Charles A. Henrikson

Antiarrhythmic Engineering of Skeletal Myoblasts for Cardiac Transplantation

Skeletal myoblasts are an attractive cell type for transplantation because they are autologous and resistant to ischemia. However, clinical trials of myoblast transplantation in heart failure have been plagued by ventricular tachyarrhythmias and sudden cardiac death. The pathogenesis of these arrhythmias is poorly understood, but may be related to the fact that skeletal muscle cells, unlike heart cells, are electrically isolated by the absence of gap junctions. Using a novel in vitro model of myoblast transplantation in cardiomyocyte monolayers, we investigated the mechanisms of transplant-associated arrhythmias. Cocultures of human skeletal myoblasts and rat cardiomyocytes resulted in reentrant arrhythmias (spiral waves) that reproduce the features of ventricular tachycardia seen in patients receiving myoblast transplants. These arrhythmias could be terminated by nitrendipine, an l-type calcium channel blocker, but not by the Na channel blocker lidocaine. Genetic modification of myoblasts to express the gap junction protein connexin43 decreased arrhythmogenicity in cocultures, suggesting a specific means for increasing the safety (and perhaps the efficacy) of myoblast transplantation in patients.

Initial experience in the use of integrated electroanatomic mapping with three-dimensional MR/CT images to guide catheter ablation of atrial fibrillation.

Introduction: No prior studies have reported the use of integrated electroanatomic mapping with preacquired magnetic resonance/computed tomographic (MR/CT) images to guide catheter ablation of atrial fibrillation (AF) in a series of patients.

Optimal Left Ventricular Endocardial Pacing Sites for Cardiac Resynchronization Therapy in Patients With Ischemic Cardiomyopathy

OBJECTIVES We sought to investigate the impact of left ventricular (LV) pacing site on mechanical response to cardiac resynchronization therapy (CRT) in patients with ischemic cardiomyopathy (ICM). BACKGROUND CRT reduces morbidity and mortality in patients with dyssynchronous LV failure; however, variability in response, particularly in ICM patients, poses ongoing challenges. Endocardial biventricular (BiV) stimulation may provide more flexibility in LV site selection and yield more natural transmural activation patterns. Whether this applies to ICM and whether optimal LV endocardial pacing locations vary among ICM patients remain unknown. METHODS Peak rate of LV pressure increase (dP/dt(max)) was measured at baseline, during VDD pacing at the right ventricular apex, and during BiV pacing from the right ventricular apex and 51 +/- 14 different LV endocardial sites in patients with ICM (n = 11). Seven patients already had an epicardial LV lead (CRT) in place, allowing comparison of epicardial BiV stimulation with that using an endocardial site directly transmural to the CRT-coronary sinus lead tip. Electroanatomic 3-dimensional maps with color-coded dP/dt(max) response defined optimal pacing regions delivering >or=85% of maximal increase in dP/dt(max). RESULTS Endocardial BiV pacing improved dP/dt(max) over right ventricular apex pacing in all patients (mean increase 241 +/- 38 mm Hg/s; p < 0.0001). In patients with pre-existing CRT leads, LV endocardial versus epicardial pacing at transmural sites yielded equivalent dP/dt(max) values. However, dP/dt(max) at the best endocardial site exceeded that achieved with the pre-implanted CRT device (mean increase 111 +/- 25 mm Hg/s; p = 0.004). An average of approximately 2 optimal endocardial sites were identified for each patient, located at the extreme basal lateral wall (8 of 11 patients) and other regions (9 of 11). Standard mid-LV free wall pacing yielded suboptimal LV function in 73% of patients. Optimal pacing sites were typically located in LV territories remote (9.3 +/- 3.6 cm) from the infarct zone. CONCLUSIONS CRT delivered at best LV endocardial sites is more effective than via pre-implanted coronary sinus lead pacing. The location of optimal LV endocardial pacing varies among patients with ICM, and individual tailoring may improve CRT efficacy in such patients.

Incidence and time course of early recovery of pulmonary vein conduction after catheter ablation of atrial fibrillation

Background: Although it is well recognized that recovery of pulmonary vein (PV) conduction is common among patients who fail atrial fibrillation (AF) ablation, little is known about the precise time course of recurrence.

Long‐Term Safety and Efficacy of Circumferential Ablation with Pulmonary Vein Isolation

Background: Each of the two main approaches to catheter ablation of atrial fibrillation (AF, segmental and circumferential) is associated with moderate long‐term efficacy.

Dual Antiplatelet Therapy and Heparin “Bridging” Significantly Increase the Risk of Bleeding Complications After Pacemaker or Implantable Cardioverter-Defibrillator Device Implantation

