Applying the new STEMI guidelines: 2. Disturbances of cardiac rhythm after ST-segment elevation myocardial infarction.
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Biomedical subjects
Paul Dorian
Publications and source records attributed to Paul Dorian.
Limitations to antiarrhythmic drug use in patients with atrial fibrillation.
BACKGROUND: Of the antiarrhythmic agents currently marketed in Canada, 5 are commonly used to treat atrial fibrillation (AF). The impact of contraindications, warnings and precautions for the use of these drugs in patients with AF is not known. We evaluated the proportion of patients with AF for whom contraindications, warnings and/or precautions might limit the use of these commonly prescribed drugs and the proportion of patients actually receiving antiarrhythmic drugs despite the presence of contraindications and/or warnings. METHODS: A total of 723 patients with electrocardiographically confirmed, new-onset paroxysmal AF who were enrolled in the Canadian Registry of Atrial Fibrillation were used in this analysis. The 1996 Compendium of Pharmaceuticals and Specialties was used to obtain contraindications, warnings and precautions for use of 5 antiarrhythmic drugs: flecainide, quinidine, sotalol, amiodarone and propafenone. Proportions of patients with contraindications, warnings and/or precautions for use of any of these drugs owing to comorbid conditions or concomitant drug therapy were calculated, regardless of whether the drugs had been prescribed. We then calculated the proportion of patients taking each antiarrhythmic drug at 3 months despite contraindications and/or warnings. RESULTS: At baseline, when conditions for contraindications and warnings were combined, 414 (57%), 235 (33%), 327 (45%), 285 (39%) and 272 (38%) patients had restrictions for the use of flecainide, quinidine, sotalol, amiodarone and propafenone respectively. Among 465 patients actually taking these medications at 3-month follow-up, 33.3% (2/6), 83.3% (40/48), 36.4% (92/253), 64.1% (25/39) and 34.5% (41/119) respectively had contraindications and/or warnings against their use. The burden of comorbid disease among patients with AF was noteworthy: 404 (56%) had structural heart disease, which included 227 (31%) with ischemic heart disease, 158 (22%) with left ventricular systolic dysfunction and 106 (15%) with heart failure. INTERPRETATION: The high burden of comorbid disease and concomitant drug use in a large proportion of patients with AF limits the suitability of existing antiarrhythmic drugs. Over one-third of patients with new-onset AF received antiarrhythmic drugs despite the presence of contraindications or warnings. Although such restrictions may not preclude the use of these drugs, the results demonstrate the need for new antiarrhythmic drugs with fewer limitations.
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Safety and efficacy of intravenously administered tedisamil for rapid conversion of recent-onset atrial fibrillation or atrial flutter.
OBJECTIVES: The goal of the present study was to assess the efficacy and safety of intravenous tedisamil, a new antiarrhythmic compound, for conversion of recent-onset atrial fibrillation (AF) or atrial flutter (AFL) to normal sinus rhythm (NSR). BACKGROUND: Tedisamil is a novel antiarrhythmic drug with predominantly class III activity. Its efficacy and safety for conversion of recent onset AF or AFL to NSR is not known. METHODS: This was a multicenter, double-blind, randomized, placebo-controlled, sequential ascending dose-group trial. A total of 201 patients with symptomatic AF or AFL of 3 to 48 h duration were enrolled in a two-stage study. During stage 1, patients were randomized to receive tedisamil at 0.4 mg/kg body weight or matching placebo; during stage 2, patients received tedisamil at 0.6 mg/kg body weight or matching placebo. Treatments were given as single intravenous infusions. The primary study end point consisted of the percentage of patients converting to NSR for at least 60 s within 2.5 h. RESULTS: Of 175 patients representing the intention-to-treat sample, conversion to NSR was observed in 41% (25/61) of the tedisamil 0.4 mg/kg group, 51% (27 of 53) of the tedisamil 0.6 mg/kg group, and 7% (4/59) of the placebo group (p < 0.001 for both tedisamil groups vs. placebo). Average time to conversion was 35 min in patients receiving tedisamil. There were two instances of self-terminating ventricular tachycardia: one episode of torsade de pointes and one of monomorphic ventricular tachycardia, both in patients receiving 0.6 mg/kg tedisamil. CONCLUSIONS: Tedisamil at dosages of 0.4 and 0.6 mg/kg was superior to placebo in converting AF or AFL. Tedisamil has a rapid onset of action leading to conversion within 30 to 40 min in the majority of responders.
