Safety and feasibility of left bundle branch area pacing following valvular interventions: Multicenter study.

OBJECTIVES: To evaluate the safety and feasibility of left bundle branch area pacing (LBBAP) in patients with valvular interventions. METHODS: Eighty-four patients were included in this study. All patients underwent recent surgical or percutaneous valvular interventions. LBBAP was attempted in all patients. Implant success rates, peri- and postprocedure electrocardiogram, pacing parameters, and complications were assessed at implant, and during follow-up. RESULTS: LBBAP implantation was successful in 80/84 (95%) patients. Mean age was 74.1 ± 13.8 years and 56% patients were male. Prior valvular replacements included: percutaneous aortic (26), surgical aortic (36), combined surgical aortic plus mitral (6), MVR (10), tricuspid (1), and pulmonic (1). Average LVEF was 52.6 ± 11%. Majority of patients underwent LBBAP due to atrioventricular block (76%) and sinus node disease (13%). Total procedure duration was 74.1 ± 12.5 min and fluoroscopic duration was 9.7 ± 6.8 min. Pacing parameters were stable during follow-up period of 10.0 ± 6.3 months. Pacing QRS duration was significantly narrower than baseline QRS duration (131.5 ± 31.4 ms vs. 114.3 ± 13.7 ms, p < .001, respectively). No acute complications were observed. Mean follow-up was 10.0 ± 6.3 months (median: 8.4 months, min: 1 and max: 24 months). During follow-up, there were three device infections and two patients had loss of LBBA capture within 1 month of implant. CONCLUSIONS: LBBAP is a feasible and safe pacing modality in patients with prior interventions for valvular heart disease.

Electrocardiographic characteristics and ablation of ventricular arrhythmias originating from the basal inferoseptal area.

AIMS: Ventricular arrhythmias (VAs) from the basal inferoseptal (BIS) area are rare and can pose unique challenges during catheter ablation (CA) due to the anatomic complexity. The study sought to describe the electrocardiographic and clinical characteristics of VAs originating from the BIS area. METHODS AND RESULTS: Patients with VAs and successful ablation at the BIS area from 2016 to 2020 were included. The 12-lead electrocardiogram (ECG), intracardiac findings, and outcomes were analysed. Of 482 patients with VAs referred for CA, 17 (3.5%) had successful ablation at BIS area. There were 12 males, mean age was 66.7 ± 9 years, 82% had ejection fraction <50%. Mean baseline premature ventricular complex burden was 28.6 ± 9%. All patients had a leftward superior axis. Left bundle branch block (LBBB) with early transition in V2 was noted in eight patients and right bundle branch block (RBBB) in nine patients. Detailed mapping of the right ventricle (RV) was performed in 15 patients (88%), coronary sinus (CS)/middle cardiac vein (MCV) in 13 (76%), right atrium (RA) adjacent to the inferoseptal process (ISP) of left ventricle (LV) in 5 (29%), ISP-LV in 13 (76%), and epicardium in 2 (12%). Successful ablation site was in LV in 10 (59%), RV in 2 (12%), CS/MCV in 1 (6%), RA in 1 (6%), and epicardium in 2 (12%). Fifteen patients (88%) required mapping in at least two chambers (range 2-5) and seven patients (41%) required ablation in at least two chambers (range 2-3). CONCLUSIONS: Ventricular arrhythmias originating in the BIS are uncommon. The most common ECG patterns were leftward superior axis, LBBB with transition in V2 or RBBB. The VA foci can be endocardial or epicardial and meticulous mapping/ablation from multiple chambers is often required to eliminate these foci successfully.

Novel quinoline derivatives as inhibitors of bacterial DNA gyrase and topoisomerase IV.

A structurally novel set of inhibitors of bacterial type II topoisomerases with potent in vitro and in vivo antibacterial activity was developed. Dual-targeting ability, hERG inhibition, and pharmacokinetic properties were also assessed.

Atrioventricular junction ablation in patients with conduction system pacing leads: A comparison of His-bundle vs left bundle branch area pacing leads.

