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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. [ABSTRACT FROM AUTHOR]

Objective To examine whether warfarin use and outcomes differ across CHADS(2) and CHA(2)DS(2)-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 42834 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 42834 NVAF patients, 22.7% were low risk on the CHADS(2) risk score (0), 27.5% were intermediate risk (1), and 49.8% were high risk (>=2). The CHA(2)DS(2)-VASc risk score reclassified 16722 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 CHADS(2) (p for trend=0.85) or CHA(2)DS(2)-VASC (p=0.35). In multivariable adjusted analyses, warfarin use was associated with substantially lower rates of death or cerebrovascular events for patients with CHADS(2) 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 CHA(2)DS(2)-VASc scores of >=2 (OR 0.60, 95% CI 0.53 to 0.68). Conclusions In elderly patients with NVAF and elevated CHADS(2) or CHA(2)DS(2)-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. [ABSTRACT FROM AUTHOR]

Importance: Major gaps in the delivery of appropriate oral anticoagulation therapy (OAC) exist, leaving a large proportion of persons with atrial fibrillation (AF) unnecessarily at risk for stroke and its sequalae., Objective: To investigate whether pharmacist-led OAC prescription can increase the delivery of stroke risk reduction therapy in individuals with AF., Design, Setting, and Participants: This prospective, open-label, patient-level randomized clinical trial of early vs delayed pharmacist intervention from January 1, 2019, to December 31, 2022, was performed in 27 community pharmacies in Alberta, Canada. Pharmacists identified patients 65 years or older with 1 additional stroke risk factor and known, untreated AF (OAC nonprescription or OAC suboptimal dosing) or performed screening using a 30-second single-lead electrocardiogram to detect previously unrecognized AF. Patients with undertreated or newly diagnosed AF eligible for OAC therapy were considered to have actionable AF. Data were analyzed from April 3 to November 30, 2023., Interventions: In the early intervention group, pharmacists prescribed OAC using guideline-based algorithms with follow-up visits at 1 and 3 months. In the delayed intervention group, which served as the usual care control, the primary care physician (PCP) was sent a notification of actionable AF along with a medication list (both enhancement over usual care). After 3 months, patients without OAC optimization in the control group underwent delayed pharmacist intervention., Main Outcomes and Measures: The primary outcome was the difference in the rate of guideline-concordant OAC use in the 2 groups at 3-month follow-up ascertained by a research pharmacist blinded to treatment allocation., Results: Eighty patients were enrolled with actionable AF (9 [11.3%] newly diagnosed in 235 individuals screened). The mean (SD) age was 79.7 (7.4) years, and 45 patients (56.3%) were female. The median CHADS2 (congestive heart failure, hypertension, age, diabetes, and stroke or transient ischemic attack) score was 2 (IQR, 2-3). Seventy patients completed follow-up. Guideline-concordant OAC use at 3 months occurred in 36 of 39 patients (92.3%) in the early intervention group vs 23 of 41 (56.1%) in the control group (P < .001), with an absolute increase of 34% and number needed to treat of 3. Of the 23 patients who received appropriate OAC prescription in the control group, the PCP called the pharmacist for prescribing advice in 6 patients., Conclusions and Relevance: This randomized clinical trial found that pharmacist OAC prescription is a potentially high-yield opportunity to effectively close gaps in the delivery of stroke risk reduction therapy for AF. Scalability and sustainability of pharmacist OAC prescription will require larger trials demonstrating effectiveness and safety., Trial Registration: ClinicalTrials.gov Identifier: NCT03126214.

