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.

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.

Predicting QT interval prolongation in patients diagnosed with the 2019 novel coronavirus infection.

INTRODUCTION: 2019 novel coronavirus (COVID-19) patients frequently develop QT interval prolongation that predisposes them to Torsades de Pointes and sudden cardiac death. Continuous cardiac monitoring has been recommended for any COVID-19 patient with a Tisdale Score of seven or more. This recommendation, however, has not been validated. METHODS: We included 178 COVID-19 patients admitted to a non-intensive care unit setting of a tertiary academic medical center. A receiver operating characteristics curve was plotted to determine the accuracy of the Tisdale Score to predict QT interval prolongation. Multivariable analysis was performed to identify additional predictors. RESULTS: The area under the curve of the Tisdale Score was 0.60 (CI 95%, 0.46-0.75). Using the cutoff of seven to stratify COVID-19, patients had a sensitivity of 85.7% and a specificity of 7.6%. Risk factors independently associated with QT interval prolongation included a history of end-stage renal disease (ESRD) (OR, 6.42; CI 95%, 1.28-32.13), QTc ≥450 ms on admission (OR, 5.90; CI 95%, 1.62-21.50), and serum potassium ≤3.5 mmol/L during hospitalization (OR, 4.97; CI 95%, 1.51-16.36). CONCLUSION: The Tisdale Score is not a useful tool to stratify hospitalized non-critical COVID-19 patients based on their risks of developing QT interval prolongation. Clinicians should initiate continuous cardiac monitoring for patients who present with a history of ESRD, QTc ≥450 ms on admission or serum potassium ≤3.5 mmol/L.

Assessment of Cardiac Arrhythmic Risk in Children With Covid-19 Infection.

Coronavirus disease of 2019 (COVID-19) is a cause of significant morbidity and mortality worldwide. Although COVID-19 clinical manifestations are mainly respiratory, major cardiac complications are being reported. The mechanism of cardiac injury and arrhythmias is unclear. Also, drugs currently used to treat the COVID-19 may prolong the QT interval and may have a proarrhythmic propensity. The study aims to investigate the effects of COVID-19 infection with asymptomatic and mild symptoms on trans-myocardial repolarization parameters in children without treatment. A total of 105 COVID-19 patients were compared with 40 healthy children. The patient and control group data were compared by calculating the QT interval, corrected QT (QTc), QT dispersion (QTd), QTc dispersion (QTcd), Tp-e, Tp-e dispersion, Tp-e/QT ratio, and Tp-e/QTc ratio on the 12-lead surface electrocardiogram. The mean age was determined as 11.2 ± 0.3 years in the patient group, and 10.8 ± 2.1 years in the control group. In the COVID-19 group, QTd, QTcd, Tp-e, Tp-e dispersion, Tp-e/QT ratio and Tp-e/QTc ratio were statistically higher than the control group. The ventricular repolarization was impaired even in asymptomatic children with COVID-19 infection. These results suggest the need to further assess the long terms risks of prolonged QT dispersion in the setting of COVID-19 infection.

Arrhythmic profile and 24-hour QT interval variability in COVID-19 patients treated with hydroxychloroquine and azithromycin.

BACKGROUND: Hydroxychloroquine and azithromycin combination therapy is often prescribed for coronavirus disease 2019 (COVID-19). Electrocardiographic (ECG) monitoring is warranted because both medications cause corrected QT-interval (QTc) prolongation. Whether QTc duration significantly varies during the day, potentially requiring multiple ECGs, remains to be established. METHODS: We performed 12­lead ECGs and 12­lead 24-h Holter ECG monitoring in all patients aged <80 years admitted to our medical unit for COVID-19, in oral therapy with hydroxychloroquine (200 mg, twice daily) and azithromycin (500 mg, once daily) for at least 3 days. A group of healthy individuals matched for age and sex served as control. RESULTS: Out of 126 patients, 22 (median age 64, 82% men) met the inclusion criteria. ECG after therapy showed longer QTc-interval than before therapy (450 vs 426 ms, p = .02). Four patients had a QTc ≥ 480 ms: they showed higher values of aspartate aminotransferase (52 vs 30 U/L, p = .03) and alanine aminotransferase (108 vs 33 U/L, p < .01) compared with those with QTc < 480 ms. At 24-h Holter ECG monitoring, 1 COVID-19 patient and no control had ≥1 run of non-sustained ventricular tachycardia (p = .4). No patients showed "R on T" premature ventricular beats. Analysis of 24-h QTc dynamics revealed that COVID-19 patients had higher QTc values than controls, with no significant hourly variability. CONCLUSION: Therapy with hydroxychloroquine and azithromycin prolongs QTc interval in patients with COVID-19, particularly in those with high levels of transaminases. Because QTc duration remains stable during the 24 h, multiple daily ECG are not recommendable.