Has COVID-19 changed the spectrum of arrhythmias and the incidence of sudden cardiac death?

Arrhythmic manifestations of COVID-19 include atrial arrhythmias such as atrial fibrillation or atrial flutter, sinus node dysfunction, atrioventricular conduction abnormalities, ventricular tachyarrhythmias, sudden cardiac arrest, and cardiovascular dysautonomias including the so-called long COVID syndrome. Various pathophysiological mechanisms have been implicated, such as direct viral invasion, hypoxemia, local and systemic inflammation, changes in ion channel physiology, immune activation, and autonomic dysregulation. The development of atrial or ventricular arrhythmias in hospitalized COVID-19 patients has been shown to portend a higher risk of in-hospital death. Management of these arrhythmias should be based on published evidence-based guidelines, with special consideration of the acuity of COVID-19 infection, concomitant use of antimicrobial and anti-inflammatory drugs, and the transient nature of some rhythm disorders. In view of new SARS-CoV­2 variants that may evolve, the development and use of newer antiviral and immunomodulator drugs, and the increasing adoption of vaccination, clinicians must remain vigilant for other arrhythmic manifestations that may occur in association with this novel but potentially deadly disease.

Sudden cardiac arrest during the COVID-19 pandemic: A two-year prospective evaluation in a North American community.

BACKGROUND: Early during the coronavirus disease 2019 (COVID-19) pandemic, higher sudden cardiac arrest (SCA) incidence and lower survival rates were reported. However, ongoing effects on SCA during the evolving pandemic have not been evaluated. OBJECTIVE: The purpose of this study was to assess the impact of COVID-19 on SCA during 2 years of the pandemic. METHODS: In a prospective study of Ventura County, California (2020 population 843,843; 44.1% Hispanic), we compared SCA incidence and outcomes during the first 2 years of the COVID-19 pandemic to the prior 4 years. RESULTS: Of 2222 out-of-hospital SCA cases identified, 907 occurred during the pandemic (March 2020 to February 2022) and 1315 occurred prepandemic (March 2016 to February 2020). Overall age-standardized annual SCA incidence increased from 39 per 100,000 (95% confidence [CI] 37-41) prepandemic to 54 per 100,000 (95% CI 50-57; P <.001) during the pandemic. Among Hispanics, incidence increased by 77%, from 38 per 100,000 (95% CI 34-43) to 68 per 100,000 (95% CI 60-76; P <.001). Among non-Hispanics, incidence increased by 26%, from 39 per 100,000 (95% CI 37-42; P <.001) to 50 per 100,000 (95% CI 46-54). SCA incidence rates closely tracked COVID-19 infection rates. During the pandemic, SCA survival was significantly reduced (15% to 10%; P <.001), and Hispanics were less likely than non-Hispanics to receive bystander cardiopulmonary resuscitation (45% vs 55%; P = .005) and to present with shockable rhythm (15% vs 24%; P = .003). CONCLUSION: Overall SCA rates remained consistently higher and survival outcomes consistently lower, with exaggerated effects during COVID infection peaks. This longer evaluation uncovered higher increases in SCA incidence among Hispanics, with worse resuscitation profiles. Potential ethnicity-specific barriers to acute SCA care warrant urgent evaluation and intervention.

Eosinophilic Infiltration of the Sino-Atrial Node in Sudden Cardiac Death Caused by Long QT Syndrome.

Sudden death is defined as the unexpected death of a healthy person that occurs within the first hour of the onset of symptoms or within 24 h of the victim being last seen alive. In some of these cases, rare deleterious variants of genes associated with inherited cardiac disorders can provide a highly probable explanation for the fatal event. We report the case of a 21-year-old obese woman who lost consciousness suddenly in a public place and was pronounced dead after hospital admission. Clinical autopsy showed an inconclusive gross examination, while in the histopathological analysis an eosinophilic inflammatory focus and interstitial fibrosis in the sino-atrial node were found. Molecular autopsy revealed an intronic variant in the KCNQ1 gene (c.683 + 5G > A), classified as likely pathogenic for long QT syndrome according to the guidelines provided by the American College of Medical Genetics and Genomics. Therefore, there were many anomalies that could have played a role in the causation of the sudden death, such as the extreme obesity, the cardiac anomalies and the KNCQ1 variant. This case depicts the difficult interpretation of rare cardiac structural abnormalities in subjects carrying rare variants responsible for inherited arrhythmic disorders and the challenge for the forensic pathologist to make causal inferences in the determinism of the unexpected decease.

