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Habitual smoking is one of the best established risk factors for cardiovascular disease. The pathogenesis of smoke-induced damage is not so well clarified, but it probably includes--among some other aspects--an activation of the hemostatic system. Recently it has been shown that smoking a single cigarette can significantly decrease the coronary blood flow in coronary patients as well as in normal subjects. We tested the hypothesis that the acute effects of smoke are mediated by the hemostatic system. Seven healthy male volunteers, aged 20-40 years (mean 32 +/- 6 years), entered the study. All were habitual smokers, but had abstained from smoking in the 12 hours preceding the test. After lying in absolute rest for about 30 minutes, each subject smoked a cigarette containing 1.2 mg of nicotine. Immediately before and after smoking, blood was drawn by clear venipuncture for the evaluation of the following hemostatic variables: collagen-induced platelet aggregation by the method of Born; thromboxane B2 (TxB2) production by platelets stimulated with collagen, radioimmunoassay (RIA); plasma beta thromboglobulin (TG) (RIA); plasma fibrinopeptide A (FPA) (RIA); plasma fibrinolytic activity in the euglobulin fraction (NEF) (fibrin plate method). The following results, respectively before and after smoking, were observed: collagen-induced platelet aggregation 55 +/- 3 vs. 57 +/- 6%; TxB2 100.5 +/- 5.9 vs. 90.3 +/- 9.0 ng/10(8) platelets; plasma beta-TG 20.8 +/- 2.2 vs. 19.2 +/- 2.3 ng/ml; plasma FPA 2.3 +/- 0.3 vs. 2.2 +/- 0.1 ng/ml; NEF, lysis diameter 16.8 +/- 1.6 vs. 16.7 +/- 1.7 mm; NEF + C1 inhibitor lysis diameter 8.8 +/- 0.7 vs. 9.1 +/- 0.7 mm.(ABSTRACT TRUNCATED AT 250 WORDS)

Aims Brugada syndrome (BrS) is associated with an increased risk of sudden cardiac death due to ventricular tachycardia/fibrillation (VT/VF) in young, otherwise healthy individuals. Despite SCN5A being the most commonly known mutated gene to date, the genotype–phenotype relationship is poorly understood and remains uncertain. This study aimed to elucidate the genotype–phenotype correlation in BrS. Methods and results Brugada syndrome probands deemed at high risk of future arrhythmic events underwent genetic testing and phenotype characterization by the means of epicardial arrhythmogenic substrate (AS) mapping, and were divided into two groups according to the presence or absence of SCN5A mutation. Two-hundred probands (160 males, 80%; mean age 42.6 ± 12.2 years) were included in this study. Patients harbouring SCN5A mutations exhibited a spontaneous type 1 pattern and experienced aborted cardiac arrest or spontaneous VT/VF more frequently than the other subjects. SCN5A-positive patients exhibited a larger epicardial AS area, more prolonged electrograms and more frequently observed non-invasive late potentials. The presence of an SCN5A mutation explained >26% of the variation in the epicardial AS area and was the strongest predictor of a large epicardial area. Conclusion In BrS, the genetic background is the main determinant for the extent of the electrophysiological abnormalities. SCN5A mutation carriers exhibit more pronounced epicardial electrical abnormalities and a more aggressive clinical presentation. These results contribute to the understanding of the genetic determinants of the BrS phenotypic expression and provide possible explanations for the varying degrees of disease expression.

Aims Balloon-based technologies have been developed to simplify catheter ablation of atrial fibrillation (AF), to improve the clinical outcome of the procedure and to achieve durable pulmonary vein isolation (PVI). The objective of this study is to evaluate the safety and efficacy of second-generation laser balloon (LB2) ablation in the treatment of AF using a continuous cardiac rhythm monitoring strategy. Atrial tachyarrhythmias (ATas) recurrences were assessed with implantable cardiac monitors (ICMs) or devices. Methods and results All patients underwent LB2 ablation procedure. The primary endpoint was the first recurrence of any, >5.5 and >24 h duration ATas after the blanking period (90 days). In-hospital visits were performed at 3, 6, and 12 months. Seventy-three patients (68% male, mean age 59.8 ± 11.3) were included in the study. The average procedure, fluoroscopy, and laser ablation times were 81.5 ± 30.1, 21.5 ± 12.4, and 33.8 ± 9.7, respectively. All PVs were isolated using the LB2 with no need of touch-up using focal catheters. No major complications occurred during or after the procedures. The one-year freedom from recurrences was 66.9% (95% CI: 57.0–76.7%), 81.0% (69.5–88.5%), and 86.8% (76.1–92.9%) considering any, 5.5-h and 24-h cut-off duration, respectively. At 3, 6, and 12 months, any ATas was recorded in 22%, 32%, and 25% of patients, with a ≥5% arrhythmic burden documented in 4%, 5%, and 3%, respectively. Few patients reported AF-related symptoms (7%, 8%, and 5%). Conclusion LB2 ablation is a safe and effective procedure, showing a high freedom from recurrences and low arrhythmic burden as documented by a continuous rhythm monitoring strategy.

Background: In Brugada syndrome (BrS), diagnosed in presence of a spontaneous or ajmaline-induced type-1 pattern, ventricular arrhythmias originate from the right ventricle outflow tract (RVOT). We developed a novel CineECG method, obtained by inverse electrocardiogram (ECG) from standard 12-lead ECG, to localize the electrical activity pathway in patients with BrS. Methods: The CineECG enabled the temporospatial localization of the ECG waveforms, deriving the mean temporospatial isochrone from standard 12-lead ECG. The study sample included (1) 15 patients with spontaneous type-1 Brugada pattern, and (2) 18 patients with ajmaline-induced BrS (at baseline and after ajmaline), in whom epicardial potential duration maps were available; (3) 17 type-3 BrS pattern patients not showing type-1 BrS pattern after ajmaline (ajmaline-negative); (4) 47 normal subjects; (5) 18 patients with right bundle branch block (RBBB). According to CineECG algorithm, each ECG was classified as Normal, Brugada, RBBB, or Undetermined. Results: In patients with spontaneous or ajmaline-induced BrS, CineECG localized the terminal mean temporospatial isochrone forces in the RVOT, congruent with the arrhythmogenic substrate location detected by epicardial potential duration maps. The RVOT location was never observed in normal, RBBB, or ajmaline-negative patients. In most patients with ajmaline-induced BrS (78%), the RVOT location was already evident at baseline. The CineECG classified all normal subjects and ajmaline-negative patients at baseline as Normal or Undetermined, all patients with RBBB as RBBB, whereas all patients with spontaneous and ajmaline-induced BrS as Brugada. Compared with standard 12-lead ECG, CineECG at baseline had a 100% positive predictive value and 81% negative predictive value in predicting ajmaline test results. Conclusions: In patients with spontaneous and ajmaline-induced BrS, the CineECG localized the late QRS activity in the RVOT, a phenomenon never observed in normal, RBBB, or ajmaline-negative patients. The possibility to identify the RVOT as the location of the arrhythmogenic substrate by the noninvasive CineECG, based on the standard 12-lead ECG, opens new prospective for diagnosing patients with BrS.

