D George Wyse

The University of Calgary, Calgary, Alberta, Canada

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Publications (234)1898.07 Total impact

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    ABSTRACT: The association between standard parameters from a simple 12-lead ECG (i.e., QRS duration and PR, JT, and QT intervals) and adverse cardiovascular outcomes (cardiovascular mortality, all-cause mortality, arrhythmic mortality, and hospitalizations) in patients with a history of atrial fibrillation (AF) has not been previously studied. : A pooled analysis of patient-level data was conducted on 5436 patients, age 68.2±8.3 years, 34.8% female, with a history of non-permanent AF randomized in AFFIRM and AF-CHF trials. The predictive value of ECG parameters was assessed in AF and sinus rhythm in multivariate Cox regression models. During a follow-up of 40.8±16.3 months, QRS duration >120 msec was independently associated with all-cause mortality [hazard ratio (HR) 1.46, 95% confidence interval (CI; 1.21-1.76) in AF, p<0.001], cardiovascular mortality [HR 1.75, 95% CI (1.15-2.65) in sinus rhythm, p = 0.009; HR 1.56, 95% CI (1.27-1.93) in AF, p<0.001], arrhythmic mortality [HR 1.90, 95% CI (1.09-3.32) in sinus, p = 0.024; HR 1.84, 95% CI (1.35-2.51) in AF, p<0.001], any hospitalization [HR 1.15, 95% CI (1.02-1.29) in AF, p = 0.027], and cardiovascular hospitalization [HR 1.21, 95% CI (1.06-1.37) in AF; p = 0.004]. Increased PR interval (>200 msec) was independently associated with cardiovascular [HR 1.56, 95% CI (1.11-2.21), p = 0.010] and arrhythmic [HR 1.91, 95% CI (1.14-3.18), p = 0.004] mortality. The JT and QTc intervals were not predictive of mortality. : Simple parameters from standard ECGs are significantly and independently associated with adverse cardiovascular outcomes in patients with a history of AF. This article is protected by copyright. All rights reserved
    No preview · Article · Jan 2016 · Journal of Cardiovascular Electrophysiology
  • D. George Wyse

    No preview · Article · Dec 2015 · JACC Clinical Electrophysiology
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    ABSTRACT: Hypertension is an established risk factor for new-onset atrial fibrillation (AF). However, the relationship between blood pressure and recurrent AF is less well understood. A pooled analysis of patient-level data from AFFIRM and AF-CHF trials was conducted on all 2715 patients with paroxysmal or persistent AF, 68 ± 8 years, 66% male, randomized to rhythm control and followed for 40.6 ± 16.5 months. We assessed the impact of a baseline systolic blood pressure [SBP; <120 mmHg (N = 1008), 120-140 mmHg (N = 930), >140 mmHg (N = 777)] on recurrent AF and proportion of time spent in AF. In patients with LVEF >40% (N = 1719), SBP was not associated with recurrent AF in multivariate regression analyses (P = 0.752). In contrast, in patients with LVEF ≤40% (N = 996), the AF recurrence rate was higher in those with a SBP >140 mmHg compared to 120-140 mmHg [hazard ratio 1.47; 95% CI (1.12-1.93), P = 0.005]. The rate of recurrent AF was similar in patients with SBP <120 mmHg compared to 120-140 mmHg [hazard ratio 1.15; 95% CI (0.92-1.43), P = 0.225]. Consistently, the proportion of time spent in AF was not influenced by SBP in patients with LVEF >40% (P = 0.645). However, in patients with LVEF ≤40%, the adjusted mean proportion of time spent in AF was 17.2% if SBP was <120 mmHg, 15.4% for SBP 120-140 mmHg, and 24.0% for SBP >140 mmHg (P = 0.025). Systolic blood pressure is an important determinant of recurrent AF and overall AF burden in patients with left ventricular dysfunction (LVEF ≤ 40%) but not in those with preserved ventricular function. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · Feb 2015 · Journal of Cardiovascular Electrophysiology
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    ABSTRACT: AimsTo investigate the association between baseline systolic blood pressure levels and mortality in patients with AF with or without LV dysfunction. Hypertension leads to cardiovascular disease but, in specific groups, low blood pressure has been associated with a paradoxical increase in mortality. In patients with AF and heart failure, the relationship between blood pressure and death remains largely unknown.Methods and resultsWe conducted a post-hoc combined analysis on pooled data from AFFIRM and AF-CHF trials and assessed the relationship between baseline systolic blood pressure (SBP) and mortality and hospitalizations. Patients were classified according to LVEF (>40%, ≤40%) and baseline SBP (<120 mmHg, 120–140 mmHg, >140 mmHg). A total of 5436 patients with non-permanent AF were followed for 41 ± 16 months. In patients with LVEF >40%, baseline SBP was not related to mortality using multivariate Cox regression analyses to adjust for baseline differences (P = 0.563). In contrast, in patients with LVEF ≤40% (n = 1980), SBP <120 mmHg and SBP >140 mmHg were both associated with a significant increase in total mortality compared with SBP 120–140 mmHg [hazard ratio (HR) 1.75, 95% confidence interval (CI) 1.41–2.17; and HR 1.40, 95% CI 1.04–1.90, respectively]. Hospitalizations were unrelated to SBP regardless of LVEF.Conclusions Mortality is modulated by baseline SBP levels in patients with AF and depressed EF but not in patients with normal EF. Targeted therapy of AF patients based on SBP merits further prospective investigation.
    No preview · Article · Nov 2014 · European Journal of Heart Failure
  • D. George Wyse

