Yoav Michowitz

Number and Adhesive Properties of Circulating Endothelial Progenitor Cells in Patients With In-Stent Restenosis

Objective—Intact endothelialization machinery is essential to facilitate vessel healing after stent placement and to prevent restenosis. Circulating endothelial progenitor cells (EPC) have been demonstrated in the peripheral blood and shown to display endothelial functional properties, along with the ability to traffic to damaged vasculature. We reasoned that robust in-stent intimal growth could be partially related to impaired endothelialization resulting from reduced circulating EPC number or function. Methods and Results—Sixteen patients with angiographically-demonstrated in-stent restenosis were compared with patients with a similar clinical presentation that exhibited patent stents (n=11). Groups were similar with respect to the use of drugs that could potentially influence EPC numbers. Circulating EPC numbers were determined by the colony-forming unit assay, and their phenotype was characterized by endothelial-cell markers. Adhesiveness of EPC from both groups to extracellular matrix and to endothelial cells was also assayed. Patients with in-stent restenosis and with patent stents displayed a similar number of circulating EPC. Fibronectin-binding was compromised in patients with in-stent restenosis as compared with their controls exhibiting patent stents. Patients with diffuse in-stent restenosis exhibited reduced numbers of EPC in comparison with subjects with focal in-stent lesions. Conclusion—Reduced numbers of circulating EPC in patients with diffuse in-stent restenosis and impaired adhesion of EPC from patients with restenosis provides a potential mechanism mediating the exuberant proliferative process. These markers, if further validated, could provide means of risk stratifying patients for likelihood of developing in-stent restenosis.

Management of Brugada Syndrome: Thirty-Three-Year Experience Using Electrophysiologically Guided Therapy With Class 1A Antiarrhythmic Drugs.

Background—Information on long-term clinical outcome of patients with Brugada syndrome treated with electrophysiologically guided class 1A antiarrhythmic drugs (AAD) is limited. Methods and Results—An aggressive protocol of programmed ventricular stimulation was performed in 96 patients with Brugada syndrome (88% males; mean age, 39.8±15.9 years). Ten patients were cardiac arrest survivors, 27 had presented with syncope, and 59 were asymptomatic. Ventricular fibrillation was induced in 66 patients, including 100%, 74%, and 61% of patients with cardiac arrest, syncope, and no symptoms, respectively. All but 6 of the 66 patients with inducible ventricular fibrillation underwent electrophysiological testing on quinidine (n=54), disopyramide (n=2), or both (n=4). Fifty-four (90%) patients were electrophysiological responders to >1 AAD with similar efficacy rates (≈90%) in all patients groups. Patients with no inducible ventricular fibrillation at baseline were left on no therapy. After a mean follow-up of 113.3±71.5 months, 92 patients were alive, whereas 4 died from noncardiac causes. No arrhythmic event occurred during class 1A AAD therapy in any of electrophysiological drug responders and in patients with no baseline inducible ventricular fibrillation. Arrhythmic events occurred in only 2 cardiac arrest survivors treated with implantable cardioverter–defibrillator alone but did not recur on quinidine. All cases of recurrent syncope (n=12) were attributed to a vasovagal (n=10) or nonarrhythmic mechanism (n=2). Class 1A AAD therapy resulted in 38% incidence of side effects that resolved after drug discontinuation. Conclusions—Our data suggest that electrophysiologically guided class 1A AAD treatment has a place in our therapeutic armamentarium for all types of patients with Brugada syndrome.

Effects of Gender on the Incidence of Cardiac Tamponade Following Catheter Ablation of Atrial Fibrillation: Results from a Worldwide Survey in 34,943 AF Ablation Procedures.

