Abstract: Unwanted phrenic nerve stimulation (PNS) has been reported in ∼1 in 4 patients undergoing left ventricular (LV) pacing. The occurrence of PNS over mid-term follow-up and the significance of PNS are less certain.
Abstract: Following recent cases of nonphysiologic noise noted early after defibrillator implantation, the Canadian Heart Rhythm Society Device Committee decided to evaluate the implications of this problem.
Abstract: Premenopausal women have a lower risk of cardiovascular disease (CVD) compared with men of a similar age. Furthermore, the regulation of factors that influence CVD appears to differ between the sexes, including control of the autonomic nervous system (ANS) and the renin-angiotensin system. We examined the cardiac ANS response to angiotensin II (Ang II) challenge in healthy subjects to determine whether differences in women and men exist. Thirty-six healthy subjects (21 women, 15 men, age 38 ± 2 years) were studied in a high-salt balance. Heart-rate variability (HRV) was calculated by spectral power analysis [low-frequency (LF) sympathetic modulation, high-frequency (HF) parasympathetic/vagal modulation, and LF:HF as a measure of overall ANS balance]. HRV was assessed at baseline and in response to graded Ang II infusions (3 ng·kg(-1)·min(-1) × 30 min; 6 ng·kg(-1)·min(-1) × 30 min). Cardiac ANS tone did not change significantly in women after each Ang II dose [3 ng·kg(-1)·min(-1) mean change (Δ)LF:HF (mean ± SE) 0.5 ± 0.3, P = 0.8, vs. baseline; 6 ng·kg(-1)·min(-1) ΔLF:HF (mean ± SE) 0.5 ± 0.4, P = 0.4, vs. baseline], whereas men exhibited an unfavorable shift in overall cardiac ANS activity in response to Ang II (ΔLF:HF 2.6 ± 0.2, P = 0.01, vs. baseline; P = 0.02 vs. female response). This imbalance in sympathovagal tone appeared to be largely driven by a withdrawal in cardioprotective vagal activity in response to Ang II challenge [ΔHF normalized units (nu), -5.8 ± 2.9, P = 0.01, vs. baseline; P = 0.006 vs. women] rather than an increase in sympathetic activity (ΔLF nu, -4.5 ± 5.7, P = 0.3, vs. baseline; P = 0.5 vs. women). Premenopausal women maintain cardiac ANS tone in response to Ang II challenge, whereas similarly aged men exhibit an unfavorable shift in cardiovagal activity. Understanding the role of gender in ANS modulation may help guide risk-reduction strategies in high-risk CVD populations.
Abstract: We undertook this analysis to assess the relationship between delayed left ventricular activation time (LVAT), assessed prior to cardiac resynchronization therapy (CRT), with the long-term clinical outcomes in CRT recipients. We also sought to determine if baseline LVAT had similar predictive value in patients who were versus were not chronically paced prior to CRT.
Abstract: Approximately 268,000 Fidelis leads were implanted worldwide until distribution was suspended because of a high rate of early failure. Careful analyses of predictors of increased lead failure hazard are required to help direct future lead design and also to inform decision making on lead replacement. We sought to perform a comprehensive analysis of all potential predictors in a multicenter study.
Abstract: Comparing ICD Implantation with and Without Intraoperative Defibrillation Testing. Introduction: The need to perform defibrillation testing (DT) at the time of implantable cardioverter defibrillator (ICD) insertion is controversial. In the absence of randomized trials, some regions now perform more than half of ICD implants without DT. Methods: During the last year of enrolment in the Resynchronization for Ambulatory Heart Failure Trial, a substudy randomized patients to ICD implantation with versus without DT. Results: Among 252 patients screened, 145 were enrolled; 75 randomized to DT and 70 to no DT. Patients were similar in terms of age (65.9 ± 9.3 years vs 67.9 ± 8.9 years); LVEF (24.7 ± 4.6% vs 23.6 ± 4.6%), QRS width (154.8 ± 23.5 vs 155.8 ± 23.6 ms), and history of atrial fibrillation (5% vs 6%). All 68 patients in the DT arm tested according to the protocol achieved a successful DT (≤25 J); 96% without requiring any system modification. No patient experienced perioperative stroke, myocardial infarction, heart failure (HF), intubation or unplanned ICU stay. The length of hospital stay was not prolonged in the DT group: 20.2 ± 26.3 hours versus 21.3 ± 23.0 hours, P = 0.79. One patient in the DT arm had a failed appropriate shock and no patient suffered an arrhythmic death. The composite of HF hospitalization or all-cause mortality occurred in 10% of patients in the no-DT arm and 19% of patients in the DT arm (HR = 0.53, 95% CI: 0.21-1.31, P = 0.14). Conclusions: In this randomized trial, perioperative complications, failed appropriate shocks, and arrhythmic death were all uncommon regardless of DT. There was a nonsignificant increase in the risk of death or HF hospitalization with DT. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1313-1316, December 2012).
Abstract: Cardiac resynchronization (CRT) prolongs survival in patients with systolic heart failure and QRS prolongation. However, most trials excluded patients with permanent atrial fibrillation.