OBJECTIVES This study was designed to assess the risk of significant bleeding complications in patients receiving antiplatelet or anticoagulation medications at the time of implantable cardioverter-defibrillator (ICD) device implantation. BACKGROUND Periprocedural management of antiplatelet or anticoagulation therapy at the time of device implantation remains controversial. METHODS We performed a retrospective chart review of bleeding complications in all patients undergoing ICD or pacemaker implantation from August 2004 to August 2007. Aspirin or clopidogrel use was defined as taken within 5 days of the procedure. A significant bleeding complication was defined as need for pocket exploration or blood transfusion; hematoma requiring pressure dressing or change in anticoagulation therapy; or prolonged hospitalization. RESULTS Of the 1,388 device implantations, 71 had bleeding complications (5.1%). Compared with controls not taking antiplatelet agents (n = 255), the combination of aspirin and clopidogrel (n = 139) significantly increased bleeding risk (7.2% vs. 1.6%; p = 0.004). In patients taking aspirin alone (n = 536), bleeding risk was marginally higher than it was for patients taking no antiplatelet agents (3.9% vs. 1.6%, p = 0.078). The use of periprocedural heparin (n = 154) markedly increased risk of bleeding when compared with holding warfarin until the international normalized ratio (INR) was normal (n = 258; 14.3% vs. 4.3%; p < 0.001) and compared with patients receiving no anticoagulation therapy (14.3% vs.1.6%; p < 0.0001). There was no statistical difference in bleeding risk between patients continued on warfarin with an INR > or =1.5 (n = 46) and patients who had warfarin withheld until the INR was normal (n = 258; 6.5% vs. 4.3%; p = 0.50). CONCLUSIONS Dual antiplatelet therapy and periprocedural heparin significantly increase the risk of bleeding complications at the time of pacemaker or ICD implantation.

A Prospective Study Evaluating the Role of Obesity and Obstructive Sleep Apnea for Outcomes After Catheter Ablation of Atrial Fibrillation

Effect of Obesity and OSA on Outcomes Post AF Ablation. Background: Obesity and obstructive sleep apnea (OSA) have a strong association with atrial fibrillation (AF). The purpose of this study was to prospectively determine the effects of obesity, assessed by the body mass index (BMI) and OSA on the efficacy of catheter ablation of AF.

Continuation of warfarin during pacemaker or implantable cardioverter-defibrillator implantation: A randomized clinical trial

BACKGROUND Management of oral anticoagulation in patients undergoing pacemaker (PPM) or implantable cardioverter-defibrillator (ICD) implantation remains controversial. Prior studies demonstrate that continuation of warfarin may be safer when compared with strategies requiring interruption and/or heparin bridging. Limited data from randomized trials exist. OBJECTIVE We conducted a randomized trial to determine whether warfarin continuation is superior to warfarin interruption during PPM or ICD implantation. METHODS Patients on oral anticoagulation referred for PPM or ICD implantation were randomized to warfarin continuation versus interruption. Patients randomized to warfarin interruption were further stratified into two groups based on their risk for thromboembolic events in the absence of warfarin. Moderate-risk patients were randomized to warfarin continuation versus warfarin interruption. High-risk patients were randomized to warfarin continuation versus warfarin interruption with heparin bridging. The primary combined outcome included thromboembolic events, anticoagulant-related complications, or any significant bleeding necessitating additional intervention or discontinuation of anticoagulation. RESULTS We studied 100 patients (average age 70.8 years, 21% female, mean body mass index 28.4) who underwent 64 ICD and 36 PPM implantations. Fifty patients were assigned to continue warfarin. The randomized groups were well matched. Among patients randomized to warfarin interruption, there were two pocket hematomas, one pericardial effusion, one transient ischemic attack, and one patient who developed heparin-induced thrombocytopenia. No events were noted among patients continuing warfarin (P = .056). CONCLUSIONS While the results were not statistically significant, there was a trend toward reduced complications in patients randomized to warfarin continuation. This strategy should be considered in patients undergoing PPM or ICD implantation.

Lead Extraction Is Preferred for Lead Revisions and System Upgrades: When Less Is More

Cardiovascular implantable electronic device (CIED) use has increased exponentially during the past decade,1,–,3 with >4.5 million active devices and >1 million new leads implanted annually.4,5 With expanded CIED use and indications for device therapy, observed complications have increased in parallel.6,–,14 The occurrence of more frequent device system revisions for complications,6,–,8 system upgrades,15,–,17 and/or lead malfunction9,–,13 and longer patient life expectancies have mandated a paradigm shift toward premeditated lead management strategies from implant to removal or replacement. Consequently, clinicians increasingly are faced with the challenging choice of extraction or abandonment of sterile, superfluous leads. The decision is difficult and highly controversial,4,18,–,26 with limited rigorous evidence and passionate arguments on either side. Response by Henrikson on p 424 We contend that although decisions regarding extraction in these situations must be made on a case-by-case basis after considering multiple patient- and physician-related variables, lead extraction should be the preferred management strategy for lead revisions and system upgrades. Randomized, controlled trials of extraction versus abandonment are lacking, but the available evidence from observational, cohort, and registry studies supports the contention that the potential future benefit of lead extraction outweighs the risks of lead abandonment and that lead abandonment should be viewed as a “palliative procedure” that “just postpones the inevitable future lead extraction.”27 In patients with venous occlusion undergoing the addition of a lead with plans to preserve the existing leads (eg, VVI to DDD implantable cardioverter defibrillator, or DDD implantable cardioverter defibrillator upgrade to BiV implantable cardioverter defibrillator), venoplasty, when possible, is the preferred approach. In many such patients, the venous obstruction is short in length and …

Computed Tomography to Assess Possible Cardiac Lead Perforation

Background: Chest radiography and echocardiography are standard techniques to evaluate possible extracardiac migration of pacemaker and defibrillator leads, but computed tomography (CT) scanning may be a helpful adjunct.