Raymond Yee

Cardiac-Resynchronization Therapy for Mild-to-Moderate Heart Failure

BACKGROUND Cardiac-resynchronization therapy (CRT) benefits patients with left ventricular systolic dysfunction and a wide QRS complex. Most of these patients are candidates for an implantable cardioverter-defibrillator (ICD). We evaluated whether adding CRT to an ICD and optimal medical therapy might reduce mortality and morbidity among such patients. METHODS We randomly assigned patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more or a paced QRS duration of 200 msec or more to receive either an ICD alone or an ICD plus CRT. The primary outcome was death from any cause or hospitalization for heart failure. RESULTS We followed 1798 patients for a mean of 40 months. The primary outcome occurred in 297 of 894 patients (33.2%) in the ICD-CRT group and 364 of 904 patients (40.3%) in the ICD group (hazard ratio in the ICD-CRT group, 0.75; 95% confidence interval [CI], 0.64 to 0.87; P<0.001). In the ICD-CRT group, 186 patients died, as compared with 236 in the ICD group (hazard ratio, 0.75; 95% CI, 0.62 to 0.91; P = 0.003), and 174 patients were hospitalized for heart failure, as compared with 236 in the ICD group (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). However, at 30 days after device implantation, adverse events had occurred in 124 patients in the ICD-CRT group, as compared with 58 in the ICD group (P<0.001). CONCLUSIONS Among patients with NYHA class II or III heart failure, a wide QRS complex, and left ventricular systolic dysfunction, the addition of CRT to an ICD reduced rates of death and hospitalization for heart failure. This improvement was accompanied by more adverse events. (Funded by the Canadian Institutes of Health Research and Medtronic of Canada; ClinicalTrials.gov number, NCT00251251.).

Prognostic importance of defibrillator shocks in patients with heart failure.

BACKGROUND Patients with heart failure who receive an implantable cardioverter-defibrillator (ICD) for primary prevention (i.e., prevention of a first life-threatening arrhythmic event) may later receive therapeutic shocks from the ICD. Information about long-term prognosis after ICD therapy in such patients is limited. METHODS Of 829 patients with heart failure who were randomly assigned to ICD therapy, we implanted the ICD in 811. ICD shocks that followed the onset of ventricular tachycardia or ventricular fibrillation were considered to be appropriate. All other ICD shocks were considered to be inappropriate. RESULTS Over a median follow-up period of 45.5 months, 269 patients (33.2%) received at least one ICD shock, with 128 patients receiving only appropriate shocks, 87 receiving only inappropriate shocks, and 54 receiving both types of shock. In a Cox proportional-hazards model adjusted for baseline prognostic factors, an appropriate ICD shock, as compared with no appropriate shock, was associated with a significant increase in the subsequent risk of death from all causes (hazard ratio, 5.68; 95% confidence interval [CI], 3.97 to 8.12; P<0.001). An inappropriate ICD shock, as compared with no inappropriate shock, was also associated with a significant increase in the risk of death (hazard ratio, 1.98; 95% CI, 1.29 to 3.05; P=0.002). For patients who survived longer than 24 hours after an appropriate ICD shock, the risk of death remained elevated (hazard ratio, 2.99; 95% CI, 2.04 to 4.37; P<0.001). The most common cause of death among patients who received any ICD shock was progressive heart failure. CONCLUSIONS Among patients with heart failure in whom an ICD is implanted for primary prevention, those who receive shocks for any arrhythmia have a substantially higher risk of death than similar patients who do not receive such shocks.

Atrial High Rate Episodes Detected by Pacemaker Diagnostics Predict Death and Stroke Report of the Atrial Diagnostics Ancillary Study of the MOde Selection Trial (MOST)

