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Electrocardiogram-based Deep Learning and Clinical Risk Factors to Predict Atrial Fibrillation.

Shaan Khurshid, Samuel Friedman, Christopher Reeder, Paolo Di Achille, Nathaniel Diamant, Pulkit Singh, Lia X Harrington, Xin Wang, Mostafa A Al-Alusi, Gopal Sarma, Andrea S Foulkes, Patrick T Ellinor, Christopher D Anderson, Jennifer E Ho, Anthony A Philippakis, Puneet Batra, Steven A Lubitz,

<b>Background:</b> Artificial intelligence (AI)-enabled analysis of 12-lead electrocardiograms (ECGs) may facilitate efficient estimation of incident atrial fibrillation (AF) risk. However, it remains unclear whether AI provides meaningful and generalizable improvement in predictive accuracy beyond clinical risk factors for AF. <b>Methods:</b> We trained a convolutional neural network ("ECG-AI") to infer 5-year ... Read more >>

Circulation (Circulation)
[2021, :]

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Re-CHARGE-AF: Recalibration of the CHARGE-AF Model for Atrial Fibrillation Risk Prediction in Patients With Acute Stroke.

Jeffrey M Ashburner, Xin Wang, Xinye Li, Shaan Khurshid, Darae Ko, Ana Trisini Lipsanopoulos, Priscilla R Lee, Taylor Carmichael, Ashby C Turner, Corban Jackson, Patrick T Ellinor, Emelia J Benjamin, Steven J Atlas, Daniel E Singer, Ludovic Trinquart, Steven A Lubitz, Christopher D Anderson,

Background Performance of existing atrial fibrillation (AF) risk prediction models in poststroke populations is unclear. We evaluated predictive utility of an AF risk model in patients with acute stroke and assessed performance of a fully refitted model. Methods and Results Within an academic hospital, we included patients aged 46 to ... Read more >>

J Am Heart Assoc (Journal of the American Heart Association)
[2021, 10(21):e022363]

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Deep learning enables genetic analysis of the human thoracic aorta.

James P Pirruccello, Mark D Chaffin, Elizabeth L Chou, Stephen J Fleming, Honghuang Lin, Mahan Nekoui, Shaan Khurshid, Samuel F Friedman, Alexander G Bick, Alessandro Arduini, Lu-Chen Weng, Seung Hoan Choi, Amer-Denis Akkad, Puneet Batra, Nathan R Tucker, Amelia W Hall, Carolina Roselli, Emelia J Benjamin, Shamsudheen K Vellarikkal, Rajat M Gupta, Christian M Stegmann, Dejan Juric, James R Stone, Ramachandran S Vasan, Jennifer E Ho, Udo Hoffmann, Steven A Lubitz, Anthony A Philippakis, Mark E Lindsay, Patrick T Ellinor,

Enlargement or aneurysm of the aorta predisposes to dissection, an important cause of sudden death. We trained a deep learning model to evaluate the dimensions of the ascending and descending thoracic aorta in 4.6 million cardiac magnetic resonance images from the UK Biobank. We then conducted genome-wide association studies in ... Read more >>

Nat Genet (Nature genetics)
[2021, :]

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Genetics of Myocardial Interstitial Fibrosis in the Human Heart and Association with Disease

Victor Nauffal, Paolo Di Achille, Marcus. Klarqvist, Jonathan Cunningham, James Pirruccello, Lu-Chen Weng, Valerie Morrill, Seung Hoan Choi, Shaan Khurshid, Samuel Friedman, Mahan Nekoui, Carolina Roselli, Kenney Ng, Anthony Philippakis, Puneet Batra, Patrick Ellinor, Steven Lubitz,

<h4>ABSTRACT</h4> Myocardial interstitial fibrosis is a common thread in multiple cardiovascular diseases including heart failure, atrial fibrillation, conduction disease and sudden cardiac death. To investigate the biologic pathways that underlie interstitial fibrosis in the human heart, we developed a machine learning model to measure myocardial T1 time, a marker of ... Read more >>

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Pacing-Induced Cardiomyopathy.

