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Objectives: There are studies in the literature showing the clinical importance of fragmented QRS (fQRS) in many systemic diseases. In this study, we aimed to investigate the frequency and prognostic value of fQRS on electrocardiogram (ECG) in patients with acute ischemic stroke., Materials and Methods: We prospectively enrolled 241 patients with acute ischemic stroke between January 2018 and January 2020. ST depression and elevation, QRS duration, PR interval, RR interval, QTc interval, QTc dispersion (QTcd), T negativity, Q wave, and fQRS were evaluated on ECG. Brain computed tomography (CT) and diffusion magnetic resonance imaging (MRI) images were obtained in the acute period and the National Institute of Health Stroke Scale (NIHSS) score was calculated for each patient. Patients were followed up for a period of two years., Results: The 241 patients comprised 121 (50.2%) men and 120 (49.8%) women with a mean age of 67.52 ± 13.00 years. In Cox regression analysis, age, NIHSS, QTcd, and fQRS were found to be independent predictors of mortality (age, hazard ratio [HR]: 1.063, p < 0.001; NIHSS, HR: 1.116, p = 0.006; QTcd, HR: 1.029, p = 0.042; fQRS, HR: 2.048, p = 0.037). Two-year mortality was higher in patients with fQRS than in patients without fQRS (31% vs. 9%, p = 0.001)., Conclusions: The fQRS is associated with poor prognosis in patients with acute ischemic stroke., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The overall incidence of sudden cardiac death is considerably lower among women than men, reflecting significant and often under-recognized sex differences. Women are older at time of sudden cardiac death, less likely to have a prior cardiac diagnosis, and less likely to have coronary artery disease identified on postmortem examination. They are more likely to experience their death at home, during sleep, and less likely witnessed. Women are also more likely to present in pulseless electrical activity or systole rather than ventricular fibrillation or ventricular tachycardia. Conversely, women are less likely to receive bystander cardiopulmonary resuscitation or receive cardiac intervention post-arrest. Underpinning sex disparities in sudden cardiac death is a paucity of women recruited to clinical trials, coupled with an overall lack of prespecified sex-disaggregated evidence. Thus, predominantly male-derived data form the basis of clinical guidelines. This review outlines the critical sex differences concerning epidemiology, cause, risk factors, prevention, and outcomes. We propose 4 broad areas of importance to consider: physiological, personal, community, and professional factors.