Abstract: The rationale for cardiac resynchronization therapy (CRT), expectations in terms of patient benefit, patient selection for CRT, selection of a CRT pacemaker (CRT-P) vs CRT plus implantable cardioverter-defibrillator (CRT-D) platform, and studies evaluating device programming to enhance benefit from CRT are reviewed. The notion of an "optimal" left ventricular (LV) pacing site, the rationale for identifying and avoiding LV pacing in regions of scar, the use of anatomic, hemodynamic, and electrical parameters to identify an optimal LV pacing site, and the potential utility of multisite LV pacing to enhance benefit from CRT are discussed. Finally, the advantages and disadvantages of the various methods for LV lead delivery are reviewed.
Abstract: To develop a computer model to test shock reduction strategies such as antitachycardia pacing and shock withholding for supraventricular rhythms, oversensing, and nonsustained ventricular tachycardia.
Abstract: AIMS: Left-ventricular (LV) pacing with optimized atrio-ventricular (AV) timing may provide similar or greater benefit in comparison with bi-ventricular (BiV) pacing in a subset of cardiac resynchronization therapy (CRT) patients with sinus rhythm and preserved AV conduction. We hypothesized that the optimal device AV delays during LV pacing can be predicted using electrocardiogram (ECG) and device electrograms. METHODS AND RESULTS PATIENTS: (n= 55) with sinus rhythm and PR interval < 300 ms had their CRT devices programmed to atrial and LV pacing with a range of AVs as well as to echocardiographically optimized BiV and no ventricular pacing. At each setting, LV function was evaluated using echocardiography and AVs corresponding to the highest LV ejection fraction (LVEF), lowest LV end-systolic volume (LVESV), and the average of the two (by EF and ESV) were determined. Correlation between the optimal AVs and the following intervals was investigated: intrinsic QRS duration (QRSs), intervals from atrial pacing (Ap) to right-ventricular (RV) sensing (Ap-RVs), from RV sensing to LV activation (RVs-LVs), and from LV pacing to RV sensing (LVp-RVs). Optimal AVs moderately correlated with intrinsic Ap-RVs interval, whereas other parameters showed weak or no correlation. The best correlation (R = 0.66, P< 0.0001) was between the optimal AV delay according to EF and ESV, and Ap-RVs interval. Programming of AVs during LV pacing to the shortest of 70% of the intrinsic Ap-RVs interval, or Ap-RVs--40 ms resulted in significant improvement in LV function similar to that in case of BiV. CONCLUSION: Optimal AV during LV pacing can be approximated from the intrinsic AV conduction time.
Abstract: Whether the benefits observed with cardiac resynchronization therapy (CRT) are similar in patients with versus those without atrial fibrillation (AF) is unclear. Furthermore, whether patients with AF receiving CRT should undergo atrioventricular nodal (AVN) ablation remains uncertain.
Abstract: Whether patients with persistent atrial fibrillation (AF) obtain the same degree of benefit with cardiac resynchronization therapy (CRT) as those in sinus rhythm remains unclear.
Abstract: This consensus guideline was prepared on behalf of the International Society for Holter and Noninvasive Electrocardiology and is cosponsored by the Japanese Circulation Society, the Computers in Cardiology Working Group on e-Cardiology of the European Society of Cardiology, and the European Cardiac Arrhythmia Society. It discusses the electrocardiographic phenomenon of T-wave alternans (TWA) (i.e., a beat-to-beat alternation in the morphology and amplitude of the ST-segment or T-wave). This statement focuses on its physiological basis and measurement technologies and its clinical utility in stratifying risk for life-threatening ventricular arrhythmias. Signal processing techniques including the frequency-domain Spectral Method and the time-domain Modified Moving Average method have demonstrated the utility of TWA in arrhythmia risk stratification in prospective studies in >12,000 patients. The majority of exercise-based studies using both methods have reported high relative risks for cardiovascular mortality and for sudden cardiac death in patients with preserved as well as depressed left ventricular ejection fraction. Studies with ambulatory electrocardiogram-based TWA analysis with Modified Moving Average method have yielded significant predictive capacity. However, negative studies with the Spectral Method have also appeared, including 2 interventional studies in patients with implantable defibrillators. Meta-analyses have been performed to gain insights into this issue. Frontiers of TWA research include use in arrhythmia risk stratification of individuals with preserved ejection fraction, improvements in predictivity with quantitative analysis, and utility in guiding medical as well as device-based therapy. Overall, although TWA appears to be a useful marker of risk for arrhythmic and cardiovascular death, there is as yet no definitive evidence that it can guide therapy.
Abstract: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in appropriately selected patients with heart failure. Optimal left ventricular (LV) lead placement is useful in enhancing response from CRT. Three significant obstacles to LV lead placement are patient-specific variations in coronary venous anatomy, phrenic nerve stimulation, and a significant rate of LV lead dislodgement or microdislodgement.
Abstract: It has been observed that replacement of an implantable cardioverter-defibrillator generator in response to a device advisory may be associated with a substantial rate of complications, including death. The risk of lead revision in response to a lead advisory has not been determined previously.