Shaan Khurshid, David S Frankel,

Right ventricular (RV) pacing-induced cardiomyopathy (PICM) is typically defined as left ventricular systolic dysfunction resulting from electrical and mechanical dyssynchrony caused by RV pacing. RV PICM is common, occurring in 10-20% of individuals exposed to frequent RV pacing. Multiple risk factors for PICM have been identified, including male sex, wider ... Read more >>

Card Electrophysiol Clin (Cardiac electrophysiology clinics)
[2021, 13(4):741-753]

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Characterizing and Quantifying Performance Heterogeneity in Cardiovascular Risk Prediction Models — A Step Towards Improved Disease Risk Assessment

Uri Kartoun, Shaan Khurshid, Bum Chul Kwon, Aniruddh Patel, Puneet Batra, Anthony Philippakis, Amit Khera, Patrick Ellinor, Steve Lubitz, Kenney Ng,

Prediction models are commonly used to estimate risk for cardiovascular diseases; however, performance may vary substantially across relevant subgroups of the population. Here we investigated the variability of performance and fairness across a variety of subgroups for risk prediction of two common diseases, atherosclerotic cardiovascular disease (ASCVD) and atrial fibrillation ... Read more >>

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Endophenotype Effect Sizes Provide Evidence Supporting Variant Pathogenicity in Monogenic Disease Susceptibility Genes

Valerie Morrill, Jennifer Halford, Seung Hoan Choi, Sean Jurgens, Giorgio Melloni, Nicholas Marston, Lu-Chen Weng, Victor Nauffal, Amelia Hall, Sophia Gunn, Christina Austin-Tse, James Pirruccello, Shaan Khurshid, Heidi Rehm, Emelia Benjamin, Eric Boerwinkle, Jennifer Brody, Adolfo Correa, Brandon Fornwalt, Namrata Gupta, Christopher Haggerty, Stephanie Harris, Susan Heckbert, Charles Hong, Charles Kooperberg, Henry Lin, Ruth Loos, Braxton Mitchell, Alanna Morrison, Wendy Post, Bruce Psaty, Susan Redline, Kenneth Rice, Stephen Rich, Jerome Rotter, Peter Schnatz, Elsayed Soliman, Nona Sotoodehnia, Eugene Wong, Marc Sabatine, Christian Ruff, Kathryn Lunetta, Patrick Ellinor, Steven Lubitz, ,

<h4>ABSTRACT</h4> Accurate and efficient classification of variant pathogenicity is critical for research and clinical care. Using data from three large studies, we demonstrate that population-based associations between rare variants and quantitative endophenotypes for three monogenic diseases (low-density-lipoprotein cholesterol for familial hypercholesterolemia, electrocardiographic QTc interval for long QT syndrome, and glycosylated ... Read more >>

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Screening for Atrial Fibrillation in Older Adults at Primary Care Visits: the VITAL-AF Randomized Controlled Trial

Steven Lubitz, Steven Atlas, Jeffrey Ashburner, Ana Trisini Lipsanopoulos, Leila Borowsky, Wyliena Guan, Shaan Khurshid, Patrick Ellinor, Yuchiao Chang, David McManus, Daniel Singer,

<h4>ABSTRACT</h4> <h4>Background</h4> Undiagnosed atrial fibrillation (AF) may cause preventable strokes. Guidelines differ regarding AF screening recommendations. We tested whether point-of-care screening with a handheld single lead electrocardiogram (ECG) at primary care practice visits increases diagnoses of AF. <h4>Methods</h4> We randomized 16 primary care clinics 1:1 to AF screening using a ... Read more >>

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Predictive Accuracy of a Clinical and Genetic Risk Model for Atrial Fibrillation.

Shaan Khurshid, Nina Mars, Christopher M Haggerty, Qiuxi Huang, Lu-Chen Weng, Dustin N Hartzel, , Kathryn L Lunetta, Jeffrey M Ashburner, Christopher D Anderson, Emelia J Benjamin, Veikko Salomaa, Patrick T Ellinor, Brandon K Fornwalt, Samuli Ripatti, Ludovic Trinquart, Steven A Lubitz,

<h4>Background</h4>Atrial fibrillation (AF) risk estimation using clinical factors with or without genetic information may identify AF screening candidates more accurately than the guideline-based age threshold of ≥65 years.<h4>Methods</h4>We analyzed 4 samples across the United States and Europe (derivation: UK Biobank; validation: FINRISK, Geisinger MyCode Initiative, and Framingham Heart Study). We ... Read more >>

Circ Genom Precis Med (Circulation. Genomic and precision medicine)
[2021, 14(5):e003355]

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Accelerometer-Derived and Genetically Inferred Physical Activity and Human Disease

