Roopinder K. Sandhu

2015 Heart Rhythm Society Expert Consensus Statement on the Diagnosis and Treatment of Postural Tachycardia Syndrome, Inappropriate Sinus Tachycardia, and Vasovagal Syncope

Robert S. Sheldon, Blair P. Grubb II, Brian Olshansky, Win-Kuang Shen, Hugh Calkins, Michele Brignole, Satish R. Raj, Andrew D. Krahn, Carlos A. Morillo, Julian M. Stewart, Richard Sutton, Paola Sandroni, Karen J. Friday, Denise Tessariol Hachul, Mitchell I. Cohen, Dennis H. Lau, Kenneth A. Mayuga, Jeffrey P. Moak, Roopinder K. Sandhu, Khalil Kanjwal

Screening for Atrial Fibrillation A Report of the AF-SCREEN International Collaboration

Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country- and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.

Risk stratification schemes, anticoagulation use and outcomes: the risk–treatment paradox in patients with newly diagnosed non-valvular atrial fibrillation

Objective To examine whether warfarin use and outcomes differ across CHADS2 and CHA2DS2-VASc risk strata for non-valvular atrial fibrillation (NVAF). Design Population-based cohort study using linked administrative databases in Alberta, Canada. Setting Inpatient and outpatient. Patients 42 834 consecutive patients ≥20 years of age with newly diagnosed NVAF. Main outcome measures Cerebrovascular events and/or mortality in the first year after diagnosis. Results Of 42 834 NVAF patients, 22.7% were low risk on the CHADS2 risk score (0), 27.5% were intermediate risk (1), and 49.8% were high risk (≥2). The CHA2DS2-VASc risk score reclassified 16 722 patients such that 7.8% were defined low risk, 13.8% intermediate risk and 78.4% high risk. Of the elderly cohort (≥65 years) with definite NVAF visits (at least two encounters 30 days apart, n=8780), 49% were taking warfarin within 90 days of diagnosis. Warfarin use did not differ across risk strata using either the CHADS2 (p for trend=0.85) or CHA2DS2-VASC (p=0.35). In multivariable adjusted analyses, warfarin use was associated with substantially lower rates of death or cerebrovascular events for patients with CHADS2 scores of 1 (OR 0.52, 95% CI 0.41 to 0.67) or ≥2 (OR 0.61, 95% CI 0.53 to 0.71), or CHA2DS2-VASc scores of ≥2 (OR 0.60, 95% CI 0.53 to 0.68). Conclusions In elderly patients with NVAF and elevated CHADS2 or CHA2DS2-VASC scores, warfarin users exhibited lower rates of cerebrovascular events and mortality. However, warfarin use did not differ across risk strata, another example of the risk–treatment paradox in cardiovascular disease.

Positive predictive value of device-detected atrial high-rate episodes at different rates and durations: An analysis from ASSERT

BACKGROUND Pacemakers can automatically identify and catalog atrial high-rate episodes (AHREs). While most AHREs represent true atrial tachyarrhythmia/atrial fibrillation (AT/AF), a review of stored electrograms suggests that a substantial proportion do not. As AHREs may lead to the initiation of oral anticoagulation, it is crucial to understand the relationship between AHREs and true AT/AF. OBJECTIVE To compare the positive predictive value of AHREs for electrogram-confirmed AT/AF for various atrial rates and episode durations. METHODS By using data from 2580 patients who participated in the ASymptomatic atrial fibrillation and Stroke Evaluation in pacemaker patients and the AF Reduction atrial pacing Trial, all AHREs >6 minutes and >190 beats/min with available electrograms were reviewed to determine whether they represented true AT/AF. The positive predictive value of these AHREs was assessed for episode durations of 6 minutes, 30 minutes, 6 hours, and 24 hours at atrial rates of 190 and 250 beats/min. RESULTS Of 5769 AHREs >6 minutes and >190 beats/min, 82.7% were true AT/AF and 17.3% were false positives (predominantly due to repetitive non-re-entrant ventriculoatrial synchrony). False positives dropped to 6.8%, 3.3%, and 1.8% when the threshold duration was increased to 30 minutes, 6 hours, and 24 hours, respectively. Increasing the threshold heart rate to 250 beats/min added little to the positive predictive value when longer threshold durations were used. CONCLUSIONS By using a cutoff of >6 minutes and >190 beats/min, the rate of false-positive AHREs is 17.3%, making physician review of electrograms essential. For AHREs lasting >6 hours, the rate of false positives is 3.3%, making physician review less crucial.

