Daniel Kim

All Publications

• One-year real-world experience with mavacamten and its physiologic effects on obstructive hypertrophic cardiomyopathy FRONTIERS IN CARDIOVASCULAR MEDICINE Kim, D., Chu, E. L., Keamy-Minor, E. E., Paranjpe, I., Tang, W. L., O'Sullivan, J. W., Desai, Y. B., Liu, M. B., Munsey, E., Hecker, K., Cuenco, I., Kao, B., Bacolor, E., Bonnett, C., Linder, A., Lacar, K., Robles, N., Lamendola, C., Smith, A., Knowles, J. W., Perez, M. V., Kawana, M., Sallam, K. I., Weldy, C. S., Wheeler, M. T., Parikh, V. N., Salisbury, H., Ashley, E. A., Stanford Ctr Inherited Cardiovasc Dis 2024; 11

  View details for DOI 10.3389/fcvm.2024.1429230

  View details for Web of Science ID 001312496500001

• One-year real-world experience with mavacamten and its physiologic effects on obstructive hypertrophic cardiomyopathy. Frontiers in cardiovascular medicine Kim, D. S., Chu, E. L., Keamy-Minor, E. E., Paranjpe, I. D., Tang, W. L., O'Sullivan, J. W., Desai, Y. B., Liu, M. B., Munsey, E., Hecker, K., Cuenco, I., Kao, B., Bacolor, E., Bonnett, C., Linder, A., Lacar, K., Robles, N., Lamendola, C., Smith, A., Knowles, J. W., Perez, M. V., Kawana, M., Sallam, K. I., Weldy, C. S., Wheeler, M. T., Parikh, V. N., Salisbury, H., Ashley, E. A. 2024; 11: 1429230

  Abstract

  Mavacamten is a first-in-class cardiac myosin ATPase inhibitor, approved by the United States Food and Drug Administration for the treatment of hypertrophic cardiomyopathy with obstructive physiology (oHCM). Here, we present the real-world use of mavacamten in 50 patients with oHCM at a tertiary care referral center. In both our highlighted case and in our aggregate data, we report significant improvement in wall thickness, mitral regurgitation, left ventricular outflow tract obstruction and New York Heart Association symptom class. Moreover, in our center's experience, neither arrhythmia burden, nor contractility have worsened in the vast majority of patients: we note a clinically insignificant mean decrease in left ventricular ejection fraction (LVEF), with only two patients requiring temporary mavacamten discontinuance for LVEF < 50%. Adverse events were rare, unrelated to mavacamten itself, and seen solely in patients with disease too advanced to have been represented in clinical trials. Moreover, our multidisciplinary pathway enabled us to provide a large number of patients with a novel closely-monitored therapeutic within just a few months of commercial availability. These data lead us to conclude that mavacamten, as a first-in-class cardiac myosin inhibitor, is safe and efficacious in real-world settings.

  View details for DOI 10.3389/fcvm.2024.1429230

  View details for PubMedID 39314763

  View details for PubMedCentralID PMC11417615

• Classification of Premature Ventricular Contractions in Athletes During Routine Preparticipation Exams. Circulation. Arrhythmia and electrophysiology Gomez, S. E., Perez, M. V., Wheeler, M. T., Hadley, D., Hwang, C. E., Kussman, A., Kim, D. S., Froelicher, V. 2024: e012835

  Abstract

  Large-scale data on incidental premature ventricular contraction (PVC) prevalence and morphologies have been lacking, leaving many providers without guidance on further cardiac testing for patients with incidental PVCs on ECG. Athletes offer an intriguing cohort to understand the clinical significance, prevalence, and common morphologies of incidental PVCs because they often undergo ECG screening during preparticipation exams.Digital ECGs were obtained from 10 728 screened athletes aged 14 to 35 years during mass screenings in schools and professional sports teams between 2014 and 2021. A retrospective analysis of ECGs with PVCs was performed using the simultaneous display of frontal (limb) and horizontal (precordial) plane leads. PVCs were coded for morphology and categorized as benign or nonbenign using recommended criteria.Twenty-six athletes (0.24%) were found to have at least 1 PVC. Among these, 50% were female, 65% were White, 8% were Asian, 4% were Hispanic, and 23% were Black. Nineteen of the 26 (73%) ECGs had PVCs with a left bundle branch block pattern compared with 7 (27%) with a right bundle branch block pattern. Twenty-four ECGs (96%) had PVCs with benign patterns, including 18 with right ventricular outflow tract, 5 with left anterior fascicle, and 2 with left posterior fascicle morphology.There is a low prevalence of PVCs on routine ECG screening of young athletes, and most PVCs are of benign morphology in this population. This study highlights the value of using digital ECG recorders with simultaneous lead display to guide decision-making about further cardiac testing and referrals in young athletes with PVCs. Using our results and review of the literature, we propose methods and algorithms of PVC evaluation on screening ECGs to help guide many providers with risk stratification and decision-making about further cardiac testing and electrophysiology referrals in young athletes with PVCs.