Syncope is common in the general population and a common presenting symptom in acute care settings. Substantial costs are attributed to the care of patients with syncope. Current challenges include differentiating syncope from its mimickers, identifying serious underlying conditions that caused the syncope, and wide variations in current management. Although validated risk tools exist, especially for short-term prognosis, there is inconsistent application, and the current approach does not meet patient needs and expectations. Artificial intelligence (AI) techniques, such as machine learning methods including natural language processing, can potentially address the current challenges in syncope management. Preliminary evidence from published studies indicates that it is possible to accurately differentiate syncope from its mimickers and predict short-term prognosis and hospitalisation. More recently, AI analysis of electrocardiograms has shown promise in detection of serious structural and functional cardiac abnormalities, which has the potential to improve syncope care. Future AI studies have the potential to address current issues in syncope management. AI can automatically prognosticate risk in real time by accessing traditional and nontraditional data. However, steps to mitigate known problems such as generalisability, patient privacy, data protection, and liability will be needed. In the past AI has had limited impact due to underdeveloped analytical methods, lack of computing power, poor access to powerful computing systems, and availability of reliable high-quality data. All impediments except data have been solved. AI will live up to its promise to transform syncope care if the health care system can satisfy AI requirement of large scale, robust, accurate, and reliable data., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Atrial fibrillation (AF) often escapes detection, given its frequent paroxysmal and asymptomatic presentation. Deep learning of transthoracic echocardiograms (TTEs), which have structural information, could help identify occult AF. We created a two-stage deep learning algorithm using a video-based convolutional neural network model that (1) distinguished whether TTEs were in sinus rhythm or AF and then (2) predicted which of the TTEs in sinus rhythm were in patients who had experienced AF within 90 days. Our model, trained on 111,319 TTE videos, distinguished TTEs in AF from those in sinus rhythm with high accuracy in a held-out test cohort (AUC 0.96 (0.95-0.96), AUPRC 0.91 (0.90-0.92)). Among TTEs in sinus rhythm, the model predicted the presence of concurrent paroxysmal AF (AUC 0.74 (0.71-0.77), AUPRC 0.19 (0.16-0.23)). Model discrimination remained similar in an external cohort of 10,203 TTEs (AUC of 0.69 (0.67-0.70), AUPRC 0.34 (0.31-0.36)). Performance held across patients who were women (AUC 0.76 (0.72-0.81)), older than 65 years (0.73 (0.69-0.76)), or had a CHA 2 DS 2 VASc ≥2 (0.73 (0.79-0.77)). The model performed better than using clinical risk factors (AUC 0.64 (0.62-0.67)), TTE measurements (0.64 (0.62-0.67)), left atrial size (0.63 (0.62-0.64)), or CHA 2 DS 2 VASc (0.61 (0.60-0.62)). An ensemble model in a cohort subset combining the TTE model with an electrocardiogram (ECGs) deep learning model performed better than using the ECG model alone (AUC 0.81 vs. 0.79, p = 0.01). Deep learning using TTEs can predict patients with active or occult AF and could be used for opportunistic AF screening that could lead to earlier treatment., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Preoperative risk assessments used in clinical practice are insufficient in their ability to identify risk for postoperative mortality. Deep-learning analysis of electrocardiography can identify hidden risk markers that can help to prognosticate postoperative mortality. We aimed to develop a prognostic model that accurately predicts postoperative mortality in patients undergoing medical procedures and who had received preoperative electrocardiographic diagnostic testing., Methods: In a derivation cohort of preoperative patients with available electrocardiograms (ECGs) from Cedars-Sinai Medical Center (Los Angeles, CA, USA) between Jan 1, 2015 and Dec 31, 2019, a deep-learning algorithm was developed to leverage waveform signals to discriminate postoperative mortality. We randomly split patients (8:1:1) into subsets for training, internal validation, and final algorithm test analyses. Model performance was assessed using area under the receiver operating characteristic curve (AUC) values in the hold-out test dataset and in two external hospital cohorts and compared with the established Revised Cardiac Risk Index (RCRI) score. The primary outcome was post-procedural mortality across three health-care systems., Findings: 45 969 patients had a complete ECG waveform image available for at least one 12-lead ECG performed within the 30 days before the procedure date (59 975 inpatient procedures and 112 794 ECGs): 36 839 patients in the training dataset, 4549 in the internal validation dataset, and 4581 in the internal test dataset. In the held-out internal test cohort, the algorithm discriminates mortality with an AUC value of 0·83 (95% CI 0·79-0·87), surpassing the discrimination of the RCRI score with an AUC of 0·67 (0·61-0·72). The algorithm similarly discriminated risk for mortality in two independent US health-care systems, with AUCs of 0·79 (0·75-0·83) and 0·75 (0·74-0·76), respectively. Patients determined to be high risk by the deep-learning model had an unadjusted odds ratio (OR) of 8·83 (5·57-13·20) for postoperative mortality compared with an unadjusted OR of 2·08 (0·77-3·50) for postoperative mortality for RCRI scores of more than 2. The deep-learning algorithm performed similarly for patients undergoing cardiac surgery (AUC 0·85 [0·77-0·92]), non-cardiac surgery (AUC 0·83 [0·79-0·88]), and catheterisation or endoscopy suite procedures (AUC 0·76 [0·72-0·81])., Interpretation: A deep-learning algorithm interpreting preoperative ECGs can improve discrimination of postoperative mortality. The deep-learning algorithm worked equally well for risk stratification of cardiac surgeries, non-cardiac surgeries, and catheterisation laboratory procedures, and was validated in three independent health-care systems. This algorithm can provide additional information to clinicians making the decision to perform medical procedures and stratify the risk of future complications., Funding: National Heart, Lung, and Blood Institute., Competing Interests: Declaration of interests DO reports support from the National Institute of Health (NIH; NHLBI R00HL157421) and Alexion, and consulting or honoraria for lectures from EchoIQ, Ultromics, Pfizer, InVision, the Korean Society of Echo, and the Japanese Society of Echo. JWH reports funding from the National Science Foundation (DGE-1656518). PE reports research support from the NIH (T32HL007854-21) and serves on the American College of Cardiology Innovation Council. BC reports consulting from Alnylam, Cardurion, Corvia, CVRX, Cytokinetics, Intellia, and Rocket. TP reports stock in Abbot and Baxter, and research support from the American Heart Association, Eido, Pfizer, Edwards, and the New York Academy of Medicine. JHC reports research funding from NIH/National Institute of Aging (AI17812101), NIH/National Institute on Drug Abuse (UG1DA015815-CTN-0136), AIMI-HAI Partnership, Doris Duke Charitable Foundation (20211260), Google (SPO136094), American Heart Association, and Clinical and Translational Sciences Awards Program by the National Center for Advancing Translational Sciences (R56LM013365); is a co-founder of Reaction Explorer; and receives consulting fees from Sutton Pierce and Younker Hyde MacFarlane. MP reports research support from the NIH (HL136390), patents for ECG-based cardiac arrhythmia detection (WO2014205310A3), and consulting fees from Apple, Biotronik, Boston Scientific, QALY, Johnson and Johnson, and Bristol Myers Squibb. CMA reports support from NIH (HL165840), consulting fees from Medtronic, Novartis, Illumina, and Medtronic, and participation in advisory boards for Boston Scientific, Medtronic, and Element Science; and is a trustee on the board for the Heart Rhythm Society. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Background: Sustained forms of atrial fibrillation (AF) are associated with lower treatment success rates and poorer prognosis compared with paroxysmal AF. Yet, little is known about risk factors that predispose to persistent AF on initial presentation. Our objective was to define risk factors associated with new-onset persistent AF., Methods: We prospectively examined the differential associations between lifestyle, clinical, and socioeconomic risk factors and AF pattern (persistent versus paroxysmal) at the time of diagnosis among 25 119 participants without a history of cardiovascular disease, AF, or cancer in the VITAL rhythm study (Vitamin D and Omega-3)., Results: During a median follow-up of 5.3 years, 900 participants developed AF and 346 (38.4%) were classified as persistent at the time of diagnosis. In multivariable competing risk models, increasing age, male sex, White race, height, weight, body mass index ≥30 kg/m 2 , hypertension, current or past smoking, alcohol intake ≥2 drinks/day, postcollege education, and randomized treatment with vitamin D were significantly associated with incident persistent AF. Compared with paroxysmal AF, increasing age, male sex, weight, body mass index ≥30 kg/m 2 , and postcollege education were more strongly associated with persistent AF in multivariable models regardless of whether interim cardiovascular disease and heart failure events were censored., Conclusions: In a prospective cohort without baseline AF or cardiovascular disease, over one-third of AF at the time of diagnosis is persistent. Older age, male sex, postcollege education, and obesity were preferentially associated with persistent AF and represent a high-risk AF subset for population-based intervention., Competing Interests: Disclosures Dr Albert reported receipt of research grants from St. Jude Medical, Abbott, and Roche Diagnostics and has served as a consultant for Medtronic, Boston Scientific, Element Science, and Novartis. The other authors report no conflicts.

Background: Healthcare resource use for atrial fibrillation (AF) is high, but it may not be equivalent across all patients. We examined whether sex differences exist for AF high-cost users (HCUs), who account for the top 10% of total acute care costs., Methods: All patients aged ≥ 20 years who presented to the emergency department (ED) or were hospitalized with AF were identified in Alberta, Canada, between 2011 and 2015. The cohort was categorized by sex into HCUs and non-HCUs. Healthcare utilization was defined as ED, hospital, and physician visits, and costs included those for hospitalization, ambulatory care, physician billing, and drugs. All costs were inflated to 2022 Canadian dollars (CAD$)., Results: Among 48,030 AF patients, 45.1% were female. Of these, 31.8% were HCUs, and the proportions of female and male patients were equal (31.9% vs 31.7%). Female HCUs were older, more likely to have hypertension and heart failure, and had a higher stroke risk than male HCUs. Mean healthcare utilization did not differ among HCUs by sex, except for number of ED visits, which was higher in male patients (12.7% vs 9.2%, P < 0.0001). Overall, HCUs accounted for 65.8% of the total costs (CAD$3.4 billion). Almost half of total HCU costs were attributable to female HCUs (CAD$966.1 million). Significant differences were present in the distributions of HCU-related costs (male patients: 74.6% hospitalization, 9.5% ambulatory care, 12.4% physician billing, 3.5% drugs; female patients: 77.7% hospitalization, 7.4% ambulatory care, 11.5% physician billing, 3.5% drugs, P < 0.0001)., Conclusions: Despite having a lower AF prevalence, female patients represent an equal proportion of HCUs, and account for almost half the total HCU costs. Interventions targeted at reducing the number of AF HCU are needed, particularly for female patients., (© 2023 The Authors.)

