Noseworthy, Peter A.

Introduction: Congenital long QT syndrome (LQTS) is a sudden cardiac death-predisposing genetic disorder that has a characteristic electrocardiographic signature. Specific LQTS genotypes have been associated classically with different qualitative electrocardiographic ST - T wave patterns; however, clinical recognition of these patterns could be improved by an automated and quantitative method. We therefore aimed to use a novel, quantitative T wave morphological analysis technique from 12-lead surface ECGs to identify genotype specific LQTS ECG patterns. Methods: We analyzed a genotyped cohort of 420 patients (22 ± 15.7years, 43% male) with either LQT1 (61%) or LQT2 (39%). ECG analysis was conducted using a custom T wave program to automatically detect subtle changes in T wave morphology across all 12 Leads. Classification was performed using the top three T wave features in a linear discriminant classifier by 10x10 cross-validation. Results: The top three discriminant features were (1) a steeper T wave left slope for LQT1 in lead II (2950 vs 1700 mV/ms, p < 0.0001), (2) a greater center of gravity in 1st segment of T wave in lead aVR in LQT1 (0.248 vs 0.209, p<0.0001) and (3) a smaller Tpeak - Tend/QT ratio in lead aVR in LQT1 (0.20 vs 0.24, p<0.0001). Using these top three features, we were able to successfully differentiate LQT1 and LQT2 in 79% of cases (figure 1). Conclusions: An automated morphological T wave analysis was able to discriminate between the two most common LQTS genotypes. This novel method enhances phenotypic characterization of LQT and could have a significant clinical impact on the diagnosis and management of patients with suspected LQTS.

Background: Transcatheter aortic valve replacement (TAVR) is often complicated by AV block requiring pacing, but whether patients recover AV conduction and whether the need for pacing affects outcomes is unknown. Methods: We retrospectively studied 534 patients who underwent TAVR at Mayo Clinic in Rochester, Minnesota between November 2008 and January 2015. Of these, 115 patients had implantable cardiac devices. Data was collected from subsequent device follow-ups to determine pacemaker dependency and percentage pacing. Results: 44 patients (8.2%) had devices implanted in the immediate post procedural period. The most common indications for implantation were high grade AV block (18 patients) and complete heart block (14 patients). 17/44 (38.6%) patients were pacemaker-dependent at implant and only 4 of these patients were no longer pacemaker-dependent during subsequent followup. The indication for pacing among these four patients was high grade atrio-ventricular block (2 patients), asystole (1 patient) and complete heart block (1). Among non-pacemaker-dependent patients, no significant change in the ventricular pacing percentages was noted over time. Survival was similar between patients who required device implantation post TAVR and those who did not after adjustment for age and gender (HR 0.73 [0.39-1.36], p=ns; figure) Conclusion: Patients requiring pacing after TAVR are often pacemaker-dependent at the time of implant. It is uncommon for patients who are dependent at the time of implant to regain AV conduction, but the need for cardiac pacing is not associated with increased mortality.

Introduction: Mobile thrombi are commonly observed on endovascular leads at the time of catheter ablation. Transseptal puncture poses a risk of paradoxical embolism. We sought to examine the risk of stroke or systemic embolism after transseptal ablation in patients with and without cardiac implantable electronic devices (CIEDs). Methods: Using a large, national administrative claims database we identified 31,720 patients who underwent a catheter ablation requiring transseptal puncture between 1/1/2004 and 9/30/2014. We created two propensity-matched cohorts, matching on age, gender, race, household income, region, Charlson index, CHADS-Vasc score, and year and indication for ablation (5,533 patients with CIEDs and 11,300 patients without devices). Incidence rates (events/100 patient-years) and propensity score-matched cox proportional hazards models (with 95% confidence intervals) were used to estimate risk of stroke, transient ischemic attack, or systemic embolism for patients with or without CIEDs. We also examined the impact of presence of a CIED and oral anticoagulation (OAC) use on risk of stroke or systemic embolism within the matched cohort. Average follow up was 2.1 years. Results: The event rate was 1.5 per 100 person years in patients without device, and 1.9 per 100 person years in patients with device. Among patients not on OAC, presence of a cardiac device was associated with an increased risk of stroke or systemic embolism (HR 1.71 [1.24-2.35], P<0.01) whereas there was no association among patients treated with OAC (0.98 [0.75_1.28], p=ns) (Figure). Conclusions: Cardiac devices are associated with an increased risk of stroke or systemic embolism after transseptal ablation, but this risk is attenuated with post ablation OAC use. Anticoagulation should be considered for all patients with CIEDs post transseptal ablation, regardless of the presence of another compelling indication for anticoagulation.

