Publications by authors named "Nathaniel M Hawkins"

71 Publications

Identifying heart failure in patients with chronic obstructive lung disease through the Canadian Primary Care Sentinel Surveillance Network in British Columbia: a case derivation study.

CMAJ Open 2021 Apr-Jun;9(2):E376-E383. Epub 2021 Apr 16.

School of Population and Public Health (Vijh), Centre for Health Services and Policy Research (Wong, Peterson, Ezzat, Gibb) and School of Nursing (Wong, Ezzat), University of British Columbia, Vancouver, BC; Primary Care Research Unit (Grandy) and Department of Family Medicine (Grandy), Dalhousie University, Halifax, NS; Division of Cardiology (Hawkins), University of British Columbia, Vancouver, BC.

Background: Heart failure (HF) poses a substantial global health burden, particularly in patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to validate an electronic medical record-based definition of HF in patients with COPD in primary care practices in the province of British Columbia, Canada.

Methods: We conducted a cross-sectional retrospective chart review from Sept. 1, 2018, to Dec. 31, 2018, for a cohort of patients from primary care practices in BC whose physicians were recruited through the BC node of the Canadian Primary Care Sentinel Surveillance Network. Heart failure case definitions were developed by combining diagnostic codes, medication information and laboratory values available in primary care electronic medical records. These were compared with HF diagnoses identified through detailed chart review as the gold standard. Sensitivity, specificity, negative (NPV) and positive predictive values (PPV) were calculated for each definition.

Results: Charts of 311 patients with COPD were reviewed, of whom 72 (23.2%) had HF. Five categories of definitions were constructed, all of which had appropriate sensitivity, specificity and NPV. The optimal case definition consisted of 1 HF billing code or a specific combination of medications for HF. This definition had an excellent specificity (93.3%, 95% confidence interval [CI] 89.4%-96.1%), sensitivity (90.3%, 95% CI 81.0%-96.0%), PPV (80.2%, 95% CI 69.9%-88.3%) and NPV (97.0%, 95% CI 93.8%-98.8%).

Interpretation: This comprehensive case definition improves upon previous primary care HF definitions to include medication codes and laboratory data, along with previously used billing codes. A case definition for HF was derived and validated and can be used with data from electronic medical records to identify HF in patients with COPD in primary care accurately.
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http://dx.doi.org/10.9778/cmajo.20200183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084551PMC
April 2021

Anticoagulation management of postoperative atrial fibrillation after cardiac surgery: A systematic review.

J Card Surg 2021 Mar 26. Epub 2021 Mar 26.

Division of Cardiovascular Surgery, University of British Columbia, Vancouver, British Columbia, Canada.

Background: Postoperative atrial fibrillation (POAF) often complicates cardiac surgery and is associated with increased mortality and risk of thromboembolism. However, the optimal oral anticoagulation (OAC) strategy is uncertain. We performed a systematic review to examine the OAC practice patterns and efficacy in these circumstances.

Methods: MEDLINE and EMBASE were searched from 2000 to 2019 using the search terms cardiac surgical procedures, cardiac surgery, postoperative complications, atrial fibrillation, atrial flutter, and terms for anticoagulants. Collected data included anticoagulation patterns (time of initiation, type, and duration) and outcomes (stroke, bleeding, and mortality).

Results: From 763 records, 4 prospective and 13 retrospective studies were included totaling 44,908 patients with 8929 (19.9%) who developed POAF. Anticoagulation rates ranged from 4% to 43% (mean 21% overall). Sixteen studies used warfarin, 3 nonvitamin K OAC (NOAC), and 2 both. Four studies reported the use of bridging unfractionated or low-molecular-weight heparin. Concomitant antiplatelet therapy was reported in half the studies, ranging from 80% to 99%. OAC use was associated with lower risk of thromboembolic events in two retrospective studies (including a national Danish cohort with 2108 patients with POAF). Patients discharged on warfarin experienced reduced mortality in a large, single center, retrospective analysis, but no association was observed in the Danish cohort.

Conclusion: There is wide practice variation in the uptake, timing of initiation, duration, and choice of OAC for POAF following cardiac surgery. The evidence is largely retrospective and insufficient to assess the efficacy of different OAC strategies. Further studies are warranted to guide clinical practice.
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http://dx.doi.org/10.1111/jocs.15396DOI Listing
March 2021

Validity of different dose reduction criteria for apixaban.

Am Heart J 2021 Mar 21. Epub 2021 Mar 21.

Centre for Cardiovascular Innovation, University of British Columbia, Vancouver, Canada.

Reduced-dose apixaban is recommended in patients fulfilling 2 of 3 criteria: age ≥80 years, body weight ≤60 kg, and serum creatinine ≥1.5 mg/dL. However, patient weight is often not available in electronic health data. We examined the validity of alternative definitions based on age and renal function alone using an observational dataset of patients with atrial fibrillation and chronic kidney disease which included weight measurements.
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http://dx.doi.org/10.1016/j.ahj.2021.03.004DOI Listing
March 2021

Autonomic Alterations After Pulmonary Vein Isolation in the CIRCA-DOSE (Cryoballoon vs Irrigated Radiofrequency Catheter Ablation) Study.

J Am Heart Assoc 2021 Feb 26;10(5):e018610. Epub 2021 Feb 26.

Center for Cardiovascular Innovation Vancouver Canada.

