Noseworthy, Peter A.

ABSTRACT Atrial fibrillation (AF) in lifetime athletes (e.g., ≥5 years of participation) is a growing concern but remains enigmatic. Intriguingly, a direct relationship between lifetime training hours and risk of developing AF exists. Professionals in exercise and sport science are at the forefront to help recognize symptoms and direct the athlete to appropriate medical clinicians for expedient care. Although AF in athletes is usually not accompanied by structural heart disease or stroke risk factors (i.e., termed lone AF), it may, nonetheless, pose health risks. In this study, we review various types of AF, proposed mechanisms, and treatment strategies for athletes with AF.

Catheter ablation has brought major advances in the management of patients with atrial fibrillation (AF). As evidenced by multiple randomized trials, AF catheter ablation can reduce the risk of recurrent AF and improve quality of life. In some studies, AF ablation significantly reduced cardiovascular hospitalizations. Despite the existing data on AF catheter ablation, numerous knowledge gaps remain concerning this intervention. This report is based on a recent virtual workshop convened by the National Heart, Lung, and Blood Institute to identify key research opportunities in AF ablation. We outline knowledge gaps related to emerging technologies, the relationship between cardiac structure and function and the success of AF ablation in patient subgroups in whom clinical benefit from ablation varies, and potential platforms to advance clinical research in this area. This report also considers the potential value and challenges of a sham ablation randomized trial. Prioritized research opportunities are identified and highlighted to empower relevant stakeholders to collaborate in designing and conducting effective, cost-efficient, and transformative research to optimize the use and outcomes of AF ablation.

Sotalol, a Vaughan-Williams Class III antiarrhythmic medication, is used to manage atrial arrhythmias. Due to its QT-prolonging effect and subsequent increased risk of torsade de pointes, many centers admit patients during the initial dosing period. Despite its widespread use, little information is available regarding dosing protocols during this period. In this multicenter investigation, dosing protocols in patients initiating sotalol therapy were examined to identify predictors of successful sotalol initiation. Over a 4-year period, patients admitted to 5 hospitals in the United States for inpatient telemetry monitoring during initiation for nonresearch purposes were enrolled. A 3-day course of 5 of 6 doses of sotalol was considered successful completion of the loading protocol. Of the 213 enrolled patients, over 90% were successfully discharged on sotalol. Significant bradycardia, ineffectiveness, and excessive QT prolongation were reasons for failed completion. Absence of a dose adjustment was a strong predictor of successful initiation (odds ratio: 6.6, 95% confidence interval: 1.3-32.7, P = .02). Hypertension, use of a calcium channel blocker, use of a separate β-blocker, and presence of a pacemaker were predictors of dose adjustments. Marginal structural models (ie, inverse probability weighting based on probability of a dose adjustment) verified that these factors also predicted successful initiation via preventing any dose adjustment and suggests that considering these factors may result in a higher likelihood of successful initiation in future investigations. In conclusion, we found that the majority of patients admitted for sotalol initiation are successfully discharged on the medication. The study findings suggest that factors predicting need for dose adjustment can be used to identify patients who could undergo outpatient initiation. Prospective studies are needed to verify this approach.

AbstractBackgroundInappropriate sinus tachycardia (IST) remains a clinical challenge because patients often are highly symptomatic and not responsive to medical therapy.ObjectiveTo study the safety and efficacy of stellate ganglion (SG) block and cardiac sympathetic denervation (CSD) in patients with IST.MethodsTwelve consecutive patients who had drug‐refractory IST (10 women) were studied. According to a prospectively initiated protocol, five patients underwent an electrophysiologic study before and after SG block (electrophysiology study group). The subsequent seven patients had ambulatory Holter monitoring before and after SG block (ambulatory group). All patients underwent SG block on the right side first, and then on the left side. Selected patients who had heart rate reduction ≥15 beats per minute (bpm) were recommended to consider CSD.ResultsThe mean (SD) baseline heart rate (HR) was 106 (21) bpm. The HR significantly decreased to 93 (20) bpm (P = .02) at 10 minutes after right SG block and remained significantly slower at 97(19) bpm at 60 minutes. Left SG block reduced HR from 99 (21) to 87(16) bpm (P = .02) at 60 minutes. SG block had no significant effect on blood pressure or HR response to isoproterenol or exercise (all P > .05). Five patients underwent right (n = 4) or bilateral (n = 1) CSD. The clinical outcomes were heterogeneous: one patient had complete and two had partial symptomatic relief, and two did not have improvement.ConclusionSG blockade modestly reduces resting HR but has no significant effect on HR during exercise. Permanent CSD may have a modest role in alleviating symptoms in selected patients with IST.

Background The American College of Cardiology and American Heart Association periodically revise clinical practice guidelines. We evaluated changes in the evidence underlying guidelines published over a 10‐year period. Methods and Results Thirty‐five American College of Cardiology/American Heart Association guidelines were divided into 2 time periods: 2008 to 2012 and 2013 to 2017. Guidelines were categorized into the following topic areas: arrhythmias, prevention, acute and stable ischemia, heart failure, valvular heart disease, and vascular medicine. Changes in recommendations were assessed for each topic area. American College of Cardiology/American Heart Association designated class of recommendation as level I, II , or III (I represented “strongly recommended”) and levels of evidence ( LOE ) as A, C, or C (A represented “highest quality”). The median number of recommendations per each topic area was 281 (198–536, interquartile range) in 2008 to 2012 versus 247 (190–451.3, interquartile range) in 2013 to 2017. The median proportion of class of recommendation I was 49.3% and 44.4% in the 2 time periods, 38.0% and 44.5% for class of recommendation II , and 12.5% and 11.2% for class of recommendation III . Median proportions for LOE A were 15.7% and 14.1%, 41.0% and 52.8% for LOE B, and 46.9% and 32.5% for LOE C. The decrease in the proportion of LOE C was highest in heart failure (24.8%), valvular heart disease (22.3%), and arrhythmia (19.2%). An increase in the proportion of LOE B was observed for these same areas: 31.8%, 23.8%, and 19.2%, respectively. Conclusions There has been a decrease in American College of Cardiology/American Heart Association guidelines recommendations, driven by removal of recommendations based on lower quality of evidence, although there was no corresponding increase in the highest quality of evidence.

