Heart failure with preserved ejection fraction: everything the clinician needs to know.

Heart failure with preserved ejection fraction (HFpEF) is increasingly recognised and diagnosed in clinical practice, a trend driven by an ageing population and a rise in contributing comorbidities, such as obesity and diabetes. Representing at least half of all heart failure cases, HFpEF is recognised as a complex clinical syndrome. Its diagnosis and management are challenging due to its diverse pathophysiology, varied epidemiological patterns, and evolving diagnostic and treatment approaches. This Seminar synthesises the latest insights on HFpEF, integrating findings from recent clinical trials, epidemiological research, and the latest guideline recommendations. We delve into the definition, pathogenesis, epidemiology, diagnostic criteria, and management strategies (non-pharmacological and pharmacological) for HFpEF. We highlight ongoing clinical trials and future developments in the field. Specifically, this Seminar offers practical guidance tailored for primary care practitioners, generalists, and cardiologists who do not specialise in heart failure, simplifying the complexities in the diagnosis and management of HFpEF. We provide practical, evidence-based recommendations, emphasising the importance of addressing comorbidities and integrating the latest pharmacological treatments, such as SGLT2 inhibitors.

Atrial fibrillation progression after cryoablation vs. radiofrequency ablation: the CIRCA-DOSE trial.

BACKGROUND AND AIMS: Atrial fibrillation (AF) is a chronic progressive disorder. Persistent forms of AF are associated with increased rates of thromboembolism, heart failure, and death. Catheter ablation modifies the pathogenic mechanism of AF progression. No randomized studies have evaluated the impact of the ablation energy on progression to persistent atrial tachyarrhythmia. METHODS: Three hundred forty-six patients with drug-refractory paroxysmal AF were enrolled and randomly assigned to contact-force-guided RF ablation (CF-RF ablation, 115), 4 min cryoballoon ablation (CRYO-4, 115), or 2 min cryoballoon ablation (CRYO-2, 116). Implantable cardiac monitors placed at study entry were used for follow-up. The main outcome was the first episode of persistent atrial tachyarrhythmia. Secondary outcomes included atrial tachyarrhythmia recurrence and arrhythmia burden on the implantable monitor. RESULTS: At a median of 944.0 (interquartile range [IQR], 612.5-1104) days, 0 of 115 patients (0.0%) randomly assigned to CF-RF, 8 of 115 patients (7.0%) assigned to CRYO-4, and 5 of 116 patients (4.3%) assigned to CRYO-2 experienced an episode of persistent atrial tachyarrhythmia (P = .03). A documented recurrence of any atrial tachyarrhythmia ≥30 s occurred in 56.5%, 53.9%, and 62.9% of those randomized to CF-RF, CRYO-4, and CRYO-2, respectively; P = .65. Compared with that of the pre-ablation monitoring period, AF burden was reduced by a median of 99.5% (IQR 94.0%, 100.0%) with CF-RF, 99.9% (IQR 93.3%-100.0%) with CRYO-4, and 99.1%% (IQR 87.0%-100.0%) with CRYO-2 (P = .38). CONCLUSIONS: Catheter ablation of paroxysmal AF using radiofrequency energy was associated with fewer patients developing persistent AF on follow-up.

Healthcare utilization and quality of life for atrial fibrillation burden: the CIRCA-DOSE study.

