Sex differences in outcomes of primary prevention implantable cardioverter-defibrillator therapy: combined registry data from eleven European countries.

Aims: Therapy with an implantable cardioverter defibrillator (ICD) is established for the prevention of sudden cardiac death (SCD) in high risk patients. We aimed to determine the effectiveness of primary prevention ICD therapy by analysing registry data from 14 centres in 11 European countries compiled between 2002 and 2014, with emphasis on outcomes in women who have been underrepresented in all trials. Methods and results: Retrospective data of 14 local registries of primary prevention ICD implantations between 2002 and 2014 were compiled in a central database. Predefined primary outcome measures were overall mortality and first appropriate and first inappropriate shocks. A multivariable model enforcing a common hazard ratio for sex category across the centres, but allowing for centre-specific baseline hazards and centre specific effects of other covariates, was adjusted for age, the presence of ischaemic cardiomyopathy or a CRT-D, and left ventricular ejection fraction ≤25%. Of the 5033 patients, 957 (19%) were women. During a median follow-up of 33 months (IQR 16-55 months) 129 women (13%) and 807 men (20%) died (HR 0.65; 95% CI: [0.53, 0.79], P-value < 0.0001). An appropriate ICD shock occurred in 66 women (8%) and 514 men (14%; HR 0.61; 95% CI: 0.47-0.79; P = 0.0002). Conclusion: Our retrospective analysis of 14 local registries in 11 European countries demonstrates that fewer women than men undergo ICD implantation for primary prevention. After multivariate adjustment, women have a significantly lower mortality and receive fewer appropriate ICD shocks.

First prospective, multi-centre clinical experience with a novel left ventricular quadripolar lead.

AIMS: Cardiac resynchronization therapy (CRT) is sometimes complicated by elevated pacing thresholds and phrenic nerve stimulation (PNS), both of which may require that the coronary sinus lead be repositioned. The purpose of this study was to evaluate the performance of a novel quadripolar electrode lead and cardiac resynchronization therapy-defibrillator (CRT-D) device that enables electrical repositioning, potentially obviating a lead reposition procedure. METHODS AND RESULTS: Patients indicated for CRT were enrolled and received a quadripolar electrode lead and CRT-D device (Quartetmodel 1458Q and Promote Q; St Jude Medical, Sylmar, CA, USA). Electrical data, and the presence of PNS during pacing from each left ventricular (LV) configuration, were documented at pre-hospital discharge and at 1 month. Seventy-five patients were enrolled and 71 were successfully implanted with a Quartetlead. Electrical measurements were stable over the follow-up period. Ninety-seven per cent (64 of 66) of patients had one or more programmable configurations with a threshold < 2.5 V and no PNS vs. 86% (57 of 66) if only conventional bipolar configurations were considered. Physicians were able to use the increased programming options to manage threshold changes and PNS. CONCLUSION: The new quadripolar electrode LV lead provides more programming options to address common problems faced when managing CRT patients. Electrical measurements from new vectors are comparable with conventional configurations. Furthermore, 11% of patients in the study suffered PNS on all conventional bipolar vectors.

Acute hemodynamic effects of right and left ventricular lead positions during the implantation of cardiac resynchronization therapy defibrillators.

BACKGROUND: To evaluate the acute hemodynamic effects of different right (RV) and left ventricular (LV) pacing sites in patients undergoing the implantation of a cardiac resynchronization therapy defibrillator (CRT-D). METHODS: Stroke volume index (SVI), assessed via pulse contour analysis, and dp/dt max, obtained in the abdominal aorta, were analyzed in 21 patients with New York Heart Association class III heart failure and left bundle branch block (mean ejection fraction of 24 ± 6%), scheduled for CRT-D implantation under general anesthesia. We compared the hemodynamic effects of RV apical (A), RV septal (B), and biventricular pacing using the worst (lowest SVI; C) and best (highest SVI; D) coronary sinus lead positions. RESULTS: Mean arterial pressure, SVI, and dp/dt max did not differ significantly between RV apical and septal pacing. Dp/dt max and SVI increased significantly during biventricular pacing (dp/dt max: B, 588 ± 160 mmHg/s; C, 651 ± 218 mmHg/s, P = 0.03 vs B; D, 690 ± 220 mmHg/s, P = 0.02 vs C; SVI: B, 33.6 ± 5.5 mL/m², C, 34.8 ± 6.1 mL/m², P = 0.08 vs B, D 36.0 ± 6.0 mL/m², P < 0.001 vs C). The best hemodynamic response was associated with lateral or inferior lead positions in 15 patients. Other LV lead positions were most effective in six patients. CONCLUSIONS: The optimal LV lead position varies significantly among patients and should be individually determined during CRT-D implantation. The impact of the RV stimulation site in patients with intraventricular conduction delay, undergoing CRT-D implantation, has to be investigated in further studies.