Background—Some current pacing systems can automatically detect and record atrial tachyarrhythmias that may be asymptomatic. We prospectively studied a 312-patient (pt) subgroup of MOST (MOde Selection Trial), a 2010-patient, 6-year randomized trial of DDDR versus VVIR pacing in sinus node dysfunction (SND). The purpose of the study was to correlate atrial high rate events (AHREs) detected by pacemaker diagnostics with clinical outcomes. Methods and Results—Pacemakers were programmed to log an AHRE when the atrial rate was >220 bpm for 10 consecutive beats. Analysis was confined to patients with at least 1 AHRE duration exceeding 5 minutes. The 312 patients were median age 74 years, 55% female, and 60% had a history of SVT. 160 of 312 (51.3%) patients enrolled had at least 1 AHRE >5 minutes duration over median follow-up of 27 months. Cox proportional hazards analysis assessed the relationship of AHREs with clinical events, adjusting for prognostic variables and baseline covariates. The presence of any AHRE was an independent predictor of the following: total mortality (hazard ratio AHRE versus no AHRE and 95% confidence intervals=2.48 [1.25, 4.91], P =0.0092); death or nonfatal stroke (2.79 [1.51, 5.15], P =0.0011); and atrial fibrillation (5.93 [2.88, 12.2], P =0.0001). There was no significant effect of pacing mode on the presence or absence of AHREs. Conclusions—AHRE detected by pacemakers in patients with SND identify patients that are more than twice as likely to die or have a stroke, and 6 times as likely to develop atrial fibrillation as similar patients without AHRE.

Use of an Extended Monitoring Strategy in Patients With Problematic Syncope

BACKGROUND The conventional investigation of patients who present with syncope involves short-term ECG monitoring or provocative testing with head-up tilt and electrophysiological testing. A symptom-rhythm correlation is often difficult to obtain during spontaneous syncope because of its sporadic, infrequent, and unpredictable nature. METHODS AND RESULTS We used a prolonged monitoring strategy to determine the cause of syncope in 85 patients (age, 59+/-18 years; 44 men) with recurrent undiagnosed syncope with an implantable loop recorder capable of cardiac monitoring for up to 18 months. During a mean of 10.5+/-4.0 months of follow-up, symptoms recurred in 58 patients (68%) 71+/-79 days (2.3+/-2.6 months) after implantable loop recorder insertion. An arrhythmia was detected in 42% of patients who recorded a rhythm during recurrent symptoms, with bradycardia present in 18 and tachycardia in 3. Five of the 18 bradycardic patients and 2 additional sinus rhythm patients received a clinical diagnosis of neurally mediated syncope. Patients who experienced presyncope were much less likely to record an arrhythmia during symptoms compared with recurrence of syncope (24% versus 70%, P=0.0005). There were no adverse events associated with recurrent symptoms, and there were no sudden deaths. Inability to freeze after an event occurred in 8 patients, and pocket infection occurred in 3. CONCLUSIONS The strategy of prolonged monitoring is effective and safe in patients with problematic syncope.

Randomized Assessment of Syncope Trial Conventional Diagnostic Testing Versus a Prolonged Monitoring Strategy

Background—Establishing a diagnosis in patients with unexplained syncope is complicated by infrequent and unpredictable events. Prolonged monitoring may be an alternative strategy to conventional testing with short-term monitoring and provocative tilt and electrophysiological testing. Methods and Results—Sixty patients (aged 66±14 years, 33 male) with unexplained syncope were randomized to “conventional” testing with an external loop recorder and tilt and electrophysiological testing or to prolonged monitoring with an implantable loop recorder with 1 year of monitoring. If patients remained undiagnosed after their assigned strategy, they were offered crossover to the alternate strategy. A diagnosis was obtained in 14 of 27 patients randomized to prolonged monitoring compared with 6 of 30 patients undergoing conventional testing (52% versus 20%, P =0.012). Crossover was associated with a diagnosis in 1 of 6 patients undergoing conventional testing compared with 8 of 13 patients who completed monitoring (17% versus 62%, P =0.069). Overall, prolonged monitoring was more likely to result in a diagnosis than was conventional testing (55% versus 19%, P =0.0014). Bradycardia was detected in 14 patients undergoing monitoring compared with 3 patients undergoing conventional testing (40% versus 8%, P =0.005). Conclusions—A prolonged monitoring strategy is more likely to provide a diagnosis than conventional testing in patients with unexplained syncope. Consideration should be given to earlier implementation of a monitoring strategy.