    No preview · Article · Oct 2014 · The Canadian journal of cardiology
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    ABSTRACT: Introduction: Despite amiodarone's established safety profile in the setting of heart failure, it is unknown whether its impact on cardiovascular outcomes in patients with atrial fibrillation is modulated by left ventricular function. Methods and results: A pooled analysis of 3,307 patients (age 68.0 ± 0.2 years; 31.1% female) enrolled in AFFIRM and AF-CHF trials was conducted to assess the effect of rhythm control with amiodarone on cardiovascular outcomes, according to left ventricular systolic function. In amiodarone-treated patients (N = 1,107), freedom from recurrent atrial fibrillation was 84% and 45% at 1 and 5 years, respectively, with no differences according to left ventricular function (P = 0.8754). Similarly, the adjusted proportion of time spent in atrial fibrillation (15.0 ± 1.8%) did not vary according to ventricular function (P = 0.6094). Over 40.0 ± 0.3 months of follow-up, 1,963 (59.4%) patients required at least one hospitalization, 1,401 (42.6%) of whom had cardiovascular-related hospitalizations. Adjusted all-cause and cardiovascular hospitalization rates were similar with amiodarone versus rate control in all patients and in subgroups with and without severe left ventricular dysfunction. A total of 729 (22.0%) patients died, 498 (15.1%) from cardiovascular causes. Adjusted all-cause and cardiovascular mortality rates were similar with amiodarone versus rate control overall and in subgroups with and without severe left ventricular dysfunction. Conclusion: Amiodarone's efficacy in maintaining sinus rhythm and reducing the burden of atrial fibrillation is similar in the presence or absence of severe left ventricular dysfunction. Rhythm control with amiodarone is associated with comparable hospitalization and mortality rates to rate control in patients with and without left ventricular dysfunction.
    No preview · Article · Sep 2014 · Journal of Cardiovascular Electrophysiology
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    ABSTRACT: The historical origin of the term ‘lone atrial fibrillation (AF)’ predates by 80 years our current understanding of the pathophysiology of AF, the multitude of known etiologies for AF, and our ability to image and diagnose heart disease. The term was meant to indicate AF in whom subsequent investigations could not demonstrate heart disease, but for many practitioners has become synonymous with ‘idiopathic AF’. As the list of heart diseases has expanded and diagnostic techniques have improved, the prevalence of ‘lone AF’ has fallen. The legacy of the intervening years is that definitions of ‘lone AF’ in the literature are inconsistent such that studies of ‘lone AF’ are not comparable Guidelines provide a vague definition of ‘lone AF’ but do not provide direction about how much or what kind of imaging and other testing are necessary to exclude heart disease. There has been an explosion in the understanding of the pathophysiology of AF in the last 20 years in particular. Nevertheless, there are no apparently unique mechanisms for AF in patients categorized as ‘lone AF’. In addition, the term ‘lone AF’ is not invariably useful in making treatment decisions, and other tools for doing so have been more thoroughly and carefully validated. It is therefore recommended that use of the term ‘lone AF’ be avoided.
    No preview · Article · Jan 2014 · Journal of the American College of Cardiology
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    Full-text · Article · Oct 2013 · The Canadian journal of cardiology
  • D George Wyse
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    ABSTRACT: Catheter ablation for atrial fibrillation (AF) is a procedural treatment option that has yet to find its final place in AF rhythm management. So far, other than pulmonary vein isolation, it does not have an indisputable mechanistic basis. It is empirical, not truly individualized on the basis of a diagnostic procedure. Success for the procedure is usually couched in terms of a measure of recurrence of AF. Existing data concerning recurrence have several confounders. Recurrence data are often subjective: They are based on surveys and symptoms rather than objective electrocardiogram (ECG) determination of recurrence, patients are highly selected, concurrent use of antiarrhythmic drugs is included or excluded, redo procedures may or may not be included, and follow-up is frequently a year or less. The nature of the AF (paroxysmal, persistent, long-standing persistent) greatly impacts success rates, which range from 20% to 85%. The procedure is probably infrequently a lifelong "cure" for AF. Best estimate of the risk of a complication from each procedure is about 4.5%, the commonest being tamponade (1.3%), vascular access complications (1.5%), and stroke or transient ischemic attach (1%). Risk of a fatal complication is estimated at 0.15%. There is no convincing evidence that the procedure decreases the risk of death, stroke, or hospitalization for heart failure, but the available randomized trials have enrolled patients inappropriate for assessment of impact on these clinical outcomes. Much remains to be done. Currently the procedure is indicated for relief of symptoms in selected patients, usually who have failed antiarrhythmic drug therapy.
