Spencer Rosero

Inappropriate Implantable Cardioverter-Defibrillator Shocks in MADIT II : Frequency, Mechanisms, Predictors, and Survival Impact

OBJECTIVES This study sought to identify the incidence and outcome related to inappropriate implantable cardioverter-defibrillator (ICD) shocks, that is, those for nonventricular arrhythmias. BACKGROUND The MADIT (Multicenter Automatic Defibrillator Implantation Trial) II showed that prophylactic ICD implantation improves survival in post-myocardial infarction patients with reduced ejection fraction. Inappropriate ICD shocks are common adverse consequences that may impair quality of life. METHODS Stored ICD electrograms from all shock episodes were adjudicated centrally. An inappropriate shock episode was defined as an episode during which 1 or more inappropriate shocks occurred; another inappropriate ICD episode occurring within 5 min was not counted. Programmed parameters for patients with and without inappropriate shocks were compared. RESULTS One or more inappropriate shocks occurred in 83 (11.5%) of the 719 MADIT II ICD patients. Inappropriate shock episodes constituted 184 of the 590 total shock episodes (31.2%). Smoking, prior atrial fibrillation, diastolic hypertension, and antecedent appropriate shock predicted inappropriate shock occurrence. Atrial fibrillation was the most common trigger for inappropriate shock (44%), followed by supraventricular tachycardia (36%), and then abnormal sensing (20%). The stability detection algorithm was programmed less frequently in patients receiving inappropriate shocks (17% vs. 36%, p = 0.030), whereas other programming parameters did not differ significantly from those without inappropriate shocks. Importantly, patients with inappropriate shocks had a greater likelihood of all-cause mortality in follow-up (hazard ratio 2.29, p = 0.025). CONCLUSIONS Inappropriate ICD shocks occurred commonly in the MADIT II study, and were associated with increased risk of all-cause mortality.

Venous Thrombosis and Stenosis After Implantation of Pacemakers and Defibrillators

Venous complications of pacemaker/ implantable cardioverter defibrillator (ICD) system implantation rarely cause immediate clinical problems. The challenge starts when patients come for system revision or upgrade. Numerous reports of venous complications such as stenosis, occlusions, and superior vena cava syndrome have been published. We reviewed current knowledge of these complications, management, and their impact on upgrade/revision procedures. One study has suggested that intravenous lead infection promotes local vein stenosis. Another found that the presence of a temporary wire before implantation is associated with an increased risk of stenosis. Although data for ICD leads is based only on three studies—it suggests that the rate of venous complications is very similar to that of pacing systems, and probably data from pacing leads can be extrapolated to ICD leads. Despite 40 years of experience with transcutaneous implanted intravenous pacing systems and dozens of studies, we were unable to identify clear risk factors (confirmed by independent studies) that lead to venous stenosis. Neither the hardware (lead size, number and material) nor the access site choice (cephalic cut down, subclavian or axillary puncture) appears to affect rate of venous complications. A few factors were proposed as predictors of severe venous stenosis/occlusion: presence of multiple pacemaker leads (compared to a single lead), use of hormone therapy, personal history of venous thrombosis, the presence of temporary wire before implantation, previous presence of a pacemaker (ICD as an upgrade) and the use of dual-coil leads. Anticoagulant therapy (for other reasons than pacemaker lead) seemed to have protective antithrombotic effect.

Lidocaine block of LQT-3 mutant human Na+ channels

In transiently transfected mammalian cells we have identified pharmacological consequences of a naturally occurring deletion mutation, delta KPQ, of the human heart Na+ channel alpha subunit that previously has been linked to one form of the long QT syndrome, an inherited heart disease. Our results show that the Class IB antiarrhythmic agent lidocaine blocks maintained inward current through and slows recovery from inactivation of delta KPQ-encoded Na+ channels. Block is greater for maintained than for peak current. Because incomplete inactivation of mutant Na+ channels is now thought to underlie the prolonged ventricular action potential, which is the phenotype of this disease, and we find that the delta KPQ mutation speeds the recovery from inactivation of drug-free mutant channels, our results provide evidence, for the first time, that clinically relevant dysfunctional properties of an ion channel can be selectively targeted on the basis of the molecular properties conferred on the channel by an inherited genetic disorder.

