Riya Nilkant

All Publications

• Impact of leaflet stiffness in aortic valve neocuspidization in ex vivo biomechanical simulation. JTCVS open Shibata, M., Lee, J. Y., Sharir, A., Nilkant, R., Kim, J. B., Mullis, D. M., Okamura, K., Choi, P., Ono, Y., Zhu, Y., Park, M., Woo, J., Ma, M. 2026; 29: 101558

  Abstract

  This study aimed to analyze how varying glutaraldehyde fixation of porcine pericardium impacts the biomechanics of aortic valve neocuspidization (ie, Ozaki procedure).Four bovine aortic roots were mounted in a 3-dimensional printed left heart simulator. Leaflets were tanned for 2, 6, and 10 minutes in 0.625% glutaraldehyde and used to create the Ozaki models in the same aortic root. Three models were biomechanically compared with a native aortic control valve. Hemodynamics, high-speed videography, and echocardiography data were collected. The flexibility and strength of each pericardium were tested using tensile strength.Tensile stress and strain were best at 10-minute tanning. As neo-leaflet tanning duration increased from 2 to 10 minutes, the transvalvular pressure gradient decreased by 38.0% (13.7 ± 4.0 mm Hg vs 8.5 ± 4.8 mm Hg, P < .0001). Ozaki models had smaller orifices than native valves (2.0 ± 0.6 cm2 vs 1.3 ± 0.2 cm2, 1.4 ± 0.3 cm2, and 1.5 ± 0.1 cm2 for 2, 6, and 10 minutes: P = .0003, P < .002 for 2 and 10 minutes). When tanning time extended from 2 to 10 minutes, valve regurgitation decreased by 31.1% (18.0% vs 12.4%, P < .001). The average valve opening and closing leaflet velocities increased by 38.6% and 22.5% from 2 to 10 minutes of tanning (298.7 vs 486.1 mm/s, P = .048; 188.1 vs 242.7 mm/s, P = .14), respectively.Porcine pericardium tanned in glutaraldehyde for 10 minutes resulted in the lowest valve regurgitation, lowest pressure gradient, and highest leaflet velocities in ex vivo simulation. These observations can be used to optimize valve function and enhance aortic valve reconstruction techniques.

  View details for DOI 10.1016/j.xjon.2025.101558

  View details for PubMedID 41960121

  View details for PubMedCentralID PMC13059995

• In vivo growing leporine model of pulmonary artery banding induces inflammation and vascular remodeling via pathways conserved across species. JTCVS open Mullis, D. M., Lee, J. Y., Shibata, M., Arana, V. T., Kidambi, S., Sharir, A., Choi, P. S., Ikeda, G., Nilkant, R., Takashima, H., Ueyama, T., Huber, J. A., Woo, Y. J., Ma, M. 2026; 29: 101560

  Abstract

  Characterization of pulmonary artery banding in a growing leporine model with comparison to human tissue has yet to be published. We hypothesized that there would be inflammatory changes that occur to the myocardium despite small changes to the gradients across the pulmonary arteries in rabbits that underwent pulmonary artery banding. Additionally, we analyzed tissue from humans to determine whether these are pathways preserved across species.Female 2-month-old New Zealand white rabbits were anesthetized, and a band was placed loosely around the main pulmonary artery (n = 4). The rabbits underwent either echocardiographic or magnetic resonance imaging, and the hearts were harvested when the rabbits weighed approximately 3.9 kg. Right ventricle samples from humans (tissues that would have been discarded otherwise) were obtained for comparison.The right ventricles of the rabbits that underwent pulmonary artery banding exhibit significantly more CD31+α-SMA+ expression than the control rabbits (P = .03). The right ventricles at the level of the infundibulum also had significantly more fibrosis than the control rabbit confirmed with Masson's trichrome and picrosirius red staining (P = .03 and P < .001, respectively) and significantly more transforming growth factor-β+ expression (P = .04). Human samples demonstrate similar findings.Even with minimal changes to the pulmonary artery gradient, growing leporine rabbits exhibit significant inflammation, vascular remodeling, and fibrosis in the right ventricle in response to pulmonary artery banding. These changes are conserved across species, because we found that the right ventricles of patients with pulmonary arterial hypertension or that had undergone pulmonary artery banding also exhibit similar expression of inflammation, vascular remodeling, and fibrosis.

  View details for DOI 10.1016/j.xjon.2025.101560

  View details for PubMedID 41960063

  View details for PubMedCentralID PMC13059996

• Histologic changes in systemically loaded right ventricles at time of transplantation. Frontiers in cardiovascular medicine Nilkant, R., Choi, P. S., Mullis, D. M., Chang, R., Sharir, A., Reddy, S., Pelletier, G. J., Ma, M. 2025; 12: 1640561

