Ventricular arrhythmias and sudden cardiac death.

Management strategies for ventricular arrhythmias are guided by the risk of sudden death and severity of symptoms. Patients with a substantial risk of sudden death usually need an implantable cardioverter defibrillator (ICD). Although ICDs effectively end most episodes of ventricular tachycardia or ventricular fibrillation and decrease mortality in specific populations of patients, they have inherent risks and limitations. Generally, antiarrhythmic drugs do not provide sufficient protection from sudden death, but do have a role in reducing arrhythmias that cause symptoms. Catheter ablation is likewise important for reducing the frequency of spontaneous arrhythmias and is curative for some patients, usually those with idiopathic arrhythmias and no heart disease. Arrhythmia surgery is now infrequent, offered by only a few specialised centres for refractory arrhythmias. Advances in understanding of genetic arrhythmia syndromes and in technology for mapping and ablation of ventricular arrhythmias, and enhanced algorithms in implantable devices for rhythm management, have contributed to improved outcomes.

Analysis of ventricular activation using surface electrocardiography to predict left ventricular reverse volumetric remodeling during cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy for heart failure with left bundle branch block reduces left ventricular (LV) conduction delay, contraction asynchrony, and LV end-systolic volume ("reverse remodeling"). Up to one third of patients do not improve, and the electric requirements for reverse remodeling are unclear. We hypothesized that reverse remodeling is predicted by the left bundle branch block ventricular activation sequence, the paced activation sequence, and interactions between these 2 conditions. METHODS AND RESULTS: Twelve-lead ECGs during left bundle branch block and cardiac resynchronization therapy were analyzed in 202 consecutive patients (New York Heart Association class III to IV heart failure, ejection fraction < or =35%) for predictors of reverse remodeling (> or =10% reduction in end-systolic volume) at 6 months. Greater longest baseline LV activation time predicted increased odds of reverse remodeling (odds ratio [confidence interval]=1.30 [1.11, 1.52] per 10-ms increase), whereas higher QRS scores for LV scar predicted reduced reverse remodeling (odds ratio [confidence interval]=0.49 [0.27, 0.88] for each 1-point increase from 0 to 4; 0.92 [0.83, 1.01] for each 1-point increase >4). After cardiac resynchronization therapy, increasing R amplitudes in leads V(1) through V(2) (odds ratio [confidence interval]=2.76 [1.01, 7.51] for each 1x increase over [baseline Rx4.5]) and left-->right frontal axis shift (odds ratio [confidence interval]=2.00 [0.99, 4.02]), indicators of ventricular activation wavefront fusion, were positive predictors of reverse remodeling. Predicted probability of reverse remodeling ranged from <20% for patients with adverse predictors to 99% for those with positive predictors. CONCLUSIONS: Ventricular activation with the use of the ECG accurately predicts LV reverse remodeling during cardiac resynchronization therapy. Greater longest baseline LV activation time and smaller scar volume combined with wavefront fusion on the paced ECG, anticipate higher probability of reverse remodeling.

Non-invasive Thoracic Impedance Changes in COVID-19 Pulmonary Infection.

Graphical abstract.

Minimizing ventricular pacing to reduce atrial fibrillation in sinus-node disease.

BACKGROUND: Conventional dual-chamber pacing maintains atrioventricular synchrony but results in high percentages of ventricular pacing, which causes ventricular desynchronization and has been linked to an increased risk of atrial fibrillation in patients with sinus-node disease. METHODS: We randomly assigned 1065 patients with sinus-node disease, intact atrioventricular conduction, and a normal QRS interval to receive conventional dual-chamber pacing (535 patients) or dual-chamber minimal ventricular pacing with the use of new pacemaker features designed to promote atrioventricular conduction, preserve ventricular conduction, and prevent ventricular desynchronization (530 patients). The primary end point was time to persistent atrial fibrillation. RESULTS: The mean (+/-SD) follow-up period was 1.7+/-1.0 years when the trial was stopped because it had met the primary end point. The median percentage of ventricular beats that were paced was lower in dual-chamber minimal ventricular pacing than in conventional dual-chamber pacing (9.1% vs. 99.0%, P<0.001), whereas the percentage of atrial beats that were paced was similar in the two groups (71.4% vs. 70.4%, P=0.96). Persistent atrial fibrillation developed in 110 patients, 68 (12.7%) in the group assigned to conventional dual-chamber pacing and 42 (7.9%) in the group assigned to dual-chamber minimal ventricular pacing. The hazard ratio for development of persistent atrial fibrillation in patients with dual-chamber minimal ventricular pacing as compared with those with conventional dual-chamber pacing was 0.60 (95% confidence interval, 0.41 to 0.88; P=0.009), indicating a 40% reduction in relative risk. The absolute reduction in risk was 4.8%. The mortality rate was similar in the two groups (4.9% in the group receiving dual-chamber minimal ventricular pacing vs. 5.4% in the group receiving conventional dual-chamber pacing, P=0.54). CONCLUSIONS: Dual-chamber minimal ventricular pacing, as compared with conventional dual-chamber pacing, prevents ventricular desynchronization and moderately reduces the risk of persistent atrial fibrillation in patients with sinus-node disease. (ClinicalTrials.gov number, NCT00284830 [ClinicalTrials.gov].).