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Long-term comparison of the implantable cardioverter defibrillator versus amiodarone: eleven-year follow-up of a subset of patients in the Canadian Implantable Defibrillator Study (CIDS).
BACKGROUND: The implantable cardioverter defibrillator (ICD) is superior to amiodarone for secondary prophylaxis of sudden cardiac death. However, the magnitude of this benefit over long-term follow-up is not known. Thus, our objective was to evaluate the long-term consequences of using amiodarone versus an ICD as first-line monotherapy in patients with a prior history of sustained ventricular tachycardia/ventricular fibrillation or cardiac arrest. METHODS AND RESULTS: A total of 120 patients were enrolled at St Michael's Hospital in the Canadian Implantable Defibrillator Study (CIDS) and were randomly assigned to receive either amiodarone (n=60) or an ICD (n=60). The treatment strategy was not altered after the end of CIDS unless the initial assigned therapy was not effective or was associated with serious side effects. After a mean follow-up of 5.6+/-2.6 years, there were 28 deaths (47%) in the amiodarone group, compared with 16 deaths (27%) in the ICD group (P=0.0213). Total mortality was 5.5% per year in the amiodarone group versus 2.8% per year in the ICD group (hazard ratio of amiodarone: ICD, 2.011; 95% confidence interval, 1.087 to 3.721; P=0.0261). In the amiodarone group, 49 patients (82% of all patients) had side effects related to amiodarone, of which 30 patients (50% of all patients) required discontinuation or dose reduction; 19 patients crossed over to ICD because of amiodarone failure (n=7) or side effects (n=12). CONCLUSIONS: In a subset of CIDS, the benefit of the ICD over amiodarone increases with time; most amiodarone-treated patients eventually develop side effects, have arrhythmia recurrences, or die.
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Prognostic differences between atrial fibrillation and atrial flutter.
This report presents the outcome of a cohort of 94 patients with atrial fibrillation from the Canadian Registry of Atrial Fibrillation, in which we paid particular attention to the probability of stroke and death. We also evaluated warfarin use over time and compared left atrial dimensions in patients with atrial flutter with those with atrial fibrillation.
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A randomized trial comparing monophasic and biphasic waveform shocks for external cardioversion of atrial fibrillation.
BACKGROUND: We compared efficacy of and pain felt after biphasic truncated exponential (BTE) and monophasic damped sine (MDS) shocks in patients undergoing external cardioversion of atrial fibrillation (AF). METHODS: Patients with AF were randomized to BTE or MDS waveform cardioversion. Successive shocks were delivered at 70, 100, 200, and 360 J until successful cardioversion, with one 360 J attempt of the alternate waveform when all 4 shocks failed. Success was determined by blinded over-read of electrocardiograms. Peak current was calculated from energy and impedance. Patients rated their pain at 1 and 24 hours after cardioversion. RESULTS: Fourteen of 37 (38%) patients treated with MDS and 34 of 35 (97%) treated with BTE shocks were cardioverted at < or =200 J (P <.0001). Success rates of MDS versus BTE shocks were 5.4% versus 60% for 70 J, 19% versus 80% for < or =100 J, and 86% versus 97% for < or =360 J. BTE shocks cardioverted with less peak current (14.0 +/- 4.3 vs 39.5 +/- 11.2 A, P <.0001), less energy (97 +/- 47 vs 278 +/- 120 J, P <.0001), and less cumulative energy (146 +/- 116 vs 546 +/- 265 J, P <.0001). Patients felt less pain after BTE than MDS shocks at 1 hour (P <.0001) and 24 hours (P <.0001) after cardioversion. CONCLUSION: This BTE waveform is superior to the MDS waveform for cardioversion of AF, requiring much less energy and current, and causing less postprocedural pain.
