A Dual-Chamber Leadless Pacemaker.

BACKGROUND: Single-chamber ventricular leadless pacemakers do not support atrial pacing or consistent atrioventricular synchrony. A dual-chamber leadless pacemaker system consisting of two devices implanted percutaneously, one in the right atrium and one in the right ventricle, would make leadless pacemaker therapy a treatment option for a wider range of indications. METHODS: We conducted a prospective, multicenter, single-group study to evaluate the safety and performance of a dual-chamber leadless pacemaker system. Patients with a conventional indication for dual-chamber pacing were eligible for participation. The primary safety end point was freedom from complications (i.e., device- or procedure-related serious adverse events) at 90 days. The first primary performance end point was a combination of adequate atrial capture threshold and sensing amplitude at 3 months. The second primary performance end point was at least 70% atrioventricular synchrony at 3 months while the patient was sitting. RESULTS: Among the 300 patients enrolled, 190 (63.3%) had sinus-node dysfunction and 100 (33.3%) had atrioventricular block as the primary pacing indication. The implantation procedure was successful (i.e., two functioning leadless pacemakers were implanted and had established implant-to-implant communication) in 295 patients (98.3%). A total of 35 device- or procedure-related serious adverse events occurred in 29 patients. The primary safety end point was met in 271 patients (90.3%; 95% confidence interval [CI], 87.0 to 93.7), which exceeded the performance goal of 78% (P<0.001). The first primary performance end point was met in 90.2% of the patients (95% CI, 86.8 to 93.6), which exceeded the performance goal of 82.5% (P<0.001). The mean (±SD) atrial capture threshold was 0.82±0.70 V, and the mean P-wave amplitude was 3.58±1.88 mV. Of the 21 patients (7%) with a P-wave amplitude of less than 1.0 mV, none required device revision for inadequate sensing. At least 70% atrioventricular synchrony was achieved in 97.3% of the patients (95% CI, 95.4 to 99.3), which exceeded the performance goal of 83% (P<0.001). CONCLUSIONS: The dual-chamber leadless pacemaker system met the primary safety end point and provided atrial pacing and reliable atrioventricular synchrony for 3 months after implantation. (Funded by Abbott Medical; Aveir DR i2i ClinicalTrials.gov number, NCT05252702.).

Evaluating Cardiac Lead Safety Using Observational, Real-World Data: EP PASSION Proof-of-Concept Study.

BACKGROUND: Traditional post-approval study (PAS) designs have been accepted by regulatory authorities to fulfill post-marketing requirements for cardiac leads but they have several limitations. OBJECTIVES: The authors conducted a proof-of-concept study of alternative methods that utilize real-world data (RWD) to evaluate lead safety in large patient populations. METHODS: Abbott patient device databases were linked with Medicare Fee-For-Service (FFS) claims to identify lead complications among patients implanted with Abbott Optisure™ lead. A 1:1 comparison between the PAS method and RWD method of detecting mechanical lead-related complication events was conducted in 444 PAS subjects who were enrolled in Medicare FFS. Agreement between methods was evaluated using McNemar's test and Cohen's kappa. Survival free from complications at 3 years was compared between the PAS and RWD cohorts using an equivalence acceptance criterion of ±2.5%. RESULTS: There were 1,171 PAS patients and 5,804 Medicare FFS patients who received an Optisure™ lead between August 27, 2014 - June 14, 2016. Patients were followed through December 31, 2018. Complete agreement was found between PAS-reported and claims-detected complications (McNemar's p-value=1.00, Cohen's Kappa = 1.0). Survival free from complications at 3 years using the RWD method was 98.4% (95% CL: 98.0%-98.7%), which was within the acceptable range of the PAS 98.4% (95% CL: 97.6%-99.0%). CONCLUSION: These results show a close agreement between RWD-detected and PAS-reported lead complication rates, which highlight the potential benefits of RWD-based methods to enhance the generation of clinical evidence for lead safety.

Implantation success and infection in cardiovascular implantable electronic device procedures utilizing an antibacterial envelope.