The Etiology of Syncope in Patients With Negative Tilt Table⇓ and Electrophysiological Testing

BACKGROUND Patients with syncope of unknown etiology after negative noninvasive and electrophysiological testing may suffer from recurrent disability. Syncopal episodes are often too infrequent and unpredictable for detection by conventional ambulatory monitoring techniques. METHODS AND RESULTS A long-term subcutaneous monitoring device was implanted in patients with negative ambulatory monitoring, tilt table and electrophysiological testing to establish cardiac rhythm during spontaneous syncope. Sixteen patients aged 57 +/- 19 years with a mean of 8.4 +/- 4.4 previous episodes of syncope underwent device implantation. Fifteen patients (94%) had recurrent syncope 4.4 +/- 4.2 months after implantation. The remaining patient has not had recurrent syncope and continues to be followed. A diagnosis was obtained in every patient who had recurrent episode. Syncope was secondary to sinus arrest in 5, atrioventricular block in 2, ventricular tachycardia in 1, supraventricular tachycardia in 1, and nonarrhythmic in 6. Successful therapy was implemented in all 15 patients, without recurrence of syncope during 13.0 +/- 8.4 months of follow-up. CONCLUSIONS Unexplained syncope in patients with negative investigations has a broad spectrum of etiologies, the most common of which is bradycardia. An implantable long-term monitoring device is useful for establishing a diagnosis when symptoms are recurrent but too infrequent for conventional monitoring techniques.

Progression to chronic atrial fibrillation after pacing: the Canadian Trial of Physiologic Pacing☆

OBJECTIVES This study examined the effect of physiologic pacing on the development of chronic atrial fibrillation (CAF) in the Canadian Trial Of Physiologic Pacing (CTOPP). BACKGROUND The role of physiologic pacing to prevent CAF remains unclear. Small randomized studies have suggested a benefit for patients with sick sinus syndrome. No data from a large randomized trial are available. METHODS The CTOPP randomized patients undergoing first pacemaker implant to ventricular-based or physiologic pacing (AAI or DDD). Patients who were prospectively found to have persistent atrial fibrillation (AF) lasting greater than or equal to one week were defined as having CAF. Kaplan-Meier plots for the development of CAF were compared by log-rank test. The effect of baseline variables on the benefit of physiologic pacing was evaluated by Cox proportional hazards modeling. RESULTS Physiologic pacing reduced the development of CAF by 27.1%, from 3.84% per year to 2.8% per year (p = 0.016). Three clinical factors predicted the development of CAF: age > or =74 years (p = 0.057), sinoatrial (SA) node disease (p < 0.001) and prior AF (p < 0.001). Subgroup analysis demonstrated a trend for patients with no history of myocardial infarction or coronary disease (p = 0.09) as well as apparently normal left ventricular function (p = 0.11) to derive greatest benefit. CONCLUSIONS Physiologic pacing reduces the annual rate of development of chronic AF in patients undergoing first pacemaker implant. Age > or =74 years, SA node disease and prior AF predicted the development of CAF. Patients with structurally normal hearts appear to derive greatest benefits.

Systematic Assessment of Patients With Unexplained Cardiac Arrest Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER)

Background— 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. Methods and Results— Patients with apparently unexplained cardiac arrest and no evident cardiac disease (normal cardiac function on echocardiogram, no evidence of coronary artery disease, and a normal ECG) underwent systematic evaluation that included cardiac magnetic resonance imaging, signal-averaged ECG, exercise testing, drug challenge, and selective electrophysiological testing. Diagnostic criteria were based on accepted criteria or provocation of the characteristic clinical features for long-QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, early repolarization, arrhythmogenic right ventricular cardiomyopathy, coronary spasm, and myocarditis. Sixty-three patients in 9 centers were enrolled (age 43.0±13.4 years, 29 women). A diagnosis was obtained in 35 patients (56%): Long-QT syndrome in 8, catecholaminergic polymorphic ventricular tachycardia in 8, arrhythmogenic right ventricular cardiomyopathy in 6, early repolarization in 5, coronary spasm in 4, Brugada syndrome in 3, and myocarditis in 1. Targeted genetic testing demonstrated evidence of causative mutations in 9 (47%) of 19 patients. Screening of 64 family members of these patients identified 15 affected individuals who were treated (24%). The remaining 28 patients (44%) were considered to have idiopathic ventricular fibrillation. Conclusions— Systematic clinical testing, including drug provocation and advanced imaging, results in unmasking of the cause of apparently unexplained cardiac arrest in >50% of patients. This approach assists in directing genetic testing to diagnose genetically mediated arrhythmia syndromes, which results in successful family screening.

