Vikki Alex Krysov

All Publications

• RBM20 Truncating Variants and Human Cardiomyopathy. JAMA cardiology Floyd, B. J., Njoroge, J. N., Krysov, V. A., Gomes, B., Murtha, R., Aribeana, C., Cannie, D., Smith, E., Paldino, A., Brown, E. E., Barth, A., Ilhan, E., Johnson, R., Wojciak, J., Alkhayat, M., Graw, S., Medo, K., Haas, J., Chahal, C. A., Fenzl, K., Steinmetz, L., Gollob, M., Ashley, E., Day, S., Judge, D., Roberts, J. D., Vedantham, V., Mao, C. Y., Fatkin, D., Lakdawala, N. K., Taylor, M. R., Mestroni, L., Saguner, A. M., Tayal, U., Cadrin-Tourigny, J., Krahn, A. D., James, C., Dal Ferro, M., Sinagra, G., Merlo, M., Owens, A., Reza, N., Saberi, S., Helms, A., Elliott, P., Meder, B., Lancaster, M., Parikh, V. N. 2026

  Abstract

  Importance: Genetic diagnosis has become increasingly important to guide clinical decision-making for patients with dilated cardiomyopathy (DCM). Pathogenic or likely pathogenic (P/LP) missense variants in the gene RBM20 cause a highly penetrant arrhythmogenic DCM, but the role of RBM20 truncating variants (RBM20tvs) is unclear.Objective: To assess the contribution of RBM20 variants to arrhythmogenic DCM.Design, Setting, and Participants: In this cohort study, participants in the genome-first UK Biobank (UKB) and All of Us populations were evaluated to assess the etiologic fraction, natural history and penetrance of RBM20 variants. Retrospective data were collected from an international cohort of patients with DCM and RBM20 variants identified at centers of excellence for genetic heart disease and compared based on time to event. Study dates are not disclosed because the institutional review board did not authorize the sharing of this information.Exposures: RBM20 variants were compared to known P/LP variants and variants of uncertain significance in RBM20 as well as titin truncating variants (TTNtvs).Main Outcomes and Measures: Major ventricular arrhythmias, end-stage heart failure, and heart failure hospitalization as measured by medical record review (retrospective cohort) and diagnostic codes (UKB).Results: Two main cohorts were studied for this project. In UK Biobank, a cohort of participants with RBM20tvs, RBM20 synonymous variants, and TTNtvs was studied. Of these 4249 participants, 1869 (44%) were male. The mean (SD) age at enrollment was 56 (8.2) years. In the RBM20 registry, of 179 patients, 105 (58.6%) were male, and the mean (SD) age at enrollment was 43.8 (19.1) years. A validation cohort from the All of Us biobank was also used. This consisted of 7002 participants, 4342 of whom (62.0%) were male, and the mean (SD) age was 52.7 (16.7) years. The etiologic fraction of RBM20 variants in arrhythmogenic DCM was 0.53 (95% CI, 0.32-0.67; P<.001). In genome-first biobanks, lifetime incidence of cardiomyopathy, heart failure, or major ventricular arrhythmia diagnosis was lower in participants with RBM20 variants than in those with TTNtvs (hazard ratio, 0.55; 95% CI, 0.36-0.84; P<.001). Patients with RBM20tvs and DCM presented to referral centers later in life than those with P/LP RBM20 and DCM (mean [SD], 53 [10] vs 34 [18] years; P<.001) and were less likely to have a family history of sudden cardiac arrest (2 of 10 [20%] vs 11 of 17 [65%]; P=.046) or cardiomyopathy (2 of 10 [20%] vs 14 of 18 [78%]; P<.001). There was no significant difference in age- and sex-adjusted incident major heart failure or arrhythmia events between patients with RBM20tv and DCM or those with P/LP RBM20 and DCM, though sex-adjusted lifetime hazard was reduced in those with RBM20tv and DCM (hazard ratio, 0.13; 95% CI, 0.03-0.56; P=.01).Conclusions and Relevance: This study found that RBM20 variants contributed to arrhythmogenic DCM phenotypes but conferred reduced lifetime disease penetrance compared to TTNtvs and milder disease severity alone than P/LP RBM20 variants. Their potential for additive interactions with other damaging variants should be considered in patients with DCM and their families.