Brugada syndrome (BrS) is diagnosed by the presence of an elevated ST-segment and can result in sudden cardiac death. The most commonly found mutated gene is SCN5A, which some argue is the only gene that has been definitively confirmed to cause BrS, while the potential causative effect of other genes is still under debate. While the issue of BrS genetics is currently a hot topic, current knowledge is not able to result in molecular confirmation of over half of BrS cases. Therefore, it is difficult to develop research models with wide potential. Instead, the clinical genetics first need to be better understood. In this study, we provide crucial human data on the novel heterozygous variant NM_198056.2:c.4285G>A (p.Val1429Met) in the SCN5A gene, and demonstrate its segregation with BrS, suggesting a pathogenic effect. These results provide the first disease association with this variant and are crucial clinical data to communicate to basic scientists, who could perform functional studies to better understand the molecular effects of this clinically-relevant variant in BrS.

Background Hydroxychloroquine (HCQ) and azithromycin (AZT) have been proposed for COVID-19 treatment. Data available in the literature reported a potential increased risk of fatal arrhythmias under these therapies. The aim of this study was to assess the effects of these drugs on QT interval and outcome in a COVID-19 population. Methods A total of 112 consecutive COVID-19 patients were included in this analysis and were divided in 3 groups according to the receiving therapeutic regimens: 19 (17%) patients in Group 1 (no treatment), 40 (36%) in Group 2 (HCQ only), 53 (47%) in Group 3 (HCQ/AZT). Results A prolonged QTc interval was found in 61% of patients treated with HCQ alone or in combination with AZT, but only 4 (4%) patients showed a QTc > 500 ms. HCQ/AZT combination determined a greater increase of QTc duration compared to the other two strategies (Group 3452 ± 26.4 vs Group 2436.3 ± 28.4 vs Group 1424.4 ± 24.3 ms, respectively; p, Highlights • Only the use of HCQ in combination with AZT causes a significant increase of QT interval. • Older patients are at higher risk of prolonged QT when treated with HCQ with/without AZT. • The use of HCQ alone or in combination with AZT might be considered as safe relating to arrhythmic risk in the treatment of COVID-19 patients.

Background: The relationship between the typical electrocardiographic pattern and electromechanical abnormalities has never been systematically explored in Brugada syndrome (BrS). Objectives: The aims of this study were to characterize the electromechanical substrate in patients with BrS and to evaluate the relationship between electrical and mechanical abnormalities. Methods: We enrolled 50 consecutive high-risk patients with BrS (mean age 42 ± 7.2 years), with implantable cardioverter-defibrillator implantation for primary or secondary prevention of ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]), undergoing substrate mapping and ablation. Patients underwent 3-dimensional (3D) echocardiography with 3D wall motion/deformation quantification and electroanatomic mapping before and after ajmaline administration (1 mg/kg in 5 minutes); 3D mechanical changes were compared with 50 age- and sex-matched controls. The effect of substrate ablation on electromechanical abnormalities was also assessed. Results: In all patients, ajmaline administration induced Brugada type 1 pattern, with a significant increase in the electrical substrate (P

Background: Multipoint left ventricular (LV) pacing (MultiPoint™ Pacing [MPP], Abbott, Sylmar, CA, USA) improves the response rate to cardiac resynchronization therapy (CRT). We evaluated the feasibility of noninvasive radial artery tonometry (RAT) to characterize arterial pressure morphology changes (pre-ejection period [PEP] and ejection duration [ED]) between conventional CRT and MPP pacing interventions. Methods: Patients with a MPP-enabled CRT device (Quadra Assura MP™, Abbott) underwent noninvasive RAT assessment (SphygmoCor CVMS, AtCor Medical Inc., Itasca, IL, USA) at 3–6 months after implantation. A pacing protocol was performed in a randomized order including one optimized conventional biventricular CRT (CONV) configuration using the distal electrode and five MPP configurations. The PEP, ED, and PEP/ED ratio were determined for each intervention from the RAT pressure waveform and electrocardiogram. Results: Pressure waveforms were successfully recorded in 19 patients (89% male, QRS 147 ± 16ms, 63% ischemic). In 17/19 (89%) patients, at least one MPP intervention resulted in improved PEP, ED, and PEP/ED compared to CONV. The MPP intervention with greatest separation of LV cathodes and minimum intra-LV delay significantly improved PEP (mean PEP –15 ± 33%vs –8 ± 32% [CONV], P=0.04) and ED (mean ED +8 ± 8% [MPP] vs +4 ± 7% [CONV], P=0.02), and PEP/ED (–0.07 ± 0.14 [MPP] vs –0.04 ± 0.13 [CONV], P=0.02) compared with CONV. Conclusions: Noninvasive RAT efficiently characterizes changes in PEP and ED between CONV and MPP interventions. MPP configurations using the widest separation among LV cathodes and minimum intra-LV delay may significantly improve RAT-derived parameters as compared to conventional CRT.

Brugada syndrome (BrS) is marked by an elevated ST-segment elevation and increased risk of sudden cardiac death. Variants in the SCN5A gene are considered to be molecular confirmation of the syndrome in about one third of cases, while the genetics remain a mystery in about half of the cases, with the remaining cases being attributed to variants in any of a number of genes. Before research models can be developed, it is imperative to understand the genetics in patients. Even data from humans is complicated, since variants in the most common gene in BrS, SCN5A, are associated with a number of pathologies, or could even be considered benign, depending on the variant. Here, we provide crucial human data on a novel NM_198056.2:c.2091G>A (p.Trp697X) point-nonsense heterozygous variant in the SCN5A gene, as well as its segregation with BrS. The results herein suggest a pathogenic effect of this variant. These results could be used as a stepping stone for functional studies to better understand the molecular effects of this variant in BrS.

Aims Brugada syndrome (BrS) represents a major cause of sudden cardiac death in young individuals. The risk stratification to forecast future life-threatening events is still controversial. Non-invasive assessment of late potentials (LPs) has been proposed as a risk stratification tool. However, their nature in BrS is still undetermined. The purpose of this study is to assess the electrophysiological determinants of non-invasive LPs. Methods and Results Two hundred and fifty consecutive patients with (Group 1, n = 96) and without (Group 2, n = 154) BrS-related symptoms were prospectively enrolled in the registry. Signal-averaged electrocardiogram (SAECG) was performed in all subjects before undergoing epicardial mapping. Group 1 patients exhibited larger arrhythmogenic substrates (AS; 5.8 ± 2.8 vs. 2.6 ± 2.1 cm2, P Conclusion The results of this study support the role of the epicardial AS as an electrophysiological determinant of non-invasive LPs, which may serve as a tool in the non-invasive assessment of the BrS substrate, as SAECG-LPs could be considered an expression of the abnormal epicardial electrical activity. ClinicalTrials.gov number (NCT02641431; NCT03106701).

Aims Clinical outcomes after radiofrequency catheter ablation (RFCA) remain suboptimal in the treatment of non-paroxysmal atrial fibrillation (AF). Electrophysiological mapping may improve understanding of the underlying mechanisms. To describe the arrhythmia substrate in patients with persistent (Pers) and long-standing persistent (LSPers) AF, undergoing RFCA, using an integrated mechanism mapping technique. Methods and results Patients underwent high-density electroanatomical mapping before and after catheter ablation. Integrated maps characterized electrogram (EGM) cycle length (CL) in regions with repetitive–regular (RR) activations, stable wavefront propagation, fragmentation, and peak-to-peak bipolar voltage. Among 83 patients (72% male, 60 ± 11 years old), RR activations were identified in 376 regions (mean CL 180 ± 31 ms). PersAF patients (n = 43) showed more RR sites per patient (5.3 ± 2.4 vs. 3.7 ± 2.1, P = 0.002) with faster CL (166 ± 29 vs. 190 ± 29 ms; P 75% of RR sites (Q4 82.6%, Q3 63.1%, Q2 35.1%, and Q1 0%; P Conclusion The integrated mapping technique allowed characterization of multiple arrhythmic substrates in non-paroxysmal AF patients. This technique might serve as tool for a substrate-targeted ablation approach.

