Focus on malignant ventricular premature contractions.

Premature ventricular contractions (PVCs) are common. Although often benign, they can also be associated with increased morbidity and mortality. The aim of this review was to assess the risk evaluation of PVCs in patients with or without structural heart disease and discuss the management of this arrhythmia. Reports published in English were searched in PubMed with the following search terms: premature ventricular contraction, ectopic ventricular beat, ventricular extrasystole, antiarrhythmic drugs, ablation, ventricular arrhythmia, ventricular tachycardia, ventricular fibrillation and torsade de pointe. This analysis suggests that all patients with frequent PVCs should be assessed for PVC burden, symptom status and the presence of structural heart disease. PVCs in patients with structurally normal hearts was once considered a benign phenomenon. Uncommonly, PVCs may provoke life-threatening arrhythmias. Ventricular fibrillation is the initial mode of malignant rapid ventricular arrhythmias (MRVAs). Patients with malignant PVC and PVC burden >10% are at increased risk of MRVA in case of myocardial infarction and heart failure. MRVA is the primary cause of sudden cardiac death in patients with and without structural heart disease. Therapeutic options include medical therapy and catheter ablation, the latter more effective and potentially curable, particularly in patients with left ventricular dysfunction. The timely recognition and effective treatment of malignant PVCs in symptomatic patients with underling cardiomyopathy are mandatory to initiate early therapies before the occurrence of adverse clinical outcomes and to improve the long-term prognosis.

Androgenic effects on ventricular repolarization: A translational study from the international pharmacovigilance database to iPSC-cardiomyocytes.

BACKGROUND: Male hypogonadism, arising from a range of etiologies including androgen-deprivation therapies (ADTs), has been reported as a risk factor for acquired long-QT syndrome (aLQTS) and torsades de pointes (TdP). A full description of the clinical features of aLQTS associated with ADT and of underlying mechanisms is lacking. METHODS: We searched the international pharmacovigilance database VigiBase for men (n=6 560 565 individual case safety reports) presenting with aLQTS, TdP, or sudden death associated with ADT. In cardiomyocytes derived from induced pluripotent stem cells from men, we studied electrophysiological effects of ADT and dihydrotestosterone. RESULTS: Among subjects receiving ADT in VigiBase, we identified 184 cases of aLQTS (n=168) and/or TdP (n=68; 11% fatal), and 99 with sudden death. Of the 10 ADT drugs examined, 7 had a disproportional association (reporting odds ratio=1.4-4.7; P<0.05) with aLQTS, TdP, or sudden death. The minimum and median times to sudden death were 0.25 and 92 days, respectively. The androgen receptor antagonist enzalutamide was associated with more deaths (5430/31 896 [17%]; P<0.0001) than other ADT used for prostate cancer (4208/52 089 [8.1%]). In induced pluripotent stem cells, acute and chronic enzalutamide (25µM) significantly prolonged action potential durations (action potential duration at 90% when paced at 0.5Hz; 429.7±27.1 (control) versus 982.4±33.2 (acute, P<0.001) and 1062.3±28.9ms (chronic; P<0.001), and generated afterdepolarizations and/or triggered activity in drug-treated cells (11/20 acutely and 8/15 chronically). Enzalutamide acutely and chronically inhibited delayed rectifier potassium current, and chronically enhanced late sodium current. Dihydrotestosterone (30nM) reversed enzalutamide electrophysiological effects on induced pluripotent stem cells. CONCLUSION: QT prolongation and TdP are a risk in men receiving enzalutamide and other ADTs. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03193138.

Pregnancy and newborn outcomes in arrhythmogenic right ventricular cardiomyopathy/dysplasia.

INTRODUCTION: The prognosis of pregnancy in patients with Arrhythmogenic Right Ventricular Cardiomyopathy/dysplasia (ARVC/D) is poorly documented. The aim of this study is to assess the cardiac risks during pregnancy and the impact of ARVC/D on fetuses/neonates/children. METHODS: We included all ARVC/D women with a history of pregnancy from the ARVC/D Pitié-Salpêtrière registry. Cardiac and obstetrical events having occurred during pregnancy/delivery/post-partum periods and neonatal data/follow-up were collected. RESULTS: Sixty pregnancies in twenty-three patients were identified between 1968 and 2016. Only two major non-fatal cardiac events (one sustained non-documented tachycardia and one ventricular tachycardia) were recorded during pregnancy in two different mothers (3% of pregnancies, 9% of mothers). None occurred during delivery or in the postpartum period. No mother developed heart failure. Beta-blocker therapy during pregnancy (n=15) was associated with lower birthweight (2730 vs 3400g, p=0.004). Only two preterm deliveries occurred, unrelated to cardiac condition. Caesarean section was performed in 13% of cases. Premature sudden-death occurred in 10% (n=5) of children before 25years-old including two in the first year of life. CONCLUSION: ARVC/D is associated with a low rate of major cardiac events during pregnancy and vaginal delivery appears safe. The risk of sustained ventricular arrhythmia seems poorly predictable and supports the continuation of beta-blockers during pregnancy. Major cardiac events were frequent in childhood, justifying close cardiac monitoring.