Aims: Whether electrocardiographic (ECG) measurements predict mortality in chronic heart failure with reduced ejection fraction (HFrEF) is unknown., Methods and Results: We studied 4880 patients from the Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial with a baseline 12-lead ECG. Associations between ECG measurements and mortality were estimated as hazard ratios (HR) and adjusted for the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score, N-terminal pro-B-type natriuretic peptide, and index event. Select interactions between ECG measurements, patient characteristics and mortality were examined. Over a median of 10.8 months, there were 824 cardiovascular (CV) deaths (214 sudden) and 1005 all-cause deaths. Median age was 68 years (interquartile range [IQR] 60-76), 24% were women, median ejection fraction was 30% (IQR 23-35), 41% had New York Heart Association class III/IV, and median MAGGIC score was 24 (IQR 19-28). After multivariable adjustment, significant associations existed between heart rate (per 5 bpm: HR 1.02), QRS duration (per 10 ms: HR 1.02), absence of left ventricular hypertrophy (HR 0.64) and CV death, and similarly so with all-cause death (HR 1.02; HR 1.02; HR 0.61, respectively). Contiguous pathologic Q waves were significantly associated with sudden death (HR 1.46), and right ventricular hypertrophy with all-cause death (HR 1.44). The only sex-based interaction observed was for pathologic Q waves on CV (men: HR 1.05; women: HR 1.64, p interaction  = 0.024) and all-cause death (men: HR 0.99; women: HR 1.57; p interaction  = 0.010). Whereas sudden death doubled in females, it did not differ among males (male: HR 1.25, 95% confidence interval [CI] 0.87-1.79; female: HR 2.50, 95% CI 1.23-5.06; p interaction  = 0.141)., Conclusion: Routine ECG measurements provide additional prognostication of mortality in high-risk HFrEF patients, particularly in women with contiguous pathologic Q waves., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Vasovagal syncope (VVS) is common, recurs, and is associated with markedly reduced quality of life, anxiety, and frequent injuries. The few pharmacological therapies for VVS proven to have a moderate benefit in reducing recurrences are limited to patients without coexisting conditions such as hypertension or heart failure. Although there is some data to suggest Atomoxetine, a norepinephrine reuptake transport inhibitor (NET), may be a promising treatment option, an adequately powered randomized placebo-controlled trial is needed., Study Design: POST VII is a multicenter, randomized, double-blind, placebo-controlled, crossover study that will randomize 180 patients with VVS and at least 2 syncopal spells in the preceding year to a target daily dose of atomoxetine 80 mg daily or to a matching placebo, with an observation period of 6 months in each phase and with a 1-week washout period between phases. The primary end point will be the proportion of patients with at least one syncope recurrence in each arm analyzed with an intention-to-treat approach. The secondary end points include total syncope burden, quality of life, cost, and cost-effectiveness., Power Calculations: Assuming a 33% relative risk reduction in syncope recurrence with atomoxetine, and a dropout rate of 16%, the enrollment of 180 patients will give an 85% power of reaching a positive conclusion about atomoxetine, with P = .05., Conclusions: This will be the first adequately powered trial to determine whether atomoxetine is effective in preventing VVS. If proven effective, atomoxetine might become the first-line pharmacological treatment for recurrent VVS., Competing Interests: Conflict of interest None reported., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Patients with new-onset left bundle branch block (LBBB) after transcatheter aortic valve implantation (TAVI) are at risk of developing delayed high-degree atrioventricular block. Management of new-onset LBBB post-TAVI remains controversial. In the Co mparison of a Clinical M onitoring Strategy Versus E lectrophysiology-Guided Algorithmic Approach in Patients With a New LBBB After TAVI (COME-TAVI) trial, consenting patients with new-onset LBBB that persists on day 2 after TAVI, meeting exclusion/inclusion criteria, are randomized to an electrophysiological study (EPS)-guided approach or 30-day electrocardiographic monitoring. In the EPS-guided approach, patients with a His to ventricle (HV) interval ≥ 65 ms undergo permanent pacemaker implantation. Patients randomized to noninvasive monitoring receive a wearable continuous electrocardiographic recording and transmitting device for 30 days. Follow-up will be performed at 3, 6, and 12 months. The primary endpoint is a composite outcome designed to capture net clinical benefit. The endpoint incorporates major consequences of both strategies in patients with new-onset LBBB after TAVI, as follows: (i) sudden cardiac death; (ii) syncope; (iii) atrioventricular conduction disorder requiring a pacemaker (for a class I or IIa indication); and (iv) complications related to the pacemaker or EPS. The trial incorporates a Bayesian design with a noninformative prior, outcome-adaptive randomization (initially 1:1), and 2 prespecified interim analyses once 25% and 50% of the anticipated number of primary endpoints are reached. The trial is event-driven, with an anticipated upper limit of 452 patients required to reach 77 primary outcome events over 12 months of follow-up. In summary, the aim of this Bayesian multicentre randomized trial is to compare 2 management strategies in patients with new-onset LBBB post-TAVI-an EPS-guided approach vs noninvasive 30-day monitoring. Trial registration number: NCT03303612., (© 2023 The Authors.)

Background: Undiagnosed chronic kidney disease (CKD) is a common and usually asymptomatic disorder that causes a high burden of morbidity and early mortality worldwide. We developed a deep learning model for CKD screening from routinely acquired ECGs., Methods: We collected data from a primary cohort with 111,370 patients which had 247,655 ECGs between 2005 and 2019. Using this data, we developed, trained, validated, and tested a deep learning model to predict whether an ECG was taken within one year of the patient receiving a CKD diagnosis. The model was additionally validated using an external cohort from another healthcare system which had 312,145 patients with 896,620 ECGs between 2005 and 2018., Results: Using 12-lead ECG waveforms, our deep learning algorithm achieves discrimination for CKD of any stage with an AUC of 0.767 (95% CI 0.760-0.773) in a held-out test set and an AUC of 0.709 (0.708-0.710) in the external cohort. Our 12-lead ECG-based model performance is consistent across the severity of CKD, with an AUC of 0.753 (0.735-0.770) for mild CKD, AUC of 0.759 (0.750-0.767) for moderate-severe CKD, and an AUC of 0.783 (0.773-0.793) for ESRD. In patients under 60 years old, our model achieves high performance in detecting any stage CKD with both 12-lead (AUC 0.843 [0.836-0.852]) and 1-lead ECG waveform (0.824 [0.815-0.832])., Conclusions: Our deep learning algorithm is able to detect CKD using ECG waveforms, with stronger performance in younger patients and more severe CKD stages. This ECG algorithm has the potential to augment screening for CKD., (© 2023. The Author(s).)