Introduction: There is limited literature on coronavirus disease 2019 (COVID -19) complications such as thromboembolism, cardiac complications etc. as possible trigger for stroke. Hence, we aim to evaluate the prevalence and outcomes of COVID-19 related cardiovascular complications and secondary infection and their possibility as potential triggers for the stroke., Methods: Data from observational studies describing the complications [acute cardiac injury (ACI), cardiac arrhythmias (CA), disseminated intravascular coagulation (DIC), septic shock, secondary infection] and outcomes of COVID-19 hospitalized patients from December 1, 2019 to June 30, 2020, were extracted following PRISMA guidelines. Adverse outcomes defined as intensive care units, oxygen saturation less than 90%, invasive mechanical ventilation, severe disease, and in-hospital mortality. The odds ratio and 95% confidence interval were obtained, and forest plots were created using random-effects models. A short review of these complications as triggers of stroke was conducted., Results: 16 studies with 3480 confirmed COVID-19 patients, prevalence of ACI [38%vs5.9%], CA [26%vs5.3%], DIC [4%vs0.74%], septic shock [18%vs0.36%], and infection [30%vs12.5%] was higher among patients with poor outcomes. In meta-analysis, ACI [aOR:9.93(95%CI:3.95-25.00], CA [7.52(3.29-17.18)], DIC [7.36(1.24-43.73)], septic shock [30.12(7.56-120.10)], and infection [10.41(4.47-24.27)] had higher odds of adverse outcomes. Patients hospitalized with acute ischemic stroke and intracerebral hemorrhage, had complications like pulmonary embolism, venous thromboembolism, DIC, etc. and had poor outcomes CONCLUSION: The complications like acute cardiac injury, cardiac arrhythmias, DIC, septic shock, and secondary infection had poor outcomes. Patients with stroke were having history of these complications. Long term monitoring is required in such patients to prevent stroke and mitigate adverse outcomes., Competing Interests: Declaration of Competing Interest The authors report no disclosures relevant to the manuscript. The authors declare that there is no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), tafamidis significantly reduced mortality and cardiovascular (CV)-related hospitalizations compared with placebo in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). This analysis aimed to assess the causes of CV-related death and hospitalization in ATTR-ACT to provide further insight into the progression of ATTR-CM and efficacy of tafamidis. ATTR-ACT was an international, double-blind, placebo-controlled, and randomized study. Patients with hereditary or wild-type ATTR-CM were randomized to tafamidis (n = 264) or placebo (n = 177) for 30 months. The independent Endpoint Adjudication Committee determined whether certain investigator-reported events met the definition of disease-related efficacy endpoints using predefined criteria. Cause-specific reasons for CV-related deaths (heart failure [HF], arrhythmia, myocardial infarction, sudden death, stroke, and other CV causes) and hospitalizations (HF, arrhythmia, myocardial infarction, transient ischemic attack/stroke, and other CV causes) were assessed. Total CV-related deaths was 53 (20.1%) with tafamidis and 50 (28.2%) with placebo, with HF (15.5% tafamidis, 22.6% placebo), followed by sudden death (2.7% tafamidis, 5.1% placebo), the most common causes. The number of patients with a CV-related hospitalization was 138 (52.3%) with tafamidis and 107 (60.5%) with placebo; with HF the most common cause (43.2% tafamidis, 50.3% placebo). All predefined causes of CV-related death or hospitalization were less frequent with tafamidis than placebo. In conclusion, these data provide further insight into CV disease progression in patients with ATTR-CM, with HF the most common adjudicated cause of CV-related hospitalization or death in ATTR-ACT. Clinical trial registration ClinicalTrials.gov: NCT01994889., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: With the growing adult congenital heart disease (ACHD) population, the number of catheter ablation procedures is expected to dramatically increase. Data reporting experience and evolution of catheter ablation in patients with ACHD, over a significant period of time, remain scarce., Aim: We aimed to describe temporal trends in volume and outcomes of catheter ablation in patients with ACHD., Methods: This was a retrospective observational study including all consecutive patients with ACHD undergoing attempted catheter ablation in a large tertiary referral centre over a 15-year period. Acute procedural success rate and freedom from recurrence at 12 and 24 months were analysed., Results: From November 2004 to November 2019, 302 catheter ablations were performed in 221 patients with ACHD (mean age 43.6±15.0 years; 58.9% male sex). The annual number of catheter ablations increased progressively from four to 60 cases per year (P<0.001). Intra-atrial reentrant tachycardia/focal atrial tachycardia was the most common arrhythmia (n=217, 71.9%). Over the study period, acute procedural success rate increased from 45.0% to 93.4% (P<0.001). Use of irrigated catheters (odds ratio [OR] 4.03, 95% confidence interval [CI] 1.86-8.55), a three-dimensional mapping system (OR 3.70, 95% CI 1.72-7.74), contact force catheters (OR 3.60, 95% CI 1.81-7.38) and high-density mapping (OR 3.69, 95% CI 1.82-8.14) were associated with acute procedural success. The rate of freedom from any recurrence at 12 months increased from 29.4% to 66.2% (P=0.001). Seven (2.3%) non-fatal complications occurred., Conclusions: The number of catheter ablation procedures in patients with ACHD has increased considerably over the past 15 years. Growing experience and advances in ablative technologies appear to be associated with a significant improvement in acute and mid-term outcomes., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Introduction: Cardiac dysfunction directly caused by spontaneous intracerebral hemorrhage (ICH) is a poorly understood phenomenon, and its impact on outcome is still uncertain. The aim of this study is to investigate the relationship between electrocardiographic (EKG) abnormalities and mortality in ICH., Methods: This is a retrospective study analyzing EKG patterns on admission in patients admitted with ICH at a tertiary care center over an eight-year period. For each patient, demographics, medical history, clinical presentation, EKG on admission and during hospitalization, and head CT at presentation were reviewed. Mortality was noted., Results: A total of 301 ICH patients were included in the study. The most prevalent EKG abnormalities were QTc prolongation in 56% of patients (n = 168) followed by inversion of T waves (TWI) in 37% of patients (n = 110). QTc prolongation was associated with ganglionic location (p = 0.03) and intraventricular hemorrhage (IVH) (p = 0.01), TWIs were associated with ganglionic location (p = 0.02), and PR prolongation was associated with IVH (p = 0.01), while QRS prolongation was associated with lobar location (p < 0.01). Volume of ICH, hemispheric laterality, and involvement of insular cortex were not correlated with specific EKG patterns. In a logistic regression model, after correcting for ICH severity and prior cardiac history, presence of TWI was independently associated with mortality (OR: 3.04, CI:1.6-5.8, p < 0.01). Adding TWI to ICH score improved its prognostic accuracy (AUC 0.81, p = 0.04). Disappearance of TWI during hospitalization did not translate into improvement of survival (p = 0.5)., Conclusion: Presence of TWI on admission is an independent and unmodifiable factor associated with mortality in ICH. Further research is needed to elucidate the pathophysiologic mechanisms underlying electrocardiographic changes after primary intracerebral hemorrhage., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Management of young adults with hypertrophic cardiomyopathy (HCM) is challenging., Aims: To evaluate the profile of young adults (16-25 years) with HCM included in the French prospective HCM registry., Methods: Patients were compared according to occurrence of major adverse cardiac events (MACE), comprising sudden cardiac death (SCD) events (implantable cardioverter defibrillator [ICD] discharge, SCD, sustained ventricular tachycardia), atrial fibrillation/embolic stroke, heart failure hospitalisation and unexplained syncope, at a mean follow-up of 4.4±2.2 years., Results: At baseline, among 61 patients (20.5±3.0 years; 16 women, 26.2%), 13 (21.3%) had a prophylactic ICD, 24.6% a family history of SCD, 29.5% obstruction, 86.0% magnetic resonance imaging myocardial fibrosis, 11.8% abnormal exercise blood pressure and 52.8% a European Society of Cardiology (ESC) 5-year SCD score<4% (24.5%≥6%). At follow-up, 15 patients (24.6%; seven women; all with fibrosis) presented 17 MACE, comprising: SCD events (n=7, 41.2%; including three patients with an ICD, five with at least one SCD major classical risk factor and an ESC score≥5% and two with no risk factors and an ESC score<4%); atrial fibrillation/stroke (n=6, 35.3%); heart failure (n=1, 5.9%); syncope (n=3, 17.6%). An ICD was implanted in 11 patients (four for secondary prevention), but in only 61.5% of patients with a score≥6%. Only obstruction significantly increased MACE risk (odds ratio 3.96; P=0.035), with a non-significant trend towards a lower risk in men (OR 0.29; P=0.065)., Conclusions: In young adults with HCM, MACE are common in the short term, especially in obstructive HCM and women, mostly arrhythmic in origin. Prophylactic ICD implantation is frequent and does not strictly follow the guidelines, while the use of European/USA guidelines is helpful but imperfect in identifying SCD risk., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: The American Heart Association guidelines instruct use of postoperative telemetry (POT) should be reserved for patients undergoing cardiac procedures and/or those with ischemic cardiac symptoms, but acknowledge that major vascular procedures deserve unique consideration. Telemetry remains a limited resource in many hospitals; however, it has been poorly defined which vascular patients have greatest need for POT. The purpose of this study is to define the rates of postoperative arrhythmias (POAs) after major vascular operations using the Society for Vascular Surgery Vascular Quality Initiative (VQI) registry, identify independent predictors of POA, and determine the effect of POA on mortality to guide the use of POT in vascular patients., Methods: A retrospective cohort study was performed using the following VQI modules: open abdominal aortic aneurysm repair (oAAA), complex endovascular aneurysm repair (EVAR) (thoracic endovascular aortic repair [TEVAR]/c-EVAR), EVAR, suprainguinal bypass (SIB), and infrainguinal bypass (IIB). POA was defined in the VQI as a new rhythm disturbance requiring treatment with medication or cardioversion. The incidence of POA, preoperative risk factors, and demographics were determined for each procedure., Results: A total of 121,652 procedures were identified with an overall POA event rate of 5.1% (n = 6,265). Procedure-specific event rates for POA among VQI registries are as follows: oAAA 14.4%, TEVAR/c-EVAR 8.5%, EVAR 2.7%, SIB 6.2%, and IIB 3.8%. Across all procedure types, POA was associated with emergent operations and increased procedure time. Procedure-specific multivariable regression revealed additional independent preoperative intraoperative factors associated with POA that were unique with each procedure. Across all procedural groups, the presence of POA was associated with increased rates of clinical myocardial infarction and decreased survival on Kaplan-Meier analysis., Conclusions: Rates of POA in patients undergoing vascular procedures appear higher than previously reported, and POA is associated with decreased survival. Our study elucidated patient- and procedure-specific predictor factors associated with POA that can be used to inform the use of POT., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background The role of late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (c-MRI) for predicting outcomes of patients with hypertrophic cardiomyopathy (HCM) has been debated. Methods We searched PubMed and Embase and various published bibliographies for prospective studies published in English between January 1990 and February 2019. Two investigators screened 2646 abstracts and full-text articles for inclusion and relevant outcomes. We then performed a systematic review and meta-analysis to calculate pooled odds ratios for LGE on c-MRI and a pooled sensitivity and specificity analysis. Results Our systematic review included 8 prospective studies and 3808 patients. LGE positivity was associated with higher odds of the endpoint of sudden cardiac death (SCD;OR 1.69, 95%CI 1.03-2.78), aborted SCD or appropriate implantable cardioverter- defibrillator (ICD) discharge (OR 3.27 [1.75-6.10]), SCD or aborted SCD or appropriate ICD discharge (OR 2.32 [1.56-3.43]), and all-cause mortality (OR 2.10 [CI 1.00-4.41]). The pooled sensitivity and specificity of positive LGE on c-MRI for SCD were 65% and 42%, respectively; for aborted SCD or appropriate ICD discharge, 79% and 39%; for SCD or aborted SCD or appropriate ICD discharge, 74% and 39%; and for all-cause mortality, 78% and 39%. Conclusion In patients with HCM, LGE on c-MRI is a strong predictor of arrhythmic outcomes including SCD, aborted SCD, and appropriate ICD therapy. These data support the routine use of LGE on c-MRI as a marker of SCD risk in this population., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Specific details about cardiovascular complications, especially arrhythmias, related to the coronavirus disease of 2019 (COVID-19) are not well described., Objective: We sought to evaluate the incidence and predictive factors of cardiovascular complications and new-onset arrhythmias in Black and White hospitalized COVID-19 patients and determine the impact of new-onset arrhythmia on outcomes., Methods: We collected and analyzed baseline demographic and clinical data from COVID-19 patients hospitalized at the Tulane Medical Center in New Orleans, Louisiana, between March 1 and May 1, 2020., Results: Among 310 hospitalized COVID-19 patients, the mean age was 61.4 ± 16.5 years, with 58,7% females, and 67% Black patients. Black patients were more likely to be younger, have diabetes and obesity. The incidence of cardiac complications was 20%, with 9% of patients having new-onset arrhythmia. There was no significant difference in cardiovascular outcomes between Black and White patients. A multivariate analysis determined age ≥60 years to be a predictor of new-onset arrhythmia (OR = 7.36, 95% CI [1.95;27.76], p = .003). D-dimer levels positively correlated with cardiac and new-onset arrhythmic event. New onset atrial arrhythmias predicted in-hospital mortality (OR = 2.99 95% CI [1.35;6.63], p = .007), a longer intensive care unit length of stay (mean of 6.14 days, 95% CI [2.51;9.77], p = .001) and mechanical ventilation duration(mean of 9.08 days, 95% CI [3.75;14.40], p = .001)., Conclusion: Our results indicate that new onset atrial arrhythmias are commonly encountered in COVID-19 patients and can predict in-hospital mortality. Early elevation in D-dimer in COVID-19 patients is a significant predictor of new onset arrhythmias. Our finding suggest continuous rhythm monitoring should be adopted in this patient population during hospitalization to better risk stratify hospitalized patients and prompt earlier intervention., (© 2021 Wiley Periodicals LLC.)

Background: Left ventricular (LV) scar on late gadolinium enhancement (LGE) cardiac magnetic resonance has been correlated with life-threatening arrhythmic events in patients with apparently idiopathic ventricular arrhythmias (VAs). We investigated the prognostic significance of a specific LV-LGE phenotype characterized by a ringlike pattern of fibrosis., Methods: A total of 686 patients with apparently idiopathic nonsustained VA underwent contrast-enhanced cardiac magnetic resonance. A ringlike pattern of LV scar was defined as LV subepicardial/midmyocardial LGE involving at least 3 contiguous segments in the same short-axis slice. The end point of the study was time to the composite outcome of all-cause death, resuscitated cardiac arrest because of ventricular fibrillation or hemodynamically unstable ventricular tachycardia and appropriate implantable cardioverter defibrillator therapy., Results: A total of 28 patients (4%) had a ringlike pattern of scar (group A), 78 (11%) had a non-ringlike pattern (group B), and 580 (85%) had normal cardiac magnetic resonance with no LGE (group C). Group A patients were younger compared with groups B and C (median age, 40 vs 52 vs 45 years; P <0.01), more frequently men (96% vs 82% vs 55%; P <0.01), with a higher prevalence of family history of sudden cardiac death or cardiomyopathy (39% vs 14% vs 6%; P <0.01) and more frequent history of unexplained syncope (18% vs 9% vs 3%; P <0.01). All patients in group A showed VA with a right bundle-branch block morphology versus 69% in group B and 21% in group C ( P <0.01). Multifocal VAs were observed in 46% of group A patients compared with 26% of group B and 4% of group C ( P <0.01). After a median follow-up of 61 months (range, 34-84 months), the composite outcome occurred in 14 patients (50.0%) in group A versus 15 (19.0%) in group B and 2 (0.3%) in group C ( P <0.01). After multivariable adjustment, the presence of LGE with ringlike pattern remained independently associated with increased risk of the composite end point (hazard ratio, 68.98 [95% CI, 14.67-324.39], P <0.01)., Conclusions: In patients with apparently idiopathic nonsustained VA, nonischemic LV scar with a ringlike pattern is associated with malignant arrhythmic events.