Background The natural history of autonomic alterations following catheter ablation of drug-refractory paroxysmal atrial fibrillation is poorly defined, largely because of the historical reliance on non-invasive intermittent rhythm monitoring for outcome ascertainment. Methods and Results The study included 346 patients with drug-refractory paroxysmal atrial fibrillation undergoing pulmonary vein isolation using contemporary advanced-generation ablation technologies. All patients underwent insertion of a Reveal LINQ (Medtronic) implantable cardiac monitor before ablation. The implantable cardiac monitor continuously recorded physical activity, heart rate variability (measured as the SD of the average normal-to-normal), daytime heart rate, and nighttime heart rate. Longitudinal autonomic data in the 2-month period leading up to the date of ablation were compared with the period from 91 to 365 days following ablation. Following ablation there was a significant decrease in SD of the average normal-to-normal (mean difference versus baseline of 19.3 ms; range, 12.9-25.7; <0.0001), and significant increases in daytime and nighttime heart rates (mean difference versus baseline of 9.6 bpm; range, 7.4-11.8; <0.0001, and 7.4 bpm; range, 5.4-9.3; <0.0001, respectively). Patients free of arrhythmia recurrence had significantly faster daytime (11±11 versus 8±12 bpm, =0.001) and nighttime heart rates (8±9 versus 6±8 bpm, =0.049), but no difference in SD of the average normal-to-normal (=0.09) compared with those with atrial fibrillation recurrence. Ablation technology and cryoablation duration did not influence these autonomic nervous system effects. Conclusions Pulmonary vein isolation results in significant sustained changes in the heart rate parameters related to autonomic function. These changes are correlated with procedural outcome and are independent of the ablation technology used. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01913522.
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http://dx.doi.org/10.1161/JAHA.120.018610DOI Listing
February 2021

Pharmacotherapy for heart failure with reduced ejection fraction and health-related quality of life: a systematic review and meta-analysis.

Eur J Heart Fail 2021 Feb 25. Epub 2021 Feb 25.

Woodward Library, University of British Columbia, Vancouver, Canada.

Aims: The aim of this study was to synthesize the evidence on the effect of heart failure with reduced ejection fraction (HFrEF) pharmacotherapy on health-related quality of life (HRQoL).

Methods And Results: We searched MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform in June 2020. Randomized placebo-controlled trials evaluating contemporary HFrEF pharmacotherapy and reporting HRQoL as an outcome were included. Two reviewers independently assessed studies for eligibility, extracted data, and assessed risk of bias and GRADE certainty of evidence. The primary outcome was HRQoL at last available follow-up analysed using a random-effects model. We included 37 studies from 5770 identified articles. Risk of bias was low in 10 trials and high/unclear in 27 trials. High certainty evidence from meta-analyses demonstrated improved HRQoL over placebo with sodium-glucose co-transporter 2 (SGLT2) inhibitors [standardized mean difference (SMD) 0.16, 95% confidence interval (CI) 0.08-0.23] and intravenous iron (SMD 0.52, 95% CI 0.04-1.00). Furthermore, high certainty evidence from ≥1 landmark trial further supported improved HRQoL with angiotensin receptor blockers (ARBs) (SMD 0.09, 95% CI 0.02-0.17), ivabradine (SMD 0.14, 95% CI 0.04-0.23), hydralazine-nitrate (SMD 0.24, 95% CI 0.04-0.44) vs. placebo, and for angiotensin receptor-neprilysin inhibitor (ARNI) compared with an angiotensin-converting enzyme (ACE) inhibitor (SMD 0.09, 95% CI 0.02-0.17). Findings were inconclusive for ACE inhibitors, beta-blockers, digoxin, and oral iron based on low-to-moderate certainty evidence.

Conclusion: ARBs, ARNIs, SGLT2 inhibitors, ivabradine, hydralazine-nitrate, and intravenous iron improved HRQoL in patients with HFrEF. These findings can be incorporated into discussions with patients to enable shared decision-making.
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http://dx.doi.org/10.1002/ejhf.2141DOI Listing
February 2021

Clinical Characteristics and Outcomes of Patients With Heart Failure With Reduced Ejection Fraction and Chronic Obstructive Pulmonary Disease: Insights From PARADIGM-HF.

J Am Heart Assoc 2021 Feb 30;10(4):e019238. Epub 2021 Jan 30.

Division of Cardiology University of British Columbia Vancouver Canada.

Background Chronic obstructive pulmonary disease (COPD) is a common comorbidity in heart failure with reduced ejection fraction, associated with undertreatment and worse outcomes. New treatments for heart failure with reduced ejection fraction may be particularly important in patients with concomitant COPD. Methods and Results We examined outcomes in 8399 patients with heart failure with reduced ejection fraction, according to COPD status, in the PARADIGM-HF (Prospective Comparison of Angiotensin Receptor Blocker-Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. Cox regression models were used to compare COPD versus non-COPD subgroups and the effects of sacubitril/valsartan versus enalapril. Patients with COPD (n=1080, 12.9%) were older than patients without COPD (mean 67 versus 63 years; <0.001), with similar left ventricular ejection fraction (29.9% versus 29.4%), but higher NT-proBNP (N-terminal pro-B-type natriuretic peptide; median, 1741 pg/mL versus 1591 pg/mL; P=0.01), worse functional class (New York Heart Association III/IV 37% versus 23%; <0.001) and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (73 versus 81; <0.001), and more congestion and comorbidity. Medical therapy was similar in patients with and without COPD except for beta-blockade (87% versus 94%; <0.001) and diuretics (85% versus 80%; <0.001). After multivariable adjustment, COPD was associated with higher risks of heart failure hospitalization (hazard ratio [HR], 1.32; 95% CI, 1.13-1.54), and the composite of cardiovascular death or heart failure hospitalization (HR, 1.18; 95% CI, 1.05-1.34), but not cardiovascular death (HR, 1.10; 95% CI, 0.94-1.30), or all-cause mortality (HR, 1.14; 95% CI, 0.99-1.31). COPD was also associated with higher risk of all cardiovascular hospitalization (HR, 1.17; 95% CI, 1.05-1.31) and noncardiovascular hospitalization (HR, 1.45; 95% CI, 1.29-1.64). The benefit of sacubitril/valsartan over enalapril was consistent in patients with and without COPD for all end points. Conclusions In PARADIGM-HF, COPD was associated with lower use of beta-blockers and worse health status and was an independent predictor of cardiovascular and noncardiovascular hospitalization. Sacubitril/valsartan was beneficial in this high-risk subgroup. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01035255.
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http://dx.doi.org/10.1161/JAHA.120.019238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955331PMC
February 2021

Real world Data on the Concurrent Use of P-glycoprotein or Cytochrome 3A4 Drugs and Non-vitamin K Antagonist Oral Anticoagulants in Non-Valvular Atrial Fibrillation.

Eur Heart J Qual Care Clin Outcomes 2021 Jan 22. Epub 2021 Jan 22.