Sports-Related Sudden Cardiac Death Attributable to Myocarditis: A Systematic Review and Meta-analysis.

BACKGROUND: The incidence of sports-related sudden cardiac death (SrSCD) attributable to myocarditis is unknown. With the known association between SARS-CoV-2 (COVID-19) and myocarditis, an understanding of pre-pandemic rates of SrSCD due to myocarditis will be important in assessing a change of risk in the future. The objective was to ascertain the incidence of SrSCD or aborted sudden cardiac death (SCD) attributable to myocarditis in the general population. METHODS: A literature search through PubMed/Medline and Ovid/Embase was completed. Studies of SrSCD with autopsy data or clear-cause aborted SrSCD were included. SrSCD was defined as SCD which occurred within 1 hour of exercise. Data were abstracted by 2 independent reviewers using the MOOSE guidelines. Risk assessment was performed with the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies. Random-effects models were used to report the incidence and 95% CIs. The primary outcome was the incidence of SrSCD attributable to myocarditis, and the secondary outcome was SrSCD overall. RESULTS: Fifteen studies were included comprising 347,092,437 person-years (PY). There were 1955 SrSCD or aborted SrSCD overall with an incidence of 0.93 (95% CI 0.47-1.82) per 100,000 PY. Fifty-three SrSCD were attributed to myocarditis with an incidence of 0.047 (95% CI 0.018-0.123) per 100,000 PY, or 1 death attributable to myocarditis in 2.13 million PY. CONCLUSIONS: In this meta-analysis, the overall incidence of SrSCD was low. Furthermore, SrSCD attributed to myocarditis is exceedingly rare.

Dilated cardiomyopathy in the era of precision medicine: latest concepts and developments.

Dilated cardiomyopathy (DCM) is an umbrella term entailing a wide variety of genetic and non-genetic etiologies, leading to left ventricular systolic dysfunction and dilatation, not explained by abnormal loading conditions or coronary artery disease. The clinical presentation can vary from asymptomatic to heart failure symptoms or sudden cardiac death (SCD) even in previously asymptomatic individuals. In the last 2 decades, there has been striking progress in the understanding of the complex genetic basis of DCM, with the discovery of additional genes and genotype-phenotype correlation studies. Rigorous clinical work-up of DCM patients, meticulous family screening, and the implementation of advanced imaging techniques pave the way for a more efficient and earlier diagnosis as well as more precise indications for implantable cardioverter defibrillator implantation and prevention of SCD. In the era of precision medicine, genotype-directed therapies have started to emerge. In this review, we focus on updates of the genetic background of DCM, characteristic phenotypes caused by recently described pathogenic variants, specific indications for prevention of SCD in those individuals and genotype-directed treatments under development. Finally, the latest developments in distinguishing athletic heart syndrome from subclinical DCM are described.

What accounts for the high mortality of anorexia nervosa?

The exact medical complications, leading to the well-known high risk of death in patients with anorexia nervosa (AN), remain elusive. Such deaths are often abrupt with no satisfactory explanation. Suspected causes include cardiac QTc prolongation and, in turn, torsade de pointes (TdP). Psychotropic medications often prescribed to these patients are linked to QTc prolongation. AN is also presumed to cause heart failure due to malnutrition with increased susceptibility to QTc prolongation, and TdP, resulting in sudden cardiac death. Recent literature, however, is conflicting, and the likely cause of death may involve other cardiac abnormalities, such as low heart rate, abnormal heart rate variability, or increased QT dispersion. With an ongoing gap in research explaining the high mortality rate in AN, a compelling need to define the exact proximate causes of death in these patients remains. Because low serum potassium is the most common trigger for TdP, we postulate the early signal of sudden cardiac death, especially in patients with AN who purge, is hypokalemia. We also speculate that hypoglycemia could be a major factor in the sudden death of patients with AN as well as bradycardia or sinus arrest. A path forward to elucidate potential causes is offered.

ACSM-AMSSM Call to Action: Adapting Preparticipation Cardiovascular Screening to the COVID-19 Pandemic.