AIMS: Atrial tachyarrhythmia recurrence ≥30 s remains the primary endpoint of clinical trials; however, this definition has not been correlated with clinical outcomes or pathophysiological processes. This study sought to determine the atrial tachyarrhythmia duration and burden associated with meaningful clinical outcomes. METHODS AND RESULTS: The time and duration of every atrial tachyarrhythmia episode recorded on implantable cardiac monitor were evaluated. Healthcare utilization and quality of life in the year following ablation were prospectively collected. Three hundred and forty-six patients provided 126 110 monitoring days. One-year freedom from recurrence increased with arrhythmia duration thresholds, from 52.6 (182/346) to 93.3% (323/346; P < 0.0001). Patients with atrial fibrillation (AF) recurrence limited to durations ≤1 h had rates of healthcare utilization comparable with patients free of recurrence, while patients with AF recurrences lasting >1 h had a relative risk for emergency department consultation of 3.2 [95% confidence interval (CI) 2.0-5.3], hospitalization of 5.3 (95% CI 2.9-9.6), and repeat ablation of 27.1 (95% CI 10.5-71.0). Patients with AF burden of ≤0.1% had rates of healthcare utilization comparable with patients free of recurrence, while patients with AF burden of >0.1% had a relative risk for emergency department consultation of 2.4 (95% CI 1.9-3.9), hospitalization of 6.8 (95% CI 3.6-13.0), cardioversion of 9.1 (95% CI 3.3-25.6), and repeat ablation of 21.8 (95% CI 9.2-52.2). Compared with patients free of recurrence, the disease-specific quality of life was significantly impaired with AF episode durations >24 h, or AF burdens >0.1%. CONCLUSION: AF recurrence, as defined by 30 s of arrhythmia, lacks clinical relevance. AF episode durations >1 h or burdens >0.1% were associated with increased rates of healthcare utilization.

Influence of Monitoring Strategy on Assessment of Ablation Success and Postablation Atrial Fibrillation Burden Assessment: Implications for Practice and Clinical Trial Design.

BACKGROUND: Various noninvasive intermittent rhythm monitoring strategies have been used to assess arrhythmia recurrences in trials evaluating pharmacological and invasive therapeutic interventions for atrial fibrillation (AF). We determined whether a frequency and duration of noninvasive rhythm monitoring could be identified that accurately detects arrhythmia recurrences and approximates the AF burden derived from continuous monitoring using an implantable cardiac monitor (ICM). METHODS: The rhythm history of 346 patients enrolled in the CIRCA-DOSE trial (Cryoballoon Versus Contact-Force Irrigated Radiofrequency Catheter Ablation) was reconstructed. Using computer simulations, we evaluated event-free survival, sensitivity, negative predictive value, and AF burden of a range of noninvasive monitoring strategies, including those used in contemporary AF ablation trials. RESULTS: A total of 126 290 monitoring days were included in the analysis. At 12 months, 164 patients experienced atrial arrhythmia recurrence as documented by the ICM (1-year event-free survival, 52.6%). Most noninvasive monitoring strategies used in AF ablation trials had poor sensitivity for detecting arrhythmia recurrence. Sensitivity increased with the intensity of monitoring, with serial (3) short-duration monitors (24-/48-hour ECG monitors) missing a substantial proportion of recurrences (sensitivity, 15.8% [95% CI, 8.9%-20.7%] and 24.5% [95% CI, 16.2%-30.6%], respectively). Serial (3) longer-term monitors (14-day ECG monitors) more closely approximated the gold standard ICM (sensitivity, 64.6% [95% CI, 53.6%-74.3%]). AF burden derived from short-duration monitors significantly overestimated the true AF burden in patients with recurrences. Increasing monitoring duration resulted in improved correlation and concordance between noninvasive estimates of the invasive AF burden (R2 = 0.85 and interclass correlation coefficient = 0.91 for serial [3] 14-day ECG monitors versus ICM). CONCLUSIONS: The observed rate of postablation atrial tachyarrhythmia recurrence is highly dependent on the arrhythmia monitoring strategy employed. Between-trial discrepancies in outcomes may reflect different monitoring protocols. On the basis of measures of agreement, serial long-term (7-14 day) intermittent monitors accumulating at least 28 days of annual monitoring provide estimates of AF burden comparable with ICM. However, ICMs outperform intermittent monitoring for arrhythmia detection, and should be considered the gold standard for clinical trials. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01913522.

DREAM-ICD-II Study.