Reduced ejection fraction, sudden cardiac death, and heart failure death in the mode selection trial (MOST): implications for device selection in elderly patients with sinus node disease.

UNLABELLED: Sudden Cardiac Death in Elderly Pacemaker Patients. BACKGROUND: The purpose of this study was to describe the incidence and predictors of sudden cardiac death (SCD) and heart failure (HF) death, and coexisting indications for ICDs and CRT, in patients with sinus node disease (SND) treated with pacemakers. METHODS AND RESULTS: Baseline variables were used to predict SCD and HF death among 1,135 patients in the Mode Selection Trial, a 6-year trial of pacing mode in SND. There were 73 deaths among 177 patients with EF or= 50%. SCD accounted for 21.9%, 23.9%, and 14.3% of deaths with EF or= 50%. HF deaths accounted for 23.3%, 19.6%, and 3.4% of deaths with EF or= 50%. EF or= 120 ms. However, >40% died within 33 months (4-year noncardiac death rate approximately 22%). CONCLUSIONS: Reduced EF predicts SCD and HF death in SND treated with pacemakers. SCD rates among patients with EF

Severe atrioventricular decoupling, uncoupling, and ventriculoatrial coupling during enhanced atrial pacing: incidence, mechanisms, and implications for minimizing right ventricular pacing in ICD patients.

UNLABELLED: AV Decoupling During Enhanced AAIR Pacing. BACKGROUND: Enhanced AAI/R pacing minimizes right ventricular pacing but may permit or induce AV decoupling (AV-DC) due to unrestricted AV intervals (AVIs). The purpose of this study was to characterize and quantify AVI behavior in a randomized trial of enhanced AAI/R pacing in ICD patients. METHODS: One hundred twenty-one patients in the Marquis ICD MVPtrade mark Study, a randomized 1-month crossover comparison of cumulative% ventricular pacing (Cum%VP) in enhanced AAIR (MVP) vs DDD/R, were analyzed. AV-DC was defined as >or=40% AVIs >300 ms; VA coupling (VA-C) was defined as%V-atrial pace (AP) intervals <300 ms. Dynamic AVI behavior and increases in Cum%VP due to AV block (AV uncoupling, AV-UC) were characterized using Holters with real-time ICD telemetry. RESULTS: AV-DC occurred in 17 (14%) of patients. Baseline PR, amiodarone, nighttime, lower rate >60 beats/min, rate response, and Cum%AP were associated with longer AVIs. Logistic regression identified baseline PR (odds ratio [OR]= 1.024, 95% confidence interval [CI] 1.007-1.042; P = 0.005), and Cum%AP (OR = 1.089, 95% CI 1.027-1.154; P = 0.004) as predictors of AV-DC. AV-DC was associated with approximately 10-fold increases in both Cum%VP (13.6 +/- 28.3% vs 1.2 +/- 3.9%; P = 0.023) due to transient AV-UC) and VA-C (6.0 +/- 17.5% vs 0.5 +/- 1.2%, P = 0.028). AV coupling (<40% AVIs >300 ms) was preserved in 104 (86%) patients. CONCLUSIONS: AV-DC, VA-C, and AV-UC may be worsened or induced by enhanced AAI/R pacing. Conservative programming of lower rate and rate response should reduce the risk of AV-DC by reducing Cum%AP.

Heart failure during cardiac pacing.

