COVID-19 and cardiac arrhythmias: a global perspective on arrhythmia characteristics and management strategies.

BACKGROUND: Cardiovascular and arrhythmic events have been reported in hospitalized COVID-19 patients. However, arrhythmia manifestations and treatment strategies used in these patients have not been well-described. We sought to better understand the cardiac arrhythmic manifestations and treatment strategies in hospitalized COVID-19 patients through a worldwide cross-sectional survey. METHODS: The Heart Rhythm Society (HRS) sent an online survey (via SurveyMonkey) to electrophysiology (EP) professionals (physicians, scientists, and allied professionals) across the globe. The survey was active from March 27 to April 13, 2020. RESULTS: A total of 1197 respondents completed the survey with 50% of respondents from outside the USA, representing 76 countries and 6 continents. Of respondents, 905 (76%) reported having COVID-19-positive patients in their hospital. Atrial fibrillation was the most commonly reported tachyarrhythmia whereas severe sinus bradycardia and complete heart block were the most common bradyarrhythmias. Ventricular tachycardia/ventricular fibrillation arrest and pulseless electrical activity were reported by 4.8% and 5.6% of respondents, respectively. There were 140 of 631 (22.2%) respondents who reported using anticoagulation therapy in all COVID-19-positive patients who did not otherwise have an indication. One hundred fifty-five of 498 (31%) reported regular use of hydroxychloroquine/chloroquine (HCQ) + azithromycin (AZM); concomitant use of AZM was more common in the USA. Sixty of 489 respondents (12.3%) reported having to discontinue therapy with HCQ + AZM due to significant QTc prolongation and 20 (4.1%) reported cases of Torsade de Pointes in patients on HCQ/chloroquine and AZM. Amiodarone was the most common antiarrhythmic drug used for ventricular arrhythmia management. CONCLUSIONS: In this global survey of > 1100 EP professionals regarding hospitalized COVID-19 patients, a variety of arrhythmic manifestations were observed, ranging from benign to potentially life-threatening. Observed adverse events related to use of HCQ + AZM included prolonged QTc requiring drug discontinuation as well as Torsade de Pointes. Large prospective studies to better define arrhythmic manifestations as well as the safety of treatment strategies in COVID-19 patients are warranted.

Potentially modifiable factors of dofetilide-associated risk of torsades de pointes among hospitalized patients with atrial fibrillation.

PURPOSE: There is a significant variation in the clinical approach of initiation and dose adjustment of dofetilide in atrial fibrillation (AF). Excessive QT prolongation could predispose patients to torsades de pointes (TdP), which can be fatal. METHODS: We performed a retrospective case-control study at Mayo Clinic Rochester (January 1, 2003 to December 31, 2016). "TdP risk" cases were defined as patients on dofetilide therapy for AF with subsequent TdP or excessive QTc prolongation requiring dose reduction or discontinuation (N = 31). A control group was matched 1:1 with cases by age, gender, year of admission, and dofetilide dose (N = 31). RESULTS: Using multivariate regression analysis, independent predictors of TdP risk included baseline QTc exceeding recommendations (adjusted odd ratio [AOR] 4.57; P = 0.023); underlying AF with rapid ventricular rate (AOR 16.95; P = 0.004); and diuretic therapy for acute heart failure (AOR 8.42; P = 0.007). Poor inter-observer agreement was identified among QT interval measurement in patients with AF and rapid ventricular rate compared to those in rate controlled AF or sinus rhythm. TdP risk cases receiving diuretics for acute heart failure had a significant decline in creatinine clearance than controls, although serum electrolytes and replacement did not differ among the two groups. CONCLUSIONS: Excessive QTc prolongation and AF with rapid ventricular rate at time of dofetilide initiation (likely due to difficulty in measuring QT intervals), and diuretic therapy for acute heart failure were independent factors for dofetilide-related TdP risk. Based on these data, possible preventive strategies could be adapted for safety protocols among hospitalized patients.

In-hospital monitoring of T-wave alternans in a case of amiodarone-induced torsade de pointes: clinical and methodologic insights.

We report a case of macroscopic T-wave alternans occurring 30 min before the onset of amiodarone-induced torsade de pointes, illustrating a means to monitor for proarrhythmia.

Complete atrioventricular block associated with takotsubo cardiomyopathy.

An 82-year-old woman was admitted to the hospital due to repeated episodes of syncope with incontinence. Electrocardiography showed torsades de pointes, complete atrioventricular (AV) block, T-wave inversions and a prolonged QTc interval. Urgent coronary angiography showed no significant coronary stenosis and left ventriculography demonstrated typical abnormal wall motion of takotusbo cardiomyopathy. Electrophysiology study suggested that the damaged structure might be the bundle of His. After temporary transvenous pacing and administration of intravenous lidocaine, no recurrence of torsade de pointes was found. Symptoms of worsening heart failure were not found. Although abnormal left ventricular wall motion improved, a complete AV block remained and the patient needed pacemaker implantation on Day 18 after admission. This case demonstrated that complete AV block associated with takotsubo cardiomyopathy may persist after improvement of left ventricular wall motion, and implantation of a pacemaker may be needed.