AbstractWe conducted systematic reviews of predefined clinical questions and used the Grading of Recommendations, Assessment, Development and Evaluations approach to develop recommendations for the periendoscopic management of anticoagulant and antiplatelet drugs during acute gastrointestinal (GI) bleeding and the elective endoscopic setting. The following recommendations target patients presenting with acute GI bleeding: For patients on warfarin, we suggest against giving fresh frozen plasma or vitamin K; if needed, we suggest prothrombin complex concentrate (PCC) compared with fresh frozen plasma administration; for patients on direct oral anticoagulants (DOACs), we suggest against PCC administration; if on dabigatran, we suggest against the administration of idarucizumab, and if on rivaroxaban or apixaban, we suggest against andexanet alfa administration; for patients on antiplatelet agents, we suggest against platelet transfusions; and for patients on cardiac acetylsalicylic acid (ASA) for secondary prevention, we suggest against holding it, but if the ASA has been interrupted, we suggest resumption on the day hemostasis is endoscopically confirmed. The following recommendations target patients in the elective (planned) endoscopy setting: For patients on warfarin, we suggest continuation as opposed to temporary interruption (1–7 days), but if it is held for procedures with high risk of GI bleeding, we suggest against bridging anticoagulation unless the patient has a mechanical heart valve; for patients on DOACs, we suggest temporarily interrupting rather than continuing these; for patients on dual antiplatelet therapy for secondary prevention, we suggest temporary interruption of the P2Y12 receptor inhibitor while continuing ASA; and if on cardiac ASA monotherapy for secondary prevention, we suggest against its interruption. Evidence was insufficient in the following settings to permit recommendations. With acute GI bleeding in patients on warfarin, we could not recommend for or against PCC administration when compared with placebo. In the elective periprocedural endoscopy setting, we could not recommend for or against temporary interruption of the P2Y12 receptor inhibitor for patients on a single P2Y12 inhibiting agent. We were also unable to make a recommendation regarding same-day resumption of the drug vs 1–7 days after the procedure among patients prescribed anticoagulants (warfarin or DOACs) or P2Y12 receptor inhibitor drugs because of insufficient evidence.

We conducted systematic reviews of predefined clinical questions and used the Grading of Recommendations, Assessment, Development and Evaluations approach to develop recommendations for the periendoscopic management of anticoagulant and antiplatelet drugs during acute gastrointestinal (GI) bleeding and the elective endoscopic setting. The following recommendations target patients presenting with acute GI bleeding: For patients on warfarin, we suggest against giving fresh frozen plasma or vitamin K; if needed, we suggest prothrombin complex concentrate (PCC) compared with fresh frozen plasma administration; for patients on direct oral anticoagulants (DOACs), we suggest against PCC administration; if on dabigatran, we suggest against the administration of idarucizumab, and if on rivaroxaban or apixaban, we suggest against andexanet alfa administration; for patients on antiplatelet agents, we suggest against platelet transfusions; and for patients on cardiac acetylsalicylic acid (ASA) for secondary prevention, we suggest against holding it, but if the ASA has been interrupted, we suggest resumption on the day hemostasis is endoscopically confirmed. The following recommendations target patients in the elective (planned) endoscopy setting: For patients on warfarin, we suggest continuation as opposed to temporary interruption (1–7 days), but if it is held for procedures with high risk of GI bleeding, we suggest against bridging anticoagulation unless the patient has a mechanical heart valve; for patients on DOACs, we suggest temporarily interrupting rather than continuing these; for patients on dual antiplatelet therapy for secondary prevention, we suggest temporary interruption of the P2Y 12 receptor inhibitor while continuing ASA; and if on cardiac ASA monotherapy for secondary prevention, we suggest against its interruption. Evidence was insufficient in the following settings to permit recommendations. With acute GI bleeding in patients on warfarin, we could not recommend for or against PCC administration when compared with placebo. In the elective periprocedural endoscopy setting, we could not recommend for or against temporary interruption of the P2Y 12 receptor inhibitor for patients on a single P2Y 12 inhibiting agent. We were also unable to make a recommendation regarding same-day resumption of the drug vs 1–7 days after the procedure among patients prescribed anticoagulants (warfarin or DOACs) or P2Y 12 receptor inhibitor drugs because of insufficient evidence.