BACKGROUND: Right ventricular apical (RVA) pacing creates abnormal left ventricular contraction, hypertrophy, and reduced pump function. The adverse effects of ventricular desynchronization may explain the association of RVA pacing with an increased risk of heart failure hospitalization (HFH) in clinical trials. METHODS AND RESULTS: Baseline and postimplantation variables were used to predict HFH in the Mode Selection Trial, a 2010-patient, 6-year trial of dual-chamber (DDDR) versus ventricular (VVIR) pacing in sinus node dysfunction. A Cox model showed that New York Heart Association (NYHA) class at baseline and follow-up predicted HFH (hazard ratio [HR], 3.99; 95% confidence interval [CI], 2.74-5.79 for NYHA class III/IV and HR, 2.17; 95% CI, 1.54-3.04 for NYHA class II versus class I); other predictors were heart failure (HR, 2.30; 95% CI, 1.70-3.11), atrioventricular (AV) block (HR, 1.48; 95% CI, 1.11-1.97), and myocardial infarction (MI)(HR, 1.37; 95% CI, 1.00-1.86). Postimplantation predictors were VVIR cumulative percent ventricular pacing (Cum%VP) >80 (HR, 3.58; 95% CI, 1.72-7.45), DDDR Cum%VP >40 or VVIR Cum%VP < or =80 (HR, 1.81; 95% CI, 0.94-3.50) versus DDDR Cum%VP < or =40; whether QRS duration (QRSd) was paced or spontaneous (HR, 2.21; 95% CI, 1.39-3.54; spontaneous versus paced); and drugs for atrial fibrillation (HR, 1.60; 95% CI, 1.19-2.15). Low baseline ejection fraction (EF) and postimplantation RVA-paced or spontaneous QRSd predicted HFH; the increased risk with QRSd was steeper for normal versus low EF (HR, 1.18; 95% CI, 1.11-1.27; versus HR, 1.08; 95% CI, 1.01-1.15; for a 10-ms increase); at a QRSd of approximately 200 ms, normal- and low-EF patients had equivalent risk. HFH risk nearly doubled when VVIR Cum%VP was < or =80 or DDDR Cum%VP was >40 versus DDDR Cum%VP < or =40 and was additive with other risk factors. CONCLUSIONS: Differences in HFH risk can be explained by interactions between substrate (atrial fibrillation, AV conduction, heart failure, MI, EF) and pacing promoters (ventricular desynchronization-paced QRSd and Cum%VP, and AV desynchronization-pacing mode). Management of RVA pacing is important for reducing the risk of HFH, particularly among patients with low EF and heart failure.

Ventricular pacing or dual-chamber pacing for sinus-node dysfunction.

BACKGROUND: Dual-chamber (atrioventricular) and single-chamber (ventricular) pacing are alternative treatment approaches for sinus-node dysfunction that causes clinically significant bradycardia. However, it is unknown which type of pacing results in the better outcome. METHODS: We randomly assigned a total of 2010 patients with sinus-node dysfunction to dual-chamber pacing (1014 patients) or ventricular pacing (996 patients) and followed them for a median of 33.1 months. The primary end point was death from any cause or nonfatal stroke. Secondary end points included the composite of death, stroke, or hospitalization for heart failure; atrial fibrillation; heart-failure score; the pacemaker syndrome; and the quality of life. RESULTS: The incidence of the primary end point did not differ significantly between the dual-chamber group (21.5 percent) and the ventricular-paced group (23.0 percent, P=0.48). In patients assigned to dual-chamber pacing, the risk of atrial fibrillation was lower (hazard ratio, 0.79; 95 percent confidence interval, 0.66 to 0.94; P=0.008), and heart-failure scores were better (P<0.001). The differences in the rates of hospitalization for heart failure and of death, stroke, or hospitalization for heart failure were not significant in unadjusted analyses but became marginally significant in adjusted analyses. Dual-chamber pacing resulted in a small but measurable increase in the quality of life, as compared with ventricular pacing. CONCLUSIONS: In sinus-node dysfunction, dual-chamber pacing does not improve stroke-free survival, as compared with ventricular pacing. However, dual-chamber pacing reduces the risk of atrial fibrillation, reduces signs and symptoms of heart failure, and slightly improves the quality of life. Overall, dual-chamber pacing offers significant improvement as compared with ventricular pacing.

Impact of rate-modulated pacing on quality of life and exercise capacity--evidence from the Advanced Elements of Pacing Randomized Controlled Trial (ADEPT).