Smoking, Smoking Cessation, and Risk of Sudden Cardiac Death in Women

Background— Few prospective studies have examined quantitative cigarette consumption and smoking cessation on sudden cardiac death (SCD) risk with long-term follow-up. Methods and Results— We prospectively examined the association between cigarette smoking and smoking cessation on the risk of SCD among 101 018 women participating in the Nurses’ Health Study without known coronary heart disease, stroke, and cancer at baseline 1980. During 30 years of follow-up, we identified 351 SCD events. Compared with never smokers, current smokers had a 2.44-fold (95% CI, 1.80–3.31) increased risk of SCD after controlling for coronary risk factors. In multivariable analyses, quantity of cigarettes smoked daily (P value for trend, <0.0001) and smoking duration (P value for trend, <0.0001) were linearly associated with SCD risk among current smokers. Small-to-moderate amounts of cigarette consumption (1–14 per day) were associated with a significant 1.84-fold (95% CI, 1.16–2.92) increase in SCD risk and every 5 years of continued smoking was associated with an 8% increase in SCD risk (hazard ratio, 1.08; 95% CI, 1.05–1.12; P<0.0001). The SCD risk linearly decreased over time after quitting and was equivalent to that of a never smoker after 20 years of cessation (P value for trend, <0.0001). Conclusions— In this large prospective cohort of women without coronary heart disease at baseline, a strong dose–response relationship between cigarette smoking and SCD risk was observed, and smoking cessation significantly reduced and eventually eliminated excess SCD risk. This suggests efforts to prevent SCD among women should include aggressive strategies for smoking cessation.

The epidemiology of atrial fibrillation in adults depends on locale of diagnosis

BACKGROUND Previous studies on atrial fibrillation (AF) epidemiology have used various case definitions for AF, but the effect of location of diagnosis on the apparent epidemiology of AF is unknown. METHODS Population-based study of 46,440 consecutive patients with newly diagnosed AF in Alberta, Canada, from 2000 to 2005. RESULTS Of adults newly diagnosed with AF (52.8% men, median 73 years), 51.8% were first diagnosed in hospital, 19.2% in emergency department (ED), and 29.0% in outpatient clinics. Prevalence of AF increased from 613 per 100,000 to 1,148 per 100,000 population over 5 years; however, the age- and sex-standardized incidence of AF remained relatively stable (350 per 100,000 in 2000 and 352 per 100,000 in 2005). The proportion of AF cases diagnosed in hospital declined 21% between 2000 and 2005, whereas the proportion of cases diagnosed in the outpatient setting rose by 50% (P < .0001). Patients diagnosed with AF in the hospital or the ED had more comorbidities and higher CHADS(2) (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack) scores than those diagnosed in the outpatient setting (all P < .0001). Multivariate adjusted risk of cerebrovascular events or mortality (adjusted odds ratios 4.3, 95% CI 3.9-4.7) was significant for hospital and ED AF diagnosis (adjusted odds ratios 2.4, 95% CI 2.2-2.7) compared with those diagnosed in primary care clinics. New heart failure in the year after diagnosis of AF was 4.5% for inpatients, 3.8% in ED patients, and 2.5% in outpatients. CONCLUSIONS Use of hospitalizations alone to define an AF cohort may underestimate incidence while overestimating comorbiditities, thromboembolic risk, and outcomes.

