Generation of Monophasic Action Potentials and Intermediate Forms.

The monophasic action potential (MAP) is a near replica of the transmembrane potential recorded when an electrode is pushed firmly against cardiac tissue. Despite its many practical uses, the mechanism of MAP signal generation and the reason it is so different from unipolar recordings are not completely known and are a matter of controversy. In this work, we describe a method to simulate realistic MAP and intermediate forms, which are multiphasic electrograms different from an ideal MAP. The key ideas of our method are the formation of compressed zones and junctional spaces-regions of the extracellular and bath or blood pool directly in contact with electrodes that exhibit a pressure-induced reduction in electrical conductivity-and the presence of a complex network of passive components that acts as a high-pass filter to distort and attenuate the signal that reaches the recording amplifier. The network is formed by the interaction between the passive tissue properties and the double-layer capacitance of electrodes. The MAP and intermediate forms reside on a continuum of signals, which can be generated by the change of the model parameters. Our model helps to decipher the mechanisms of signal generation and can lead to a better design for electrodes, recording amplifiers, and experimental setups.

Clinical Performance of Magnetic Resonance Imaging Conditional and Nonconditional Cardiac Implantable Electronic Devices.

OBJECTIVES: This study compared risks associated with magnetic resonance imaging (MRI) in patients with non-MRI conditional and MRI conditional pacing and defibrillator systems with particular attention to clinically actionable outcomes. BACKGROUND: While recipients of new MRI conditional pacemaker and defibrillator systems may undergo MRI scanning with very low risk, safety and regulatory concerns persist regarding such scanning in recipients of non-MRI conditional systems. METHODS: Patients with any cardiac device who were referred for MRI were prospectively enrolled at a single center and underwent scanning at 1.5 Tesla. Pre- and postscan lead characteristic changes, system integrity, and symptoms were analyzed. A comparison was made between non-MRI conditional and MRI conditional devices. RESULTS: 105 patients were evaluated allowing for comparison of 97 scans with non-MRI conditional devices and 16 scans with MRI conditional devices. The cohort included those with pacemaker dependency, defibrillator, and cardiac resynchronization devices. Small, nonsignificant changes were observed in lead characteristics following scanning, and there was no significant difference when comparing non-MRI and MRI conditional devices. Lead parameter changes did not require lead revision or programming changes. No device reset, failures, or premature scan termination was observed. CONCLUSIONS: 1.5 T MRI scanning in patients with MRI conditional and non-MRI conditional cardiac devices was performed with similar, low clinical risk.

Critical phase transitions during ablation of atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia with significant morbidity and mortality. Pharmacological agents are not very effective in the management of AF. Therefore, ablation procedures have become the mainstay of AF management. The irregular and seemingly chaotic atrial activity in AF is caused by one or more meandering spiral waves. Previously, we have shown the presence of sudden rhythm organization during ablation of persistent AF. We hypothesize that the observed transitions from a disorganized to an organized rhythm is a critical phase transition. Here, we explore this hypothesis by simulating ablation in an anatomically-correct 3D AF model. In 722 out of 2160 simulated ablation, at least one sudden transition from AF to an organized rhythm (flutter) was noted (33%). They were marked by a sudden decrease in the cycle length entropy and increase in the mean cycle length. At the same time, the number of reentrant wavelets decreased from 2.99 ± 0.06 in AF to 1.76 ± 0.05 during flutter, and the correlation length scale increased from 13.3 ± 1.0 mm to 196.5 ± 86.6 mm (both P < 0.0001). These findings are consistent with the hypothesis that transitions from AF to an anatomical flutter behave as phase transitions in complex non-equilibrium dynamical systems with flutter acting as an absorbing state. Clinically, the facilitation of phase transition should be considered a novel mechanism of ablation and may help to design effective ablation strategies.

Electrogram Characteristics of Ablated and Non-Ablated Myocardium in Humans: A Comparison of Miniaturized Embedded Electrodes and Conventional Ablation Electrodes.