Electrocardiographic Findings in Patients With Diphenhydramine Overdose

QT interval prolongation and torsades de pointes ventricular tachycardia have been reported after therapeutic doses and overdosage of second generation antihistamines, such terfenadine and astemizol. Diphenhydramine (DPHM), a first generation H1 antagonist, is the most frequently used antihistaminic drug. Despite its widespread use, there are no data about cardiac action and electrocardiographic consequences of DPHM overdose. The 12-lead electrocardiograms of 126 patients (mean age 26 +/- 11 years) who had DPHM overdose were evaluated. The ingestion of large doses of DPHM (in majority of cases the dose was >500 mg) was primarily suicidal. Repolarization duration, dispersion, and morphology were evaluated in DPHM overdose patients and compared with those of healthy subjects. Mean heart rate of DPHM overdose patients was 103 +/- 25 beats/min. The QTc duration was significantly longer (453 +/- 43 vs 416 +/- 35 ms, respectively, p <0.001) and mean T-wave amplitude significantly lower (0.20 +/- 0.10 vs 0.33 +/- 0.15 mV, respectively, p <0.001) in DPHM-overdose patients than in control subjects. Dispersion of repolarization was significantly lower in DPHM-overdose patients than in control subjects (42 +/- 25 vs 52 +/- 21 ms, respectively; p = 0.003). None of the DPHM-overdose patients experienced torsades de pointes. In conclusion, DPHM overdose is associated with a significant increase in heart rate and a significant but moderate QTc prolongation. None of the studied patients, including those who had apparent QTc prolongation, experienced torsades de pointes ventricular tachycardia.

The HARMONY Trial: Combined Ranolazine and Dronedarone in the Management of Paroxysmal Atrial Fibrillation: Mechanistic and Therapeutic Synergism

Background—Atrial fibrillation (AF) requires arrhythmogenic changes in atrial ion channels/receptors and usually altered atrial structure. AF is commonly treated with antiarrhythmic drugs; the most effective block many ion channels/receptors. Modest efficacy, intolerance, and safety concerns limit current antiarrhythmic drugs. We hypothesized that combining agents with multiple anti-AF mechanisms at reduced individual drug doses might produce synergistic efficacy plus better tolerance/safety. Methods and Results—HARMONY tested midrange ranolazine (750 mg BID) combined with 2 reduced dronedarone doses (150 mg BID and 225 mg BID; chosen to reduce dronedarone’s negative inotropic effect—see text below) over 12 weeks in 134 patients with paroxysmal AF and implanted pacemakers where AF burden (AFB) could be continuously assessed. Patients were randomized double-blind to placebo, ranolazine alone (750 mg BID), dronedarone alone (225 mg BID), or one of the combinations. Neither placebo nor either drugs alone significantly reduced AFB. Conversely, ranolazine 750 mg BID/dronedarone 225 mg BID reduced AFB by 59% versus placebo (P=0.008), whereas ranolazine 750 mg BID/dronedarone 150 mg BID reduced AFB by 43% (P=0.072). Both combinations were well tolerated. Conclusions—HARMONY showed synergistic AFB reduction by moderate dose ranolazine plus reduced dose dronedarone, with good tolerance/safety, in the population enrolled. Clinical Trial Registration—ClinicalTrials.gov; Unique identifier: NCT01522651.

Time-dependent risk of Fidelis lead failure.

The Medtronic Sprint Fidelis leads (models 6930, 6931, 6948, 6949) are 6.6-F bipolar high-voltage implantable cardioverter-defibrillator electrodes that were first introduced in September 2004. In October 2007, Fidelis leads were removed from the market. We sought to determine the time-dependent hazard of the Fidelis failure rate to date. A retrospective chart review was conducted in all patients who underwent implantation of a Sprint Fidelis lead (426 leads) at our center. We primarily implanted models 6931 and 6949. With 1,056 years of combined follow-up (average 2.3 +/- 1), 38 of 426 (8.92%) Sprint Fidelis leads failed (3.6%/year). The hazard of fracture increased exponentially over time by a power of 2.13 (95% confidence interval [CI] 1.98 to 2.27, p <0.001) and the 3-year survival was 90.8% (95% CI 87.4 to 94.3). If a Fidelis lead was functioning normally at 1 year, the chance it would survive another year was 97.4% (95% CI 95.7 to 99.1); if functioning at 2 years, the chance of surviving another year was 94.7% (95% CI 91.8 to 97.7); and if functioning at 3 years, the chance of surviving 1 more year was 86.7% (95% CI 78.8 to 95.5). Other commonly used implantable cardioverter-defibrillator leads showed no evidence of increased failure rates. In conclusion, to date, the hazard of Fidelis lead fracture is increasing exponentially with time and, based on our data, occurring at a higher rate than the latest manufacturers performance update. Further accumulative data are needed because it remains unknown if the fracture rate will level off or continue to increase.