BACKGROUND: Ninety-nine percent of pacemakers implanted in the United States include an option for rate modulation. OBJECTIVE: The purpose of this study was to determine whether dual-chamber rate-modulated pacing, when compared with dual-chamber pacing alone, improved quality of life. METHODS: This was a single-blind randomized controlled trial comparing dual-chamber with rate-modulated dual-chamber pacing. Patients were enrolled between January 12, 2000, and January 10, 2002, with 1-year follow-up ending December 19, 2002. The study was a U.S. multicenter trial, with 95 sites participating. All patients received a rate modulation-capable dual-chamber pacemaker for standard indications. Patients were screened with an exercise test (Chronotropic Assessment Exercise Protocol) 1 month later. One thousand two hundred seventy-three patients were enrolled; 401 proved ineligible, and 872 (68%) made up the randomized patient cohort. Randomized patients had a mean age of 71 years, 64% were men, and 64% had sinus node dysfunction. Randomization was in a factorial design to (1) dual-chamber rate-modulated pacing versus dual-chamber pacing and (2) automatic mode switching versus no automatic mode switching. The present report is limited to the comparison of rate modulation with no rate modulation (DDDR vs. DDD). The primary endpoint was the score on the Specific Activity Scale, an activity-based cardiovascular disease-specific instrument at 1 year. Secondary endpoints included 6-month treadmill time and additional cardiovascular disease-specific, and generic health-related quality-of-life instruments at 1 year. RESULTS: At 6 months, patients with rate modulation had a higher peak exercise heart rate (rate modulation 113.3 +/- 19.6, no rate modulation 101.1 +/- 21.1; P <.0001). Total exercise time was not different between groups. At 1 year, there were no significant differences between groups with respect to Specific Activity Scale or the secondary quality-of-life endpoints. CONCLUSIONS: We conclude that rate modulation is ineffective in improving the functional status or quality of life of patients with a bradycardia indication for dual-chamber pacing.

Association of prolonged QRS duration with death in a clinical trial of pacemaker therapy for sinus node dysfunction.

BACKGROUND: Prolonged QRS duration (QRSd) is an important prognostic indicator for death and heart failure hospitalization in patients with systolic heart failure. The relationship of baseline QRSd to death and heart failure hospitalization in patients with sinus node dysfunction who require pacemaker therapy is unknown. METHODS AND RESULTS: Baseline QRSd from 12-lead ECGs before pacemaker implantation were analyzed in the Mode Selection Trial (MOST), a 6-year, 2010-patient randomized trial of dual-chamber versus ventricular pacing in sinus node dysfunction. Baseline QRSd was > or =120 ms in 23.4% of patients and was associated with older age, lower ejection fraction, cardiomyopathy, and prior heart failure. Adjusted Cox models demonstrated baseline QRSd > or =120 ms was a strong independent predictor of death (hazard ratio [95% CI] 1.35 [1.07, 1.70], P=0.010) but not heart failure hospitalization. The risk of death increased with increased QRSd from 60 to 120 ms (P=0.002 and hazard ratio [95% CI] 1.14 [1.05, 1.23] for 10-ms increase in this range) after adjustment for other death predictors. CONCLUSIONS: Baseline QRSd > or =120 ms was associated with increased risk of death during pacemaker therapy for sinus node dysfunction.

Appropriate and inappropriate ventricular therapies, quality of life, and mortality among primary and secondary prevention implantable cardioverter defibrillator patients: results from the Pacing Fast VT REduces Shock ThErapies (PainFREE Rx II) trial.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) reduce mortality in primary and secondary prevention. Quality of life, mortality, appropriate therapies for specific ventricular rhythms, and inappropriate therapies for supraventricular tachycardia (SVT) were compared among 582 patients (primary prevention=248; secondary prevention=334) in PainFREE Rx II, a 634-patient prospective, randomized study of antitachycardia pacing or shocks for fast ventricular tachycardia (FVT). METHODS AND RESULTS: ICDs were programmed identically with 3 zones (ventricular tachycardia [VT] <188 bpm; FVT=188 to 250 bpm; ventricular fibrillation [VF] >250 bpm) but randomized to antitachycardia pacing or shock as initial therapy for FVT. All treated episodes with electrograms were adjudicated. Primary prevention patients had lower ejection fractions and more coronary artery disease. beta-Blocker use, antiarrhythmic drug use, and follow-up duration were similar. Over 11+/-3 months, 1563 treated episodes were classified as VT (n=740), FVT (n=350), VF (n=77), and SVT (n=396). The distribution of VT, FVT, and VF was not different between primary and secondary prevention patients (respectively, VT 52% versus 54%, FVT 35% versus 35%, and VF 14% versus 10%). More secondary prevention patients had appropriate therapies (26% versus 18%, P=0.02), but among these patients, the median number of episodes per patient was similar. Inappropriate therapies occurred in 15% of both groups and accounted for similar proportions of all detected and treated episodes (46% in primary prevention patients versus 34% in secondary prevention patients, P=0.09). Quality of life improved modestly in both groups, and mortality was similar. CONCLUSIONS: Primary prevention patients are slightly less likely to have appropriate therapies than secondary prevention patients, but episode density is similar among patients with appropriate therapies. SVT resulted in more than one third of therapies in both groups, but quality of life and mortality were similar.

