James Pirruccello, MD
Associate Professor
Medicine
School of Medicine

Dr. Pirruccello studies cardiovascular and aortic diseases using machine learning and genetics. He uses machine learning to quantify the heart, and to create new types of measurements that can help us to better understand health and disease. He uses genetics to analyze these measurements to gain insight into mechanisms of disease. Further, Dr. Pirruccello uses both genetics and machine learning to develop tools to better understand risk, before the onset of disease.

• The Role of Socioeconomic Status in the Association between Genetic Predisposition and Cardiovascular Events: A UK Biobank Study.
  The American journal of cardiology 2026 Bhaskar SS, Pirruccello JP, Hoffmann TJ, Beatty AL
• Modifiable Lifestyle Factors, Left Atrial Indices, and Atrial Fibrillation.
  Journal of the American Heart Association 2026 Elias A, Pirruccello JP, Delling FN, Lee C, Marcus GM
• Artificial Intelligence-Enabled ECG Analysis to Predict Incident Heart Failure.
  Circulation. Heart failure 2026 Khurshid S, Friedman SF, Kany S, D'Souza V, Roshandelpoor A, Kosyakovsky LB, Chitsazan M, Cunningham JW, Singh P, Lau ES, Pipilas D, Al-Alusi MA, Rämö JT, Pirruccello JP, Reeder C, Waks JW, Lubitz SA,…
• Physical Activity and Cardiovascular Outcomes in Phenotype-Negative Cardiomyopathy Variant Carriers.
  JAMA cardiology 2026 Ajufo E, Kany S, Jurgens SJ, Churchill TW, Guseh JS, Aragam KG, Nauffal V, Pirruccello JP, Choi SH, Lakdawala NK, Ho CY, Ellinor PT, Khurshid S
• Multitrait analyses identify genetic variants associated with aortic valve function and aortic stenosis risk.
  Nature genetics 2025 Kany S, Rämö JT, Hou C, Jurgens SJ, Khurshid S, Nauffal V, Cunningham JW, Lau ES, Koyama S, FinnGen, Ho JE, Olgin JE, Elmariah S, Palotie A, Lindsay ME, Ellinor PT, Pirruccello JP
• Estimating Ascending Aortic Diameter From the Electrocardiogram.
  Journal of the American College of Cardiology 2025 Demarais ZS, Olgin JE, Pirruccello JP
• An African ancestry-specific nonsense variant in CD36 is associated with a higher risk of dilated cardiomyopathy.
  Nature genetics 2025 Huffman JE, Gaziano L, Al Sayed ZR, Judy RL, Raffield LM, Biddinger KJ, Charest B, Chopra A, Gagnon D, Guo X, Koledova V, Levin MG, Min YI, Pirruccello JP, Reza N, Ruan R, Verma SS, Venkatesh BA, …
• Mendelian Randomization Suggests a Causal Link Between Glycemic Traits and Thoracic Aortic Structures and Diseases.
  JACC. Basic to translational science 2025 Daria T, Iyer K, Alkhairo H, Kho PF, Suzuki K, Hatzikotoulas K, Southam L, Taylor HJ, Yin X, Mandla R, Huerta-Chagoya A, Rayner WN, Levin MG, Damrauer SM, Tsao PS, Priest JR, Klarin D, Pirruccello J, …
• Moving Beyond the Model: Our Perspective on Meaningful AI Research in Cardiovascular Care.
  Journal of the American College of Cardiology 2025 Jain SS, Mortazavi BJ, Chan You S, Yao X, Lam CSP, Elias P, Poterucha TJ, Avram R, Tison GH, Pirruccello J, Huang C, Wiens J, Schwamm L, Ruan X, Dunn J, Luo Y, Spatz ES, Krumholz HM
• Pathogenic Cardiomyopathy-Associated Gene Variants and Prognosis in Atrial Fibrillation: Results in 18,000 Clinical Trial Participants.