Shaan Khurshid, Lu-Chen Weng, Victor Nauffal, James Pirruccello, Rachael Venn, Mostafa Al-Alusi, Emelia Benjamin, Patrick Ellinor, Steven Lubitz,

Physical activity is favorable to health but the relations with human disease and causal effects are poorly quantified. Previous studies have largely relied on self-reported estimates 1–3 which are subject to recall bias, confounding, and reverse causality. Using wrist-worn accelerometer measurements from the UK Biobank, we tested associations between moderate-to-vigorous ... Read more >>

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Deep Learning of Left Atrial Structure and Function Provides Link to Atrial Fibrillation Risk

James Pirruccello, Paolo Di Achille, Seung Hoan Choi, Shaan Khurshid, Mahan Nekoui, Sean Jurgens, Victor Nauffal, Kenney Ng, Samuel Friedman, Kathryn Lunetta, Anthony Philippakis, Jennifer Ho, Steven Lubitz, Patrick Ellinor,

<h4>Aims</h4> Increased left atrial (LA) volume is a known risk factor for atrial fibrillation (AF). There is also emerging evidence that alterations in LA function due to an atrial cardiomyopathy are associated with an increased risk of AF. The availability of large-scale cardiac MRI data paired with genetic data provides ... Read more >>

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Comparative Effectiveness of Implantable Defibrillators for Asymptomatic Brugada Syndrome: A Decision-Analytic Model.

Shaan Khurshid, Wanyi Chen, Weeranun D Bode, Jason H Wasfy, Jagpreet Chhatwal, Steven A Lubitz,

Background Optimal management of asymptomatic Brugada syndrome (BrS) with spontaneous type I electrocardiographic pattern is uncertain. Methods and Results We developed an individual-level simulation comprising 2 000 000 average-risk individuals with asymptomatic BrS and spontaneous type I electrocardiographic pattern. We compared (1) observation, (2) electrophysiologic study (EPS)-guided implantable cardioverter-defibrillator (ICD), and (3) ... Read more >>

J Am Heart Assoc (Journal of the American Heart Association)
[2021, 10(16):e021144]

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Comparative Clinical Effectiveness of Population-Based Atrial Fibrillation Screening Using Contemporary Modalities: A Decision-Analytic Model.

Shaan Khurshid, Wanyi Chen, Daniel E Singer, Steven J Atlas, Jeffrey M Ashburner, Jin G Choi, Chin Hur, Patrick T Ellinor, David D McManus, Jagpreet Chhatwal, Steven A Lubitz,

Background Atrial fibrillation (AF) screening is endorsed by certain guidelines for individuals aged ≥65 years. Yet many AF screening strategies exist, including the use of wrist-worn wearable devices, and their comparative effectiveness is not well-understood. Methods and Results We developed a decision-analytic model simulating 50 million individuals with an age, sex, and ... Read more >>

J Am Heart Assoc (Journal of the American Heart Association)
[2021, 10(18):e020330]

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Deep Learning to Predict Cardiac Magnetic Resonance-Derived Left Ventricular Mass and Hypertrophy From 12-Lead ECGs.

Shaan Khurshid, Samuel Friedman, James P Pirruccello, Paolo Di Achille, Nathaniel Diamant, Christopher D Anderson, Patrick T Ellinor, Puneet Batra, Jennifer E Ho, Anthony A Philippakis, Steven A Lubitz,

<h4>Background</h4>Classical methods for detecting left ventricular (LV) hypertrophy (LVH) using 12-lead ECGs are insensitive. Deep learning models using ECG to infer cardiac magnetic resonance (CMR)-derived LV mass may improve LVH detection.<h4>Methods</h4>Within 32 239 individuals of the UK Biobank prospective cohort who underwent CMR and 12-lead ECG, we trained a convolutional ... Read more >>

Circ Cardiovasc Imaging (Circulation. Cardiovascular imaging)
[2021, 14(6):e012281]

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Accelerometer-derived physical activity and risk of atrial fibrillation.