BACKGROUND: Single-center studies have shown feasibility of conduction system pacing (CSP) via His-bundle pacing (HBP) or left bundle branch area pacing (LBBAP) in atrial fibrillation (AF) patients undergoing atrioventricular junction ablation (AVJA). OBJECTIVE: The purpose of this study was to compare outcomes in patients with HBP and LBBAP leads undergoing AVJA. METHODS: Consecutive patients with CSP leads referred for AVJA between October 2014 and May 2021 were included. Pacing lead characteristics, procedural characteristics, complications, and long-term outcomes were assessed. RESULTS: One hundred five AVJA procedures (55 HBP, 50 LBBAP) were performed in 98 patients (48 HBP, 50 LBBAP). The acute success rate of the AVJA procedure was 94% vs 100% (P = .11) in HBP vs LBBAP groups. Seven (14%) redo AVJA procedures were required in the HBP group. Mean procedural time (44 ± 24 min vs 34 ± 16 min; P = .02) and mean fluoroscopy time (16 ± 18 min vs 7 ± 6 min; P <.001) were significantly longer in the HBP vs LBBAP group. An acute rise in threshold was noted in 8 cases (14.5%), and 4 (8%) developed exit block after AVJA in HBP patients. Chronic HBP threshold ≥2.5 V was seen in 23 patients (48%), and 4 (8%) HBP leads were deactivated. CSP preserved ejection fraction (EF) in the overall cohort (N = 70; 53% ± 10% vs 55% ± 10%; P = .09) and significantly improved in those with reduced EF <50% at baseline (N = 16; 37% ± 7.6% vs 46% ± 13%; P = .02). CONCLUSION: AVJA in the presence of an LBBAP lead is associated with a higher success rate and fewer acute and chronic lead-related complications. CSP with either HBP or LBBAP preserves left ventricular systolic function in patients with refractory atrial fibrillation post AVJA.

Left bundle branch area pacing in patients with atrioventricular conduction disease: A prospective multicenter study.

BACKGROUND: The reported success rate of His-bundle pacing (HBP) in patients with infranodal atrioventricular (AV) conduction disease is only 52%-76%. The success rate of left bundle branch area pacing (LBBAP) in this cohort is not well studied. OBJECTIVE: The purpose of this study was to evaluate the feasibility, safety, and electrophysiological characteristics of LBBAP in patients with AV conduction disease. METHODS: Patients with AV conduction disease referred for pacemaker implantation at 2 centers between February 2019 and June 2021 were considered for LBBAP. Baseline demographic characteristics, procedural success rates, electrophysiological parameters, and complications were assessed. RESULTS: LBBAP was successful in 340 of 364 patients (93%). Mean age was 72 ± 13 years, and mean follow-up was 331 ± 244 days. Pacing indications were Mobitz I in 27 patients (7%), Mobitz II or 2:1 AV block or high-grade AV block in 94 patients (26%), complete heart block in 199 patients (55%), and sick sinus syndrome with isolated bundle branch block in 44 patients (12%). Left bundle branch block and right bundle branch block were present in 57 patients (16%) and 140 patients (38%), respectively. Procedural success rates did not differ between indications (92.6%, 93.6%, 92.9%, and 95%, respectively) or between patients with narrow (<120 ms) vs wide QRS (≥120 ms). Mean LBBAP threshold was 0.77 ± 0.34 V at 0.4 ms at implant and remained stable during follow-up. There were 4 (1.2%) acute LBBAP lead dislodgments. CONCLUSION: LBBAP is safe and feasible with high success rates for patients with AV conduction disease. In contrast to HBP, LBBAP success rates remain high over the entire spectrum of AV conduction disease, and lead parameters remain stable during follow-up.

The CD40 agonist antibody CP-870,893 enhances dendritic cell and B-cell activity and promotes anti-tumor efficacy in SCID-hu mice.

