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1,378 results on '"Chung, Mina K."'

1. Pre-exposure immunohematologic features of heart failure associate with COVID-19 mortality

Author

Zidar, David A., Wilson, Brigid M., Al-Kindi, Sadeer G., Sweet, David, Juchnowski, Steven, Huntington, Lauren, Shive, Carey, Bosch, Jürgen, King, Christopher, Karn, Jonathan, Chung, Mina K., Gillombardo, Carl B., Karnib, Mohammad, Sundaram, Varun, Parikh, Sahil A., Jain, Mukesh, Gunzler, Douglas D., Skarbinski, Jacek, Tang, W. H. Wilson, Anthony, Donald D., Chan, Timothy A., and Dalton, Jarrod E.

Published
2024
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2. Whole-genome sequencing in 333,100 individuals reveals rare non-coding single variant and aggregate associations with height

Author

Hawkes, Gareth, Beaumont, Robin N., Li, Zilin, Mandla, Ravi, Li, Xihao, Albert, Christine M., Arnett, Donna K., Ashley-Koch, Allison E., Ashrani, Aneel A., Barnes, Kathleen C., Boerwinkle, Eric, Brody, Jennifer A., Carson, April P., Chami, Nathalie, Chen, Yii-Der Ida, Chung, Mina K., Curran, Joanne E., Darbar, Dawood, Ellinor, Patrick T., Fornage, Myrian, Gordeuk, Victor R., Guo, Xiuqing, He, Jiang, Hwu, Chii-Min, Kalyani, Rita R., Kaplan, Robert, Kardia, Sharon L. R., Kooperberg, Charles, Loos, Ruth J. F., Lubitz, Steven A., Minster, Ryan L., Naseri, Take, Viali, Satupa’itea, Mitchell, Braxton D., Murabito, Joanne M., Palmer, Nicholette D., Psaty, Bruce M., Redline, Susan, Shoemaker, M. Benjamin, Silverman, Edwin K., Telen, Marilyn J., Weiss, Scott T., Yanek, Lisa R., Zhou, Hufeng, Liu, Ching-Ti, North, Kari E., Justice, Anne E., Locke, Jonathan M., Owens, Nick, Murray, Anna, Patel, Kashyap, Frayling, Timothy M., Wright, Caroline F., Wood, Andrew R., Lin, Xihong, Manning, Alisa, and Weedon, Michael N.

Published
2024
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5. Women Trainees in Electrophysiology and the Effect of Role Models

Author

Baykaner, Tina, Greif, Shana, Vajapey, Ramya S., Albert, Christine M., Aziz, Zaid, Badhwar, Nitish, Bunch, T. Jared, Cheung, Jim W., Chrispin, Jonathan, Chung, Mina K., Clopton, Paul, Cooper, Daniel H., Cooper, Joshua M., Costea, Alexandru, Huang, Henry D., Hurwitz, Jodie L., Jankelson, Lior, Kapoor, Ridhima, Kroman, Anne, Latchamsetty, Rakesh, Liang, Jackson J., Mansour, Moussa, Marrouche, Nassir F., Merchant, Faisal M., Miller, John M., Mountantonakis, Stavros, Piccini, Jonathan P., Russo, Andrea M., Steinberg, Benjamin A., Tedrow, Usha, Tzou, Wendy S., Wan, Elaine Y., Wang, Paul J., and Han, Janet K.

Published
2024
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6. Assessing the contribution of rare variants to complex trait heritability from whole-genome sequence data

Author

Wainschtein, Pierrick, Jain, Deepti, Zheng, Zhili, Cupples, L Adrienne, Shadyab, Aladdin H, McKnight, Barbara, Shoemaker, Benjamin M, Mitchell, Braxton D, Psaty, Bruce M, Kooperberg, Charles, Liu, Ching-Ti, Albert, Christine M, Roden, Dan, Chasman, Daniel I, Darbar, Dawood, Lloyd-Jones, Donald M, Arnett, Donna K, Regan, Elizabeth A, Boerwinkle, Eric, Rotter, Jerome I, O’Connell, Jeffrey R, Yanek, Lisa R, de Andrade, Mariza, Allison, Matthew A, McDonald, Merry-Lynn N, Chung, Mina K, Fornage, Myriam, Chami, Nathalie, Smith, Nicholas L, Ellinor, Patrick T, Vasan, Ramachandran S, Mathias, Rasika A, Loos, Ruth JF, Rich, Stephen S, Lubitz, Steven A, Heckbert, Susan R, Redline, Susan, Guo, Xiuqing, Chen, Y-D Ida, Laurie, Cecelia A, Hernandez, Ryan D, McGarvey, Stephen T, Goddard, Michael E, Laurie, Cathy C, North, Kari E, Lange, Leslie A, Weir, Bruce S, Yengo, Loic, Yang, Jian, and Visscher, Peter M

Subjects
Human Genome, Genetics, 2.1 Biological and endogenous factors, Aetiology, Generic health relevance, Alleles, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Multifactorial Inheritance, Polymorphism, Single Nucleotide, TOPMed Anthropometry Working Group, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Analyses of data from genome-wide association studies on unrelated individuals have shown that, for human traits and diseases, approximately one-third to two-thirds of heritability is captured by common SNPs. However, it is not known whether the remaining heritability is due to the imperfect tagging of causal variants by common SNPs, in particular whether the causal variants are rare, or whether it is overestimated due to bias in inference from pedigree data. Here we estimated heritability for height and body mass index (BMI) from whole-genome sequence data on 25,465 unrelated individuals of European ancestry. The estimated heritability was 0.68 (standard error 0.10) for height and 0.30 (standard error 0.10) for body mass index. Low minor allele frequency variants in low linkage disequilibrium (LD) with neighboring variants were enriched for heritability, to a greater extent for protein-altering variants, consistent with negative selection. Our results imply that rare variants, in particular those in regions of low linkage disequilibrium, are a major source of the still missing heritability of complex traits and disease.