    No preview · Article · May 2013 · The Canadian journal of cardiology
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    Full-text · Article · Mar 2013 · Journal of the American College of Cardiology
  • D George Wyse
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    ABSTRACT: QUESTIONS In adults with persistent atrial fibrillation (AF), is flecainide better than no antiarrhythmic drug therapy for preventing recurrent AF or death after cardioversion? Is short-term flecainide noninferior to long-term flecainide? METHODS DESIGN Randomized controlled noninferiority trial (Flecainide Short-Long [Flec-SL] trial). Current Controlled Trials ISRCTN 62728742. ALLOCATION Concealed.* BLINDING Blinded* (primary outcome assessors). FOLLOW-UP PERIOD 4 weeks and 6 months. SETTING 44 centers in Germany. PATIENTS 635 patients ≥ 18 years of age (mean age 64 y, 66% men) who had persistent electrocardiograph-confirmed AF and planned cardioversion that was successful. Exclusion criteria included use of other antiarrhythmic drugs for 5 half-lives before enrollment or amiodarone in the past 6 months. INTERVENTION Flecainide, 200 to 300 mg/d, for 4 weeks (short term, n = 273); flecainide for 6 months (long term, n = 281); or no antiarrhythmic drug therapy (control, n = 81). All patients received flecainide for ≥ 48 hours before cardioversion. OUTCOMES Primary outcome was a composite of recurrent persistent AF or death. Enrollment in the control group was stopped after a preplanned analysis at 4 weeks of follow-up. Noninferiority criterion was ≤ 12% absolute difference between short- and long-term flecainide for Kaplan-Meier point estimates of the primary outcome (1-sided α = 0.025). PATIENT FOLLOW-UP 95% included in the primary per-protocol analysis. MAIN RESULTS At 4 weeks, flecainide improved survival without recurrent AF more than no treatment (n = 242†, 70% vs 53%, P = 0.016). At 6 months, fewer patients in the short-term than the long-term flecainide group survived without recurrent AF; noninferiority criterion for short-term flecainide was not met in per-protocol (Table) or intention-to-treat analysis. Post hoc landmark analysis of the 62% of patients receiving flecainide without AF recurrence at 4 weeks found that long-term was better than short-term flecainide for preventing AF recurrence or death at 6 months (hazard ratio 0.31, 95% CI 0.18 to 0.56). CONCLUSION In adults with persistent atrial fibrillation, flecainide after cardioversion was better than no antiarrhythmic drug therapy for preventing recurrence; short-term flecainide was less effective than long-term flecainide.Flecainide for 4 wk vs 6 mo after cardioversion in patients with persistent AF‡OutcomeFlecainide for 4 wkFlecainide for 6 moAt 6 mo, difference (95% CI)Survival without recurrent AF§48%56%7.9% (-1.9 to 18)||‡AF = atrial fibrillation; CI defined in Glossary.§No deaths occurred.||Per-protocol analysis. Noninferiority criterion (upper bound of CI ≤ 12%) was not met.
    No preview · Article · Sep 2012 · Annals of internal medicine
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    ABSTRACT: The detection of undiagnosed atrial tachycardia/atrial fibrillation (AT/AF) among patients with stroke risk factors could be useful for primary stroke prevention. We analyzed newly detected AT/AF (NDAF) using continuous monitoring in patients with stroke risk factors but without previous stroke or evidence of AT/AF. NDAF (AT/AF >5 minutes on any day) was determined in patients with implantable cardiac rhythm devices and ≥1 stroke risk factors (congestive heart failure, hypertension, age ≥75 years, or diabetes). All devices were capable of continuously monitoring the daily cumulative time in AT/AF. Of 1,368 eligible patients, NDAF was identified in 416 (30%) during a follow-up of 1.1 ± 0.7 years and was unrelated to the CHADS(2) score (congestive heart failure, hypertension [blood pressure consistently >140/90 mm Hg or hypertension treated with medication], age ≥75 years, diabetes mellitus, previous stroke or transient ischemic attack). The presence of AT/AF >6 hours on ≥1 day increased significantly with increased CHADS(2) scores and was present in 158 (54%) of 294 patients with NDAF and a CHADS(2) score of ≥2. NDAF was sporadic, and 78% of patients with a CHADS(2) score of ≥2 with NDAF experienced AT/AF on <10% of the follow-up days. The median interval to NDAF detection in these higher risk patients was 72 days (interquartile range 13 to 177). In conclusion, continuous monitoring identified NDAF in 30% of patients with stroke risk factors. In patients with NDAF, AT/AF occurred sporadically, highlighting the difficulty in detecting paroxysmal AT/AF using traditional monitoring methods. However, AT/AF also persisted for >6 hours on ≥1 days in most patients with NDAF and multiple stroke risk factors. Whether patients with CHADS(2) risk factors but without a history of AF might benefit from implantable monitors for the selection and administration of anticoagulation for primary stroke prevention merits additional investigation.
    No preview · Article · Jul 2012 · The American journal of cardiology
  • D George Wyse