The feasibility and value of linking electrocardiogram (ECG) data to longitudinal population-level administrative health data to facilitate the development of a learning healthcare system has not been fully explored. We developed ECG-based machine learning models to predict risk of mortality among patients presenting to an emergency department or hospital for any reason. Using the 12-lead ECG traces and measurements from 1,605,268 ECGs from 748,773 healthcare episodes of 244,077 patients (2007-2020) in Alberta, Canada, we developed and validated ResNet-based Deep Learning (DL) and gradient boosting-based XGBoost (XGB) models to predict 30-day, 1-year, and 5-year mortality. The models for 30-day, 1-year, and 5-year mortality were trained on 146,173, 141,072, and 111,020 patients and evaluated on 97,144, 89,379, and 55,650 patients, respectively. In the evaluation cohort, 7.6%, 17.3%, and 32.9% patients died by 30-days, 1-year, and 5-years, respectively. ResNet models based on ECG traces alone had good-to-excellent performance with area under receiver operating characteristic curve (AUROC) of 0.843 (95% CI: 0.838-0.848), 0.812 (0.808-0.816), and 0.798 (0.792-0.803) for 30-day, 1-year and 5-year prediction, respectively; and were superior to XGB models based on ECG measurements with AUROC of 0.782 (0.776-0.789), 0.784 (0.780-0.788), and 0.746 (0.740-0.751). This study demonstrates the validity of ECG-based DL mortality prediction models at the population-level that can be leveraged for prognostication at point of care., (© 2023. The Author(s).)

Objective: Vasovagal syncope (VVS) is a common clinical condition with few effective medical therapies. The study aimed to evaluate the effectiveness of atomoxetine in suppressing syncope in patients with recurrent VVS., Methods: This was a retrospective, open-label, observational case series of 12 patients taking atomoxetine for suppression of recurrent vasovagal syncope. We compared syncope frequency in the 1 year before atomoxetine and while subjects were taking atomoxetine. We used novel applications of the Poisson distribution to describe the results as a collection of n = 1 studies., Results: There were 12 subjects, eight female, with a mean age 47 ± 22 years and a mean Calgary Syncope Symptom Score of 2 (diagnostic of vasovagal syncope). The patients received a mean dose of atomoxetine of 66 ± 16 mg (1.06 ± 0.21 mg/kg). The mean follow-up period was 1.21 ± 1.01 years. While taking atomoxetine, 11/12 patients appeared to improve and 7/12 had no syncope in follow-up (p = 0.0046). The annualized syncope frequency decreased from a median 5.5 (IQR 4, 6.75) syncope per year to 0 (IQR 0, 0.88) syncope per year (p = 0.002, Wilcoxon rank-sum test). According to the Poisson distribution, 7/12 subjects significantly improved with p values of < 0.0001 to 0.0235, 3/12 did not faint but had too brief follow-up times to detect significance, and 2/12 did not improve significantly., Conclusions: In this case series, atomoxetine was a promising oral agent for the prevention of vasovagal syncope. The Poisson distribution permits individual patient-level assessment of improvement and detects insufficient follow-up despite apparent improvement., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: A familial predisposition to sudden and/or arrhythmic death (SAD) in the setting of coronary artery disease (CAD) exists; however, the genetic basis is poorly understood., Objectives: The purpose of this study was to determine whether a genome-wide polygenic score for coronary artery disease (GPS CAD ) might have utility in SAD risk stratification in CAD patients without severe systolic dysfunction., Methods: A previously validated GPS CAD was generated utilizing genome-wide genotyping in 4,698 PRE-DETERMINE participants of European ancestry with CAD and left ventricular ejection fraction >30%-35%. The population was dichotomized according to top GPS CAD decile as defined by the general population, and absolute, proportional, and relative risks for SAD and non-SAD were estimated using competing risk analyses., Results: Over a median follow-up of 8.0 years, participants in the top GPS CAD decile were at elevated absolute SAD risk (8.0%; 95% CI: 5.1%-12.4% vs 4.8%; 95% CI: 3.3%-7.0%; P = 0.005) and proportional SAD risk (29% vs 16%; P = 0.0003) compared with the remainder. After controlling for left ventricular ejection fraction, clinical factors, and electrocardiogram parameters, the top GPS CAD decile was associated with SAD (subdistribution HR: 1.77; 95% CI: 1.23-2.54; P = 0.002) but not non-SAD (subdistribution HR: 1.00; 95% CI: 0.80-1.25; P = 0.98) (P for Δ = 0.003). The addition of the top GPS CAD decile to the multivariable model significantly improved net reclassification indexes (NRIs) (continuous NRI: 14.0%; P = 0.024; and categorical NRI: 6.6%; P = 0.005) but not the C-index (difference in C-index: 0.007; P = 0.143)., Conclusions: Among CAD patients without severe systolic dysfunction, high GPS CAD specifically predicted SAD and enriched for both absolute and proportional SAD risk, identifying a population who might benefit from defibrillator therapy., Competing Interests: Funding Support and Author Disclosures PRE-DETERMINE was supported by research grants from the National Heart, Lung, and Blood Institute R01HL091069, St Jude Medical Inc, and St Jude Medical Foundation (to Dr Albert). Genetic analysis was supported by grants 1K08HG010155 and 1U01HG011719 (to Dr Khera) from the National Human Genome Research Institute. Dr Khera is an employee of and holds equity in Verve Therapeutics; has served as a scientific advisor to Amgen, Maze Therapeutics, Navitor Pharmaceuticals, Sarepta Therapeutics, Novartis, Silence Therapeutics, Korro Bio, Veritas International, Color Health, Third Rock Ventures, Illumina, Foresite Labs, and Columbia University (National Institutes of Health); has received speaker fees from Illumina, MedGenome, Amgen, and the Novartis Institute for Biomedical Research; has received a sponsored research agreement from IBM Research; and is listed as a coinventor on a patent application for use of imaging data in assessing body fat distribution and associated cardiometabolic risk. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: An unanswered question is whether the combination of advances in medical and device therapy over the past decade has translated into improved outcomes for patients with heart failure (HF) in Canada., Methods: The Canadian Institute for Health Information (CIHI) Hospital Morbidity Database was used to identify hospitalizations for HF among patients aged 18 years and older in Canadian hospitals during fiscal years 2009/2010 and 2018/2019. We assessed interprovincial differences in age, sex, length of stay (LOS), discharge disposition, type of admitting hospital, and most responsible service, for all HF admissions. National and provincial rates of HF admissions and all-cause 30-day readmissions were calculated., Results: After adjusting for age, the rate of HF admissions in Canada was 216 per 100,000 population in 2009/2010 and 2018/2019. The majority of patients with HF were admitted to general internal medicine and community hospitals in both 2009/2010 and 2018/2019. The national, crude, all-cause 30-day readmission rate stayed constant at 20.6%, and the majority of patients were readmitted with the diagnosis of HF in both 2009/2010 (62.5%) and 2018/2019 (59.0%). Median and interquartile range of HF LOS also remained unchanged at 7 days (3-14)., Conclusions: The national rate of HF admissions, 30-day readmissions, and HF LOS have remained unchanged from 2009/2010 to 2018/2019, despite advances in medical and device therapy during this timeframe., (© 2022 The Authors.)