Published
2022

8. 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

Author

Krahn, Andrew D., Andrade, Jason G., Beavers, Craig J., Bischoff, James M., Bunch, T. Jared, Campbell, Kristen Bova, Chen, Lin Yee, Dharia, Robin, Dorsch, Michael P., Gerstenfeld, Edward P., Jones, Aubrey E., Kaluzna, Stephanie Dwyer, Masha, Luke, Nault, Isabelle, Noseworthy, Peter A., Pellegrini, Cara N., Tzeis, Stylianos E., Volgman, Annabelle Santos, Zeitler, Emily P., Joglar, José A., Chung, Mina K., Armbruster, Anastasia L., Benjamin, Emelia J., Chyou, Janice Y., Cronin, Edmond M., Deswal, Anita, Eckhardt, Lee L., Goldberger, Zachary D., Gopinathannair, Rakesh, Gorenek, Bulent, Hess, Paul L., Hlatky, Mark, Hogan, Gail, Ibeh, Chinwe, Indik, Julia H., Kido, Kazuhiko, Kusumoto, Fred, Link, Mark S., Linta, Kathleen T., Marcus, Gregory M., McCarthy, Patrick M., Patel, Nimesh, Patton, Kristen K., Perez, Marco V., Piccini, Jonathan P., Russo, Andrea M., Sanders, Prashanthan, Streur, Megan M., Thomas, Kevin L., Times, Sabrina, Tisdale, James E., Valente, Anne Marie, and Van Wagoner, David R.

Published
2024
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9. HRS Policy Statement on Catheter Ablation of Atrial Fibrillation

Author

Liu, Christopher F., Berman, Adam E., Chung, Mina K., Dukes, Jonathan, Ellenbogen, Kenneth A., Greenberg, Scott J., Hadziabdulahovic, Sabina, Kanagasundram, Arvindh N., Larsen, Timothy R., Mainigi, Sumeet K., Sachdev, Molly, Schoenfeld, Mark H., Slotwiner, David J., Thosani, Amit, Weiss, J. Peter, Miller, Lisa, Smith, Anne Marie, and Shanker, Amit J.

Published
2024
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10. A novel scoring system and correlative analysis of the strength and effectiveness of nationwide high school cardiopulmonary resuscitation mandates: Insights from a high school CPR study

Author

Katapadi, Aashish, Lakkireddy, Avani, Korlakunta, Sneha, Maganti, Lasya, Ghazal, Rachad, MUDR, Aditya Mansabdar, Pham, Nicholas, Bawa, Danish, Ahmed, Adnan, Baratham, Anjali, Chelikam, Nikhila, Darden, Douglas, Shan, Ehtesham, Garg, Jalaj, Kabra, Rajesh, Gopinathannair, Rakesh, Atkins, Donita, Biga, Cathie, Ellenbogen, Kenneth A., Chung, Mina K., Kovacs, Richard, and Lakkireddy, Dhanunjaya

Published
2024
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12. 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

Author

Joglar, José A., Chung, Mina K., Armbruster, Anastasia L., Benjamin, Emelia J., Chyou, Janice Y., Cronin, Edmond M., Deswal, Anita, Eckhardt, Lee L., Goldberger, Zachary D., Gopinathannair, Rakesh, Gorenek, Bulent, Hess, Paul L., Hlatky, Mark, Hogan, Gail, Ibeh, Chinwe, Indik, Julia H., Kido, Kazuhiko, Kusumoto, Fred, Link, Mark S., Linta, Kathleen T., Marcus, Gregory M., McCarthy, Patrick M., Patel, Nimesh, Patton, Kristen K., Perez, Marco V., Piccini, Jonathan P., Russo, Andrea M., Sanders, Prashanthan, Streur, Megan M., Thomas, Kevin L., Times, Sabrina, Tisdale, James E., Valente, Anne Marie, and Van Wagoner, David R.

Published
2024
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14. 2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure

Author

Chung, Mina K., Patton, Kristen K., Lau, Chu-Pak, Dal Forno, Alexander R.J., Al-Khatib, Sana M., Arora, Vanita, Birgersdotter-Green, Ulrika Maria, Cha, Yong-Mei, Chung, Eugene H., Cronin, Edmond M., Curtis, Anne B., Cygankiewicz, Iwona, Dandamudi, Gopi, Dubin, Anne M., Ensch, Douglas P., Glotzer, Taya V., Gold, Michael R., Goldberger, Zachary D., Gopinathannair, Rakesh, Gorodeski, Eiran Z., Gutierrez, Alejandra, Guzman, Juan C., Huang, Weijian, Imrey, Peter B., Indik, Julia H., Karim, Saima, Karpawich, Peter P., Khaykin, Yaariv, Kiehl, Erich L., Kron, Jordana, Kutyifa, Valentina, Link, Mark S., Marine, Joseph E., Mullens, Wilfried, Park, Seung-Jung, Parkash, Ratika, Patete, Manuel F., Pathak, Rajeev Kumar, Perona, Carlos A., Rickard, John, Schoenfeld, Mark H., Seow, Swee-Chong, Shen, Win-Kuang, Shoda, Morio, Singh, Jagmeet P., Slotwiner, David J., Sridhar, Arun Raghav M., Srivatsa, Uma N., Stecker, Eric C., Tanawuttiwat, Tanyanan, Tang, W.H. Wilson, Tapias, Carlos Andres, Tracy, Cynthia M., Upadhyay, Gaurav A., Varma, Niraj, Vernooy, Kevin, Vijayaraman, Pugazhendhi, Worsnick, Sarah Ann, Zareba, Wojciech, and Zeitler, Emily P.