Background Sudden cardiac death (SCD) constitutes a major health problem worldwide. We investigated whether birth weight (BW), small for gestational age (SGA), and large for gestational age are associated with altered risk of SCD among the young (aged 1-36 years). Methods and Results We included all people born in Denmark from 1973 to 2008 utilizing the Danish Medical Birth Register. All SCDs in Denmark in 2000 to 2009 have previously been identified. We defined 5 BW groups, SGA, and large for gestational age as exposure and SCD as the outcome. We estimated the age-specific relative risk of SCD with 95% CI. Additionally, we investigated if SGA and large for gestational age are associated with pathological findings at autopsy. The study population for the BW analyses comprised 2 234 501 people with 389 SCD cases, and the SGA and large for gestational age analyses comprised 1 786 281 people with 193 SCD cases. The relative risk for SCD was 6.69 for people with BW between 1500 and 2499 g (95% CI, 2.38-18.80, P <0.001) and 5.89 for people with BW ≥4500 g (95% CI, 1.81-19.12, P =0.003) at age 5 years. BW 2500 to 3400 g was the reference group. Compared with an appropriate gestational age, the relative risk for SGA was 2.85 (95% CI, 1.35-6.00, P =0.006) at age 10 years. For the autopsied cases, the relative risk of sudden arrhythmic death syndrome at age 5 years was 4.19 for SGA (95% CI, 1.08-16.22, P =0.038). Conclusions We found an association between BW and SCD in the young, with an increased risk among SGA infants. In addition, we found an association between SGA and sudden arrhythmic death syndrome.

The wearable cardioverter-defibrillator (WCD) was first approved for clinical use in 2002, and is routinely used in select populations at high risk for sudden cardiac death. WCDs are frequently considered as a bridge to definitive therapy or in circumstances where insertion of conventional implantable cardioverter-defibrillators (ICD) is temporarily contraindicated. In this review, we summarize the literature on WCDs. From prospective trials to the first randomized controlled trial with WCD, there is a growing body of evidence that suggests that the WCD is safe and effective. In the first randomized controlled trial of the WCD (VEST Trial), there was no reduction in arrhythmia death but there was a reduction in all-cause mortality. We discuss the mortality impact, rate of inappropriate shocks, compliance, and potential quality of life implications with the WCD. Finally, we present the evidence for WCD use in select populations (e.g., post-myocardial infarction, device extraction), and the current guideline recommendations for WCD use., (Copyright © 2020. Published by Elsevier Inc.)

Background: The Fourth Universal Definition of Myocardial Infarction (MI) differentiates MI from myocardial injury. We characterised the temporal course of cardiac and non-cardiac outcomes associated with MI, acute and chronic myocardial injury., Methods: We included all patients presenting to public emergency departments in South Australia between June 2011-Sept 2019. Episodes of care (EOCs) were classified into 5 groups based on high-sensitivity troponin-T (hs-cTnT) and diagnostic codes: 1) Acute MI [rise/fall in hs-cTnT and primary diagnosis of acute coronary syndrome], 2) Acute myocardial injury with coronary artery disease (CAD) [rise/fall in hs-cTnT and diagnosis of CAD], 3) Acute myocardial injury without CAD [rise/fall in hs-cTnT without diagnosis of CAD], 4) Chronic myocardial injury [elevated hs-cTnT without rise/fall], and 5) No myocardial injury. Multivariable flexible parametric models were used to characterize the temporal hazard of death, MI, heart failure (HF), and ventricular arrhythmia., Results: 372,310 EOCs (218,878 individuals) were included: acute MI (19,052 [5.12%]), acute myocardial injury with CAD (6,928 [1.86%]), acute myocardial injury without CAD (32,231 [8.66%]), chronic myocardial injury (55,056 [14.79%]), and no myocardial injury (259,043 [69.58%]). We observed an early hazard of MI and HF after acute MI and acute myocardial injury with CAD. In contrast, subsequent MI risk was lower and more constant in patients with acute injury without CAD or chronic injury. All patterns of myocardial injury were associated with significantly higher risk of all-cause mortality and ventricular arrhythmia., Conclusions: Different patterns of myocardial injury were associated with divergent profiles of subsequent cardiac and non-cardiac risk. The therapeutic approach and modifiability of such excess risks require further research., Competing Interests: The authors have declared that no competing interests exist.

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Due to the lack of prospective, randomized, controlled clinical studies on inflammation and cardiovascular involvement, the exact mechanism of cardiac injury among patients with Coronavirus Disease 2019 (COVID-19) still remains uncertain. It was demonstrated that there is a high and significantly positive linear correlation between troponin T and plasma high-sensitivity C-reactive protein levels, biomarkers of cardiac injury and systemic inflammation, respectively. Cardiac injury and inflammation is a relatively common association among patients hospitalized with COVID-19, and it is related to higher risk of in-hospital mortality. In our literature search, we identified several potential mechanisms of myocardial tissue damage, namely, coronavirus-associated acute myocarditis, angiotensin-converting enzyme 2 receptor binding affinity to the virus Spike protein, increased cytokine secretion, and hypoxia-induced cardiac myocyte apoptosis. Elucidation of the disease pathogenesis and prospective histopathological studies are crucial for future proper treatment in case of renewed outbreaks. Of interest is that with hundred of thousands of bodies available for autopsy studies, no prospective investigation has been reported so far. Strong efforts and continued research of the cardiovascular complications and identification of risk factors for poor prognosis in COVID-19 are steadily needed. The high morbidity and mortality of COVID-19, its monumental economic burden and social impact, the despair of a new pandemic outbreak, and the thread of potential utilization of novel severe acute respiratory syndrome coronavirus 2 as biologic weapons make it a preponderant necessity to better comprehend the therapeutic management of this lethal disease. Emerging as an acute infectious disease, COVID-19 may become a chronic epidemic because of genetic recombination. Therefore, we should be ready for the reemergence of COVID-19 or other coronaviruses., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

[Figure: see text].

Orthotropic heart transplantation remains the most effective therapy for patients with end-stage heart failure, with a median survival of ≈13 years. Yet, a number of complications are observed after orthotropic heart transplantation, including atrial and ventricular arrhythmias. Several factors contribute to arrhythmias, such as autonomic denervation, effect of the surgical technique, acute and chronic rejection, and transplant vasculopathy among others. To minimize risk of future arrhythmias, the bicaval technique and minimizing ischemic time are current surgical standards. Sinus node dysfunction is the most common indication for early (within 30 days) pacemaker implantation, whereas atrioventricular block incidence increases as time from transplant increases. Atrial fibrillation can occur in the first few weeks following transplantation but is uncommon in the long term unless secondary to a precipitant such as acute rejection. The most common atrial arrhythmias are atrial flutters, which are mainly typical, but atypical circuits can be observed such as those that involve the remnant donor atrium in regions immediately adjacent to the atrioatrial anastomosis suture line. Choosing the appropriate pharmacological therapy requires careful consideration due to the potential interaction with immunosuppressive agents. Despite historical concerns, adenosine is effective and safe at reduced doses if administered under cardiac monitoring. Catheter ablation has emerged as an effective treatment strategy for symptomatic supraventricular tachycardias, including ablation of atypical flutter circuits. Cardiac allograft vasculopathy is an important risk factor for sudden cardiac death, yet the role of prophylactic implantable cardioverter-defibrillator implant for sudden death prevention is unclear. Current indications for implantable cardioverter-defibrillator implantation are as in the nontransplant population. A number of questions for future research are posed.