Respective role of surface electrocardiogram and His bundle recordings to assess the risk of atrioventricular block after transcatheter aortic valve replacement.

BACKGROUND: Atrioventricular block (AVB) is common after transcatheter aortic valve replacement (TAVR) and permanent pacemaker (PPM) implantation is needed in up to 30% of patients. Main predictors of long term AVB are electrocardiographic. The purpose of this study is to assess the prognostic value of serial HV intervals measured before and after TAVR to shorten the timing of PPM implantation. METHODS: His bundle recordings were performed before (HV1), immediately after TAVR (HV2) and at day 2 for Edwards Sapien (ES) and 5 for Medtronic CoreValve (CV) (HV3). PPM indications were high degree AVB before day 5 or prolonged HV interval ≥80ms at the last recording. High degree AVB after discharge was evaluated from the pacemaker memories and ECG at 1 and 6months. RESULTS: Data were obtained in 84 patients (33% CV and 67% ES). HV values were not associated with early or late AVB. PPM were implanted in 27 patients (34%) for documented AVB (n=17, 24%), prolonged HV interval (n=9) or sick sinus syndrome (n=1). Persistent complete AVB during the procedure and postoperative high degree AVB were the only perioperative factors associated with further long term occurrence of high degree AVB (p=0.001 and p<0.001). On multivariate analysis, only postoperative high degree AVB was significant (p=0.001). CONCLUSION: Pre- and post-operative HV measurements were not correlated with late AVB after TAVR. Perioperative persistent complete AVB and postoperative high degree AVB are the only factors to predict late AVB and should be considered for the decision of PPM implantation.

Plakophilin 2A is the dominant isoform in human heart tissue: consequences for the genetic screening of arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease in which mutations affecting Plakophilin-2 (PKP2) are the most frequently detected. However, pathogenicity of variants is not always fully determined. PKP2 encodes two isoforms, the longest (PKP2b) includes the alternatively spliced exon 6, which is routinely screened for molecular diagnosis, despite the absence of data on cardiac expression of PKP2 isoforms. OBJECTIVE: To examine the pathogenicity of PKP2 exon 6 mutations by focusing on a missense variant located in this exon. METHODS AND RESULTS: The PKP2 heterozygous p.Arg490Trp variant was identified in two unrelated ARVC probands (absent from 470 controls). In silico analysis suggested that PKP2 exon 6 is an Alu-derived sequence with very low expression level. PKP2a mRNA, which does not include the sequence encoded by exon 6, was the dominant isoform transcribed; at western blot analysis PKP2A was the only clearly detectable isoform in all human heart samples analysed (from six different controls and the proband). Moreover, in the proband's sample, p.Arg490Trp was not associated with aberrant exon 6 splicing or mutant mRNA downregulation. Finally, a heterozygous missense variant (p.Glu2343Lys) in Desmoplakin was identified in this proband and is likely to be the disease-causing mutation. CONCLUSION: PKP2A was shown to be the major isoform expressed in human heart tissue and PKP2B protein was undetectable. The results strongly suggest that p.Arg490Trp and other variants located in PKP2 exon 6 may not be disease causing. Variant splicing also has important consequences for the interpretation of mutation analysis and genetic counselling in ARVC and other hereditary cardiac diseases.

[Survey into cardiac pacing in the Ile-de-France area for the year 2001: evaluation of indications]. / Enquête sur la stimulation cardiaque en Ile-de-France pour l'année 2001: evaluation des indications.

UNLABELLED: A survey into the implantation of cardiac pacemakers during 2001 in the Ile-de-France area was carried out by the French National Insurance Medical Service in order to evaluate performance in all centres performing more than 10 primary implantations per year. METHODS AND RESULTS: In 2001, 12 centres out of a total of 49 performed less than 50 primary implantations per year, representing 5% of the total regional activity, which was estimated to be 6414 procedures. The remaining 95% of procedures were spread evenly among 8 high-throughput centres (> 200 primary implantations per year) and 29 medium-throughput centres (50 to 200 primary implantations per year). Indications for pacing were analysed retrospectively by a team of regulatory doctors on a sample of 2176 patients with reference to the ACC/AHA/NASPE guidelines. After examination of the medical records, the indication was ranked as being class I, II or Ill (absence of indication). A valid indication was lacking in 8.2% of cases. Sinus node dysfunction represented 74.6% of the non-indications, and this classification had the predictive factors of asymptomatic dysfunction, and treatment with anti-arrhythmic or bradycardic medication. The proportion of class III interventions was significantly lower in the high-throughput centres (5.8 vs 9.9%, p < 0.05). CONCLUSION: 8.2% of primary pacing procedures were not indicated and resulted principally from asymptomatic sinus node dysfunction.