Published
2023
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16. Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program

Author

Taliun, Daniel, Harris, Daniel N, Kessler, Michael D, Carlson, Jedidiah, Szpiech, Zachary A, Torres, Raul, Taliun, Sarah A Gagliano, Corvelo, André, Gogarten, Stephanie M, Kang, Hyun Min, Pitsillides, Achilleas N, LeFaive, Jonathon, Lee, Seung-been, Tian, Xiaowen, Browning, Brian L, Das, Sayantan, Emde, Anne-Katrin, Clarke, Wayne E, Loesch, Douglas P, Shetty, Amol C, Blackwell, Thomas W, Smith, Albert V, Wong, Quenna, Liu, Xiaoming, Conomos, Matthew P, Bobo, Dean M, Aguet, François, Albert, Christine, Alonso, Alvaro, Ardlie, Kristin G, Arking, Dan E, Aslibekyan, Stella, Auer, Paul L, Barnard, John, Barr, R Graham, Barwick, Lucas, Becker, Lewis C, Beer, Rebecca L, Benjamin, Emelia J, Bielak, Lawrence F, Blangero, John, Boehnke, Michael, Bowden, Donald W, Brody, Jennifer A, Burchard, Esteban G, Cade, Brian E, Casella, James F, Chalazan, Brandon, Chasman, Daniel I, Chen, Yii-Der Ida, Cho, Michael H, Choi, Seung Hoan, Chung, Mina K, Clish, Clary B, Correa, Adolfo, Curran, Joanne E, Custer, Brian, Darbar, Dawood, Daya, Michelle, de Andrade, Mariza, DeMeo, Dawn L, Dutcher, Susan K, Ellinor, Patrick T, Emery, Leslie S, Eng, Celeste, Fatkin, Diane, Fingerlin, Tasha, Forer, Lukas, Fornage, Myriam, Franceschini, Nora, Fuchsberger, Christian, Fullerton, Stephanie M, Germer, Soren, Gladwin, Mark T, Gottlieb, Daniel J, Guo, Xiuqing, Hall, Michael E, He, Jiang, Heard-Costa, Nancy L, Heckbert, Susan R, Irvin, Marguerite R, Johnsen, Jill M, Johnson, Andrew D, Kaplan, Robert, Kardia, Sharon LR, Kelly, Tanika, Kelly, Shannon, Kenny, Eimear E, Kiel, Douglas P, Klemmer, Robert, Konkle, Barbara A, Kooperberg, Charles, Köttgen, Anna, Lange, Leslie A, Lasky-Su, Jessica, Levy, Daniel, Lin, Xihong, Lin, Keng-Han, Liu, Chunyu, and Loos, Ruth JF

Subjects
Genetics, Biotechnology, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Generic health relevance, Good Health and Well Being, Cytochrome P-450 CYP2D6, Genetic Variation, Genome, Human, Genomics, Haplotypes, Heterozygote, Humans, INDEL Mutation, Loss of Function Mutation, Mutagenesis, National Heart, Lung, and Blood Institute (U.S.), Phenotype, Polymorphism, Single Nucleotide, Population Density, Precision Medicine, Quality Control, Sample Size, United States, Whole Genome Sequencing, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, General Science & Technology
Abstract

The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data. The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes)1. In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01%.

Published
2021

17. Mineral oil: safety and use as placebo in REDUCE-IT and other clinical studies

Author

Olshansky, Brian, Chung, Mina K, Budoff, Matthew J, Philip, Sephy, Jiao, Lixia, Doyle, Ralph T, Copland, Christina, Giaquinto, Alex, Juliano, Rebecca A, and Bhatt, Deepak L

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Trials and Supportive Activities, Atherosclerosis, Cardiovascular, Complementary and Integrative Health, Prevention, Patient Safety, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Mineral oil, Placebo, LDL-chotesterol, Triglycerides, C-reactive protein, HMG CoA statins, LDL-cholesterol, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

Mineral oil is often used as a clinical trial placebo. Pharmaceutical-grade mineral oil consists of a mixture of saturated hydrocarbons, with a purity and chemical structure that differs substantially from food-grade or technical-/industrial-grade mineral oils. Interest in mineral oil was piqued by suggestions that a portion of the substantially positive results of the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) might be attributable to the theoretical negative effects of mineral oil rather than being due to the clinical benefits of icosapent ethyl. The objective of this review was to explore possible mineral oil safety and efficacy effects and contextualize these findings in light of the REDUCE-IT conclusions. A literature search identified studies employing mineral oil placebos. Eighty studies were identified and relevant data extracted. Adverse events associated with mineral oil were generally gastrointestinal and consistent with use as a lubricant laxative. Changes in triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and other biomarkers were inconsistent and generally not statistically significant, or clinically meaningful with mineral oil, as were changes in blood pressure. There was no consistent evidence that mineral oil in the amounts used in the REDUCE-IT or Effect of Vascepa on Progression of Coronary Atherosclerosis in Patients With Elevated Triglycerides on Statin Therapy (EVAPORATE) trials affects absorption of essential nutrients or drugs, including statins. These results were then considered alongside publicly available data from REDUCE-IT. Based on available evidence, mineral oil does not appear to impact medication absorption or efficacy, or related clinical outcomes, and, therefore, does not meaningfully affect study conclusions when used as a placebo at the quantities used in clinical trials.