Asthma and the risk of cardiac events in the long QT syndrome

While acquiring data for the International Long QT Syndrome Registry, we noticed that a number of patients referred for long QT syndrome (LQTS) were affected by asthma. The effect of asthma comorbidity on clinical course of LQTS has not been studied. This study aimed to evaluate the prevalence of asthma in patients with LQTS, determine the influence of asthma comorbidity on outcome of LQTS patients, and to investigate the confounding effects of beta mimetics and beta blockers on the occurrence of cardiac events in asthmatic patients. The influence of asthma on risk of cardiac events (syncope, aborted cardiac arrest, or LQTS death) was evaluated after accounting for age, gender, QTc, and RR interval duration, beta-blocker and beta-mimetic use. Asthma was identified in 226 (5.2%) of 4,310 studied LQTS family members. Longer QTc duration was associated with higher incidence of asthma (p <0.001). Asthma was independently associated with significantly increased risk of cardiac events in affected LQTS patients (hazard ratio 1.32; p = 0.048) and in borderline-affected family members (hazard ratio 2.08; p = 0.004) after adjustment for QTc, RR interval, and gender. An increased risk of cardiac events in asthmatic patients observed before beta-blocker therapy was reduced after initiation of treatment with beta blockers. In conclusion, the occurrence of asthma in LQTS patients increases with QTc duration. Asthma comorbidity in LQTS patients is associated with an increased risk of cardiac events. The asthma-associated increase in the risk of LQTS-related cardiac events is diminished after initiation of beta-blocker therapy, suggesting a possible role of beta-receptor modulation underlying asthma-LQTS association.

Impact of the right ventricular lead position on clinical outcome and on the incidence of ventricular tachyarrhythmias in patients with CRT-D

BACKGROUND Data on the impact of right ventricular (RV) lead location on clinical outcome and ventricular tachyarrhythmias in cardiac resynchronization therapy with defibrillator (CRT-D) patients are limited. OBJECTIVE To evaluate the impact of different RV lead locations on clinical outcome in CRT-D patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy trial. METHODS We investigated 742 of 1089 CRT-D patients (68%) with adjudicated RV lead location enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy trial to evaluate the impact of RV lead location on cardiac events. The primary end point was heart failure or death; secondary end points included ventricular tachycardia (VT), ventricular fibrillation (VF), or death and VT or VF alone. RESULTS Eighty-six patients had the RV lead positioned at the RV septal or right ventricular outflow tract region, combined as nonapical RV group, and 656 patients had apical RV lead location. There was no difference in the primary end point in patients with nonapical RV lead location versus those with apical RV lead location (hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.54-1.80; P = .983). Echocardiographic response to CRT-D was comparable across RV lead location groups (P > .05 for left ventricular end-diastolic volume, left ventricular end-systolic volume, and left atrial volume percent change). However, nonapical RV lead location was associated with significantly higher risk of VT/VF/death (HR 2.45; 95% CI 1.36-4.41; P = .003) and VT/VF alone (HR 2.52; 95% CI 1.36-4.65; P = .002), predominantly in the first year after device implantation. Results were consistent in patients with left bundle branch block. CONCLUSIONS In CRT-D patients, there is no benefit of nonapical RV lead location in clinical outcome or echocardiographic response. Moreover, nonapical RV lead location is associated with an increased risk of ventricular tachyarrhythmias, particularly in the first year after device implantation.

Gene‐Specific Therapy for Long QT Syndrome

Background: One form of the hereditary long QT syndrome (LQT‐3) has recently been shown to be caused by the SCN5A mutation of the human cardiac sodium channel. Cellular studies have suggested that type lb antiarrhythmics may be potentially therapeutic via preferential blockade of the resulting abnormal late inward sodium current. To test this hypothesis, we implemented a pilot study to evaluate the potential for long‐term, gene‐specific therapy in patients with this disease.

Ambulatory ECG Monitoring in Atrial Fibrillation Management

Ambulatory ECG monitoring technology has rapidly evolved over the last few decades and has been shown to identify life-threatening and non-life threatening arrhythmias and provide actionable data to guide clinical decision making. Atrial fibrillation episodes can often be asymptomatic, even after catheter ablation for atrial fibrillation, creating a disconnect between symptoms and actual arrhythmia burden which may alter clinical management. In this review, we aim to provide a comprehensive overview of invasive and non-invasive ECG monitoring strategies in patients with atrial fibrillation, with a special focus on the diagnosis of atrial fibrillation, and on follow-up of patients after catheter ablation for atrial fibrillation ablation.