Division of Cardiology, University of Alberta, Edmonton, Canada.

Aim: To determine the concurrent use of P-glycoprotein (P-gp) or Cytochrome (CYP) 3A4 drugs and non-vitamin K antagonist oral anticoagulants (NOACs) among non-valvular AF (NVAF) patients in clinical practice.

Methods And Results: Administrative databases identified all adults (≥ 18 years) with incident or prevalent NVAF who initiated a NOAC in an outpatient or inpatient setting, between July 2012-March 2019 in Alberta, Canada. Concurrent use was defined as a P-gp or CYP3A4 dispensation in the 100 days prior to and overlapping NOAC dispensation. The P-gp and CYP3A4 drugs were categorized into 3 groups and drug-drug interactions classified according to the 2018 European Heart Rhythm Association practical guide. Time-varying Cox models calculated crude hazard ratio (HR) of outcomes at 1-year. A total of 642,255 NOAC dispensations occurred for 36,566 NVAF patients. Of these, 71,643 (11.2%) had a concurrent dispensation of an interacting P-gp or CYP3A4 drug. Overall, the drug-drug interaction was defined as contraindicated in 2.5%, avoid/caution in 2.3%, and for another 6.7% should require a dose adjustment. When all drug-drug interactions were considered, inappropriate NOAC prescribing occurred in 63% (n = 45,080) of dispensations. There was a significantly higher risk of death (HR 1.58, 1.47-1.70) for a drug-drug interaction but not for stroke (p = 0.89) or major bleeding risk (p = 0.13).

Conclusions: The concurrent use of P-gp or CYP3A4 drugs and NOACs was uncommon but important since almost two-thirds of patients with drug-drug interactions had inappropriate NOAC dosing and a higher risk of death. More attention to this issue is needed.
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http://dx.doi.org/10.1093/ehjqcco/qcab002DOI Listing
January 2021

Effects of dapagliflozin in heart failure with reduced ejection fraction, and chronic obstructive pulmonary disease: an analysis of DAPA-HF.

Eur J Heart Fail 2020 Dec 23. Epub 2020 Dec 23.

BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.

Aims: Chronic obstructive pulmonary disease (COPD) is an important comorbidity in heart failure (HF) with reduced ejection fraction (HFrEF), associated with worse outcomes and often suboptimal treatment because of under-prescription of beta-blockers. Consequently, additional effective therapies are especially relevant in patients with COPD. The aim of this study was to examine outcomes related to COPD in a post hoc analysis of the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial.

Methods And Results: We examined whether the effects of dapagliflozin in DAPA-HF were modified by COPD status. The primary outcome was the composite of an episode of worsening HF or cardiovascular death. Overall, 585 (12.3%) of the 4744 patients randomized had a history of COPD. Patients with COPD were more likely to be older men with a history of smoking, worse renal function, and higher baseline N-terminal pro B-type natriuretic peptide, and less likely to be treated with a beta-blocker or mineralocorticoid receptor antagonist. The incidence of the primary outcome was higher in patients with COPD than in those without [18.9 (95% confidence interval 16.0-22.2) vs. 13.0 (12.1-14.0) per 100 person-years; hazard ratio (HR) for COPD vs. no COPD 1.44 (1.21-1.72); P < 0.001]. The effect of dapagliflozin, compared with placebo, on the primary outcome, was consistent in patients with [HR 0.67 (95% confidence interval 0.48-0.93)] and without COPD [0.76 (0.65-0.87); interaction P-value 0.47].

Conclusions: In DAPA-HF, one in eight patients with HFrEF had concomitant COPD. Participants with COPD had a higher risk of the primary outcome. The benefit of dapagliflozin on all pre-specified outcomes was consistent in patients with and without COPD.

Clinical Trial Registration: ClinicalTrials.gov ID NCT03036124.
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http://dx.doi.org/10.1002/ejhf.2083DOI Listing
December 2020

Anticoagulation for Patients With Atrial Fibrillation and End-Stage Renal Disease on Dialysis: A National Survey.

Can J Cardiol 2020 Dec 10. Epub 2020 Dec 10.

Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada.

Patients with atrial fibrillation (AF) have a significant increased risk of embolic stroke. Patients with end-stage renal disease who are on dialysis have an increased risk of both embolic stroke and bleeding. Stroke-prevention studies with the use of anticoagulation for AF patients have excluded patients on dialysis, so there remains no consensus on their management. We developed and implemented a pan-Canadian multidisciplinary survey to explore the current beliefs and practices concerning patients with AF on dialysis. We developed an online investigator-designed survey with both quantitative and qualitative responses with the use of a secure university-affiliated electronic service. The survey was distributed to physicians via the QxMD platform and directly to internal medicine, cardiology, and nephrology residency program directors for distribution to faculty members. 130 participants responded, including 46 cardiologists, 45 nephrologists, 30 general internists, and 9 other physicians. The preferred anticoagulant was warfarin. The CHADS score used to initiate anticoagulation was highly variable, with specialties differing in use of a CHADS threshold of ≥ 1 (P < 0.001) and the impact of previous transient ischemic attack/stroke (P = 0.02). Calciphylaxis history affected the decision to prescribe anticoagulation. Specialties differed in thresholds used to consider direct oral anticoagulants for dialysis patients, with nephrologists more likely to prescribe anticoagulation at higher CHADS scores. Our survey demonstrated significant heterogeneity of anticoagulation use for stroke prevention in patients with AF on dialysis. Physician specialty and patient risk profiles contributed to the observed variability. This study reemphasises the need for clinical trials, large observational studies, and consensus guidelines to address evidence-based equipoise.
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http://dx.doi.org/10.1016/j.cjca.2020.12.005DOI Listing
December 2020

Impact of Female Sex on Clinical Presentation and Ablation Outcomes in the CIRCA-DOSE Study.

JACC Clin Electrophysiol 2020 08 29;6(8):945-954. Epub 2020 Jul 29.

