1.1–3.4)], history of non-sustained ventricular tachycardia [HR 1.7 (95% CI: 1.1–2.8)], natural logarithm of 24-h premature ventricular contraction burden [HR 1.3 (95% CI: 1.1–1.4)], LVEF < 50% [HR 1.5 (95% CI:.95–2.5)], and presence of moderate to severe right ventricular systolic dysfunction [HR 6.0 (95% CI: 2.9–12.5)]. The model demonstrated good risk discrimination within both the development [ c -statistic.782 (95% CI:.77–.80)] and external validation [ c -statistic.791 (95% CI:.75–.83)] cohorts. The negative predictive value for DSP patients in the external validation cohort deemed to be at low risk for VA (<5% at 5 years; n = 26) was 100%. Conclusions The DSP risk score is a novel model that leverages readily available clinical parameters to provide individualized VA risk assessment for DSP patients. This tool may help guide decision-making for primary prevention implantable cardioverter-defibrillator placement in this high-risk population and supports a gene-first risk stratification approach. [ABSTRACT FROM AUTHOR]

Aims Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by progressive myocardial dysfunction and associated with an increased risk of major cardiovascular (CV) events. To determine right heart strain (ventricular and atrial global longitudinal strain (RVGLS and RAGLS) in patients with definite ARVC and its association with adverse events during follow-up. Methods and results RVGLS and RAGLS were analysed in focused right heart apical views from 70 patients using TomTec ImageArena and association with a composite endpoint was determined (sustained ventricular arrhythmia and cardiovascular death). Over a median follow-up duration of 4.9 years, 26 (37%) patients met the endpoint. RVGLS was significantly impaired in the event group (−11.5 [−13.3 to −10.2] %) vs. the no-event group (−15.8 [−17.1 to −14.5] %, P < 0.001), and so was RAGLS (22.8 [21.4–27.4] % vs. 31.5 [25.1–39.6] %, respectively, P < 0.001). In Cox regression, RVGLS (HR 1.36, P < 0.001) and RAGLS (HR 0.92, P = 0.002) were associated with a higher risk of adverse events. In multivariable Cox regression models, RVGLS and RAGLS remained independent of and were incremental to age, gender, and conventional RV parameters, and model fitness was improved when RVGLS and RAGLS were applied together rather than alone. Conclusion RVGLS and RAGLS are more impaired in patients with adverse events and associated with adverse events independent of age, gender, and conventional RV parameters. When RVGLS and RAGLS are applied together, prediction models are improved suggesting that right heart strain may form part of the echocardiographic routine protocol in patients with ARVC. [ABSTRACT FROM AUTHOR]

Abstract 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.

Abstract Aims The coronavirus disease 2019 (COVID‐19) has spread rapidly around the globe, causing significant morbidity and mortality. This study aims to describe electrocardiographic (ECG) characteristics of COVID‐19 patients and to identify ECG parameters that are associated with cardiac involvement. Methods and results The study included patients who were hospitalized with COVID‐19 diagnosis and had cardiac biomarker assessments and simultaneous 12‐lead surface ECGs. Sixty‐three hospitalized patients (median 53 [inter‐quartile range, 43–65] years, 76.2% male) were enrolled, including patients with (n = 23) and without (n = 40) cardiac injury. Patients with cardiac injury were older, had more pre‐existing co‐morbidities, and had higher mortality than those without cardiac injury. They also had prolonged QTc intervals and more T wave changes. Logistic regression model identified that the number of abnormal T waves (odds ratio (OR), 2.36 [95% confidence interval (CI), 1.38–4.04], P = 0.002) and QTc interval (OR, 1.31 [95% CI, 1.03–1.66], P = 0.027) were independent indicators for cardiac injury. The combination model of these two parameters along with age could well discriminate cardiac injury (area the under curve 0.881, P

Abstract Aims Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with life‐threatening ventricular arrhythmia and progressive ventricular dysfunction. Previous studies suggested that sex hormones play an important role in the onset and prognosis of ARVC. This study aimed to investigate the role of testosterone in predicting major adverse cardiac events in the Chinese ARVC cohort. Methods and results Ninety‐nine ARVC patients (median age, 40 years; 70.7% male) and 96 healthy controls (median age, 41 years; 62.5% male) were enrolled. The circulating levels of testosterone were measured by enzyme‐linked immunosorbent assays (ELISA). The median follow‐up time of all ARVC male patients was 17 months (interquartile range/IQR 9–29). Cox proportional hazards regression was used to analyse the effect of plasma testosterone and other well‐described risk factors on malignant arrhythmic events in male ARVC patients. The male ARVC patients had significantly elevated levels of total testosterone [TT, 6.390 (4.438–8.768) ng/mL vs. 3.617 (2.073–4.479) ng/mL, P 0.05). During the follow‐up, the levels of testosterone were higher in male patients who experienced malignant arrhythmic events (N = 22) than in those who did not (N = 25) [TT, 9.034 (7.222–15.370) ng/mL vs. 4.633 (3.363–6.375) ng/mL, P

Arrhythmogenic cardiomyopathy (ACM) is a progressive inheritable disease which is characterized by a gradual fibro-(fatty) replacement of the myocardium. Visualization of diffuse and patchy fibrosis patterns is challenging using clinically applied cardiac imaging modalities (e.g., late gadolinium enhancement, LGE). During collagen synthesis and breakdown, carboxy–peptides are released into the bloodstream, specifically procollagen type-I carboxy-terminal propeptides (PICP) and collagen type-I carboxy-terminal telopeptides (ICTP). We collected the serum and EDTA blood samples and clinical data of 45 ACM patients (age 50.11 ± 15.53 years, 44% female), divided into 35 diagnosed ACM patients with a 2010 ARVC Task Force Criteria score (TFC) ≥ 4, and 10 preclinical variant carriers with a TFC < 4. PICP levels were measured using an enzyme-linked immune sorbent assay and ICTP levels with a radio immunoassay. Increased PICP/ICTP ratios suggest a higher collagen deposition. We found significantly higher PICP and PICP/ICTP levels in diagnosed patients compared to preclinical variant carriers (p < 0.036 and p < 0.027). A moderate negative correlation existed between right ventricular ejection fractions (RVEF) and the PICP/ICTP ratio (r = −0.46, p = 0.06). In addition, significant correlations with left ventricular function (LVEF r = −0.53, p = 0.03 and end-systolic volume r = 0.63, p = 0.02) were found. These findings indicate impaired contractile performance due to pro-fibrotic remodeling. Follow-up studies including a larger number of patients should be performed to substantiate our findings and the validity of those levels as potential promising biomarkers in ACM.