ABSTRACT: Preparticipation cardiovascular screening, designed to identify cardiovascular pathology responsible for sudden unexpected death, is recommended by all major professional medical organizations overseeing the clinical care of competitive athletes. Data from several large, prospective, cohort studies indicate that cardiac imaging findings consistent with inflammatory heart disease following COVID-19 infection are more common than most forms of heart disease associated with sudden death during exercise. This call-to-action document is intended to provide recommendations about how routine preparticipation cardiovascular screening for young competitive athletes - which has the capacity to detect both COVID-19 cardiovascular complications and pathology unrelated to infection - should be altered to account for recent scientific advances.

Patient-specific, re-engineered cardiomyocyte model confirms the circumstance-dependent arrhythmia risk associated with the African-specific common SCN5A polymorphism p.S1103Y: Implications for the increased sudden deaths observed in black individuals during the COVID-19 pandemic.

BACKGROUND: During the early stages of the coronavirus disease 2019 (COVID-19) pandemic, a marked increase in sudden cardiac death (SCD) was observed. The p.S1103Y-SCN5A common variant, which is present in ∼8% of individuals of African descent, may be a circumstance-dependent, SCD-predisposing, proarrhythmic polymorphism in the setting of hypoxia-induced acidosis or QT-prolonging drug use. OBJECTIVE: The purpose of this study was to ascertain the effects of acidosis and hydroxychloroquine (HCQ) on the action potential duration (APD) in a patient-specific induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) model of p.S1103Y-SCN5A. METHODS: iPSC-CMs were generated from a 14-year-old p.S1103Y-SCN5A-positive African American male. The patient's variant-corrected iPSC-CMs (isogenic control [IC]) were generated using CRISPR/Cas9 technology. FluoVolt voltage-sensitive dye was used to assess APD90 values in p.S1103Y-SCN5A iPSC-CMs compared to IC before and after an acidotic state (pH 6.9) or 24 hours of treatment with 10 µM HCQ. RESULTS: Under baseline conditions (pH 7.4), there was no difference in APD90 values of p.S1103Y-SCN5A vs IC iPSC-CMs (P = NS). In the setting of acidosis (pH 6.9), there was a significant increase in fold-change of APD90 in p.S1103Y-SCN5A iPSC-CMs compared to IC iPSC-CMs (P <.0001). Similarly, with 24-hour 10 µM HCQ treatment, the fold-change of APD90 was significantly higher in p.S1103Y-SCN5A iPSC-CMs compared to IC iPSC-CMs (P <.0001). CONCLUSION: Although the African-specific p.S1103Y-SCN5A common variant had no effect on APD90 under baseline conditions, the physiological stress of either acidosis or HCQ treatment significantly prolonged APD90 in patient-specific, re-engineered heart cells.

Urgent Guidance for Navigating and Circumventing the QTc-Prolonging and Torsadogenic Potential of Possible Pharmacotherapies for Coronavirus Disease 19 (COVID-19).

As the coronavirus disease 19 (COVID-19) global pandemic rages across the globe, the race to prevent and treat this deadly disease has led to the "off-label" repurposing of drugs such as hydroxychloroquine and lopinavir/ritonavir, which have the potential for unwanted QT-interval prolongation and a risk of drug-induced sudden cardiac death. With the possibility that a considerable proportion of the world's population soon could receive COVID-19 pharmacotherapies with torsadogenic potential for therapy or postexposure prophylaxis, this document serves to help health care professionals mitigate the risk of drug-induced ventricular arrhythmias while minimizing risk of COVID-19 exposure to personnel and conserving the limited supply of personal protective equipment.

Sudden cardiac death in a young boy with multisystemic inflammatory syndrome in children (MISC).

A previously healthy 12-year-old boy presented to the emergency department on the seventh day of illness with classical symptoms of postinflammatory multisystemic syndrome in children temporally associated with SARS-CoV-2 (fever, vomiting, loose stools and rashes all over the body) with COVID-19 seropositivity, high inflammatory markers and elevated cardiac enzymes with cardiogenic shock with multiple organ dysfunction syndrome. After having improved over the first 48 hours following intravenous immunoglobulin and pulsed steroids, this young boy developed sudden cardiac arrest and died. No reversible cause could be identified at the time of resuscitation. Despite an apparent clinical recovery in the myocardial function, it is likely that the myocardium remains arrhythmogenic due to cytokine-induced myocardial inflammation. There are several reports in the literature of fatality in multisystemic inflammatory syndrome in children (MISC) due to cardiovascular complication during the acute phase of the illness. To the best of our knowledge, this is the first report of sudden cardiac death in a child with MISC days after recovery from critical illness, suggesting that fatal outcome remains a potential risk during follow-up, even when there is no evidence of coronary aneurysm. Further studies are needed to identify clinical characteristics of such high-risk children presenting with MISC. We will need to follow these children closely to understand what implications they may have in the long term, and this helps in raising awareness among families of such children.

