Electrogram morphology discriminators in implantable cardioverter defibrillators: A comparative evaluation.

BACKGROUND: Morphology algorithms are currently recommended as a standalone discriminator in single-chamber implantable cardioverter defibrillators (ICDs). However, these proprietary algorithms differ in both design and nominal programming. OBJECTIVE: To compare three different algorithms with nominal versus advanced programming in their ability to discriminate between ventricular (VT) and supraventricular tachycardia (SVT). METHODS: In nine European centers, VT and SVTs were collected from Abbott, Boston Scientific, and Medtronic dual- and triple-chamber ICDs via their respective remote monitoring portals. Percentage morphology matches were recorded for selected episodes which were classified as VT or SVT by means of atrioventricular comparison. The sensitivity and related specificity of each manufacturer discriminator was determined at various values of template match percentage from receiving operating characteristics (ROC) curve analysis. RESULTS: A total of 534 episodes were retained for the analysis. In ROC analyses, Abbott Far Field MD (area under the curve [AUC]: 0.91; P < .001) and Boston Scientific RhythmID (AUC: 0.95; P < .001) show higher AUC than Medtronic Wavelet (AUC: 0.81; P < .001) when tested for their ability to discriminate VT from SVT. At nominal % match threshold all devices provided high sensitivity in VT identification, (91%, 100%, and 90%, respectively, for Abbott, Boston Scientific, and Medtronic) but contrasted specificities in SVT discrimination (85%, 41%, and 62%, respectively). Abbott and Medtronic's nominal thresholds were similar to the optimal thresholds. Optimization of the % match threshold improved the Boston Scientific specificity to 79% without compromising the sensitivity. CONCLUSION: Proprietary morphology discriminators show important differences in their ability to discriminate SVT. How much this impact the overall discrimination process remains to be investigated.

Impact of pacing site on QRS duration and its relationship to hemodynamic response in cardiac resynchronization therapy for congestive heart failure.

INTRODUCTION: Recent studies have demonstrated that left ventricular (LV) pacing site is a critical parameter in optimizing cardiac resynchronization therapy (CRT). The present study evaluates the effect of pacing from different LV locations on QRS duration (QRSd) and their relationship to acute hemodynamic response in congestive heart failure patients. METHODS AND RESULTS: Thirty-five patients with nonischemic dilated cardiomyopathy and left bundle branch block referred for CRT device implantation were studied. Eleven predetermined LV pacing sites were systematically assessed in random order: epicardial: coronary sinus (CS); endocardial: basal and mid-cavity (septal, anterior, lateral, and inferior), apex, and the endocardial site facing the CS pacing site. For each patient QRSd and +dP/dtmax during baseline (AAI) and DDD LV pacing at 2 atrioventricular delays were compared. Response to CRT was significantly better in patients with wider baseline QRSd (≥150 milliseconds). Hemodynamic response was inversely correlated to increase of QRSd during LV pacing (short atrioventricular [AV] delay: r = 0.44, P < 0.001; long AV delay: r = 0.59, P < 0.001). Compared to baseline, LV pacing at the site of shortest QRSd significantly improved +dP/dtmax (+18 ± 25%, P < 0.001) but was not superior to other conventional strategy (lateral wall, CS pacing, and echo-guided) and was inferior to a hemodynamically guided strategy. CONCLUSIONS: In our study, we have demonstrated that changes of QRSd during LV pacing correlated with acute hemodynamic response and that LV pacing location was a primary determinant of paced QRSd. Although QRSd did not predict the maximum hemodynamic response, our results confirm the link between electrical activation and hemodynamic response of the LV during CRT.

Contributions of a hemodynamic sensor embedded in an atrial lead in a porcine model.

INTRODUCTION: Preliminary studies have revealed a high correlation between peak endocardial acceleration (PEA) measured with a sensor embedded in a ventricular lead and human cardiac contractility. In this study we assessed (1) the contributions made by measurements of PEA1, an index of ventricular systolic contraction, from the right atrium, and (2) the feasibility of recording a fourth component of PEA (PEA4), coincident with atrial contraction and corresponding to the phonocardiographic fourth heart sound. METHODS: We placed a PEA sensor embedded at the tip of a right atrial lead in 9 pigs. A 7F Millar catheter tip micromanometer was introduced into the left ventricular (LV) cavity to measure dP/dt(max). Myocardial contractility was increased by infusion of dobutamine and depressed by the infusion of esmolol. We searched, during VDD pacing, for PEA4 following atrial systole, while gradually lengthening the atrioventricular delay. Ventricular fibrillation was then triggered by rapid stimulation. RESULTS: The changes in PEA1 were correlated with the changes in LV dP/dt(max) (r = 0.91; P < 0.001). A low-frequency component of the endocardial signal (PEA4) was visible approximately 50 milliseconds after the atrial electrogram in all experiments. Following the induction of ventricular fibrillation, PEA4 remained visible on the endocardial recording, simultaneous with the sensed atrial electrogram. CONCLUSIONS: This study confirms the merit of embedding a PEA sensor in an atrial lead. The exploitation of the information provided by the PEA1 signal remains pertinent and the possibility to record an additional PEA4 component offers the perspective of new clinical applications.