Abstract: Autonomic dysfunction tends to improve over time after acute myocardial infarction (MI), but the clinical significance of autonomic remodeling is not well known.
Abstract: Catheter ablation is a promising therapy for atrial fibrillation (AF), but its utility in patients with left ventricular systolic dysfunction (LVSD) is uncertain. The objectives of this study were to perform a systematic review and meta-analysis of randomized and observational studies comparing the rates of recurrent AF, atrial tachycardia (AT), and complications after AF catheter ablation in those with versus without LVSD and to summarize the impact of catheter ablation on the left ventricular ejection fraction. Seven observational studies and 1 randomized trial were included (total n = 1,851). Follow-up ranged from 6 to 27 months. In those with LVSD, 28% to 55% were free of AF or AT on follow-up after 1 AF catheter ablation, increasing to 64% to 96% after a mean of 1.4 procedures. The relative risk for recurrent AF or AT in those with versus without LVSD was 1.5 (95% confidence interval 1.2 to 1.8, p <0.001) after 1 procedure and 1.2 (95% confidence interval 0.9 to 1.5, p = 0.2) after multiple procedures. No difference in complications was observed in patients with (3.5%) versus without (2.5%) heart failure (p = 0.55). After catheter ablation, those with LVSD experienced a pooled absolute improvement in the left ventricular ejection fraction of 0.11 (95% confidence interval 0.07 to 0.14, p <0.001). In conclusion, patients with and without LVSD had similar risk for recurrent AF or AT after catheter ablation, but repeat procedures were required more often in those with LVSD. Significant improvements in left ventricular ejection fractions after ablation were observed in those with LVSD. Randomized trials are needed given the limitations of present data.
Abstract: The implantable cardioverter defibrillator (ICD) is an effective therapy for sudden cardiac death (SCD). Identifying patients who will benefit from an ICD is key. Most SCD events occur in patients with less severe left ventricular (LV) dysfunction, yet past trials and guidelines focus on those with severe LV dysfunction. Given the large pool of patients with less severe LV dysfunction and a modest risk of SCD, methods to identify those who might benefit from an ICD are required.
Abstract: Despite advances in medical and surgical therapy for patients with heart disease, sudden cardiac death remains an important public health problem that prematurely ends the lives of more than 300,000 persons each year in North America. Many of these deaths occur in patients with a history of myocardial infarction (MI). Although severe left ventricular (LV) systolic dysfunction is used to identify patients at risk of sudden death after MI, most cardiac arrests occur in those with only mild LV dysfunction. Further, severe LV dysfunction is not a specific indicator for cardiac arrest. Risk stratification, to identify patients most likely to benefit from implantable defibrillator therapy after MI, is an essential area of investigation. Because the development of cardiac arrest is complex and likely requires the confluence of several factors, using a single test to predict the risk of sudden death or to guide implantable defibrillator therapy is unlikely to be successful. Tests that assess cardiac structure, including repolarization, and those that evaluate autonomic modulation and other factors have been developed with the goal of identifying patients at highest risk of cardiac arrest after MI. These tests, particularly in combination, appear to identify patients who may benefit from implantable defibrillator therapy after MI. Ongoing and planned randomized controlled trials will assess whether these tests can be used to guide implantable defibrillator therapy. Until the data from these studies are available, severe LV dysfunction remains the only proven approach to guide implantable defibrillator therapy after MI.
Abstract: Despite advances in therapies for myocardial infarction (MI), death attributed to a cardiac arrest from ventricular tachycardia (VT) or ventricular fibrillation (VF) remains an important problem. The implantable cardioverter defibrillator (ICD) is effective in preventing death from VT/VF, but reliably identifying which post-MI patients would benefit from an ICD remains a major challenge. Beyond the initial post-MI period, the presence of significant left ventricular (LV) dysfunction, alone or in combination with the induction of sustained VT/VF during invasive testing, is the only proven means of selecting patients for a prophylactic ICD. However, these approaches identify only a fraction of those at risk. Furthermore, most patients with significant LV dysfunction after MI have a low, near-term risk of VT/VF. Noninvasive risk stratification tools have been developed to better identify patients likely to benefit from an ICD. To date, none of these tools has been proven useful in this regard. The factors leading to a cardiac arrest are complex, and a single test is unlikely to reliably predict risk. Noninvasive assessment of cardiac structure, conduction and repolarization along with autonomic modulation appear to be useful in predicting the risk of a cardiac arrest after MI, particularly when assessed in combination. However, randomized trials assessing the efficacy of ICD therapy in patients identified as being at risk are required. Until such data are available, significant LV dysfunction alone and in combination with the induction of VT/VF during invasive testing in the nonacute post-MI period remain the only proven methods to guide prophylactic ICD therapy.
Abstract: To describe the 12-month prevalence of major depression in relation to smoking status, nicotine dependence levels, commitment to quit, attempts to quit, and maintenance of smoking cessation in the Canadian general population.