CD40 is a member of the TNF family of receptors that has been shown to play a crucial role in enhancing dendritic cell activity and fostering anti-tumor immune responses. In this study, we demonstrate the in vitro properties and in vivo efficacious activity of the CD40 agonist antibody, CP-870,893. CP-870,893 is a fully human, IgG2 antibody that selectively interacts with CD40 at a site distinct from its ligand-binding region with a KD of 0.4 nM. It enhances the expression of MHC class II, CD54, CD86, and CD23 on human B cells in vitro. CP-870,893 also enhances dendritic cell activity as evidenced by cytokine secretion (IL-12, IL-23, IL-8), the upregulation of CD86 and CD83, and the ability to prime T cells to secrete IFNγ. In SCID-beige mice, a single parenteral injection of CP-870,893 was therapeutically effective against several CD40(pos) human tumors (B-cell lymphoma, breast, colon, and prostate) indicating direct effects on tumor cell survival and/or growth. When mice were co-implanted with human T cells and dendritic cells, the activity of CP-870,893 against CD40(pos) tumors increased, and efficacy was also observed against CD40(neg) and CD40(low) tumors demonstrating the ability of CP-870,893 to enhance anti-tumor immune function in vivo. These studies suggest that CP-870,893 has the potential to be efficacious against a wide range of tumor types through both direct and immune-mediated effects.

Discovery, synthesis and SAR of azinyl- and azolylbenzamides antagonists of the P2X7 receptor.

The discovery, of a series of 2-Cl-5-heteroaryl-benzamide antagonists of the P2X(7) receptor via parallel medicinal chemistry is described. Initial analogs suffered from poor metabolic stability and low Vd(ss). Multi parametric optimization led to identification of pyrazole 39 as a viable lead with excellent potency and oral bioavailability. Further attempts to improve the low Vd(ss) of 39 via introduction of amines led to analogs 40 and 41 which maintained the favorable pharmacology profile of 39 and improved Vd(ss) after iv dosing. But these analogs suffered from poor oral absorption, probably driven by poor permeability.

Intermediate-term performance and safety of His-bundle pacing leads: A single-center experience.

BACKGROUND: The short-term safety, feasibility, and performance of His-bundle pacing (HBP) leads have been reported; however, their longer-term performance beyond 1 year remains unclear. OBJECTIVE: The purpose of this study was to examine the intermediate-term performance and safety of HBP. METHODS: All HBP lead implants at Virginia Commonwealth University between January 2014 and January 2019 were analyzed. HBP was performed using a Medtronic SelectSecure 3830-69 cm pacing lead. RESULTS: Of 295 attempts, successful HBP implantation (selective or nonselective) was seen in 274 cases (93%). Mean follow-up duration was 22.8 ± 19.5 months (median 19.5; interquartile range 11-33). Mean age was 69 ± 15 years; 58% were males; and ejection fraction <50% was noted in 30%. Indications for pacemaker included sick sinus syndrome in 41%, atrioventricular block in 36%, cardiac resynchronization therapy in 7%, and refractory atrial fibrillation in 15%. Selective HBP was achieved in 33%. Mean HBP capture threshold at implant was 1.1 ± 0.9 V at 0.8 ± 0.2 ms, which significantly increased at chronic follow-up to 1.7 ± 1.1 V at 0.8 ± 0.3 ms (P <.001). Threshold was ≥2.5 V in 24% of patients, and 28% had an increase in HBP threshold ≥1 V. Loss of His-bundle capture at follow-up (septal right ventricular pacing) was seen in 17%. There was a total of 31 (11%) lead revisions, primarily for unacceptably high thresholds. CONCLUSION: Although HBP can prevent or improve pacing-induced cardiomyopathy, the elevated capture thresholds, loss of His-bundle capture, and lead revision rates at intermediate follow-up are of concern. Longer-term follow-up data from multiple centers are needed.

Imaging-Based Localization of His Bundle Pacing Electrodes: Results From the Prospective IMAGE-HBP Study.

OBJECTIVES: This study sought to evaluate the correlation between His bundle (HB) pacing (HBP) implantation characteristics, lead-tip location, and association of intraprocedural His recordings with approximated HB anatomic landmarks using computed tomography (CT) imaging. BACKGROUND: HBP continues to grow in clinical practice due to offering true physiological pacing. However, a clear understanding of HB anatomy and the lead-tip location's influence on pacing characteristics is lacking. METHODS: The IMAGE-HBP study (Imaging Study of Lead Implant for His Bundle Pacing) was a prospective, multicenter study designed to assess implantation characteristics of the SelectSecure Model 3830 lead placed at the HB, evaluate protocol-specified HBP success (His recording present on electrogram and HBP threshold ≤2.5 V at 1 ms), and correlation between lead-tip location by CT imaging and HBP characteristics as well as lead-related complications through 12 months. RESULTS: Sixty-nine patients underwent a lead implantation attempt at the HB. Of these, 61 patients (88%) had a lead successfully implanted at the HB, and 52 patients (75%) met the pre-specified definition of successful HBP. In 51 patients with CT imaging, 11 leads (22%) were placed in the atrial aspect of the HB region (36% selective HBP), and 40 leads (78%) were placed in the ventricular aspect (28% selective HBP). Four of the 51 patients had P-wave oversensing, all with leads in the atrium. Freedom from lead-related complication at 12 months was 93%. CONCLUSIONS: Successful HBP could be achieved at lead-tip locations in the atrium or ventricle but is preferable in the ventricle to eliminate risk of oversensing. The IMAGE-HBP study offers better insight into approximated HB anatomic landmarks, lead-tip location, and correlation with pacing characteristics. (Imaging Study of Lead Implant for His Bundle Pacing [IMAGE-HBP]; NCT03294317).