Published
2020

18. REDUCE-IT USA: Results from the 3,146 Patients Randomized in the United States

Author

Bhatt, Deepak L, Miller, Michael, Brinton, Eliot A, Jacobson, Terry A, Steg, Ph Gabriel, Ketchum, Steven B, Doyle, Ralph T, Juliano, Rebecca A, Jiao, Lixia, Granowitz, Craig, Tardif, Jean-Claude, Olshansky, Brian, Chung, Mina K, Gibson, C Michael, Giugliano, Robert P, Budoff, Matthew J, and Ballantyne, Christie M

Subjects
Biomedical and Clinical Sciences, Public Health, Health Sciences, Clinical Research, Cardiovascular, Clinical Trials and Supportive Activities, Heart Disease - Coronary Heart Disease, Atherosclerosis, Heart Disease, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Good Health and Well Being, Aged, Cholesterol, LDL, Double-Blind Method, Eicosapentaenoic Acid, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Male, Middle Aged, Myocardial Infarction, Risk Factors, Stroke, United States, eicosapentaenoic acid ethyl ester, fatty acids, omega-3, lipids, prevention and control, triglycerides, REDUCE-IT Investigators, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences, Sports science and exercise
Abstract

BackgroundSome trials have found that patients from the United States derive less benefit than patients enrolled outside the United States. This prespecified REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl - Intervention Trial) subgroup analysis was conducted to determine the degree of benefit of icosapent ethyl in the United States.MethodsREDUCE-IT randomized 8179 statin-treated patients with qualifying triglycerides ≥135 and 40 and ≤100 mg/dL and a history of atherosclerosis or diabetes mellitus to icosapent ethyl 4 g/d or placebo. The primary composite end point was cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary composite end point was cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. A hierarchy was prespecified for examination of individual and composite end points.ResultsA total of 3146 US patients (38.5% of the trial) were randomized and followed for a median of 4.9 years; 32.3% were women and 9.7% were Hispanic. The primary composite end point occurred in 24.7% of placebo-treated patients versus 18.2% of icosapent ethyl-treated patients (hazard ratio [HR], 0.69 [95% CI, 0.59-0.80]; P=0.000001); the key secondary composite end point occurred in 16.6% versus 12.1% (HR, 0.69 [95% CI, 0.57-0.83]; P=0.00008). All prespecified hierarchical end points were meaningfully and significantly reduced, including cardiovascular death (6.7% to 4.7%; HR, 0.66 [95% CI, 0.49-0.90]; P=0.007), myocardial infarction (8.8% to 6.7%; HR, 0.72 [95% CI, 0.56-0.93]; P=0.01), stroke (4.1% to 2.6%; HR, 0.63 [95% CI, 0.43-0.93]; P=0.02), and all-cause mortality (9.8% to 7.2%; HR, 0.70 [95% CI, 0.55-0.90]; P=0.004); for all-cause mortality in the US versus non-US patients, Pinteraction=0.02. Safety and tolerability findings were consistent with the full study cohort.ConclusionsWhereas the non-US subgroup showed significant reductions in the primary and key secondary end points, the US subgroup demonstrated particularly robust risk reductions across a variety of individual and composite end points, including all-cause mortality.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01492361.

Published
2020

25. Abstract 17865: Machine Learning With Multimodal Pre Ablation Imaging for Predicting Recurrence in Atrial Fibrillation Patients

Author

Midya, Abhishek, Asaeikheybari, Golnoush, Hiremath, Amogh, Viswanathan, Vidya Sankar, Sun, Han, Harwood, Samuel, Kim, Hyun Su, Schilling, Taylor, Telfer, William, Jin, Alison, Baraboo, Justin, Pradella, Maurice, Markl, Michael, Passman, Rod S, El-Harasis, Majd, Shoemaker, Ben B, Tandon, Animesh A, Barnard, John, Chung, Mina K, and Madabhushi, Anant

Published
2023
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28. Emerging role of artificial intelligence in cardiac electrophysiology

Author

Kabra, Rajesh, Israni, Sharat, Vijay, Bharat, Baru, Chaitanya, Mendu, Raghuveer, Fellman, Mark, Sridhar, Arun, Mason, Pamela, Cheung, Jim W., DiBiase, Luigi, Mahapatra, Srijoy, Kalifa, Jerome, Lubitz, Steven A., Noseworthy, Peter A., Navara, Rachita, McManus, David D., Cohen, Mitchell, Chung, Mina K., Trayanova, Natalia, Gopinathannair, Rakesh, and Lakkireddy, Dhanunjaya

Published
2022
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30. Opportunities and challenges in heart rhythm research: Rationale and development of an electrophysiology collaboratory

Author

Nguyen, Duy T., Bilchick, Kenneth C., Narayan, Sanjiv M., Chung, Mina K., Thomas, Kevin L., Laurita, Kenneth R., Vaseghi, Marmar, Sandhu, Roopinder, Chelu, Mihail G., Kannankeril, Prince J., Packer, Douglas L., McManus, David D., Verma, Atul, Singleton, Matthew, Tarakji, Khaldoun, Al-Khatib, Sana M., Kaltman, Jonathan R., Balijepalli, Ravi C., Van Hare, George F., Hurwitz, Jodie L., Russo, Andrea M., Kusumoto, Fred M., and Albert, Christine M.