Addition of a second LV pacing site in CRT nonresponders rationale and design of the multicenter randomized V(3) trial.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an effective treatment of heart failure (HF) in presence of a depressed left ventricular (LV) ejection fraction and a wide QRS complex. It is limited by a high proportion of nonresponders. Attempts have been made, in small studies, to increase the number of stimulation sites to optimize the resynchronization therapy. V(3) is a planned multicenter, randomized trial whose objective is to evaluate the clinical benefit conferred by the addition of a second LV lead in nonresponders after at least 6 months of standard biventricular stimulation. METHODS AND RESULTS: A total of 84 patients will be enrolled in 11 French medical centers. Patients will be randomly assigned to receive either an additional LV lead (test group) or to keep their current stimulation system unchanged (control group). Enrollment is planned to begin in March 2010 and is expected to end within 1 year. The primary study end point will be the HF clinical composite score evaluated at 1 year follow-up. Secondary end points include degree of echocardiographic reverse remodeling and changes in clinical measurements. CONCLUSIONS: The V(3) trial will examine the clinical benefit conferred by the addition of a second LV lead in nonresponders to standard CRT.

Electrocardiogram-based algorithm to predict the left ventricular lead position in recipients of cardiac resynchronization systems.

INTRODUCTION: Biventricular pacing is associated with various electrocardiographic patterns depending on the position of the left ventricular (LV) lead. We aimed to develop an electrocardiogram-based algorithm to predict the position of the LV lead. METHODS: The algorithm was developed in 100 consecutive recipients of cardiac resynchronization therapy (CRT) systems. QRS axis, morphology, and polarity were analyzed with a view to define the specific electrocardiographic characteristics associated with the various LV lead positions. The algorithm was prospectively validated in 50 consecutive CRT device recipients. RESULTS: The first analysis of the algorithm was the QRS morphology in V(1). A positive R wave in V(1) suggested LV lateral or posterior wall stimulation. A QS pattern was specific of anterior LV leads. In the presence of an R wave in V(1), V(6) was analyzed to distinguish between an inferior and anterior LV lead. Inferior leads were never associated with a positive V(6). To differentiate between lateral and posterior positions, we analyzed the pattern in V(2). Lateral leads were associated with an R morphology in V(1) and a negative V(2). Posterior leads were associated with an R morphology in V(1) and V(2). The algorithm allowed a reliable distinction between an inferior or anterior and a lateral or posterior lead position in 90% of patients. Inferior, anterior, lateral, and posterior positions were reliably distinguished in 80% of patients. CONCLUSION: This algorithm predicted the position of the LV lead with a high sensitivity and predictive value.

High prevalence of sleep apnea syndrome in patients with long-term pacing: the European Multicenter Polysomnographic Study.

BACKGROUND: Cardiovascular diseases leading to pacemaker implantations are suspected of being associated with a high rate of undiagnosed sleep apnea syndrome (SAS). We sought to determine the prevalence and consequences of SAS in pacemaker patients according to pacing indications: heart failure, symptomatic diurnal bradycardia, and atrioventricular block. METHODS AND RESULTS: Ninety-eight consecutive patients (mean age, 64+/-8 years) not known to have sleep apnea were included; 29 patients were paced for dilated cardiomyopathy (29%), 33 for high-degree atrioventricular block (34%), and 36 for sinus node disease (37%). All underwent Epworth Sleepiness Scale assessment and polysomnography with the pacemaker programmed to right ventricular DDI pacing mode (lower pacing rate, 50 pulses per minute). SAS was defined as an apnea-hypopnea index > or = 10/h. Mean Epworth Sleepiness Scale was in the normal range (7+/-4), although 13 patients (25%) had an abnormal score > 11/h. Fifty-seven patients (59%) had SAS; of these, 21 (21.4%) had a severe SAS (apnea-hypopnea index > 30/h). In patients with heart failure, 50% presented with SAS (mean apnea-hypopnea index, 11+/-7) compared with 68% of patients with atrioventricular block (mean apnea-hypopnea index, 24+/-29) and 58% with sinus node disease (mean apnea-hypopnea index, 19+/-23). CONCLUSIONS: In paced patients, there is an excessively high prevalence of undiagnosed SAS (59%). Whether treating SAS would have changed the need for pacing is unknown. Treatment effects should be further evaluated particularly because these patients are less symptomatic than typical SAS patients. In any case, SAS should be systematically searched for in paced patients owing to potential detrimental effects on their cardiovascular evolution.