    No preview · Article · Feb 2012 · Europace
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    ABSTRACT: Vernakalant is a novel, relatively atrial-selective antiarrhythmic agent for conversion of atrial fibrillation (AF) to sinus rhythm. This study examined the safety and efficacy of vernakalant in converting atrial flutter (AFL) to sinus rhythm. This was a phase 2/3, randomized, double-blind, placebo-controlled trial. Adults with AFL received either a 10 min infusion of 3.0 mg/kg vernakalant (n = 39) or placebo (n = 15). If AFL or AF persisted at the end of a 15 min observation period, a second 10 min infusion of 2.0 mg/kg vernakalant or placebo was administered. The primary efficacy outcome was the proportion of patients who had treatment-induced conversion of AFL to sinus rhythm for a minimum duration of 1 min within 90 min after the start of the first infusion. No patient in the placebo group met the primary outcome. Only one patient receiving vernakalant (1 of 39, 3%) converted to sinus rhythm. A reduced mean absolute ventricular response rate occurred within 50 min in patients receiving vernakalant (mean change from baseline -8.2 b.p.m.) vs. patients receiving placebo (-0.2 b.p.m.) (P = 0.037). A post-hoc analysis revealed that vernakalant increased AFL cycle length by an average of 55 ms, whereas the AFL cycle length was unchanged in the placebo group (P < 0.001). There was no occurrence of 1 : 1 atrio-ventricular conduction. Dysgeusia and sneezing were the most common treatment-related adverse events, consistent with previous reports. Vernakalant did not restore sinus rhythm in patients with AFL. Vernakalant modestly slowed AFL and ventricular response rates, and was well tolerated.
    Full-text · Article · Jan 2012 · Europace
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    ABSTRACT: The impact of individual antiarrhythmic drugs (AADs) on mortality and hospital stay in atrial fibrillation (AF) was evaluated. Cardiovascular (CV) outcomes in AF patients receiving pharmacologic rhythm control therapy have not been compared with rate control therapy on the basis of AAD selection. We compared CV outcomes in the AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) trial in subgroups defined by the initial AAD selected with propensity score matched subgroups from the rate arm (Rate). Seven hundred twenty-nine amiodarone patients, 606 sotalol patients, and 268 Class 1C patients were matched. The composite outcome of mortality or cardiovascular hospital stays (CVH) showed better outcomes with Rate compared with amiodarone (hazard ratio [HR]: 1.18, 95% confidence interval [CI]: 1.03 to 1.36, p = 0.02), sotalol (HR: 1.32, 95% CI: 1.13 to 1.54, p < 0.001), and Class 1C (HR: 1.22, 95% CI: 0.97 to 1.56, p = 0.10). There was a nonsignificant increase in mortality with amiodarone (HR: 1.20, 95% CI: 0.94 to 1.53, p = 0.15) with the risk of non-CV death being significantly higher with amiodarone versus Rate (HR: 1.11, 95% CI: 1.01 to 1.24, p = 0.04). First CVH event rates at 3 years were 47% for amiodarone, 50% for sotalol, and 44% for Class 1C versus 40%, 40%, and 36%, respectively, for Rate (amiodarone HR: 1.20, 95% CI: 1.03 to 1.40, p = 0.02, sotalol HR: 1.364, 95% CI: 1.16 to 1.611, p < 0.001, Class 1C HR: 1.24, 95% CI: 0.96 to 1.60, p = 0.09). Time to CVH with intensive care unit stay or death was shorter with amiodarone (HR: 1.22, 95% CI: 1.02 to 1.46, p = 0.03). In AFFIRM, composite mortality and CVH outcomes differed for Rate and AADs due to differences in CVH; CVH event rates during follow-up were high for all cohorts, but they were higher for all groups on AADs. Death, intensive care unit hospital stay, and non-CV death were more frequent with amiodarone.
    Full-text · Article · Nov 2011 · Journal of the American College of Cardiology
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    D George Wyse