[Wolff-Parkinson-White syndrome in the child. A case report with associated atrial fibrillation]. / Syndrome de Wolff-Parkinson-White de l'enfant. A propos d'un cas de fibrillation atriale conduite par la voie accessoire.

UNLABELLED: In children, Wolff-Parkinson-White (WPW) syndrome is often revealed by reentrant tachycardia episodes. Rarely, this syndrome can be the cause of syncope or of sudden death, resulting from rapid conduction of atrial fibrillation to the ventricles through the accessory pathway. CASE REPORT: The authors report the case of a child, who had a WPW syndrome diagnosed after birth because of a supraventricular tachycardia and who was later asymptomatic. At ten years of age, he was admitted because of palpitations due to atrial fibrillation and rapid conduction through the accessory pathway. CONCLUSION: In a child with WPW syndrome, tachycardia with wide and irregular QRS complexes should evoke the involvement of atrial fibrillation, with rapid conduction to the ventricle. Drugs blocking conduction through the atrio-ventricular node are contra-indicated and the condition is an indication for radiofrequency ablation.

[Effects of 50 to 60 Hz and of 20 to 50 kHz magnetic fields on the operation of implanted cardiac pacemakers]. / Effets des champs magnétiques de 50 et 60 Hz et de 20 à 50 kHz sur le fonctionnement des cardiostimulateurs implantés.

UNLABELLED: The effect of 50 Hz and 60 Hz (frequencies of current distribution) and 20 kHz to 50 kHz (frequencies of induction cooktop) magnetic interference on implanted pacemakers have been assessed with the present generation of device technology. Sixty patients implanted in 1998 and 1999 with dual chamber pacemakers from 9 different manufacturers were monitored with telemetry while passing through, and standing between a system of two coils. They generated a 50 Hz or a 60 Hz magnetic field at 50 microT. Then, patients used a cooktop at different power. The recordings were made with the standard setting of "medically correct" sensing parameters chosen for the patients. Then pacemakers were reprogrammed to the unipolar mode, with the highest atrial (A) and ventricular (V) sensitivity that did not induce muscular inhibition while moving. Between each exposure (50 Hz, 60 Hz or 20 kHz to 50 kHz), the pacemaker programmation was controlled. At the end of the tests, pacemakers will be reprogrammed with the standard setting. The medical observer being blind to the existence or not of the magnetic field. No pacemaker was influenced by the vicinity of the magnetic field at medically correct settings. At unipolar high sensitivity, no inhibition nor reprogramming was observed. Transient reversion to interference mode was observed in 6 cases, 3 transient acceleration due to atrial detection of the interference, and one T wave detection by the ventricular lead. All were observed with the 60 Hz, and only 3 with the 50 Hz magnetic field. One device (Biotronik) shifted out of its special program (hysteresis research) during the tests with the induction cooktop, but it maintained its standard program, and the event could not be repeated despite further testing. CONCLUSION: Actual pacemakers do not present any electromagnetic interference with 50 Hz and 60 Hz or induction cooktop frequency working. They are insensitive with medically correct settings. Unusual high sensitivity leads only to noise reversion mode, or transient ventricular tracking.

[Cardiac Pacemakers, implantable defibrillators and IRM]. / Stimulateurs cardiaques, défibrillateurs implantables et IRM.

The IRM is formally contraindicated to the pacemaker and cardiac defibrillator wearers because of the risk of inhibition or inappropriate stimulations during the examination. However if the examination is essential, suitable programming of the apparatus and a constant monitoring of the heartbeat rate by a qualified doctor in cardiac stimulation must make it possible to avoid any accident.

[Burst of idiopathic ventricular tachycardia complicated by arrhythmia-induced cardiomyopathy]. / Tachycardie ventriculaire idiopathique en salves compliquée de cardiomyopathie rythmique.

The authors report the case of a young man with idiopathic ventricular tachycardia occurring in bursts and arising from the pulmonary infundibulum. During follow-up, progressive, severe, dilated cardiomyopathy was observed. Radiofrequency ablation of the site of origin of this very active arrhythmia resulted in total regression of the cardiomyopathy. Contrary to generally accepted concepts, paroxystic ventricular tachycardia, usually qualified as benign, may be complicated by cardiomyopathy when the ventricular extrasystole is incessant and repetitive.