A placebo-controlled trial of intravenous and oral disopyramide for prevention of neurally mediated syncope induced by heap-up tilt☆

Abstract Objectives. A double-blind randomised trial was designed to determine the efficacy of intravenous and oral disopyramide phosphate in preventing neurally syncope induced by a head-up tilt test. Background. Neurally mediated syncope is a frequent cause of syncope and may be induced by head-up tilt, testing. Recent uncontrolled trials have suggested that disopyramide may be an effective therapy in patients with neurally mediated syncope. Methods. Twenty-two consecutive patients with recurrent neurally mediated syncope and two or successive positive head-up tilt test responses were randomly allocated to receive either intravenous disopyramide or placebo. Head-up tilt testing at 60 ° was performed for 15 min. If presyncope or syncope was not provoked, isoproterenol infusion was started at a rate of 1 μg/min and the rate gradually increased until a 25% increase in heart rate was achieved. Eleven patients were subsequently randomised in crossover fashion to receive oral disepyramide (800 mg/day) or placebo during 1 week. The primary end point was prevention of syncope or presyncope provoked by head-up tilt testing. Results. Head-up tilt test results were positive for syncope in 12 (75%) of 16 patients receiving intravenous placebo and in 12 (60%) of 20 patients receiving disopyramide (p = 0.55 Fisher exact test, 95% confidence interval [CI] −14% to 40%). In the intravenous phase, complete crossover was achieved in 15 patients. Head-up tilt test results during this were positive in 13 patients (87%) receiving placebo and in 12 patients (80%) receiving disopyramide (p = 0.50 Fisher exact test, 95% CI −19% to 32%) and were positive in all patients receiving their initially randomized drug or placebo. In the oral phase, head-up tilt results were positive in only two patients (18%) assigned to placebo and in three patients (27%) receiving disopyramide (p = 0.54 Fisher exact test, 95% CI −42% to 24%). A mean follow-up time of 29 ± 8 months was obtained in 21 of the 22 patients. Syncope recurred in 3 (27%) of the 11 patients receiving disopyramide and 3 (30%) of the 10 patients not treated pharmacologically (p > 0.05). Conclusions. Intravenous disopyramide was ineffective for the prevention of neurally mediated syncope provoked by head-up tilt testing. No significant effect was observed after oral therapy with disopyramide. There was a striking decrease in the incidence of positive tilt test results over time regardless of intervention, thus discouraging the use of head-up tilt as the single method of assessing therapeutic efficacy. Recurrence of syncope after the investigative protocol was infrequent over long-term follow-up regardless of treatment group.

Prognostic value of electrophysiology testing in asymptomatic patients with Wolff-Parkinson-White pattern.

The prognostic value of electrophysiology testing was studied in 75 asymptomatic patients with the Wolff-Parkinson-White electrocardiographic pattern. All patients underwent electrophysiology testing at entry to the study and were followed up annually for a total of 348 patient-years (median, 4.3 years). There were 44 male and 31 female patients, and age at enrollment ranged from 7 to 77 years (mean, 34 +/- 14 years). The median effective refractory period of the accessory pathway was 293 msec (interquartile range, 280-310 msec), and the median shortest RR interval between preexcited beats during atrial fibrillation (SRR) [corrected] was 274 msec (240-320 msec). Twenty-three patients had an SRR of 250 msec or less and eight patients had a median shortest SRR interval of 200 msec or less. Twelve patients had inducible sustained reciprocating tachycardia, 10 patients had inducible nonsustained reciprocating tachycardia, and 23 patients had inducible sustained atrial fibrillation. Twenty patients (27%) lacked retrograde conduction over the accessory pathway. No patient died suddenly during a median follow-up of 4.3 years. Six patients (8%) became symptomatic with documented supraventricular tachycardia, of whom two underwent operative ablation of their accessory pathways. No patient with absent retrograde accessory pathway conduction during the electrophysiology study became symptomatic. Inducible sustained or nonsustained reciprocating tachycardia at electrophysiology study did not predict the development of subsequent symptomatic supraventricular tachycardia. Nine patients lost preexcitation during follow-up. Age at enrollment (relative risk/decade, 1.4; 95% confidence interval, 1.0-1.8) and anterograde accessory pathway refractory period (relative risk, 1.06/10 msec; 95% confidence interval, 1.0-1.12) were independent predictors of loss of preexcitation.(ABSTRACT TRUNCATED AT 250 WORDS)