Outcome after implantation of a cardioverter-defibrillator in patients with Brugada syndrome: a multicenter study.

BACKGROUND: Brugada syndrome is an arrhythmogenic disease characterized by an increased risk of sudden cardiac death (SCD) by ventricular fibrillation. At present, an implantable cardioverter-defibrillator (ICD) is the recommended therapy in high-risk patients. This multicenter study reports the outcome of a large series of patients implanted with an ICD for Brugada syndrome. METHODS AND RESULTS: All patients (n=220, 46+/-12 years, 183 male) with a type 1 Brugada ECG pattern implanted with an ICD in 14 centers between 1993 and 2005 were investigated. ICD indication was based on resuscitated SCD (18 patients, 8%), syncope (88 patients, 40%), or positive electrophysiological study in asymptomatic patients (99 patients, 45%). The remaining 15 patients received an ICD because of a family history of SCD or nonsustained ventricular arrhythmia. During a mean follow-up of 38+/-27 months, no patient died and 18 patients (8%) had appropriate device therapy (10+/-15 shocks/patient, 26+/-33 months after implantation). The complication rate was 28%, including inappropriate shocks, which occurred in 45 patients (20%, 4+/-3 shocks/patient, 21+/-20 months after implantation). The reasons for inappropriate therapy were lead failure (19 patients), T-wave oversensing (10 patients), sinus tachycardia (10 patients), and supraventricular tachycardia (9 patients). Among implantation parameters, high defibrillation threshold, high pacing threshold, and low R-wave amplitude occurred, respectively, in 12%, 27%, and 15% of cases. CONCLUSIONS: In this large Brugada syndrome population, a low incidence of arrhythmic events was found, with an annual event rate of 2.6% during a follow-up of >3 years, in addition to a significant risk of device-related complications (8.9%/year). Inappropriate shocks were 2.5 times more frequent than appropriate ones.

Catheter ablation for atrial fibrillation in congestive heart failure.

BACKGROUND: Congestive heart failure and atrial fibrillation often coexist, and each adversely affects the other with respect to management and prognosis. We prospectively evaluated the effect of catheter ablation for atrial fibrillation on left ventricular function in patients with heart failure. METHODS: We studied 58 consecutive patients with congestive heart failure and a left ventricular ejection fraction of less than 45 percent who were undergoing catheter ablation for atrial fibrillation. We selected as controls 58 patients without congestive heart failure who were undergoing ablation for atrial fibrillation, matched according to age, sex, and classification of atrial fibrillation. We evaluated the patients' left ventricular function and dimensions, symptom score, exercise capacity, and quality of life at baseline and at months 1, 3, 6, and 12. RESULTS: After a mean (+/-SD) of 12+/-7 months, 78 percent of the patients with congestive heart failure and 84 percent of the controls remained in sinus rhythm (P=0.34) (69 percent and 71 percent, respectively, were in sinus rhythm without the administration of antiarrhythmic drugs). The patients with congestive heart failure had significant improvement in left ventricular function (increases in the ejection fraction and fractional shortening of 21+/-13 percent and 11+/-7 percent, respectively; P<0.001 for both comparisons), left ventricular dimensions (decreases in the diastolic and systolic diameters of 6+/-6 mm and 8+/-7 mm, respectively; P=0.03 and P<0.001, respectively), exercise capacity, symptoms, and quality of life. The ejection fraction improved significantly not only in patients without concurrent structural heart disease (24+/-10 percent, P<0.001) and those with inadequate rate control before ablation (23+/-10 percent, P<0.001), but also in those with coexisting heart disease (16+/-14 percent, P<0.001) and adequate rate control before ablation (17+/-15 percent, P<0.001). CONCLUSIONS: Restoration and maintenance of sinus rhythm by catheter ablation without the use of drugs in patients with congestive heart failure and atrial fibrillation significantly improve cardiac function, symptoms, exercise capacity, and quality of life.