  Journal of the American College of Cardiology 2025 Jurgens SJ, Melloni GEM, Kany S, Fabritz L, Rämö JT, Goette A, Kamanu FK, Berg DD, Magnussen C, Choi SH, Bonaca MP, Giugliano RP, Scirica BM, Wiviott SD, Bhatt DL, Steg PG, Raz I, Braunwald E, …
• Whole-genome sequencing analysis of left ventricular structure and sphericity in 80,000 people.
  medRxiv : the preprint server for health sciences 2025 Pirruccello JP
• Estimating ascending aortic diameter from the electrocardiogram.
  medRxiv : the preprint server for health sciences 2025 Demarais ZS, Olgin JE, Pirruccello JP
• Electrocardiogram-Based Artificial Intelligence to Identify Coronary Artery Disease.
  JACC. Advances 2025 Kany S, Friedman SF, Al-Alusi M, Khurshid S, Rämö JT, Pipilas D, Pirruccello JP, Reeder C, Philippakis AA, Ho JE, Maddah M, Ellinor PT, Fahed AC
• Improved multiancestry fine-mapping identifies cis-regulatory variants underlying molecular traits and disease risk.
  Nature genetics 2025 Lu Z, Wang X, Carr M, Kim A, Gazal S, Mohammadi P, Wu L, Pirruccello J, Kachuri L, Gusev A, Mancuso N
• Predicting Thoracic Aortic Dissection in a Diverse Biobank Using a Polygenic Risk Score.
  JACC. Advances 2025 DePaolo J, Zamirpour S, Abramowitz S, Biagetti G, Judy R, Beeche C, Duda J, Gee J, Witschey WR, Chirinos JA, Goel NJ, Desai N, Szeto WY, Guo D, Milewicz DM, Levin MG, Pirruccello JP, Damrauer SM
• New Threshold for Defining Mild Aortic Stenosis Derived From Velocity-Encoded MRI in 60,000 Individuals.
  Journal of the American College of Cardiology 2025 Kany S, Rämö JT, Playford D, Strange G, Hou C, Jurgens SJ, Nauffal V, Cunningham JW, Lau ES, Butte AJ, Ho JE, Olgin JE, Elmariah S, Lindsay ME, Chan YK, Stewart S, Ellinor PT, Pirruccello JP
• Meta-analysis of genome-wide associations and polygenic risk prediction for atrial fibrillation in more than 180,000 cases.
  Nature genetics 2025 Roselli C, Surakka I, Olesen MS, Sveinbjornsson G, Marston NA, Choi SH, Holm H, Chaffin M, Gudbjartsson D, Hill MC, Aegisdottir H, Albert CM, Alonso A, Anderson CD, Arking DE, Arnar DO, Barnard J, …
• Sequencing in over 50,000 cases identifies coding and structural variation underlying atrial fibrillation risk.
  Nature genetics 2025 Choi SH, Jurgens SJ, Xiao L, Hill MC, Haggerty CM, Sveinbjörnsson G, Morrill VN, Marston NA, Weng LC, Pirruccello JP, Arnar DO, Gudbjartsson DF, Mantineo H, von Falkenhausen AS, Natale A, Tveit A, …
• A deep learning digital biomarker to detect hypertension and stratify cardiovascular risk from the electrocardiogram.
  NPJ digital medicine 2025 Al-Alusi MA, Friedman SF, Kany S, Rämö JT, Pipilas D, Singh P, Reeder C, Khurshid S, Pirruccello JP, Maddah M, Ho JE, Ellinor PT
• "Weekend Warrior" Physical Activity and Adipose Tissue Deposition.
  JACC. Advances 2025 Kany S, Al-Alusi MA, Rämö JT, Pirruccello JP, Ajufo E, Churchill TW, Lubitz SA, Maddah M, Guseh JS, Ellinor PT, Khurshid S
• Unsupervised deep learning of electrocardiograms enables scalable human disease profiling.
  NPJ digital medicine 2025 Friedman SF, Khurshid S, Venn RA, Wang X, Diamant N, Di Achille P, Weng LC, Choi SH, Reeder C, Pirruccello JP, Singh P, Lau ES, Philippakis A, Anderson CD, Maddah M, Batra P, Ellinor PT, Ho JE, Lubitz…
• The AORTA Gene score for detection and risk stratification of ascending aortic dilation.
  European heart journal 2024 Pirruccello JP, Khurshid S, Lin H, Weng LC, Zamirpour S, Kany S, Raghavan A, Koyama S, Vasan RS, Benjamin EJ, Lindsay ME, Ellinor PT
• Epicardial and Pericardial Fat-Separated But Under the Same Roof-Reply.