Background: Transcatheter aortic valve replacement (TAVR) has become quite common. Atrioventricular conduction defects remain a frequent complication resulting with permanent pacemaker (PPM) implantation. Past studies showed conflicting results regarding PPM effect on mortality., Objective: The purpose of this study was to assess the influence of PPM implantation on mid- and long-term mortality in a large cohort of patients who underwent TAVR., Methods: Patients undergoing TAVR between 2009 and 2019 were categorized into groups: no PPM implanted (no-PPM), PPM implanted before the procedure (pre-PPM), and PPM implanted postprocedure (post-PPM). All-cause mortality up to 6 years was compared. Subanalyses were performed according to pacing burden. Proportion of patients who had decreased left ventricular ejection fraction within 1 year of the procedure after TAVR was also recorded., Results: A total of 1489 patients were followed. Unadjusted mortality was similar for patients regardless of PPM status within 12 months (P > .187), yet within 72 months, mortality was similar for the post-PPM (P = .257) and higher for pre-PPM (hazard ratio 1.53; P = .002) groups. Analysis adjusted by clinical characteristics did not show any independent long- or mid-term survival effects of PPM (P > .563). Analysis according to pacing burden showed no significant mortality difference (P > .8). Analysis of post-PPM patients with "high" or "near constant" (>40%) pacing burden vs no-PPM patients showed similar mortality for both mid- and long-term mortality (P = .055 and P = .513). Left ventricular ejection fraction decrease within 1 year was more common in both PPM groups, with a higher proportion with higher pacing burden (P < .001)., Conclusion: This cohort of consecutive patients undergoing TAVR showed that postprocedure PPM was not associated with increased long-term mortality. This conclusion was not altered by ventricular pacing burden., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Short QT syndrome is a rare, inherited channelopathy associated with sudden cardiac arrest (SCA) but the characteristics and prognosis of short QT interval (SQTI) in Korean patients remain unclear. This study aimed to determine the clinical characteristics and outcomes of SQTI in a Korean population., Methods: Consecutive patients with SQTI from January 1999 to March 2019 in three university hospitals in South Korea were recruited. SQTI was defined as a Bazett's formula-corrected QT interval (QTc) ≤ 340 ms in serial electrocardiograms. Age- and sex-matched patients with a normal QTc and without overt cardiovascular disease were included in a 1:4 ratio. Clinical and ECG features and outcomes were compared between patients with and without SQTI., Results: 34 patients with SQTI [age, 23.5 (21-30.5) years; 31 male] were followed up for 4.8 (2.0-7.8) years. Early repolarization, tall T wave, and U wave were significantly more frequent in patients with SQTI than in those without SQTI. QT dispersion [44.0 (28.0-73.0) vs. 20.0 (12.0-35.0) ms, P < 0.001] was significantly wider and heart rate [52.0 (47.0-58.0) vs. 70.0 (62.3-84.0)/min, P < 0.001] was significantly slower in patients with SQTI than in those without. Atrial fibrillation (AF, 11.8% vs. 2.2%, P = 0.030) and ventricular arrhythmia (VA)/SCA (8.7% vs. 0%, P = 0.007) were significantly more frequent in patients with SQTI than in those without. SQTI was significantly associated with AF [odds ratio, 5.911; 95% confidence interval, 1.257-27.808; P = 0.025] and VA/SCA., Conclusions: In this subset of Korean population, SQTI was associated with AF and VA/SCA.

Congenitally corrected transposition of the great arteries (ccTGA) is associated with various types of arrhythmia, including supraventricular tachycardia (SVT) and complete atrioventricular block (cAVB). Our study aims to characterize the arrhythmia burden, associated risk factors, arrhythmia mechanisms, and the long-term follow-up results in patients with ccTGA in a large Asian cohort., Methods: We enrolled 104 patients (43 women and 61 men) diagnosed with ccTGA at our institution. The mean age at last follow-up was 20.8 years., Results: For 40 patients (38%) with tachyarrhythmia, paroxysmal SVT (PSVT) and atrial arrhythmia were observed in 17 (16%) and 27 (26%) patients, respectively, with 4 patients (4%) having both types of SVT. The 20-year and 30-year SVT-free survival rates were 68% and 54%, respectively. Seven patients (7%) developed cAVB: 2 (2%) developed spontaneously, and the other 5 (5%) was surgically complicated (surgical risk of cAVB: 7%, all associated with ventricular septal defect repair surgery). PSVT was mostly associated with accessory pathways (5/9) but also related to twin atrioventricular nodal reentry tachycardia (3/9) and atrioventricular nodal reentry tachycardia (1/9). Most of the accessory pathways were located at tricuspid valve (9/10). Catheter ablation successfully eliminated all PSVT substrates (10/10) and most of the atrial arrhythmia substrates (3/5), with low recurrence rate., Conclusions: The arrhythmia burden in patients with ccTGA is high and increases over time. However, cAVB incidence was relatively low and kept stationary in this Asian cohort. The mechanisms of SVT are complicated and can be controlled through catheter ablation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Opioid poisoning is a frequent cause of death in drug addicts and occurs with opioid treatment. Quetiapine is often found in forensic autopsies and may increase the risk of fatal opioid poisoning by enhancing sedation, respiratory depression, hypotension and QT prolongation. We systematically searched for studies of acute toxicity of quetiapine or other antipsychotics combined with morphine or methadone. Case reports describing toxicity of quetiapine combined with morphine or methadone were also included. We retrieved one human study that observed pharmacokinetic interaction between quetiapine and methadone, and 16 other human studies. Fourteen investigated the combination of droperidol and morphine in treatment doses, and some indicated an additive sedative effect. Five animal studies with acepromazine in combination with morphine or methadone were located and indicated an additive effect on sedation and hypotension. Six forensic case reports in which death could have been caused solely by quetiapine, the opioid, or other drugs were found. Thus, acute toxicity of quetiapine combined with morphine or methadone has not been studied. Because of quetiapine's effects on alpha-adrenoceptors, muscarinic and histamine receptors, human ether-a-go-go-channels and methadone kinetics, we suggest further research to clarify if the indicated additive effects of opioids and droperidol or acepromazine are also true for quetiapine., (© 2020 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Arrhythmias have been reported frequently in COVID-19 patients, but the incidence and nature have not been well characterized. Patients admitted with COVID-19 and monitored by telemetry were prospectively enrolled in the study. Baseline characteristics, hospital course, treatment and complications were collected from the patients' medical records. Telemetry was monitored to detect the incidence of cardiac arrhythmias. The incidence and types of cardiac arrhythmias were analyzed and compared between survivors and non-survivors. Among 143 patients admitted with telemetry monitoring, overall in-hospital mortality was 25.2% (36/143 patients) during the period of observation (mean follow-up 23.7 days). Survivors were less tachycardic on initial presentation (heart rate 90.6 ± 19.6 vs. 99.3 ± 23.1 bpm, p = 0.030) and had lower troponin (peak troponin 0.03 vs. 0.18 ng/ml. p = 0.004), C-reactive protein (peak C-reactive protein 97 vs. 181 mg/dl, p = 0.029), and interleukin-6 levels (peak interleukin-6 30 vs. 246 pg/ml, p = 0.003). Sinus tachycardia, the most common arrhythmia (detected in 39.9% [57/143] of patients), occurred more frequently in non-survivors (58.3% vs. 33.6% in survivors, p = 0.009). Premature ventricular complexes occurred in 28.7% (41/143), and non-sustained ventricular tachycardia in 15.4% (22/143) of patients, with no difference between survivors and non-survivors. Sustained ventricular tachycardia and ventricular fibrillation were not frequent (seen only in 1.4% and 0.7% of patients, respectively). Contrary to reports from other regions, overall mortality was higher and ventricular arrhythmias were infrequent in this hospitalized and monitored COVID-19 population. Either disease or management-related factors could explain this divergence of clinical outcomes, and should be urgently investigated., Competing Interests: The authors have declared that no competing interests exist.

Objective: To investigate the obesity paradox and its interrelationship with objective physical activity (PA) in patients at high risk of sudden cardiac death., Methods: A total of 782 patients with implantable cardioverter-defibrillators/cardiac resynchronization therapy defibrillators in the Study of Home Monitoring System Safety and Efficacy in Cardiac Implantable Electronic Device-Implantable Patients registry were retrospectively analyzed and grouped by body mass index (BMI) (kg/m2): normal weight (18.5 ≤ BMI < 25) and overweight or class I obesity (25 ≤ BMI < 35). PA was measured with home monitoring and categorized into 4 groups (Q1-Q4) by the baseline quartiles. The main endpoint was all-cause mortality., Results: During a mean follow-up period of 59.9 ± 21.9 months, 182 all-cause mortality events occurred. Mortality tended to be lower in overweight and obesity patients (18.9% vs 25.1%, P = 0.061) and decreased by PA quartiles (44.1% vs 22.6% vs 15.3% vs 11.2%, Q1-Q4, P < 0.001). Multivariate Cox analysis indicated BMI (hazard ratio, 0.918; 95% confidence interval, 0.866-0.974; P = 0.004) and PA (0.436, 0.301-0.631, Q2 vs Q1; 0.280, 0.181-0.431, Q3 vs Q1; 0.257, 0.158-0.419, Q4 vs Q1; P < 0.001 for all) were associated with reduced risk. The obesity paradox was significant in the total cohort (log rank P = 0.049) and low PA group (log rank P = 0.010), but disappeared in the high PA group (log rank P = 0.692). Dose-response curves showed a significant reduction in risk with low-moderate PA, and the pattern varied between different BMI groups., Conclusions: The obesity paradox only persisted in physically inactive patients. PA might be related to the development of the obesity paradox., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Diabetic nephropathy, a pathologically diagnosed microvascular complication of diabetes, is a strong risk factor for cardiovascular events, which mainly involve arteries larger than those affected in diabetic nephropathy. However, the association between diabetic nephropathy pathological findings and cardiovascular events has not been well studied. We aimed to investigate whether the pathological findings in diabetic nephropathy are closely associated with cardiovascular event development., Methods: This retrospective cohort study analysed 377 people with type 2 diabetes and biopsy-proven diabetic nephropathy, with a median follow-up of 5.9 years (interquartile range 2.0 to 13.5). We investigated how cardiovascular events were impacted by two vascular diabetic nephropathy lesions, namely arteriolar hyalinosis and arterial intimal thickening, and by glomerular and interstitial lesions., Results: Of the 377 people with diabetic nephropathy, 331 (88%) and 295 (78%) had arteriolar hyalinosis and arterial intimal thickening, respectively. During the entire follow-up period, those with arteriolar hyalinosis had higher cardiovascular event rates in the crude Kaplan-Meier analysis than those without these lesions (P = 0.005, log-rank test). When fully adjusted for clinically relevant confounders, arteriolar hyalinosis independently predicted cardiovascular events [hazard ratio (HR) 1.99; 95% confidence interval (CI) 1.12, 3.86], but we did not find any relationship between arterial intimal thickening and cardiovascular events (HR 0.89; 95% CI 0.60, 1.37). Additionally, neither glomerular nor interstitial lesions were independently associated with cardiovascular events in the fully adjusted model., Conclusions: Arteriolar hyalinosis, but not intimal thickening of large arteries, was strongly associated with cardiovascular events in people with diabetic nephropathy., (© 2020 Diabetes UK.)