Purpose: Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing (MultiPoint™ Pacing [MPP]) improves long-term LV reverse remodeling, though questions persist about how to program LV pacing vectors and delays. We evaluated if an empirical method of programming MPP vectors and delays between pacing pulses improved CRT response similar to pressure-volume loop (PVL) optimized MPP programming. Methods: Patients undergoing CRT implant (Quadra Assura MP™ CRT-D and Quartet™ LV lead) received MPP with programmed settings optimized either by PVL measurements at implant (PVL-OPT group) or empirically determined by maximizing the spatial separation between the two cathodes and minimal delays between the three ventricular pacing pulses (MAX-SEP group). CRT response was prospectively defined as a reduction in end-systolic volume (ESV) of ≥ 15% relative to baseline at 6months as determined by a blinded observer. Results: Patient characteristics at baseline (NYHA II–III, ejection fraction [EF] 27 ± 6%, QRS 151 ± 17ms) were not significantly different between the PVL-OPT (n = 27) and MAX-SEP (n = 26) groups. During the follow-up period, there were no differences in the number of patients requiring reprogramming due to phrenic nerve stimulation or a high threshold for PVL-OPT vs. MAX-SEP (5/27 [19%] vs. 7/26 [27%], p= 0.53). After 6months, ESV reduction, EF increase, and CRT response rate (RR) were similar for PVL-OPT vs. MAX-SEP (ESV − 20 ± 11 vs. − 22 ± 11%, p = 0.59; EF + 10 ± 4 vs. + 9 ± 7%, p = 0.53; RR 20/27 [74%] vs. 21/26 [81%], p = 0.74), while fewer patients in the PVL-OPT group experienced NYHA class reduction ≥ 2 (4/27 [15%] vs.15/26 [58%], p = 0.002). Conclusions: Both evaluated methods of MPP programming resulted in similar CRT outcomes. Empirical MPP programming by maximum spatial separation of LV cathodes may be an effective, simple, and non-invasive alternative to pressure-volume optimization.

Aims Continuous rhythm monitoring is valuable for adequate atrial fibrillation (AF) management in the clinical setting. Subcutaneous leadless implantable cardiac monitors (ICMs) yield an improved AF detection, overcoming the intrinsic limitations of the currently available external recording systems, thus resulting in a more accurate patient treatment. The study purpose was to assess the detection performance of a novel three-vector ICM device equipped with a dedicated AF algorithm. Methods and results Sixty-six patients (86.4% males; mean age 60.4 ± 9.4 years) at risk to present AF episodes, having undergone the novel ICM implant (BioMonitor, Biotronik SE&Co. KG, Berlin, Germany), were enrolled. External 48-h ECG Holter was performed 4 weeks after the device implantation. The automatic ICM AF classification was compared with the manual Holter arrhythmia recordings. Of the overall study population, 63/66 (95.5%) had analysable Holter data, 39/63 (62%) showed at least one true AF episode. All these patients had at least one AF episode stored in the ICM. On Holter monitoring, 24/63 (38%) patients did not show AF episodes, in 16 of them (16/24, 67%), the ICM confirmed the absence of AF. The AF detection sensitivity and positive predictive value for episodes' analysis were 95.4 and 76.3%, respectively. Conclusion Continuous monitoring using this novel device, equipped with a dedicated detection algorithm, yields an accurate and reliable detection of AF episodes. The ICM is a promising tool for tailoring individual AF patient management. Further long-term prospective studies are necessary to confirm these encouraging results.

Background: Guidelines recommend the use of implanted cardioverter-defibrillators in patients with Brugada syndrome and induced ventricular tachyarrhythmias, but there is no evidence supporting it. Objectives: This prospective registry study was designed to explore clinical and electrophysiological predictors of malignant ventricular tachyarrhythmia inducibility in Brugada syndrome. Methods: A total of 191 consecutive selected patients with (group 1; n = 88) and without (group 2; n = 103) Brugada syndrome–related symptoms were prospectively enrolled in the registry. Patients underwent electrophysiological study and substrate mapping or ablation before and after ajmaline testing (1 mg/kg/5 min). Results: Overall, before ajmaline testing, 53.4% of patients had ventricular tachyarrhythmia inducibility, which was more frequent in group 1 (65.9%) than in group 2 (42.7%; p < 0.001). Regardless of clinical presentation, larger substrates with more fragmented long-duration ventricular potentials were found in patients with inducible arrhythmias than in patients without inducible arrhythmias (p < 0.001). One extrastimulus was used in more extensive substrates (median 13 cm2; p < 0.001), and ventricular fibrillation was the more frequently induced rhythm (p < 0.001). After ajmaline, patients without arrhythmia inducibility had arrhythmia inducibility without a difference in substrate characteristics between the 2 groups. The substrate size was the only independent predictor of inducibility (odds ratio: 4.51; 95% confidence interval: 2.51 to 8.09; p < 0.001). A substrate size of 4 cm2 best identified patients with inducible arrhythmias (area under the curve: 0.98; p < 0.001). Substrate ablation prevented ventricular tachyarrhythmia reinducibility. Conclusions: In Brugada syndrome dynamic substrate variability represents the pathophysiological basis of lethal ventricular tachyarrhythmias. Substrate size is independently associated with arrhythmia inducibility, and its determination after ajmaline identifies high-risk patients missed by clinical criteria. Substrate ablation is associated with electrocardiogram normalization and not arrhythmia reinducibility. (Epicardial Ablation in Brugada Syndrome [BRUGADA_I]; NCT02641431; Epicardial Ablation in Brugada Syndrome: An Extension Study of 200 BrS Patients; NCT03106701)

Background: Clinical outcomes after ablation of persistent atrial fibrillation remain suboptimal. Identification of AF drivers using a novel integrated mapping technique may be crucial to ameliorate the clinical outcome. Methods and Results: Persistent AF patients were prospectively enrolled to undergo high-density electrophysiological mapping to identify repetitive-regular activities (RRas) before modified circumferential pulmonary vein (PV) ablation. They have been randomly assigned (1:1 ratio) to ablation of RRa followed by modified circumferential PV ablation (mapping group; n=41) or modified circumferential PV ablation alone (control group; n=40). The primary end point was freedom from arrhythmic recurrences at 1 year. In total, 81 persistent AF patients (74% male; mean age, 61.7±10.6 years) underwent mapping/ablation procedure. The regions exhibiting RRa were 479 in 81 patients (5.9±2.4 RRa per patient): 232 regions in the mapping group (n=41) and 247 in the control group (n=40). Overall, 185 of 479 (39%) RRas were identified within the PVs, whereas 294 of 479 (61%) in non-PV regions. Mapping-guided ablation resulted in higher arrhythmia termination rate when compared with conventional strategy (25/41, 61% versus 12/40, 30%; P P =0.38), mapping ( P =0.46), and fluoroscopy times ( P =0.69) were not significantly different between the groups. No major procedure-related adverse events occurred. After 1 year, 73.2% of mapping group patients were free from recurrences versus 50% of control group ( P =0.03). Conclusions: Targeted ablation of regions showing RRa provided an adjunctive benefit in terms of arrhythmia freedom at 1-year follow-up in the treatment of persistent AF. These findings might support a patient-tailored strategy in subjects with nonparoxysmal AF and should be confirmed by additional larger, randomized, multicenter studies. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier NCT02571218.