BACKGROUND: Cardiovascular implantable electronic device (CIED) infection rates are increasing faster than implantation rates. More effective antimicrobial prophylaxis may help reduce CIED infections and improve clinical outcomes. The AIGIS(Rx)(®) antibacterial envelope is a polymer mesh implanted in the generator pocket with the CIED. After implantation it releases two antibiotics, minocycline and rifampin, that have been shown to reduce infections associated with other medical devices. The purpose of this retrospective cohort study is to determine the rate of CIED implantation success and CIED infection in procedures utilizing the antibacterial envelope. METHODS: This study enrolled consecutive CIED procedures utilizing the antibacterial envelope at 10 US academic, community, and Veterans Affairs medical centers. Procedures following an explantation for a prior CIED infection or off-label use of the antibacterial envelope were excluded. RESULTS: The 624 eligible procedures (age 70 ± 13 years, 68.1% men, 27.2% renal insufficiency, 35.4% oral anticoagulant use, 67.8% replacement/revision procedures) utilized pacemakers (35%), implantable cardioverter-defibrillators (ICD)(29%), and cardiac resynchronization therapy with defibrillator devices (CRT-D)(36%). Nearly half of the patients (49%) had at least three predefined risk factors for CIED infection. CIED implantation was successful in 621 procedures (99.5%[95% confidence interval (CI) 98.8-99.9]). There were three major infections (0.48%[95%CI 0.17-1.40]) after 1.9 ± 2.4 months follow-up. The infections followed one ICD revision and two CRT-D replacements. There were seven deaths; none was a result of the antibacterial envelope or the CIED procedure. CONCLUSIONS: CIED procedures that utilized an antibacterial envelope had a high rate of CIED implantation success (>99%). Although the follow-up to date is short, there was also a low rate of infection (<0.50%) in this population at high risk for CIED infection.

Renal insufficiency predicts the time to first appropriate defibrillator shock.

BACKGROUND: Indications for implantable cardioverter defibrillator (ICD) implantation are expanding, but many primary and secondary ICD trials have excluded patients with advanced renal insufficiency. We investigated the effect of renal function on the incidence and time to first appropriate ICD shock. METHOD: We analyzed data from all new ICD implantations at a tertiary care center from July 2001 to December 2002. RESULTS: During a mean follow-up time of 445 +/- 285 days, 29 (13%) of 230 patients (age 63 +/- 14 years, 79% men, 77% white, 75% coronary artery disease, left ventricular ejection fraction 0.28 +/- 0.14) received 41 appropriate shocks. Patients were divided into tertiles according to their serum creatinine level. The 1-year incidence of appropriate ICD shock was 3.8%, 10.8%, and 22.7% in the first, second, and third tertiles, respectively (P = .003). Using the same cut off values of serum creatinine, the 1-year incidence of appropriate ICD therapy (shock and antitachycardia pacing) was 8.8%, 20.8%, and 26.3% (P = .02). After correcting for age, sex, race, left ventricular ejection fraction, indication for ICD implantation, and use of beta-blockers in a Cox regression model, serum creatinine was still an independent predictor of the time to first appropriate ICD shock (hazard ratio 6.0 for the third compared with the first tertile, P = .001). CONCLUSION: Renal insufficiency is a strong predictor of appropriate ICD shocks. Defibrillator therapy should therefore not be withheld based on the presence of this comorbidity. The mechanisms underlying the relationship between renal function and ventricular arrhythmias deserve further investigation.

Implantable cardioverter-defibrillators for secondary prevention: is it worth it in the elderly?

Aging is associated with structural alterations in the heart that predispose the elderly to life-threatening ventricular arrhythmias. The majority of sudden cardiac deaths occur in people aged 65 and older. As the proportion of elderly in our population continues to grow, a greater number of elderly patients with malignant ventricular arrhythmias will require appropriate medical management. Clinical outcome trials have demonstrated that implantable cardioverter-defibrillators (ICDs) improve overall survival compared with pharmacologic therapy when used for the secondary prevention of cardiac arrest. Despite proven efficacy, physicians may be reluctant to implant a defibrillator in an older patient. This review summarizes the data pertaining to the use of defibrillators for secondary prevention in the elderly. ICD use for secondary prevention reduces all-cause mortality and appears to be economically advantageous in an older patient population. Currently, there is no convincing data to suggest that ICD therapy should be withheld from a patient based on age alone.

