Proarrhythmic effect of bipolar epicardial left ventricular stimulation in CRT resolved maintaining biventricular pacing with unipolar-cathodical configuration: A peculiar case report.

Background: The effect of cardiac resynchronization therapy (CRT) on the risk of ventricular arrhythmias is controversial. Several studies reported a decreased risk, but some studies reported a potential proarrhythmic effect of epicardial left ventricular pacing resolved upon discontinuation of biventricular pacing (BiVp). Case Summary: A 67-year-old woman with a history of heart failure due to nonischemic cardiomyopathy and left bundle branch block was hospitalized for CRT device implantation. Unpredictably, as soon as the leads have been connected to the generator, an electrical storm (ES) occurred with relapsing self-resolving polymorphic ventricular tachycardia (PVT) triggered by ventricular extra beats with short-long-short sequences. The ES was resolved without interrupting BiVp switching to unipolar left ventricular (LV) pacing. This allowed to keep CRT active with extreme clinical benefit for the patient and to demonstrate that the cause of the PVT was the anodic capture of bipolar LV stimulation. Reverse electrical remodeling was also demonstrated after 3 months of effective BiVp. Discussion: Proarrhythmic effect of CRT is a rare but significant complication of CRT, and it may compel to discontinuation of the BiVp. The reversal of the physiological transmural activation sequence of epicardial LV pacing and subsequent prolonging of corrected QT interval have been speculated as the most probable explanation, but our case highlights the possibility that the anodic capture may play a relevant role in PVT genesis.

Exposure-Response Analysis to Assess the Concentration-QTc Relationship of Psilocybin/Psilocin.

Psilocybin is being developed for treating major depressive disorder. Psilocybin is readily dephosphorylated to psilocin upon absorption. The potential for psilocin proarrhythmic effect was assessed using a concentration-QTc interval (C-QTc) analysis from an open-label single ascending dose study of psilocybin. Psilocybin doses ranged from 0.3 to 0.6 mg/kg. This trial showed a significant but shallow C-QTc relationship. At the clinical dose of 25 mg, the mean psilocin maximum concentration is 18.7 ng/mL, and the associated mean (upper 90% confidence interval of mean) QTcF change is 2.1 (6.6) milliseconds. Given the short half-life of psilocin of about 4 hours, there would be no accumulation after monthly oral doses used in clinical trials. The upper limit of the 90% confidence interval of the model-predicted mean ΔQTcF crossed 10 milliseconds at a psilocin concentration of 31.1 ng/mL. At a supraclinical psilocin maximum concentration of about 60 ng/mL, ΔQTcF remains low, with a mean (upper limit of the 90% confidence interval) of 9.1 (17.9) milliseconds. This analysis enabled the characterization of the C-QTc relationship and prediction of QTc prolongation at the expected clinical and possible higher psilocybin doses.

Hazard of acquired long QT syndrome during coronavirus pandemic. Focus on hydroxychloroquine / [A szerzett hosszú-QT-szindróma veszélye a koronavírus-járvány idején. Fókuszban a hidroxiklorokin]

Hydroxychloroquine is an immunomodulatory drug that has been used to treat malaria and autoimmune diseases such as systemic lupus erythematosus and inflammatory arthritis. The authors conclude the proarrhytmic effects of hydroxychloroquine and the most important signs of drug-induced long QT syndrome. This article is especially relevant and timely due to the more frequent (currently not evidence-based) use of the drug during the 2019­2020 coronavirus pandemic. Orv Hetil. 2020; 161(17): 689­691.

Top-down, Bottom-up and Middle-out Strategies for Drug Cardiac Safety Assessment via Modeling and Simulations.

Cardiac safety is an issue causing early terminations at various stages of drug development. Efforts are put into the elimination of false negatives as well as false positives resulting from the current testing paradigm. In silico approaches offer mathematical system and data description from the ion current, through cardiomyocytes level, up to incorporation of inter-individual variability at the population level. The article aims to review three main modelling and simulation approaches, i.e. "top-down" which refers to models built on the observed data, "bottom-up", which stands for a mechanistic description of human physiology, and "middle-out" which combines both strategies. Modelling and simulation is a well-established tool in the assessment of drug proarrhythmic potency with an impact on research and development as well as on regulatory decisions, and it is certainly here to stay. What is more, the shift to systems biology and physiology-based models makes the cardiac effect more predictable.

Adenosine-induced sinus tachycardia in a patient with Myotonic Dystrophy type 1.

We report the case of a 32-year-old man with Myotonic Dystrophy type 1 showing adenosine-induced sinus tachycardia during transesophageal electrophysiological evaluation.

1:1 atrial-flutter. Prevalence and clinical characteristics.

UNLABELLED: Little is known about the epidemiology of 1:1 atrial flutter (AFL). Our objectives were to determine its prevalence and predisposing conditions. METHODS: 1037 patients aged 16 to 93 years (mean 64±12) were consecutively referred for AFL ablation. 791 had heart disease (HD). Patients admitted with 1/1 AFL were collected. Patients were followed 3±3 years. RESULTS: 1:1 AFL-related tachycardiomyopathy was found in 85 patients, 59 men (69%) with a mean age of 59±12 years. The prevalence was 8%. They were compared to 952 patients, 741 men (78%, 0.04), with a mean age of 65±12 years (0.002) without 1:1 AFL. Factors favoring 1:1 AFL was the absence of HD (35 vs 23%, 0.006), the history of AF (42 vs 30.5%)(0.025) and the use of class I antiarrhythmic drugs (34 vs 13%)(p<0.0001), while use of amiodarone or beta blockers was less frequent in patients with 1:1 AFL (5, 3.5%) than in patients without 1:1 AFL (25, 15%) (p<0.0001, 0.03). The failure of ablation (9.4 vs 11%), ablation-related complications (2.3 vs 1.4%), risk of subsequent atrial fibrillation (AF) (20 vs 24%), risk of AFL recurrences (19 vs 13%) and risk of cardiac death (5 vs 6%) were similar in patients with and without 1:1 AFL. CONCLUSIONS: The prevalence of 1:1 AFL in patients admitted for AFL ablation was 8%. These patients were younger, had less frequent HD, had more frequent history of AF and received more frequently class I antiarrhythmic drugs than patients without 1:1 AFL. Their prognosis was similar to patients without 1:1 AFL.

Wide QRS tachycardia during treatment with class ic antiarrhythmic agents in a patient with atrial fibrillation: report of 2 cases / 대한내과학회지

Wide QRS tachycardia may represent a rare proarrhythmic effect of some antiarrhythmic agents. Class Ic antiarrhythmic agents produce rate- dependent ventricular conduction slowing due to use-dependent sodium channel blockade, causing QRS prolongation in cases with an increased heart rate. The authors describe two cases of atrial flutter with 1:1 atrioventricular conduction exhibiting a wide QRS tachycardia while on therapy using flecainide and propafenone, and the difficulty in interpreting the ECG.

Wide QRS tachycardia during treatment with class ic antiarrhythmic agents in a patient with atrial fibrillation: report of 2 cases / 대한내과학회지

Wide QRS tachycardia may represent a rare proarrhythmic effect of some antiarrhythmic agents. Class Ic antiarrhythmic agents produce rate- dependent ventricular conduction slowing due to use-dependent sodium channel blockade, causing QRS prolongation in cases with an increased heart rate. The authors describe two cases of atrial flutter with 1:1 atrioventricular conduction exhibiting a wide QRS tachycardia while on therapy using flecainide and propafenone, and the difficulty in interpreting the ECG.