Background Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing (MultiPoint™ Pacing [MPP], St. Jude Medical) improves acute LV function and LV reverse remodeling at 3 months. Objective The purpose of this study was to test the hypothesis that MPP can also improve LV function at 12 months. Methods Consecutive patients receiving a CRT implant (Unify Quadra MP™ or Quadra Assura MP™ CRT-D and Quartet™ LV lead, St. Jude Medical) were randomized to receive pressure–volume (PV) loop optimized biventricular pacing with either conventional cardiac resynchronization therapy (CONV) or MPP. CRT response was defined by a reduction in end-systolic volume (ESV) ≥15% relative to BASELINE as determined by a blinded observer and alive status. Results Forty-four patients (New York Heart Association class III, ejection fraction [EF] 29% ± 6%, QRS 152 ± 17 ms) were enrolled and randomized to either CONV (N = 22) or MPP (N = 22). During the observation period, 2 patients died of noncardiac causes and 2 patients were lost to follow-up. After 12 months, 12 of 21 patients (57%) in the CONV group and 16 of 21 patients (76%) in the MPP group were classified as CRT responders ( P = .33). ESV reduction and EF increase relative to BASELINE were significantly greater with MPP than with CONV (ESV: median –25%, interquartile range [IQR] [–39% to –20%] vs median –18%, IQR [–25% to –2%], P = .03; EF: median +15%, IQR [8% to 20%] vs median +5%, IQR [–1% to 8%], P Conclusion Sustaining the trend observed 3 months postimplant, PV loop-guided multipoint LV pacing resulted in greater LV reverse remodeling and increased LV function at 12 months compared to PV loop-guided conventional CRT.

The aim of this article is to understand the natural history of WPW syndrome to prevent sudden death is important to clinicians in establishing accurate prognosis and appropriate treatment. We report our experience on untreated WPW patients purely looking at the natural history of the disease. In a 15-year period (1995-2010), among 11 237 WPW patients referred to our Arrhythmology Department, a total of 1847 selected patients (820 symptomatic) underwent electrophysiological testing without ablation and were followed for a median (25th-75th) follow-up of 8 (5-8) years. During follow-up, malignant arrhythmias (MA) occurred in 16 patients (0.9%) of whom 14 (1.4%) were initially asymptomatic and two (0.2%) symptomatic (P = 0.01). Potentially MA developed in 143 patients (7.7%) without difference between asymptomatic and symptomatic population (P = 0.663). Benign recurrences developed in 295 patients (16%) while ventricular pre-excitation disappeared in 356 patients (19.3%) of whom 155 were initially asymptomatic. All patients were successfully ablated after arrhythmia occurrence. Patients with MA had similar accessory pathways antegrade refractory periods (AP-AERP) (P = 0.064) and more frequently inducible atrioventricular reciprocating tachycardia triggering atrial fibrillation (AVRT-AF) than those with potentially MA (P < 0.001). Symptoms did not predict MA, which were predicted by AP-AERP (HR 0.912, 95% CI 0.887-0.939, P < 0.001) and AVRT-AF (HR 8.306, 95% CI 2.269-30.405, P = 0.001). The natural history of WPW syndrome and the risk of sudden death essentially depend on intrinsic electrophysiological accessory pathway properties rather than on symptoms and electrophysiologic testing is the gold standard to identify patients at risk. The Authors encourage more intensive screening programs to identify asymptomatic patients at risk for prophylactic ablation.

The Remote Monitoring (RM) technology has recently become available in insertable cardiac monitors (ICM) [(1)][1]. The purpose of this analysis was to assess feasibility, clinical reactions, and arrhythmic alerts burden of remote management for patients implanted with the novel long-dipole ICM (

A huge thrombus, developing after percutaneous left atrial appendage occlusion, has been successfully treated with dabigatran and aspirin as combination therapy.Although novel oral anticoagulants alone may be effective in thrombus dissolution, the association of an antiplatelet drug may safely enhance this process.

Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia. The trigger for initiation of AF is generally an enhanced vulnerability of pulmonary vein cardiomyocyte sleeves to either focal or re-entrant activity. The maintenance of AF is based on a "driver" mechanism in a vulnerable substrate. Cardiac mapping technology is providing further insight into these extremely dynamic processes. AF can lead to electrophysiological and structural remodelling, thereby promoting the condition. The management includes prevention of stroke by oral anticoagulation or left atrial appendage (LAA) occlusion, upstream therapy of concomitant conditions, and symptomatic improvement using rate control and/or rhythm control. Nonpharmacological strategies include electrical cardioversion and catheter ablation. There are substantial geographical variations in the management of AF, though European data indicate that 80% of patients receive adequate anticoagulation and 79% adequate rate control. High rates of morbidity and mortality weigh against perceived difficulties in management. Clinical research and growing experience are helping refine clinical indications and provide better technical approaches. Active research in cardiac electrophysiology is producing new antiarrhythmic agents that are reaching the experimental clinical arena, inhibiting novel ion channels. Future research should give better understanding of the underlying aetiology of AF and identification of drug targets, to help the move toward patient-specific therapy.

Nonirrigated magnetic ablation may result in potential char, ineffective lesions, and longer procedure times.This study sought to report the safety and long-term efficacy of irrigated-tip magnetic ablation of atrial fibrillation (AF).Catheter ablation was remotely performed using a new irrigated-tip magnetic catheter (ThermoCool NaviStar-RMT, Biosense Webster, Diamond Bar, CA) in 130 consecutive patients (mean age 59.7 ± 10.5 years) with symptomatic paroxysmal (81 patients) or persistent (49 patients) AF. The radiofrequency (RF) generator was set to fixed power of 30 W. The primary end point of the study was freedom from atrial tachycardia (AT)/AF off antiarrhythmic drugs.The procedure was safely performed in all conventional ablation targets, but crossover to manual catheters was required in 12 patients to complete the mitral isthmus line. The total procedure time was 94.6 ± 15.3 minutes. Impedance values significantly decreased during RF applications (P.001) and the maximum temperature on the catheter tip was 36.4°C ± 0.8°C. The follow-up duration was 15.3 ± 4.9 months. The primary end point was achieved in 66 of 81(81.4%) patients with paroxysmal AF and in 33 of 49 (67.3%) with persistent AF (P = .035, by log-rank test). Patients with paroxysmal AF had higher late AF recurrence (P =.044). Overall, postablation incessant left AT developed in 7 of 130 (5.4%) patients. Major complications were not observed. Left atrial diameter (P.001) and heart failure (P = .032) predicted arrhythmia recurrence after remote irrigated-tip ablation.Remote ablation with irrigated-tip magnetic catheters can be safely and effectively performed in patients with AF, but longer follow-up periods are required to evaluate late AF recurrences.

Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing [MultiPoint™ Pacing (MPP), St. Jude Medical, Sylmar, CA, USA] improves LV function and clinical response relative to conventional CRT in patients receiving a de novo device implant. We hypothesized that patients with a previously implanted conventional CRT device would receive additional benefit by switching to MPP. Patients receiving a CRT implant (Unify Quadra MP™ or Quadra Assura MP™ CRT-D and Quartet™ LV lead, St. Jude Medical) were programmed to conventional CRT (i.e. biventricular pacing with right ventricular and single LV sites) optimized by intraoperative haemodynamic measurements. After 12 months of conventional therapy, patients were reprogrammed to MPP and re-evaluated at 16 months post-implant. Response to CRT was prospectively defined as reduction in end-systolic volume (ESV) of ≥15% relative to baseline as determined by a blinded observer. Eight patients with an implanted CRT device [New York Heart Association III, ejection fraction (EF) 30 ± 5%, QRS 149 ± 18 ms] received 12 months of conventional CRT and were switched to MPP. After 12 months of conventional CRT, ESV reduction and EF increase relative to baseline were −18 ± 12 and +5 ± 4%, respectively, and six of eight (75%) patients were considered CRT responders. After 4 months of MPP, two of two (100%) patients classified as non-responders to conventional CRT became responders with additional reduction in ESV of −33 and −20% and improvement in EF of +15 and +4%. The remaining six patients classified as responders experienced additional reduction in ESV of −13 ± 21% and improvement in EF of +7 ± 7% after switching to MPP. Multipoint LV pacing may provide additional improvement to LV function in patients receiving conventional CRT.

Background— Whether Brugada syndrome (BrS) depends on functional epicardial substrates, which may be definitively eliminated by radiofrequency ablation, remains unknown. Methods and Results— Patients with BrS underwent epicardial mapping to identify areas of abnormal electrograms as target for radiofrequency ablation. Substrate identification consisted in mapping right ventricle epicardial surface before and after flecainide (2 mg/kg per 10 minutes). After radiofrequency ablation, flecainide and remap confirmed elimination of abnormal substrate, BrS ECG pattern, and ventricular tachycardia/ventricular fibrillation inducibility. Flecainide testing was performed at each follow-up visits ≤6 months. Fourteen patients with BrS, median age 39 years (30.3–42.3) with implantable cardioverter–defibrillator were enrolled. Low-voltage areas (2 (12.1–24.2) to 28.5 cm 2 (21.6–30.2; P =0.001). Similarly, areas with abnormal electrograms increased after flecainide from 19.0 (17.5–23.6) to 27.3 cm 2 (24.0–31.2; P =0.001). After 23.8 minutes (18.1–28.5) of radiofrequency ablation, abnormal electrograms disappeared, whereas low-voltage areas were replaced by scar areas (2 (19.6–31.0). Substrate elimination resulted in BrS ECG pattern disappearance and no ventricular tachycardia/ventricular fibrillation inducibility without complications. After a median follow-up of 5 months (3.8–5.3), ECG remained normal despite flecainide. Conclusions— In patients with BrS, there is a relationship between abnormal ECG pattern, the extent of abnormal epicardial substrate, and ventricular tachycardia/ventricular fibrillation inducibility. Ablation of the substrate identified in the presence of flecainide can eliminate the BrS phenotype and warrants further study.

We thank Fenici et al for their interest in our experience on the natural history of the Wolff-Parkinson-White (WPW) syndrome.1 The authors, on the basis of their experience, suggest the routine use of ambulatory transesophageal atrial pacing (TEAP) as an intermediate approach to minimize “invasiveness” for risk assessment in the asymptomatic WPW population. It is well known that, unlike invasive electrophysiological testing (EPT), TEAP provides less accurate information about “the real electrophysiological profile of the risk” in WPW patients. Potential limitations are an approximate value of the anterograde refractory period of accessory pathways (APs), no identification of multiple APs, no reproducibility or inducibility of atrial fibrillation, no information on AP …

We conducted a randomized, controlled trial of circumferential pulmonary-vein ablation for the treatment of chronic atrial fibrillation.A total of 146 patients with a mean (+/-SD) age of 57+/-9 years who had chronic atrial fibrillation were randomly assigned to receive amiodarone and undergo two cardioversions during the first three months alone (the control group) or in combination with circumferential pulmonary-vein ablation. Cardiac rhythm was assessed with daily telephonic transmissions for one year. The left atrial diameter and the severity of symptoms were assessed at 12 months.Among the 77 patients assigned to undergo circumferential pulmonary-vein ablation, ablation was repeated because of recurrent atrial fibrillation in 26 percent of patients and atypical atrial flutter in 6 percent. An intention-to-treat analysis showed that 74 percent of patients in the ablation group and 58 percent of those in the control group were free of recurrent atrial fibrillation or flutter without antiarrhythmic-drug therapy at one year (P=0.05). Among the 69 patients in the control group, 53 (77 percent) crossed over to undergo circumferential pulmonary-vein ablation for recurrent atrial fibrillation by one year and only 3 (4 percent) were in sinus rhythm without antiarrhythmic-drug therapy or ablation. There were significant decreases in the left atrial diameter (12+/-11 percent, P0.001) and the symptom severity score (59+/-21 percent, P0.001) among patients who remained in sinus rhythm after circumferential pulmonary-vein ablation. Except for atypical atrial flutter, there were no complications attributable to circumferential pulmonary-vein ablation.Sinus rhythm can be maintained long term in the majority of patients with chronic atrial fibrillation by means of circumferential pulmonary-vein ablation independently of the effects of antiarrhythmic-drug therapy, cardioversion, or both. The maintenance of sinus rhythm is associated with a significant decrease in both the severity of symptoms and the left atrial diameter.

Background— The management of Wolff-Parkinson-White is based on the distinction between asymptomatic and symptomatic presentations, but evidence is limited in the asymptomatic population. Methods and Results— The Wolff-Parkinson-White registry was an 8-year prospective study of either symptomatic or asymptomatic Wolff-Parkinson-White patients referred to our Arrhythmology Department for evaluation or ablation. Inclusion criteria were a baseline electrophysiological testing with or without radiofrequency catheter ablation (RFA). Primary end points were the percentage of patients who experienced ventricular fibrillation (VF) or potentially malignant arrhythmias and risk factors. Among 2169 enrolled patients, 1001 (550 asymptomatic) did not undergo RFA (no-RFA group) and 1168 (206 asymptomatic) underwent ablation (RFA group). There were no differences in clinical and electrophysiological characteristics between the 2 groups except for symptoms. In the no-RFA group, VF occurred in 1.5% of patients, virtually exclusively (13 of 15) in children (median age, 11 years), and was associated with a short accessory pathway antegrade refractory period ( P P P Conclusions— The prognosis of the Wolff-Parkinson-White syndrome essentially depends on intrinsic electrophysiological properties of AP rather than on symptoms. RFA performed during the same procedure after electrophysiological testing is of benefit in improving the long-term outcomes.