Abstract: Selective atrial pacing algorithms have been developed for prevention of atrial tachycardia/atrial fibrillation (AT/AF). Although short-term studies have shown modest to minimal incremental benefit of these algorithms compared with conventional dual-chamber (DDD/R) pacing for prevention of AT/AF, the long-term effects of these algorithms are unknown. Accordingly, we compared atrial antitachycardia pacing (ATP) therapy and combined atrial ATP and atrial pace prevention (ATP + Prevention) algorithms to conventional DDD/R pacing for prevention of AT/AF over long-term follow-up.
Abstract: The Canadian Heart Rhythm Society (CHRS) Device Advisory Committee was commissioned in 2006 to develop a mechanism for responding to advisories regarding cardiac rhythm device and lead performance.
Abstract: We sought to evaluate the utility of T-wave alternans (TWA) assessment in the immediate post-exercise period to identify and validate cutpoints for the modified moving average (MMA) assessment method.
Abstract: The Canadian Heart Rhythm Society (CHRS) Device Advisory Committee was commissioned to respond to advisories regarding cardiac rhythm device and lead performance on behalf of the CHRS. In the event of an advisory, the Chair uses an e-mail network to disseminate advisory information to Committee members broadly representative of the Canadian device community. A consensus recommendation is prepared by the Committee and made available to all Canadian centres on the CHRS Web site after approval by the CHRS executive. This collaborative approach using an e-mail network has proven very efficient in providing a rapid national response to device advisories. The network is an ideal tool to collect specific data on implanted device system performance and allows for prompt reporting of clinically relevant data to front-line clinicians and patients.
Abstract: A single, markedly elevated B-type natriuretic peptide (BNP) serum concentration predicts an increased risk of death after myocardial infarction (MI), though its sensitivity and predictive accuracy are low. We compared the predictive value of a modestly and persistently elevated, versus a single, markedly elevated measurement of N terminal pro-BNP (NT-BNP) early after MI.
Abstract: Cardiac arrest without evident cardiac disease may be caused by subclinical genetic conditions. Provocative testing to unmask a phenotype is often necessary to detect primary electrical disease, direct genetic testing, and perform family screening.
Abstract: Defibrillation threshold (DFT) testing has traditionally been a routine part of implantable cardioverter-defibrillator (ICD) implantation, despite a lack of compelling evidence that it predicts or improves outcomes. In the past, when devices were much less reliable, DFT testing seemed prudent; however, modern ICD systems have such a high rate of successful defibrillation that many electrophysiologists now question whether DFT testing is still worthwhile, particularly since DFT testing may now be the highest acute risk component of ICD implantation.
Abstract: Implantable cardioverter defibrillator (ICD) generator advisories present management dilemmas for physicians regarding competing risks of ICD failure and replacement-related complications. There is currently a paucity of long-term data concerning the complications associated with advisory ICD replacement.
Abstract: Diagnostic supraventricular tachycardia (SVT) features and pacing maneuvers tend to be specific but insensitive. Therefore, diagnosis often requires the integration of multiple pieces of information and/or pacing maneuvers, which adds to the complexity of catheter ablation procedures.
Abstract: Data suggest that atrial pacing, statins, angiotensin-converting enzyme-inhibitors and angiotensin receptor blocking drugs prevent atrial tachycardia/atrial fibrillation (AT/AF) in some patients. The clinical predictors of at/af recurrence following dual-chamber pacemaker insertion were examined in 185 consecutive patients with paroxysmal AF.
Abstract: The purpose of this study was to use a candidate gene approach to identify common polymorphisms that are associated with resting sinus heart rate in a population without overt cardiovascular disease.
Abstract: The Medtronic Sprint Fidelis family of leads has recently been the subject of a widespread advisory. Lead failure rates are estimated at 2.3% at 30 months, 2.6 times the failure rate of the reference Medtronic 6947 lead.
Abstract: Mitral insufficiency is known to occur in a substantial proportion of patients with heart failure. Its relationship with morbidity and mortality is poorly described.
Abstract: The quality of life (QOL) of patients with ventricular dysrhythmias is well studied, but less is known about the QOL of their partners. This study describes the QOL of partners of patients with serious ventricular dysrhythmias enrolled in the Antiarrhythmics Versus Implantable Defibrillators trial.
Abstract: This study sought to determine whether combined assessment of autonomic tone plus cardiac electrical substrate identifies most patients at risk of serious events after myocardial infarction (MI) and to compare assessment at 2 to 4 weeks versus 10 to 14 weeks after MI.
Abstract: Amiodarone has been proposed to decrease atrial fibrillation after cardiac surgery. The literature was systematically reviewed for randomized trials comparing amiodarone with control for prevention of atrial fibrillation. Data were extracted on study characteristics, quality, and incidence of atrial fibrillation, cardiovascular outcomes, and length of hospitalization. Nineteen trials were included. Amiodarone reduced the odds ratio of atrial fibrillation (0.50; 95% confidence interval [CI]: 0.43 to 0.59, p < 0.0001), ventricular tachyarrhythmias (0.39; 95% CI: 0.26 to 0.58, p < 0.0001), and strokes (0.53; 95% CI: 0.30 to 0.92, p = 0.02). Amiodarone reduced hospital stay (0.6 days; 95% CI: 0.4 to 0.8, p < 0.0001). Amiodarone decreased atrial fibrillation, reduced perioperative ventricular tachyarrhythmias and strokes, and reduced duration of hospitalization. The current evidence supports recommending the routine use of perioperative amiodarone for cardiac surgery.