Repolarization characteristics and incidence of Torsades de Pointes in patients with acquired complete atrioventricular block.

OBJECTIVE: Torsades de pointes (TdP) during bradyarrhythmias have been reported to be associated with gender, degree of QT prolongation and duration of bradyarrhythmia. We sought to investigate the repolarization characteristics on 12-lead electrocardiogram (ECG) and the incidence of TdP in patients with acquired complete atrioventricular block (CAVB). METHODS: Fifty consecutive patients with acquired CAVB were included in the study. Patients with coronary artery disease, systolic dysfunction and previous cardiac surgery were excluded. Patients were monitored during hospitalization for ventricular arrhythmias (VA). Serum potassium, magnesium, calcium levels and thyroid-stimulating hormone were measured. Heart rate, QRS duration, QT/QTc, JT/JTc and Tpeak-Tend intervals were measured. Pathologic U waves, T-U complex, and QT morphologies were remarked. RESULTS: Patients presented with presyncope (n=39, 78%), syncope (n=12, 24%), and palpitations (n=8, 16%). All patients were in sinus rhythm. Duration of CAVB was 8.5 days (median). Patients were divided into two groups based on JT interval. Group 1 (JT=or>500 ms, n=13) tended to have more female patients and more VAs in comparison to Group 2 (JT<500 ms, n=37). Group 1 patients had more pathologic U waves and T-U complexes, longer Tpeak-Tend intervals, and more long QT2 syndrome (LQT2)-like QT morphology in comparison to Group 2 patients. Group 2 patients had more often syncope. One patient in Group 2 developed ventricular fibrillation in the presence of hypokalemia and hypomagnesemia. CONCLUSION: Torsades de Pointes during CAVB was rare among our patient population. The predictors of VA during CAVB were presence of prolonged QTc/JTc intervals, pathologic U wave and T-U complex, prolonged Tpeak-Tend interval, and LQT2-like QT morphology.

Association of takotsubo cardiomyopathy and long QT syndrome.

A young woman presented with takotsubo cardiomyopathy after a syncopal attack caused by torsades de pointes. Two-dimensional echocardiography on admission showed left ventricular apical akinesis (ballooning) and basal hyperkinesis, compatible with takotsubo cardiomyopathy. This gradually normalized in 2 months. ECG on admission showed remarkable QT prolongation, U waves, and negative T waves, which also gradually normalized. Coronary angiography revealed no organic stenosis; however, acetylcholine provocation test caused the QT interval to again become prolonged. During treadmill exercise stress testing, the QT interval shortened as heart rate increased. Therefore, without genetic analysis, this patient was considered to have sporadic long QT syndrome in which takotsubo cardiomyopathy developed after the syncopal attack caused by torsades de pointes.

QT interval prolongation and risk of life-threatening arrhythmias during toxoplasmosis prophylaxis with spiramycin in neonates.

We recently reported two cases of QT interval prolongation and cardiac arrest in newborns receiving antibiotic therapy with spiramycin, a macrolide agent extensively used for toxoplasmosis prophylaxis. In this study we assessed the effects of this drug on ventricular repolarization and on the potential risk of lethal arrhythmias in eight newborn infants in whom toxoplasmosis prophylaxis after birth was necessary. Electrocardiograms (ECGs) and echocardiograms were recorded during spiramycin therapy (350,000 i.u./kg/ day) and after its withdrawal. In a control group of eight healthy newborns matched for age and sex, no differences were found between two ECGs analogously recorded. The QT interval corrected for heart rate (QTc) was longer during spiramycin therapy than after drug withdrawal (448 +/- 32 msec vs 412 +/- 10 msec, +9%, p = 0.021). QTc dispersion, expressed as the difference between the longest and the shortest value in 12 different leads (QTcmax-min), was also higher during spiramycin therapy (60 +/- 32 msec vs 34 +/- 8 msec, +76%, p = 0.021), mainly because of a major lengthening of the longest QTc (QTcmax). QTc and QTc dispersion were markedly increased in the two newborns who experienced cardiac arrest after beginning treatment compared with the six neonates who had no drug-induced symptoms. During therapy seven of eight newborns had a rare abnormality in the thickening of the left ventricular posterior wall similar to that observed in patients with congenital long QT syndrome. This abnormality disappeared after drug withdrawal. Thus antibiotic therapy with spiramycin in the neonatal period may induce QT interval prolongation and increase QT dispersion. When this effect on ventricular repolarization is more marked, it may favor the occurrence of torsades des pointes and lead to cardiac arrest.