Predisposing Factors Associated With Development of Persistent Compared With Paroxysmal Atrial Fibrillation

Background Once atrial fibrillation (AF) progresses to sustained forms, adverse outcomes increase and treatment success rates decrease. Therefore, identification of risk factors predisposing to persistence of AF may have a significant impact on AF morbidity. Methods and Results We prospectively examined the differential associations between traditional, lifestyle, and biomarker AF risk factors and development of paroxysmal versus nonparoxysmal AF (persistent/permanent) among 34 720 women enrolled in the Womens Health Study who were free of cardiovascular disease and AF at baseline. AF patterns were defined based on current guidelines and classified according to the most sustained form of AF within 2 years of diagnosis. During a median follow‐up of 16.4 years, 690 women developed paroxysmal AF and 349 women developed nonparoxysmal AF. In multivariable time‐varying competing risk models, increasing age (hazard ratio [HR] 1.11, 95% CI 1.10 to 1.13, versus HR 1.08, 1.07 to 1.09, per year), body mass index (HR 1.07, 1.05 to 1.09, versus HR 1.03, 1.02 to 1.05, per kg/m2), and weight (HR 1.30, 1.22 to 1.39, versus HR 1.14, 1.08 to 1.20, per 10 kg) were more strongly associated with the development of nonparoxysmal AF compared with paroxysmal AF. Hemoglobin A1c levels at baseline were directly related to the development of nonparoxysmal AF but inversely associated with paroxysmal AF in multivariable competing risk models (P for nonequal association=0.01). Conclusions In women without AF or CVD at baseline, increasing age, adiposity, and higher hemoglobin A1c levels were preferentially associated with the early development of nonparoxysmal AF. These data raise the hypothesis that efforts aimed at weight reduction or glycemic control may affect the proportion of the population with sustained AF.

Relationship Between Degree of Left Ventricular Dysfunction, Symptom Status, and Risk of Embolic Events in Patients With Atrial Fibrillation and Heart Failure

Background and Purpose— Limited data exists regarding the relationship between left ventricular systolic dysfunction (LVSD) and heart failure (HF) symptoms and embolic risk among patients with atrial fibrillation. Methods— Participants in the Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE) trials with HF, but not randomized to oral anticoagulation, were categorized as having preserved versus reduced ejection fraction. If reduced, LVSD was classified as mild, moderate, or severe. Symptoms were quantified using New York Heart Association class.The primary outcome was a composite of stroke, transient ischemic attack, and systemic embolism. Results— There were 3487 antiplatelet-treated patients with HF at baseline. Of these patients, 969 (46.8%) had HF with preserved ejection fraction and 1103 (53.2%) had HF with reduced ejection fraction. During 3.6 years of mean follow-up, first occurrence of stroke, transient ischemic attack, or systemic embolism occurred in 386 patients.The strongest independent predictors of embolic events were age ≥75 years (hazard ratio 2.55; confidence interval, 1.85–3.53), prior stroke or transient ischemic attack (hazard ratio 2.07; 95% confidence interval, 1.65–2.60), and female sex (hazard ratio 1.37; confidence interval, 1.11–1.69). However, ejection fraction <0.50, degree of LVSD, and New York Heart Association class did not predict embolic events. Patients with HF with preserved ejection fraction exhibited similar risk of embolic events as those with HR with reduced ejection fraction: 4.3% versus 4.4% per 100 person-years (hazard ration 1.01; 95% confidence interval, 0.78–1.31). Risk of embolic events was similar across categories of LVSD (P for trend =0.96) and New York Heart Association class (P for trend =0.57). Conclusion— Among HF patients in ACTIVE, neither the presence of LVSD or degree of symptom severity influenced risk of embolic events.

Risk of Malignant Cancer Among Women With New-Onset Atrial Fibrillation.

