Cardiac crises: Cardiac arrhythmias and cardiomyopathy during TANGO2 deficiency related metabolic crises

Abstract

Background: TANGO2 deficiency disorder (TDD) is an autosomal recessive disease associated with metabolic crisis, lethal cardiac arrhythmias, and cardiomyopathy. Data regarding treatment, management, and outcomes of cardiac manifestations of TDD are lacking.

Objective: The purpose of this study was to describe TDD-related cardiac crises.

Methods: Retrospective multicenter chart review was made of TDD patients admitted with cardiac crises, defined as development of ventricular tachycardia (VT), cardiomyopathy, or cardiac arrest during metabolic crises.

Results: Twenty-seven children were admitted for 43 cardiac crises (median age 6.4 years; interquartile range [IQR] 2.4-9.8 years) at 14 centers. During crisis, QTc prolongation occurred in all (median 547 ms; IQR 504-600 ms) and a type I Brugada pattern in 8 (26%). Arrhythmias included VT in 21 (78%), supraventricular tachycardia in 3 (11%), and heart block in 1 (4%). Nineteen patients (70%) developed cardiomyopathy, and 20 (74%) experienced a cardiac arrest. There were 10 deaths (37%), 6 related to arrhythmias. In 5 patients, recalcitrant VT occurred despite use of antiarrhythmic drugs. In 6 patients, arrhythmias were controlled after extracorporeal membrane oxygenation (ECMO) support; 5 of these patients survived. Among 10 patients who survived VT without ECMO, successful treatment included intravenous magnesium, isoproterenol, and atrial pacing in multiple cases and verapamil in 1 patient. Initiation of feeds seemed to decrease VT events.

Conclusion: TDD-related cardiac crises are associated with a high risk of arrhythmias, cardiomyopathy, cardiac arrest, and death. Although further studies are needed, early recognition and appropriate treatment are critical. Acutely, intravenous magnesium, isoproterenol, atrial pacing, and ECMO as a last resort seem to be the best current treatment options, and early initiation of feeds may prevent VT events.

Keywords: Arrhythmia; Brugada syndrome; Cardiac arrest; Cardiomyopathy; Crisis; Death; Long QT syndrome; TANGO2; Treatment; Ventricular tachycardia.

Figure 1

Electrocardiographic (ECG) changes during metabolic crises demonstrate both prolonged QTc and intermittent Brugada type I pattern. All ECGs are from the same subject (family 6, individual 9). A: Baseline ECG when not in crisis is normal, including QTc. B: During metabolic crisis, QTc is prolonged. No Brugada pattern is seen. C: During the same crisis, the ECG demonstrates both QTc prolongation and concurrent type I Brugada pattern. D: ECG captures frequent isolated ventricular ectopy and nonsustained polymorphic ventricular tachycardia (NSVT).

Figure 2

Typical progression of ventricular arrhythmias during cardiac crises. The telemetry strips are from the same subject (family 6, individual 9). Salvos of nonsustained and sustained polymorphic ventricular tachycardia. A: VT is slower, begin monormorphic and degenerates. B: Hemodynamically unstable torsade de pointes resulted in loss of consciousness.