Biological pacemaker created by percutaneous gene delivery via venous catheters in a porcine model of complete heart block.

BACKGROUND: Pacemaker-dependent patients with device infection require temporary pacing while the infection is treated. External transthoracic pacing is painful and variably effective, while temporary pacing leads are susceptible to superinfection. OBJECTIVE: To create a biological pacemaker delivered via venous catheters in a porcine model of complete heart block, providing a temporary alternative/adjunct to external pacing devices without additional indwelling hardware. METHODS: Complete atrioventricular (AV) nodal block was induced in pigs by radiofrequency ablation after the implantation of a single-chamber electronic pacemaker to maintain a ventricular backup rate of 50 beats/min. An adenoviral vector cocktail (K(AAA) + H2), expressing dominant-negative inward rectifier potassium channel (Kir2.1AAA) and hyperpolarization-activated cation channel (HCN2) genes, was injected into the AV junctional region via a NOGA Myostar catheter advanced through the femoral vein. RESULTS: Animals injected with K(AAA) + H2 maintained a physiologically relevant ventricular rate of 93.5 ± 7 beats/min (n = 4) compared with control animals (average rate, 59.4 ± 4 beats/min; n = 6 at day 7 postinjection; P <.05). Backup electronic pacemaker utilization decreased by almost 4-fold in the K(AAA) + H2 group compared with the control (P <.05), an effect maintained for the entire 14-day window. In contrast to the efficacy of gene delivery into the AV junctional region, open-chest, direct injection of K(AAA) + H2 (or its individual vectors) into the ventricular myocardium failed to elicit significant pacemaker activity. CONCLUSIONS: The right-sided delivery of K(AAA) + H2 to the AV junctional region provided physiologically relevant biological pacing over a 14-day period. Our approach may provide temporary, bridge-to-device pacing for the effective clearance of infection prior to the reimplantation of a definitive electronic pacemaker.

Electrophysiological characteristics of focal atrial tachycardia surrounding the aortic coronary cusps.

BACKGROUND: Catheter ablation of atrial tachycardia (AT) arising near the coronary cusps has been reported in limited numbers of patients. We investigated the electrophysiological characteristics of these ATs in 22 consecutive patients. METHODS AND RESULTS: This study included 22 patients (mean age ± SD, 53 ± 11 years; 86% female) with ATs arising near the aortic coronary cusps who underwent successful ablation. Activation mapping was performed during tachycardia to identify the earliest activation site. All patients achieved successful ablation through either a retrograde aortic (n=19) or a transseptal (n=3) approach. The successful ablation sites were located in the noncoronary cusp (NCC) (n=16), including 3 near the junction between the NCC and right coronary cusp. The remaining 6 cases were ablated from the left coronary cusp (LCC) (n=3) or the left atrium posterior to the LCC (n=3). For most tachycardias, there were distinctive P-wave morphological features recorded for each cusp location. Furthermore, analysis of the electrogram morphological features recorded during tachycardia at successful ablation sites revealed an atrial/ventricular (A/V) ratio >1 in 14 of 16 NCC ATs; the remaining 2, from the NCC near the junction with the right coronary cusp, showed an A/V ratio ≤ 1. At ablation sites in the LCC, the A/V ratio was <1 (4 of 6 patients) or 1 (remaining 2 patients). During a follow-up duration of 30 ± 13 months, all patients were free of arrhythmias without antiarrhythmic drugs. CONCLUSIONS: ATs surrounding the aortic coronary cusps can be safely and effectively ablated, with good long-term outcomes. In addition to the P-wave morphological features, the A/V ratio of the local electrogram recording during tachycardia facilitated the localization of successful sites.

Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial.

CONTEXT: Clinical studies of omega-3 polyunsaturated fatty acids (PUFAs) have shown a reduction in sudden cardiac death, suggesting that omega-3 PUFAs may have antiarrhythmic effects. OBJECTIVE: To determine whether omega-3 PUFAs have beneficial antiarrhythmic effects in patients with a history of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial performed at 6 US medical centers with enrollment from February 1999 until January 2003. PATIENTS: Two hundred patients with an implantable cardioverter defibrillator (ICD) and a recent episode of sustained VT or VF. INTERVENTION: Patients were randomly assigned to receive fish oil, 1.8 g/d, 72% omega-3 PUFAs, or placebo and were followed up for a median of 718 days (range, 20-828 days). MAIN OUTCOME MEASURES: Time to first episode of ICD treatment for VT/VF, changes in red blood cell concentrations of omega-3 PUFAs, frequency of recurrent VT/VF events, and predetermined subgroup analyses. RESULTS: Patients randomized to receive fish oil had an increase in the mean percentage of omega-3 PUFAs in red blood cell membranes from 4.7% to 8.3% (P<.001), with no change observed in patients receiving placebo. At 6, 12, and 24 months, 46% (SE, 5%), 51% (5%), and 65% (5%) of patients randomized to receive fish oil had ICD therapy for VT/VF compared with 36% (5%), 41% (5%), and 59% (5%) for patients randomized to receive placebo (P = .19). In the subset of 133 patients whose qualifying arrhythmia was VT, 61% (SE, 6%), 66% (6%), and 79% (6%) of patients in the fish oil group had VT/VF at 6, 12, and 24 months compared with 37% (6%), 43% (6%), and 65% (6%) of patients in the control group (P = .007). Recurrent VT/VF events were more common in patients randomized to receive fish oil (P<.001). CONCLUSION: Among patients with a recent episode of sustained ventricular arrhythmia and an ICD, fish oil supplementation does not reduce the risk of VT/VF and may be proarrhythmic in some patients.

Nonautomatic focal atrial tachycardia: characterization and ablation of a poorly understood arrhythmia in 38 patients.

Nonautomatic focal atrial tachycardia (NAFAT) is a rare and poorly understood arrhythmia either due to microreentry or triggered mechanism. NAFAT was defined as a focal atrial tachycardia which was inducible with pacing maneuvers in the electrophysiology lab. We reviewed the charts and EP study reports of all 38 patients with NAFAT, who underwent an EP study at our center between April 1994 and September 2000. Patients' were predominantly female (n = 31, 82%), aged 11-78 years (median 46). The mean age at presentation was 31 years (range 7-71 years). None of the patients had structural heart disease or had undergone prior heart surgery. Electroanatomic mapping (EAM) was performed in 22 patients and showed no scars in the atrium. A total of 45 foci were identified (range 1-3 foci/patient). Anatomically NAFAT foci were predominantly right atrial (n = 35) rather than left (n = 10). The NAFAT cycle length ranged from 270 to 490 (mean +/- SD; 380 +/- 69 ms) and was significantly lower in patients younger than 24 years of age. Ablation, attempted for 42 foci was successful in 33 (79%). The success rate in the EAM group was 20/25 foci (80%) compared to 13/18 (72%) in the non-EAM group. In conclusion, NAFAT is a rare arrhythmia which predominantly affects women with no other associated cardiac disease. It mainly occurs in the right atrium, affects all ages and is amenable to catheter ablation.