Introduction: Electrocardiographic characteristics in COVID-19-related mortality have not yet been reported, particularly in racial/ethnic minorities., Methods and Results: We reviewed demographics, laboratory and cardiac tests, medications, and cardiac rhythm proximate to death or initiation of comfort care for patients hospitalized with a positive SARS-CoV-2 reverse-transcriptase polymerase chain reaction in three New York City hospitals between March 1 and April 3, 2020 who died. We described clinical characteristics and compared factors contributing toward arrhythmic versus nonarrhythmic death. Of 1258 patients screened, 133 died and were enrolled. Of these, 55.6% (74/133) were male, 69.9% (93/133) were racial/ethnic minorities, and 88.0% (117/133) had cardiovascular disease. The last cardiac rhythm recorded was VT or fibrillation in 5.3% (7/133), pulseless electrical activity in 7.5% (10/133), unspecified bradycardia in 0.8% (1/133), and asystole in 26.3% (35/133). Most 74.4% (99/133) died receiving comfort measures only. The most common abnormalities on admission electrocardiogram included abnormal QRS axis (25.8%), atrial fibrillation/flutter (14.3%), atrial ectopy (12.0%), and right bundle branch block (11.9%). During hospitalization, an additional 17.6% developed atrial ectopy, 14.7% ventricular ectopy, 10.1% atrial fibrillation/flutter, and 7.8% a right ventricular abnormality. Arrhythmic death was confirmed or suspected in 8.3% (11/133) associated with age, coronary artery disease, asthma, vasopressor use, longer admission corrected QT interval, and left bundle branch block (LBBB)., Conclusions: Conduction, rhythm, and electrocardiographic abnormalities were common during COVID-19-related hospitalization. Arrhythmic death was associated with age, coronary artery disease, asthma, longer admission corrected QT interval, LBBB, ventricular ectopy, and usage of vasopressors. Most died receiving comfort measures., (© 2020 Wiley Periodicals LLC.)

Aims: Chronic heart failure may lead to chronic kidney disease. Previous studies suggest tubular markers N-acetyl-b-D-glucosaminidase (NAG) and Kidney-injury-molecule-1 (KIM-1) as potential markers for the cardiorenal syndrome (CRS). The prognostic value of NAG and KIM-1 regarding implantable cardioverter defibrillator (ICD) shock therapies is unknown., Methods: We included 314 patients with an ICD and collected plasma and urine samples. Urine-values of NAG and KIM-1 got related to urinary creatinine. Outcomes of interest were sustained adequate shock therapies and a combined endpoint of all-cause mortality, rehospitalisation due to congestive heart failure and adequate shock therapies. Follow up time was 32 months (IQR 6-35 months)., Results: KIM-1 and NAG were positively correlated with NT-proBNP (KIM-1: r = .34, P < .001; NAG: r = .47, P < .001). NAG was significantly elevated in patients with primary prevention compared with secondary prevention ICD indication (P = .003). According to Kaplan Meier analysis, NAG as well as NT-proBNP were significant predictors for adequate ICD shock therapies and for the combined endpoint (each P < .001). Elevated KIM-1 showed no significant differences (each P = n.s.). In multivariate cox regression analysis, NAG as well as NT-proBNP were both independent predictors for adequate ICD shock therapies as well as the combined endpoint, beside ejection fraction <35% (each P < .05). Diabetes, primary prevention ICD indication, coronary artery disease, eGFR and age were no significant predictors for both endpoints (each P = n.s.)., Conclusion: Similar to NT-proBNP, NAG showed promising value for overall prognostication in ICD patients. Especially, NAG seems to incorporate an additional prognostic value regarding occurrence of ICD shock therapies., (© 2020 The Authors. Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology.)

Background: This study investigates the impact of the occurrence of Osborn waves during therapeutic hypothermia (TH) on the recurrence of future fatal arrhythmias in patients resuscitated after sudden cardiac arrest (SCA)., Methods: Of all survivors of out-of-hospital SCA, 100 consecutive patients (mean age, 52 ± 15 years; 80% men) who received TH were included in this study., Results: The most common first documented arrhythmia was ventricular fibrillation (VF) (77%), and ischemic heart disease (44%) and idiopathic VF (22%) were the most common causes of SCA in resuscitated patients. During TH, Osborn waves developed in 29 patients (29%). Osborn waves occurred more frequently in patients with Brugada syndrome. Patients with Osborn waves had lower in-hospital (10.3% vs 26.8%; P = .072) and 1-year death rates (20.7% vs 39.4%; P = .073) and better cerebral function (cerebral performance category scale, 2.0 ± 1.5 vs 2.7 ± 1.8; P = .053) than those without Osborn waves, although there was no statistical significance. Among 78 in-hospital survivors, 31 (40%) underwent implantable cardioverter-defibrillator (ICD) implantation. Appropriate ICD shocks from fatal arrhythmias were more frequent in patients who had Osborn waves than in those without Osborn waves (43% vs 6%; P = .032)., Conclusions: Osborn waves during TH had no significant effect on the survival and cerebral function of patients resuscitated SCA. However, appropriate ICD shocks due to the recurrence of VF were more frequent in patients with Osborn waves during long-term follow-up., (© 2020 Wiley Periodicals LLC.)

Objective : We study whether the carotid artery stenting (CAS) and carotid endarterectomy (CEA) differ from each other in postoperative ventricular arrhythmia, along with neurological complications (perioperative stroke and transient ischemic attack), in-hospital mortality, and estimated medical cost. Methods : This study used data of patients with carotid artery stenosis from the National Inpatient Sample (NIS) database (2011-2014) from the United States of America. Based on the procedure that patients received, individuals were categorized into groups of CAS and CEA. Multilevel analyses were conducted to examine the difference in the following outcomes: postoperative ventricular arrhythmia, neurological complications, in-hospital mortality, and medical costs between CAS and CEA. The patient age, gender, race, Charlson Comorbidity Index, primary payer, emergency department service record, bed size of hospital, region of the hospital, and location of the hospital were adjusted in each model. In addition, preexisting cardiovascular diseases (CVDs) were adjusted for when predicting postoperative ventricular arrhythmia; postoperative CVDs were adjusted for in the model of in-hospital mortality. Results : A total of 127,321 carotid artery stenosis hospitalizations were included in our analyses ( n = 17,074 in CAS, n = 110,247 in CEA). Multivariate logistic regressions showed that compared with patients underwent CAS, those with CEA had a lower odds of postoperative ventricular arrhythmia (odds ratio [OR] = 0.81, 95% confidence interval [CI]: [0.66-0.98]), less neurological complications (OR = 0.55, 95% CI: [0.51-0.59] in general; OR = 0.63, 95% CI: [0.57-0.69] in ischemic stroke; OR = 0.26, 95% CI: [0.20-0.32] in hemorrhagic stroke; and OR = 0.58, 95% CI: [0.47-0.71] in transient ischemic attack), and in-hospital mortality (OR = 0.52, 95% CI: [0.42-0.64]). Generalized linear model indicated patients undergoing CEA had lower medical cost (β = -4329.99, 95% CI: [-4552.61, -4107.38]) than patients undergoing CAS. Conclusions : In short-term outcomes, CEA was associated with a lower risk of postoperative ventricular arrhythmia, neurological complications, in-hospital mortality, and lower cost as compared with CAS.