    Preview · Article · Aug 2011 · Journal of the American College of Cardiology
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    ABSTRACT: The temporal relationship between atrial tachyarrhythmias (atrial tachycardia [AT] and atrial fibrillation [AF]) and cerebrovascular events/systemic emboli (CVE/SE) is unknown. The purpose of this study was to evaluate this relationship using stored AT/AF diagnostic data from implanted devices in patients with and those without AF. The TRENDS study enrolled 2,486 patients with an indication for an implantable device, at least one stroke risk factor, and available device data. The current study includes the subgroup of 40 (1.6%) patients enrolled in TRENDS who experienced CVE/SE. AT/AF was detected prior to CVE/SE in 20 (50%) of 40 patients. Other than average and maximum daily AT/AF burden and duration of device monitoring prior to CVE/SE, no statistically significant differences were found between patients with and those without AT/AF prior to CVE/SE. For the 20 patients with AT/AF detected prior to CVE/SE, 9 (45%) did not have any AT/AF in the 30 days prior to CVE/SE. Therefore, 29 (73%) of 40 patients with CVE/SE had zero AT/AF burden within 30 days prior to CVE/SE. Fourteen (70%) of the 20 patients with AT/AF detected prior to CVE/SE were not in AT/AF at diagnosis of CVE/SE. The last episode of AT/AF in these 14 patients was 168 ± 199 days (range 3-642 days) before CVE/SE. The majority of CVE/SE in this population did not occur proximal to recent AT/AF episodes. These data imply that the mechanisms of CVE/SE in patients with implantable devices may importantly involve mechanisms other than cardioembolism due to atrial tachyarrhythmias.
    No preview · Article · Apr 2011 · Heart rhythm: the official journal of the Heart Rhythm Society
  • D George Wyse