An unusual source of electromagnetic interference: a device-device interaction.

INTRODUCTION: Implantable cardioverter-defibrillators (ICDs) are susceptible to oversensing of extracardiac signals, also known as electromagnetic interference (EMI). We report a case of an unusual source of electrical interference of only the high voltage (HV) impedance measurement in the Teligen ICD (Boston Scientific, St. Paul, MN, USA) caused by electrical interference from an electrosurgical generator with an electrocautery patch located in close proximity to the ICD pulse generator. METHOD AND RESULTS: A patient underwent an uneventful implant of a Boston Scientific Teligen 100 ICD. Once the device was inserted in a pocket, interrogation of the device repeatedly demonstrated HV electrode impedance measurements between <20 and 40 Omega and noise only on the HV electrode. A new lead and generator were implanted without a change in the interrogation results. The erroneous measurements of HV impedance were caused by a combination of the close proximity of the electrocautery patch to the ICD generator. The continuous low-amplitude current emitted by the contact quality monitoring system of the electrosurgical cautery generator interfered with an equally weak current delivered through the lead by the device to measurement HV impedance. The Medtronic Virtuoso (Medtronic Inc., Minneapolis, MN, USA) ICD and the St. Jude Medical Current DR (St. Jude Medical, St. Paul, MN, USA) ICD were not affected by the patch due to greater magnitude of current delivered by the device to measure HV electrode impedance. CONCLUSION: It is important that the operator must be aware of any potential source of EMI, as it may affect the device and require immediate troubleshooting. Failure to recognize this interaction may result in inappropriate and unnecessary pulse generator replacement.

Initial Experience, Safety, and Feasibility of Left Bundle Branch Area Pacing: A Multicenter Prospective Study.

OBJECTIVES: This study sought to evaluate the safety and feasibility of conduction system pacing by performing left bundle branch area pacing (LBBAP). BACKGROUND: There are limited data from single centers showing that LBBAP may circumvent the technical and electrophysiological challenges encountered with His bundle pacing. METHODS: Patients referred for pacemaker implantation at 2 centers between February 1, 2019, and March 31, 2020, were considered for LBBAP. LBBAP was performed by implanting a lumen-less, exposed helix lead approximately 2 cm distal to the His bundle and deep into the septum using a specialized delivery sheath. Implant success rates, complications, and electrophysiological parameters were assessed. RESULTS: LBBAP was successful in 305 of 341 patients (89%). Mean age was 72 ± 12 years; 45% were women; and 39% had QRS duration (QRSd) >130 ms, 22% right bundle branch block, 11% left bundle branch block, and 6% intraventricular conduction defect. Pacing indications were sinus node dysfunction in 28.7%, atrioventricular block in 52.5%, cardiac resynchronization therapy in 8.8%, and refractory atrial fibrillation in 10% of patients. Procedural duration was 74.7 ± 34 min and fluoroscopic time was 10.4 ± 8.1 min. The mean baseline QRSd and paced QRSd in the overall cohort was 114 ± 29.8 ms versus 112 ± 11.7 ms (p < 0.001) and in patients with infra-Hisian disease was 144.5 ± 19 ms versus 115 ± 12 ms (p < 0.001), respectively. Mean left ventricular activation time was 71.7 ± 11 ms at high output and 74.7 ± 11 ms at low output. LBB potentials were noted in 41% patients. Pacing threshold and R waves were 0.74 ± 0.3 V at 0.4 ms and 10.7 ± 4.9 mV at time of implantation and were stable at 1-, 3-, 6-, and 12-month follow-ups. The only major complications were 3 LBBAP lead dislodgements, 2 within 24 h and 1 at 2 weeks. CONCLUSIONS: LBBA pacing is safe, feasible, and a reliable alternative to His bundle pacing for providing physiological pacing. Randomized controlled studies are needed to confirm the safety, feasibility, and clinical outcomes of LBBAP.