Abstract: Atrial tachyarrhythmias after cardiac surgery are associated with adverse outcomes and increased costs. Previous trials of amiodarone prophylaxis, while promising, were relatively small and yielded conflicting results.
Abstract: We conducted a systematic review and meta-analysis of observational studies to assess the risk of thromboembolism associated with atrial flutter.
Abstract: The purpose of this study was to evaluate the frequency and clinical significance of ventricular high-rate (VHR) episodes (ventricular rate >162 bpm) in patients with symptomatic bradycardia and paroxysmal atrial fibrillation (AF).
Abstract: Atrial fibrillation (AF) is associated with a significant morbidity and mortality, mainly due to an increased risk of thromboembolic stroke. Several large randomized trials have demonstrated the efficacy of oral anticoagulation to reduce this risk of ischemic events in patients with non-valvular AF. Despite the translation of these results into clear practice guidelines, oral anticoagulation remains underused. This reflects doubts about the real effectiveness of oral anticoagulation in daily practice. This paper gives an overview of the available evidence of the effectiveness of oral anticoagulation in population studies and tries to identify some remaining barriers in the prescription of oral anticoagulation in real life.
Abstract: Catheter ablation of the atrioventricular junction (AVJ) is a widely accepted treatment for drug refractory atrial fibrillation. Unfortunately, there have been some reports of pause dependent ventricular arrhythmias associated with QT interval prolongation, mainly in patients with reduced LV function. The present investigation evaluates the association of LV function with QT dispersion in response to a sudden rate drop. ECGs were' recorded on 20 patients (13 with normal LV function) on the day following AVJ ablation while paced at a range of ventricular rates (40-120 beats/min), and during a sudden drop from 80 to 40 beats/min. The maximum QT interval (QTmax), minimum QT interval (QTmin), and QT interval dispersion (QTdisp) were compared. In both groups, the QTmax and QTmin increased at slower paced heart rates while the QTdisp did not change. In response to a sudden rate drop from 80 to 40 beats/min, the QTmax increased in both groups of LV function (trend), while the QTmin increased in those with normal LV function (24 +/- 22 ms), but not in those with reduced LV function (0 +/- 14 ms; P = 0.01). Consequently, the QTdisp increased significantly in those with reduced LV function (31 +/- 23 ms) but not in normal LV function (-5 +/- 29 ms; P = 0.01). Morphological QTU changes developed following the sudden rate drop in 67% of the reduced LV versus 8% of the normal LV (P = 0.02) function groups. Following AVJ ablation, QTdisp increased during a sudden rate drop in patients with reduced LV function, but not in patients with normal LV function.
Abstract: Ablation of the AV junction is a widely accepted treatment of drug-refractory atrial fibrillation. Long-term pacing of the right ventricular (RV) apex following AV junction ablation can result in adverse cardiac remodeling. However, anecdotal studies report that pacing too slowly following AV junction ablation was associated with propensity to sudden cardiac death. The aim of this study was to provide information about the balance between measures of quality of life versus measures of electrical remodeling achieved by pacing with different rate modalities in a randomized pilot clinical trial.
Abstract: The defibrillator has been shown to reduce mortality in a number of patient groups with cardiac disease. Given the number of individuals with defibrillators it is important to understand the influence of these devices quality of life. Advances have led to smaller devices, less-invasive implantation, and more refined arrhythmia management. The potential impact of the defibrillator on quality of life continues to evolve with these advances. This review discusses the impact of the defibrillator on psychological well-being and quality of life, particularly the results of recent large randomized trials. Observational studies evaluating the relationship between defibrillator implantation and quality of life have not shown consistent results, but recent data from randomized trials provide important insights. Among patients who have survived life-threatening arrhythmias the defibrillator is associated with similar or perhaps superior quality of life versus antiarrhythmic drug therapy. However, patients who experience shocks have poorer quality of life versus those who do not. The reduction in quality of life with multiple shocks is of similar magnitude to serious side effects from antiarrhythmic drugs. While patients with defibrillators are at risk for poor quality of life. The advantages and disadvantages of defibrillator therapy versus amiodarone or usual medical care should be discussed with patients in whom a defibrillator is recommended. Those undergoing defibrillator implantation should be advised that adverse events and/or multiple shocks occur in a minority of patients, but may lead to reduced quality of life and it is vital that support resources be made available for these individuals.
Abstract: Implantable cardioverter defibrillator (ICD) use reduces mortality in patients with serious ventricular arrhythmias compared with antiarrhythmic drug (AAD) use. However, the relative impact of these therapies on self-perceived quality of life (QoL) is unknown.
Abstract: This article contains the results of an attempt by appointed members of the North American Society of Pacing and Electrophysiology to define the research frontier in electrophysiology and suggest areas of study as an aid in setting the research agenda.