INTRODUCTION: Intracardiac electrogram voltage remains an important metric for radiofrequency lesion application. Embedded micro-electrodes within ablation catheters are now approved for use in humans. OBJECTIVE: This study examined electrogram characteristics of miniaturized electrode bipoles (iEGMmini ) compared to distal ablation tip bipoles (iEGMstandard ) in the setting of typical atrial flutter in humans. METHODS: This was a single-center prospective trial involving 21 patients. A total of 54 non-ablated and 56 ablated sites were analyzed offline by separate blinded observers for iEGM voltage after a clinically successful radiofrequency (RF) ablation for typical atrial flutter. Ablation sites were defined as sites that were localized anatomically within the RF lesion set and did not have atrial capture at 10 mA and 2 milliseconds. Non-ablated sites were defined as sites adjacent to or remote from the ablation lesion set with capture at 10 mA and 2 milliseconds. RESULTS: iEGMmini had greater voltages at non-ablated sites and lower voltages at ablated sites than iEGMstandard (non-ablated sites iEGMstandard 0.64 mV vs. iEGMmini 1.0 mV; ablated sites iEGMstandard 0.15 mV, iEGMmini 0.08 mV, P < 0.001). The difference for each patient between ablated and non-ablated sites was greater for iEGMmini compared to iEGMstandard (0.94 mV ± 0.57 iEGMmini vs. 0.52 mV ± 0.35 iEGMstandard , P < 0.001). Inter-observer agreement was good among all non-ablated sites and iEGMmini ablated sites, but was less robust for ablated sites using iEGMstandard . CONCLUSIONS: Imbedded mini-electrode iEGM bipoles had higher voltages in non-ablated tissue, lower voltages in ablated tissue, and significantly greater intra-patient differences between ablated and non-ablated sites. These data suggest a potential role for miniaturized electrode bipole use in RF lesion monitoring.

Sudden and Fatal Malfunction of a Durata Defibrillator Lead due to External Insulation Failure.

Defibrillator lead malfunction can be a disastrous complication, leading to loss of protection from sudden cardiac death in a high-risk patient population. Recognition of lead-specific risk for failure can assist in development of focused screening or surveillance, as in the case of the Riata lead (St. Jude Medical, St. Paul, MN, USA) or the Sprint Fidelis lead (Medtronic Inc., Minneapolis, MN, USA). A case of defibrillation failure secondary to a Durata lead insulation failure is presented. A brief review of the literature and current St. Jude Medical implantable cardiac defibrillator lead design is presented. Identification of arcing is identified as a potential sign of catastrophic insulation failure.

Outcome of Subcutaneous Implantable Cardioverter Defibrillator Implantation in Patients with End-Stage Renal Disease on Dialysis.

BACKGROUND: Although the subcutaneous ICD (S-ICD®) is an attractive alternative in patients with end-stage renal disease (ESRD), data on S-ICD outcomes in dialysis patients are lacking. METHODS: Patients with cardiomyopathy undergoing S-ICD implantation in our center were stratified by need for chronic dialysis at the time of implant. The primary endpoint was incidence of death, heart failure hospitalization or appropriate S-ICD shocks, and secondary endpoints were incidence of inappropriate shocks or implant related complications requiring surgical re-intervention. Mean follow-up was longer in the nondialysis cohort (514 ± 495 vs. 227 ± 233 days, P = 0.006), so all endpoints were analyzed using time-dependent comparisons and reported as annual event rates. RESULTS: Out of 79 S-ICD implants included in this analysis, 27 patients were on dialysis. Dialysis patients were older and more likely to be diabetic. Mean ejection fraction across the entire cohort was 26.9% without significant difference between dialysis and nondialysis groups. Although not significant, the incidence of the primary endpoint was higher in the dialysis cohort (23.8%/year vs. 10.9%/year, P = 0.317), driven primarily by a higher rate of appropriate shocks. The rate of inappropriate shocks was similar between groups (dialysis 6.0%/year vs. nondialysis 6.8%/year, P = 0.509). No patients in the dialysis cohort had complications requiring surgical re-intervention versus 6 patients in the nondialysis cohort (P = 0.086). CONCLUSIONS: Our data suggest that S-ICD implantation in dialysis patients is not associated with an excess risk of implant related complications or inappropriate shocks.

Pulse Generator Exchange Does Not Accelerate the Rate of Electrical Failure in a Recalled Small Caliber ICD Lead.

BACKGROUND: St. Jude Riata/Riata ST defibrillator leads (St. Jude Medical, Sylmar, CA, USA) were recalled by the Food and Drug Administration in 2011 for an increased rate of failure. More than 227,000 leads were implanted and at least 79,000 patients still have active Riata leads. Studies have examined clinical predictors of lead failure in Riata leads, but none have addressed the effect of implantable cardioverter defibrillator (ICD) generator exchange on lead failure. The purpose of this study is to assess the effect of ICD generator exchange on the rate of electrical failure in the Riata lead at 1 year. METHODS: A retrospective chart review was conducted in patients who underwent implantation of a Riata/Riata ST lead at one center. Patients with a functioning Riata lead (with/without externalized conductor) at the time of ICD exchange were compared to controls with Riata leads implanted for a comparable amount of time who did not undergo generator replacement. RESULTS: Riata leads were implanted in 1,042 patients prior to the recall and 153 of these patients underwent generator exchange without lead replacement. Conductor externalization was noted in 21.5% of Riata leads in the ICD exchange cohort, which was not different from the control group (19.2%; P = 0.32). Two leads failed in the first year after generator replacement (1.5%) which did not significantly differ from the control group (2.0%; P = 0.57). At change-out, 54% received a commanded shock (18.6 ± 0.9 J) that did not result in any change in the high-voltage lead impedance (46.1 ± 1.1 ohms). CONCLUSIONS: Conductor externalization was seen frequently in our cohort of patients. ICD generator exchange did not accelerate the rate of Riata lead failure at 1 year. Although both the control and the change-out cohorts failed at a rate much greater than nonrecalled leads, generator exchange did not appear to add to the problem.