  View details for DOI 10.1161/CIRCEP.124.012835

  View details for PubMedID 39193774

• Personalized digital behaviour interventions increase short-term physical activity: a randomized control crossover trial substudy of the MyHeart Counts Cardiovascular Health Study. European heart journal. Digital health Javed, A., Kim, D. S., Hershman, S. G., Shcherbina, A., Johnson, A., Tolas, A., O'Sullivan, J. W., McConnell, M. V., Lazzeroni, L., King, A. C., Christle, J. W., Oppezzo, M., Mattsson, C. M., Harrington, R. A., Wheeler, M. T., Ashley, E. A. 2023; 4 (5): 411-419

  Abstract

  Physical activity is associated with decreased incidence of the chronic diseases associated with aging. We previously demonstrated that digital interventions delivered through a smartphone app can increase short-term physical activity.We offered enrolment to community-living iPhone-using adults aged ≥18 years in the USA, UK, and Hong Kong who downloaded the MyHeart Counts app. After completion of a 1-week baseline period, e-consented participants were randomized to four 7-day interventions. Interventions consisted of: (i) daily personalized e-coaching based on the individual's baseline activity patterns, (ii) daily prompts to complete 10 000 steps, (iii) hourly prompts to stand following inactivity, and (iv) daily instructions to read guidelines from the American Heart Association (AHA) website. After completion of one 7-day intervention, participants subsequently randomized to the next intervention of the crossover trial. The trial was completed in a free-living setting, where neither the participants nor investigators were blinded to the intervention. The primary outcome was change in mean daily step count from baseline for each of the four interventions, assessed in a modified intention-to-treat analysis (modified in that participants had to complete 7 days of baseline monitoring and at least 1 day of an intervention to be included in analyses). This trial is registered with ClinicalTrials.gov, NCT03090321.Between 1 January 2017 and 1 April 2022, 4500 participants consented to enrol in the trial (a subset of the approximately 50 000 participants in the larger MyHeart Counts study), of whom 2458 completed 7 days of baseline monitoring (mean daily steps 4232 ± 73) and at least 1 day of one of the four interventions. Personalized e-coaching prompts, tailored to an individual based on their baseline activity, increased step count significantly (+402 ± 71 steps from baseline, P = 7.1⨯10-8). Hourly stand prompts (+292 steps from baseline, P = 0.00029) and a daily prompt to read AHA guidelines (+215 steps from baseline, P = 0.021) were significantly associated with increased mean daily step count, while a daily reminder to complete 10 000 steps was not (+170 steps from baseline, P = 0.11). Digital studies have a significant advantage over traditional clinical trials in that they can continuously recruit participants in a cost-effective manner, allowing for new insights provided by increased statistical power and refinement of prior signals. Here, we present a novel finding that digital interventions tailored to an individual are effective in increasing short-term physical activity in a free-living cohort. These data suggest that participants are more likely to react positively and increase their physical activity when prompts are personalized. Further studies are needed to determine the effects of digital interventions on long-term outcomes.

  View details for DOI 10.1093/ehjdh/ztad047

  View details for PubMedID 37794870

  View details for PubMedCentralID PMC10545510

• Premature ventricular contractions (PVCs) in young athletes. Progress in cardiovascular diseases Gomez, S. E., Hwang, C. E., Kim, D. S., Froelicher, V. F., Wheeler, M. T., Perez, M. V. 2022

  Abstract

  There is a growing body of literature focusing on the morphology, management, and outcomes of PVCs in athletes. This review summarizes this literature and establishes recommendations on management, treatment, and indications for specialist referral in this patient population. The sports medicine physician's responses and recommendation should be made in conjunction with the athletes wishes. Medications or ablations are not always necessary in all athletes if they are followed with regular evaluations.

  View details for DOI 10.1016/j.pcad.2022.10.011

  View details for PubMedID 36309100

• Mind the Gap: The Complete Human Genome Unlocks Benefits for Clinical Genomics. Clinical chemistry Kim, D. S., Wiel, L., Ashley, E. A. 2022

  View details for DOI 10.1093/clinchem/hvac133

  View details for PubMedID 36112529

• Lipoprotein(a) and Incident Atrial Fibrillation: Leveraging Nature's Randomization to Identify Novel Causal Associations. Journal of the American College of Cardiology Kim, D. S., Khandelwal, A. 2022; 79 (16): 1591-1593

  View details for DOI 10.1016/j.jacc.2022.02.026

  View details for PubMedID 35450576

• The genetics of human performance. Nature reviews. Genetics Kim, D. S., Wheeler, M. T., Ashley, E. A. 2021

  Abstract

  Human physiology is likely to have been selected for endurance physical activity. However, modern humans have become largely sedentary, with physical activity becoming a leisure-time pursuit for most. Whereas inactivity is a strong risk factor for disease, regular physical activity reduces the risk of chronic disease and mortality. Although substantial epidemiological evidence supports the beneficial effects of exercise, comparatively little is known about the molecular mechanisms through which these effects operate. Genetic and genomic analyses have identified genetic variation associated with human performance and, together with recent proteomic, metabolomic and multi-omic analyses, are beginning to elucidate the molecular genetic mechanisms underlying the beneficial effects of physical activity on human health.