Abstract: Patients with ischemic LV dysfunction are at high risk of sudden death. However, no benefit from prophylactic defibrillator therapy was observed in a group of patients with LV dysfunction undergoing CABG (CABG Patch trial). Thus, the effect of CABG on future risk of sudden death in patients with LV dysfunction is of considerable interest.
Abstract: Black patients with heart failure have a poorer prognosis than white patients, a difference that has not been adequately explained. Whether racial differences in the response to drug treatment contribute to differences in outcome is unclear. To address this issue, we pooled and analyzed data from the Studies of Left Ventricular Dysfunction (SOLVD) prevention and treatment trials, two large, randomized trials comparing enalapril with placebo in patients with left ventricular dysfunction.
Abstract: Electrical storm, multiple temporally related episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF), is a frequent problem among recipients of implantable cardioverter defibrillators (ICDs). However, insufficient data exist regarding its prognostic significance.
Abstract: Our purpose was to evaluate whether baseline characteristics predictive of implantable cardioverter defibrillator (ICD) efficacy in the Canadian Implantable Defibrillator Study (CIDS) are predictive in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial.
Abstract: ACE inhibitors are standard therapy for treating both symptomatic and asymptomatic patients with left ventricular dysfunction. However, recent clinical trials have shown that beta blockers further reduce mortality in patients with symptomatic heart failure treated with ACE inhibitors. However, the evidence in support of adding beta blockers to ACE inhibitor therapy in patients with asymptomatic left ventricular dysfunction is less certain. The mechanisms by which ACE inhibitors and beta blockers may exert benefit in patients with heart failure are discussed, and studies assessing the association of beta blockade with outcome in patients with mild heart failure receiving ACE inhibitor therapy are reviewed. (c)2000 by CHF, Inc.
Abstract: Prior clinical research indicates that conduction slowing is the primary mechanism leading to the spontaneous termination of reentrant tachycardia in humans. Yet, some experimental models indicate that cycle length oscillations and enhanced conduction are important prerequisites. The role of oscillations in conduction times and enhanced conduction in the spontaneous termination of human reentrant tachycardia has not been adequately investigated. The electrophysiologic features preceding the spontaneous termination of orthodromic atrioventricular (AV) reciprocating tachycardia (RT) were evaluated in 21 patients, each of whom had a sustained (>60 seconds) and a spontaneously terminating (>/=10 beats and </=60 seconds) episode of AVRT during the same electrophysiologic study. Atrio-His, His-ventricular, interventricular, ventriculoatrial and atrial conduction times were measured for each beat of spontaneously terminating AVRT and for paired beats of sustained AVRT. Beats of spontaneously terminating and sustained tachycardia were pooled and Hadi multivariate outlier analysis was used to identify whether significant beat-to-beat alterations in conduction times preceded the spontaneous termination of reentry. Cycle lengths of sustained (348+/-62 msec) and spontaneously terminating AVRT (351+/-70 msec) were similar. Significant beat-to-beat oscillations in conduction times preceded the spontaneous termination of AVRT in 10 of the 21 (48%) patients. An apparent enhancement in atrio-His or ventriculoatrial conduction times immediately preceded the spontaneous termination of AVRT in 11 patients (52%), while an apparent conduction delay occurred in only 2 patients (10%). Moreover, significant oscillations in conduction times were present in 9 of the 11 patients (82%) with enhanced conduction, but only in 1 of the 10 (10%) remaining patients (p=0.002. Conduction time oscillations, which are related to apparent enhancement in atrio-His or ventriculoatrial conduction, frequently precede the spontaneous termination of reentry in humans.
Abstract: beta-Blockers have emerged as an important therapy in patients with symptomatic left ventricular systolic dysfunction. Early studies demonstrated that beta-blocker therapy improved left ventricular function, reduced neurohumoral activity and reduced heart failure symptoms in these patients. While none of these small studies demonstrated a significant benefit in terms of overall survival, several meta-analyses suggested that beta-blocker therapy could, in fact, reduce mortality in patients with left ventricular systolic dysfunction and mild to moderate heart failure symptoms (New York Heart Association class II or III). Three large, recently completed, trials have confirmed the benefit of beta-blockade in these patients. This report reviews some of the initial clinical studies of beta-blockade in heart failure, examines the findings of the three large multicentre trials and other relevant research. Finally, ongoing trials designed to assess the relative efficacy of different beta-blockers and evaluate the utility of beta-blockade in specific subsets of patients with heart failure are discussed.
Abstract: The study evaluated the relationship between light-to-moderate alcohol consumption and prognosis in patients with left ventricular (LV) systolic dysfunction.
Abstract: The present analysis examines the prognostic implications of moderate renal insufficiency in patients with asymptomatic and symptomatic left ventricular systolic dysfunction.
Abstract: Estimate the effect of angiotensin converting enzyme (ACE) inhibitors on the risk of sudden cardiac death (SCD) following myocardial infarction (MI).