Shaan Khurshid, Lu-Chen Weng, Mostafa A Al-Alusi, Jennifer L Halford, Julian S Haimovich, Emelia J Benjamin, Ludovic Trinquart, Patrick T Ellinor, David D McManus, Steven A Lubitz,

<h4>Aims</h4>Physical activity may be an important modifiable risk factor for atrial fibrillation (AF), but associations have been variable and generally based on self-reported activity.<h4>Methods and results</h4>We analysed 93 669 participants of the UK Biobank prospective cohort study without prevalent AF who wore a wrist-based accelerometer for 1 week. We categorized whether ... Read more >>

Eur Heart J (European heart journal)
[2021, 42(25):2472-2483]

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Cohort Design and Natural Language Processing to Reduce Bias in Electronic Health Records Research: The Community Care Cohort Project

Shaan Khurshid, Christopher Reeder, Lia Harrington, Pulkit Singh, Gopal Sarma, Samuel Friedman, Paolo Di Achille, Nathaniel Diamant, Jonathan Cunningham, Ashby Turner, Emily Lau, Julian Haimovich, Mostafa Al-Alusi, Xin Wang, Marcus D.R. Klarqvist, Jeffrey Ashburner, Christian Diedrich, Mercedeh Ghadessi, Johanna Mielke, Hanna Eilken, Alice McElhinney, Andrea Derix, Steven Atlas, Patrick Ellinor, Anthony Philippakis, Christopher Anderson, Jennifer Ho, Puneet Batra, Steven Lubitz,

<h4>ABSTRACT</h4> <h4>Background</h4> Electronic health records (EHRs) promise to enable broad-ranging discovery with power exceeding that of conventional research cohort studies. However, research using EHR datasets may be subject to selection bias, which can be compounded by missing data, limiting the generalizability of derived insights. <h4>Methods</h4> Mass General Brigham (MGB) is ... Read more >>

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Genetic Analysis of Right Heart Structure and Function in 40,000 People

James Pirruccello, Paolo Di Achille, Victor Nauffal, Mahan Nekoui, Samuel Friedman, Marcus Klarqvist, Mark Chaffin, Shaan Khurshid, Carolina Roselli, Puneet Batra, Kenney Ng, Steven Lubitz, Jennifer Ho, Mark Lindsay, Anthony Philippakis, Patrick Ellinor,

The heart evolved hundreds of millions of years ago. During mammalian evolution, the cardiovascular system developed with complete separation between pulmonary and systemic circulations incorporated into a single pump with chambers dedicated to each circulation. A lower pressure right heart chamber supplies deoxygenated blood to the lungs, while a high ... Read more >>

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Usefulness of Rhythm Monitoring Following Acute Ischemic Stroke.

Shaan Khurshid, Xinye Li, Jeffrey M Ashburner, Ana T Trisini Lipsanopoulos, Priscilla R Lee, Aimee K Lin, Darae Ko, Patrick T Ellinor, Lee H Schwamm, Emelia J Benjamin, Steven J Atlas, Daniel E Singer, Christopher D Anderson, Ludovic Trinquart, Steven A Lubitz,

We characterized monitor utilization in stroke survivors and assessed associations with underlying clinical atrial fibrillation (AF) risk. We retrospectively analyzed consecutive patients with acute ischemic stroke 10/2018-6/2019 without prevalent AF and assessed the 6-month incidence of monitor utilization (Holter/ECG, event/patch, implantable loop recorder [ILR]) using Fine-Gray models accounting for the ... Read more >>

Am J Cardiol (The American journal of cardiology)
[2021, 147:44-51]

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Performance of Atrial Fibrillation Risk Prediction Models in Over 4 Million Individuals.

Shaan Khurshid, Uri Kartoun, Jeffrey M Ashburner, Ludovic Trinquart, Anthony Philippakis, Amit V Khera, Patrick T Ellinor, Kenney Ng, Steven A Lubitz,

<h4>Background</h4>Atrial fibrillation (AF) is associated with increased risks of stroke and heart failure. Electronic health record (EHR)-based AF risk prediction may facilitate efficient deployment of interventions to diagnose or prevent AF altogether.<h4>Methods</h4>We externally validated an electronic health record AF (EHR-AF) score in IBM Explorys Life Sciences, a multi-institutional dataset containing ... Read more >>

Circ Arrhythm Electrophysiol (Circulation. Arrhythmia and electrophysiology)
[2021, 14(1):e008997]

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Deep Learning to Estimate Cardiac Magnetic Resonance-Derived Left Ventricular Mass

Shaan Khurshid, Samuel Friedman, James Pirruccello, Paolo Di Achille, Nathaniel Diamant, Christopher Anderson, Patrick Ellinor, Puneet Batra, Jennifer Ho, Anthony Philippakis, Steven Lubitz,

<h4>ABSTRACT</h4> <h4>Background</h4> Cardiac magnetic resonance (CMR) is the gold standard for left ventricular hypertrophy (LVH) diagnosis. CMR-derived LV mass can be estimated using proprietary algorithms (e.g., inlineVF), but their accuracy and availability may be limited. <h4>Objective</h4> To develop an open-source deep learning model to estimate CMR-derived LV mass. <h4>Methods</h4> Within ... Read more >>

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Associations Between Alcohol Intake and Genetic Predisposition With Atrial Fibrillation Risk in a National Biobank.