Published
2022
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32. Racial and ethnic disparities in arrhythmia care: A call for action

Author

Thomas, Kevin L., Garg, Jalaj, Velagapudi, Poonam, Gopinathannair, Rakesh, Chung, Mina K., Kusumoto, Fred, Ajijola, Olujimi, Jackson, Larry R., II, Turagam, Mohit K., Joglar, Jose A., Sogade, Felix O., Fontaine, John M., Krahn, Andrew D., Russo, Andrea M., Albert, Christine, and Lakkireddy, Dhanunjaya R.

Published
2022
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34. Transcriptomic Insights into the Atrial Fibrillation Susceptibility Locus near the MYOZ1 and SYNPO2L Genes.

Author

Wass, Sojin Y., Sun, Han, Tchou, Gregory, Liu, Nana, Van Wagoner, David R., Chung, Mina K., Barnard, John, and Smith, Jonathan D.

Subjects
GENE expression, REPORTER genes, GENE transfection, LINKAGE disequilibrium, GENOME-wide association studies
Abstract

Genome-wide association studies have identified a locus on chromosome 10q22, where many co-inherited single nucleotide polymorphisms (SNPs) are associated with atrial fibrillation (AF). This study seeks to identify the impact of this locus on gene expression at the transcript isoform level in human left atria and to gain insight into potential causal variants. Bulk RNA sequencing was analyzed to identify myozenin 1 (MYOZ1) and synaptopodin 2-like (SYNPO2L) transcript isoforms and the association of common SNPs in this region with transcript isoform expression levels. Chromatin marks were used to suggest candidate regulatory SNPs in this region. Protein amino acid changes were examined for predicted functional consequences. Transfection of MYOZ1 and two SYNPO2L isoforms were performed to localize their encoded proteins in cardiomyocytes derived from stem cells. We identified one MYOZ1 transcript isoform and four SYNPO2L transcript isoforms, two of which encode proteins, while the other two encode long noncoding RNAs (lncRNAs). The risk allele of the strongest AF susceptibility SNP on chromosome 10q22 is associated with decreased MYOZ1 expression and increased expression of the two SNYPO2L lncRNA isoforms. There are many SNPs co-inherited with the top AF-associated SNP due to linkage disequilibrium (LD), including rs11000728, which we propose as the MYOZ1 regulatory SNP, confirmed by reporter gene transfection. In addition, this LD block includes three missense SNPs in the SYNPO2L gene, with the minor protective haplotype predicted to be detrimental to protein function. MYOZ1 and both protein isoforms of SYNPO2L were localized to the sarcomere. This is a complex locus with the potential for several SNPs in a haplotype to alter AF susceptibility by opposing effects on MYOZ1 and SYNPO2L lncRNA expression, along with effects on SYNPO2L protein function. [ABSTRACT FROM AUTHOR]

Published
2024
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35. Cardioneuroablation can be an effective strategy to treat glossopharyngeal neuralgia‐related sinus bradycardia and pauses.

Author

Liu, Nana, Prasad, Rohan, Iyer, Indiresha, Sheikh, Shehryar, Turka, Jashanjit, Dweik, Loai, Bain, Mark, Santangeli, Pasquale, and Chung, Mina K.

Subjects
BRADYCARDIA treatment, NECK pain treatment, NEURALGIA, ABLATION techniques, SYNCOPE, CARBAMAZEPINE, GLOSSOPHARYNGEAL nerve, CRANIAL nerve diseases, DISEASE complications
Abstract

Introduction: Cardioneuroablation (CNA) has proven effectiveness in addressing hypervagotonia symptoms, such as neurocardiogenic syncope. Methods and Results: In this case, we present the first‐time application of CNA in a case of vago‐glossopharyngeal neuralgia (VGPN). A 59‐year‐old female with near‐syncope, sinus bradycardia, and sinus pauses triggered by recurrent right‐sided neck pain was diagnosed with VGPN. The patient underwent successful treatment with carbamazepine and CNA. Subsequent follow‐up revealed the sustained absence of sinus bradycardia or pauses, even upon neck pain resurgence after discontinuing carbamazepine. Conclusion: In this patient, CNA successfully prevented pauses associated with VGPN, avoiding permanent pacemaker implantation. [ABSTRACT FROM AUTHOR]

Published
2024
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36. Genetic testing in early-onset atrial fibrillation.