Background—Cardiac tamponade is the most dramatic complication observed during atrial fibrillation (AF) ablation and the leading cause of procedure-related mortality. Female sex is a known risk factor for complications during AF ablation; however, it is unknown whether women have a higher risk of tamponade. Methods and Results—A systematic Medline search was used to locate academic electrophysiological centers that reported cases of tamponade occurring during AF ablation. Centers were asked to provide information on cases of acute tamponade according to sex and their mode of management including any case of related mortality. Nineteen electrophysiological centers provided information on 34u2009943 ablation procedures involving 25u2009261 (72%) men. Overall, 289 (0.9%) cases of tamponade were reported: 120 (1.24%) in women and 169 (0.67%) in men (odds ratio, 1.83; P<0.001). There was a reciprocal association between center volume and the occurrence of tamponade with substantially lower risk in high-volume centers. Most cases of tamponade occurred during catheter manipulation or ablation; women tended to develop more tamponades during transseptal catheterization. No sex difference in the mode of management was observed. However, 16% cases of tamponade required surgery with lower rates in high-volume centers. Three cases of tamponade (1%) culminated in death. Conclusions—Tamponade during AF ablation procedures is relatively rare. Women have an ≈2-fold higher risk for developing this complication. The risk of tamponade among women decreases substantially in high-volume centers. Surgical backup and acute management skills for treating tamponade are important in centers performing AF ablation.

Radiofrequency ablation of paroxysmal atrial fibrillation with the new irrigated multipolar nMARQ ablation catheter: verification of intracardiac signals with a second circular mapping catheter.

BACKGROUNDnDuring radiofrequency (RF) ablation of paroxysmal atrial fibrillation, a circular multielectrode recording lasso catheter is generally positioned within each pulmonary vein (PV) to determine when pulmonary vein potentials (PVPs) are present and when they have been ablated. The new irrigated multipolar nMARQ circular ablation catheter is positioned within the left atrium to create contiguous circular ablation lines around each PV ostium.nnnOBJECTIVEnTo determine whether the recordings obtained from the nMARQ catheter position around the PV ostium accurately reproduce the recordings obtained from a lasso catheter positioned within that vein.nnnMETHODSnIn 10 patients undergoing RF ablation of paroxysmal atrial fibrillation, we placed an nMARQ and a lasso catheter around and within each PV, respectively. Recordings obtained from both catheters at baseline and after RF ablation were compared.nnnRESULTSnAt baseline, recordings of PVPs in both catheters were concordant in 92% of all PVs. However, after RF delivery, the concordance between the nMARQ and lasso recordings was poor. The discordant result most commonly observed was disappearance of PVPs from the nMARQ catheter with persistence of PVPs in the lasso catheter (12 of 39 [30%]). Conversely, the delivery of RF frequently resulted in fragmented electrograms (pseudo-PVPs) on the nMARQ catheter despite evidence of PV isolation by lasso catheter recordings.nnnCONCLUSIONSnThe use of an nMARQ catheter alone, as currently recommended, may lead to underestimation and overestimation of the number of RF applications required to achieve PV isolation.

Atrioventricular block during radiofrequency catheter ablation of atrial flutter: incidence, mechanism, and clinical implications

AIMSnTo evaluate the incidence, mechanism, and clinical implications of atrioventricular (AV) block during catheter radiofrequency (RF) ablation of the cavotricuspid isthmus (CTI). Although RF ablation of atrial flutter is the most frequently performed ablation procedure, data on the incidence and significance of an AV block occurring during the procedure are scarce.nnnMETHODS AND RESULTSnConsecutive patients (n=845, 73.5% male) undergoing CTI ablation (913 procedures) between 1998 and 2010 were studied. Data on the occurrence of complete AV block (lasting≥3 s) during the procedure were prospectively collected. Sixteen (1.9%) patients experienced AV block, 12 during delivery of RF pulses (Group 1) and 4 (Group 2) during manipulation of catheters in the cardiac chambers. The AV block was short lived (<1 min), located in the AV node, and associated with septal isthmus RF lines in 11 Group 1 patients. It was long-lasting and led to pacemaker implantation in one Group 1 patient. Atrioventricular blocks had an infranodal location in four Group 2 patients, all of whom had a pre-existing complete left bundle branch block (LBBB). One Group 2 patient had an AV block during his two ablation procedures. Permanent pacemakers were implanted in five (0.6%) patients (one from Group 1 and four from Group 2).nnnCONCLUSIONSnAtrioventricular blocks requiring pacemaker implantation following administration of RF pulses at the CTI are rare (0.12%). The occurrence rate of AV block related to the procedure and requiring pacemaker implantation is, however, not negligible (0.6%) and mostly affects patients with a pre-existing complete LBBB.