Heart Rhythm Services, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Montreal Heart Institute, Department of Medicine, Université de Montréal, Montreal, Quebec, Canada. Electronic address:

Objectives: This study sought to evaluate sex-specific differences in atrial fibrillation (AF) presentation and catheter ablation outcomes in the prospective, multicenter, randomized CIRCA-DOSE (Cryoballoon vs. Irrigated Radiofrequency Catheter Ablation: Double Short vs. Standard Exposure Duration) study.

Background: Similar to other cardiovascular conditions, significant sex-specific differences have been observed in the epidemiology, pathophysiology, presentation, and natural history of AF. Unfortunately, there are major gaps in our understanding of the pathophysiological basis for the observed sex-specific differences and their implications on therapy and prognosis.

Methods: This study examined sex-specific differences in AF presentation, symptom severity and health-related quality of life, symptomatic and asymptomatic arrhythmia recurrence, AF burden, and health care utilization.

Results: Freedom from any atrial tachyarrhythmia and symptomatic atrial tachyarrhythmia were similar between male (hazard ratio: 1.18; 95% confidence interval: 0.85 to 1.64; p = 0.39) and female patients (hazard ratio: 1.00; 95% confidence interval: 0.62 to 1.59; p = 0.92). Post-ablation, the median AF burden (percentage time in AF) was 0.00% (interquartile range: 0.00% to 0.16%) in male patients and 0.00% (interquartile range: 0.00% to 0.17%) in female patients, with no difference observed between the sexes (p = 0.30). Periprocedural complications occurred twice as frequently in female patients (3.5% vs. 7.0%; p = 0.18). In comparison to male patients, female patients reported a significantly worse symptom score and quality of life at baseline and all follow-up intervals, but they derived similar magnitude of improvement post-ablation. There was no difference between male and female patients with respect to emergency department visits, hospitalization, cardioversion, or repeat ablation.

Conclusions: When compared with male patients, female patients have significantly worse symptom scores and quality of life at baseline. Despite this, female patients with symptomatic paroxysmal AF derive similar benefit in freedom from recurrent arrhythmia and similar improvements in quality of life following AF ablation. (Cryoballoon vs. Irrigated Radiofrequency Catheter Ablation: Double Short vs. Standard Exposure Duration [CIRCA-DOSE]; NCT01913522).
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http://dx.doi.org/10.1016/j.jacep.2020.04.032DOI Listing
August 2020

Establishing reference ranges for ambulatory electrocardiography parameters: meta-analysis.

Heart 2020 Nov 20;106(22):1732-1739. Epub 2020 Jul 20.

Heart Rhythm Services, Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

Objective: Despite the widespread and increasing use of ambulatory electrocardiography (ECG), there is no consensus on reference ranges for ambulatory electrocardiogram parameters to guide interpretation. We sought to determine population distribution-based reference ranges for parameters measured during ambulatory electrocardiogram in healthy adults, based on existing literature.

Methods: We searched multiple databases from 1950 to 2020. Articles reporting original data from ≥24-hour ambulatory electrocardiogram monitoring in healthy adults were included. Data extraction and synthesis were performed according to Meta-analysis of Observational Studies in Epidemiology guidelines. The prevalence/mean and SD for common parameters (sinus pauses, conduction abnormalities and ectopy) were extracted by age group (18-39, 40-59, 60-79 and 80+ years).

Results: We identified 33 studies involving 6466 patients. Sinus pauses of >3 s were rare (pooled prevalence <1%) across all ages. Supraventricular ectopy of >1000/24 hours increased with age, from 0% (95% CI 0% to 0%) in those aged 18-39 years to 6% (95% CI 0% to 17%) in those aged 60-79 years. Episodes of supraventricular tachycardia increased from 3% (95% CI 1% to 6%) in those aged 18-39 years to 28% (95% CI 9% to 52%) in those aged 60-79 years. Ventricular ectopy of >1000/24 hours also increased with age, from 1% (95% CI 0% to 2%) in those aged 18-39 years to 5% (95% CI 1% to 10%) in those aged 60-79 years. Episodes of non-sustained ventricular tachycardia ranged from 0% (95% CI 0% to 1%) in those aged 18-39 years to 2% (95% CI 0% to 5%) in those aged 60-79 years.

Conclusion: Despite the limitations of existing published data, this meta-analysis provides evidence-based reference ranges for ambulatory electrocardiogram parameters and highlights significant age-dependent differences that should be taken into account during interpretation.
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http://dx.doi.org/10.1136/heartjnl-2020-316925DOI Listing
November 2020

Changes to the electrocardiogram during exercise in anorexia nervosa.

J Electrocardiol 2020 Jul - Aug;61:99-105. Epub 2020 Jun 10.

Hearts in Rhythm Organization, Division of Cardiology, Department of Medicine, University of British Columbia, 220-1033 Davie St., Vancouver V6E 1M7, B.C., Canada. Electronic address:

Background: Anorexia Nervosa (AN) is an eating disorder characterized by low body weight, distorted body image, and an intense fear of gaining weight. Electrocardiogram (ECG) changes, particularly in the QT interval, have been implicated in AN-associated sudden death but not well defined.

Objectives: To characterize QT interval changes during exercise in anorexia nervosa.

Methods: The QT interval was evaluated in a prospective cohort undergoing structured exercise. Patients from the St. Paul's Hospital Provincial Adult Tertiary Eating Disorders Program underwent a 6-minute modified exercise test protocol. A single lead ECG patch recording device was used to record a Lead I equivalent, due to challenges applying standard ECG monitoring in subjects with low body mass. Heart rate (HR) and QT interval were assessed.

Results: Eighteen eating disorder patients (16 female) completed testing (age 31 ± 12 years, BMI 16.5 ± 3.8 kg/m). Patients were compared to age- and sex-matched healthy controls. HR was similar between patients and controls (baseline: 65 (55-70)bpm vs. 69 (53-73)bpm, p = 0.83; maximum: 110 (94-139) bpm vs. 108 (93-141) bpm, p = 0.96; end recovery: 62 (54-68) bpm vs. 66 (55-75) bpm, p = 0.39). QTc intervals were similar between groups at baseline (381 ± 17 ms vs. 381 ± 46 ms, p = 0.93) and end recovery (397 ± 42 ms vs 398 ± 42 ms, p = 0.91). However, AN patients demonstrated QTc prolongation while controls showed QTc shortening at maximum HR (426 ± 70 ms vs. 345 ± 59 ms, p = 0.001).