Backgound Conventional cardiac resynchronization therapy (CRT) improves acute cardiac hemodynamics. Objective To investigate if CRT with multipoint left ventricular (LV) pacing in a single coronary sinus branch (MultiPoint Pacing [MPP], St Jude Medical, Sylmar, CA) can offer further hemodynamic benefits to patients. Methods Forty-four consecutive patients (80% men, New York Heart Association III, end-systolic volume 180 ± 77 mL, ejection fraction 27% ± 6%, and QRS duration 152 ± 17 ms) receiving a CRT device implant (Unify Quadra MP or Quadra Assura MP and Quartet LV lead, St Jude Medical) underwent intraoperative assessment of LV hemodynamics by using a pressure-volume loop system (Inca, CD Leycom). A pacing protocol was performed, including 9 biventricular pacing interventions with conventional CRT (CONV) using distal and proximal LV electrodes and various MPP configurations. Each pacing intervention was performed twice in randomized order with right ventricular pacing (BASELINE) repeated after every intervention. Results Evaluable recordings were obtained in 42 patients. Relative to BASELINE, the best MPP intervention significantly increased the rate of pressure change (dP/dtmax; 15.9% ± 10.0% vs 13.5% ± 8.8%; P

Background —We treated paroxysmal recurrent atrial fibrillation (AF) with radiofrequency (RF) catheter ablation by creating long linear lesions in the atria. To achieve line continuity, a 3D electroanatomic nonfluoroscopic mapping system was used. Methods and Results —In 27 patients with recurrent AF, a catheter incorporating a passive magnetic field sensor was navigated in both atria to construct a 3D activation map. RF energy was delivered to create continuous linear lesions: 3 lines (intercaval, isthmic, and anteroseptal) in the right atrium and a long line encircling the pulmonary veins in the left atrium. After RF application, the atria were remapped to validate completeness of the block lines, demonstrated by late activation of the areas circumscribed by the lines. The mean procedure duration was 312±103 minutes (range, 187 to 495), with mean fluoroscopy time of 107±44 minutes (range, 32 to 185 minutes). No acute complications occurred, but 1 patient experienced early prolonged sinus pauses and received a pacemaker. During the first day, 17 patients (63%) had AF episodes, but at discharge, 25 patients were in sinus rhythm. After a follow-up of 6.0 to 15.3 months (average, 10.5±3.0 months), 16 patients are asymptomatic, 3 have an almost complete disappearance of symptoms, 1 patient is improved, and 7 patients have their AF attacks unchanged. Conclusions —Paroxysmal recurrent drug-refractory AF can be treated by RF catheter ablation. Creation of long continuous linear lesions necessary to compartmentalize the atria is facilitated by a nonfluoroscopic electroanatomic mapping system.

Objectives. This study sought to investigate whether residual viability of infarcted myocardium may play a role in the pathogenesis of exercise-induced ventricular arrhythmias. Background. We previously showed that transient ischemia within partially infarcted areas often precipitates ventricular arrhythmias during exercise that are consistently obliterated by intravenous nitrates. Methods. We studied 60 patients with chronic stable angina and a previous myocardial infarction, All underwent at least two consecutive exercise stress tests, coronary angiography and stress/rest myocardial perfusion tomography by Tc-99m 2-methoxy isobutyl isonitrile (MIBI). In the last 26 consecutive patients, residual viability was assessed by single-photon emission computed tomography (SPECT) using fluorine (F)-18 fluorodeoxyglucose. Perfusion and metabolic data were evaluated qualitatively by three independent observers in blinded manner, Results. With exercise, 30 patients (group A) consistently developed ventricular arrhythmias (>10 ventricular ectopic beats/min, couplets, nonsustained ventricular tachycardia); the remaining 30 patients (group B) did not, The severity of coronary artery disease (Gensini score) was similar in the two groups. Posterercise SPECT shun ed partial reperfusion of an infarcted area in 28 of 30 patients of group A but in only 9 of 30 of group B (p < 0.0001). Uptake of F-18 fluorodeoxyglucose was observed within the infarcted zone in 10 of 13 and 1 of 13 patients in groups A and B, respectively (p = 0.0003). Conclusions. In patients with myocardial infarction, exercise-induced ventricular arrhythmias appear to be triggered by transient ischemia occurring within a partially necrotic area containing large amounts of viable myocardium. Therefore, occurrence of arrhythmias during exercise may represent a clue to the presence of residual viability within a previously infarcted area. RI Lucignani, Giovanni/C-6773-2008

AIMS: To evaluate the prevalence, clinical significance, and prognosis of latent Brugada syndrome (BrS) in patients with new-onset atrial fibrillation (AF) unmasked by class 1C antiarrhythmic drugs. METHODS AND RESULTS: Between January 2000 and June 2008, all consecutive patients with new-onset AF, who after flecainide exhibited typical Brugada ECG pattern, underwent electrophysiologic, pharmacologic, and genetic testing. Among 346 patients [median age 53 years; interquartile range (IQR), 15], 11 (3.2%; median age 51 years; IQR, 19) diagnosed as lone AF exhibited typical Brugada ECG pattern. Genetic testing was negative. Ventricular tachycardia/ventricular fibrillation (VT/VF) was induced by electrophysiologic testing (five patients) or during flecainide infusion (one patient). Six patients with type 1 ECG pattern and inducible VT/VF underwent ICD implantation. During a median follow-up of 31.5 months (range: 10-85) after ICD implantation, three patients developed BrS and one of them experienced VF. Patients without ICD (five patients) remained asymptomatic during a median follow-up of 74 months. Persistent type 1 pattern occurred only in the three patients who developed BrS. CONCLUSION: This study, for the first time, reveals the prevalence of latent BrS in patients with new-onset lone AF, which may precede VT/VF. Persistence of type 1 and ventricular tachyarrhythmias inducibility represents a marker of electrical instability leading to sudden death.

BACKGROUND Circumferential pulmonary vein ablation (CPVA) is an effective treatment for atrial fibrillation (AF). Accurate left atrial (LA) mapping is essential for creating lesions at the LA‐ pulmonary vein (PV) junction, avoiding PV stenosis. OBJECTIVES The purpose of this study was to establish whether endocardial impedance varies within the LA and PVs and whether it is a useful tool for mapping and ablation. METHODS Pilot Phase: Three-dimensional LA maps were created using CARTO. Impedance (Z) was measured using a radiofrequency generator at multiple points in the LA, PV ostia (PVO), and deep PVs in 79 patients undergoing their first AF ablation (group 1) and 29 patients undergoing repeat CPVA (group 2). Prospective Phase: In an additional 20 patients, using pilot phase data, one operator defined catheter tip location as either LA or PVO based on CARTO and fluoroscopy. A second operator blinded to CARTO simultaneously did the same based on impedance at 15 4 points per patient. RESULTS Group 1: ZLA was 99.4 9.0 .Z PVO was higher (109.2 8.5 ), rising further as the catheter advanced into deep PV (137 18). ZPVO differed from ZLA by 9 4 . Group 2 had a lower ZLA and ZPVO compared with group 1 (P .05). Impedance monitoring differentiated between LA and PVO, with 91% specificity and sensitivity, 96% positive predictive value, and 81% negative predictive value. At 3-month follow-up, no patients had evidence of PV stenosis on magnetic resonance imaging. CONCLUSION Impedance mapping reliably identifies the LA‐PV transitional zone, facilitating AF ablation, and its use is associated with a low incidence of PV stenosis.