Author

Kany, Shinwan, Jurgens, Sean J, Rämö, Joel T, Christophersen, Ingrid E, Rienstra, Michiel, Chung, Mina K, Olesen, Morten S, Ackerman, Michael J, McNally, Elizabeth M, Semsarian, Christopher, Schnabel, Renate B, Wilde, Arthur A M, Benjamin, Emelia J, Rehm, Heidi L, Kirchhof, Paulus, Bezzina, Connie R, Roden, Dan M, Shoemaker, M Benjamin, and Ellinor, Patrick T

Subjects
GENETIC testing, ATRIAL fibrillation, PATIENT education, MEDICAL screening, CARDIOMYOPATHIES
Abstract

Atrial fibrillation (AF) is a globally prevalent cardiac arrhythmia with significant genetic underpinnings, as highlighted by recent large-scale genetic studies. A prominent clinical and genetic overlap exists between AF, heritable ventricular cardiomyopathies, and arrhythmia syndromes, underlining the potential of AF as an early indicator of severe ventricular disease in younger individuals. Indeed, several recent studies have demonstrated meaningful yields of rare pathogenic variants among early-onset AF patients (∼4%–11%), most notably for cardiomyopathy genes in which rare variants are considered clinically actionable. Genetic testing thus presents a promising opportunity to identify monogenetic defects linked to AF and inherited cardiac conditions, such as cardiomyopathy, and may contribute to prognosis and management in early-onset AF patients. A first step towards recognizing this monogenic contribution was taken with the Class IIb recommendation for genetic testing in AF patients aged 45 years or younger by the 2023 American College of Cardiology/American Heart Association guidelines for AF. By identifying pathogenic genetic variants known to underlie inherited cardiomyopathies and arrhythmia syndromes, a personalized care pathway can be developed, encompassing more tailored screening, cascade testing, and potentially genotype-informed prognosis and preventive measures. However, this can only be ensured by frameworks that are developed and supported by all stakeholders. Ambiguity in test results such as variants of uncertain significance remain a major challenge and as many as ∼60% of people with early-onset AF might carry such variants. Patient education (including pretest counselling), training of genetic teams, selection of high-confidence genes, and careful reporting are strategies to mitigate this. Further challenges to implementation include financial barriers, insurability issues, workforce limitations, and the need for standardized definitions in a fast-moving field. Moreover, the prevailing genetic evidence largely rests on European descent populations, underscoring the need for diverse research cohorts and international collaboration. Embracing these challenges and the potential of genetic testing may improve AF care. However, further research—mechanistic, translational, and clinical—is urgently needed. [ABSTRACT FROM AUTHOR]

Published
2024
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37. Multi-ethnic genome-wide association study for atrial fibrillation

Author

Roselli, Carolina, Chaffin, Mark D, Weng, Lu-Chen, Aeschbacher, Stefanie, Ahlberg, Gustav, Albert, Christine M, Almgren, Peter, Alonso, Alvaro, Anderson, Christopher D, Aragam, Krishna G, Arking, Dan E, Barnard, John, Bartz, Traci M, Benjamin, Emelia J, Bihlmeyer, Nathan A, Bis, Joshua C, Bloom, Heather L, Boerwinkle, Eric, Bottinger, Erwin B, Brody, Jennifer A, Calkins, Hugh, Campbell, Archie, Cappola, Thomas P, Carlquist, John, Chasman, Daniel I, Chen, Lin Y, Chen, Yii-Der Ida, Choi, Eue-Keun, Choi, Seung Hoan, Christophersen, Ingrid E, Chung, Mina K, Cole, John W, Conen, David, Cook, James, Crijns, Harry J, Cutler, Michael J, Damrauer, Scott M, Daniels, Brian R, Darbar, Dawood, Delgado, Graciela, Denny, Joshua C, Dichgans, Martin, Dörr, Marcus, Dudink, Elton A, Dudley, Samuel C, Esa, Nada, Esko, Tonu, Eskola, Markku, Fatkin, Diane, Felix, Stephan B, Ford, Ian, Franco, Oscar H, Geelhoed, Bastiaan, Grewal, Raji P, Gudnason, Vilmundur, Guo, Xiuqing, Gupta, Namrata, Gustafsson, Stefan, Gutmann, Rebecca, Hamsten, Anders, Harris, Tamara B, Hayward, Caroline, Heckbert, Susan R, Hernesniemi, Jussi, Hocking, Lynne J, Hofman, Albert, Horimoto, Andrea RVR, Huang, Jie, Huang, Paul L, Huffman, Jennifer, Ingelsson, Erik, Ipek, Esra Gucuk, Ito, Kaoru, Jimenez-Conde, Jordi, Johnson, Renee, Jukema, J Wouter, Kääb, Stefan, Kähönen, Mika, Kamatani, Yoichiro, Kane, John P, Kastrati, Adnan, Kathiresan, Sekar, Katschnig-Winter, Petra, Kavousi, Maryam, Kessler, Thorsten, Kietselaer, Bas L, Kirchhof, Paulus, Kleber, Marcus E, Knight, Stacey, Krieger, Jose E, Kubo, Michiaki, Launer, Lenore J, Laurikka, Jari, Lehtimäki, Terho, Leineweber, Kirsten, Lemaitre, Rozenn N, Li, Man, Lim, Hong Euy, Lin, Henry J, and Lin, Honghuang

Subjects
Biological Sciences, Genetics, Heart Disease, Cardiovascular, Human Genome, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Atrial Fibrillation, Case-Control Studies, Ethnicity, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Quantitative Trait Loci, Transcriptome, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Atrial fibrillation (AF) affects more than 33 million individuals worldwide1 and has a complex heritability2. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.