Adult↗
The association of left atrial size and occurrence of atrial fibrillation: a prospective cohort study from the Canadian Registry of Atrial Fibrillation.
BACKGROUND: The effect of left atrial (LA) dimension on the recurrence of atrial fibrillation (AF) has been examined in small studies. We evaluated the effect of LA dimension on the occurrence of AF using 2- and 4-year echocardiographic data in a large cohort of patients with new onset AF. METHODS: The Canadian Registry of AF (CARAF) enrolled subjects with AF at the first electrocardiographically confirmed diagnosis. Patients were classified at 2 and 4 years as no recurrent AF (No RAF), paroxysmal AF (PAF), or chronic AF (CAF) based on clinical symptoms and electrocardiographic documentation. The association between baseline, 2-, and 4-year LA dimensions with occurrence of AF as determined by echocardiography was evaluated using a multivariate analysis. RESULTS: The No RAF group (n = 176) had a significantly smaller LA dimension (36.9 +/- 6.8 mm) at baseline compared to the CAF group (n = 227) (42.8 +/- 7.5 mm, P <.0001). The No RAF and PAF (n = 153) groups did not have a significant change in LA dimension at 2 or 4 years. Only those with CAF had a significant increase in LA dimension at 2 and 4 years, +1.39 mm (95% CI 0.01-2.8) and +3.48 mm (95% CI 1.8-5.2), respectively. CONCLUSIONS: A larger baseline LA dimension is associated with progression to CAF. Patients with no or paroxysmal recurrence had no change in LA dimension over a 4-year period. These findings have implications in tailoring modes of therapy in patients with AF.
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Randomized controlled study of detection enhancements versus rate-only detection to prevent inappropriate therapy in a dual-chamber implantable cardioverter-defibrillator.
OBJECTIVES: The purpose of this study was to compare rate-only detection to enhanced detection in a dual-chamber implantable cardioverter-defibrillator (ICD), to discriminate ventricular tachycardia from supraventricular tachycardia. BACKGROUND: ICDs are highly effective in treating ventricular tachycardia (VT) or ventricular fibrillation (VF). However, they frequently deliver inappropriate therapy during supraventricular tachycardia (SVT). METHODS: We conducted a randomized clinical trial of detection enhancements in a dual-chamber ICD compared to control (rate-only) detection to discriminate VT from SVT. Detection enhancements included a specific standardized protocol identical for all patients for programming rate stability, sudden onset, atrial-to-ventricular relationship (sudden onset = 9% and rate stability = 10 ms; V > A "on"), and "sustained rate duration" (3 minutes). The primary endpoint was the time to first inappropriate therapy classified by a blinded events committee. RESULTS: One hundred forty-nine patients had a history of sustained VT or VF. Mean age (+/- SD) was 60 +/- 13 years; 83% were male, and mean ejection fraction was 35 +/- 15%. Control (n = 70) and "enhanced" (n = 79) groups did not differ with regard to age, sex, ejection fraction, or primary arrhythmia. The proportion of patients free of inappropriate therapy over time was significantly higher in the enhanced versus the control group (hazard ratio = 0.47, P = .011). High-energy shocks were reduced from 0.58 +/- 4.23 shocks/patient/month in the control group to 0.04 +/- 0.15 shocks/patient/month in the enhanced group (P = .0425). No patient programmed per protocol failed to receive therapy for VT detected by the ICD (422 VT episodes). CONCLUSIONS: Standardized programming in a dual-chamber ICD leads to a significant and clinically important reduction in inappropriate therapies compared to rate-only detection and does not compromise safety with respect to appropriate treatment of VT.
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Feasibility of implantable cardioverter defibrillator use in elderly patients: a case series of octogenarians.