  View details for DOI 10.1001/jamacardio.2026.0401

  View details for PubMedID 41949880

• Truncating Variants in TTN are Associated With Primary Atrial Myopathy. Journal of the American Heart Association de Castro, D., Fatkin, D., Rodriguez-Rubio, E., Haddad, F., Hernández-Terciado, F., Purohit, A., Bagherzadeh, S. P., Nair, P., Rad, A., Krysov, V. A., Parikh, V. N., García-Pavia, P., Lakdawala, N. K. 2026: eJAHA2025047740T

  Abstract

  Truncating TTN variants (TTNtv) are the main genetic cause of dilated cardiomyopathy (DCM) and are independently associated with atrial fibrillation (AF). In DCM, AF usually arises from left atrial (LA) remodeling attributable to left ventricular systolic dysfunction. Whether TTNtv are linked to primary LA dysfunction independent of left ventricular systolic dysfunction remains unclear.This retrospective, multicenter study evaluated atrial function by strain echocardiography in TTNtv carriers across the left ventricular ejection fraction (LVEF) spectrum and its relationship with AF. Individuals with TTNtv and LVEF ≥50% (TTNtv+/DCM-) were compared with matched healthy controls, and those with LVEF <50% (TTNtv+/DCM+) were compared with matched patients with idiopathic, variant-negative DCM (iDCM).Among 460 participants, 153 carried a TTNtv (87 with LVEF ≥50%, 66 with LVEF <50%). All LA strain parameters were significantly lower in TTNtv+/DCM- than in controls (P<0.001). In TTNtv+/DCM+, only LA contractile strain was reduced compared with iDCM (P<0.001). LA contractile strain correlated with LVEF only when LVEF was <50% (TTNtv+/DCM+, r=0.50, P<0.001; iDCM, r=0.47, P<0.001). In TTNtv+/DCM-, all LA strain parameters except contractile strain correlated with LV strain. AF incidence was higher in TTNtv+/DCM+ (3.15/100 person-years) than in TTNtv+/DCM- (1.48) and iDCM (2.27), though cumulative incidence was not significantly different (P=0.200).LA myopathy, detected by strain imaging, appears early in TTNtv+/DCM- individuals and may represent an early phenotypic marker independent of left ventricular systolic dysfunction. When LVEF declines below 50%, atrial dysfunction worsens in parallel. AF was more frequent in TTNtv carriers, supporting further research on LA strain for AF risk stratification within this population.

  View details for DOI 10.1161/JAHA.125.047740

  View details for PubMedID 41804889

• Prognostic Role of Myocarditis-Like Episodes and Their Treatment in Patients With Pathogenic Desmoplakin Variants. Circulation Gasperetti, A., Muller, S. A., Peretto, G., Asatryan, B., Protonotarios, A., Laredo, M., Tarlet, P. Y., Syrris, P., Carrick, R. T., Murray, B., Tichnell, C., Scheel, P., Gigli, M., Yap, S. C., Pilichou, K., Basso, C., Medo, K., Jason, M., Rossi, V. A., Saguner, A. M., Duru, F., Abrams, D., Cadrin-Tourigny, J., Targetti, M., Pieroni, M., Graziosi, M., Biagini, E., Charron, P., Cox, M., Casella, M., Tondo, C., Ware, J. S., Prasad, S. K., Calò, L., Smith, E., Ingles, J., Tandri, H., Ader, F., Peters, S., Zentner, D., Russo, J., Ravaro, S., Crotti, L., Dittmann, S., Shulze-Bahr, E., Carruth, E. D., Krysov, V. A., Parikh, V. N., Conte, G., Wilde, A., van Tintelen, J. P., Te Riele, A. S., Sinagra, G., Mestroni, L., Taylor, M., Merlo, M., Adamo, L., Calkins, H., Bauce, B., Arbelo, E., Elliott, P. M., Gandjbakhch, E., Lakdawala, N., Helms, A., James, C. A., Gilotra, N. A. 2025

  Abstract

  Inflammatory, myocarditis-like episodes precede and are associated with higher risk of sustained ventricular arrhythmias and heart failure in patients with pathogenic or likely pathogenic desmoplakin (DSP) variants. Whether the recurrence and treatment of myocarditis-like episodes influence the outcomes in this population is unknown. This study aimed to assess the prognostic impact of the recurrence and treatment of myocarditis-like episodes in patients with pathogenic or likely pathogenic DSP variants.The study was designed as an observational cohort study using all patients with pathogenic or likely pathogenic DSP variants in the DSP-ERADOS Network (Desmopakin Specific Effort for a Rare Disease Outcome Study) enrolled at 31 institutions up until April 30, 2024. Survival from ventricular arrhythmia and heart failure end points and recurrent myocarditis-like episodes was evaluated for both first and recurrent documented myocarditis-like episodes and the impact of immunosuppressive treatment on outcomes assessed.A total of 1014 patients with pathogenic or likely pathogenic DSP variants (62.4% female; mean age, 40.4±17.4 years; 47.1% probands) were included. Among them, 177 individuals (17.5%) experienced ≥1 documented myocarditis-like episode, with 63 of them (35.6%) receiving immunosuppressive treatment. Immunosuppressive treatment of the first documented myocarditis-like episode was associated with reduced risk of ventricular arrhythmia and heart failure outcomes (hazard ratio, 0.18 [95% CI, 0.07-0.45]; P<0.001; and hazard ratio, 0.09 [95% CI, 0.02-0.39; P=0.001, respectively) over a median follow-up of 6.4 years (95% CI, 4.0-10.5). This risk was comparable to that of patients with no history of myocarditis-like episode but did not correlate with a reduction in recurrent episodes after completion of initial immunosuppression (hazard ratio, 0.85 [95% CI, 0.47-1.54]; P=0.599). In contrast, nonsteroidal anti-inflammatory drugs or colchicine treatment did not influence outcomes.Immunosuppressive treatment of myocarditis-like episodes in DSP patients was associated with improved combined ventricular arrhythmia or heart failure outcomes, supporting future prospective evaluation in DSP cohorts.