Novel Method for Assessment of His Bundle Pacing Morphology Using Near Field and Far Field Device Electrograms.

BACKGROUND: The 12-lead ECG is considered the gold standard to differentiate between selective (S), nonselective (NS) His bundle pacing (HBP), and right ventricular septal capture in routine clinical practice. We sought to assess the utility of device EGM recordings as a tool to identify the type of HBP morphology. METHODS: One hundred forty-eight consecutive patients underwent HBP with a 3830 Select Secure lead (Medtronic, Inc) at 3 centers between October 2016 and October 2017. The near field V-EGM morphology (NF EGM), near field V-EGM time to peak (NFTime to peak), and far-field EGM QRS duration (QRSd) were recorded while pacing the His lead with simultaneous 12-lead ECG rhythm strips. RESULTS: Indications for HBP were sinus node dysfunction, atrioventricular conduction disease, and cardiac resynchronization therapy in 68 (46%), 56 (38%), and 24 (16%) patients, respectively. Baseline QRSd was 108±38 ms with QRSd >120 ms in 57 (39%) patients (27 right bundle branch block, 18 left bundle branch block, and 12 intraventricular conduction delay). S-HBP was noted in 54 (36%) patients. A positive NFEGM and NFTime to peak >40 ms were highly sensitive (94% and 93%, respectively) and specific (90% and 94%) for S-HBP irrespective of baseline QRSd. All 3 parameters (+NFEGM, NFTime to peak >40 ms, and far-field EGM QRSd <120 ms) had high negative predictive value (97%, 95%, and 92%). A novel device-based algorithm for S-HBP was proposed. EGM transitions correlated with ECG transitions during threshold testing and can help accurately differentiate between S-HBP, NS-HBP, and right ventricular septal pacing with a cumulative positive predictive value of 91% (positive predictive value =100% in patients with baseline QRSd <120 ms). CONCLUSIONS: We propose a novel and simple criteria for accurate differentiation between S-HBP, NS-HBP, and right ventricular septal capture morphologies by careful analysis of device EGMs alone. This study paves the way for future studies to assess autocapture algorithms for devices with HBP.

Benefit of primary prevention implantable cardioverter-defibrillators in the setting of chronic kidney disease: a decision model analysis.

INTRODUCTION: Primary prevention ICD trials have excluded patients with CKD. Comorbidities and lower life expectancy in patients with CKD make the benefit of primary prevention ICD implantation uncertain. METHODS: A decision analysis model was devised to evaluate the risks and benefits of implantable cardioverter-defibrillators (ICD) implantation in patients with chronic kidney disease (CKD) who meet current criteria for a primary prevention ICD. Published data capturing event rates, infection risks, and overall survival in CKD patients with and without ICDs were utilized. Variables included patient's age, GFR and stage of CKD, probability of sudden cardiac death (SCD), and device implantation mortality. RESULTS: The benefit of an ICD for primary prevention of SCD in patients with CKD depends primarily on the patient's age and stage of kidney disease. With stages 1 and 2 CKD, ICD implantation reduces mortality. However, in patients with more advanced stages of CKD, the benefit is less significant and age-dependent. This is attributed to patients with advanced CKD having a higher procedural risk and decreased life expectancy. With average procedural mortality, ICD implantation is favored at ages <80 for stage 3, ages <75 for stage 4, and ages <65 for stage 5. As procedural mortality rates increase, age thresholds for ICD implantation decrease. CONCLUSIONS: Our model shows that benefit from primary prevention ICD implantation is determined by the patient's age and stage of kidney disease. While there is limited impact with lower stages of CKD, careful consideration of ICD implantation is suggested for older patients with more advanced stages of kidney disease.

Sensing failure associated with the Medtronic Sprint Fidelis defibrillator lead.

