Fernando Mera

Downregulation of endocardial nitric oxide synthase expression and nitric oxide production in atrial fibrillation: Potential mechanisms for atrial thrombosis and stroke

Background—In the arterial endothelium, laminar flow and cyclical stretch induce expression of NO synthase (NOS). We hypothesized that atrial fibrillation (AF) causes a downregulation of atrial endocardial NOS expression and NO·production. Because NO·has antithrombotic properties, this may contribute to thromboembolism in AF. Methods and Results—In pigs, AF was produced with rapid atrial pacing at 600 bpm for 1 week, whereas controls had atrial pacing at 100 bpm. All animals had catheter ablation of the AV junction and ventricular pacing at 100 bpm. NO·production from freshly isolated tissue was measured by a NO·-specific microelectrode. Left atrial basal and stimulated NO·production was decreased in AF by 73% and 71% (P <0.01). Endocardial NOS expression, determined by Western analysis, was also significantly decreased by 46%. Expression of the prothombotic protein plasminogen activator inhibitor 1 (PAI-1) is known to be regulated by NO·and was increased in the left atrium by 1.8-fold in AF (P <0.05). NO·concentration was decreased in the left atrial appendage, although NOS expression was not affected. Neither NOS concentration, NO·levels, nor PAI-1 expression were altered in the aortas or right atria of animals with AF. Conclusions—AF is associated with a marked decrease in endocardial NOS expression and NO·bioavailability and an increase in PAI-1 expression in the left atrium. These data suggest that organized atrial contraction is needed to maintain normal endocardial expression of NOS. It is likely that loss of this antithrombotic enzyme contributes to the thromboembolic phenomena commonly observed in AF.

Renal insufficiency and the risk of infection from pacemaker or defibrillator surgery.

Background: Pacemakers and implanted cardioverter defibrillator (ICD) infection rates are rising. Renal insufficiency impairs immune function and is known to increase the risk of infection following implantation of orthopedic hardware. The purpose of the current study is to characterize the risk factors for pacemaker and ICD infection and to evaluate the role of renal insufficiency in this complication.

A Comparison of Ventricular Function During High Right Ventricular Septal and Apical Pacing after His-Bundle Ablation for Refractory Atrial Fibrillation

This study compares LV performance during high right ventricular septal (RVS) and apical (RVA) pacing in patients with LV dysfunction who underwent His‐bundle ablation for chronic AF. We inserted a passive fixation pacing electrode into the RVA and an active fixation electrode in the RVS. A dual chamber, rate responsive pulse generator stimulated the RVA through the ventricular port and the RVS via the atrial port. Patients were randomized to initial RVA (VVIR) or RVS (AAIR) pacing for 2 months. The pacing site was reversed during the next 2 months. At the 2 and 4 month follow‐up visit, each patient underwent a transthoracic echocardiographical study and a rest/exercise first pass radionuclide ventriculogram. We studied nine men and three women (mean age of 68 ± 7 years) with congestive heart failure functional Class (NYHA Classification): I (3 patients), II (7 patients), and III (2 patients). The QRS duration was shorter during RVS stimulation (158 ± 10vs 170 ± 11 ms, P < 0.001). Chronic capture threshold and lead impedance did not significantly differ. LV fractional shortening improved during RVS pacing (0.31 ± 0.05 vs 0.26 ± 0.07, P < 0.01). RVS activation increased the resting first pass LV ejection fraction (0.51 ± 0.14 vs 0.43 ± 0.10, P < 0.01). No significant difference was observed during RVS and RVA pacing in the exercise time (5.6 ± 3.2 vs 5.4 ± 3.1, P = 0.6) or the exercise first pass LV ejection fraction (0.58 ± 0.15 vs 0.55 ± 0.16, P = 0.2). The relative changes in QRS duration and LV ejection fraction at both pacing sites showed a significant correlation (P < 0.01). We conclude that RVS pacing produces shorter QRS duration and better chronic LV function than RVA pacing in patients with mild to moderate LV dysfunction and chronic AF after His‐bundle ablation.

The Impact of Cardiac Resynchronization Therapy on Ventricular Tachycardia/Fibrillation: An Analysis from the Combined Contak-CD and InSync-ICD Studies

Objectives: To determine the potential influence of cardiac resynchronization therapy (CRT) on the frequency and types of ventricular arrhythmia (VA) in patients with an indication for the implantable cardioverter‐defibrillator (ICD), we performed a retrospective electrogram (EGM) analysis of stored VA events from the two largest CRT‐ICD trials.

Practical Approach to Implanting Left Ventricular Pacing Leads for Cardiac Resynchronization

Our approach to implanting cardiac resynchronization therapy (CRT) devices combines an understanding of the anatomy of the failing heart and the coronary veins, standard pacing lead insertion skills, and techniques common to diagnostic cardiac catheterization and interventional cardiology. The method we have devised over the past 5 years has provided CRT safely and effectively to a large volume of compromised patients with congestive heart failure (CHF) and conduction system disease.

Transvenous Cardioverter Defibrillator Lead Malfunction Due to Terminal Connector Damage in Pectoral Implants

Lead failure places patients with implantable cardioverter defibrillators (ICD) at risk for sudden cardiac death or results in delivery of inappropriate shocks. This study describes a mechanism of lead malfunction occurring at the junction of the terminal ring with the conductor coil of the rate sensing terminal connector in one specific model of a transvenous ICD lead. We detected the problem in a population of 179 patients with a mean age of 61 ± 10 years and a mean lead implant duration of 16 ± 11 months. All patients underwent pectoral ICD implantation using a submuscular approach. The implanting physician chose to place the ICD on the left side in 155 patients (87%) and on the right side 24 patients (13%). Cephalic vein cutdown provided central venous access in 147 patients (82%), and sub‐clavian vein puncture provided access in 32 patients (18%). Follow‐up examination detected lead failure in six patients (3.5% over 31 months) due to insulation damage with or without conductor coil fracture at the junction of the terminal ring and conductor coil of the IS‐1 rate sense terminal. We detected lead disruption 17 ± 9 months (range 5–31 months) after implantation. Multiple nonsustained arrhythmia episodes exhibiting nonphysiologic intervals associated with noisy rate sensing electrograms during pocket manipulation led to discovery in three patients. The other three patients presented with inappropriate device discharges confirmed by stored high‐energy lead electrograms showing normal rhythm. Pacing lead impedance abnormally dropped in two patients. Impedance remained stable in the other four patients. In conclusion, the generator pocket represents an important site of ICD transvenous lead vulnerability. Lead failure may result from conductor coil and/or insulation disruption at the interface with the rate sensing terminal connector.

Right Ventricular Outflow Tract Tachycardia as a Result of Blunt Chest Trauma

Two patients presented with monomorphic ventricular tachycardia after blunt chest trauma. In both cases, the arrhythmia had a left bundle branch block, inferior axis morphology comparable to that seen with idiopathic ventricular tachycardia originating from the right ventricular outflow tract (RVOT). In one patient, the arrhythmia persisted and required catheter ablation. A history of cardiac trauma should be considered in patients presenting with RVOT tachycardia.