Loperamide-induced cardiotoxicity: a case overlooked?

A young man presented to the emergency department with seizures and recurrent episodes of polymorphic ventricular tachycardia (PMVT)/torsades de pointes (TdP) requiring cardioversion and administration of intravenous magnesium. A battery of tests performed to identify a cause for his arrhythmias and seizures were all normal. A revisit of history with family revealed he had consumed over 100 tablets/day of loperamide for the past 1 year. A prolonged QT interval on his ECG raised concerns for long QT syndrome (LQTS) (congenital or acquired). Our patient was suspected to have loperamide-induced cardiotoxicity. TdP is a specific PMVT that occurs with a prolonged QT interval and is usually drug-induced. Less frequently, congenital LQTS may be implicated. With supportive care, including mechanical ventilation, vasopressors and temporary transvenous overdrive pacing, our patient recovered completely. We describe the importance of a systematic and time-sensitive approach to diagnosing critical illness. Loperamide overdose may cause QT prolongation, life-threatening arrhythmias/cardiogenic shock, or cardiac arrest. Seizures/epilepsy may also be a manifestation in young patients. There is a substantial need to revisit the safety of over-the-counter medications and increasing awareness of manifestations of drug overdose.

Territory-Wide Chinese Cohort of Long QT Syndrome: Random Survival Forest and Cox Analyses

Introduction: Congenital long QT syndrome (LQTS) is a cardiac ion channelopathy that predisposes affected individuals to spontaneous ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death (SCD). The main aims of the study were to: (1) provide a description of the local epidemiology of LQTS, (2) identify significant risk factors of ventricular arrhythmias in this cohort, and (3) compare the performance of traditional Cox regression with that of random survival forests.Methods: This was a territory-wide retrospective cohort study of patients diagnosed with congenital LQTS between 1997 and 2019. The primary outcome was spontaneous VT/VF.Results: This study included 121 patients [median age of initial presentation: 20 (interquartile range: 8–44) years, 62% female] with a median follow-up of 88 (51–143) months. Genetic analysis identified novel mutations in KCNQ1, KCNH2, SCN5A, ANK2, CACNA1C, CAV3, and AKAP9. During follow-up, 23 patients developed VT/VF. Univariate Cox regression analysis revealed that age [hazard ratio (HR): 1.02 (1.01–1.04), P = 0.007; optimum cut-off: 19 years], presentation with syncope [HR: 3.86 (1.43–10.42), P = 0.008] or VT/VF [HR: 3.68 (1.62–8.37), P = 0.002] and the presence of PVCs [HR: 2.89 (1.22–6.83), P = 0.015] were significant predictors of spontaneous VT/VF. Only initial presentation with syncope remained significant after multivariate adjustment [HR: 3.58 (1.32–9.71), P = 0.011]. Random survival forest (RSF) model provided significant improvement in prediction performance over Cox regression (precision: 0.80 vs. 0.69; recall: 0.79 vs. 0.68; AUC: 0.77 vs. 0.68; c-statistic: 0.79 vs. 0.67). Decision rules were generated by RSF model to predict VT/VF post-diagnosis.Conclusions: Effective risk stratification in congenital LQTS can be achieved by clinical history, electrocardiographic indices, and different investigation results, irrespective of underlying genetic defects. A machine learning approach using RSF can improve risk prediction over traditional Cox regression models.

Artificial Intelligence-Enabled Assessment of the Heart Rate Corrected QT Interval Using a Mobile Electrocardiogram Device