Background: Percutaneous stellate ganglion blockade (SGB) has been used for drug-refractory electrical storm due to ventricular arrhythmia (VA); however, the effects and long-term outcomes have not been well studied. Methods: This study included 30 consecutive patients who had drug-refractory electrical storm and underwent percutaneous SGB between October 1, 2013, and March 31, 2018. Bupivacaine, alone or combined with lidocaine, was injected into the neck with good local anesthetic spread in the vicinity of the left stellate ganglion (n=15) or both stellate ganglia (n=15). Data were collected for patient clinical characteristics, immediate and long-term outcomes, and procedure-related complications. Results: Clinical characteristics included age, 58±14 years; men, 73.3%; and left ventricular ejection fraction, 34±16%. At 24 hours, 60% of patients were free of VA. Patients whose VA was controlled had a lower hospital mortality rate than patients whose VA continued (5.6% versus 50.0%; P =0.009). Implantable cardioverter-defibrillator interrogation showed a significant 92% reduction in VA episodes from 26±41 to 2±4 in the 72 hours after SGB ( P <0.001). Patients who died during the same hospitalization (n=7) were more likely to have ischemic cardiomyopathy (100% versus 43.5%; P =0.03) and recurrent VA within 24 hours (85.7% versus 26.1%; P =0.009). There were no procedure-related major complications. Conclusions: SGB effectively attenuated electrical storm in more than half of patients without procedure-related complications. Percutaneous SGB may be considered for stabilizing ventricular rhythm in patients for whom other therapies have failed.

Background: Sex and age have long been known to affect the ECG. Several biologic variables and anatomic factors may contribute to sex and age-related differences on the ECG. We hypothesized that a convolutional neural network (CNN) could be trained through a process called deep learning to predict a person’s age and self-reported sex using only 12-lead ECG signals. We further hypothesized that discrepancies between CNN-predicted age and chronological age may serve as a physiological measure of health. Methods: We trained CNNs using 10-second samples of 12-lead ECG signals from 499 727 patients to predict sex and age. The networks were tested on a separate cohort of 275 056 patients. Subsequently, 100 randomly selected patients with multiple ECGs over the course of decades were identified to assess within-individual accuracy of CNN age estimation. Results: Of 275 056 patients tested, 52% were males and mean age was 58.6±16.2 years. For sex classification, the model obtained 90.4% classification accuracy with an area under the curve of 0.97 in the independent test data. Age was estimated as a continuous variable with an average error of 6.9±5.6 years (R-squared =0.7). Among 100 patients with multiple ECGs over the course of at least 2 decades of life, most patients (51%) had an average error between real age and CNN-predicted age of <7 years. Major factors seen among patients with a CNN-predicted age that exceeded chronologic age by >7 years included: low ejection fraction, hypertension, and coronary disease ( P <0.01). In the 27% of patients where correlation was >0.8 between CNN-predicted and chronologic age, no incident events occurred over follow-up (33±12 years). Conclusions: Applying artificial intelligence to the ECG allows prediction of patient sex and estimation of age. The ability of an artificial intelligence algorithm to determine physiological age, with further validation, may serve as a measure of overall health.

Background: Stroke prevention using warfarin is challenging in AF patients with CKD, due to high bleeding risk and difficulties in the INR control. NOACs provide alternative options, but all have greater degrees of renal clearance. This study aimed to compare the outcomes of apixaban, dabigatran, rivaroxaban, and warfarin across the range of kidney function in patients with AF. Methods: Using a US administrative database including private insurance or Medicare Advantage patients with linked claims and laboratory data, we identified 34,569 new users of oral anticoagulants with AF and eGFR ≥15 between 10/1/2010-11/29/2017. Stabilized IPTW balanced four treatment groups on 66 baseline characteristics. The primary outcomes included stroke, major bleeding, and mortality. Weighted Cox proportional hazards models compared treatments in the overall population and in each eGFR subgroup, with mortality as a competing risk for stroke and major bleeding. Results: The proportion of patients using warfarin increased as the kidney function declined - 26.5%, 30.4%, 34.6%, 40.5%, and 55.0% of patients were prescribed warfarin in eGFR ≥90, 60-90, 45-60, 30-45, 15-30 groups, respectively. In comparison to warfarin, apixaban was associated with a lower risk of stroke, major bleeding, and mortality; dabigatran was associated with a similar risk of stroke, and a lower risk of major bleeding and mortality; rivaroxaban was associated with a lower risk of stroke, major bleeding, and mortality (Figure). When comparing one NOAC to another NOAC, apixaban and dabigatran were associated with a lower risk of major bleeding than rivaroxaban (HR 0.61 [0.51-0.73], p<0.001 for apixaban versus rivaroxaban; HR 0.67 [0.50-0.90], p=0.007 for dabigatran versus rivaroxaban); dabigatran was associated with a higher risk of stroke than apixaban (HR 1.65 [1.11-2.46], p=0.01); there was no difference in mortality. There was no significant interaction between treatment and eGFR categories for any outcome, but the number of patients with low eGFR was small. Conclusions: In practice, relative to warfarin, NOACs are progressively less commonly used with increasing degree of renal dysfunction. However, each NOAC was consistently associated with at least equivalent effectiveness and safety compared with warfarin across the range of kidney function.