Chloroquine (CQ) and hydroxychloroquine (HCQ) were among the first drugs repurposed for the treatment of SARS-CoV-2 infection. A few in vitro studies confirmed that both drugs exhibited dose dependent anti-SARS-CoV-2 activities. These observations and the encouraging results from early poorly conducted observational studies created a major hype about the therapeutic potential of these drugs in the treatment of COVID-19 disease. This was further catalyzed by media and political influences leading to a widespread use of these agents. Subsequent randomized trials revealed lack of efficacy of these agents in improving the outcomes of COVID-19 or in preventing infection in post-exposure prophylaxis studies. Nevertheless, many ongoing trials continue to actively recruit tens of thousands of patients to receive HCQ worldwide. In this perspective, we address the possible mechanisms behind the lack of efficacy and the increased risk of cardiac toxicity of HCQ in COVID-19 disease. For the lack of efficacy, we discuss the fundamental differences of treatment initiation between in vitro and in vivo studies, the pitfalls of the pharmacological calculations of effective blood drug concentrations and related dosing regimens, and the possible negative effect of HCQ on the antiviral type-I interferon response. Although it has been repeatedly claimed that HCQ has a longstanding safety track record for many decades in use, we present counterarguments for this contention due to disease-drug and drug-drug interactions. We discuss the molecular mechanisms and the cumulative epidemiological evidence of HCQ cardiac toxicity., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Patients with coronavirus disease 2019 (COVID-19) who develop cardiac injury are reported to experience higher rates of malignant cardiac arrhythmias. However, little is known about these arrhythmias-their frequency, the underlying mechanisms, and their impact on mortality., Methods: We extracted data from a registry (NCT04358029) regarding consecutive inpatients with confirmed COVID-19 who were receiving continuous telemetric ECG monitoring and had a definitive disposition of hospital discharge or death. Between patients who died versus discharged, we compared a primary composite end point of cardiac arrest from ventricular tachycardia/fibrillation or bradyarrhythmias such as atrioventricular block., Results: Among 800 patients with COVID-19 at Mount Sinai Hospital with definitive dispositions, 140 patients had telemetric monitoring, and either died (52) or were discharged (88). The median (interquartile range) age was 61 years (48-74); 73% men; and ethnicity was White in 34%. Comorbidities included hypertension in 61%, coronary artery disease in 25%, ventricular arrhythmia history in 1.4%, and no significant comorbidities in 16%. Compared with discharged patients, those who died had elevated peak troponin I levels (0.27 versus 0.02 ng/mL) and more primary end point events (17% versus 4%, P =0.01)-a difference driven by tachyarrhythmias. Fatal tachyarrhythmias invariably occurred in the presence of severe metabolic imbalance, while atrioventricular block was largely an independent primary event., Conclusions: Hospitalized patients with COVID-19 who die experience malignant cardiac arrhythmias more often than those surviving to discharge. However, these events represent a minority of cardiovascular deaths, and ventricular tachyarrhythmias are mainly associated with severe metabolic derangement. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04358029.

Introduction: Coronavirus disease 2019 (COVID-19) is a worldwide pandemic, and cardiovascular complications and arrhythmias in these patients are common. Cardiac monitoring is recommended for at risk patients; however, the availability of telemetry capable hospital beds is limited. We sought to evaluate a patch-based mobile telemetry system for inpatient cardiac monitoring during the pandemic., Methods: A prospective cohort study was performed of inpatients hospitalized during the pandemic who had mobile telemetry devices placed; patients were studied up until the time of discharge or death. The primary outcome was a composite of management changes based on data obtained from the system and detection of new arrhythmias. Other clinical outcomes and performance characteristics of the mobile telemetry system were studied., Results: Eighty-two patients underwent mobile telemetry device placement, of which 31 (37.8%) met the primary outcome, which consisted of 24 (29.3%) with new arrhythmias detected and 18 (22.2%) with management changes. Twenty-one patients (25.6%) died during the study, but none from primary arrhythmias. In analyses, age and heart failure were associated with the primary outcome. Monitoring occurred for an average of 5.3 ± 3.4 days, with 432 total patient-days of monitoring performed; of these, QT-interval measurements were feasible in 400 (92.6%)., Conclusion: A mobile telemetry system was successfully implemented for inpatient use during the COVID-19 pandemic and was shown to be useful to inform patient management, detect occult arrhythmias, and monitor the QT-interval. Patients with advanced age and structural heart disease may be more likely to benefit from this system., (© 2020 Wiley Periodicals LLC.)

Background: Pathologic examination of conduction system (CS) is not routinely performed, and histologic changes are mostly reported in forensic practice., Methods: We studied the value of dissecting the CS in a cohort of pediatric patients with unexplained sudden death or severe, inexplicable arrhythmias. Histopathologic changes present in CS components were recorded and correlated with findings noted in other cardiac structures., Results: Twenty-one subjects (11 unexplained sudden deaths and 10 life-threatening arrhythmias) were identified; 18 (86%) had CS pathologic abnormalities. In 13 patients (62%), the CS findings mirrored those found in other cardiac sections (inflammation, allograft vasculopathy, vascular fibromuscular dysplasia, cardiomyopathy-related changes, and tumor/tumor-like conditions). Five cases (24%) had abnormalities restricted to CS (bundle of His [BH] with fibrotic scar and patch material following ventricular septal defect repair, inflammation, BH with fibrosis and calcifications, and intimal fibroplasia of sinoatrial node artery)., Conclusions: Pathologic changes within the CS are present in a high number of pediatric patients presenting with unexplained sudden death or life-threatening arrhythmias. Frequently, the findings mirror those observed in other cardiac structures. However, in a significant number of cases (24%), the changes are restricted to CS and likely explain the patients' symptoms or cause of death, suggesting that systematic dissection of CS unveils valuable information.

Background: There is clear evidence that patients with prior myocardial infarction and a reduced ejection fraction benefit from implantation of a cardioverter-defibrillator (ICD). It is unclear whether this benefit is altered by whether or not revascularization is performed prior to ICD implantation., Methods: This was a retrospective cohort study following patients who underwent ICD implantation from 2002 to 2014. Patients with ischemic cardiomyopathy and either primary or secondary prevention ICDs were selected for inclusion. Using the electronic medical record, cardiac catheterization data, revascularization status (percutaneous coronary intervention or coronary bypass surgery) were recorded. The outcomes were mortality and ventricular arrhythmia., Results: There were 606 patients included in the analysis. The mean age was 66.3 ± 10.1 years, 11.9% were women, and the mean LVEF was 30.5 ± 12.0, 58.9% had a primary indication for ICD, 82.0% of the cohort had undergone coronary catheterization prior to ICD implantation. In the overall cohort, there were fewer mortality and ventricular arrhythmia events in patients who had undergone prior revascularization. In patients who had an ICD for secondary prevention, revascularization was associated with a decrease in mortality (HR 0.46, 95% CI (0.24, 0.85) p = 0.015), and a trend towards fewer ventricular arrhythmia (HR 0.62, 95% CI (0.38, 1.00) p = 0.051). There was no association between death or ventricular arrhythmia with revascularization in patients with primary prevention ICDs., Conclusion: Revascularization may be beneficial in preventing recurrent ventricular arrhythmia, and should be considered as adjunctive therapy to ICD implantation to improve cardiovascular outcomes.

Background: The toxicity of silica nanoparticles (SiNPs) on cardiac electrophysiology has seldom been evaluated., Methods: Patch-clamp was used to investigate the acute effects of SiNP-100 (100 nm) and SiNP-20 (20 nm) on the transmembrane potentials (TMPs) and ion channels in cultured neonatal mouse ventricular myocytes. Calcium mobilization in vitro, cardiomyocyte ROS generation, and LDH leakage after exposure to SiNPs in vitro and in vivo were measured using a microplate reader. Surface electrocardiograms were recorded in adult mice to evaluate the arrhythmogenic effects of SiNPs in vivo. SiNP endocytosis was observed using transmission electron microscopy., Results: Within 30 min, both SiNPs (10 -8 -10 -6 g/mL) did not affect the resting potential and I K1 channels. SiNP-100 increased the action potential amplitude (APA) and the I Na current density, but SiNP-20 decreased APA and I Na density. SiNP-100 prolonged the action potential duration (APD) and decreased the I to current density, while SiNP-20 prolonged or shortened the APD, depending on exposure concentrations and increased I to density. Both SiNPs (10 -6 g/mL) induced calcium mobilization but did not increase ROS and LDH levels and were not endocytosed within 10 min in cardiomyocytes in vitro. In vivo, SiNP-100 (4-10 mg/kg) and SiNP-20 (4-30 mg/kg) did not elevate myocardial ROS but increased LDH levels depending on dose and exposure time. The same higher dose of SiNPs (intravenously injected) induced tachyarrhythmias and lethal bradyarrhythmias within 90 min in adult mice., Conclusion: SiNPs (i) exert rapid toxic effects on the TMPs of cardiomyocytes in vitro largely owing to their direct interfering effects on the I Na and I to channels and Ca 2+ homeostasis but not I K1 channels and ROS levels, and (ii) induce tachyarrhythmias and lethal bradyarrhythmias in vivo. SiNP-100 is more toxic than SiNP-20 on cardiac electrophysiology, and the toxicity mechanism is likely more complicated in vivo., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Liu et al.)