Utilization of implantable cardioverter-defibrillators in survivors of cardiac arrest in the United States from 1996 to 2001.

OBJECTIVES: We analyzed the incidence of implantable cardioverter-defibrillator (ICD) therapy in survivors of cardiac arrest (CA) in the U.S. from 1996 through 2001. BACKGROUND: Cardiac arrest is a class I indication for ICD therapy. The current patterns of ICD utilization in survivors of CA have not been fully examined. METHODS: We searched a representative sample of all hospital discharges for patients admitted with the primary diagnosis of CA who survived to hospital discharge. Patients with a concomitant diagnosis of acute myocardial infarction or previous ICD in situ were excluded. RESULTS: From 1996 to 2001, 113,262 patients were admitted for CA. Of those, 63,745 (56.3%) did not survive to hospital discharge. Of the remaining 49,517 patients, 30.7% received an ICD before discharge, with a gradual increase in implantation rates from 1996 (23.6%) to 2001 (46.3%). Using logistic regression for the years 2000 and 2001, patients who were discharged without an ICD were older (odds ratio [OR] 0.93 for every 10-year increase in age, p < 0.001), more likely to be African American (OR 0.19, p < 0.001), and more likely to be admitted to a smaller hospital (OR 2.24 for each additional 100 beds, p < 0.001). These predictors were independent of other co-morbid illnesses. CONCLUSIONS: Although they are increasing, the rates of ICD therapy after CA remain very low. There are gross discrepancies by race. At a time when newer indications for ICD implantation are emerging, efforts should be focused on identifying the causes of this underutilization and discrepancies in survivors of CA.

Utility of echocardiographic radial strain imaging to quantify left ventricular dyssynchrony and predict acute response to cardiac resynchronization therapy.

Echocardiographic strain imaging was used to quantify radial mechanical dyssynchrony in 38 patients who underwent cardiac resynchronization therapy. Dyssynchrony, defined as the time difference of peak radial strain in the septum versus the posterior wall, was significantly greater in patients with acute hemodynamic responses, and changes in radial dyssynchrony correlated with changes in stroke volume. A > or =130-ms difference in septal versus posterior wall peak strain when combined with a favorable left ventricular lead position was strongly predictive of immediate improvement in stroke volume with resynchronization therapy (95% sensitivity, 88% specificity), regardless of electrocardiographic QRS duration.

New method for real-time discrimination and management of ventricular and supraventricular tachyarrhythmias applicable to patients with dual-chamber cardioverter-defibrillators.

In this study we describe a highly sensitive and specific method for discriminating between ventricular and supraventricular tachyarrhythmias based on the response to simultaneous atrial and ventricular antitachycardia pacing. This new method, which can terminate supraventricular tachycardias in >50% of patients, can be easily implemented in a new generation of dual-chamber defibrillators.

Epidemiology and determinants of outcome of admissions for atrial fibrillation in the United States from 1996 to 2001.

Despite numerous epidemiologic studies, few data exist on recent trends in admissions to United States hospitals of patients with atrial fibrillation (AF) as a primary diagnosis and on the determinants of outcome of these hospitalizations. In the present study, we investigated recent trends in the incidence of AF admissions to United States hospitals from 1996 to 2001 using a representative sample of all acute-care hospital admissions in the United States provided by the Centers for Disease Control, with special attention to the importance of age, gender, race, and other determinants of outcome, namely, in-hospital mortality.

Selected patients listed for cardiac transplantation may benefit from defibrillator implantation regardless of an established indication.