INTRODUCTION: The diameter of implantable cardioverter-defibrillator (ICD) leads has become progressively smaller over time. However, the long-term performance characteristics of these smaller ICD leads are unknown. METHODS: We retrospectively evaluated 357 patients who underwent implantation of a Medtronic Sprint Fidelis defibrillating lead at two separate centers between September 2004 and October 2006. Lead characteristics were measured at implant, at early follow-up (1-4 days post implant), and every 3-6 months thereafter. RESULTS: During the study period, 357 patients underwent implantation of the Medtronic Sprint Fidelis lead. The mean R-wave measured at implant through the device was not different (P = NS) when compared with that measured at first follow-up (10.5 +/- 5.0 mV vs 10.7 +/- 5.1 mV). Forty-one patients (13%) had an R-wave amplitude

Long-term follow-up after radiofrequency catheter ablation for atrial fibrillation.

AIMS: Data on long-term follow-up of patients who have undergone catheter ablation for atrial fibrillation (AF) are very limited. This report aimed at presenting clinical outcome and AF-free survival after pulmonary vein (PV) isolation over an extended (>3 years) follow-up period. METHODS AND RESULTS: Thirty-nine patients subjected to PV isolation for paroxysmal AF were followed-up for at least 3 years according to a strict protocol. Fourteen patients (35.8%) had one, 19 patients (50%) had two, and 6 patients (15.4%) had three ablation procedures. At end of follow-up (42.2 +/- 6.0 months), 17 patients (43.5%) were completely free of AF or other atrial arrhythmia, and 26 patients (66.6%) had symptomatic improvement. The long-term success rate was 21.4% for patients subjected to a single ablation procedure, 52.6% for patients subjected to two catheter ablation procedures, and 66.7% for patients who underwent three ablation procedures (P = 0.094). There was also a trend for patients who underwent a combination of different ablation procedures (ostial, antral, and/or circumferential) to have a higher AF-free survival when compared with patients subjected to the same procedure (P-value for log-rank test = 0.036). CONCLUSION: Catheter ablation does not eliminate paroxysmal AF in up to 56% of patients in the long term, despite the use of two or three ablation procedures in two-thirds of them. However, it confers symptomatic improvement in 67% of treated patients.

Clinical judgment versus decision analysis for managing device advisories.

INTRODUCTION: Implantable cardioverter-defibrillator (ICD) and pacemaker (PM) advisories may have a significant impact on patient management. Surveys of clinical practice have shown a great deal of variability in patient management after a device advisory. We compared our management of consecutive patients in a single large university practice with device advisories to the "best" patient management strategy predicted by a decision analysis model. METHODS: We performed a retrospective review of all patients who had implanted devices affected by an advisory at our medical center between March 2005 and May 2006 and compared our actual patient management strategy with that subsequently predicted by a decision analysis model. RESULTS: Over 14 months, 11 advisories from three different manufacturers affected 436 patients. Twelve patients (2.8%) were deceased and 39 patients (8.9%) were followed at outside facilities. Management of the 385 remaining patients varied based on type of malfunction or potential malfunction, manufacturer recommendations, device dependency, and patient or physician preferences. Management consisted of the following: 57 device replacements (15.2%), 44 devices reprogrammed or magnets issued (11.7%), and 268 patients underwent more frequent follow-up (71.3%). No major complications, related to device malfunction or device replacement, occurred among any patient affected with a device advisory. Concordance between the decision analysis model and our management strategy occurred in 57.1% of cases and 25 devices were replaced when it was not the preferred treatment strategy predicted by the decision model (43.9%, 37.3% when excluding devices replaced based on patient preference). The decision analysis favored replacement for all patients with PM dependency, but only for four patients with ICDs for secondary prevention. No devices were left implanted that the decision analysis model predicted should have been replaced. CONCLUSIONS: We found that despite a fairly conservative device replacement strategy for advisories, we still replaced more devices when it was not the preferred device management strategy predicted by a decision analysis model. This study demonstrates that even when risks and benefits are being considered by experienced clinicians, a formal decision analysis can help to develop a systematic evidence based approach and potentially avoid unnecessary procedures.

Profound Sinoatrial Arrest Associated with Ibrutinib.