Benefit of atrial pacing in sleep apnea syndrome.

BACKGROUND: Many patients with sleep apnea syndrome have nocturnal bradycardia, paroxysmal tachyarrhythmias, or both, which can be prevented by permanent atrial pacing. We evaluated the effect of using cardiac pacing to increase the heart rate during sleep in patients with sleep apnea syndrome. METHODS: We studied 15 patients (11 men and 4 women; mean [+/-SD] age, 69+/-9 years) with central or obstructive sleep apnea who had received permanent atrial-synchronous ventricular pacemakers for symptomatic sinus bradycardia. All patients underwent three polysomnographic evaluations on consecutive nights, the first night for base-line evaluation and then, in random order, one night in spontaneous rhythm and one in dual-chamber pacing mode with atrial overdrive (basic rate, 15 beats per minute faster than the mean nocturnal sinus rate). The total duration and number of episodes of central or obstructive sleep apnea or hypopnea were analyzed and compared. RESULTS: The mean 24-hour sinus rate during spontaneous rhythm was 57 +/- 5 beats per minute at base line, as compared with 72 +/- 3 beats per minute with atrial overdrive pacing (P<0.001). The total duration of sleep was 321 +/- 49 minutes in spontaneous rhythm, as compared with 331 +/- 46 minutes with atrial overdrive pacing (P=0.48). The hypopnea index (the total number of episodes of hypopnea divided by the number of hours of sleep) was reduced from 9 +/- 4 in spontaneous rhythm to 3 +/-3 with atrial overdrive pacing (P<0.001). For both apnea and hypopnea, the value for the index was 28 +/- 22 in spontaneous rhythm, as compared with 11 +/- 14 with atrial overdrive pacing (P<0.001). CONCLUSIONS: In patients with sleep apnea syndrome, atrial overdrive pacing significantly reduces the number of episodes of central or obstructive sleep apnea without reducing the total sleep time.

Spectral analysis identifies sites of high-frequency activity maintaining atrial fibrillation in humans.

BACKGROUND: The identification of sites of dominant activation frequency during atrial fibrillation (AF) in humans and the effect of ablation at these sites have not been reported. METHODS AND RESULTS: Thirty-two patients undergoing AF ablation (19 paroxysmal, 13 permanent) during ongoing arrhythmia were studied. Electroanatomic mapping was performed, acquiring 126+/-13 points per patient throughout both atria and coronary sinus. At each point, 5-second electrograms were obtained to determine the highest-amplitude frequency on spectral analysis and to construct 3D dominant frequency (DF) maps. The temporal stability of the recording interval was confirmed in a subset. Ablation was performed with the operator blinded to the DF maps. The effect of ablation at sites with or without high-frequency DF sites (maximal frequencies surrounded by a decreasing frequency gradient > or =20%) was evaluated by determining the change in AF cycle length (AFCL) and the termination and inducibility of AF. The spatial distribution of the DF sites was different in patients with paroxysmal and permanent AF; paroxysmal AF patients were more likely to harbor the DF site within the pulmonary vein, whereas in permanent AF, atrial DF sites were more prevalent. Ablation at a DF site resulted in significant prolongation of the AFCL (180+/-30 to 198+/-40 ms; P<0.0001; kappa=0.77), whereas in the absence of a DF site, there was no change in AFCL (169+/-22 to 170+/-22 ms; P=0.4). AF terminated during ablation in 17 of 19 patients with paroxysmal and 0 of 13 with permanent AF (P<0.0001). When 2 patients with nonsustained AF during mapping were excluded, 13 of 15 (87%) had AF termination at DF sites (54% at the initially ablated DF site): 11 pulmonary veins and 2 atrial. In addition, AF could no longer be induced in 69% with termination of AF at a DF site. There were no significant differences in the number or percentage of DF sites detected (5.4+/-1.6 versus 4.9+/-2.1; P=0.3) and ablated (1.9+/-1.0 versus 2.4+/-1.0; P=0.3) in those with and without AF termination. The duration of radiofrequency ablation to achieve termination was significantly shorter than that delivered in those with persisting AF (34.8+/-24.0 versus 73.5+/-22.9 minutes; P=0.0002). All patients with persisting AF had additional DF sites outside the ablated zones. CONCLUSIONS: Spectral analysis and frequency mapping identify localized sites of high-frequency activity during AF in humans with different distributions in paroxysmal and permanent AF. Ablation at these sites results in prolongation of the AFCL and termination of paroxysmal AF, indicating their role in the maintenance of AF.