BACKGROUND: Regulatory authorities of most industrialized countries recommend 6 months of private driving restriction after implantation of a secondary prevention implantable cardioverter-defibrillator (ICD). These driving restrictions result in significant inconvenience and social implications. This study aimed to assess the incidence rate of appropriate device therapies in contemporary recipients of a secondary prevention ICD. METHODS: This retrospective study at 3 Canadian tertiary care centers enrolled consecutive patients with new secondary prevention ICD implants between 2016 and 2020. RESULTS: For a median of 760 days (324, 1190 days), 721 patients were followed up. The risk of recurrent ventricular arrhythmia was highest during the first 3 months after device insertion (34.4%) and decreased over time (10.6% between 3 and 6 months, 11.7% between 6 and 12 months). The corresponding incidence rate per 100 patient-days was 0.48 (95% CI, 0.35-0.64) at 90 days, 0.28 (95% CI, 0.17-0.45) at 180 days, and 0.21 (95% CI, 0.13-0.33) between 181 and 365 days after ICD insertion (P<0.001). The cumulative incidence of arrhythmic syncope resulting in sudden cardiac incapacitation was 1.8% within the first 90 days and subsequently dropped to 0.4% between 91 and 180 days (P<0.001) after ICD insertion. CONCLUSIONS: The incidence rate of appropriate therapies resulting in sudden cardiac incapacitation in contemporary recipients of a secondary prevention ICD is much lower than previously reported and declines significantly after the first 3 months. Lowering driving restrictions to 3 months after the index cardiac event seems safe, and revision of existing guidelines should be considered in countries still adhering to a 6-month period. Existing restrictions for private driving after implantation of a secondary prevention ICD should be reconsidered.

Same-day discharge for atrial fibrillation ablation: outcomes and impact of ablation modality.

AIMS: Same-day discharge is increasingly common after catheter ablation for atrial fibrillation (AF). However, the impact of same-day discharge on healthcare utilization after ablation and whether this differs by ablation modality remains uncertain. We examined the safety, efficacy, and subsequent healthcare utilization of a same-day discharge protocol for AF ablation, including radiofrequency (RF) and cryoballoon ablation, in a contemporary cohort. METHODS AND RESULTS: All consecutive patients for whom full healthcare utilization data were available at two centres and who underwent AF ablation from 2018 to 2019 were included. Same-day discharge was the default strategy for all patients. The efficacy and safety outcomes were proportions of same-day discharge and readmission/emergency room (ER) visits, and post-discharge complications, respectively. Of the 421 patients who underwent AF ablation (mean 63.3 ± 10.2 years, 33% female), 90.5% (381/421) achieved same-day discharge with no difference between RF and cryoballoon ablation (89.8 vs. 95.1%, adjusted P = 0.327). Readmission ≤30 days occurred in 4.8%, with ER visits ≤30 days seen in 26.1% with no difference between ablation modalities (P = 0.634). Patients admitted overnight were more likely to present to the ER (40.0 vs. 24.7% with same-day discharge, P = 0.036). The overall post-discharge complication rate was low at 4/421 (1.0%), with no difference between ablation modality (P = 0.324) and admission/same-day discharge (P = 0.485). CONCLUSION: Same-day discharge can be achieved in a majority of patients undergoing RF or cryoballoon ablation for AF. Healthcare utilization, particularly ER visits, remains high after AF ablation, regardless of ablation modality or same-day discharge.