BACKGROUND: Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor approved for second-line treatment for mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and Waldenström macroglobulinemia. Ibrutinib use has been linked to increased incidence of atrial fibrillation and hypertension in multiple studies. Other forms of cardiac toxicities have also been reported in isolated case reports. Bradycardia and asystole have not been associated with ibrutinib use in the past. CASE REPORT: We present a case of a 76-year-old female with no prior cardiac history, who initiated treatment with ibrutinib for relapsing mantle cell lymphoma and was noted to have symptomatic bradycardia, greater than 20 second long pauses on her cardiac monitor requiring placement of a permanent pacemaker. CONCLUSION: This is the first case associating bradycardia and asystole with tyrosine kinase inhibitor use. Irreversible inhibition of certain cardioprotective tyrosine kinases has been a growing topic of research in oncology therapeutics.

Development and testing of an algorithm to detect implantable cardioverter-defibrillator lead failure.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) lead failures often present as inappropriate shock therapy. An algorithm that can reliably discriminate between ventricular tachyarrhythmias and noise due to lead failure may prevent patient discomfort and anxiety and avoid device-induced proarrhythmia by preventing inappropriate ICD shocks. OBJECTIVES: The goal of this analysis was to test an ICD tachycardia detection algorithm that differentiates noise due to lead failure from ventricular tachyarrhythmias. METHODS: We tested an algorithm that uses a measure of the ventricular intracardiac electrogram baseline to discriminate the sinus rhythm isoelectric line from the right ventricular coil-can (i.e., far-field) electrogram during oversensing of noise caused by a lead failure. The baseline measure was defined as the product of the sum (mV) and standard deviation (mV) of the voltage samples for a 188-ms window centered on each sensed electrogram. If the minimum baseline measure of the last 12 beats was <0.35 mV-mV, then the detected rhythm was considered noise due to a lead failure. The first ICD-detected episode of lead failure and inappropriate detection from 24 ICD patients with a pace/sense lead failure and all ventricular arrhythmias from 56 ICD patients without a lead failure were selected. The stored data were analyzed to determine the sensitivity and specificity of the algorithm to detect lead failures. RESULTS: The minimum baseline measure for the 24 lead failure episodes (0.28 +/- 0.34 mV-mV) was smaller than the 135 ventricular tachycardia (40.8 +/- 43.0 mV-mV, P <.0001) and 55 ventricular fibrillation episodes (19.1 +/- 22.8 mV-mV, P <.05). A minimum baseline <0.35 mV-mV threshold had a sensitivity of 83% (20/24) with a 100% (190/190) specificity. CONCLUSION: A baseline measure of the far-field electrogram had a high sensitivity and specificity to detect lead failure noise compared with ventricular tachycardia or fibrillation.

Atrial arrhythmias following ostial or circumferential pulmonary vein ablation.

AIMS: The incidence, clinical significance and optimum treatment of AF ablation-induced proarrhythmia is not entirely known. This report describes the incidence and management of atrial arrhythmias occurring after various techniques for the ablative therapy of atrial fibrillation (AF). METHODS: Five hundred and forty-four patients with paroxysmal atrial fibrillation were subjected to ostial pulmonary vein (PV) (n = 204), antral (n = 300), or circumferential (n = 40) ablation around the PV ostia. RESULTS: Atrial tachycardia or flutter during the first 6 months after AF ablation was detected in 14 patients and was more common among patients subjected to circumferential or circumferential and linear ablation (18% and 22%, respectively) than to other techniques (p < 0.001). The risk of atrial tachycardia or flutter among patients who underwent ostial, ostial with lines and antral ablation was 1%, 8% and 1%, respectively. No difference was observed in the risk of atrial arrhythmia between patients who underwent ablation with or without additional lines, either ostial (p = 0.17) or circumferential (p = 0.99). Re-ablation was performed in patients with sustained atrial arrhythmia (11 out of 14 patients). At 6 months, no recurrence was seen in 10 of these patients as well as in 3 patients with non-sustained atrial tachycardia or flutter. CONCLUSIONS: The incidence of atrial tachycardia or flutter following AF ablation is lower for ostial than circumferential ablation. The addition of lines along the mitral isthmus and between the superior PVs does not significantly affect the risk of ablation-induced arrhythmia. Non-sustained atrial tachycardia or flutter following AF ablation procedures does not always require additional ablation.