Published
2018

38. Common Coding Variants in SCN10A Are Associated With the Nav1.8 Late Current and Cardiac Conduction

Author

Macri, Vincenzo, Brody, Jennifer A, Arking, Dan E, Hucker, William J, Yin, Xiaoyan, Lin, Honghuang, Mills, Robert W, Sinner, Moritz F, Lubitz, Steven A, Liu, Ching-Ti, Morrison, Alanna C, Alonso, Alvaro, Li, Ning, Fedorov, Vadim V, Janssen, Paul M, Bis, Joshua C, Heckbert, Susan R, Dolmatova, Elena V, Lumley, Thomas, Sitlani, Colleen M, Cupples, L Adrienne, Pulit, Sara L, Newton-Cheh, Christopher, Barnard, John, Smith, Jonathan D, Van Wagoner, David R, Chung, Mina K, Vlahakes, Gus J, O'Donnell, Christopher J, Rotter, Jerome I, Margulies, Kenneth B, Morley, Michael P, Cappola, Thomas P, Benjamin, Emelia J, Muzny, Donna, Gibbs, Richard A, Jackson, Rebecca D, Magnani, Jared W, Herndon, Caroline N, Rich, Stephen S, Psaty, Bruce M, Milan, David J, Boerwinkle, Eric, Mohler, Peter J, Sotoodehnia, Nona, and Ellinor, Patrick T

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Genetics, Heart Disease, Biotechnology, Cardiovascular, Aetiology, 2.1 Biological and endogenous factors, Biophysical Phenomena, Electrocardiography, Genetic Association Studies, Haplotypes, Heart Conduction System, Humans, Ion Channel Gating, Mutation, Missense, NAV1.8 Voltage-Gated Sodium Channel, Polymorphism, Single Nucleotide, Quantitative Trait Loci, atrial fibrillation, electrocardiography, haplotypes, Na plus channels, population genetics, Na+ channels, genetics, population, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BACKGROUND:Genetic variants at the SCN5A/SCN10A locus are strongly associated with electrocardiographic PR and QRS intervals. While SCN5A is the canonical cardiac sodium channel gene, the role of SCN10A in cardiac conduction is less well characterized. METHODS:We sequenced the SCN10A locus in 3699 European-ancestry individuals to identify variants associated with cardiac conduction, and replicated our findings in 21,000 individuals of European ancestry. We examined association with expression in human atrial tissue. We explored the biophysical effect of variation on channel function using cellular electrophysiology. RESULTS:We identified 2 intronic single nucleotide polymorphisms in high linkage disequilibrium (r  2=0.86) with each other to be the strongest signals for PR (rs10428132, β=-4.74, P=1.52×10-14) and QRS intervals (rs6599251, QRS β=-0.73; P=1.2×10-4), respectively. Although these variants were not associated with SCN5A or SCN10A expression in human atrial tissue (n=490), they were in high linkage disequilibrium (r  2≥0.72) with a common SCN10A missense variant, rs6795970 (V1073A). In total, we identified 7 missense variants, 4 of which (I962V, P1045T, V1073A, and L1092P) were associated with cardiac conduction. These 4 missense variants cluster in the cytoplasmic linker of the second and third domains of the SCN10A protein and together form 6 common haplotypes. Using cellular electrophysiology, we found that haplotypes associated with shorter PR intervals had a significantly larger percentage of late current compared with wild-type (I962V+V1073A+L1092P, 20.2±3.3%, P=0.03, and I962V+V1073A, 22.4±0.8%, P=0.0004 versus wild-type 11.7±1.6%), and the haplotype associated with the longest PR interval had a significantly smaller late current percentage (P1045T, 6.4±1.2%, P=0.03). CONCLUSIONS:Our findings suggest an association between genetic variation in SCN10A, the late sodium current, and alterations in cardiac conduction.

Published
2018

39. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Author

van Setten, Jessica, Brody, Jennifer A, Jamshidi, Yalda, Swenson, Brenton R, Butler, Anne M, Campbell, Harry, Del Greco, Fabiola M, Evans, Daniel S, Gibson, Quince, Gudbjartsson, Daniel F, Kerr, Kathleen F, Krijthe, Bouwe P, Lyytikäinen, Leo-Pekka, Müller, Christian, Müller-Nurasyid, Martina, Nolte, Ilja M, Padmanabhan, Sandosh, Ritchie, Marylyn D, Robino, Antonietta, Smith, Albert V, Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O, Asselbergs, Folkert W, Bader, Joel S, Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M, Chung, Mina K, Crawford, Dana, den Hoed, Marcel, Denny, Josh C, Dominiczak, Anna F, Ehret, Georg B, Eijgelsheim, Mark, Ellinor, Patrick T, Felix, Stephan B, Franco, Oscar H, Franke, Lude, Harris, Tamara B, Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kähönen, Mika, Kolcic, Ivana, Kors, Jan A, Lakatta, Edward G, Launer, Lenore J, Lin, Honghuang, Lin, Henry J, Loos, Ruth JF, Lubitz, Steven A, Macfarlane, Peter W, Magnani, Jared W, Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D, Munzel, Thomas, Papanicolaou, George J, Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P, Raitakari, Olli T, Rotter, Jerome I, Rudan, Igor, Samani, Nilesh J, Schlessinger, David, Silva Aldana, Claudia T, Sinner, Moritz F, Smith, Jonathan D, Snieder, Harold, Soliman, Elsayed Z, Spector, Timothy D, Stott, David J, Strauch, Konstantin, Tarasov, Kirill V, Thorsteinsdottir, Unnur, Uitterlinden, Andre G, Van Wagoner, David R, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Jan Westra, Harm, Wild, Philipp S, Zeller, Tanja, Alonso, Alvaro, Avery, Christy L, Bandinelli, Stefania, Benjamin, Emelia J, Cucca, Francesco, Dörr, Marcus, and Ferrucci, Luigi

Subjects
Biological Sciences, Genetics, Human Genome, Heart Disease, Biotechnology, Cardiovascular, Aetiology, 2.1 Biological and endogenous factors, Atrial Function, Atrioventricular Node, Electrocardiography, Electrophysiological Phenomena, Female, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Mutation, Missense, Risk Factors
Abstract

Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.