    No preview · Article · Jan 2011 · The Canadian journal of cardiology
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    ABSTRACT: The objective of the present study was to assess the safety and effectiveness of vernakalant hydrochloride injection (RSD1235), a novel antiarrhythmic drug, for the conversion of atrial fibrillation (AF) or atrial flutter to sinus rhythm (SR). Patients with either AF or atrial flutter were randomized in a 1:1 ratio to receive vernakalant (n = 138) or placebo (n = 138) and were stratified by an arrhythmia duration of >3 hours to ≤7 days (short duration) and 8 to ≤45 days (long duration). The first infusion of placebo or vernakalant (3 mg/kg) was given for 10 minutes followed by a second infusion of placebo or vernakalant (2 mg/kg) 15 minutes later if the arrhythmia had not terminated. A total of 265 patients were randomized and received treatment. The primary end point was conversion of AF to SR for ≥1 minute within 90 minutes of the start of the drug infusion in the short-duration AF group. Of the 86 patients receiving vernakalant in the short-duration AF group, 44 (51.2%) demonstrated conversion to SR compared to 3 (3.6%) of the 84 in the placebo group (p <0.0001). The median interval to conversion of short-duration AF to SR in the responders given vernakalant was 8 minutes. Of the entire AF population (short- and long-duration AF), 47 (39.8%) of the 118 vernakalant patients experienced conversion of AF to SR compared to 4 (3.3%) of the 121 placebo patients (p <0.0001). Transient dysgeusia and sneezing were the most common adverse events in the vernakalant patients. One vernakalant patient who had severe aortic stenosis experienced hypotension and ventricular fibrillation and died. In conclusion, vernakalant demonstrated a rapid and high rate of conversion for short-duration AF and was well tolerated.
    No preview · Article · Nov 2010 · The American journal of cardiology
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    Preview · Article · May 2010 · Stroke

Publication Stats

11k Citations
1,898.07 Total Impact Points

Institutions

  • 1984-2014
    • The University of Calgary
      • • Department of Cardiac Sciences
      • • Faculty of Medicine
      • • Department of Medicine
      Calgary, Alberta, Canada
  • 2009
    • University of Pennsylvania
      • Department of Medicine
      Philadelphia, PA, United States
  • 2005
    • Procter & Gamble
      Cincinnati, Ohio, United States
    • Calgary Scientific
      Calgary, Alberta, Canada
  • 2004
    • University of Massachusetts Amherst
      Amherst Center, Massachusetts, United States
    • McMaster University
      • Centre for Evaluation of Medicines
      Hamilton, Ontario, Canada
    • University of Alabama at Birmingham
      • Department of Medicine
      Birmingham, Alabama, United States
  • 2002
    • Rhode Island Hospital
      Providence, Rhode Island, United States
  • 1986-1988
    • University of Alberta
      Edmonton, Alberta, Canada
    • The University of Western Ontario
      London, Ontario, Canada