Conclusion: Low level exercise HR increases are similar between AN patients and controls, but the QTc interval fails to shorten, which may explain the increased arrhythmic risk in AN.
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http://dx.doi.org/10.1016/j.jelectrocard.2020.06.012DOI Listing
June 2020

Driving Restrictions and Early Arrhythmias in Patients Receiving a Primary-Prevention Implantable Cardioverter-Defibrillator (DREAM-ICD) Study.

Can J Cardiol 2020 Aug 28;36(8):1269-1277. Epub 2020 May 28.

Heart Rhythm Services, Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Background: Current guidelines recommend 4 weeks of private driving restriction after implantation of a primary-prevention implantable cardioverter-defibrillator (ICD). These driving restrictions result in significant inconvenience and social implications. Advances in medical treatment and ICD programming have lowered the overall rate of device therapies. The objective of this study was to assess the incidence of ICD therapies at 30, 60, and 180 days after implantation.

Methods: Driving Restrictions and Early Arrhythmias in Patients Receiving a Primary-Prevention Implantable Cardioverter-Defibrillator (DREAM-ICD) was a retrospective cohort study conducted at 2 Canadian university centres enrolling patients with new implantation of a primary-prevention ICD. Device programming was standardised according to current guidelines. A total of 803 patients were enrolled.

Results: The cumulative rates of appropriate ICD therapies at 30, 60, and 180 days were 0.12%, 0.50%, and 0.75%, respectively. There was no syncope during the first 6 months. The median duration to the first appropriate ICD therapy was 208 (range 23-1109) days after implantation. The rate of inappropriate ICD therapies at 30 days was only 0.2%. Overall, < 13.6% of all appropriate ICD therapies occurred within the first 6 months after implantation.

Conclusions: The rate of appropriate ICD therapies within the first 30 days after device insertion is extremely low in contemporary primary prevention cohorts with guideline-concordant device programming. There was no increased risk for ventricular arrhythmia early after ICD insertion. The results of DREAM-ICD suggest the need for a revision of the existing driving restrictions for primary-prevention ICD recipients.
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http://dx.doi.org/10.1016/j.cjca.2020.05.029DOI Listing
August 2020

Clinical assessment of AF pattern is poorly correlated with AF burden and post ablation outcomes: A CIRCA-DOSE sub-study.

J Electrocardiol 2020 May - Jun;60:159-164. Epub 2020 Mar 21.

Montreal Heart Institute, Department of Medicine, Université de Montréal, Canada.

Background: Contemporary guidelines recommend that atrial fibrillation (AF) be classified into paroxysmal and persistent AF based on clinical assessment, with these categorizations forming the basis of therapeutic recommendations. While pragmatic, clinical assessment may introduce misclassification errors, which may impact treatment decisions. We sought to determine the relationship between AF classification, baseline AF burden, and post-ablation arrhythmia outcomes.

Design: The current study is a sub-analysis of a prospective, parallel-group, multicenter, single-blinded randomized clinical trial. All 346 patients enrolled in CIRCA-DOSE received an implantable cardiac monitor a median of 72 days prior to ablation. AF was classified as low burden paroxysmal, high burden paroxysmal, or persistent based on clinical assessment prior to device implantation. Prior to ablation patients were re-classified using the same definitions based on device monitoring data. Correlation between classifications, AF burden, and post-ablation arrhythmia outcomes were assessed.

Results: There was poor agreement between clinical and device-based AF classification (Cohen's kappa: 0.192). AF classification derived from pre-ablation continuous monitoring reflected baseline and post-ablation AF burden with greater accuracy and with less overlap between the AF classes (P < 0.01 for all categorical comparisons). Patients objectively classified as "Low Burden" paroxysmal by continuous monitoring data had significantly greater freedom from recurrent AF/AT/AFL compared to those classified as "High Burden" paroxysmal (hazard ratio [HR] 0.57 for AF/AT/AFL recurrence) or persistent AF (HR 0.19 for AF/AT/AFL recurrence).

Conclusions: Classification of AF pattern based on pre-ablation continuous cardiac rhythm monitoring better predicted AF burden and freedom from recurrent AF post ablation. Despite the use of standardized definitions, classification of AF based on clinical assessment did not predict baseline AF burden, post ablation AF burden, or freedom from recurrent AF post ablation.

Trial Registration: ClinicalTrials.govNCT01913522.
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http://dx.doi.org/10.1016/j.jelectrocard.2020.03.008DOI Listing
March 2020

Clinical decision support for atrial fibrillation in primary care: Steps forward.

Am Heart J 2020 06 19;224:54-56. Epub 2020 Mar 19.

Heart Rhythm Services, Department of Medicine, University of British Columbia, Canada; Center for Cardiovascular Innovation, Vancouver, Canada; Montreal Heart Institute, Department of Medicine, Université de Montréal, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.ahj.2020.03.010DOI Listing
June 2020

Implantable cardioverter-defibrillators and survival - the fine line between efficacy concerns and ageism.

Eur J Heart Fail 2020 05 30;22(5):868-870. Epub 2020 Mar 30.

Golden Jubilee National Hospital, Glasgow, UK.

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http://dx.doi.org/10.1002/ejhf.1803DOI Listing
May 2020

Sensitivity, specificity, positive and negative predictive values of identifying atrial fibrillation using administrative data: a systematic review and meta-analysis.

Clin Epidemiol 2019 23;11:753-767. Epub 2019 Aug 23.

Division of Cardiology, University of British Columbia, Vancouver, Canada.

Introduction: Atrial fibrillation (AF) is the commonest arrhythmia and a major cause of stroke and health care utilization. Researchers and administrators use electronic health data to assess disease burden, quality and variance in care, value of interventions and prognosis. We performed a systematic review and meta-analysis to assess the validity of AF case definitions in administrative databases.

Methods: Medline was searched from 2000 to 2018. Extracted information included sensitivity, specificity, positive and negative predictive values (PPV and NPV) for various AF case definitions. Estimates were pooled using random-effects models due to significant heterogeneity between studies.