Abstract: In vitro studies indicate that nitric oxide synthase (NOS) inhibitors alter sinus node automaticity. Moreover, whereas the systemic delivery of N(G)-monomethyl-L-arginine (L-NMMA), a NOS inhibitor, results in sinus bradycardia and arterial hypertension, its intracoronary administration has little effect on sinus heart rate. Therefore whether L-NMMA directly alters sinus node function in humans is not known. By using a crossover design, we evaluated the effect of intracoronary L-NMMA (20 micromol/min x 10 min) on corrected sinus node recovery time (CSNRT), heart rate, mean arterial blood pressure, electrocardiographic intervals, and coronary artery blood flow in nine men and 13 women aged 48+/-12 years. All were in sinus rhythm and had normal baseline CSNRTs. Baseline measurements were made during a dextrose infusion, and then L-NMMA was administered, and these parameters remeasured. In 11 patients, the infusions were near the origin of the sinus node artery (Concordant), whereas in the remaining 11, they were into the opposite coronary circulation (Discordant). After L-NMMA, significant prolongations in CSNRT were seen in Concordant (p < 0.001) and Discordant patients (p < 0.05), but were most pronounced in the Concordant group (p < 0.05). Although a significant reduction in coronary artery blood flow and nonsignificant changes in blood pressure and heart rate were observed after L-NMMA, these changes were not related to changes in CSNRT (r2 < or = 0.2; p > or = 0.2). These data support the notion that NO is a modifier of human sinus node automaticity.
Abstract: The purpose of this study was to evaluate the relationship of baseline pulse pressure and mean arterial pressure to mortality in patients with left ventricular dysfunction.
Abstract: To evaluate whether use of beta-adrenergic blocking agents, alone or in combination with specific antiarrhythmic therapy, is associated with improved survival in persons with ventricular fibrillation (VF) or symptomatic ventricular tachycardia (VT).
Abstract: Lack of concealment of allocation in randomized clinical trials can invite selection bias, which is the preferential enrollment of specific patients into one treatment group over another. For example, patients more likely to respond may be enrolled only when the next treatment to be assigned is known to be the active treatment, and patients less likely to respond may be enrolled only when the next treatment to be assigned is known to be the control. Despite the fact that selection bias can compromise both the internal and external validity of trials, little methodology has been developed for its detection. An investigator may test the success of the randomization by comparing baseline characteristics across treatment groups, but such test is limited by the potential inability of the measured baseline variables to predict response. A new method for detecting selections bias, based on response data only, is developed for the case in which a small block size, and either unmasking of treatment codes or an open-label design, have compromised the concealment of allocation. This new method complements baseline comparisons, and is sensitive to detect selection bias even in situations in which baseline comparisons are not.
Abstract: Left ventricular (LV) systolic dysfunction, as indicated by a reduced LV ejection fraction (EF) is a potent predictor of cardiovascular mortality. Radionuclide angiography accurately and reproducibly assesses LVEF; however, echocardiography is used more frequently in clinical practice. Whether these methods predict similar mortality has not been fully investigated. We performed a retrospective analysis of patients with baseline radionuclide angiographic (RNA; n = 4,330) and echocardiographic (echo; n = 1,376) based EFs < or =0.35 who were enrolled in the Studies Of Left Ventricular Dysfunction (SOLVD) to address this hypothesis. After adjusting for important prognostic variables, the risk of death (RR 1.15; 95% confidence interval 1.01 to 1.30; p = 0.03) and of cardiovascular death (RR 1.15; 95% confidence interval 1.01 to 1.32; p = 0.04) was higher for patients with ECG-based EFs. To compare the 2 techniques across a range of EF values, we divided the cohort into tertiles of EF. The adjusted risk estimates for all-cause and cardiovascular mortality were similar within each tertile. Of note, the mortality difference in patients with echo- versus RNA-based EFs was most prominent in women. Further, patients with echo-based EFs had significantly higher mortality at sites where this technique was less frequently used to assess the EF. Thus, for a given EF < or =0.35, an echo-based value was associated with a higher risk of death compared with the RNA-based method of measurement. These data suggest that EF values determined by echocardiography and radionuclide angiography predict different mortality and this may, in part, be related to technical proficiency as well as patient characteristics.
Abstract: We conducted a retrospective analysis of the Studies Of Left Ventricular Dysfunction (SOLVD) trials to assess the predictive value of the baseline white blood cell (WBC) count on mortality. Mortality was higher in participants with a baseline WBC count >7,000 compared to those with a baseline WBC < or =7,000 (27% vs 21%, p <0.0001). After controlling for important covariates, each increase in WBC count of 1,000/mm3 was significantly associated with an increased risk of all-cause mortality (relative risk [RR] 1.05, p <0.001). Overall, compared with a baseline WBC count < or =7,000, a baseline WBC count >7,000 was significantly associated with an increased risk of all-cause mortality (RR 1.22, p = 0.001). In participants with ischemic left ventricular (LV) dysfunction, a WBC count >7,000 remained significantly associated with an increased risk of all-cause mortality (RR 1.26, p <0.001), whereas in participants with nonischemic LV dysfunction there was no relation between WBC count and mortality (RR 1.08, p = 0.5). Thus, baseline WBC is an independent predictor of mortality in patients with LV dysfunction, specifically in those with ischemic cardiomyopathy.