  View details for DOI 10.1161/CIRCULATIONAHA.125.073919

  View details for PubMedID 40832715

• Overcoming Hesitancy and Barriers to Care with Integration of Telemedicine in a Free Student-run Health Clinic. Journal of primary care & community health Krysov, V. A., Balshin, M. E., Azar, E. N., Cernioglo, K., Perekopskiy, D., Nurpeissova, A. T., Shi, L. Z. 2025; 16: 21501319251316338

  Abstract

  Nadezhda Clinic is a free student-run health clinic that provides culturally sensitive primary care services to the underserved Russian-speaking population of the greater Sacramento area. At the onset of the COVID-19 pandemic, the clinic suspended in-person services and solely offered telemedicine visits. Most patients were hesitant to utilize telemedicine due to poor technological literacy, privacy concerns, and a preference for in-person care.This quality improvement project aimed to evaluate whether the implementation of culturally sensitive telemedicine services and outreach strategies would help address patient hesitancy and barriers to care.Successful implementation of telemedicine was dependent on building trust with the community, providing multilingual technological assistance, and offering personalized support. Some measures that were reviewed in order to assess this included comparison of patient demographics, clinic attendance, and distance reached between in-person and telemedicine services.Telemedicine implementation was associated with increased clinic attendance rates with a no-show rate as low as 13% when compared to in-person services with a no-show rate of 20%. Telehealth services also enabled the clinic to reach patients in rural areas up to 120 miles away.With the implementation of a culturally sensitive telemedicine protocol, Nadezhda Clinic achieved greater patient retention rates and reached patients at further distances, suggesting an overall reduction in hesitancy and barriers to care. Free clinics offering telemedicine are critical to further address healthcare disparities in marginalized communities.

  View details for DOI 10.1177/21501319251316338

  View details for PubMedID 39883478

  View details for PubMedCentralID PMC11783495

• Regional Variation in Cardiovascular Genes Enables a Tractable Genome Editing Strategy. Circulation. Genomic and precision medicine Krysov, V. A., Wilson, R. H., Ten, N. S., Youlton, N., De Jong, H. N., Sutton, S., Huang, Y., Reuter, C. M., Grove, M. E., Wheeler, M. T., Ashley, E. A., Parikh, V. N. 2024: e004370

  Abstract

  To realize the potential of genome engineering therapeutics, tractable strategies must be identified that balance personalized therapy with the need for off-the-shelf availability. We hypothesized that regional clustering of pathogenic variants can inform the design of rational prime editing therapeutics to treat the majority of genetic cardiovascular diseases with a limited number of reagents.We collated 2435 high-confidence pathogenic/likely pathogenic (P/LP) variants in 82 cardiovascular disease genes from ClinVar. We assessed the regional density of these variants by defining a regional clustering index. We then combined a highly active base editor with prime editing to demonstrate the feasibility of a P/LP hotspot-directed genome engineering therapeutic strategy in vitro.P/LP variants in cardiovascular disease genes display higher regional density than rare variants found in the general population. P/LP missense variants displayed higher average regional density than P/LP truncating variants. Following hypermutagenesis at a pathogenic hotspot, mean prime editing efficiency across introduced variants was 57±27%.Designing therapeutics that target pathogenic hotspots will not only address known missense P/LP variants but also novel P/LP variants identified in these hotspots as well. Moreover, the clustering of P/LP missense rather than truncating variants in these hotspots suggests that prime editing technology is particularly valuable for dominant negative disease. Although prime editing technology in relation to cardiac health continues to improve, this study presents an approach to targeting the most impactful regions of the genome for inherited cardiovascular disease.

  View details for DOI 10.1161/CIRCGEN.123.004370

  View details for PubMedID 38506054