Results: We identified 24 studies, including 21 from North America or Scandinavia. Hospital, ambulatory and mixed data sources were assessed in 10, 4 and 10 studies, respectively. Nine different AF case definitions were evaluated, most based on ICD-9 or 10 codes. Twenty-two studies assessed case definitions in patients diagnosed with AF and thus could generate PPV alone. Half the studies sampled unrestricted populations including a mix of those with and without AF to assess sensitivity. Only 13 studies included ECG confirmation as a gold standard. The pooled random effects estimates were: sensitivity 80% (95% CI 72-86%); specificity 98% (96-99%); PPV 88% (82-94%); NPV 97% (94-99%). Only 3 studies reported all accuracy parameters and included rhythm monitoring in the gold standard definition.

Conclusion: Relatively few studies examined sensitivity, and fewer still included rhythm monitoring in the gold standard comparison. Administrative data may fail to identify a significant proportion of patients with AF. This, in turn, may bias estimates of quality of care and prognosis.
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http://dx.doi.org/10.2147/CLEP.S206267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712502PMC
August 2019

Impact of cardiology follow-up care on treatment and outcomes of patients with new atrial fibrillation discharged from the emergency department.

Europace 2020 05;22(5):695-703

Alberta SPOR Support Unit Data Platform, University of Alberta, Edmonton, AB, Canada.

Aims: The first presentation of atrial fibrillation (AF) is often to an emergency department (ED). We evaluated the association of subsequent specialist care with morbidity and mortality.

Methods And Results: Retrospective cohort study of all adults in Alberta, Canada, with a new primary diagnosis of AF treated and released during an index ED visit between 2009 and 2015. Types of physician follow-up within 3 months of ED visit was analysed using Cox proportional hazards models with time-varying covariates. Outcomes were evaluated at 1 year. Of 7986 patients, 476 (6.0%) had no physician follow-up within 3 months, whereas 2730 (34.2%) attended a non-specialist only, 1277 (16.0%) an internal medicine specialist, and 3503 (43.9%) cardiology. An increasing gradient of cardiac investigations occurred across these groups. Cardiology compared with non-cardiologist care was associated with approximately two-fold greater electrophysiology interventions and revascularization, and increased use of beta-blockers (48.9% vs. 43.0%, P < 0.0001), statins (31.4% vs. 26.7%, P < 0.0001), and oral anticoagulation in patients with CHADS2 scores ≥1 (53.7% vs. 43.6%, P < 0.0001). In the subsequent year, cardiology care was associated with fewer deaths [adjusted hazard ratio (aHR) 0.72, 95% confidence interval (CI) 0.55-0.93], strokes (aHR 0.60, 95% CI 0.37-0.96), or major bleeds (aHR 0.69, 95% CI 0.53-0.89). No differences in the risk of hospitalization or ED visits were associated with cardiology care.

Conclusion: Cardiology care after an ED visit for symptomatic new-onset AF is associated with better prognosis. The benefit may be mediated through more intensive investigation, identification, and treatment of cardiovascular risk factors and disease.
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http://dx.doi.org/10.1093/europace/euz302DOI Listing
May 2020

Empirical Insights When Defining the Population Burden of Atrial Fibrillation and Oral Anticoagulation Utilization Using Administrative Data.

Can J Cardiol 2019 10 15;35(10):1412-1415. Epub 2019 May 15.

Division of Cardiology and Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada; Canadian Vigour Centre, University of Alberta, Edmonton, Alberta, Canada.

Health administrative data are routinely used to assess disease burden, quality of care, and outcomes for atrial fibrillation (AF). Governments, administrators, and researchers define cohorts differently, based on 3 key factors: the case definition algorithm to identify AF, inclusion/exclusion of transient AF, and the lookback period to identify cases. We assessed the impact of varying these key factors on estimates of the use of guideline-indicated oral anticoagulation (OAC). Hospitalization, ED, and outpatient claim databases were linked in British Columbia. AF was defined by ICD-9 or 10 codes 427.3x or I48.x. We examined a specific (1 hospital or 1 ED or 2 outpatient) vs a sensitive (1 hospital or ED or outpatient) algorithm; inclusion/exclusion of AF associated with open-heart surgery; and lookback periods of 1 to 10 years. We found the more specific AF definition increased OAC utilization by 5% (58.7% vs 53.4%); excluding AF associated with open-heart surgery increased OAC utilization by 0.7% to 2.3%; and each additional lookback year identified more prevalent cases but reduced OAC utilization by approximately 1%. In 40 scenarios, generated by varying all 3 key factors, OAC utilization ranged from 52% to 72%. Assuming a ceiling of 90%, the estimated "treatment gap" therefore varied from 18% to 38%. The 2-fold variation in the OAC treatment gap was based entirely on cohort definition. This has significant implications for health policy and quality indicators.
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http://dx.doi.org/10.1016/j.cjca.2019.05.009DOI Listing
October 2019

Medical therapy doses at hospital discharge in patients with existing and de novo heart failure.

ESC Heart Fail 2019 08 20;6(4):774-783. Epub 2019 Jun 20.

Division of Cardiology, University of British Columbia, Vancouver, Canada.

Aims: Uptitrating angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACE-I/ARBs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) to optimal doses in heart failure with reduced ejection fraction (HFrEF) is associated with improved outcomes and recommended in guidelines. Studies of ambulatory patients found that a minority are prescribed optimal doses. However, dose at hospital discharge has rarely been reported. This information may guide quality improvement initiatives during and following discharge.

Methods And Results: We assessed 370 consecutive patients with HFrEF hospitalized at two centres in Vancouver, Canada. Of those without contraindications, 86.4%, 93.4%, and 44.7% were prescribed an ACE-I/ARB/sacubitril-valsartan, beta-blocker, or MRA, respectively. The proportion of eligible patients prescribed target dose was respectively 28.6%, 31.7%, and 4.1%. Forty-two of 248 eligible patients (16.9%) were prescribed ≥50% of target dose, and only three patients received target dosing of all three medication classes. In multivariate regression models, cardiologist involvement in care was independently associated with increased dose and prescription of ≥50% of target dose for all medications, whereas a history of HF was only predictive for beta-blockers.