Background: Sudden cardiac death (SCD) in the young is devastating. Contemporary incidence remains unclear with few recent nationwide studies and limited data addressing risk factors for causes. We aimed to determine incidence, trends, causes, and risk factors for SCD in the young., Methods and Results: The National Coronial Information System registry was reviewed for SCD in people aged 1 to 35 years from 2000 to 2016 in Australia. Subjects were identified by the International Classification of Diseases , Tenth Revision code relating to circulatory system diseases (I00-I99) from coronial reports. Baseline demographics, circumstances, and cause of SCD were obtained from coronial and police reports, alongside autopsy and toxicology analyses where available. During the study period, 2006 cases were identified (median age, 28±7 years; men, 75%; mean body mass index, 29±8 kg/m 2 ). Annual incidence ranged from 0.91 to 1.48 per 100 000 age-specific person-years, which was the lowest in 2013 to 2015 compared with previous 3-year intervals on Poisson regression model ( P =0.001). SCD incidence was higher in nonmetropolitan versus metropolitan areas (0.99 versus 0.53 per 100 000 person-years; P <0.001). The most common cause of SCD was coronary artery disease (40%), followed by sudden arrhythmic death syndrome (14%). Incidence of coronary artery disease-related SCD decreased from 2001-2003 to 2013-2015 ( P <0.001). Proportion of SCD related to sudden arrhythmic death syndrome increased during the study period ( P =0.02) although overall incidence was stable ( P =0.22). Residential remoteness was associated with coronary artery disease-related SCD (odds ratio, 1.44 [95% CI, 1.24-1.67]; P <0.001). For every 1-unit increase, body mass index was associated with increased likelihood of SCD from cardiomegaly (odds ratio, 1.08 [95% CI, 1.05-1.11]; P <0.001) and dilated cardiomyopathy (odds ratio, 1.04 [95% CI, 1.01-1.06]; P =0.005)., Conclusions: Incidence of SCD in the young and specifically coronary artery disease-related SCD has declined in recent years. Proportion of SCD related to sudden arrhythmic death syndrome increased over the study period. Geographic remoteness and obesity are risk factors for specific causes of SCD in the young.

Objectives: Despite rapid implementation of anti-arrhythmic treatment and sedation and controlling the triggering event, rare patients develop treatment-refractory electrical storm and their hemodynamic instability prevents emergency catheter ablation. In that context, venoarterial extracorporeal membrane oxygenation could rapidly restore hemodynamics and tissue perfusion and reduce myocardial oxygen consumption, until adequate anti-arrhythmic drug levels are reached to safely perform catheter ablation., Design: Retrospective, multicenter study over an 8-year period., Setting: Two French tertiary care centers., Patients: Eighty-three consecutive adults with venoarterial extracorporeal membrane oxygenation-supported treatment-refractory electrical storm (median [interquartile range] age, 55 yr [48-63 yr])., Measurements and Main Results: Fifty-nine percent of these patients had acute ischemic cardiomyopathy and 66% underwent cardiopulmonary resuscitation prior to venoarterial extracorporeal membrane oxygenation initiation, with 18% cannulated during it. Fifty patients (60%) had ventricular tachycardia and/or ventricular fibrillation alternating with short periods of sinus rhythm and 33 (40%) had refractory ventricular tachycardia and/or ventricular fibrillation. Twelve patients (15%) underwent safe catheter ablation under venoarterial extracorporeal membrane oxygenation. After a median of 3 days (1-13 d) on extracorporeal membrane oxygenation support, 37 patients (45%) were successfully weaned off and 42% were alive 6 months post-ICU admission. Multivariable analysis retained ventricular tachycardia and/or ventricular fibrillation episodes alternating with short periods of sinus rhythm (odds ratio, 0.18; 95% CI, 0.06-0.52; p = 0.002) and age less than 50 years (odds ratio, 0.32; 95% CI, 0.18-0.89; p = 0.002) as being independent protective factors with 6-month survival, regardless of the underlying electrical storm cause., Conclusions: Among venoarterial extracorporeal membrane oxygenation-supported drug-refractory electrical storm patients, 42% survived 6 months post-ICU admission. Ventricular tachycardia and/or ventricular fibrillation episodes alternating with short periods of sinus rhythm and age less than 50 years were independently associated with better survival.

Objective: To examine whether anxiety and depression at time of implantation of an implantable cardioverter defibrillator (ICD) is associated with ventricular arrhythmias (VAs) and mortality 7 years later., Methods: A cohort of 399 patients (80% men; mean (SD) age = 58.3 (12.2)) implanted with an ICD completed the Hospital Anxiety and Depression Scale (HADS) and the State-Trait Anxiety Inventory at time of implantation. Patients were followed up for VAs and mortality at 7 years., Results: At 7-years follow-up, 34% of the patients had died and 38% had experienced VAs. Baseline depression (score ≥ 8) (HR:2.10; 95% CI:1.44-3.05, p < 0.001) was associated with 7-year mortality in adjusted analyses while state anxiety (score ≥ 40) (HR:1.45; 95% CI:1.02-2.06, p = 0.039) and trait anxiety (score ≥ 40) (HR:1.51; 95% CI:1.06-2.16, p = 0.022) showed a trend towards an association with mortality. No association was found between VAs and anxiety and depression. There was a dose-response relationship with higher burden of anxiety (HR:2.13; 95% CI:1.31-3.46, p = 0.002) and depression (HR:2.13; 95% CI:1.33-3.42, p = 0.002) measured with the HADS (scores < 8, 8-10 and > 10) being associated with an increased risk of mortality., Conclusion: Patients with depression had greater risk of mortality, whereas anxiety only showed a trend. Neither anxiety nor depression was associated with VAs during follow-up., Competing Interests: Declaration of competing interest CMA, DAMJT, SSP: no conflict of interest to declare. JBJ: Speaker bureau: Medtronic and Merit Medical; Advisory board: Biotronic and Medtronic., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Hereditary transthyretin amyloidosis is a systemic infiltrative disease, caused by a mutation in the transthyretin gene. p.Glu89Gln is the most common mutation in the Balkan countries., Methods: We evaluated the clinical manifestations, cardiac involvement, morbidity and mortality in 78 patients with p.Glu89Gln mutation, verified through a DNA analysis. Clinical assessment, electrocardiogram and echocardiography were performed at the time of diagnosis. The patients have been followed for 30 months., Results: All included patients were Caucasian, 39 (50%) - men, with median age at diagnosis of 56 years (42-73), median age at onset -- 53 years (35-69), starting significantly earlier in men (4.36, P = 0.004). Cardiac and neurological involvement was found in 74 (95%) patients. Pathological ECG was present in 65 (84%) patients, infarct pattern in 43 (56%), low voltage in 24 (31%). Echocardiography revealed an infiltrative cardiomyopathy with restrictive filling in 31 (40%) and ejection fraction less than 50% in 20 (27%) patients. Twenty-two patients (28%) died: 14 (64%) because of advanced heart failure, 6 (27%) died suddenly, 2 (9%) from an ischemic stroke. The median age at death was 58.5 years (52-72). No statistically significant sex difference in survival was observed; a significant difference in survival was found for the New York Heart Association class, familial amyloidotic polyneuropathy stage, ejection fraction, filling pattern and tafamidis treatment., Conclusion: Cardiac involvement is common and has significant prognostic implications in the evaluated patients with p.Glu89Gln mutation. Heart failure and rhythm disturbances are the main causes of death. An earlier identification of the disease is crucial to improve prognosis.