Jennifer L Halford, Lu-Chen Weng, Seung Hoan Choi, Sean J Jurgens, Valerie N Morrill, Shaan Khurshid, Ludovic Trinquart, Emelia J Benjamin, Patrick T Ellinor, Steven A Lubitz,

<h4>Background</h4>Excess alcohol intake and inherited predisposition may increase risk of atrial fibrillation (AF). We assessed the association between alcohol intake, polygenic predisposition to AF, and incident AF in the UK Biobank, a prospective cohort study.<h4>Methods</h4>In 376 776 UK Biobank participants enrolled between 2006 and 2010, we tested alcohol consumption (stratified by ... Read more >>

Circ Genom Precis Med (Circulation. Genomic and precision medicine)
[2020, 13(6):e003111]

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Automated Electronic Phenotyping of Cardioembolic Stroke.

Wyliena Guan, Darae Ko, Shaan Khurshid, Ana T Trisini Lipsanopoulos, Jeffrey M Ashburner, Lia X Harrington, Natalia S Rost, Steven J Atlas, Daniel E Singer, David D McManus, Christopher D Anderson, Steven A Lubitz,

<h4>Background and purpose</h4>Oral anticoagulation is generally indicated for cardioembolic strokes, but not for other stroke causes. Consequently, subtype classification of ischemic stroke is important for risk stratification and secondary prevention. Because manual classification of ischemic stroke is time-intensive, we assessed the accuracy of automated algorithms for performing cardioembolic stroke subtyping ... Read more >>

Stroke (Stroke)
[2021, 52(1):181-189]

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Population-Based Screening for Atrial Fibrillation.

Shaan Khurshid, Jeffrey S Healey, William F McIntyre, Steven A Lubitz,

Atrial fibrillation (AF) is a common and morbid arrhythmia. Stroke is a major hazard of AF and may be preventable with oral anticoagulation. Yet since AF is often asymptomatic, many individuals with AF may be unaware and do not receive treatment that could prevent a stroke. Screening for AF has ... Read more >>

Circ Res (Circulation research)
[2020, 127(1):143-154]

Cited: 10 times

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Atrial Fibrillation Risk and Discrimination of Cardioembolic From Noncardioembolic Stroke.

Shaan Khurshid, Ludovic Trinquart, Lu-Chen Weng, Olivia L Hulme, Wyliena Guan, Darae Ko, Kristin Schwab, Natalia S Rost, Mostafa A Al-Alusi, Emelia J Benjamin, Patrick T Ellinor, Christopher D Anderson, Steven A Lubitz,

Background and Purpose- Classification of stroke as cardioembolic in etiology can be challenging, particularly since the predominant cause, atrial fibrillation (AF), may not be present at the time of stroke. Efficient tools that discriminate cardioembolic from noncardioembolic strokes may improve care as anticoagulation is frequently indicated after cardioembolism. We sought ... Read more >>

Stroke (Stroke)
[2020, 51(5):1396-1403]

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Deep learning enables genetic analysis of the human thoracic aorta

James Pirruccello, Mark Chaffin, Stephen Fleming, Alessandro Arduini, Honghuang Lin, Shaan Khurshid, Elizabeth Chou, Samuel Friedman, Alexander Bick, Lu-Chen Weng, Seung Hoan Choi, Amer-Denis Akkad, Puneet Batra, Nathan Tucker, Amelia Hall, Carolina Roselli, Emelia Benjamin, Shamsudheen Vellarikkal, Rajat Gupta, Christian Stegman, Jennifer Ho, Udo Hoffmann, Steven Lubitz, Anthony Philippakis, Mark Lindsay, Patrick Ellinor,

The aorta is the largest blood vessel in the body, and enlargement or aneurysm of the aorta can predispose to dissection, an important cause of sudden death. While rare syndromes have been identified that predispose to aortic aneurysm, the common genetic basis for the size of the aorta remains largely ... Read more >>

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