Progressive chronic SARS-CoV-2-positive giant cell myoendocarditis with atrial standstill and sudden cardiac death.

Giant cell myocarditis (GCM) is a rare condition. Its association with SARS-CoV-2 has not been described before. The 46-year-old female patient was admitted to the clinic on September 2020. She had 7 year adrenal insufficiency history and infarct-like debut of myocardial disease in November 2019. After COVID-19 in April 2020, cardiac disease progressed. The examination showed low QRS voltage, QS complexes in V1 -V5 leads, atrial standstill, left ventricular systolic and restrictive dysfunction, elevated anti-heart antibodies, and subepicardial late gadolinium enhancement by magnetic resonance imaging. Endomyocardial biopsy and pacemaker implantation were performed, but the patient died suddenly due to ventricular tachycardia or ventricular fibrillation (the resuscitation was ineffective). The autopsy revealed GCM, SARS-CoV-2, and Parvovirus B19 were detected in the myocardium. The role of SARS-CoV-2 in the pathogenesis of autoimmune myocarditis is discussed.

A Perspective on Personalized Therapies in Hypertrophic Cardiomyopathy.

ABSTRACT: A dominant mechanism of sudden cardiac death in the young is the progression of maladaptive responses to genes encoding proteins linked to hypertrophic cardiomyopathy. Most are mutant sarcomere proteins that trigger the progression by imposing a biophysical defect on the dynamics and levels of myofilament tension generation. We discuss approaches for personalized treatments that are indicated by recent advanced understanding of the progression.

Modelling sudden cardiac death risks factors in patients with coronavirus disease of 2019: the hydroxychloroquine and azithromycin case.

AIMS: Coronavirus disease of 2019 (COVID-19) has rapidly become a worldwide pandemic. Many clinical trials have been initiated to fight the disease. Among those, hydroxychloroquine and azithromycin had initially been suggested to improve clinical outcomes. Despite any demonstrated beneficial effects, they are still in use in some countries but have been reported to prolong the QT interval and induce life-threatening arrhythmia. Since a significant proportion of the world population may be treated with such COVID-19 therapies, evaluation of the arrhythmogenic risk of any candidate drug is needed. METHODS AND RESULTS: Using the O'Hara-Rudy computer model of human ventricular wedge, we evaluate the arrhythmogenic potential of clinical factors that can further alter repolarization in COVID-19 patients in addition to hydroxychloroquine (HCQ) and azithromycin (AZM) such as tachycardia, hypokalaemia, and subclinical to mild long QT syndrome. Hydroxychloroquine and AZM drugs have little impact on QT duration and do not induce any substrate prone to arrhythmia in COVID-19 patients with normal cardiac repolarization reserve. Nevertheless, in every tested condition in which this reserve is reduced, the model predicts larger electrocardiogram impairments, as with dofetilide. In subclinical conditions, the model suggests that mexiletine limits the deleterious effects of AZM and HCQ. CONCLUSION: By studying the HCQ and AZM co-administration case, we show that the easy-to-use O'Hara-Rudy model can be applied to assess the QT-prolongation potential of off-label drugs, beyond HCQ and AZM, in different conditions representative of COVID-19 patients and to evaluate the potential impact of additional drug used to limit the arrhythmogenic risk.

Myocardial Inflammation, Sports Practice, and Sudden Cardiac Death: 2021 Update.

Myocardial inflammation is an important cause of cardiovascular morbidity and sudden cardiac death in athletes. The relationship between sports practice and myocardial inflammation is complex, and recent data from studies concerning cardiac magnetic resonance imaging and endomyocardial biopsy have substantially added to our understanding of the challenges encountered in the comprehensive care of athletes with myocarditis or inflammatory cardiomyopathy (ICM). In this review, we provide an overview of the current knowledge on the epidemiology, pathophysiology, diagnosis, and treatment of myocarditis, ICM, and myopericarditis/perimyocarditis in athletes, with a special emphasis on arrhythmias, patient-tailored therapies, and sports eligibility issues.