Conclusions: In a single-region experience of hospitalized HFrEF patients, a high proportion of eligible patients were discharged on ACE-I/ARB or beta-blocker. Less than half were prescribed MRAs, and few were prescribed ≥50% or target dosing of all medications. Further exploration into barriers to medication uptitration, and improvement in processes of care, is needed.
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http://dx.doi.org/10.1002/ehf2.12454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676447PMC
August 2019

Outcomes of untreated frequent premature ventricular complexes with normal left ventricular function.

Heart 2019 09 29;105(18):1408-1413. Epub 2019 May 29.

Heart Rhythm Services, Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada.

Objective: The natural history of frequent premature ventricular complexes (PVCs) in association with preserved left ventricular ejection fraction (LVEF) is uncertain. The optimal management of this population is thus undefined. We studied the outcomes of untreated patients with frequent PVCs and preserved LVEF.

Methods: This cohort study prospectively evaluated consecutive patients from 2012 to 2017, with asymptomatic or minimally symptomatic frequent idiopathic PVCs (≥5% PVCs in 24 hours; normal LVEF; no cause identified on comprehensive evaluation). No suppressive therapy (ablation or antiarrhythmic drugs) were used and patients were followed with serial ambulatory ECG monitoring and echocardiography. The primary arrhythmic outcome was reduction in PVC burden to <1% on serial ambulatory monitoring. The primary echocardiographic outcome was a reduction of LVEF to <50%.

Results: One hundred patients met inclusion criteria (mean age 51.8 years, 57% female) with a median PVC burden of 18.4%. Reduction to <1% PVCs occurred in 44 of 100 patients (44.0%) at a median of 15.4 months (range 2.6 to 64.3). Recurrence was uncommon (4/44, 9.1%). Four patients (4.3%) with a persistently elevated PVC burden developed left ventricular dysfunction (LVEF <50%) during the follow-up period at a range of 53-71 months. The initial PVC burden did not predict subsequent resolution (HR 1.00(0.97, 1.03); p=0.86).

Conclusions: A strategy of active surveillance is appropriate for the majority of patients with frequent idiopathic PVCs in association with preserved LVEF, owing to the low risk of developing left ventricular systolic dysfunction and the high rate of spontaneous resolution.
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http://dx.doi.org/10.1136/heartjnl-2019-314922DOI Listing
September 2019

The Relationship Between Heart-Failure Hospitalization and Mortality in Patients Receiving Transcatheter Aortic Valve Replacement.

Can J Cardiol 2019 04 28;35(4):413-421. Epub 2018 Nov 28.

Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Background: Patients who have had transcatheter aortic valve replacement (TAVR) are at risk of hospitalization during the first year postprocedure. Few studies have examined the incidence of heart- failure hospitalizations (HFH) post-TAVR and the impact this has on subsequent hospitalizations and mortality. Our aim was to determine the incidence, predictors, and mortality associated with HFH post-TAVR.

Methods: We used prospectively collected data for all patients who underwent TAVR between August 1, 2010, and March 31, 2015; 742 consecutive patients who underwent TAVR during the study period were included. Patients were followed for a minimum of 1 year post-TAVR.

Results: Mean age was 80.9 ± 8.1, and 58.2% were men. Hospitalizations post-TAVR occurred in 20% of patients at 30 days and 59.7% at 1 year. Of patients hospitalized, HFH was the primary cause of hospitalization in 25.8% and 21.4% of patients at 30 days and 1 year post-TAVR, respectively. Patients with HFH at either 30 days or 1 year had higher subsequent rates of rehospitalization compared with patients who had non-HFH. Patients with HFH or non-HFH at 30 days had 1-year mortality rates of 23.1% and 21.4%, respectively, whereas those with HFH by 1 year had a higher 1-year rate of mortality compared with patients who had non-HFHs (25% vs 10.9%, P < 0.001).

Conclusions: HF accounts for a quarter of all hospitalizations post-TAVR and is associated with higher rates of subsequent rehospitalization and death compared with those who had non-HFH. Understanding predictors of readmissions post-TAVR will allow for better risk stratification and improve outcomes in patients receiving TAVR.
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http://dx.doi.org/10.1016/j.cjca.2018.11.016DOI Listing
April 2019

Cardiac resynchronization therapy improves survival in selected patients with moderately impaired ejection fraction - the importance of left ventricular remodelling.

Eur J Heart Fail 2019 03 28;21(3):370-372. Epub 2018 Dec 28.

Division of Cardiology, University of British Columbia, Vancouver, Canada.

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http://dx.doi.org/10.1002/ejhf.1401DOI Listing
March 2019

Implantable cardioverter-defibrillator use in catecholaminergic polymorphic ventricular tachycardia: A systematic review.

Heart Rhythm 2018 12 3;15(12):1791-1799. Epub 2018 Jul 3.

BC Children's Hospital, Division of Cardiology, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Background: The implantable cardioverter-defibrillator (ICD) may be associated with a high risk of complications in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). However, ICDs in this population have not been systematically evaluated.

Objective: The purpose of this study was to characterize the use and outcomes of ICDs in CPVT.

Methods: We conducted a systematic review using Embase, MEDLINE, PubMed, and Google Scholar to identify studies that included patients with CPVT who had an ICD.

Results: Fifty-three studies describing 1429 patients with CPVT were included. In total, 503 patients (35.2%) had an ICD (median age 15.0 years; interquartile range 11.0-21.0 years). Among ICD recipients with a reported medication status, 96.7% were prescribed β-blockers and 13.2% flecainide. Sympathetic denervation was performed in 23.2%. Nearly half of patients received an ICD for primary prevention (47.3%), and 12.8% were prescribed optimal antiarrhythmic therapy. During follow-up, 40.1% had ≥1 appropriate shock, 20.8% experienced ≥1 inappropriate shock, 19.6% had electrical storm, and 7 patients (1.4%) died. An ICD-associated electrical storm was implicated in 4 deaths. Additional complications such as lead failure, endocarditis, or surgical revisions were observed in 96 of 296 patients (32.4%). A subanalysis of the 10 studies encompassing 330 patients with the most detailed ICD-related data showed similar trends.