Kidney function monitoring and trajectories in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) and chronic kidney disease (CKD) frequently co-exist. The frequency of kidney monitoring and range of kidney function in patients with AF in clinical practice are uncertain. METHODS: All adult Albertans with AF between 2008 and 2017 were identified using ICD-9 and -10 codes 427.3 and I48. Kidney Disease Improving Global Outcomes (KDIGO) risk categories were defined using eGFR by the Chronic Kidney Disease Epidemiology Collaborative equation and albuminuria results within 6 months of eGFR measurement. eGFR trajectories were compared from baseline to maximum value within the following year. RESULTS: Among 105,946 patients with AF, 16.0% were KDIGO category G1 (eGFR ≥ 90), 49.0% G2 (60-89.9), 19.8% G3a (45-59.9), 11.4% G3b (30-44.9), and G4 3.8% (15-29.9). Albuminuria was normal/mild 83.4%, moderate 11.7%, and severe 4.9%. Kidney monitoring was more common among people with lower eGFR and worse albuminuria, from approximately twice annually for G1-2/A1-2 to 8 times annually in stage G4A3. Approximately 60-80% of patients received guideline-recommended monitoring, consistent across KDIGO stages. With lower baseline eGFR, annual change in eGFR decreased while the relative proportion of patients who worsened compared to improved increased: for baseline eGFR 60-89.9, 16.7% worsened vs 6.7% improved, but for eGFR 30-44.9, 8.8% worsened but only 1.0% improved. CONCLUSION: The frequency of kidney function monitoring in patients with AF increased with worsening KDIGO risk category and adhered to KDIGO guidelines in approximately three quarters of patients. A minority of patients had moderate to severe eGFR impairment, of whom most remained stable over 1 year.

Metabolic fluxes for nutritional flexibility of Mycobacterium tuberculosis.

The co-catabolism of multiple host-derived carbon substrates is required by Mycobacterium tuberculosis (Mtb) to successfully sustain a tuberculosis infection. However, the metabolic plasticity of this pathogen and the complexity of the metabolic networks present a major obstacle in identifying those nodes most amenable to therapeutic interventions. It is therefore critical that we define the metabolic phenotypes of Mtb in different conditions. We applied metabolic flux analysis using stable isotopes and lipid fingerprinting to investigate the metabolic network of Mtb growing slowly in our steady-state chemostat system. We demonstrate that Mtb efficiently co-metabolises either cholesterol or glycerol, in combination with two-carbon generating substrates without any compartmentalisation of metabolism. We discovered that partitioning of flux between the TCA cycle and the glyoxylate shunt combined with a reversible methyl citrate cycle is the critical metabolic nodes which underlie the nutritional flexibility of Mtb. These findings provide novel insights into the metabolic architecture that affords adaptability of bacteria to divergent carbon substrates and expand our fundamental knowledge about the methyl citrate cycle and the glyoxylate shunt.

Sex Differences in the Management of Oral Anticoagulation and Outcomes for Emergency Department Presentation of Incident Atrial Fibrillation.

STUDY OBJECTIVE: To examine sex differences in oral anticoagulation management and outcomes among patients with incident nonvalvular atrial fibrillation presenting to the emergency department (ED). METHODS: We identified patients older than 20 years presenting to the ED with incident nonvalvular atrial fibrillation between April 1, 2012, and March 30, 2019, using linked administrative databases in Alberta, Canada. We assessed the use of and adherence to oral anticoagulants at 1 year using the proportion of days covered for direct oral anticoagulants and time in therapeutic range for warfarin. Outcomes included stroke, heart failure, and all-cause mortality at 1 year. RESULTS: Of the 28,886 patients with nonvalvular atrial fibrillation presenting to ED, 44% were females. After adjustment, the rate of oral anticoagulant use was 5% lower in females with a guideline indication than that in males (adjusted hazard ratio 0.95, 95% confidence interval [CI] 0.91 to 0.99) discharged home, and there was no difference among admitted patients (adjusted hazard ratio 1.00, 95% CI 0.96 to 1.05). Females had high adherence to direct oral anticoagulants (≥80% proportion of days covered) compared to males (discharged: 77.7% versus 74.0%; admitted: 80.0% versus 76.7%; adjusted odds ratio for females: 1.15, 95% CI 1.02 to 1.29). More than half of the females and males had poor warfarin control (time in therapeutic range <65%) regardless of discharge status. In multivariable analyses, there was no sex difference in outcomes except a 1.48-fold (95% CI 1.14 to 1.92) higher risk of stroke in females. CONCLUSION: Females with incident nonvalvular atrial fibrillation discharged from the ED are less likely to receive oral anticoagulants than males. When oral anticoagulant treatment is initiated, females have high adherence to direct oral anticoagulants, and both the sexes have poor warfarin control. At 1 year, females were at a significantly higher risk of developing stroke.