Introduction: Elevated plasma levels of asymmetric dimethylarginine (ADMA), an inhibitor of NO synthase, are associated with adverse outcome. There is no data available, whether ADMA levels are associated with arrhythmic death (AD) in patients with ischemic cardiomyopathy (ICM) or non-ischemic, dilated cardiomyopathy (DCM)., Methods and Results: A total of 110 ICM, 52 DCM and 30 control patients were included. Primary outcome parameter of this prospective study was arrhythmic death (AD) or resuscitated cardiac arrest (RCA). Plasma levels of ADMA were significantly higher in ICM (p < 0.001) and in DCM (p < 0.001) patients compared to controls. During a median follow-up of 7.0 years, 62 (32.3%) patients died. AD occurred in 26 patients and RCA was observed in 22 patients. Plasma levels of ADMA were not associated with a significantly increased risk of AD or RCA in ICM (hazard ratio (HR) = 1.37, p = 0.109) or in DCM (HR = 1.06, p = 0.848) patients. No significant association was found with overall mortality in ICM (HR = 1.39, p = 0.079) or DCM (HR = 1.10, p = 0.666) patients. Stratified Kaplan-Meier curves for ADMA levels in the upper tertile (>0.715 µmol/l) or the two lower tertiles (≤0.715 µmol/l) did not show a higher risk for AD or RCA (p = 0.221) or overall mortality (p = 0.548). In patients with left ventricular ejection fraction ≤ 35%, ADMA was not associated with AD or RCA (HR = 1.35, p = 0.084) or with overall mortality (HR = 1.24, p = 0.162)., Conclusions: Plasma levels of ADMA were elevated in patients with ICM or DCM as compared to controls, but were not significantly predictive for overall mortality or the risk for arrhythmic death., (Copyright © 2020 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to determine, using continuous electrocardiographic monitoring (CEM) pre-transcatheter aortic valve replacement (TAVR), the incidence and type of unknown pre-existing arrhythmic events (AEs) in TAVR candidates, and to evaluate the occurrence and impact of therapeutic changes secondary to the detection of AEs pre-TAVR., Background: Scarce data exist on the arrhythmic burden of TAVR candidates (pre-procedure)., Methods: This was a prospective study including 106 patients with severe aortic stenosis and no prior permanent pacemaker screened for TAVR. A prolonged (1 week) CEM was implanted within the 3 months pre-TAVR. Following heart team evaluation, 90 patients underwent elective TAVR., Results: New AEs were detected by CEM in 51 (48.1%) patients, leading to a treatment change in 14 of 51 (27.5%) patients. Atrial fibrillation or tachycardia was detected in 8 of 79 (10.1%) patients without known atrial fibrillation or tachycardia, and nonsustained ventricular arrhythmias were detected in 31 (29.2%) patients. Significant bradyarrhythmias were observed in 22 (20.8%) patients, leading to treatment change and permanent pacemaker in 8 of 22 (36.4%) and 4 of 22 (18.2%) patients, respectively. The detection of bradyarrhythmias increased up to 30% and 47% among those patients with pre-existing first-degree atrioventricular block and right bundle branch block, respectively. Chronic renal failure, higher valve calcification, and left ventricular dysfunction determined (or tended to determine) an increased risk of AEs pre-TAVR (p = 0.028, 0.052, and 0.069, respectively). New onset AEs post-TAVR occurred in 22.1% of patients, and CEM pre-TAVR allowed early arrhythmia diagnosis in one-third of them., Conclusions: Prolonged CEM in TAVR candidates allowed identification of previously unknown AEs in nearly one-half of the patients, leading to prompt therapeutic measures (pre-TAVR) in about one-fourth of them. Pre-existing conduction disturbances (particularly right bundle branch block) and chronic renal failure were associated with a higher burden of AEs., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The timing of onset and associated predictors of late new conduction disturbances (CDs) leading to permanent pacemaker implantation (PPI) following transcatheter aortic valve implantation (TAVI) are still unknown, however, essential for an early and safe discharge. This study aimed to investigate the timing of onset and associated predictors of late onset CDs in patients requiring PPI (LCP) following TAVI., Methods and Results: We performed retrospective analysis of prospectively collected data from five large volume centres in Europe. Post-TAVI electrocardiograms and telemetry data were evaluated in patients with a PPI post-TAVI to identify the onset of new advanced CDs. Early onset CDs were defined as within 48 hours after procedure, and late onset CDs as after 48 hours. A total of 2804 patients were included for analysis. The PPI rate was 12%, of which 18% was due to late onset CDs (>48 hours). Independent predictors for LCP were pre-existing non-specific intraventricular conduction delay, pre-existing right bundle branch block, self-expandable valves and predilation. At least one of these risk factors was present in 98% of patients with LCP. Patients with a balloon-expandable valve without predilation did not develop CDs requiring PPI after 48 hours., Conclusions: Safe early discharge might be feasible in patients without CDs in the first 48 hours after TAVI if no risk factors for LCP are present., Competing Interests: Competing interests: PRS was a member of the Keystone Heart advisory board., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Left ventricular noncompaction (LVNC) is a hereditary type of cardiomyopathy. Although it is associated with high morbidity and mortality, the related ion channel gene variants in children have not been fully investigated. This study aimed to elucidate the ion channel genetic landscape of LVNC and identify genotype-phenotype correlations in a large Japanese cohort., Methods: We enrolled 206 children with LVNC from 2002 to 2017 in Japan. LVNC was classified as follows: LVNC with congenital heart defects, arrhythmia, dilated phenotype, or normal function. In the enrolled patients, 182 genes associated with cardiomyopathy were screened using next-generation sequencing., Results: We identified 99 pathogenic variants in 40 genes in 87 patients. Of the pathogenic variants, 8.8% were in genes associated with channelopathies, 27% were in sarcomere genes, and 11.5% were in mitochondrial genes. Ion channel gene variants were mostly associated with the arrhythmia classification, whereas sarcomere and mitochondrial gene variants were associated with the dilated phenotype. Echocardiography revealed that the group with ion channel gene variants had almost normal LV ejection fraction and LV diastolic diameter Z scores. Fragmented QRS, old age, and an arrhythmia phenotype were the most significant risk factors for ventricular tachycardia ( P =0.165, 0.0428, and 0.0074, respectively). Moreover, the group with ion channel variants exhibited a greater risk of a higher prevalence of arrhythmias such as ventricular tachycardia, rather than congestive heart failure., Conclusions: This is the first study that focused on genotype-phenotype correlations in a large pediatric LVNC patient cohort with ion channel gene variants that were determined using next-generation sequencing. Ion channel gene variants were strongly correlated with arrhythmia phenotypes. Genetic testing and phenotype specification allow for appropriate medical management of specific LVNC targets.

The population of patients with congenital heart disease (CHD) is continuously increasing, and a significant proportion of these patients will experience arrhythmias because of the underlying congenital heart defect itself or as a consequence of interventional or surgical treatment. Arrhythmias are a leading cause of mortality, morbidity and impaired quality of life in adults with CHD. Arrhythmias may also occur in children with or without CHD. In light of the unique issues, challenges and considerations involved in managing arrhythmias in this growing, ageing and heterogeneous patient population and in children, it appears both timely and essential to critically appraise and synthesize optimal treatment strategies. The introduction of catheter ablation techniques has greatly improved the treatment of cardiac arrhythmias. However, catheter ablation in adults or children with CHD and in children without CHD is more technically demanding, potentially causing various complications, and thus requires a high level of expertise to maximize success rates and minimize complication rates. As French recommendations regarding required technical competence and equipment are lacking in this situation, the Working Group of Pacing and Electrophysiology of the French Society of Cardiology and the Affiliate Group of Paediatric and Adult Congenital Cardiology have decided to produce a common position paper compiled from expert opinions from cardiac electrophysiology and paediatric cardiology. The paper details the features of an interventional cardiac electrophysiology centre that are required for ablation procedures in adults with CHD and in children, the importance of being able to diagnose, monitor and manage complications associated with ablations in these patients and the supplemental hospital-based resources required, such as anaesthesia, surgical back-up, intensive care, haemodynamic assistance and imaging. Lastly, the need for quality evaluations and French registries of ablations in these populations is discussed. The purpose of this consensus statement is therefore to define optimal conditions for the delivery of invasive care regarding ablation of arrhythmias in adults with CHD and in children, and to provide expert and - when possible - evidence-based recommendations on best practice for catheter-based ablation procedures in these specific populations., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

The implantable cardioverter-defibrillator (ICD) is the most effective therapy to prevent sudden cardiac death (SCD) in high-risk patients. To overcome infections and failure of transvenous leads, the most frightening complications of conventional ICDs, a completely subcutaneous ICD (S-ICD) has been developed and is currently adopted in routine clinical practice. In view of their long life-expectancy, low competitive risk of dying from non-arrhythmic causes, and high lifetime risk of lead-related complications requiring surgical revisions, young patients with cardiomyopathies and inherited arrhythmia syndromes have traditionally been considered ideal candidates for the S-ICD. However, as growing evidence supported S-ICD safety and efficacy, initial niche implant indications were abandoned in favor of a widespread use of this technology, that is currently adopted in common ICD candidates with severe left ventricular dysfunction. Indeed, guidelines recommend S-ICD implantation as an alternative to TV-ICDs in all ICD candidates, unless pacing is required. This review focuses on the contemporary experience with the S-ICD and explores future scenarios in which device-to-device communication will enable to combine leadless therapies.

Background: Cardiac injury is common in severe coronavirus disease 2019 (COVID-19) and is associated with poor outcomes. We aimed to study predictors of in-hospital death, characteristics of arrhythmias and the effects of QT-prolonging therapy in patients with cardiac injury., Methods: We conducted a retrospective cohort study involving patients with severe COVID-19 who were admitted to Tongji Hospital in Wuhan, China, between Jan. 29 and Mar. 8, 2020. Among patients who had cardiac injury, which we defined as an elevated level of cardiac troponin I (cTnI), we identified demographic and clinical characteristics associated with mortality and need for invasive ventilation., Results: Among 1284 patients with severe COVID-19, 1159 had a cTnI level measured on admission to hospital, of whom 170 (14.7%) had results that showed cardiac injury. We found that mortality was markedly higher in patients with cardiac injury (71.2% v. 6.6%, p < 0.001). We determined that initial cTnI (per 10-fold increase, hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.06-1.66) and peak cTnI level during illness (per 10-fold increase, HR 1.70, 95% CI 1.38-2.10) were associated with poor survival. Peak cTnI was also associated with the need for invasive ventilation (odds ratio 3.02, 95% CI 1.92-4.98). We found arrhythmias in 44 of the 170 patients with cardiac injury (25.9%), including 6 patients with ventricular tachycardia or fibrillation, all of whom died. We determined that patients who received QT-prolonging drugs had longer QTc intervals than those who did not receive them (difference in medians, 45 ms, p = 0.01), but such treatment was not independently associated with mortality (HR 1.04, 95% CI 0.69-1.57)., Interpretation: We found that in patients with COVID-19 and cardiac injury, initial and peak cTnI levels were associated with poor survival, and peak cTnI was a predictor of need for invasive ventilation. Patients with COVID-19 warrant assessment for cardiac injury and monitoring, especially if therapy that can prolong repolarization is started., Trial Registration: Chinese Clinical Trial Registry, No. ChiCTR2000031301., Competing Interests: Competing interests: Kumaraswamy Nanthakumar is supported by grants from the Canadian Institutes of Health Research, is an Investigator with the Heart and Stroke Foundation and is a consultant for Servier, Biosense Webster, Abbott Laboratories and BlueRock Therapeutics. Stéphane Massé is a consultant for Abbott Laboratories. No other competing interests were declared., (© 2020 Joule Inc. or its licensors.)