Electrocardiographic differentiation of common type atrioventricular nodal reentrant tachycardia from atrioventricular reciprocating tachycardia via a concealed accessory pathway.

OBJECTIVE: The present study aimed to evaluate the diagnostic value of specific ECG markers in the differentiation of common type atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular reentrant tachycardia (AVRT) via a concealed accessory pathway. METHODS: One hundred and ten ECGs with paroxysmal narrow QRS complex, short RP tachycardia were evaluated. Subjects with overt ventricular pre-excitation during sinus rhythm were excluded from the study. The mechanism of arrhythmia was established during the electrophysiological study and confirmed by the efficacy of radiofrequency ablation. RESULTS: Of the 110 patients, 74 displayed common type AVNRT and 36 AVRT. Predictors of AVNRT were the presence of pseudo r'-waves in lead V1 [sensitivity 39.19%; specificity 97.14%; positive predictive value (PPV) 96.67%; negative predictive value (NPV) 43.04%] and pseudo S-waves in inferior leads (sensitivity 28.38%; specificity 94.29%; PPV 91.30%; NPV 38.37%). In the setting of visible P-waves, an RP interval < or =90 ms favoured the diagnosis of AVNRT (sensitivity 57.14%; specificity 80.65%). Predictors of AVRT were QRS alternans (sensitivity 50%; specificity 89.19%; PPV 69.23%; NPV 78.57%) as well as ST-segment alterations during tachycardia. The overall sensitivity, specificity, PPV and NPV of ST-segment depression for discriminating AVRT from AVNRT were 97.22%, 58.11%, 53.03%, 97.73%, respectively. Similarly, the sensitivity, specificity, PPV and NPV of ST-segment elevation in lead aVR were 94.44%, 58.11%, 52.31%, and 95.56%, respectively. Multiple logistic regression analysis showed that ST-segment depression [(odds ratio (OR): 12.67, 95% confidence interval (CI): 1.77-90.81, P = 0.011)] and QRS alternans (OR: 9.43, 95% CI: 1.38-64.37, P = 0.022) displayed the highest predictive ability favouring the diagnosis of AVRT. CONCLUSIONS: Twelve-lead ECG parameters may help to differentiate the mechanism of supraventricular tachycardia prior to the ablation procedure.

Predictors of atrial tachyarrhythmias in subjects with type 1 ECG pattern of Brugada syndrome.

BACKGROUND: Previous studies have demonstrated a high incidence of atrial tachyarrhythmias (ATs) in patients with Brugada syndrome (BS). The present study aimed to investigate whether various 12-lead electrocardiogram (ECG) and electrophysiological parameters may help to differentiate subjects with a high probability to develop ATs. METHODS AND RESULTS: The clinical records of 38 individuals (31 males, age 44.4 +/- 13.9) with spontaneous (n = 15) or ajmaline-induced (n = 23) type 1 ECG pattern of BS were analyzed. During a mean follow-up period of 4.6 +/- 2.2 years, nine subjects suffered ATs (24%). Six subjects displayed paroxysmal atrial fibrillation and three typical atrial flutter. Among the studied 12-lead ECG parameters, subjects with ATs exhibited increased values of P-wave duration in lead II, P-wave dispersion, PR interval in leads II, QRS duration in leads II and V(2), Tpeak-end interval in lead II, and Tpeak-end dispersion of the 12 leads in relation to those without ATs (P < 0.05). Among the assessed electrophysiological parameters, atrial-His (AH) and His-ventricular (HV) intervals were significantly prolonged in subjects with ATs (P < 0.05). Multiple Cox proportional hazards analysis revealed that P-wave duration in lead II, P-wave dispersion, Tpeak-end in lead II, Tpeak-end dispersion of the 12 leads, as well as AH and HV intervals are independent predictors of ATs in subjects with BS (P < 0.05). Cut-off point analysis showed that an HV interval>or=56 ms displayed the highest predictive ability (P < 0.01). CONCLUSION: Our findings demonstrate that simple 12-lead ECG and electrophysiological parameters may easily be applied to identify high-risk subjects with BS ECG phenotype to develop ATs.