Low chronic pacing thresholds of steroid-eluting active-fixation ventricular pacemaker leads: a useful alternative to passive-fixation leads.

Active-fixation pacemaker leads enable pacing at various sites, have a low dislodgment rate, and are easier to extract than passive-fixation leads, though are usually not routinely implanted in the ventricle because of their higher pacing threshold. The long-term pacing threshold associated with an active-fixation steroid-eluting lead was prospectively measured in 18 women and 20 men. At a mean follow-up of 14 months (range 3-25 months), pacing threshold increased from 0.71 +/- 0.29 V to 0.96 +/- 0.28 V (P = 0.01) between implant and the first month of follow-up, then remained stable over time, consistently allowing the long-term programming of the ventricular output at 2.5 V, while lead impedance remained stable (from 647 +/- 161 omega at implant to 666 +/- 122 omega at last follow-up). If the long-term performance of this type of lead is confirmed, the routine implantation of ventricular steroid-eluting active-fixation leads should be considered since lead extraction has become a major concern.

Ventricular tachycardia catheter ablation in arrhythmogenic right ventricular dysplasia: a 16-year experience.

Arrhythmogenic right ventricular dysplasia (ARVD) is a structural heart disease affecting young adults that leads to cardiac rhythm disorders including supraventricular and mostly ventricular arrhythmias. Sudden death may be the first presentation of the disease. Ablation techniques have been used for the treatment of ventricular tachycardia in cases resistant to drug therapy. Radiofrequency is appropriate as a first approach for ventricular tachycardia ablation in ARVD; however, its effectiveness is less than 40% at the first session. Fulguration is effective for ventricular tachy-cardia ablation and should be used in the same session after ineffective radiofrequency ablation. However, fulguration requires expertise, general anesthesia, and more than one session in half of all patients. Radiofrequency and fulguration plus other common forms of treatment including pacemakers and automatic implantable cardioverter defibrillators provides a clinical success rate of 81% to 93% in a series of 50 consecutive patients studied during 16 years. Earlier poor reputation of fulguration was the result of poorly understood technical problems concerning the physics and biophysics of the procedure under control with presently available methods. This in-depth study of a large population over a long time period demonstrates that fulguration should be rehabilitated.

[Effect of external electrical interference on pacemakers]. / L'effet des interférences électriques externes sur les stimulateurs cardiaques.

Cardiac pacemaker are sensitive to many kind of electromagnetic interference (EMI). However the low rate of reported effects is due to many protective features. Risks are minimal in everyday life conditions as airport detectors, electronic anti-thief systems, domestic electrical appliances and even mobile phones with the most recent models. Interference detection can be prevented by "medically correct" setting, with the use of bipolar sensing, and ventricular sensitivity above 2 mV. The effect of EMI from the industrial world are difficult to assess and need an individual study. The most important risks occur in the medical world, with the electrocutary, thransthoracic DC shocks, and magnetic resonance imaging.

Radiofrequency catheter ablation of common atrial flutter: role of the eustachian valve.

INTRODUCTION: During radiofrequency catheter ablation of a common atrial flutter between the tricuspid annulus and the Eustachian valve "septal isthmus", double potentials were recorded along the Eustachian valve, previously described as an anatomical line of conduction block between the coronary sinus ostium and the inferior vena cava. RESULTS: Just before flutter termination, lengthening and beat to beat delay variations between the 2 components of the double potentials were correlated with simultaneous modifications of the flutter cycle length. CONCLUSION: The "septal isthmus" is a common pathway for the flutter wavefront and the impulse generating the second component of the double potential. It is also a good target for flutter ablation.

Effects of high energy shocks on pacing impedance during transvenous ICD implantation.

The purpose of the current study was to characterize the effects of transvenous ICD shocks on myocardial impedance. Rather than recording impedance during shocks, it was measured during continuous pacing in order to minimize confounding effects such as electrode polarization. Pacing impedance (reflecting the combined impedances of the electrode-tissue interface, myocardium, and blood pool) was measured every 5 seconds before and after 58 single shocks in 22 patients undergoing ICD implantation with a Transvene (n = 14) or Endotak (n = 8) lead. There was a progressive and long-lasting decrease in impedance after shocks. The magnitude of this change was similar for 0.6-J test shocks and shocks > or = 5 J (28 +/- 32 omega vs 23 +/- 16 omega; P = 0.8). However, the drop in impedance was more abrupt after high energy shocks. Because impedance continued to decline throughout the 5-minute interval between shocks, successive shocks had a cumulative effect, with a decrease of 46 +/- 42 omega after four discharges. In conclusion, a progressive decline in pacing impedance is a characteristic response to transvenous ICD discharges.