Abstract: This analysis was performed to assess whether beta-adrenergic blocking agent use is associated with reduced mortality in the Studies of Left Ventricular Dysfunction (SOLVD) and to determine if this relationship is altered by angiotensin-converting enzyme (ACE) inhibitor use.
Abstract: Population-based studies have found that black patients with congestive heart failure have a higher mortality rate than whites with the same condition. This finding has been attributed to differences in the severity, causes, and management of heart failure, the prevalence of coexisting conditions, and socioeconomic factors. Although these factors probably account for some of the higher mortality due to congestive heart failure among blacks, we hypothesized that racial differences in the natural history of left ventricular dysfunction might also have a role.
Abstract: Certain Class III anti-arrhythmic agents have been shown to interact with human leukocytes and after antigenic and mitogenic activation. We hypothesized that a binding site for the Class III anti-arrhythmic agent, dofetilide, would exist on human leukocytes. Analysis of binding isotherms defined the presence of a single high affinity binding site on mononuclear cells and neutrophils: Kd 26+/-4 nm, Bmax 61+/-14 fmol/10( 6) cells and Kd 33+/-14 nm, Bmax 163+/-45 fmol/10(6) cells, respectively. Other Class III drugs inhibited [3H]-dofetilide binding at physiologically relevant concentrations, but the IC50 values of E4031 and quinidine were significantly higher for leukocytes than for cardiac myocytes. Interestingly, verapamil inhibited [3H]-dofetilide binding to leukocytes, but not to cardiac myocytes at physiologic concentrations (10 microM). Charybdotoxin and tetraethlyammonium inhibited [3H]-dofetilide binding to leukocytes at microM mm concentrations, respectively, however, apamin did not inhibit binding even at 1 microM concentrations. These data suggest that a Ca2+-activated K+ channel, like K(Ca) mini (apamin-insensitive isoform), is a candidate for the leukocyte [3H]-dofetilide binding site. To assess the functional significance of defetilide binding to leukocyte biology, we evaluated fMLP-stimulated superoxide production in the presence or absence of dofetilide. Dofetilide, at 30 nm suppressed of superoxide production. In conclusion, dofetilide binds to human leukocytes at physiologic concentrations and this binding alters leukocyte function possibly through interaction with a Ca2+-activated K+ channel.
Abstract: Bipolar lead use has increased due to oversensing concerns with older unipolar systems. Data on contemporary unipolar devices with improved hardware design and greater programming flexibility is lacking. Using a randomized crossover design, unipolar and bipolar sensing characteristics of 22 atrial and 16 ventricular leads were compared in 34 patients who had pulse generators of programmable polarity. Unipolar and bipolar intracardiac electrogram amplitudes, pacing and sensing thresholds at rest were similar. Provocative maneuvers were used to assess for myopotential inhibition. At atrial sensitivities of 0.625-1.50 mV, myopotential inhibition occurred in 11 (50%) atrial leads in the unipolar mode compared to 1 (5%) in the bipolar mode (p < 0.001). At sensitivities of > 1.50 mV myopotential inhibition occurred in only 1 ventricular (unipolar) lead. An optimal sensitivity setting for each polarity was derived using clinic test results and assessed by ambulatory ECG (AECG). At these optimal settings, oversensing occurred in 1 (6%) atrial and 1 (8%) ventricular unipolar lead during AECG monitoring, whereas oversensing was not seen in any leads programmed to the bipolar mode. Undersensing occurred in 5 (29%) atrial unipolar versus 1 (6%) bipolar lead (p = 0.08). Undersensing was not observed in any of the ventricular leads. Myopotential inhibition may be frequently provoked by provocative maneuvers at higher sensitivity settings in atrial unipolar leads. The frequency of oversensing can be significantly reduced by defining an optimal sensitivity setting using simple isometric maneuvers. Given present day concerns over bipolar lead longevity, increased utilization of unipolar ventricular leads should be considered.
Abstract: This study undertook to determine if the presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular dysfunction was associated with increased mortality and, if so, whether the increase could be attributed to progressive heart failure or arrhythmic death.
Abstract: The follow-up prevalence of electrogram-confirmed spontaneous ventricular tachycardia with a cycle length of >280 ms (53%) exceeds the prevalence of ventricular fibrillation (23%) in patients whose only spontaneous arrhythmia before implantable cardioverter defibrillator implantation was ventricular fibrillation. Antitachycardia pacing therapy safely terminates most (89%) of these slower ventricular tachycardia episodes, recommending the use of tiered-therapy devices and anticipatory activation of ventricular tachycardia detection and treatment algorithms for ventricular fibrillation patients who receive an implantable cardioverter defibrillator.
Abstract: We hypothesized that combining biphasic waveform and sequential pulse defibrillation techniques would lower the defibrillation threshold of a nonthoracotomy lead system in humans below that obtained with biphasic or sequential pulse defibrillation alone.