Background— Circumferential pulmonary vein ablation (CPVA) is effective in curing atrial fibrillation (AF), but new-onset left atrial tachycardia (AT) is a potential complication. We evaluated whether a modified CPVA approach including additional ablation lines on posterior wall and the mitral isthmus would reduce the incidence of AT after PV ablation. Methods and Results— A total of 560 patients (291 men, 52%; age, 56.5±7.3 years) entered the study; 280 were randomized to CPVA alone (group 1) and 280 to modified CPVA (group 2). The primary end point was freedom from AT after the procedure. In group 1, 28 patients (10%) experienced new-onset AT, and 41 (14.3%) experienced recurrent AF. In group 2, 11 patients (3.9%) experienced AT, and 36 (12.9%) had recurrent AF. Group 1 was more likely to experience AT than group 2 ( P =0.005). Freedom from AF after ablation was similar in both groups ( P =0.57). Among those in group 1, gap-related macroreentrant AT was documented in 23 of the 28 patients (82%), and focal AT was found in 5 (18%). In group 2, gap-related macroreentrant AT was found in 8 of the 11 patients (73%), and focal AT was seen in 3 (27%). Two patients in group 1 and 1 patient in group 2 had both AT and AF. The strongest predictor of AT was the presence of gaps ( P Conclusions— Modified CPVA is as effective as CPVA in preventing AF but is associated with a lower risk of developing incessant AT.

Background— Radiofrequency ablation for atrial fibrillation is becoming widely practiced. Methods and Results— Two patients undergoing circumferential pulmonary vein ablation for atrial fibrillation in different centers developed symptoms compatible with endocarditis 3 to 5 days after the procedure. Their clinical condition deteriorated rapidly, and both suffered multiple gaseous and/or septic embolic events causing cerebral and myocardial damage. One patient survived after emergency cardiac and esophageal surgery; the other died of extensive systemic embolization. An atrio-esophageal fistula was identified in both patients. Conclusions— Atrio-esophageal fistulas can occur after catheter ablation in the posterior wall of the left atrium. This diagnosis should be excluded in any patient with symptoms or signs of endocarditis after left atrial ablation, and expeditious cardiac surgery is critical if the diagnosis is confirmed. Lower power and temperature settings for applications of radiofrequency energy along the posterior left atrial wall may prevent further cases of fistula formation.

Background— There are no data to evaluate the relationship between autonomic nerve function modification and recurrent atrial fibrillation (AF) after circumferential pulmonary vein ablation (CPVA). This study assesses the incremental benefit of vagal denervation by radiofrequency in preventing recurrent AF in a large series of patients undergoing CPVA for paroxysmal AF. Methods and Results— Data were collected on 297 patients undergoing CPVA for paroxysmal AF. Abolition of all evoked vagal reflexes around all pulmonary vein ostia was defined as complete vagal denervation (CVD) and was obtained in 34.3% of patients. Follow-up ended at 12 months. Heart rate variability attenuation, consistent with vagal withdrawal, was detectable for up to 3 months after CPVA, particularly in patients with reflexes and CVD, who were less likely to have recurrent AF than those without reflexes ( P =0.0002, log-rank test). Only the percentage area of left atrial isolation and CVD were predictors of AF recurrence after CPVA ( P P =0.025, respectively). Conclusions— This study suggests that adjunctive CVD during CPVA significantly reduces recurrence of AF at 12 months.

We assessed the feasibility of cardiac contractility modulation (CCM) by electric currents applied during the refractory period in patients with heart failure (HF). Extracellular electric currents modulating action potential and calcium transients have been shown to potentiate myocardial contractility in vitro and in animal models of chronic HF. CCM signals were biphasic square-wave pulses with adjustable amplitude, duration, and time delay from sensing of local electric activity. Signals were applied to the left ventricle through an epicardial vein (in 12 patients) or to the right ventricular (RV) aspect of the septum endocardially (in 6 patients). Simultaneous left ventricular (LV) and aortic pressure measurements were performed using a Millar catheter (Millar Instruments, Houston, Texas). Hemodynamics during RV temporary dual-chamber pacing was regarded as the control condition. Both LV and RV CCM stimulation increased dP/dt(max) to a similar degree (9.1 +/- 4.5% and 7.1 +/- 0.8%, respectively; p0.01 vs controls), with associated aortic pulse pressure changes of 10.3 +/- 7.2% and 10.8 +/- 1.1% (p0.01 vs controls). Regional systolic wall motion assessed quantitatively by color kinesis echocardiography was markedly enhanced near the CCM electrode, and the area of increased contractility involved 4.6 +/- 1.2 segments per patient. In 6 patients with HF with left bundle branch block, CCM signals delivered during biventricular pacing (BVP) produced an additional 16.1 +/- 3.7% increase in dP/dt(max) and a 17.0 +/- 7.5% increase in pulse pressure compared with BVP alone (p0.01). CCM stimulation in patients with HF enhanced regional and global measures of LV systolic function, regardless of the varied delivery chamber or whether modulation was performed during RV pacing or BVP.

Background Circumferential radiofrequency ablation around pulmonary vein (PV) ostia has recently been described as a new anatomic approach for atrial fibrillation (AF). Methods and Results We treated 251 consecutive patients with paroxysmal (n=179) or permanent (n=72) AF. Circular PV lesions were deployed transseptally during sinus rhythm (n=124) or AF (n=127) using 3D electroanatomic guidance. Procedures lasted 148±26 minutes. Among 980 lesions surrounding individual PVs (n=956) or 2 ipsilateral veins with close openings or common ostium (n=24), 75% were defined as complete by a bipolar electrogram amplitude 30 ms across the line. The amount of low-voltage encircled area was 3594±449 mm 2 , which accounted for 23±9% of the total left atrial (LA) map surface. Major complications (cardiac tamponade) occurred in 2 patients (0.8%). No PV stenoses were detected by transesophageal echocardiography. After 10.4±4.5 months, 152 patients with paroxysmal AF (85%) and 49 with permanent AF (68%) were AF-free. Patients with and without AF recurrence did not differ in age, AF duration, prevalence of heart disease, or ejection fraction, but the LA diameter was significantly higher ( P P Conclusions Circumferential PV ablation is a safe and effective treatment for AF. Its success is likely due to both PV trigger isolation and electroanatomic remodeling of the area encompassing the PV ostia.

Background —The pulmonary veins (PVs) and surrounding ostial areas frequently house focal triggers or reentrant circuits critical to the genesis of atrial fibrillation (AF). We developed an anatomic approach aimed at isolating each PV from the left atrium (LA) by circumferential radiofrequency (RF) lesions around their ostia. Methods and Results —We selected 26 patients with resistant AF, either paroxysmal (n=14) or permanent (n=12). A nonfluoroscopic mapping system was used to generate 3D electroanatomic LA maps and deliver RF energy. Two maps were acquired during coronary sinus and right atrial pacing to validate the lateral and septal PV lesions, respectively. Patients were followed up closely for ≥6 months. Procedures lasted 290±58 minutes, including 80±22 minutes for acquisition of all maps, and 118±16 RF pulses were deployed. Among 14 patients in AF at the beginning of the procedure, 64% had sinus rhythm restoration during ablation. PV isolation was demonstrated in 76% of 104 PVs treated by low peak-to-peak electrogram amplitude (0.08±0.02 mV) inside the circular line and by disparity in activation times (58±11 ms) across the lesion. After 9±3 months, 22 patients (85%) were AF-free, including 62% not taking and 23% taking antiarrhythmic drugs, with no difference ( P =NS) between paroxysmal and permanent AF. No thromboembolic events or PV stenoses were observed by transesophageal echocardiography. Conclusions —Radiofrequency PV isolation with electroanatomic guidance is safe and effective in either paroxysmal or permanent AF.