  JAMA cardiology 2024 Rämö JT, Ellinor PT, Pirruccello JP
• Rare Genetic Variants in LDLR, APOB, and PCSK9 Are Associated With Aortic Stenosis.
  Circulation 2024 Rämö JT, Jurgens SJ, Kany S, Choi SH, Wang X, Smirnov AN, Friedman SF, Maddah M, Khurshid S, Ellinor PT, Pirruccello JP
• Rare coding variant analysis for human diseases across biobanks and ancestries.
  Nature genetics 2024 Jurgens SJ, Wang X, Choi SH, Weng LC, Koyama S, Pirruccello JP, Nguyen T, Smadbeck P, Jang D, Chaffin M, Walsh R, Roselli C, Elliott AL, Wijdeveld LFJM, Biddinger KJ, Kany S, Rämö JT, Natarajan P, …
• Genetics of Cardiac Aging Implicate Organ-Specific Variation.
  medRxiv : the preprint server for health sciences 2024 Brundage J, Barrios JP, Tison GH, Pirruccello JP
• Noninvasive assessment of organ-specific and shared pathways in multi-organ fibrosis using T1 mapping.
  Nature medicine 2024 Nauffal V, Klarqvist MDR, Hill MC, Pace DF, Di Achille P, Choi SH, Rämö JT, Pirruccello JP, Singh P, Kany S, Hou C, Ng K, Philippakis AA, Batra P, Lubitz SA, Ellinor PT
• Deep learning of left atrial structure and function provides link to atrial fibrillation risk.
  Nature communications 2024 Pirruccello JP, Di Achille P, Choi SH, Rämö JT, Khurshid S, Nekoui M, Jurgens SJ, Nauffal V, Kany S, FinnGen, Ng K, Friedman SF, Batra P, Lunetta KL, Palotie A, Philippakis AA, Ho JE, Lubitz SA, …
• Improved multi-ancestry fine-mapping identifies cis-regulatory variants underlying molecular traits and disease risk.
  medRxiv : the preprint server for health sciences 2024 Lu Z, Wang X, Carr M, Kim A, Gazal S, Mohammadi P, Wu L, Gusev A, Pirruccello J, Kachuri L, Mancuso N
• Artificial Intelligence for Cardiovascular Care-Part 1: Advances: JACC Review Topic of the Week.
  Journal of the American College of Cardiology 2024 Elias P, Jain SS, Poterucha T, Randazzo M, Lopez Jimenez F, Khera R, Perez M, Ouyang D, Pirruccello J, Salerno M, Einstein AJ, Avram R, Tison GH, Nadkarni G, Natarajan V, Pierson E, Beecy A, Kumaraiah…
• Artificial Intelligence in Cardiovascular Care-Part 2: Applications: JACC Review Topic of the Week.
  Journal of the American College of Cardiology 2024 Jain SS, Elias P, Poterucha T, Randazzo M, Lopez Jimenez F, Khera R, Perez M, Ouyang D, Pirruccello J, Salerno M, Einstein AJ, Avram R, Tison GH, Nadkarni G, Natarajan V, Pierson E, Beecy A, Kumaraiah…
• Using Genomics to Identify Novel Therapeutic Targets for Aortic Disease.
  Arteriosclerosis, thrombosis, and vascular biology 2023 Raghavan A, Pirruccello JP, Ellinor PT, Lindsay ME
• Sex differences in ascending aortic size reporting and growth on chest computed tomography and magnetic resonance imaging.
  Clinical imaging 2023 Zamirpour S, Boskovski MT, Pirruccello JP, Pace WA, Hubbard AE, Leach JR, Ge L, Tseng EE
• Exploring the complex spectrum of dominance and recessiveness in genetic cardiomyopathies.
  Nature cardiovascular research 2023 Lipov A, Jurgens SJ, Mazzarotto F, Allouba M, Pirruccello JP, Aguib Y, Gennarelli M, Yacoub MH, Ellinor PT, Bezzina CR, Walsh R
• Clonal haematopoiesis and risk of chronic liver disease.