Abstract Background: Trial recruitment of Black, indigenous, and people of color (BIPOC) is key for interventions that interact with socioeconomic factors and cultural norms, preferences, and values. We report on our experience enrolling BIPOC participants into a multicenter trial of a shared decision-making intervention about anticoagulation to prevent strokes, in patients with atrial fibrillation (AF). Methods: We enrolled patients with AF and their clinicians in 5 healthcare systems (three academic medical centers, an urban/suburban community medical center, and a safety-net inner-city medical center) located in three states (Minnesota, Alabama, and Mississippi) in the United States. Clinical encounters were randomized to usual care with or without a shared decision-making tool about anticoagulation. Analysis: We analyzed BIPOC patient enrollment by site, categorized reasons for non-enrollment, and examined how enrollment of BIPOC patients was promoted across sites.Results: Of 2247 patients assessed, 922 were enrolled of which 147 (16%) were BIPOC patients. In comparison to trial-eligible White participants, eligible Black participants more frequently did not enroll (102 (11%) vs. 185 (15%); p <.001). The rate of BIPOC patients enrollment varied substantially by site and was generally reflective of the population served at each participating site. Enrollment of BIPOC patients benefited most from including and prioritizing practices most likely to care for BIPOC patients, with lower yield from specific efforts to reach BIPOC clinic attendees and enrolling BIPOC patients first when possible. Conclusions: Enrollment from practices that have implemented policies that favor the care of BIPOC patients can contribute to generate trustworthy estimates of the effect of these interventions in clinical practice that are applicable to BIPOC populations. Best practices to optimize the enrollment of BIPOC participants into trials that examined complex and culturally sensitive interventions remain to be developed.Clinical trial registration: ClinicalTrials.gov (NCT02905032)

Abstract Background In the context of atrial fibrillation (AF), traditional clinical practices have thus fallen short in several domains, such as identifying patients at risk of incident AF or patients with concomitant undetected paroxysmal AF. Novel approaches leveraging artificial intelligence have the potential to provide new tools to deal with some of these old problems. Aims To discuss the roles of artificial intelligence (AI)‐enabled electrocardiogram (ECG) pertaining to AF, potential roles of deep learning (DL) models in the context of current knowledge gaps, as well as limitations of these models. Materials & Methods An extensive search and review of the currently available literature on the topics. Results One key area where DL models can translate to better patient outcomes is through automated ECG interpretation. Challenges with regards to the benefits and harms of AF screening remain. In this context, a unique model was developed to detect underlying hidden AF from sinus rhythm. Discussion Knowledge gaps remain regarding the best ways to monitor patients with embolic stroke of undetermined source (ESUS) and identifying those who would benefit most from oral anticoagulation. The AI‐enabled AF model is one potential way to tackle this complex problem as it could be used to identify a subset of high‐risk ESUS patients likely to benefit from empirical oral anticoagulation. The role of DL models assessing AF burden from long‐duration ECG data is also discussed as a way of guiding management. There is a trend towards the use of consumer‐grade wristbands and watches to detect AF from photoplethysmography data. However, ECG currently remains the gold standard to detect arrythmias including AF. Lastly, the role of adequate external validation of the models and clinical trials to study true performance is discussed. Conclusion Algorithms using AI to interpret ECGs in various new ways have been developed. While still, much work needs to be done, these technologies have shown enormous potential in a short span of time. With further advancements and continuous research, these novel ways of interpretation may well become part of everyday clinical workflow.