QRS duration does not predict occurrence of ventricular tachyarrhythmias in patients with implanted cardioverter-defibrillators.

OBJECTIVES: The aim of this study was to determine whether QRS duration (QRSd) correlates with occurrence of ventricular arrhythmia in patients with coronary disease (CAD) receiving implantable cardioverter-defibrillators (ICDs). BACKGROUND: A QRSd measured on a standard electrocardiograph (ECG) correlates with total mortality risk in CAD patients at high risk for sudden death; however, the relationship between QRSd and risk of ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]) is unclear. METHODS: PainFREE Rx II was a randomized trial, comparing efficacy of antitachycardia pacing versus shock therapy for VT/VF in patients receiving ICDs. We retrospectively correlated the QRSd and specific ECG conduction abnormalities on the 12-lead ECG at study entry with occurrence of VT/VF in 431 patients with CAD enrolled in the trial. RESULTS: The QRSd was < or =120 ms in 291 of 431 (68%) patients. Left bundle branch block (LBBB) was present in 65 patients, right bundle branch block (RBBB) in 48 patients, and nonspecific intraventricular conduction delay (IVCD) was present in 124 patients. Over 12 months' follow-up, VT/VF occurred in 95 (22%) patients (22% of patients with QRSd < or =120 ms vs. 23% of patients with QRSd >120 ms, p = NS). Patients with LBBB were less likely to experience at least one VT/VF episode than patients with QRSd <120 ms. Patients with RBBB and nonspecific IVCD did not differ from patients with narrow QRS complexes with regard to occurrence of tachycardias. CONCLUSIONS: The QRSd and ECG conduction abnormalities are not useful to predict ICD benefit in patients having the characteristics of our study population. The utility of QRSd to predict VT/VF events in patients with CAD requires further prospective evaluation.

The Managed Ventricular pacing versus VVI 40 Pacing (MVP) Trial: clinical background, rationale, design, and implementation.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) reduce mortality among appropriately selected patients who have had or are at risk for life-threatening ventricular arrhythmia. Right ventricular apical (RVA) pacing has been implicated in worsening heart failure and death. The optimal pacemaker mode for bradycardia support while minimizing unnecessary and potentially harmful RVA pacing has not been determined. METHODS: The Managed Ventricular pacing vs. VVI 40 Pacing Trial (MVP) is a prospective, multicenter, randomized, single-blind, parallel, controlled clinical trial designed to establish whether atrial-based dual-chamber managed ventricular pacing mode (MVP) is equivalent or superior to back-up only ventricular pacing (VVI 40) among patients with standard indications for ICD therapy and no indication for bradycardia pacing. The MVP Trial is designed with 80% power to detect a 10% reduction in the primary endpoint of new or worsening heart failure or all-cause mortality in the MVP-treated group. Approximately 1,000 patients at 80 centers in the United States, Canada, Western Europe, and Israel will be randomized to MVP or VVI 40 pacing after successful implantation of a dual-chamber ICD. Heart failure therapies will be optimized in accordance with evidence-based guidelines. Prespecified secondary endpoints will include ventricular arrhythmias, atrial fibrillation, new indication for bradycardia pacing, health-related quality of life, and cost effectiveness. Enrollment began in October 2004 and concluded in April 2006. The study will be terminated upon recommendation of the Data Monitoring Committee or when the last patient enrolled and surviving has reached a minimum 2 years of follow-up. CONCLUSION: The MVP Trial will meet the clinical need for carefully designed prospective studies to define the benefits of atrial-based dual-chamber minimal ventricular pacing versus single-chamber ventricular pacing in conventional ICD patients.