Background Oral anticoagulation (OAC) therapy prevents morbidity and mortality in nonvalvular atrial fibrillation; whether location of diagnosis influences OAC uptake or adherence is unknown. Methods and Results Retrospective cohort study (2008-2019), identifying adults with incident nonvalvular atrial fibrillation across health care settings (emergency department, hospital, outpatient) at high risk of stroke. OAC uptake and adherence via proportion of days covered for direct OACs and time in therapeutic range for warfarin were measured. Proportion of days covered was categorized as low (0-39%), intermediate (40-79%), and high (80-100%). Warfarin control was defined as time in therapeutic range ≥65%. All-cause mortality was examined at a 3-year landmark. Among 75 389 patients with nonvalvular atrial fibrillation (47.0% women, mean 77.4 years), 19.7% were diagnosed in the emergency department, 59.1% in the hospital, and 21.2% in the outpatient setting. Ninety-day OAC uptake was 51.6% in the emergency department, 50.9% in the hospital, and 67.9% in the outpatient setting ( P <0.0001). High direct OAC adherence increased from 64.9% to 80.3% in the emergency department, 64.3% to 81.7% in the hospital, and 70.9% to 88.6% in the outpatient setting over time ( P values for trend <0.0001). Warfarin control was 40.3% overall and remained unchanged. In multivariable analysis, outpatient diagnosis compared with the hospital was associated with greater OAC uptake (odds ratio [OR], 1.79; [95% CI, 1.72-1.87]) and direct OAC (OR, 1.42; [95% CI, 1.27-1.59]) and warfarin (OR, 1.49; [95% CI, 1.36-1.63]) adherence. Varying or persistently low adherence was associated with a poor prognosis, especially for warfarin. Conclusions Locale of nonvalvular atrial fibrillation diagnosis is associated with varying OAC uptake and adherence. Interventions specific to health care settings are needed to improve stroke prevention.

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., (Copyright © 2022 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The opioid epidemic is a progressively worsening public health crisis that continues to impact healthcare system strategies such as overdose reversal and destigmatization. Even among healthcare professionals, there remains a lack of confidence in naloxone administration and a prevalence of stigma. While training can play a major impact in reducing these shortcomings, the long-term effectiveness has yet to be characterized in training healthcare professionals. This study examined the long-term retention of opioid overdose awareness and reversal training (OOART) by evaluating performance at two-time intervals, immediately post-training and at a 3-month follow-up., Methods: Voluntary training was offered to first-year (M1) medical students at the Drexel University College of Medicine in 2021. At this training, 118 students completed training, 95 completed the post-training survey, and 42 completed the 3-month follow-up., Results: Opioid reversal knowledge questions assessed significantly increased scores post-training and at the 3-month follow-up. In three of the attitude questions, scores were improved at both follow-up timepoints. In addition, three attitude questions indicating a participant's confidence to respond to an opioid overdose situation increased directly after the training, but regressed at the 3-month follow-up. The remaining questions did not show any statistical difference across the survey intervals., Conclusions: This study establishes that while OOART provides participants with the knowledge of how to respond to an opioid overdose, the retention of this knowledge at a 3-month interval is reduced. The results were mixed for longitudinal assessment of participant's attitudes toward people with opioid use disorder. Some positive increases in attitudes were retained at the 3-month interval, while others trended back toward pre-training levels. These results support the effectiveness of the training but also provide evidence that OOART must be reinforced often., (© 2022. The Author(s).)

Background: An integrated, coordinated, and patient-centered approach to atrial fibrillation (AF) care delivery may improve outcomes and reduce cost., Objective: The purpose of this study was to gain a better understanding from key stakeholder groups on current practices, needs, and potential barriers to implementing optimal integrated AF care., Methods: A series of comprehensive questionnaires were designed by the Heart Rhythm Society Atrial Fibrillation Centers of Excellence (CoE) Task Force to conduct surveys with physicians, advanced practice professionals, patients, and hospital administrators. Data collected focused on the following areas: access to care, stroke prevention, education, AF quality improvement, and AF CoE needs and barriers. Survey responses were collated and analyzed by the Task Force., Results: The surveys identified 5 major unmet needs: (1) Standardized protocols, order sets, or care pathways in the emergency department or inpatient setting were uncommon (36%-42%). (2) All stakeholders agreed stroke prevention was a top priority; however, prior bleeding or risk of bleeding was the most frequent barrier for initiation. (3) Patients indicated that education on modifiable causes, AF-related complications, and lowering stroke risk is most important. (4) Less than half (43%) of the health care systems track patients with AF or treatment status. Patients reported that stroke and heart failure prevention and access to procedures were priority areas for an AF CoE. The most common barriers to implementing AF CoE identified by clinicians were administrative support (69%) and cost (52%); administrators reported physical space (43%)., Conclusion: On the basis of the findings of this study, the Task Force identified high priority areas to develop initiatives to aid the implementation of AF CoE., (Copyright © 2022 Heart Rhythm Society. All rights reserved.)