Small or large isolation areas around the pulmonary veins for the treatment of atrial fibrillation? Results from a prospective randomized study.

BACKGROUND: Pulmonary vein (PV) isolation is a promising new treatment for atrial fibrillation (AF). We hypothesized that isolation of large areas around both ipsilateral PVs with verification of conduction block is more effective than the isolation of each individual PV. METHODS AND RESULTS: A total of 110 patients, 67 with paroxysmal AF and 43 with persistent AF, were randomly assigned to undergo either isolation of each individual PV or isolation of large areas around both ipsilateral PVs. The isolation of each individual PV was an electrophysiologically guided, ostial segmental ablation with a 64-pole basket catheter or a 20-pole circular mapping catheter (group I). Isolation of large areas was performed around the 2 ipsilateral veins with a nonfluoroscopic navigation system and a circular 20-pole mapping catheter for verification of conduction block (group II). In both groups, an irrigated-tip ablation catheter (25 to 35 W) was used to achieve complete isolation. Procedure and ablation times were longer in group II, whereas fluoroscopic time was significantly shorter (P < or = 0.001). After a follow-up period of 15+/-4 months, 27 patients in group I (49%) and 37 patients in group II (67%) remained free of symptoms of AF and had no AF or atrial flutter during repetitive Holter monitoring without antiarrhythmic drug treatment after a single procedure (P < or = 0.05). CONCLUSIONS: The rate of success was significantly higher and fluoroscopy times were significantly lower in the group with large isolation areas around both ipsilateral PVs than in those who underwent individual PV isolation.

Changes in pulse pressure variability during cardiac resynchronization therapy in mechanically ventilated patients.

INTRODUCTION: The respiratory variation in pulse pressure (PP) has been established as a dynamic variable of cardiac preload which indicates fluid responsiveness in mechanically ventilated patients. The impact of acute changes in cardiac performance on respiratory fluctuations in PP has not been evaluated until now. We used cardiac resynchronization therapy as a model to assess the acute effects of changes in left ventricular performance on respiratory PP variability without the need of pharmacological intervention. METHODS: In 19 patients undergoing the implantation of a biventricular pacing/defibrillator device under general anesthesia, dynamic blood pressure regulation was assessed during right ventricular and biventricular pacing in the frequency domain (power spectral analysis) and in the time domain (PP variation: difference between the maximal and minimal PP values, normalized by the mean value). RESULTS: PP increased slightly during biventricular pacing but without statistical significance (right ventricular pacing, 33 +/- 10 mm Hg; biventricular pacing, 35 +/- 11 mm Hg). Respiratory PP fluctuations increased significantly (logarithmically transformed PP variability -1.27 +/- 1.74 ln mm Hg2 versus -0.66 +/- 1.48 ln mm Hg2; p < 0.01); the geometric mean of respiratory PP variability increased 1.8-fold during cardiac resynchronization. PP variation, assessed in the time domain and expressed as a percentage, showed comparable changes, increasing from 5.3% (3.1%; 12.3%) during right ventricular pacing to 6.9% (4.7%; 16.4%) during biventricular pacing (median [25th percentile; 75th percentile]; p < 0.01). CONCLUSION: Changes in cardiac performance have a significant impact on respiratory hemodynamic fluctuations in ventilated patients. This influence should be taken into consideration when interpreting PP variation.

Feasibility and safety of pulmonary vein isolation using a new mapping and navigation system in patients with refractory atrial fibrillation.