Arrhythmic Risk Stratification by Programmed Ventricular Stimulation in Brugada Syndrome The End of the Debate

One of the most controversial issues debated by cardiac electrophysiologists during the past decade has been whether programmed ventricular stimulation (PVS) plays any role in the arrhythmic risk stratification of the Brugada syndrome (BrS).1–5 The results of the multicenter study published in 2003 by the Brugada brothers were unequivocal.6 In a study involving 408 BrS individuals with no previous cardiac arrest, inducibility of ventricular fibrillation (VF) was found to be a marker of poor prognosis: individuals with inducible VF had a 6 times higher risk of having sudden death because of VF during the subsequent 2 years compared with the patients with noninducible VF. Subsequent multicenter studies from Europe7,8 and Japan,9,10 as well as 2 meta-analyses studies,11,12 failed to confirm these results,6 leading to downgrade in class indication of PVS for risk stratification from IIa in 200513 to IIb in 2013.14 However, in the latest reported meta-analysis of the prognostic value of PVS in BrS, Fauchier et al15 found that PVS actually may be useful in patients with syncope and in asymptomatic patients. The strength of that meta-analysis when compared with the first 2 reported11,12 is that it distinguished the prognostic role of PVS according to the initial clinical presentation (syncope versus asymptomatic). However, this meta-analysis did not include the results of PRogrammed ELectrical stimUlation preDictive valuE registry8 because that study did not provide data discriminating between these 2 patient groups.nnArticle see p 777 nnIn this issue of Circulation: Arrhythmia and Electrophysiology , Sieira et al16 analyzed the experience of Pedro Brugada laboratories in Belgium (Alst and Brussels) during the past 20 years. They reported a cohort of 404 patients with type 1 Brugada ECG (spontaneous in …

Familial Occurrence of Atrioventricular Nodal Reentrant Tachycardia

Background— Atrioventricular nodal reentrant tachycardia (AVNRT) is considered a sporadic disease occurring in ≈22.5 cases per 10u2009000 in the general population. We define the prevalence and characteristics of familial AVNRT among patients who underwent radiofrequency ablation. Methods and Results— Ablation reports of all patients with familial AVNRT (at least 2 first-degree family members) who underwent radiofrequency ablation in our institution and in another hospital were reviewed. There were 1587 patients from our institution, of whom 20 had ≥1 first-degree relatives with AVNRT. This indicates a familial AVNRT prevalence of 127 cases per 10u2009000 (95% confidence interval, 82–196/10u2009000). First-degree relatives of patients with AVNRT presented a hazard ratio of at least 3.6 for exhibiting AVNRT compared with the general population. After inclusion of 4 families with familial AVNRT who underwent ablation at another hospital our population study comprised a total of 24 families (50 patients) with AVNRT. Patients at ablation were younger in the familial AVNRT group when compared with the sporadic AVNRT group (44.2±19 versus 54.8±18 years old, P=0.0001). The male/female ratio was similar, with female predominance. The supraventricular tachycardia mechanism was typical slow/fast reentry in most cases in both groups. The most common familial relationship in our 24 families included a parent and a child in 67% of cases and less often 2 siblings (29%). Conclusions— Familial AVNRT prevalence is higher than previously believed suggesting that this arrhythmia may have a genetic component. Autosomal dominance with incomplete penetrance is the most likely mode of inheritance.

Unmasking right atrial fibrillation: A new indication of adenosine triphosphate test?