Background: Heart failure (HF) is a leading complication of nonvalvular atrial fibrillation (NVAF), and the presence of both conditions worsens prognosis. Sex-specific associations between NVAF and outcomes focus on stroke; less is known about HF. We evaluated sex differences in incident HF in NVAF., Methods: We identified adults age ≥ 65 years hospitalized for incident NVAF without prior HF from April 2010 to March 2018 in Canada. The primary outcome was incident HF hospitalization, with a secondary composite outcome of incident HF hospitalization or all-cause mortality at 1 year. Cox proportional hazard regression models were constructed for the association between sex and outcomes, adjusting for age, comorbidities, socioeconomic status, cardioversion, and medications., Results: Of 68,909 NVAF patients, 53.8% were women. Women had a higher rate of the primary outcome (30.0% vs 25.6%, P < 0.001) and the composite outcome (39.5% vs 36.6%, P < 0.001) than men. In multivariable analysis without adjusting for medications, there was an 8% increase risk of HF (95% confidence interval [CI] 1.05-1.11, P < 0.001) for women, which was attenuated when accounting for medication (hazard ratio [HR] 1.01, 95% CI 0.98-1.04). After full adjustment, women age ≥ 75 years were at higher risk of the primary outcome (HR 1.10, 95% CI 1.06-1.13, P < 0.001) and the composite outcome (HR 1.04, 95% CI 1.01-1.07, P < 0.001), compared with men, whereas there was a significantly lower risk for those age 65-75 years., Conclusions: In this nationwide study of incident NVAF without HF, women age ≥ 75 years were more likely to develop HF or die than men. Strategies to prevent HF in older women with NVAF are needed., (© 2022 The Authors.)

Short-term outcomes are worse for patients with acute coronary syndrome (ACS) with a history of nonvalvular atrial fibrillation (NVAF). However, long-term prognosis remains unclear. We linked administrative health databases to identify patients hospitalized with ACS (ST-elevation myocardial infarction [STEMI], non-STEMI [NSTEMI], and unstable angina) between 2008 and 2019 in Alberta, Canada. Patients were stratified according to history of NVAF before hospitalization. The primary outcome was a composite of all-cause mortality, hospitalization for myocardial infarction, or stroke at 3 years. Cox models were constructed to estimate the association between ACS, NVAF, and outcomes. Of 54,309 ACS hospitalizations, 6,351 patients (11.7%) had a history of NVAF. Compared with patients without NVAF, patients with previous NVAF were older (75.6 ± 11.6 vs 64.9 ± 13.4 years), women (35.1% vs 30.0%), had higher comorbid burden (Charlson co-morbidity index 3.0 vs 1.0), and more often presented with NSTEMI (57.5% vs 49.0%). The primary outcome occurred in 37.0% of patients with previous NVAF and 17.4% without (p <0.001). In the multivariable analysis, there was a 1.14-fold (95% confidence interval [CI] 1.09 to 1.20) higher risk of the primary outcome in patients with previous NVAF. There was a significant association with STEMI (adjusted harazard ratio [aHR] 1.24, 95% CI 1.12 to 1.36) and NSTEMI (aHR 1.12, 95% CI 1.06 to 1.19) but not with unstable angina (aHR 1.04, 95% CI 0.90 to 1.22). In conclusion, in this population-based study, we identified that a history of NVAF at ACS presentation is associated with worse long-term prognosis, particularly for STEMI and NSTEMI., Competing Interests: Disclosures Dr. Sandhu receives financial support from University Hospital Foundation and Servier Canada. The remaining authors have no conflicts of interest to declare., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

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 and 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 three groups and drug-drug interactions classified according to the 2018 European Heart Rhythm Association practical guide. Time-varying Cox models calculated the 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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

There is a growing appreciation for differences in epidemiology, treatment, and outcomes of cardiovascular conditions by sex. Historically, cardiovascular clinical trials have under-represented females, but findings have nonetheless been applied to clinical care in a sex-agnostic manner. Thus, much of the collective knowledge about sex-specific cardiovascular outcomes result from post hoc and secondary analyses. In some cases, these investigations have revealed important sex-based differences with implications for optimizing care for female patients with arrhythmias. This review explores the available evidence related to cardiac arrhythmia care among females, with emphasis on areas in which important sex differences are known or suggested. Considerations related to improving female enrollment in clinical trials as a way to establish more robust clinical evidence for the treatment of females are discussed. Areas of remaining evidence gaps are provided, and recommendations for areas of future research and specific action items are suggested. The overarching goal is to improve appreciation for sex-based differences in cardiac arrhythmia care as 1 component of a comprehensive plan to optimize arrhythmia care for all patients.

Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia.

Background: The extent to which the introduction of direct oral anticoagulants (DOACs) influenced treatment patterns in frail and nonfrail patients with nonvalvular atrial fibrillation (NVAF) is unclear., Methods: This was a retrospective cohort study of all Albertans 20 years or older who were discharged from an emergency department or hospital with a new diagnosis of NVAF between April 1, 2009, and March 31, 2019. The Hospital Frailty Risk Score was used to define frailty and the CHA 2 DS 2 -VASc and CHADS-65 scores were used to identify if anticoagulation was indicated., Results: Among 75,796 patients (median age, 75 years; 45% female) with a new diagnosis of NVAF, 17,143 (22.6%) were frail. Although guideline criteria for anticoagulation were more commonly met by frail patients than nonfrail patients (92.1% vs 74.2%, for CHA 2 DS 2 -VASc, and 96.8% vs 85.8% for CHADS-65; both P < 0.0001), frail patients were less likely to receive any anticoagulant, even after those with contraindications to anticoagulation were excluded (adjusted odds ratio, 0.61; 95% confidence interval, 0.58-0.64). After DOACs became available, anticoagulant prescribing for patients with guideline indications increased more in nonfrail patients (from 42.4% to 68.2%) than in frail patients (from 29.0% to 52.2%) and frail patients were less likely to receive a DOAC than warfarin (adjusted odds ratio, 0.66; 95% confidence interval, 0.54-0.81)., Conclusions: Although they stand to potentially derive greater benefits from anticoagulation, frail patients were less likely to receive an anticoagulant and, if anticoagulated, they were more likely to receive warfarin than a DOAC. The introduction of DOACs has increased anticoagulation rates but not resolved treatment gaps for frail patients with NVAF., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Data are limited data on the prevalence of cardiovascular disease (CVD) and multimorbidity in contemporary cohorts of high-cost users (HCUs) in Canada.We examined the following: (i) the prevalence of CVD, with a comparison of total healthcare costs among HCUs with vs without CVD; (ii) the contribution of other comorbidities to costs among HCUs with CVD; and (iii) the trajectory of healthcare costs in the years before and after becoming an HCU., Methods: The study included adult Alberta patients in the Canadian Institutes of Health Research/Canadian Institute for Health Information Dynamic Cohort of Complex, High System Users from 2011-2012 through 2014-2015. We examined total healthcare costs, including hospital, ambulatory care, physician services, and drugs., Results: Among 88,536 HCUs, 23.4% had no CVD, 28.9% were hospitalized with a primary diagnosis of CVD, and 47.7% were hospitalized with a secondary diagnosis of CVD. Total healthcare costs were $2.0 billion (20.4% non-hospital costs), $2.8 billion (24.1% non-hospital costs), and $4.9 billion (19.8% non-hospital costs), respectively, in the 3 groups. Many HCUs with CVD were frail (74.2%) and many had diabetes (33.8%) or chronic obstructive pulmonary disease (27.9%), which contributed to higher costs and mortality. Healthcare expenditures in HCUs with CVD were several times higher than per capita health expenditures in the years prior to, and following, their inclusion in the dynamic HCU cohort., Conclusions: CVD is very common in HCUs of healthcare. HCUs with CVD have high rates of frailty and multimorbidity. Further research is needed to identify and intervene earlier, in order to flatten the cost curve in these complex patients., (© 2021 The Authors.)