  Nature 2023 Wong WJ, Emdin C, Bick AG, Zekavat SM, Niroula A, Pirruccello JP, Dichtel L, Griffin G, Uddin MM, Gibson CJ, Kovalcik V, Lin AE, McConkey ME, Vromman A, Sellar RS, Kim PG, Agrawal M, Weinstock J, Long…
• Adjusting for common variant polygenic scores improves yield in rare variant association analyses.
  Nature genetics 2023 Jurgens SJ, Pirruccello JP, Choi SH, Morrill VN, Chaffin M, Lubitz SA, Lunetta KL, Ellinor PT
• Clinical and genetic associations of deep learning-derived cardiac magnetic resonance-based left ventricular mass.
  Nature communications 2023 Khurshid S, Lazarte J, Pirruccello JP, Weng LC, Choi SH, Hall AW, Wang X, Friedman SF, Nauffal V, Biddinger KJ, Aragam KG, Batra P, Ho JE, Philippakis AA, Ellinor PT, Lubitz SA
• TP53-mediated clonal hematopoiesis confers increased risk for incident atherosclerotic disease.
  Nature cardiovascular research 2023 Zekavat SM, Viana-Huete V, Matesanz N, Jorshery SD, Zuriaga MA, Uddin MM, Trinder M, Paruchuri K, Zorita V, Ferrer-Pérez A, Amorós-Pérez M, Kunderfranco P, Carriero R, Greco CM, Aroca-Crevillen A, …
• Quantifying the phenome-wide disease burden of obesity using electronic health records and genomics.
  Obesity (Silver Spring, Md.) 2022 Robinson JR, Carroll RJ, Bastarache L, Chen Q, Pirruccello J, Mou Z, Wei WQ, Connolly J, Mentch F, Crane PK, Hebbring SJ, Crosslin DR, Gordon AS, Rosenthal EA, Stanaway IB, Hayes MG, Wei W, Petukhova …
• Author Correction: Genetics of 35 blood and urine biomarkers in the UK Biobank.
  Nature genetics 2021 Sinnott-Armstrong N, Tanigawa Y, Amar D, Mars N, Benner C, Aguirre M, Venkataraman GR, Wainberg M, Ollila HM, Kiiskinen T, Havulinna AS, Pirruccello JP, Qian J, Shcherbina A, FinnGen, Rodriguez F, …
• Dnmt3a-mutated clonal hematopoiesis promotes osteoporosis.
  The Journal of experimental medicine 2021 Kim PG, Niroula A, Shkolnik V, McConkey M, Lin AE, Slabicki M, Kemp JP, Bick A, Gibson CJ, Griffin G, Sekar A, Brooks DJ, Wong WJ, Cohen DN, Uddin MM, Shin WJ, Pirruccello J, Tsai JM, Agrawal M, Kiel …
• Genetics of 35 blood and urine biomarkers in the UK Biobank.
  Nature genetics 2021 Sinnott-Armstrong N, Tanigawa Y, Amar D, Mars N, Benner C, Aguirre M, Venkataraman GR, Wainberg M, Ollila HM, Kiiskinen T, Havulinna AS, Pirruccello JP, Qian J, Shcherbina A, FinnGen, Rodriguez F, …
• Titin Truncating Variants in Adults Without Known Congestive Heart Failure.
  Journal of the American College of Cardiology 2020 Pirruccello JP, Bick A, Chaffin M, Aragam KG, Choi SH, Lubitz SA, Ho CY, Ng K, Philippakis A, Ellinor PT, Kathiresan S, Khera AV
• Genetic Interleukin 6 Signaling Deficiency Attenuates Cardiovascular Risk in Clonal Hematopoiesis.
  Circulation 2019 Bick AG, Pirruccello JP, Griffin GK, Gupta N, Gabriel S, Saleheen D, Libby P, Kathiresan S, Natarajan P
• Monogenic and Polygenic Contributions to Atrial Fibrillation Risk: Results From a National Biobank.
  Circulation research 2019 Choi SH, Jurgens SJ, Weng LC, Pirruccello JP, Roselli C, Chaffin M, Lee CJ, Hall AW, Khera AV, Lunetta KL, Lubitz SA, Ellinor PT
• "Road Map" to Improving Enrollment in Cardiac Rehabilitation: Identifying Barriers and Evaluating Alternatives.