Echocardiographic assessment during exercise of heart failure patients with cardiac resynchronization therapy.

This prospective echocardiographic study investigated the respective impacts of left ventricular (LV) pacing and simultaneous and sequential biventricular pacing (BVP) on ventricular dyssynchrony during exercise in 23 patients with compensated heart failure and ventricular conduction delays. During exercise, LV pacing and BVP significantly (p <0.05) improved mitral regurgitation and LV dyssynchrony compared with spontaneous activation. LV segmental electromechanical delays were significantly prolonged during LV pacing, leading to increased systolic time (p <0.05), decreased LV filling time (p <0.05), and decreased stroke volume (p <0.05) compared with BVP. After optimization of the interventricular delay with sequential BVP, additional benefit was obtained during exercise in terms of stroke volume and mitral regurgitation (p <0.05). The optimal interventricular delay was different at rest and during exercise in 57% of the patients. Changes from at rest to exercise in LV dyssynchrony were correlated with changes in stroke volume (r = -0.61, p <0.01) and changes in mitral regurgitation (r = 0.60, p <0.01).

Cardiovascular effects and risk of syncope related to donepezil in patients with Alzheimer's disease.

BACKGROUND: When otherwise unexplained, syncope in patients with Alzheimer's disease may be attributed to bradycardia caused by cholinesterase inhibitors. We studied prospectively the clinical events and cardiovascular changes occurring during treatment with donepezil in patients with Alzheimer's disease. METHODS: Consecutive patients presenting with mild-to-moderate Alzheimer's disease were included in the study. Their clinical characteristics, blood pressure, heart rate and electrocardiogram were recorded before (baseline) and during treatment with donepezil. The drug was administered at a dosage of 5 mg/day for 1 month and 10 mg/day for the following 7 months, as tolerated. We compared the baseline observations with those made at 1, 2 and 8 months of donepezil treatment. We also examined the effects of negatively chronotropic or dromotropic drugs concomitantly administered with donepezil. RESULTS: Thirty patients were included in the study, of whom 43% were taking negatively chronotropic or dromotropic drugs. The first month of therapy (donepezil 5 mg/day) was completed by 26 patients. During the 7-month high-dosage phase (10 mg/day), four patients dropped out of the study; thus, 22 patients completed the full 8 months of the study. The mean heart rate was 66 +/- 8 beats/min at baseline in the overall study population. This decreased significantly to 62 +/- 9, 61 +/- 7 and 62 +/- 8 beats/min at the 1, 2 and 8 month timepoints, respectively (all p = 0.002 vs baseline). Among patients not receiving negatively chronotropic or dromotropic drugs, heart rate decreased significantly over the course of the study (from 67 +/- 8 beats/min at baseline to 62 +/- 8 beats/min at 1 month, 62 +/- 7 beats/min at 2 months and 62 +/- 8 beats/min at 8 months [all p = 0.005 vs baseline]). There was no significant change in heart rate in patients who were receiving negatively chronotropic or dromotropic drugs. The PR interval increased over the course of the study in all patient groups, but these changes were only statistically significant in the group of patients who were not taking negatively chronotropic or dromotropic drugs (155 +/- 23ms at baseline vs 158 +/- 21, 160 +/- 22 and 163 +/- 24ms at the 1, 2 and 8 month timepoints; all p = 0.02 vs baseline). One patient developed syncope due to orthostatic hypotension; there were no cases of bradycardia-induced syncope. Gastrointestinal manifestations were reported in ten of the study patients. Abdominal pain and vomiting were the reasons for study termination in five of the eight patients who did not complete the trial. CONCLUSION: A donepezil-induced decrease in heart rate and increase in PR interval were observed only in patients with Alzheimer's disease who were not treated with negatively chronotropic or dromotropic drugs. These changes were not associated with bradycardia-induced syncope.

Assessment of cardiac resynchronisation therapy in patients with wide QRS and non-specific intraventricular conduction delay: rationale and design of the multicentre randomised NICD-CRT study.