BACKGROUND: Ostial pulmonary vein (PV) isolation by radiofrequency (RF) catheter ablation can cure patients with atrial fibrillation (AF); however, this procedure carries the risk of PV stenosis. The aim of this study was to assess the feasibility of a new mapping and navigation technique using a multipolar basket catheter (BC) for PV isolation in patients with refractory AF and to analyze its safety with regard to PV stenosis at long-term follow-up. METHODS AND RESULTS: We studied 55 patients (mean age, 53+/-11 years; 40 male) with drug-refractory AF (paroxysmal, n=37; persistent, n=18). A 64-pole BC was placed transseptally into each of the accessible PVs. By use of a nonfluoroscopic navigation system, the ablation catheter was guided to the BC electrodes at the PV ostium, with earliest activation during sinus rhythm. RF was delivered by use of maximum settings of temperature at 50 degrees C and power at 30 W. The end point of the procedure was the complete elimination of all distal and fragmented ostial PV potentials. Of 165 targeted veins, 163 were successfully isolated with a mean RF duration of 720+/-301 seconds per vein. At 1-year follow-up, 62% of the patients were in sinus rhythm without antiarrhythmic drugs. Contrast-enhanced magnetic resonance angiography revealed 2 PV stenoses of >25% out of 165 treated vessels. CONCLUSIONS: The use of a multipolar BC allowed effective and safe PV isolation by combining 3D mapping and navigation. At 1-year follow-up, 62% of the patients were in sinus rhythm without antiarrhythmic drugs, and the incidence of relevant diameter reduction of the treated PVs was 1.2%.

Platelet activation and myocardial necrosis in patients undergoing radiofrequency and cryoablation of isthmus-dependent atrial flutter.

AIMS: Lower platelet activation by cryoenergy compared with radiofrequency (RF) energy was recently demonstrated immediately following ablation procedures of cardiac arrhythmias. Due to the delayed occurrence of cryolesions it is currently unknown, if cryoenergy and RF energy are associated with similar platelet activation and myocardial necrosis in the days after the procedure. METHODS AND RESULTS: We enrolled 38 patients with common atrial flutter undergoing cavotricuspid isthmus ablation with either RF energy (n = 23) or cryoenergy (n = 13). Ten patients undergoing RF ablation and receiving aspirin served as antiplatelet control group. Troponin T and platelet surface protein expression of P-selectin were determined before and immediately after ablation as well as on day 1 and 2 thereafter. Rise in troponin T was amplified after RF ablation (0.50 +/- 0.37 microg/L) when compared with cryoablation (0.24 +/- 0.20 microg/L; P = 0.024). In patients without aspirin, a significant increase in P-selectin expression was observed on day 1 after intervention in RF ablation compared with cryoablation (80 +/- 26 vs. 63 +/- 16 arbitrary units; P = 0.048). Platelet activation was attenuated in patients receiving aspirin. CONCLUSION: Successful ablation of atrial flutter with cryoenergy is associated with less myocardial necrosis and platelet activation compared with ablation with RF energy. Increased platelet activation following RF ablation can be attenuated by concomitant treatment with aspirin.

Effects of circumferential ostial radiofrequency lesions on pulmonary vein activation recorded with a multipolar basket catheter.

AIMS: Two different ablation procedures are performed to cure patients of atrial fibrillation (AF): (1) the electrophysiological pulmonary vein (PV) isolation, and (2) the anatomical circumferential ablation of all four PV ostia. The aim of this study was to determine the effects of circumferential radiofrequency lesions around the ostia on PV activation. METHODS AND RESULTS: In 34 patients with drug refractory paroxysmal (N = 22) or persistent (N = 12) AF a 31-mm basket catheter (BC) was introduced transseptally in the PVs. After creating a circumferential ablation line around the PV ostia using a nonfluoroscopic 3D-navigation system, electrical isolation was achieved in 46% of the PVs, and prolongation of conduction time (+39 +/- 34 ms) was observed in 30%. PVs with persistent conduction (54%) were isolated by ablating the remaining conduction pathways using the BC. At 12 months follow-up, 62% of the patients were in stable sinus rhythm without antiarrhythmic drug therapy. Six patients had developed left atrial flutter. CONCLUSIONS: Anatomically guided, circumferential lesions around the PV ostia resulted in isolation in only 46% of the veins. At 12 months, 62% of the patients were free of AF without antiarrrhythmic drug treatment, however, 6 patients (18%) developed left atrial flutter.

Pulmonary haemodynamics at rest and during exercise in patients with significant pulmonary vein stenosis after radiofrequency catheter ablation for drug resistant atrial fibrillation.