This article addresses the feasibility and safety of ICD therapy in patients >80 years of age. Recent trials have expanded the indication for ICD implantation to include an increasing number and variety of patients. The feasibility of ICD implantation in elderly patients has not been adequately studied. A prospectively collected single center ICD database was analyzed to assess the safety and feasibility of ICD implantation in elderly patients. Patients were divided based on age into two groups (group 1: 70-79 years of age, n = 183; group 2: >or=80 years of age, n = 29). The two groups were similar in gender distribution, NYHA class, and indication for implantation. The actuarial survival was not significantly different between groups 1 and 2 (P > 0.05; primary endpoint), with a 1-year survival of 91% and 93% in groups 1 and 2, respectively, (P = NS). The complication rates at the time of ICD implantation were similar in groups 1 and 2 (6.6% and 13.1%, respectively, P = 0.16). Age alone may not be sufficient criteria to exclude ICD implantation. The current consensus guidelines for ICD implantation appear to be generalizable to treating octogenarians who are otherwise medically fit.
Actuarial Analysis↗
The burden of atrial fibrillation: should we abandon antiarrhythmic drug therapy?
Atrial fibrillation (AF) is the most common sustained arrhythmia, exacting a substantial toll in cardiovascular morbidity and mortality. Until recently, the prevailing philosophy has been that restoration and maintenance of normal sinus rhythm, as opposed to control of ventricular response rate, was the optimal approach to treatment of AF. A series of landmark trials (AFFIRM, RACE, STAF, and PIAF) have called this strategy into question, suggesting outcomes are equivalent with both approaches. These data do not mean that rhythm control is not beneficial, but highlight the limitations of current therapies to achieve and maintain sinus rhythm. Limitations of the rhythm-control strategy may be related to our difficulty in accurately documenting symptomatic benefit from this approach, the lack of efficacy and excessive adverse-effect burden associated with currently available antiarrhythmic agents, and selection biases in the enrollment of patients in clinical trials of rhythm control versus rate control, making the trials incompletely representative of the population eligible for therapy. New pharmacologic agents under development feature increased atrial selectivity or multi-channel-blocking properties (or both). As a result, these compounds may be more effective in prolonging atrial refractoriness and may also have reduced proarrhythmic potential. It is premature to abandon the concept of rhythm control in AF until we have trials designed to include younger and highly symptomatic patients, more sensitive tools to measure symptomatic improvement, and safer, more effective antiarrhythmic agents.
Anti-Arrhythmia Agents↗
The 2004 ACC/AHA Guidelines: a perspective and adaptation for Canada by the Canadian Cardiovascular Society Working Group.
Major changes in acute ST elevation myocardial infarction (STEMI) management prompted a comprehensive rewriting of the American College of Cardiology/American Heart Association Guidelines. The Canadian Cardiovascular Society (CCS) participated in both the writing process and the external review. Subsequently, a Canadian Working Group (CWG), formed under the auspices of the CCS, developed a perspective and adaptation for Canada. Herein, accounting for specific realities of the Canadian cardiovascular health system, is a discussion of the implications for prehospital care and transport, optimal reperfusion therapy and an approach to decision making regarding reperfusion options and invasive therapy following fibrinolytic therapy. Major recent developments regarding indications for implantable cardioverter defibrillator(s) (ICDs) also prompted a review of indications for ICDs and the optimal timing of implantation given the potential for recovery of left ventricular function. At least a 40-day, preferably a 12-week, waiting period was judged to be optimal to evaluate left ventricular function post-STEMI. A recommended algorithm for the insertion of an ICD is provided. Implementation of the new STEMI guidelines has substantial implications for resources, organization and priorities of the Canadian health care system. While on the one hand, the necessary incremental funding to provide tertiary and quaternary care and to support revascularization and device implantation capability is desirable, it is equally or more important to develop enhanced prehospital care, including the capacity for early recognition, risk assessment, fibrinolytic therapy and/or triage to a tertiary care centre as part of an enlightened approach to improving cardiac care.
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Assessment of the cardiac patient for fitness to drive: drive subgroup executive summary.
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Accidents, Traffic↗
Restoring sinus rhythm in atrial fibrillation: a Pyrrhic victory?
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Amiodarone↗
Effectiveness of implantable defibrillators for preventing arrhythmic events and death: a meta-analysis.