Objectives The primary goal of our study is to evaluate the mortality rate in inpatient recipients of multivessel percutaneous coronary intervention (MVPCI) and to evaluate the demographic risk factors and medical complications that increase the risk of in-hospital mortality. Methods We conducted a cross-sectional study using the Nationwide Inpatient Sample (NIS, 2016) and included 127,145 inpatients who received MVPCI as a primary procedure in United States' hospitals. We used a multivariable logistic regression model adjusted for demographic confounders to measure the odds ratio (OR) of association of medical complications and in-hospital mortality risk in MVPCI recipients. Results The in-hospital mortality rate was 2% in MVPCI recipients and was seen majorly in older-age adults (>64 years, 74%) and males (61%). Even though the prevalence of mortality among females was comparatively low, yet in the regression model, they were at a higher risk for in-hospital mortality than males (OR 1.2; 95% CI 1.13-1.37). While comparing ethnicities, in-hospital mortality was prevalent in whites (79%) followed by blacks (9%) and Hispanics (7.5%). Patients who developed cardiogenic shock were at higher odds of in-hospital mortality (OR 9.2; 95% CI 8.27-10.24) followed by respiratory failure (OR 5.9; 95% CI 5.39-6.64) and ventricular fibrillation (OR 3.5; 95% CI 3.18-3.92). Conclusion Accelerated use of MVPCI made it important to study in-hospital mortality risk factors allowing us to devise strategies to improve the utilization and improve the quality of life of these at-risk patients. Despite its effectiveness and comparatively lower mortality profile, aggressive usage of MVPCI is restricted due to the periprocedural complications and morbidity profile of the patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Tummala et al.)

Background: Syncope may be caused by intermittent complete heart block in patients with bundle branch block. Electrophysiology studies (EPS) testing for infra-Hisian heart block are recommended by the European Society of Cardiology syncope guidelines on the basis of decades-old estimates of their negative predictive values (NPVs) for complete heart block., Objective: The aim of this study was to determine the NPV of EPS for complete heart block in patients with syncope and bundle branch block., Methods: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL without language restriction from database inception to October 2019 for Medical Subject Headings terms and keywords related to "syncope," "heart block," and "programmed electrical stimulation." A random effects meta-analysis was conducted with a primary outcome of the proportion of patients with a negative EPS who later presented with complete heart block, diagnosed with surface electrocardiographic (ECG) recordings vs continuous implantable cardiac monitor (ICM)., Results: Ten reports contained 12 cohorts with 639 patients who met the inclusion criteria. The mean age was 69 ± 7 years; 35% ± 10% were women; and 85% of patients had bifascicular block. Seven cohorts recorded clinical outcomes with external ECG recordings, and 5 cohorts featured ICMs. The mean prespecified His-to-ventricle interval criterion was ≥70 ms. In studies featuring surface ECG recordings, there were 7% (95% confidence interval 7%-17%) patients who developed complete heart block compared with 29% (95% confidence interval 24%-35%) in the studies featuring ICM (P = .0001)., Conclusion: The NPV of EPS in patients with syncope and bundle branch block is 0.71, sufficiently low to question its use., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background Recent trials comparing catheter ablation to medical therapy in patients with heart failure (HF) with symptomatic atrial fibrillation despite first-line management have demonstrated a reduction in adverse outcomes. We performed an economic evaluation to estimate the cost-utility of catheter ablation as second line therapy in patients with HF with reduced ejection fraction. Methods and Results A Markov model with health states of alive, dead, and alive with amiodarone toxicity was constructed, using the perspective of the Canadian healthcare payer. Patients in the alive states were at risk of HF and non-HF hospitalizations. Parameters were obtained from randomized trials and Alberta health system data for costs and outcomes. A lifetime time horizon was adopted, with discounting at 3.0% annually. Probabilistic and 1-way sensitivity analyses were performed. Costs are reported in 2018 Canadian dollars. A patient treated with catheter ablation experienced lifetime costs of $64 960 and 5.63 quality-adjusted life-years (QALY), compared with $49 865 and 5.18 QALYs for medical treatment. The incremental cost-effectiveness ratio was $35 360/QALY (95% CI, $21 518-77 419), with a 90% chance of being cost-effective at a willingness-to-pay threshold of $50 000/QALY. A minimum mortality reduction of 28%, or a minimum duration of benefit of >1 to 2 years was required for catheter ablation to be attractive at this threshold. Conclusions Catheter ablation is likely to be cost-effective as a second line intervention for patients with HF with symptomatic atrial fibrillation, with incremental cost-effectiveness ratio $35 360/QALY, as long as over half of the relative mortality benefit observed in extant trials is borne out in future studies.

Objectives To understand the demographic pattern of substance use disorders (SUD) in Parkinson's disease (PD) inpatients and to evaluate the impact of SUD on hospitalization outcomes including the severity of illness, length of stay (LOS), total charges, and disposition to nursing facilities. Methods We used the nationwide inpatient sample and identified adult patients (age, ≥40 years) with PD as a primary diagnosis and comorbid SUD (N = 959) and grouped by co-diagnosis of alcohol (N = 789), cannabis (N = 46), opioid (N = 30), stimulants (N = 54) and barbiturate (N = 40) use disorders. We used a binomial logistic regression model to evaluate the odds ratio (OR) for major loss of functioning and disposition to nursing facilities in PD inpatients. All regression models were adjusted for demographics, including age, sex, race, and median household income. Results Alcohol, opioid, and stimulant use disorders were prevalent in old-age adults (60-79 years), males, and whites, but cannabis use was prevalent in middle-aged adults (40-59 years), and barbiturate use among older-age (>80 years). The severity of illness is statistically higher in PD inpatients with comorbid opioid and barbiturate use disorders with major loss of body functioning, closely seconded by alcohol and stimulant use disorder cohorts (27.6% and 25.9%, respectively). Disease severity and loss of body functioning increase with advancing age (>80 years adults, OR 5.8, 95%CI 5.32-6.37), and in blacks (OR 1.7, 95%CI 1.56-1.81), and those with opioid use disorder (OR 3.8, 95%CI 1.96-7.35). PD inpatients with barbiturate use disorder had a higher LOS and charges by 17.4 days and $68,922, and six-fold increased likelihood (95%CI 2.33-15.67) for disposition to nursing facilities. Conclusions SUD is prevalent among PD patients and is associated with more severe illnesses with body loss functioning and prolonged care. A multidisciplinary care model including collaborative neuropsychiatric and addiction management is required to manage SUD among PD patients to lessen disease severity, slow down the disease progression and potentially save medical costs., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Kaur et al.)