AIMS: Iatrogenic pulmonary vein (PV) stenosis after radiofrequency catheter ablation for atrial fibrillation (AF) is a new pathology in cardiology. The effects of PV stenosis on the pulmonary circulation are not yet known. We provide long-term follow-up data in patients with significant PV stenosis including magnetic resonance imaging (MRI) and Swan Ganz (SG) right heart catheterization. METHODS AND RESULTS: One hundred and seventeen patients had MRI 12-24 months after the AF ablation procedure. Eleven patients (58+/-7 years, nine males) with significant stenosis (n=9) or occlusion of the proximal PV (n=5) at this follow-up were re-examined using MRI and SG right heart catheterization at rest and during exercise (follow-up time since PV ablation 50+/-15 months). None of these underwent previous PV angioplasty. When compared with prior MRI studies, no significant changes were noted. At rest, no patient had pulmonary hypertension. At 100 W, seven patients had elevated pulmonary artery pressures, three of them probably caused, in part, by left ventricular dysfunction. CONCLUSION: Significant stenosis/occlusions of one or two PV do not create pulmonary hypertension at rest during long-term follow-up. However, seven of the 11 patients develop pulmonary hypertension during exercise. All three patients with stenosis/occlusions of two PV were affected.

[3-d mapping of pulmonary veins using a multipolar basket catheter. Implications for catheter ablation of atrial fibrillation]. / 3-D-Mapping der Pulmonalvenen mit einem multipolaren Basketkatheter. Bedeutung für die Katheterablation von Vorhofflimmern.

BACKGROUND: Focal discharges from pulmonary veins are the major sources of paroxysmal atrial fibrillation. The aim of this study was to analyze the activation pattern of pulmonary veins during sinus rhythm and ectopy with the help of a multipolar basket catheter and to disconnect them from the left atrium by localized radiofrequency catheter ablation. PATIENTS AND METHODS: We studied 65 patients (43 male, 22 female, mean age 54 +/- 12 years) with drug-refractory atrial fibrillation (paroxysmal n = 42, persistent n = 23). A 64-pole basket catheter (Figure 1) with a diameter of 31 or 38 mm (Constellation, Boston Scientific) was placed transseptally into the pulmonary veins to record its activation during ectopic beats and during sinus rhythm or coronary sinus pacing (Figure 2). The ablation catheter was placed as ostial as possible next to the electrodes showing the earliest pulmonary vein activation during sinus rhythm or coronary sinus pacing (Figures 3 and 4a). The radiofrequency energy was delivered with a maximum temperature of 50 degrees C and a maximum power of 30 W. In 32 patients, an irrigated-tip catheter (Thermocool, Biosense-Webster) was used. Endpoint of the procedure was the complete elimination of all distal pulmonary vein potentials during sinus rhythm (Figure 4b). RESULTS: The mean number of procedures per patients was 1.25, mean procedure time 236 +/- 79 min, and mean fluoroscopy time 40 +/- 17 min, respectively. In 16 veins, repetitive discharges (more than three) could be recorded under stable conditions (Figures 2 and 5). In twelve of these 16 pulmonary veins (75%), the activation pattern during ectopic beats was identical in the same vein, but different from one vein to another (Figure 2). In four veins, changing activation patterns were observed in the same vein. Focal atrial fibrillation was recorded in four pulmonary veins (Figures 6 and 7). A total of 187 out of 190 mapped veins were successfully isolated at the ostium by ablating 2.3 +/- 1.1 separated conduction pathways. In 16 patients, a second EP study was performed for recurrence of atrial fibrillation. Recovery of conduction of a previously isolated pulmonary vein was identified as the primary reason for recurrence of atrial fibrillation. The second reason were ostial foci, localized proximal to the ablation line (Figure 8). COMPLICATIONS AND FOLLOW-UP: One pericardial tamponade occurred. Carbonization on the splines of the basket catheter-observed in twelve cases with use of a nonirrigated-tip catheter-was prevented by use of irrigated-tip catheters. At 12 months, 36 out of 65 patients (55%) are in sinus rhythm without antiarrhythmic drug use, 28 of 42 patients (67%) with paroxysmal atrial fibrillation. Only one pulmonary vein stenosis > 50% was detected by angiomagnetic resonance imaging 1 year after the procedure. CONCLUSION: 75% of the arrhythmogenic pulmonary veins showed a stable and specific pattern during repetitive ectopic activity. Ostial ablation of 2.3 +/- 1.1 separated conduction pathways from the left atrium into the pulmonary veins resulted in complete conduction block in 187 of 190 veins.