OBJECTIVES: The aim of this study was to compare the effectiveness of the implantable cardioverter defibrillator (ICD) and medical strategies for prevention of arrhythmic events and death. BACKGROUND: The ICD is a potential strategy to reduce mortality in patients at risk of sudden death. METHODS: The MEDLINE, EMBASE, and Cochrane Library electronic databases were searched from January 1966 to April 2002. All published randomized controlled trials comparing ICD implantation with medical therapy were reviewed. Four independent reviewers extracted data on all-cause mortality, nonarrhythmic death, and arrhythmic death using a standardized protocol. RESULTS: Nine studies including over 5,000 patients were synthesized using both fixed-effects and random-effects models. The primary and secondary prevention trials showed a significant benefit of the ICD with respect to arrhythmic death, with relative risks (RR) of 0.34 and 0.50, respectively (both p < 0.001). The mortality benefit of the ICD was entirely attributable to a reduction in arrhythmic death (all trials: p < 0.00001). Whereas the secondary prevention trials exhibited a robust decrease in all-cause ICD mortality (RR 0.75; p < 0.001), the pooled primary prevention trials demonstrated decreased all-cause ICD mortality (RR 0.66; p < 0.05) which was dependent on selected individual trials. The disparity in ICD-related mortality reductions in the primary prevention trials was related to variability in the incidence of arrhythmic death between individual studies. CONCLUSIONS: Although the ICD decreases the risk of arrhythmic death, its impact on all-cause mortality is related to the underlying risk of arrhythmia-related death relative to competing causes. Given the cost of the device strategy, policies of targeted intervention based on the future risk of arrhythmia are warranted.
Arrhythmias, Cardiac↗
A view from the bridge: agreement between the SF-6D utility algorithm and the Health Utilities Index.
BACKGROUND: The SF-6D is a new health state classification and utility scoring system based on 6 dimensions ('6D') of the Short Form 36, and permits a "bridging" transformation between SF-36 responses and utilities. The Health Utilities Index, mark 3 (HUI3) is a valid and reliable multi-attribute health utility scale that is widely used. We assessed within-subject agreement between SF-6D utilities and those from HUI3. METHODS: Patients at increased risk of sudden cardiac death and participating in a randomized trial of implantable defibrillator therapy completed both instruments at baseline. Score distributions were inspected by scatterplot and histogram and mean score differences compared by paired t-test. Pearson correlation was computed between instrument scores and also between dimension scores within instruments. Between-instrument agreement was by intra-class correlation coefficient (ICC). RESULTS: SF-6D and HUI3 forms were available from 246 patients. Mean scores for HUI3 and SF-6D were 0.61 (95% CI 0.60-0.63) and 0.58 (95% CI 0.54-0.62) respectively; a difference of 0.03 (p<0.03). Score intervals for HUI3 and SF-6D were (-0.21 to 1.0) and (0.30-0.95). Correlation between the instrument scores was 0.58 (95% CI 0.48-0.68) and agreement by ICC was 0.42 (95% CI 0.31-0.52). Correlations between dimensions of SF-6D were higher than for HUI3. CONCLUSIONS: Our study casts doubt on the whether utilities and QALYs estimated via SF-6D are comparable with those from HUI3. Utility differences may be due to differences in underlying concepts of health being measured, or different measurement approaches, or both. No gold standard exists for utility measurement and the SF-6D is a valuable addition that permits SF-36 data to be transformed into utilities to estimate QALYs. The challenge is developing a better understanding as to why these classification-based utility instruments differ so markedly in their distributions and point estimates of derived utilities.
Algorithms↗
Advances in the acute pharmacologic management of cardiac arrhythmias.