  View details for DOI 10.1038/s41576-021-00400-5

  View details for PubMedID 34522035

• Genetics of Type 2 Diabetes: Opportunities for Precision Medicine: JACC Focus Seminar. Journal of the American College of Cardiology Kim, D. S., Gloyn, A. L., Knowles, J. W. 2021; 78 (5): 496-512

  Abstract

  Type 2 diabetes (T2D) is highly prevalent and is a strong contributor for cardiovascular disease. However, there is significant heterogeneity in disease pathogenesis and the risk of complications. Enormous progress has been made in our ability to catalog genetic variation associated with T2D risk and variation in disease-relevant quantitative traits. These discoveries hold the potential to shed light on tractable targets and pathways for safe and effective therapeutic development, but the promise of precision medicine has been slow to be realized. Recent studies have identified subgroups of individuals with differential risk for intermediate phenotypes (eg, lipid levels, fasting insulin, body mass index) that contribute to T2D risk, helping to account for the observed clinical heterogeneity. These "partitioned genetic risk scores" not only have the potential to identify patients at greatest risk of cardiovascular disease and rapid disease progression, but also could aid patient stratification bridging the gap toward precision medicine for T2D.

  View details for DOI 10.1016/j.jacc.2021.03.346

  View details for PubMedID 34325839

• Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci. American journal of human genetics Tragante, V., Barnes, M. R., Ganesh, S. K., Lanktree, M. B., Guo, W., Franceschini, N., Smith, E. N., Johnson, T., Holmes, M. V., Padmanabhan, S., Karczewski, K. J., Almoguera, B., Barnard, J., Baumert, J., Chang, Y. C., Elbers, C. C., Farrall, M., Fischer, M. E., Gaunt, T. R., Gho, J. M., Gieger, C., Goel, A., Gong, Y., Isaacs, A., Kleber, M. E., Mateo Leach, I., McDonough, C. W., Meijs, M. F., Melander, O., Nelson, C. P., Nolte, I. M., Pankratz, N., Price, T. S., Shaffer, J., Shah, S., Tomaszewski, M., van der Most, P. J., van Iperen, E. P., Vonk, J. M., Witkowska, K., Wong, C. O., Zhang, L., Beitelshees, A. L., Berenson, G. S., Bhatt, D. L., Brown, M., Burt, A., Cooper-DeHoff, R. M., Connell, J. M., Cruickshanks, K. J., Curtis, S. P., Davey-Smith, G., Delles, C., Gansevoort, R. T., Guo, X., Haiqing, S., Hastie, C. E., Hofker, M. H., Hovingh, G. K., Kim, D. S., Kirkland, S. A., Klein, B. E., Klein, R., Li, Y. R., Maiwald, S., Newton-Cheh, C., O'Brien, E. T., Onland-Moret, N. C., Palmas, W., Parsa, A., Penninx, B. W., Pettinger, M., Vasan, R. S., Ranchalis, J. E., M Ridker, P., Rose, L. M., Sever, P., Shimbo, D., Steele, L., Stolk, R. P., Thorand, B., Trip, M. D., van Duijn, C. M., Verschuren, W. M., Wijmenga, C., Wyatt, S., Young, J. H., Zwinderman, A. H., Bezzina, C. R., Boerwinkle, E., Casas, J. P., Caulfield, M. J., Chakravarti, A., Chasman, D. I., Davidson, K. W., Doevendans, P. A., Dominiczak, A. F., FitzGerald, G. A., Gums, J. G., Fornage, M., Hakonarson, H., Halder, I., Hillege, H. L., Illig, T., Jarvik, G. P., Johnson, J. A., Kastelein, J. J., Koenig, W., Kumari, M., März, W., Murray, S. S., O'Connell, J. R., Oldehinkel, A. J., Pankow, J. S., Rader, D. J., Redline, S., Reilly, M. P., Schadt, E. E., Kottke-Marchant, K., Snieder, H., Snyder, M., Stanton, A. V., Tobin, M. D., Uitterlinden, A. G., van der Harst, P., van der Schouw, Y. T., Samani, N. J., Watkins, H., Johnson, A. D., Reiner, A. P., Zhu, X., de Bakker, P. I., Levy, D., Asselbergs, F. W., Munroe, P. B., Keating, B. J. 2014; 94 (3): 349-360

  Abstract

  Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ~50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.

  View details for DOI 10.1016/j.ajhg.2013.12.016

  View details for PubMedID 24560520