Background: Heart rate-corrected QT interval (QTc) prolongation, whether secondary to drugs, genetics including congenital long QT syndrome (LQTS), and/or systemic diseases including SARS-CoV-2-mediated COVID19, can predispose to ventricular arrhythmias and sudden cardiac death. Currently, QTc assessment and monitoring relies largely on 12-lead electrocardiography. As such, we sought to train and validate an artificial intelligence (AI)-enabled 12-lead electrocardiogram (ECG) algorithm to determine the QTc, and then prospectively test this algorithm on tracings acquired from a mobile ECG (mECG) device in a population enriched for repolarization abnormalities. Methods: Using over 1.6 million 12-lead ECGs from 538,200 patients, a deep neural network (DNN) was derived (n = 250,767 patients for training and n = 107,920 patients for testing) and validated (n = 179,513 patients) to predict the QTc using cardiologist over-read QTc values as the gold standard. The ability of this DNN to detect clinically-relevant QTc prolongation (e.g. QTc ≥ 500 ms) was then tested prospectively on 686 genetic heart disease (GHD) patients (50% with LQTS) with QTc values obtained from both a 12-lead ECG and a prototype mECG device equivalent to the commercially-available AliveCor KardiaMobile 6L. Results: In the validation sample, strong agreement was observed between human over-read and DNN-predicted QTc values (-1.76 ± 23.14 ms). Similarly, within the prospective, GHD-enriched dataset, the difference between DNN-predicted QTc values derived from mECG tracings and those annotated from 12-lead ECGs by a QT expert (-0.45 ± 24.73 ms) and a commercial core ECG laboratory [+10.52 ms ± 25.64 ms] was nominal. When applied to mECG tracings, the DNN's ability to detect a QTc value ≥ 500 ms yielded an area under the curve, sensitivity, and specificity of 0.97, 80.0%, and 94.4%, respectively. Conclusions: Using smartphone-enabled electrodes, an AI-DNN can predict accurately the QTc of a standard 12-lead ECG. QTc estimation from an AI-enabled mECG device may provide a cost-effective means of screening for both acquired and congenital LQTS in a variety of clinical settings where standard 12-lead electrocardiography is not accessible or cost-effective.

Exercise Training-Induced Repolarization Abnormalities Masquerading as Congenital Long QT Syndrome

Background: The diagnosis of long QT syndrome (LQTS) is rather straightforward. We were surprised by realizing that, despite long-standing experience, we were making occasional diagnostic errors by considering as affected subjects who, over time, resulted as not affected. These individuals were all actively practicing sports—an observation that helped in the design of our study. Methods: We focused on subjects referred to our center by sports medicine doctors on suspicion of LQTS because of marked repolarization abnormalities on the ECG performed during the mandatory medical visit necessary in Italy to obtain the certificate of eligibility to practice sports. They all underwent our standard procedures involving both a resting and 12-lead ambulatory ECG, an exercise stress test, and genetic screening. Results: There were 310 such consecutive subjects, all actively practicing sports with many hours of intensive weekly training. Of them, 111 had a normal ECG, different cardiac diseases, or were lost to follow-up and exited the study. Of the remaining 199, all with either clear QTc prolongation and/or typical repolarization abnormalities, 121 were diagnosed as affected based on combination of ECG abnormalities with positive genotyping (QTc, 482±35 ms). Genetic testing was negative in 78 subjects, but 45 were nonetheless diagnosed as affected by LQTS based on unequivocal ECG abnormalities (QTc, 472±33 ms). The remaining 33, entirely asymptomatic and with a negative family history, showed an unexpected and practically complete normalization of the ECG abnormalities (their QTc shortened from 492±37 to 423±25 ms [ P <0.001]; their Schwartz score went from 3.0 to 0.06) after detraining. They were considered not affected by congenital LQTS and are henceforth referred to as “cases.” Furthermore, among them, those who resumed similarly heavy physical training showed reappearance of the repolarization abnormalities. Conclusion: It is not uncommon to suspect LQTS among individuals actively practicing sports based on marked repolarization abnormalities. Among those who are genotype-negative, >40% normalize their ECG after detraining, but the abnormalities tend to recur with resumption of training. These individuals are not affected by congenital LQTS but could have a form of acquired LQTS. Care should be exercised to avoid diagnostic errors.

A case study on escitalopram induced QTc prolongation and adverse drug reaction

Antagonistic medication response (ADR) can be characterized as any toxic change which is suspected to be because of a medication, happens at dosages ordinarily utilized in man, requires treatment or decline in portion or shows alert later on the utilization of similar medication. Escitalopram is a medication which goes under the classification of particular serotonin reuptake inhibitors (SSRIs) (antidepressants). It is the S-enantiomer of the racemic subsidiary of citalopram, which specifically restrains the reuptake of serotonin with practically no impact on norepinephrine or dopamine reuptake. Practically all the antidepressants and antipsychotics have been connected to QT prolongation. In a patient with previously diagnosed congenital QTS, we present a drug-induced QT extension owing to the escitalopram overdose. A 15-year-old Caucasian woman was presented with an escalopram overdose after a suicide attempt. The patient has a lengthy QT period of torsade de point incidents. The patient was received and monitored in the telemetry facility. She proceeded to exhibit the persistently extended QT period after the resolution of torsades de punes. She was diagnosed with a congenital QT condition by the cardiology clinic. In this situation, an escitalopram overdose is seen to trigger an immediate QT extension for a patient who has congenital LQTS and the value of an electrocardiogram before SSRIs are started, particularly for those at high risk of QT prolongation.