Predictors of Long-Term Survival Following Transvenous Extraction of Defibrillator Leads.

BACKGROUND: Little data exist on long-term outcomes following extraction of implantable cardioverter defibrillator (ICD) leads, particularly for noninfectious indications. We sought to identify predictors of long-term survival after ICD lead extraction. METHODS: We retrospectively reviewed ICD lead extractions at our institution (n = 508). Procedural outcomes and long-term survival were ascertained by medical records review. RESULTS: Indication for lead extraction was infection in 32.5% and lead failure in 61.8%. Mean dwell time of the oldest extracted lead was 5.1 ± 5.9 years. Complete procedural success was achieved in 96.5% of cases. Major procedure-related complications occurred in 1.6% with six periprocedural deaths. During a mean follow-up of 866 ± 798 days, survival was significantly worse among patients with infection as the indication for extraction. At 1 year after extraction, survival among those with infection was 88.2%, compared to 95.0% in the lead failure cohort (P < 0.001). Procedural failure was a significant predictor of long-term mortality, even after excluding periprocedural deaths. In multivariate models, the presence of chronic kidney disease, increased number of leads requiring extraction, lower ejection fraction, and procedural failure were predictors of mortality. CONCLUSION: Despite high rates of procedural success, infectious indication for ICD lead extraction is associated with increased long-term mortality. In contrast, among patients undergoing extraction for lead failure, long-term survival was excellent. The presence of procedural failure was a significant predictor of long-term mortality. Further studies will be necessary to better understand the mechanisms by which procedural failure may adversely impact long-term outcomes.

Cardiac resynchronization therapy in adult patients with repaired tetralogy of fallot and left ventricular systolic dysfunction.

BACKGROUND: Although left ventricular (LV) systolic dysfunction is known to occur in adults with repaired Tetralogy of Fallot (TOF), the effects of cardiac resynchronization therapy (CRT) are not well characterized. METHODS: We retrospectively divided all patients with repaired TOF and impaired LV ejection fraction (LVEF ≤ 40%) undergoing CRT at our institution (n = 10) into two groups: de novo CRT (group A, n = 6) or upgrade from existing device (group B, n = 4). Echocardiograms were reviewed at baseline, medium-term (>6 months post-CRT), and long-term follow-up. CRT response was defined as reduction in LV end-systolic volume (LVESV) ≥15% at medium term. RESULTS: Age at surgical repair was 13.1 ± 16.0 years, age at CRT was 44.4 ± 12.5 years, and baseline LVEF was 24.0 ± 10.5%. Group A demonstrated a preponderance of right ventricular (RV) conduction delay, whereas all patients in group B demonstrated RV pacing at baseline. At medium-term follow-up, patients in group A showed significant improvements in LVEF, LV end-diastolic volume (LVEDV), and LVESV. Group B also demonstrated a significant improvement in LVEF with favorable trends in LV volumes. Of nine patients with complete data at medium term, eight showed evidence of CRT response. Average long-term follow-up was 53.4 ± 29.3 months. At long-term follow-up, LVEF, LVEDV, and LVESV remained numerically better than baseline, although the results were no longer significant. CONCLUSIONS: Adult patients with repaired TOF and LV systolic dysfunction demonstrate significant medium-term response to CRT, even among those with RV conduction delay. The long-term impact of CRT in this population requires further characterization.

Transient pacing in pigs with complete heart block via myocardial injection of mRNA coding for the T-box transcription factor 18.

The adenovirus-mediated somatic transfer of the embryonic T-box transcription factor 18 (TBX18) gene can convert chamber cardiomyocytes into induced pacemaker cells. However, the translation of therapeutic TBX18-induced cardiac pacing faces safety challenges. Here we show that the myocardial expression of synthetic TBX18 mRNA in animals generates de novo pacing and limits innate and inflammatory immune responses. In rats, intramyocardially injected mRNA remained localized, whereas direct myocardial injection of an adenovirus carrying a reporter gene resulted in diffuse expression and in substantial spillover to the liver, spleen and lungs. Transient expression of TBX18 mRNA in rats led to de novo automaticity and pacemaker properties and, compared with the injection of adenovirus, to substantial reductions in the expression of inflammatory genes and in activated macrophage populations. In rodent and clinically relevant porcine models of complete heart block, intramyocardially injected TBX18 mRNA provided rate-adaptive cardiac pacing for one month that strongly correlated with the animal's sinus rhythm and physical activity. TBX18 mRNA may aid the development of biological pacemakers.