BACKGROUND: End-stage heart failure (HF) patients are at high risk of sudden cardiac death. This study evaluates the role of implantable cardiac defibrillators (ICDs) in HF patients awaiting cardiac transplantation. METHODS: We identified 194 consecutive patients (age 51 +/- 12 years) with New York Heart Association Class 3 or 4 HF (ejection fraction 22 +/- 9%) listed for cardiac transplantation, 35 of whom underwent ICD implantation. Of the implanted patients, 16 (Group A) had an established indication for ICD implantation (cardiac arrest, n = 10; sustained ventricular tachycardia [VT], n = 3; and positive electrophysiology study, n = 3). Nineteen patients (Group B) underwent ICD implantation for non-established indications (syncope with non-ischemic cardiomyopathy, n = 4; non-sustained VT, n = 15). There were no procedural complications from ICD implantation. RESULTS: During follow-up of 9.2 +/- 10.1 months, there were 3 deaths in the ICD groups (A and B), and 40 in the control group (8.6% vs 25.2%, p = 0.032). Five patients in Group A and 6 in Group B (31%) received appropriate ICD therapy. The number of therapies per patient and the time to the first shock were similar between Groups A and B. Four of 6 Group B patients on outpatient inotropic therapy (67%) received appropriate ICD therapy. CONCLUSIONS: Selected end-stage heart failure patients awaiting heart transplantation, including those without established ICD indications, are at high risk for malignant arrhythmias and may benefit from ICD implantation. Patients with ICD seem to have improved survival compared to those without ICD. Randomized prospective studies are needed to confirm these findings.

Simultaneous atrial and ventricular anti-tachycardia pacing as a novel method of rhythm discrimination.

OBJECTIVE: To evaluate a new discrimination algorithm for supraventricular (SVT) and ventricular (VT) tachycardias, based on the response to simultaneous (A+V) atrial (A) and ventricular (V) anti-tachycardia pacing (ATP). METHODS: Patients undergoing electrophysiological testing or dual-chamber implantable cardioverter-defibrillator (ICD) implantation were enrolled (N = 32) and underwent A+V ATP through a Marquis ICD with investigational software. If persisting after ATP, the rhythm was classified as VT if the first electrical event was sensed on the V channel and as an SVT otherwise. RESULTS: Arrhythmia sequences (N = 275; 53 VT; 222 SVT) were analyzed in 26 patients (age = 51 +/- 17 years, 13 men, LVEF = 0.49 +/- 0.14). In response to A+V ATP, 55% of SVT versus 41% of VT episodes were terminated (P = NS). Termination of VT but not of SVT was more likely with faster (50% at ATP/arrhythmia cycle length (CL) = 0.81 vs 8% at ATP/arrhythmia CL = 0.88, P = 0.02) but not with longer ATP bursts (P = NS). Of the 115 arrhythmias that persisted after A+V ATP, the algorithm correctly classified 24 of 24 VT (GEE-adjusted sensitivity = 100%) and 85 of 91 SVT (GEE-adjusted specificity = 93%). Proarrhythmia was noted after two A+V ATP, in the form of atrial fibrillation induction and VT acceleration. CONCLUSIONS: We describe a new algorithm that can discriminate between SVT and VT with a high sensitivity and specificity. This form of ATP can terminate 55% of SVT sequences. The performance of this new algorithm merits further testing in a large population of dual-chamber ICD patients.

Utility of echocardiographic tissue synchronization imaging to redirect left ventricular lead placement for improved cardiac resynchronization therapy.

An 80-year-old woman with severe symptomatic heart failure (ejection fraction of 13%), and left bundle branch block (QRS duration of 160 ms) underwent cardiac resynchronization therapy (CRT). She had significant baseline dyssynchrony with a septal to posterior wall delay of 160 ms by echocardiographic tissue synchronization imaging (TSI). Despite exhaustive efforts, a stable posterior-lateral coronary vein lead position could not be achieved with the standard percutaneous approach, resulting in anterior coronary vein lead placement. This resulted in no improvement in the patient's symptoms or ventricular function. Follow-up TSI revealed earlier activation of the anteroseptal site and worsened dyssynchrony with septal to posterior wall delay of now 290 ms. This information prompted surgical revision of the left ventricular (LV) lead position via limited thoracotomy and posterior-lateral epicardial lead implantation. Pacing at the new lead site resulted in a 30% increase in stroke volume and symptomatic improvement. TSI in this case redirected lead position in a clinical nonresponder, resulting in a favorable response to CRT.

Rhythm classification by correlation-waveform morphology analysis of atrial and ventricular electrogram signals.