Magnetic resonance imaging (MRI) is often considered the gold-standard test for characterizing cardiac as well as noncardiac structure and function. However, many patients with cardiac implantable electronic devices (CIEDs) and/or severe renal dysfunction are unable to undergo this test because of safety concerns. In the past 10 years, newer-generation CIEDs and gadolinium-based contrast agents (GBCAs) as well as coordinated care between imaging and heart rhythm device teams have mitigated risk to patients and improved access to MRI at many hospitals. The purpose of this statement is to review published data on safety of MRI in patients with conditional and nonconditional CIEDs in addition to patient risks from older and newer GBCAs. This statement was developed through multidisciplinary collaboration of pan-Canadian experts after a relevant and independent literature search by the Canadian Agency for Drugs and Technologies in Health. All recommendations align with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Key recommendations include: (1) the development of standardized protocols for patients with a CIED undergoing MRI; (2) patients with MRI nonconditional pacemakers and pacemaker dependency should be programmed to asynchronous mode and those with MRI nonconditional transvenous defibrillators should have tachycardia therapies turned off during the scan; and (3) macrocyclic or newer linear GBCAs should be used in preference to older GBCAs because of their better safety profile in patients at higher risk of nephrogenic systemic fibrosis., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Nanoparticle-nanoparticle (NP-NP) interactions between Au and Ag NPs were studied by using sodium dilauraminocystine (SDLC)- and Gemini surfactant-stabilized NPs to demonstrate the unique NP surface adsorption behavior of SDLC in controlling and mimicking such interactions in complex mixtures. They were significantly affected by the spacer as well as the polymeric nature of the head group of Gemini surfactants. A longer spacer impeded while a polymeric head group facilitated the interactions. The Au-Ag NPs interactions in an aqueous phase were also controlled by placing surface-active magnetic NPs at an aqueous-air interface, which interacted with either or both kinds of interacting NPs in an aqueous phase and reduced their ability to interact with each other. On the other hand, water-soluble zwitterionic magnetic NPs proved to be excellent extractants of both Au and Ag NPs from the aqueous phase. Extraction efficiency depended on the strength of interactions between the water-soluble magnetic NPs and aqueous-solubilized Au and/or Ag NPs.

Aims: Post-operative pain following cardiac implantable electronic device (CIED) insertion is associated with patient dissatisfaction, emotional distress, and emergency department visits. We sought to identify factors associated with post-operative pain and develop a prediction score for post-operative pain., Methods and Results: All patients from the BRUISE CONTROL-1 and 2 trials were included in this analysis. A validated Visual Analogue Scale (VAS) was used to assess the severity of pain related to CIED implant procedures. Patients were asked to grade the most severe post-operative pain, average post-operative pain, and pain on the day of the first post-operative clinic. Multivariable regression analyses were performed to identify predictors of significant post-operative pain and to develop a pain-prediction score. A total of 1308 patients were included. Multivariable regression analysis found that the presence of post-operative clinically significant haematoma {CSH; P value < 0.001; odds ratio (OR) 3.82 [95% confidence interval (CI): 2.37-6.16]}, de novo CIED implantation [P value < 0.001; OR 1.90 (95% CI: 1.47-2.46)], female sex [P value < 0.001; OR 1.61 (95% CI: 1.22-2.12)], younger age [<65 years; P value < 0.001; OR 1.54 (95% CI: 1.14-2.10)], and lower body mass index [<20 kg/m2; P value < 0.05; OR 2.05 (95% CI: 0.98-4.28)] demonstrated strong and independent associations with increased post-operative pain. An 11-point post-operative pain prediction score was developed using the data., Conclusion: Our study has identified multiple predictors of post-operative pain after CIED insertion. We have developed a prediction score for post-operative pain that can be used to identify individuals at risk of experiencing significant post-operative pain., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Atrial fibrillation (AF) is a major, preventable cause of stroke, whose prevalence is increasing with the aging of the population. There are safe and effective anticoagulation therapies to prevent stroke and new technologies that can identify AF in asymptomatic individuals. Ongoing research will determine if AF screening is cost-effective and will define the best screening strategies. The effectiveness of AF screening can be enhanced by simultaneously screening for the cardiovascular conditions that predispose to the development and progression of AF and its complications. Future studies evaluating an integrated screening program on outcomes, health care utilization, and cost are needed., Competing Interests: Disclosure Dr R.K. Sandhu reports research grants from BMS/Pfizer and Servier, and Dr J.S. Healey reports research grants and speaking fees from BMS/Pfizer, Bayer, Servier, Medtronic, Boston Scientific, and St. Jude Medical., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Hospitalization for nonvalvular atrial fibrillation (NVAF) is common and results in substantial cost burden. Current national data trends for the incidence, stroke risk profiles, and mortality of hospitalization for NVAF and atrial flutter (AFL) are sparse., Methods: The Canadian Institute of Health Information Discharge Abstract Database was used to identify patients ≥ 20 years with incident NVAF/AFL (NVAF, ICD-9 code 427.3 or ICD-10 I48) in any diagnosis field from 2006 to 2015 in Canada, except Québec. National and provincial trends in rate over time (rate ratio, 95% confidence interval [CI]) were calculated for age-sex standardized hospitalizations. Trends in stroke risk profiles and in-hospital mortality rates adjusted for stroke risk factors were also calculated., Results: A total of 578,947 patients were hospitalized with incident NVAF/AFL. The median age was 77 years (interquartile range: 68-84), 82% were ≥ 65 years, 54% were men, 54% had a CHADS2 ≥ 2, and 69% had a CHA2DS2-Vasc ≥ 3. The overall age- and sex-standardized rate of NVAF/AFL hospitalization was 315 per 100,000 population and declined by 2% per year (P < 0.001). There was an annual rate decline in NVAF/AFL hospitalizations in every province. The majority of hospitalized patients are at high risk of stroke, and this risk remained unchanged. The average adjusted in-hospital mortality was 8.80 per 100 patients 95% CI, 8.80-8.81 with a 2% annual decline in rate (P < 0.001)., Conclusion: Between 2006 and 2015, we found national and provincial hospitalization rates for incident NVAF/AFL are declining. The majority of patients are at high risk for stroke. In-hospital mortality has declined but remains substantial., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)