INTRODUCTION: Cardiac resynchronisation therapy (CRT) was initially developed to treat patients with left bundle branch block (LBBB). However, many patients with heart failure have a widened QRS but neither left-BBB nor right-BBB; this is called non-specific intraventricular conduction delay (NICD). It is unclear whether CRT is effective in this subgroup of patients. METHODS AND ANALYSIS: The NICD-CRT study is a prospective, double-blind, randomised (1:1), parallel-arm, multicentre trial comparing the effects of CRT in patients with heart failure, a reduced left ventricular ejection fraction (LVEF <35%) and NICD, who have been implanted with a device (CRT-pacemaker or CRT-defibrillator) that has or has not been activated. Enrolment began on 15 July 2015 and should finish within 3 years; 40 patients have already been randomised and 11 centres have agreed to participate. The primary end point is the comparison of the proportion of patients improved, unchanged or worsened over the subsequent 12 months. 100 patients per group are required to demonstrate a difference between groups with a statistical power of 90%, a type I error of 0.05% (two-sided) and a loss to follow-up of 10%. This trial will add substantially to the modest amount of existing data on CRT in patients with NICD and should reduce uncertainty for guidelines and clinical practice when added to the pool of current information. ETHICS AND DISSEMINATION: Local ethics committee authorisations have been obtained since May 2015. We will publish findings from this study in a peer-reviewed scientific journal and present results at national and international conferences. TRIAL REGISTRATION NUMBER: NCT02454439; pre-results.

Changes in atrial fibrillation cycle length and inducibility during catheter ablation and their relation to outcome.

BACKGROUND: The modification of atrial fibrillation cycle length (AFCL) during catheter ablation in humans has not been evaluated. METHODS AND RESULTS: Seventy patients undergoing ablation of prolonged episodes of AF were randomized to pulmonary vein (PV) isolation or additional ablation of the mitral isthmus. Mean AFCL was determined at a distance from the ablated area (coronary sinus) at the following intervals: before ablation, after 2- and 4-PV isolations, and after linear ablation. Inducibility of sustained AF (> or =10 minutes) was determined before and after ablation. Spontaneous sustained AF (715+/-845 minutes) was present in 30 patients and induced in 26 (AFCL, 186+/-19 ms). PV isolation terminated AF in 75%, with the number of PVs requiring isolation before termination increasing with AF duration (P=0.018). PV isolation resulted in progressive or abrupt AFCL prolongation to various extents, depending on the PV: to 214+/-24 ms (P<0.0001) when AF terminated and to 194+/-19 ms (P=0.002) when AF persisted. The increase in AFCL (30+/-17 versus 14+/-11 ms; P=0.005) and the decrease in fragmentation (30.0+/-26.8% to 10.3+/-14.5%; P<0.0001) were significantly greater in patients with AF termination. Linear ablation prolonged AFCL, with a greater prolongation in patients with AF termination (44+/-13 versus 22+/-23 ms; P=0.08). Sustained AF was noninducible in 57% after PV isolation and in 77% after linear ablation. At 7+/-3 months, 74% with PV isolation and 83% with linear ablation were arrhythmia free without antiarrhythmics, which was significantly associated with noninducibility (P=0.03) with a recurrence rate of 38% and 13% in patients with and without inducibility, respectively. CONCLUSIONS: AF ablation results in a decline in AF frequency, with a magnitude correlating with termination of AF and prevention of inducibility that is predictive of subsequent clinical outcome.

Technique and results of linear ablation at the mitral isthmus.

BACKGROUND: This prospective clinical study evaluates the feasibility and efficacy of combined linear mitral isthmus ablation and pulmonary vein (PV) isolation in patients with paroxysmal atrial fibrillation (AF). METHODS AND RESULTS: One hundred consecutive patients (13 women; age 55+/-10 years) with drug-refractory, symptomatic paroxysmal AF underwent PV isolation and linear ablation of the cavotricuspid isthmus and the mitral isthmus (lateral mitral annulus to the left inferior PV). They were compared with 100 consecutive patients (14 women; age, 52+/-10 years) undergoing PV isolation and cavotricuspid ablation without mitral isthmus ablation. Bidirectional mitral isthmus block was confirmed by demonstrating (1) a parallel corridor of double potentials during coronary sinus (CS) pacing, (2) an activation detour by pacing either side of the line, and (3) differential pacing techniques. Isolation of all PVs and cavotricuspid isthmus ablation were performed successfully in all. Mitral isthmus block was achieved in 92 patients after 20+/-10 minutes of endocardial radiofrequency application and an additional 5+/-4 minutes of epicardial radiofrequency application from within the CS in 68, resulting in a conduction delay of 151+/-26 ms during CS pacing. Thirty-two patients with mitral isthmus ablation compared with 49 without had recurrent atrial arrhythmia (P=0.02) requiring further ablation. At 1 year after the last procedure, 87 patients with mitral isthmus ablation and 69 without (P=0.002) were arrhythmia free without antiarrhythmic drugs, mitral isthmus ablation being the only factor associated with long-term success (RR for AF recurrence, 0.2; CI, 0.1 to 0.4; P<0.001). CONCLUSIONS: Catheter ablation of the mitral isthmus results consistently in demonstrable conduction block and is associated with a high cure rate for paroxysmal AF.

