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.

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.

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.

Clinical and mutational spectrum in a cohort of 105 unrelated patients with dilated cardiomyopathy.

Dilated Cardiomyopathy (DCM) is one of the leading causes of heart failure with high morbidity and mortality. More than 30 genes have been reported to cause DCM. To provide new insights into the pathophysiology of dilated cardiomyopathy, a mutational screening on 4 DCM-causing genes (MYH7, TNNT2, TNNI3 and LMNA) was performed in a cohort of 105 unrelated DCM (64 familial cases and 41 sporadic cases) using a High Resolution Melting (HRM)/sequencing strategy. Screening of a highly conserved arginine/serine (RS)-rich region in exon 9 of RBM20 was also performed. Nineteen different mutations were identified in 20 index patients (19%), including 10 novels. These included 8 LMNA variants in 9 (8.6%) probands, 5 TNNT2 variants in 5 probands (4.8%), 4 MYH7 variants in 3 probands (3.8%), 1 TNNI3 variant in 1 proband (0.9%), and 1 RBM20 variant in 1 proband (0.9%). One proband was double-heterozygous. LMNA mutations represent the most prevalent genetic DCM cause. Most patients carrying LMNA mutations exhibit conduction system defects and/or cardiac arrhythmias. Our study also showed than prevalence of mutations affecting TNNI3 or the (RS)-rich region of RBM20 is lower than 1%. The discovery of novel DCM mutations is crucial for clinical management of patients and their families because pre-symptomatic diagnosis is possible and precocious intervention could prevent or ameliorate the prognosis.