Cardiovascular disease remains the leading cause of death in women. Given accumulating evidence on sex- and gender-based differences in cardiovascular disease development and outcomes, the need for more effective approaches to screening for risk factors and phenotypes in women is ever urgent. Public health surveillance and health care delivery systems now continuously generate massive amounts of data that could be leveraged to enable both screening of cardiovascular risk and implementation of tailored preventive interventions across a woman’s life span. However, health care providers, clinical guidelines committees, and health policy experts are not yet sufficiently equipped to optimize the collection of data on women, use or interpret these data, or develop approaches to targeting interventions. Therefore, we provide a broad overview of the key opportunities for cardiovascular screening in women while highlighting the potential applications of artificial intelligence along with digital technologies and tools.

INTRODUCTION: Cirrhosis is associated with cardiac dysfunction and distinct electrocardiogram (ECG) abnormalities. This study aimed to develop a proof-of-concept deep learning-based artificial intelligence (AI) model that could detect cirrhosis-related signals on ECG and generate an AI-Cirrhosis-ECG (ACE) score that would correlate with disease severity. METHODS: A review of Mayo Clinic's electronic health records identified 5,212 patients with advanced cirrhosis ≥18 years who underwent liver transplantation at the 3 Mayo Clinic transplant centers between 1988 and 2019. The patients were matched by age and sex in a 1:4 ratio to controls without liver disease and then divided into training, validation, and test sets using a 70%-10%-20% split. The primary outcome was the performance of the model in distinguishing patients with cirrhosis from controls using their ECGs. In addition, the association between the ACE score and the severity of patients' liver disease was assessed. RESULTS: The model's area under the curve in the test set was 0.908 with 84.9% sensitivity and 83.2% specificity, and this performance remained consistent after additional matching for medical comorbidities. Significant elevations in the ACE scores were seen with increasing model for end-stage liver disease-sodium score. Longitudinal trends in the ACE scores before and after liver transplantation mirrored the progression and resolution of liver disease. DISCUSSION: The ACE score, a deep learning model, can accurately discriminate ECGs from patients with and without cirrhosis. This novel relationship between AI-enabled ECG analysis and cirrhosis holds promise as the basis for future low-cost tools and applications in the care of patients with liver disease.

Background Guidelines promote shared decision‐making (SDM) for anticoagulation in patients with atrial fibrillation. We recently showed that adding a within‐encounter SDM tool to usual care (UC) increases patient involvement in decision‐making and clinician satisfaction, without affecting encounter length. We aimed to estimate the extent to which use of an SDM tool changed adherence to the decided care plan and clinical safety end points. Methods and Results We conducted a multicenter, encounter‐level, randomized trial assessing the efficacy of UC with versus without an SDM conversation tool for use during the clinical encounter (Anticoagulation Choice) in patients with nonvalvular atrial fibrillation considering starting or reviewing anticoagulation treatment. We conducted a chart and pharmacy review, blinded to randomization status, at 10 months after enrollment to assess primary adherence (proportion of patients who were prescribed an anticoagulant who filled their first prescription) and secondary adherence (estimated using the proportion of days for which treatment was supplied and filled for direct oral anticoagulant, and as time in therapeutic range for warfarin). We also noted any strokes, transient ischemic attacks, major bleeding, or deaths as safety end points. We enrolled 922 evaluable patient encounters (Anticoagulation Choice=463, and UC=459), of which 814 (88%) had pharmacy and clinical follow‐up. We found no differences between arms in either primary adherence (78% of patients in the SDM arm filled their first prescription versus 81% in UC arm) or secondary adherence to anticoagulation (percentage days covered of the direct oral anticoagulant was 74.1% in SDM versus 71.6% in UC; time in therapeutic range for warfarin was 66.6% in SDM versus 64.4% in UC). Safety outcomes, mostly bleeds, occurred in 13% of participants in the SDM arm and 14% in the UC arm. Conclusions In this large, randomized trial comparing UC with a tool to promote SDM against UC alone, we found no significant differences between arms in primary or secondary adherence to anticoagulation or in clinical safety outcomes. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: clinicaltrials.gov. Identifier: NCT02905032.