Conclusion: In this population with CPVT, ICDs were common and associated with a high burden of shocks and complications. The reliance on primary prevention ICDs, and poor uptake of adjuvant antiarrhythmic therapies, suggests that improved adherence to guideline-directed management could reduce ICD use and harm.
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http://dx.doi.org/10.1016/j.hrthm.2018.06.046DOI Listing
December 2018

Variability in Non-Vitamin K Antagonist Oral Anticoagulants Dose Adjustment in Atrial Fibrillation Patients With Renal Dysfunction: The Influence of Renal Function Estimation Formulae.

Can J Cardiol 2018 08 25;34(8):1010-1018. Epub 2018 Apr 25.

Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) require renal dose adjustment. The most common estimates of renal function in clinical practice are derived from estimated glomerular filtration rate (eGFR; Modified Diet in Renal Disease [MDRD] or the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]). However, the landmark stroke prevention trials and product monographs recommend the use of the Cockcroft-Gault creatinine clearance equation (eCrCl) for drug eligibility and dose adjustment. We sought to evaluate the agreement in NOAC dosing between these 3 equations in a large population of patients with atrial fibrillation and moderate chronic kidney disease.

Methods: We identified 831 patients with non-dialysis-dependent chronic kidney disease and atrial fibrillation (CHADS-VASc 3.9). For each patient, eCrCl, MDRD eGFR, and CKD-EPI eGFR were prospectively calculated. Eligibility criteria for NOAC medications were evaluated by comparing the eGFR as estimated by MDRD or CKD-EPI equation with the eCrCl as estimated by Cockcroft-Gault, with the latter regarded as the "gold standard."

Results: The use of eGFR resulted in significant misclassification with respect to NOAC dosing. Compared with eCrCl, the MDRD eGFR and CKD-EPI eGFR misclassified 36.2% and 35.8% of patients, respectively. The misclassification resulted in undertreatment (eg, inappropriate dose reduction; 26.9% MDRD, 28.8% CKD-EPI), and to a lesser extent overtreatment (eg, inappropriate use of standard dose; 9.3% MDRD, 7.0% CKD-EPI).

Conclusions: MDRD and CKD-EPI eGFR fail to correctly identify a significant proportion of patients who require NOAC dose adjustment, limiting their clinical utility. Cockcroft-Gault eCrCl should be calculated for all patients in whom a NOAC is being prescribed.
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http://dx.doi.org/10.1016/j.cjca.2018.04.019DOI Listing
August 2018

Eligibility for cardiac resynchronization therapy in patients hospitalized with heart failure.

ESC Heart Fail 2018 08 25;5(4):668-674. Epub 2018 Jun 25.

Division of Cardiology, University of British Columbia, Vancouver, BC, Canada.

Aims: Recent guidelines recommend cardiac resynchronization therapy (CRT) in mildly symptomatic heart failure (HF) but favour left bundle branch block (LBBB) morphology in patients with moderate QRS prolongation (120-150 ms). We defined how many patients hospitalized with HF fulfil these criteria.

Methods And Results: A single-centre retrospective cohort study of 363 consecutive patients hospitalized with HF (438 admissions) was performed. Electronic imaging, electrocardiograms, and records were reviewed. Overall, 153 patients (42%) had left ventricular ejection fraction (LVEF) ≤ 35%, and 34% of patients had QRS prolongation. Eighty patients (22%) were potentially eligible with LVEF ≤ 35% and QRS ≥ 120 ms or existing CRT. The majority (68 of 80) had a Class I or IIa recommendation according to international guidelines (LBBB or non-LBBB QRS ≥ 150 ms or right ventricular pacing). Only a minority (12 of 80) had moderate QRS prolongation of non-LBBB morphology. One-quarter (n = 22) of patients fulfilling criteria were ineligible for reasons including dementia, co-morbidities, or palliative care. A further eight patients required optimization of medical therapy. CRT was therefore immediately indicated in 50 patients. Of these, 29 were implanted or had existing CRT systems. Twenty-one of the 80 patients eligible for CRT were not identified or treated (6% of the total hospitalized cohort).

Conclusions: Twenty-two per cent of elderly real-life patients hospitalized with HF fulfil LVEF and QRS criteria for CRT, most having a Class I or IIa indication. However, a large proportion is ineligible owing to co-morbidities or requires medical optimization. Although uptake of CRT was reasonable, there remain opportunities for improvement.
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http://dx.doi.org/10.1002/ehf2.12297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073034PMC
August 2018

Catheter ablation of atrial fibrillation in heart failure with reduced ejection fraction.

J Cardiovasc Electrophysiol 2018 07 23;29(7):1049-1058. Epub 2018 Apr 23.

Heart Rhythm Services, Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.

Atrial fibrillation and heart failure are increasing in prevalence, and frequently coexist. Despite the desire to restore sinus rhythm in heart failure patients, large studies comparing rate control to pharmacologic rhythm control have failed to show superiority of either approach. This may in part be due to the inefficacy and higher risk of adverse effects with antiarrhythmic drugs in HF patients. As such, catheter ablation for atrial fibrillation in patients with heart failure with reduced ejection fraction has been increasingly explored as a treatment modality. We review the contemporary evidence regarding patient selection, efficacy, safety, and impact of catheter ablation on outcomes in patients with atrial fibrillation and heart failure with reduced ejection fraction.
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http://dx.doi.org/10.1111/jce.13497DOI Listing
July 2018

Chronic obstructive pulmonary disease and ventricular arrhythmia-Association or causation?

Heart Rhythm 2018 06 16;15(6):839-840. Epub 2017 Oct 16.

Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.hrthm.2017.10.018DOI Listing
June 2018

Chronic obstructive pulmonary disease and heart failure in Europe-further evidence of the need for integrated care.

Eur J Heart Fail 2018 01 26;20(1):111-113. Epub 2017 Sep 26.

Division of Cardiology, University of British Columbia, Vancouver, Canada.

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http://dx.doi.org/10.1002/ejhf.986DOI Listing
January 2018