Management of Atrial Tachyarrhythmias in Heart Failure-an Interventionalist's Point of View.

PURPOSE OF REVIEW: Atrial fibrillation (AF) and heart failure (HF) are commonly encountered clinical disorders that often co-exist, accelerating disease progression and adverse outcomes. It is known that restoration of sinus rhythm positively impacts this population; however, the complex comorbidity profile associated with HF introduces intricacies not encountered in other patient populations. The current review focuses on the safety and efficacy of an interventional-based management for atrial tachyarrhythmias in HF. RECENT FINDINGS: While pharmacotherapy has been the standard treatment of cardiac dysrhythmias in the HF population, recent evidence suggests catheter ablation is more effective and causes less harm than antiarrhythmic drugs (AADs) in the HF population. For the maintenance of sinus rhythm, catheter ablation results in improved freedom from recurrent arrhythmia, with secondary benefit on mortality and hospitalization in those with HF and reduced ejection fraction. For those with permanent AF, cardiac resynchronization therapy and atrioventricular junction ablation result in improved quality of life, physical functioning, and cardiac function.

Validity of different dose reduction criteria for apixaban.

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.

Effectiveness of medical therapy for treatment of idiopathic frequent premature ventricular complexes.

INTRODUCTION: The relative effectiveness of medical therapy compared with a conservative approach of monitoring in patients with idiopathic frequent premature ventricular complexes (PVCs) is uncertain. We evaluated the effectiveness of medical versus conservative therapy for frequent PVCs. METHODS: Patients with frequent PVCs (≥5%) were prospectively enrolled in this cohort study between 2016 and 2020. In patients with normal cardiac function and no structural heart disease, those receiving medical therapy were compared with controls without therapy. Patients were followed longitudinally for change in PVC burden and with serial echocardiography. RESULTS: Overall, 120 patients met inclusion criteria (mean: 56.5 ± 14.6 years, 54.2% female) with 53 on beta-blockers or calcium channel blockers (BBs/CCBs), 27 on Class I or III antiarrhythmic drugs (AADs), and 40 patients treated conservatively. Median initial PVC burden ranged from 15.5% to 20.6%. The median relative reduction of PVCs was 32.7%, 30.5%, and 81.3%, in the conservative therapy, BBs/CCBs, and AADs cohorts, respectively. AADs had greater PVC reduction compared with BBs/CCBs (p = 0.017) and conservative therapy (p = 0.045). PVC reduction to <1% was comparable across groups at 35.0%, 17.0%, 33.3%, respectively. Four patients (4/120, 3.3%) developed left ventricular dysfunction. Rates of adverse drug reactions and medication discontinuation were similar between groups, with no serious adverse events noted. CONCLUSION: In patients with idiopathic frequent PVCs, BB, and CCB have limited effectiveness in PVC reduction. Class I and III AADs have superior effectiveness for medical therapy in symptomatic patients, but only achieved complete PVC resolution suppression in one-third of patients.

Epidemiology of cardiac implantable electronic device infections: incidence and risk factors.

Cardiac implantable electronic device (CIED) infection is a potentially devastating complication of CIED procedures, causing significant morbidity and mortality for patients. Of all CIED complications, infection has the greatest impact on mortality, requirement for re-intervention and additional hospital treatment days. Based on large prospective studies, the infection rate at 12-months after a CIED procedure is approximately 1%. The risk of CIED infection may be related to several factors which should be considered with regards to risk minimization. These include technical factors, patient factors, and periprocedural factors. Technical factors include the number of leads and size of generator, the absolute number of interventions which have been performed for the patient, and the operative approach. Patient factors include various non-modifiable underlying comorbidities and potentially modifiable transient conditions. Procedural factors include both peri-operative and post-operative factors. The contemporary PADIT score, derived from a large cohort of CIED patients, is useful for the prediction of infection risk. In this review, we summarize the key information regarding epidemiology, incidence and risk factors for CIED infection.

