Means for distinguishing the very common "benign early repolarization" from the very rare but malignant form are needed. Recently, the presence of early repolarization with "horizontal ST segment" ...was found to predict arrhythmic death during long-term follow-up in a large population study. We therefore speculated that the combination of "J waves with horizontal ST segment" would correlate with a history of idiopathic ventricular fibrillation (VF) better than the mere presence of J waves.
To determine whether the morphology of the ST segment adds diagnostic value to the mere presence of J waves in a case-control series of idiopathic VF.
We reanalyzed our case-control study showing that the presence of J waves strongly correlates with a history of idiopathic VF among 45 patients with this disorder, 124 controls matched for age and gender ("matched-control" group), and 121 young athletes. This time we focused only on those patients with J waves and graded their ST-segment morphology as either "horizontal" or "ascending" according to predefined criteria.
The presence of J waves was associated with a history of idiopathic VF with an odds ratio of 4.0 (95% confidence intervals = 2.0-7.9), but having both J waves and horizontal ST segment yielded an odds ratio of 13.8 (95% confidence intervals = 5.1-37.2) for having idiopathic VF.
We report, for the first time, that the combination of J waves with horizontal/descending ST segment improved our ability to distinguish patients with idiopathic VF from controls matched by gender and age.
Objectives The goal of this study was to establish a patient-specific human-induced pluripotent stem cells (hiPSCs) model of catecholaminergic polymorphic ventricular tachycardia (CPVT). Background ...CPVT is a familial arrhythmogenic syndrome characterized by abnormal calcium (Ca2+ ) handling, ventricular arrhythmias, and sudden cardiac death. Methods Dermal fibroblasts were obtained from a CPVT patient due to the M4109R heterozygous point RYR2 mutation and reprogrammed to generate the CPVT-hiPSCs. The patient-specific hiPSCs were coaxed to differentiate into the cardiac lineage and compared with healthy control hiPSCs-derived cardiomyocytes (hiPSCs-CMs). Results Intracellular electrophysiological recordings demonstrated the development of delayed afterdepolarizations in 69% of the CPVT-hiPSCs-CMs compared with 11% in healthy control cardiomyocytes. Adrenergic stimulation by isoproterenol (1 μM) or forskolin (5 μM) increased the frequency and magnitude of afterdepolarizations and also led to development of triggered activity in the CPVT-hiPSCs-CMs. In contrast, flecainide (10 μM) and thapsigargin (10 μM) eliminated all afterdepolarizations in these cells. The latter finding suggests an important role for internal Ca2+ stores in the pathogenesis of delayed afterdepolarizations. Laser-confocal Ca2+ imaging revealed significant whole-cell Ca2+ transient irregularities (frequent local and large-storage Ca2+ -release events, broad and double-humped transients, and triggered activity) in the CPVT cardiomyocytes that worsened with adrenergic stimulation and Ca2+ overload and improved with beta-blockers. Store-overload–induced Ca2+ release was also identified in the hiPSCs-CMs and the threshold for such events was significantly reduced in the CPVT cells. Conclusions This study highlights the potential of hiPSCs for studying inherited arrhythmogenic syndromes, in general, and CPVT specifically. As such, it represents a promising paradigm to study disease mechanisms, optimize patient care, and aid in the development of new therapies.
In 1 study involving middle-aged apparently healthy subjects (4), OSA was found in 25% of men and in 9% of women. ...it represents an important medical issue in the predominantly male patient ...population candidate to AF ablation procedures. ...the authors used a definition of "blanking period" (2 weeks) that was much shorter than the 1 recommended in an international consensus document (3 months) (13).
Objectives The aim of this study was to determine the availability of quinidine throughout the world. Background Quinidine is the only oral medication that is effective for preventing ...life-threatening ventricular arrhythmias due to Brugada syndrome and idiopathic ventricular fibrillation. However, because of its low price and restricted indication, this medication is not marketed in many countries. Methods We conducted a survey of the availability of quinidine by contacting professional medical societies and arrhythmia specialists worldwide. Physicians were e-mailed questionnaires requesting information concerning the quinidine preparation available at their hospital. We also requested information concerning cases of adverse arrhythmic events resulting from unavailability of quinidine. Results A total of 273 physicians from 131 countries provided information regarding the availability of quinidine. Quinidine was readily available in 19 countries (14%), not accessible in 99 countries (76%), and available only through specific regulatory processes that require 4 to 90 days for completion in 13 countries (10%). We were able to gather information concerning 22 patients who had serious arrhythmias probably related (10 cases) or possibility related (12 cases) to the absence of quinidine, including 2 fatalities possibly attributable to the unavailability of quinidine. Conclusions The lack of accessibility of quinidine is a serious medical hazard at the global level.
The Morphology of the QT Interval Predicts Torsade de Pointes During Acquired Bradyarrhythmias Ian Topilski, Ori Rogowski, Rafael Rosso, Dan Justo, Yitschak Copperman, Michael Glikson, Bernard ...Belhassen, Marek Hochenberg, Sami Viskin In a case-controlled study comparing 30 cases of acquired bradyarrhythmias complicated by torsade de pointes (TdP) and 113 cases with uncomplicated bradyarrhythmias, prolonged QT, corrected QT, and Tpeak -Tend intervals were strong predictors of TdP, with the best single discriminator being a prolonged Tpeak -Tend . The only parameter that proved to be independent from the QT interval and added to the prediction of TdP was the presence of “LQT2-like” notched T waves. A 2-step model, based on QT duration and the presence of LQT2-like T waves, identified patients at risk for TdP with a positive predictive value of 84%.
The mainstay of therapy for catecholaminergic polymorphic ventricular tachycardia (CPVT) is maximal doses of beta-blockers. However, although beta-blockers prevent exercise-induced ventricular ...tachycardia (VT), most patients continue to have ventricular ectopy during exercise, and some studies report high mortality rates despite beta-blockade.
The purpose of this study was to investigate whether combining a calcium channel blocker with beta-blockers would prevent ventricular arrhythmias during exercise better than beta-blockers alone since the mutations causing CPVT lead to intracellular calcium overload.
Five patients with CPVT and one with polymorphic VT (PVT) and hypertrophic cardiomyopathy who had exercise-induced ventricular ectopy despite beta-blocker therapy were studied. Symptom-limited exercise was first performed during maximal beta-blocker therapy and repeated after addition of oral verapamil.
When comparing exercise during beta-blockers with exercise during beta-blockers + verapamil, exercise-induced arrhythmias were reduced: (1) Three patients had nonsustained VT on beta-blockers, and none of them had VT on combination therapy. (2) The number of ventricular ectopics during the whole exercise test went down from 78 +/- 59 beats to 6 +/- 8 beats; the ratio of ventricular ectopic to sinus beats during the 10-second period recorded at the time of the worst ventricular arrhythmia went down from 0.9 +/- 0.4 to 0.2 +/- 0.2. One patient with recurrent spontaneous VT leading to multiple shocks from her implanted cardioverter-defibrillator (ICD) despite maximal beta-blocker therapy (14 ICD shocks over 6 months while on beta-blockers) has remained free of arrhythmias (for 7 months) since the addition of verapamil therapy.
This preliminary evidence suggests that beta-blockers and calcium blockers could be better than beta-blockers alone for preventing exercise-induced arrhythmias in CPVT.
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