Background-The pulmonary veins (PVs) have been demonstrated to often play an important role in generating atrial fibrillation (AF). The purpose of this study was to determine the safety and efficacy of segmental PV isolation in patients with paroxysmal or persistent AF. Methods and Results-In 70 consecutive patients (mean age, 53Ϯ11 years) with paroxysmal (58) or persistent (12) AF, segmental PV isolation guided by ostial PV potentials was performed. The left superior, left inferior, and right superior PVs were targeted for isolation in all patients, and the right inferior PV was isolated in 20 patients. Among the 230 targeted PVs, 217 (94%) were completely isolated, with a mean of 6.5Ϯ4.2 minutes of radiofrequency energy applied at a maximum power setting of 35 W. A second PV isolation procedure was performed in 6 patients (9%). At 5 months of follow-up, 70% of patients with paroxysmal and 22% of patients with persistent AF were free from recurrent AF (PϽ0.001), and 83% of patients with paroxysmal AF were either free of symptomatic AF or had significant improvement. Among various clinical characteristics, only paroxysmal AF was an independent predictor of freedom from recurrence of AF (PϽ0.05). One patient developed unilateral quadrantopsia after the procedure. There were no other complications. Conclusions-With a segmental isolation approach that targets at least 3 PVs, a clinically satisfactory result can be achieved in Ͼ80% of patients with paroxysmal AF. The clinical efficacy of pulmonary vein isolation is much lower when AF is persistent than when it is paroxysmal.

Early recurrences of AF occur in approximately 35% of patients within two weeks after isolation of three to four PVs, and are associated with a lower long-term success rate than in patients without ERAF. However, approximately 30% of patients with ERAF have no further symptomatic AF during long-term follow-up. Therefore, temporary antiarrhythmic drug therapy may be more appropriate than early repeat ablation in patients with ERAF.

Intermittent bursts of tachycardia are observed within multiple PVs during persistent AF in a majority of patients. After PV isolation, PV tachycardias almost always resolve, and AF is less likely to be inducible or persistent. These observations suggest a dynamic interplay between the atria and PVs, with intermittent bursts of PV tachycardia being dependent on left atrial input and with the probability of persistent AF diminishing when PV tachycardias are eliminated by PV isolation.

To provide a frame of reference for studies of renal divalent cation and phosphate metabolism, we assessed the cellular localization of kidney calcium receptor (RaKCaR), parathyroid hormone-related protein (PTHrP), and parathyroid hormone/ parathyroid hormone-related protein (PTH/PTHrP) receptor mRNA. The studies used using reverse transcription-polymerase chain reaction (RT-PCR) applied to cDNA prepared from dissected rat nephron segments and from primary cultures of mouse juxtaglomerular granular cells. With species-specific primers, PCR products of expected size were obtained for RaKCaR (967 bp), PTHrP (420 bp), and PTH/PTHrP receptor (817 bp), with product identity being confirmed by restriction digestion. RaKCaR mRNA was found in medullary and cortical thick ascending limbs (MTAL and CTAL, respectively), the macula densa-containing segment, distal convoluted tubules (DCT), and, to a lesser extent, in cortical collecting ducts (CCD). It was not found in glomeruli, proximal convoluted and straight tubules (PCT and PST, respectively), outer and inner medullary collecting ducts (OMCD and IMCD, respectively), or in juxtaglomerular granular cell isolates. PTHrP mRNA was predominantly expressed in glomeruli and at lower levels in PCT and the macula densacontaining segment but was not detectable in CTAL, MTAL, DCT, and CD segments. Presence of PTH/PTHrP receptor mRNA was demonstrated in glomeruli, PCT, PST, CTAL, MTAL, and DCT but not in CD segments. These results suggest that the function of TAL and DCT cells, in addition to being affected by PTH, may be directly altered by extracellular divalent cations through RaKCaR and that PTHrP may act in the glomerulus and proximal tubule as an autocrine or paracrine regulator of hemodynamics and phosphate transport.

Segmental ostial ablation guided by PV tachycardia during AF is feasible and as efficacious as during sinus rhythm. The responses to cardioversion, ablation, and rapid pacing observed in this study imply that IRAF is triggered by the PVs and that PV tachycardias may play an important role in the perpetuation of AF.

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