Detrimental ventricular remodeling in patients with congenital complete heart block and chronic right ventricular apical pacing.

BACKGROUND: Although dual-chamber pacing improves cardiac function in patients with complete congenital atrioventricular block (CCAVB) by restoring physiological heart rate and atrioventricular synchronization, the long-term detrimental effect of asynchronous electromechanical activation induced by apical right ventricular pacing (RVP) has not been well clarified. METHODS AND RESULTS: Twenty-three CCAVB adults (24+/-3 years) with a DDD transvenous pacemaker underwent conventional echocardiography before implantation and, after at least 5 years of RVP, an exercise test and echocardiography coupled with tissue Doppler imaging and tissue tracking. They were compared with 30 matched healthy control subjects. After 10+/-3 years of RVP, CCAVB adults had significantly higher values versus controls in terms of intra-left ventricular (LV) asynchrony (respectively, 59+/-18 versus 19+/-9 ms, P<0.001), extent of LV myocardium displaying delayed longitudinal contraction (39+/-15% versus 10+/-7%, P<0.01), and septal-to-posterior wall-motion delay (84+/-26 versus 18+/-9 ms, P<0.01). The ratio of late-activated posterior to early-activated septal wall thickness was higher after long-term RVP than before (1.3+/-0.2 vs 1+/-0.1, P=0.05) and was higher than in controls (1+/-0.1, P<0.05). The percentage of patients with increased LV end-diastolic diameter was higher after long-term RVP than before implantation and was higher than in controls (57% versus 13%, P<0.05, and 57% versus 0%, P<0.01, respectively). CCAVB patients with long-term RVP had a lower cardiac output than controls (3.8+/-0.6 versus 4.9+/-0.8 L/min, P<0.05) and lower exercise performance (123+/-24 versus 185+/-39 W, P<0.001). CONCLUSIONS: Prolonged ventricular dyssynchrony induced by long-term endovenous RVP is associated with deleterious LV remodeling, LV dilatation, LV asymmetrical hypertrophy, and low exercise capacity. These new data highlight the importance of the ventricular activation sequence in all patients with chronic ventricular pacing.

Distinctive electrophysiological properties of pulmonary veins in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is frequently initiated from pulmonary veins (PVs), but little is known of the electrophysiological properties of PVs. METHODS AND RESULTS: Two groups were studied: 28 patients (49+/-13 years old) with paroxysmal AF and 20 control patients (49+/-14 years old) without AF. Effective and functional refractory period and conduction time from PV to left atrium (LA) were compared in the 2 groups by use of programmed stimulation with a single extrastimulus in the PVs and LA. In the AF group, the venous effective refractory periods (ERPs) were shorter than that of the LA: 185+/-71 versus 253+/-21 ms, P<0.001, whereas in the control group, they were longer (282+/-45 versus 253+/-41 ms, P=0.009). The venous ERPs and functional refractory periods in patients with AF were also shorter than that observed in control subjects (185+/-71 versus 282+/-45 ms and 210+/-77 versus 315+/-43 ms, respectively, P<0.001), whereas LA ERPs were not significantly different. Decremental conduction in PVs was more frequent (93% versus 56%, P=0.01) and had a greater increment (102+/-65 versus 42+/-40 ms, P<0.001) in patients with AF. Finally, AF was more frequently induced when pacing was performed in PVs (22 of 90) versus LA (1 of 81) in patients with AF (P<0.001). CONCLUSIONS: The PVs of patients with AF exhibited distinctive electrophysiological properties, which were strikingly different from those of patients devoid of AF, potentially explaining their arrhythmogenicity.

Reverse remodeling of sinus node function after catheter ablation of atrial fibrillation in patients with prolonged sinus pauses.