Published
2018

44. Contributors

Author

Alomar, Mohammed, primary, Amarh, Enoch, additional, Baranchuk, Adrian, additional, Beach, Scott, additional, Boutjdir, Mohamed, additional, Campbell, Kristen Bova, additional, Capecchi, Pier Leopoldo, additional, Chandrasekhar, Sanjay, additional, Chung, Mina K., additional, Curtis, Michael J., additional, Fradley, Michael G., additional, Funk, Margo, additional, Haigney, Mark C.P., additional, Hancox, Jules C., additional, Kovacs, Richard J., additional, Krahn, Andrew D., additional, Krantz, Mori J., additional, Laghi-Pasini, Franco, additional, Laksman, Zachary W.M., additional, Lazzerini, Pietro Enea, additional, Overholser, Brian R., additional, Roberts, Jason D., additional, Roston, Thomas M., additional, Sowinski, Kevin M., additional, Tisdale, James E., additional, Wass, Sojin Youn, additional, Wilde, Arthur AM, additional, Woosley, Raymond L., additional, and Yeung, Cynthia, additional

Published
2022
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45. Atrial fibrillation future clinic. Novel platform to integrate smart device electrocardiogram into clinical practice

Author

Lambert, Cameron T., Patel, Divyang, Bumgarner, Joseph M., Kanj, Mohamed, Cantillon, Daniel, Saliba, Walid, Hussein, Ayman, Baranowski, Bryan, Dresing, Thomas, Chung, Mina K., Rickard, John, Varma, Niraj, Callahan, Thomas, Martin, David, Tchou, Patrick, Bhargava, Mandeep, Wolski, Kathy, Wazni, Oussama, and Tarakji, Khaldoun G.

Published
2021
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46. Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation: The AFGen Consortium

Author

Weng, Lu-Chen, Lunetta, Kathryn L, Müller-Nurasyid, Martina, Smith, Albert Vernon, Thériault, Sébastien, Weeke, Peter E, Barnard, John, Bis, Joshua C, Lyytikäinen, Leo-Pekka, Kleber, Marcus E, Martinsson, Andreas, Lin, Henry J, Rienstra, Michiel, Trompet, Stella, Krijthe, Bouwe P, Dörr, Marcus, Klarin, Derek, Chasman, Daniel I, Sinner, Moritz F, Waldenberger, Melanie, Launer, Lenore J, Harris, Tamara B, Soliman, Elsayed Z, Alonso, Alvaro, Paré, Guillaume, Teixeira, Pedro L, Denny, Joshua C, Shoemaker, M Benjamin, Van Wagoner, David R, Smith, Jonathan D, Psaty, Bruce M, Sotoodehnia, Nona, Taylor, Kent D, Kähönen, Mika, Nikus, Kjell, Delgado, Graciela E, Melander, Olle, Engström, Gunnar, Yao, Jie, Guo, Xiuqing, Christophersen, Ingrid E, Ellinor, Patrick T, Geelhoed, Bastiaan, Verweij, Niek, Macfarlane, Peter, Ford, Ian, Heeringa, Jan, Franco, Oscar H, Uitterlinden, André G, Völker, Uwe, Teumer, Alexander, Rose, Lynda M, Kääb, Stefan, Gudnason, Vilmundur, Arking, Dan E, Conen, David, Roden, Dan M, Chung, Mina K, Heckbert, Susan R, Benjamin, Emelia J, Lehtimäki, Terho, März, Winfried, Smith, J Gustav, Rotter, Jerome I, van der Harst, Pim, Jukema, J Wouter, Stricker, Bruno H, Felix, Stephan B, Albert, Christine M, and Lubitz, Steven A

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Heart Disease, Cardiovascular, Prevention, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Age Factors, Aged, Atrial Fibrillation, Body Mass Index, Chromosomes, Human, Pair 4, Epistasis, Genetic, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Hypertension, Male, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide, Reproducibility of Results, Risk Factors, Sex Characteristics
Abstract

It is unclear whether genetic markers interact with risk factors to influence atrial fibrillation (AF) risk. We performed genome-wide interaction analyses between genetic variants and age, sex, hypertension, and body mass index in the AFGen Consortium. Study-specific results were combined using meta-analysis (88,383 individuals of European descent, including 7,292 with AF). Variants with nominal interaction associations in the discovery analysis were tested for association in four independent studies (131,441 individuals, including 5,722 with AF). In the discovery analysis, the AF risk associated with the minor rs6817105 allele (at the PITX2 locus) was greater among subjects ≤ 65 years of age than among those > 65 years (interaction p-value = 4.0 × 10-5). The interaction p-value exceeded genome-wide significance in combined discovery and replication analyses (interaction p-value = 1.7 × 10-8). We observed one genome-wide significant interaction with body mass index and several suggestive interactions with age, sex, and body mass index in the discovery analysis. However, none was replicated in the independent sample. Our findings suggest that the pathogenesis of AF may differ according to age in individuals of European descent, but we did not observe evidence of statistically significant genetic interactions with sex, body mass index, or hypertension on AF risk.

Published
2017

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