Impact of Atrial Fibrillation Case Volume in the Emergency Department on Early and Late Outcomes of Patients With New Atrial Fibrillation.

STUDY OBJECTIVE: To define the association between atrial fibrillation case volume in the emergency department and death or all-cause hospitalization at 30 days and 1 year in patients with new atrial fibrillation. Secondary objectives examined repeat ED visits and the management of atrial fibrillation within 90 days. METHODS: We identified all adults presenting to an ED in Alberta, Canada, with a new primary diagnosis of atrial fibrillation/flutter between 2009 and 2015 using International Classification of Diseases, 10th Revision code I48. Volume was classified in tertiles weighted by annual ED number of atrial fibrillation cases. The association between volume and outcomes was evaluated using generalized linear mixed models, adjusting for prognostically important covariates as fixed effects and ED as a random effect to account for potential clustering within EDs. RESULTS: The tertiles consisted of 4 high, 9 medium, and 68 low atrial fibrillation volume EDs, with 4,217, 4,193, and 4,112 patients, respectively. Volume was not independently associated with the primary outcome or individual components. However, medium- and high-volume EDs had fewer repeat ED visits at 30 days (respective adjusted odds ratio [aOR] 0.75 [95% confidence interval {CI} 0.66 to 0.87] and 0.64 [0.52 to 0.79]) and 1 year (respective aOR 0.77 [95% CI 0.67 to 0.90] and 0.71 [0.56 to 0.90]). Fewer patients were admitted from medium- (37.1%) and high- (32.0%) compared with low-volume (39.5%) EDs. Patients attending medium- and high-volume EDs were more likely to be cardioverted (aOR 3.28 [95% CI 1.94 to 5.53] and 3.81 [1.39 to 10.48] for medium- and high-volume EDs, respectively). CONCLUSION: Treatment in higher volume EDs was associated with significantly lower admission rates and repeat ED visits but no difference in survival.

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

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.

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

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.

Changes to the electrocardiogram during exercise in anorexia nervosa.

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/m2). 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.

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

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.

Polled Digital Cell Sorter (p-DCS): Automatic identification of hematological cell types from single cell RNA-sequencing clusters.

BACKGROUND: Single cell RNA sequencing (scRNA-seq) brings unprecedented opportunities for mapping the heterogeneity of complex cellular environments such as bone marrow, and provides insight into many cellular processes. Single cell RNA-seq has a far larger fraction of missing data reported as zeros (dropouts) than traditional bulk RNA-seq, and unsupervised clustering combined with Principal Component Analysis (PCA) can be used to overcome this limitation. After clustering, however, one has to interpret the average expression of markers on each cluster to identify the corresponding cell types, and this is normally done by hand by an expert curator. RESULTS: We present a computational tool for processing single cell RNA-seq data that uses a voting algorithm to automatically identify cells based on approval votes received by known molecular markers. Using a stochastic procedure that accounts for imbalances in the number of known molecular signatures for different cell types, the method computes the statistical significance of the final approval score and automatically assigns a cell type to clusters without an expert curator. We demonstrate the utility of the tool in the analysis of eight samples of bone marrow from the Human Cell Atlas. The tool provides a systematic identification of cell types in bone marrow based on a list of markers of immune cell types, and incorporates a suite of visualization tools that can be overlaid on a t-SNE representation. The software is freely available as a Python package at https://github.com/sdomanskyi/DigitalCellSorter . CONCLUSIONS: This methodology assures that extensive marker to cell type matching information is taken into account in a systematic way when assigning cell clusters to cell types. Moreover, the method allows for a high throughput processing of multiple scRNA-seq datasets, since it does not involve an expert curator, and it can be applied recursively to obtain cell sub-types. The software is designed to allow the user to substitute the marker to cell type matching information and apply the methodology to different cellular environments.