BACKGROUND: Symptomatic prolonged sinus pauses on termination of atrial fibrillation (AF) are an indication for pacemaker implantation. We evaluated sinus node function and clinical outcome in patients with prolonged sinus pauses on termination of arrhythmia who underwent ablation of paroxysmal AF. METHODS AND RESULTS: Twenty patients with paroxysmal AF and prolonged sinus pauses (> or =3 seconds) on termination of AF underwent ablation between May 1995 and November 2002. Patients with sinus pauses independent of episodes of AF were excluded from the analysis. The procedure included pulmonary vein and linear atrial ablation. After ablation, sinus node function was assessed during the first week and at 1, 3, and 6 months, by 24-hour ambulatory monitoring to determine the mean heart rate and heart rate range, and by exercise testing to determine the maximal heart rate. Corrected sinus node recovery time was determined at the completion of ablation and at 24.0+/-11.3 months at 600 and 400 ms. After AF ablation, there was a significant improvement of sinus node function, with an increase in the mean heart rate (P=0.001), maximal heart rate (P<0.0001), and heart rate range (P<0.0001). The corrected sinus node recovery time decreased in all patients evaluated at 600 ms (P=0.016) and 400 ms (P=0.019). At 26.0+/-17.6 months, 18 patients (85%) had no recurrence of AF (in the absence of medication), with no symptoms attributable to bradycardia or sinus pauses on ambulatory monitoring. Two patients had infrequent episodes of AF, 1 requiring pacemaker implantation. CONCLUSIONS: Prolonged sinus pauses after paroxysms of AF may result from depression of sinus node function that can be eliminated by curative ablation of AF. This is accompanied by improvement in parameters of sinus node function, suggesting reverse remodeling of the sinus node.

Mapping and ablation of ventricular fibrillation associated with long-QT and Brugada syndromes.

BACKGROUND: The long-QT and Brugada syndromes are important substrates of malignant ventricular arrhythmia. The feasibility of mapping and ablation of ventricular arrhythmias in these conditions has not been reported. METHODS AND RESULTS: Seven patients (4 men; age, 38+/-7 years; 4 with long-QT and 3 with Brugada syndrome) with episodes of ventricular fibrillation or polymorphic ventricular tachycardia and frequent isolated or repetitive premature beats were studied. These premature beats were observed to trigger ventricular arrhythmias and were localized by mapping the earliest endocardial activity. In 4 patients, premature beats originated from the peripheral right (1 Brugada) or left (3 long-QT) Purkinje conducting system and were associated with variable Purkinje-to-muscle conduction times (30 to 110 ms). In the remaining 3 patients, premature beats originated from the right ventricular outflow tract, being 25 to 40 ms ahead of the QRS. The accuracy of mapping was confirmed by acute elimination of premature beats after 12+/-6 minutes of radiofrequency applications. During a follow-up of 17+/-17 months using ambulatory monitoring and defibrillator memory interrogation, no patients had recurrence of symptomatic ventricular arrhythmia but 1 had persistent premature beats. CONCLUSIONS: Triggers from the Purkinje arborization or the right ventricular outflow tract have a crucial role in initiating ventricular fibrillation associated with the long-QT and Brugada syndromes. These can be eliminated by focal radiofrequency ablation.

Mapping and ablation of idiopathic ventricular fibrillation.

BACKGROUND: Ventricular fibrillation is the main mechanism of sudden cardiac death. The feasibility of eliminating recurrent episodes by catheter ablation has not been reported. METHODS AND RESULTS: Twenty-seven patients without known heart disease (13 men, 14 women, 41+/-14 years of age) were studied after being resuscitated from recurrent (10+/-12) episodes of primary idiopathic ventricular fibrillation; 23 had received a defibrillator. The first initiating beat of ventricular fibrillation had an identical electrocardiographic morphology and coupling interval (297+/-41 ms) to preceding isolated premature beats typically noted in the aftermath of resuscitation. These triggers were localized by mapping the earliest electrical activity and ablated by local radiofrequency delivery. Outcome was assessed by Holter and defibrillator memory interrogation. Premature beats were elicited from the Purkinje conducting system in 23 patients: from the left ventricular septum in 10, from the anterior right ventricle in 9, and from both in 4. The interval from the Purkinje potential to the following myocardial activation varied from 10 to 150 ms during premature beat but was 11+/-5 ms during sinus rhythm, indicating location at peripheral Purkinje arborization. The premature beats originated from the right ventricular outflow tract muscle in 4 patients. The accuracy of mapping was confirmed by acute elimination of premature beats during local radiofrequency delivery. During a follow-up of 24+/-28 months, 24 patients (89%) had no recurrence of ventricular fibrillation without drug. CONCLUSIONS: Primary idiopathic ventricular fibrillation is a syndrome characterized by dominant triggers from the distal Purkinje system. These sources can be eliminated by focal energy delivery.