  Journal of the American Heart Association 2017 Pirruccello JP, Traynor K, Aragam KG
• Role of angiopoietin-like 3 (ANGPTL3) in regulating plasma level of low-density lipoprotein cholesterol.
  Atherosclerosis 2017 Xu YX, Redon V, Yu H, Querbes W, Pirruccello J, Liebow A, Deik A, Trindade K, Wang X, Musunuru K, Clish CB, Cowan C, Fizgerald K, Rader D, Kathiresan S
• An electronic cardiac rehabilitation referral system increases cardiac rehabilitation referrals.
  Coronary artery disease 2017 Pirruccello JP, Traynor KC, Natarajan P, Brown C, Hidrue MK, Rosenfield KA, Kathiresan S, Wasfy JH
• Targeted exonic sequencing of GWAS loci in the high extremes of the plasma lipids distribution.
  Atherosclerosis 2016 Patel AP, Peloso GM, Pirruccello JP, Johansen CT, Dubé JB, Larach DB, Ban MR, Dallinge-Thie GM, Gupta N, Boehnke M, Abecasis GR, Kastelein JJ, Hovingh GK, Hegele RA, Rader DJ, Kathiresan S
• A novel APOB mutation identified by exome sequencing cosegregates with steatosis, liver cancer, and hypocholesterolemia.
  Arteriosclerosis, thrombosis, and vascular biology 2013 Cefalù AB, Pirruccello JP, Noto D, Gabriel S, Valenti V, Gupta N, Spina R, Tarugi P, Kathiresan S, Averna MR
• Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study.
  Lancet (London, England) 2012 Voight BF, Peloso GM, Orho-Melander M, Frikke-Schmidt R, Barbalic M, Jensen MK, Hindy G, Hólm H, Ding EL, Johnson T, Schunkert H, Samani NJ, Clarke R, Hopewell JC, Thompson JF, Li M, Thorleifsson G, …
• Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.
  PLoS genetics 2012 Dastani Z, Hivert MF, Timpson N, Perry JR, Yuan X, Scott RA, Henneman P, Heid IM, Kizer JR, Lyytikäinen LP, Fuchsberger C, Tanaka T, Morris AP, Small K, Isaacs A, Beekman M, Coassin S, Lohman K, Qi L,…
• Advances in genetics show the need for extending screening strategies for autosomal dominant hypercholesterolaemia.
  European heart journal 2012 Motazacker MM, Pirruccello J, Huijgen R, Do R, Gabriel S, Peter J, Kuivenhoven JA, Defesche JC, Kastelein JJ, Hovingh GK, Zelcer N, Kathiresan S, Fouchier SW
• Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia.
  The New England journal of medicine 2010 Musunuru K, Pirruccello JP, Do R, Peloso GM, Guiducci C, Sougnez C, Garimella KV, Fisher S, Abreu J, Barry AJ, Fennell T, Banks E, Ambrogio L, Cibulskis K, Kernytsky A, Gonzalez E, Rudzicz N, Engert …
• Biological, clinical and population relevance of 95 loci for blood lipids.
  Nature 2010 Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, Pirruccello JP, Ripatti S, Chasman DI, Willer CJ, Johansen CT, Fouchier SW, Isaacs A, Peloso GM, Barbalic M, Ricketts SL, Bis …
• From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus.
  Nature 2010 Musunuru K, Strong A, Frank-Kamenetsky M, Lee NE, Ahfeldt T, Sachs KV, Li X, Li H, Kuperwasser N, Ruda VM, Pirruccello JP, Muchmore B, Prokunina-Olsson L, Hall JL, Schadt EE, Morales CR, Lund-Katz S, …
• Genetics of lipid disorders.
  Current opinion in cardiology 2010 Pirruccello J, Kathiresan S
• Candidate gene association resource (CARe): design, methods, and proof of concept.
  Circulation. Cardiovascular genetics 2010 Musunuru K, Lettre G, Young T, Farlow DN, Pirruccello JP, Ejebe KG, Keating BJ, Yang Q, Chen MH, Lapchyk N, Crenshaw A, Ziaugra L, Rachupka A, Benjamin EJ, Cupples LA, Fornage M, Fox ER, Heckbert SR, …