We tested the use of correlation-waveform analysis (CWA) of atrial and ventricular electrograms (EGMs) to distinguish ventricular tachycardia (VT) from supraventricular tachycardia (SVT). Patients undergoing electrophysiologic testing were enrolled. EGMs recorded during induced tachycardias were compared with EGMs recorded during sinus and paced rhythms, taken as templates, by assigning a CWA percent-match (CPM) score. Twenty-two patients were studied: 15 men and 7 women (mean age 48 years); 16 with SVT and 6 with VT. Using a sinus-rhythm template, the atrial CPM scores for SVT and VT were 66%+/- 20% and 93%+/- 5%, respectively (P = 0.0034). With a CPM-score cutoff of 85%, the sensitivity for correctly identifying VT was 100% and the specificity for rejection of SVT was 80%. The corresponding ventricular-CPM scores for SVT and VT were 81%+/- 12% and 72%+/- 24%, respectively (P = 0.13, cutoff = 65%, sensitivity = 50%, and specificity = 90%). Using a ventricular template with atrial pacing, the ventricular-CPM scores for SVT and VT were 87%+/- 9% and 76%+/- 14%, respectively (P = 0.028, cutoff = 70%, sensitivity = 50%, and specificity = 93%). Atrial CWA matching is superior to ventricular CWA matching in discriminating between SVT and VT. CWA matching in both chambers could potentially achieve better discrimination.

Primary prevention of sudden cardiac death.

Sudden cardiac death (SCD) is the leading cause of death in the United States. Although SCD occurs most commonly in patients with established heart disease, SCD can also be the initial manifestation of cardiovascular disease. Efforts to reduce the incidence of SCD include aggressive treatment of heart disease and its risk factors with pharmacologic and nonpharmacologic strategies. Public health measures to improve the response to cardiac arrest, including dissemination of automated external defibrillators in the community, are extremely important. Implantation of implantable cardioverter defibrillators (ICDs) in patients at high risk of SCD improves survival in these patients. Clinical trials have identified patients with ischemic and nonischemic cardiomyopathy who may benefit from prophylactic ICD implantation.

Autonomic blockade unmasks maturational differences in rate-dependent atrioventricular nodal conduction and facilitation in the mouse.

INTRODUCTION: In large animals, rate-dependent AV nodal (AVN) properties of conduction are modulated by autonomic inputs. In this study, we investigated whether the properties of AVN conduction and facilitation are altered by autonomic blockade in the mouse and whether this effect is age dependent. METHODS AND RESULTS: Young (age 4-6 weeks; n = 11) and adult (age 8-9 months; n = 11) female mice underwent in vivo electrophysiologic testing, before and after autonomic blockade. After autonomic blockade, the adult mice had significantly longer AVN effective refractory period (AVNERP; 67 +/- 14 msec vs 56 +/- 4 msec, P = 0.05) and functional refractory period (AVNFRP; 81 +/- 10 msec vs 72 +/- 4 msec, P = 0.05). With autonomic blockade, the increase from baseline of AVN Wenckebach cycle length (deltaAVW; 1.8 +/- 8.1 msec vs 8.8 +/- 3.3 msec, P = 0.04), as well as of AVNERP (deltaAVNERP; 3.5 +/- 3.5 msec vs 21.4 +/- 12.6 msec, P = 0.002) and AVNFRP (deltaAVNFRP; 2.3 +/- 3.2 msec vs 12.8 +/- 9.0 msec, P = 0.008), was significantly larger in adult than in young mice. Compared with young mice, adult mice were less likely to exhibit AVN facilitation (44% vs 90%, P = 0.03) and had smaller maximal shortening of AVN conduction times after the "test beat" for any coupling of the "facilitating beat" (4 +/- 4 msec vs 7 +/- 3 msec, P = 0.05). CONCLUSION: Complete autonomic blockade significantly increases AVN conduction times and refractory periods in adult but not in young mice. Adult mice also exhibit less AVN facilitation. Our results confirm that, like in larger animals, rate-dependent murine AVN properties of conduction are under autonomic regulation. Adult mice have higher sympathetic AVN inputs at baseline, leading to slower conduction after autonomic blockade.