IMPORTANCE A substantial proportion of patients with atrial fibrillation (AF) die of noncardiovascular causes, and recent studies suggest a link between AF and cancer. OBJECTIVE To evaluate the associations between AF and cancer in a large, long-term prospective cohort study. DESIGN, SETTING, AND PARTICIPANTS In this cohort study, a total of 34 691 women 45 years or older and free of AF, cardiovascular disease, and cancer at baseline were prospectively followed up between 1993 and 2013, for incident AF and malignant cancer within the Womens Health Study, a randomized clinical trial of aspirin and vitamin E for the prevention of cardiovascular disease and cancer. Cox proportional hazards models using time-updated covariates were constructed to assess the association of new-onset AF with subsequent cancer and to adjust for potential confounders. Data analysis was performed from December 2014 to May 2015. EXPOSURE New-onset AF. MAIN OUTCOMES AND MEASURES Incident malignant cancer confirmed by an end point committee. RESULTS During a median follow-up of 19.1 years of 34 691 study participants (interquartile range [IQR], 17.6-19.7 years), new-onset AF and malignant cancer were confirmed among 1467 (4.2%) and 5130 (14.8%) participants, respectively. Median age at baseline among participants with new-onset AF and new-onset cancer during follow-up was 58 years (IQR, 52-64 years) and 55 years (IQR, 50-61 years), respectively. Atrial fibrillation was a significant risk factor for incident cancer in age-adjusted (hazard ratio [HR], 1.58; 95% CI, 1.34-1.87; P < .001) and multivariable-adjusted (HR, 1.48; 95% CI, 1.25-1.75; P < .001) models. The relative risk of cancer was highest in the first 3 months after new-onset AF (HR, 3.54; 95% CI, 2.05-6.10; P < .001) but remained significant beyond 1 year after new-onset AF (adjusted HR, 1.42; 95% CI, 1.18-1.71; P < .001), and a trend toward an increased cancer mortality was observed (adjusted HR, 1.32; 95% CI, 0.98-1.79; P = .07). In contrast, among women with new-onset cancer, the relative risk of AF was increased only within the first 3 months (HR, 4.67; 95% CI, 2.85-7.64; P < .001) but not thereafter (HR, 1.15; 95% CI, 0.95-1.39; P = .15). CONCLUSIONS AND RELEVANCE In this large, initially healthy cohort, women with new-onset AF had an elevated cancer risk beyond 1 year of AF diagnosis. Shared risk factors and/or common systemic disease processes might underlie this association.

Paradoxical Association of Lipoprotein Measures with Incident Atrial Fibrillation

Background—Low-density lipoprotein (LDL) cholesterol is a strong risk factor for atherosclerosis but has an inverse association with atrial fibrillation (AF). We aimed to provide insight into the paradoxical association of LDL cholesterol with AF by evaluating the relationship of various lipoprotein measures and incident AF. Methods and Results—We prospectively evaluated lipoprotein measures among 23 738 healthy middle-aged and older women (median follow-up 16.4 years; N=795 incident AF events). Baseline LDL cholesterol was directly measured, lipoprotein particle concentrations and size were measured by nuclear magnetic resonance spectroscopy, and apolipoproteins were measured by immunoassay. Cox regression models were adjusted for age, AF risk factors, inflammatory, and dysglycemic biomarkers. After multivariable adjustment, inverse associations with AF were observed (hazard ratio, 95% confidence interval for top versus bottom quintile, P value) for LDL cholesterol (0.72, 0.56–0.92, P=0.009), the total number of LDL particles (0.77, 0.60–0.99, P=0.045), and very-low-density lipoprotein particles (0.78, 0.61–0.99, P=0.04), which was driven by the number of cholesterol-poor small LDL (0.78, 0.61–1.00, P=0.05) and small very-low-density lipoprotein particles (0.78, 0.62–0.99, P=0.04). By contrast, the larger cholesterol-rich LDL particles and all high-density lipoprotein measures were not associated with AF in multivariable models. Adjustment for inflammatory and dysglycemic biomarkers had minimal impact on these associations. Conclusions—In this prospective study, the inverse association between LDL cholesterol and AF extended to several other atherogenic lipoproteins, and these associations are unlikely to be mediated by direct cholesterol effects. Clinical Trial Registration—ClinicalTrials.gov; Unique Identifier: NCT00000479.