Involvement of the right atrium (RA) in the mechanism of atrial fibrillation (AF) has been suggested in some patients before the pioneering work of the Bordeaux group on the pivotal role of pulmonary vein (PV) ectopy in the initiation of AF. Complex linear radiofrequency lesions in the RA were associated with 53% to 56% satisfactory results at 11-month follow-up. Interestingly, all 16 patients described by Gaita et al suffered from “vagal AF.” Later studies showed initiation of AF from the superior vena cava (SVC), inferior vena cava, coronary sinus ostium, and crista terminalis. In a study reported in this issue of HeartRhythm, Hasebe et al investigated the characteristics of paroxysmal AF initiation in 79 consecutive patients with paroxysmal lone AF referred for ablation. The authors used a carefully designed protocol for initiating AF, including observation for spontaneous AF initiation, burst atrial pacing, cardioversion, and observation again for spontaneous initiation with or without isoproterenol infusion. The methods used to provoke spontaneous AF were attempted at least twice in all patients to ensure reproducibility of results. If these maneuvers failed, a 20-mg bolus of adenosine triphosphate (ATP) was injected. Patients were divided into 3 groups according to the site of origin of AF initiation: (1) RA ectopy group (n 1⁄4 7), including 5 patients who also had PV ectopies and 2 prior PV isolation; (2) PV ectopy group, with no documented triggers beyond the PVs (n1⁄4 32); and (3) unknown initiation group (n 1⁄4 40). Importantly, the SVC was carefully mapped during repeated ATP injections to accurately differentiate RA ectopy from SVC ectopy. Spectral analysis was used to define the site of reentrant driver according to calculation of dominant frequency (DF) during both AF and ATP injection in all RA ectopy patients and in 6 patients of the PV ectopy group. All patients underwent PV isolation, and patients with RA ectopies underwent an ablation attempt to eliminate these ectopies. The authors observed differences between the RA ectopy group and the PV ectopy group: (1) patients in the RA ectopy group were younger and more commonly had a familial

Morbidity and mortality with cardiac resynchronization therapy with pacing vs. with defibrillation in octogenarian patients in a real-world setting

AimsnCardiac resynchronization therapy (CRT) with a defibrillator (CRT-D) has downsides of high cost and inappropriate shocks compared to CRT without a defibrillator (CRT-P). Recent data suggest that the survival benefit of implantable cardioverter defibrillator (ICD) therapy is attenuated in the older age group. We hypothesized that, among octogenarians eligible for cardiac resynchronization therapy, CRT-P confers similar morbidity and mortality benefits as CRT-D.nnnMethods and resultsnWe compared morbidity and mortality outcomes between consecutive octogenarian patients eligible for CRT therapy who underwent CRT-P implantation at Barzilai MC (n = 142) vs. those implanted with CRT-D for primary prevention indication who were prospectively enrolled in the Israeli ICD Registry (n = 104). Among the 246 study patients, mean age was 84 ± 3 years, 74% were males, and 66% had ischaemic cardiomyopathy. Kaplan-Meier survival analysis showed that at 5 years of follow-up the rate of all-cause mortality was 43% in CRT-P vs. 57% in the CRT-D group [log-rank P = 0.13; adjusted hazard ratio (HR) = 0.79, 95% CI 0.46-1.35, P = 0.37]. Kaplan-Meier analysis also showed no significant difference in the rates of the combined endpoint of heart failure or death (46 vs. 60%, respectively, log-rank P = 0.36; adjusted HR was 0.85, 95% CI 0.51-1.44, P = 0.55). A Cox proportional hazard with competing risk model showed that re-hospitalizations for cardiac cause were not different for the two groups (adjusted HR 1.35, 95% CI 0.7-2.6, P = 0.37).nnnConclusionnOur data suggest that, in octogenarians with systolic heart failure, CRT-P therapy is associated with similar morbidity and mortality outcomes as CRT-D therapy.

Exercise-induced Ventricular Tachycardia/Ventricular Fibrillation in the Normal Heart: Risk Stratification and Management

Exercise-induced ventricular tachycardia (VT) rarely occurs in the absence of organic heart disease. Idiopathic monomorphic VT has an excellent prognosis. The main aspect of the risk stratification process is recognizing subtle forms of organic heart disease, particularly arrhythmogenic right ventricular cardiomyopathy. Exercise-induced polymorphic VT is potentially malignant. Exercise-induced polymorphic VT has also been seen in mitral valve prolapse. Some patients with stable coronary disease, and even healthy athletes, sometimes have short bursts of polymorphic VT during exercise tests but these arrhythmias are usually not reproducible during repeated testing and have unknown long-term clinical significance.