The vascular response to local administration of acetylcholine is used, clinically, to assess endothelial function in vivo. However, whether this response predominantly reflects the functional state of the vascular endothelium, or rather results from smooth muscle reactivity per se is not clear. In 15 patients with chronic stable angina and angiographically significant coronary disease, we studied the effects of increasing doses of intracoronary acetylcholine (5, 10, 30, 50, and 80 μg) and nitroglycerin (200 μg) on coronary vascular tone. In three patients the protocol was perfrnned at the time of diagnostic coronary angiographv and 7 and 24 hours after angioplasty. The remaining five underwent acetylcholine administration before and after percutaneous transluminl coronary angioplasty (PTCA). We quantitatively assessed the diameter of 54 coronary arterial segments; 12 stenotic segments, 13 post-PICA segments with residual irregularities, 18 reference segments of the ranee arteries taken proximal to the stenosis or to the dilatation site, and II remote segments ofnonstenotic vessels. They all showed a bimodal response to acetylcholine. At the lowest concentration (5 μg) the agent invariably caused dilatation (9.22 ± 6.55%), which was not significantly different in the various segments and was always less than that induced by nitroglycerin (24.56 ± 12.82%, P < 0.0001). At the highest doses (50 or 80 μg) acetylcholine always induced vasoconstriction, which was significantly more pronounced in the post-PTCA (-31.54 ± 10.65%) and stenotic segments (-23.08 ± 11.88%) than in the reference and remote segments (respectively, -14.88 + 7.63% and - 18.67 + 8.37%, P < 0.05). We conclude that: (l) some degree of endothelial dependent vasodilatation is preserved even in the presence of atheroma and intimal injury induced by angioplasty; (2) atheroma and especially acute intimal injury augment the vasoconstrictor response to high dose acetylcholine, the effect being most probably mediated by primary smooth muscle supersensivity: (3) since acetylcholine has direct and endothelium-mediated vasoactive effects, this agent may not be the ideal one for testing endothelial integrity. (J Interven Cardiol 1994; 7:57–64)

The endothelium-derived peptide, endothelin, has been shown to exert powerful constrictor activity in both isolated and in situ coronary arteries. Recent in vitro data on isolated cardiac myocytes suggest that the substance might also possess electrophysiologic properties. We investigated the possibility that endothelin (ET-1) may exert proarrhythmic effects when infused selectively in the coronary circulation of open-chest-anesthetized dogs. Animals were instrumented for the measurement of left anterior descending (LAD) or left circumflex (LCX) coronary artery blood flow, left systolic ventricular pressure (LSVP), dP/dtmax, mean arterial pressure (MAP), and epicardial electrocardiogram (ECG; three leads). Data were recorded during infusion (2 min) of saline (n = 5) or increasing doses of endothelin (5-80 pmol/kg) given selectively in either the LCX (n = 10) or the LAD (n = 10). When infused into the LCX, endothelin produced a dose-dependent decrease in flow (40 +/- 23% at 80 pmol/kg, mean +/- SD, p less than 0.01) with a concomitant increase in coronary resistance and a decrease in dP/dtmax and MAP. ECG changes typical of myocardial ischemia paralleled the decrease in flow and culminated in ventricular fibrillation at the highest dose (80% of dogs). Endothelin caused similar hemodynamic effects when infused in the LAD, but fatal arrhythmias occurred for lower doses and for little or no change in coronary blood flow. Thirty percent of the animals died at 10 and 60% died at 20 pmol/kg, doses that induced only a moderate decrease (8 +/- 7 and 21 +/- 12%, respectively) in LAD total blood flow. Ventricular tachycardia always preceded ventricular fibrillation and death.(ABSTRACT TRUNCATED AT 250 WORDS)

Technetium-99m labeled bis(1,2-diethylphosphino)ethane was evaluated as a cardiac perfusion agent in mice, dogs and normal human volunteers. The agent produced as a single cationic compound was prepared by a simple kit type method and had a rapid myocardial uptake in animals. The cardiac uptake of the agent in dogs averaged 4.6% of administered dose and delineated left and right ventricles by in vivo imaging. In dogs with experimental myocardial infarction, the agent was distributed according to the regional myocardial blood flow, had excellent correlation with myocardial distribution of 85Sr microspheres (r = 0.96, 0.93)] and 201 Tl (r = 0.91 and 0.83) , and enabled us to detect perfusion defects by in vivo scintigraphy. The agent, however, failed to have a useful degree of cardiac uptake in humans.

Plasma beta-thromboglobulin (beta TG) was assayed in 10 insulin-dependent uncomplicated diabetic subjects and in 10 age- and sex-matched metabolically healthy controls, both at rest and after maximal physical exercise. Diabetic patients showed significantly higher (p less than 0.005) resting beta TG values as compared to the control group. After physical exercise, beta TG rose significantly (p less than 0.05) only in the control group, thus abolishing the difference (evaluated through beta TG values) between the two groups observed at rest. Platelet hyperactivity seems thus to be present even in uncomplicated diabetes, at rest, while exercise does not lead to a further increase in beta TG values contrary to what is observed in controls.

Heart rate, blood pressure, and left ventricular ejection fraction (LVEF) were measured by means of Au 195 m first-pass angiocardiography, during maximal supine bicycle exercise in 20 young asymptomatic patients with insulin-dependent diabetes (IDD) (10 retinopathic and 10 uncomplicated) and in 10 control subjects. Five patients with retinopathic IDD also had mild subclinical autonomic neuropathy. Exercise capacity was diminished, although not significantly, in patients with retinopathic IDD. Heart rate and LVEF were similar in all groups at rest and at submaximal exercise. At peak exercise patients with retinopathic IDD had significantly lower heart rate (134 +/- 4 bpm) and LVEF (62.9 +/- 3.7%) than those with umcomplicated IDD (158 +/- 8 bpm and 76.6 +/- 2.4%, respectively) and control subjects (152 +/- 6 bpm and 73.5 +/- 1.9%, respectively). LVEF increased vs baseline in all control subjects and patients with uncomplicated IDD, but in only three with retinopathic IDD. Leg muscle blood flow (MBF) was also evaluated at rest and during exercise by 133Xe washout. Exercise MBF was significantly lower in patients with retinopathic IDD (40.5 +/- 2.23 ml X min-1 X 100 gm-1) than in control subjects (49.9 +/- 1.87 ml X min-1 X 100 gm-1) and in those with uncomplicated IDD (49.0 +/- 1.87 ml X min-1 X 100 gm-1). Diffuse microangiopathy, alone or in combination with neuropathy, might be responsible for the impairment of cardiovascular function in diabetes.

846-5 Cryoablation for Treatment of Paroxysmal Atrial Fibrillation: Initial Results of a Prospective Multicenter 1188 Cardiac Electrophysiology and Clinical Trial Arrhythmias II Huah Calkins Robert Hoyt, Mark A. Wood, Emile Daoud. Gregory M. Ayers, Neal Kay, Johns Hopkins Medical Institutions, Baltimore, MD Tuesday, April 01, 2003, Noon-2:00 p.m. Background: Pulmonary vein stenosis is a known complication of RF ablation of atrial McCormick Place, Hall A fibrillation (AF). Cryoablatlon represents an alternative energy source that may prevent Presentation Hour: I:00 p.m.-2:OO p.m this complication. The purpose of this multicenter clinical trial is to test the safety and eflicacy of dryoablation orthe pulmonary vein ostia for treatment of AF. Methods: Fourteen patients (12 males, 5828 yrs) with drug refractory paroxysmal AF 1186-3 Effects of Intravenous lbutilide on the Complexity of