Safe and effective control of rapid ventricular rates in acute-onset atrial fibrillation (AF) can be accomplished with intravenous calcium antagonists, beta-blockers or amiodarone; digoxin is less effective. If pharmacologic cardioversion of AF is desired, single oral doses of propafenone or flecainide are safe and effective in patients without structural heart disease. Intravenous ibulitide is moderately effective in the conversion of persistent AF or atrial flutter, with a small risk of proarrhythmia. In wide QRS complex tachycardia of uncertain origin, adenosine and lidocaine are no longer recommended. Procainamide or amiodarone are the treatment options, but attempts should be made to define the origin of tachycardia. In the treatment of monomorphic ventricular tachycardia, lidocaine is no longer recommended; procainamide or amiodarone are the recommended therapies. In polymorphic ventricular tachycardia with a normal QT interval, beta-blockers are recommended. In shock-refractory ventricular fibrillation, lidocaine, and magnesium are ineffective; intravenous amiodarone should be the treatment of choice.
Anti-Arrhythmia Agents↗
Effect of an implantable cardioverter defibrillator with atrial detection and shock therapies on patient-perceived, health-related quality of life.
BACKGROUND: This study used a device (DDD implantable cardioverter defibrillator [ICD]) capable of delivering pacing and shock therapies to restore normal sinus rhythm in patients with atrial tachycardias or atrial fibrillation (AF). The purpose of this study was to assess the effect of the device on patient-perceived, health-related quality of life (QOL). METHODS: The DDD ICD was implanted in 267 patients with drug refractory, symptomatic AF from 45 centers across Europe, the United States, and Canada. Patients completed self-reported, validated QOL assessments at baseline and at 3- and 6-month follow-up visits (The Medical Outcomes Short Form 36 [SF-36] and the Symptom Checklist [SCL]). RESULTS: The mean age of the study group was 62 +/- 12 years, and 73% of the patients were male. A total of 150 patients completed SF-36 assessments, and 138 patients completed SCL assessments at all 3 times. Baseline scores were more impaired (P <.05) on most SF-36 scales compared with norms for a general population, but were similar to a comparison group of patients with AF who were referred to tertiary care centers. The role-physical, physical functioning, vitality, mental health, and social functioning scales all improved significantly with time (all P <.04). Similarly, symptom frequency and severity (SCL) also improved significantly from baseline to 6 months (both P <.01). Shock therapy was delivered in 86 of the 150 patients (57%) with complete SF-36 evaluations. There was no evidence that receiving shocks decreased the relative improvement in QOL associated with implantation of the device. CONCLUSIONS: In a 6-month period, QOL improves after implantation of a DDD ICD with atrial shock and pacing therapies. These improvements were not attenuated by receipt of shocks.
Atrial Fibrillation↗
Is inappropriate implantable defibrillator shock therapy predictable?
OBJECTIVE: To identify implantable cardioverter defibrillator (ICD) patients who are at risk of receiving inappropriate shock. BACKGROUND: Inappropriate ICD shock, usually from atrial fibrillation (AF) or sinus tachycardia (ST), is a common problem. We hypothesized that clinical variables would predict which patients with single chamber ICDs would be more likely to receive inappropriate therapy and be candidates for more accurate discriminators such as those available in dual chamber ICDs. METHODS: The ICD registry at St. Michael's Hospital has it's clinical information and demographic data updated after each clinic visit. Inappropriate shock was considered as the outcome variable. Possible predictors considered were age, gender, ejection fraction, NYHA class, prior CABG and prior history of AF. Univariate predictors were identified using t-test for continuous variables and Chi-square test for categorical variables. Multivariate predictors were identified using stepwise logistic regression analyses. RESULTS: Of 299 patients, 261 had complete data for analysis. In this population 78% were male, mean age was 60 +/- 13 years, mean ejection fraction was 37 +/- 15% and mean follow up was 53 +/- 36 months. One hundred and sixteen of the 261 patients (44%) received one or more inappropriate therapies (73% within 2 years of receiving their device), and 140 (51%) received one or more appropriate therapies. Significant predictors of inappropriate therapy by multivariate model were prior AF (OR 2.6, 95% CI 1.5-4.5) and NYHA class 1 vs. classes 2-4 (OR 2.2, 95% CI 1.2-3.7). CONCLUSION: Clinical characteristics of ICD patients can predict those at risk for inappropriate shock and should be considered for interventions to decrease such shocks.
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