Electrocardiographic Screening in the First Days of Life for Diagnosing Long QT Syndrome: Findings from a Birth Cohort Study in Germany

<b><i>Introduction:</i></b> Newborn sudden infant death syndrome (SIDS) has failed to decrease in the last decades, and a third of the neonatal cases occurred within the first 6 days of life. The long QT syndrome (LQTS) is a genetic disease with a prevalence of 1 in 2,000 live births and contributes to almost 10% of SIDS cases. Early identification of LQTS through electrocardiogram (ECG) screening is likely to reduce mortality. <b><i>Methods and Results:</i></b> In this ongoing prospective study we evaluated 2,251 ECGs from newborns participating in the KUNO Kids birth cohort study between July 2015 and July 2018. ECGs were recorded at a mean age of 2.0 days (IQR 0 days). The QT interval was corrected for heart rate using Bazett’s formula (QTc). A QTc between 451 and 460, 461–470, and &#x3e;470 ms was measured in 23 (1.0), 14 (0.6), and 62 (2.8%) participants, respectively. Fourteen neonates (0.62%) were admitted and monitored because their initial QTc was ≥500 ms. In 2 genetically analyzed participants, a mutation was found. One disease-causing for LQTS type 1 and the other of unclear significance. Cascade screening revealed affected members in both families. <b><i>Conclusion:</i></b> A standardized neonatal ECG screening in the first days of life is able to identify neonates with a relevant transient form of prolonged QT intervals and to aid diagnosing congenital LQTS.

A rare indication of permanent pacemaker implantation in children: congenital long QT syndrome

Congenital Long QT Syndrome (LQTS) is a dangerous arrhythmic disorder that can be diagnosed in children with bradycardia. It is characterised by a prolonged QT interval and torsades de pointes that may cause sudden death. Long QT syndrome is an ion channelopathy with complex molecular and physiological infrastructure. Unlike the acquired type, congenital LQTS has a genetic inheritance and it may be diagnosed by syncope, stress in activity, cardiac dysfunction, sudden death or sometimes incidentally. Permanent pacemaker implantation is required for LQTS with resistant bradycardia even in children to resolve symptoms and avoid sudden death.

Sympathectomy via a posterior approach after a failed trans-thoracic approach: a case of its use for arrhythmia

OBJECTIVECongenital long QT syndrome (LQTS) provides an opportunity for neurosurgical intervention. Medication and implantable cardiac defibrillator (ICD)–refractory patients often require left cardiac sympathetic denervation (LCSD) via anterior video-assisted thoracoscopic surgery (VATS). However, this approach has major pulmonary contraindications and risks, with a common concern in children being their inability to tolerate single-lung ventilation. At Oregon Health & Science University, the authors have developed a posterior approach—extrapleural, minimally invasive, T1–5 LCSD—that minimizes this risk.METHODSA 9-year-old girl with LQTS type III presented to the emergency department while experiencing ventricular tachycardia (VT) and ventricular fibrillation (VF) with multiple ICD firings. Medical management failed to resolve the VF/VT. VATS was attempted but could not be safely performed due to respiratory insufficiency. The patient was reintubated for dual-lung ventilation and repositioned prone. Her respiratory insufficiency resolved. Using METRx serial dilating tubes under the microscope, the left T1–5 sympathetic ganglia were sectioned and removed.RESULTSPostoperatively, the patient had no episodes of VF/VT, pneumothorax, hemothorax, or Horner syndrome. With mexiletine and propranolol, she has remained largely VF/VT free, with only one VT episode during the 2-year follow-up period.CONCLUSIONSMinimally invasive, posterior, extrapleural, T1–5 LCSD is safe and effective for treating congenital LQTS in children, while minimizing the risks associated with VATS.

Acquired Long QT Syndrome and Electrophysiology of Torsade de Pointes

Congenital long QT syndrome (LQTS) has been the most investigated cardiac ion channelopathy. Although congenital LQTS remains the domain of cardiologists, cardiac electrophysiologists and specialised centres, the much more frequently acquired LQTS is the domain of physicians and other members of healthcare teams required to make therapeutic decisions. This paper reviews the electrophysiological mechanisms of acquired LQTS, its ECG characteristics, clinical presentation, and management. The paper concludes with a comprehensive review of the electrophysiological mechanisms of torsade de pointes.