  Abstract

  In a subset of complex congenital heart disease patients, the right ventricle (RV) is connected to the higher-resistance systemic circulation, often leading to RV dysfunction. This study characterizes the systemic RV histology at time of heart transplantation in two groups - patients with hypoplastic left heart syndrome with Fontan palliation (HLHS-F) and those with dextro-transposition of the great arteries post atrial switch operation (d-TGA-AS). We sought to better understand histological differences between the systemic RV in the single ventricle vs. biventricular circulations.We procured RV tissue samples at the mid-cavity free walls from nine explanted recipient hearts: six HLHS-F and three d-TGA-AS. RV and LV muscle samples from two organ donors whose hearts were unused for non-cardiac reasons served as controls. Tissue sections were stained with Masson's Trichrome and Hematoxylin and Eosin. Given the small cohort size and heterogeneity, analyses were descriptive. Continuous variables are reported as median (range).The d-TGA-AS population was older than the HLHS-F population (median: 42 years; range: 38-44 vs. median: 24 years; range: 12-32, respectively). RV fibrosis in the d-TGA-AS population was greater at 28% (7-35) vs. the HLHS-F population which was 4% (2-24) and donor controls (median: 2% range: 0-4). In contrast, RV wall thickness was greater in HLHS-F (median: 12,303 µm; range: 9,976-15,745) than in d-TGA-AS (median: 9,063 µm; range: 8,316-10,322) and donors (median 7,984 µm; range: 2,582-13,386). Donor LV thickness (median: 17,056 µm; range: 16,688-17,423) exceeded all RV groups.The primary histologic finding for the d-TGA-AS group was fibrosis, while the HLHS-F group showed predominantly hypertrophy. The temporal presentation of the patients was different, with the HLHS-F patients presenting earlier for transplant than the d-TGA-AS. These observations suggest that different histologic changes may occur in response to longstanding systemic pressures in these two anatomic subgroups of patients with systemic RV.

  View details for DOI 10.3389/fcvm.2025.1640561

  View details for PubMedID 41189996

  View details for PubMedCentralID PMC12580193

• A Low-Cost, Open-Source 3D Printer for Multimaterial and High-Throughput Direct Ink Writing of Soft and Living Materials. Advanced materials (Deerfield Beach, Fla.) Weiss, J. D., Mermin-Bunnell, A., Solberg, F. S., Tam, T., Rosalia, L., Sharir, A., Rütsche, D., Sinha, S., Choi, P. S., Shibata, M., Palagani, Y., Nilkant, R., Paulvannan, K., Ma, M., Skylar-Scott, M. A. 2025: e2414971

  Abstract

  Direct ink writing is a 3D printing method that is compatible with a wide range of structural, elastomeric, electronic, and living materials, and it continues to expand its uses into physics, engineering, and biology laboratories. However, the large footprint, closed hardware and software ecosystems, and expense of commercial systems often hamper widespread adoption. This work introduces a compact, low-cost, multimaterial, and high-throughput direct ink writing 3D printer platform with detailed assembly files and instructions provided freely online. In contrast to existing low-cost 3D printers and bioprinters, which typically modify off-the-shelf plastic 3D printers, this system is built from scratch, offering a lower cost and full customizability. Active mixing of cell-laden bioinks, high-throughput production of auxetic lattices using multimaterial multinozzle 3D (MM3D) printing methods, and a high-toughness, photocurable hydrogel for fabrication of heart valves are introduced. Finally, hardware for embedded multinozzle and 3D gradient nozzle printing is developed for producing high-throughput and graded 3D parts. This powerful, simple-to-build, and customizable printing platform can help stimulate a vibrant biomaker community of engineers, biologists, and educators.

  View details for DOI 10.1002/adma.202414971

  View details for PubMedID 39748617

• Unlocking the promise of mesenchymal stem cells and extracorporeal photopheresis to address rejection and graft failure in intestinal transplant recipients. Human immunology Levitte, S., Nilkant, R., Jensen, A. R., Zhang, K. Y. 2024; 85 (6): 111160

  Abstract

  In patients with irreversible intestinal failure, intestinal transplant has become a standard treatment option. Graft failure secondary to acute or chronic cellular rejection continues to be a significant challenge following transplant. Even with optimal immune suppression, some patients continue to struggle with refractory rejection. Both extracorporeal photopheresis (ECP) and extracellular vesicles derived from mesenchymal stem cells (EVs) have been used to treat refractory rejection following intestinal transplantation, although their use remains limited and consistent treatment protocols are lacking.Intestinal transplant recipients who received ECP only or ECP and EVs as rescue therapy for acute cellular rejection or chronic inflammation between 2016 and 2022 were included in this single-center retrospective analysis. Baseline demographics, pre- and post-treatment histopathology, endoscopic and biochemical findings, and long-term transplant outcomes were analyzed.Three patients (two pediatric and one adult) with acute steroid- and biologic-refractory rejection were treated with ECP and/or EVs, as was one patient (pediatric) with chronic graft rejection and inflammation. Patients received twice weekly ECP for 4 weeks and once weekly thereafter. EVs were administered in three doses each separated by 72 h. Immunosuppression at the time of treatment initiation included high-dose tacrolimus and sirolimus. Histologic resolution of rejection was achieved in all patients over 12-16 weeks. Steroids were weaned to low-dose or withdrawn in every patient within 4 weeks of ECP/EV treatment. C-reactive protein decreased from an average of 14.75 to 1.6 mg/dL post-treatment and fecal calprotectin decreased from average 800 mg/g to 31 mg/g. Donor-induced cytotoxic T cell populations were quantified for two of the patients with acute rejection, and in both cases decreased dramatically following treatment. There were no complications associated with either treatment.Both ECP and EVs present novel opportunities to address graft rejection and inflammation in bowel transplant recipients. More work will be needed to define the optimal therapeutic parameters for each treatment modality.

  View details for DOI 10.1016/j.humimm.2024.111160

  View details for PubMedID 39471538

• Minimally invasive 2-patch repair technique for sinus venosus atrial septal defects. JTCVS techniques Reed, A. K., Nilkant, R., Hochstein, J., Choi, P. S., Ma, M., Woo, Y. J. 2024; 27: 116-118

  View details for DOI 10.1016/j.xjtc.2024.07.001

  View details for PubMedID 39478923

  View details for PubMedCentralID PMC11518897

• Pediatric Combined Heart-liver Transplantation: A Single-center Long-term Experience. Transplantation direct Levitte, S., Nilkant, R., Chen, S., Beadles, A., Lee, J., Bonham, C. A., Rosenthal, D., Gallo, A., Hollander, S., Esquivel, C., Ma, M., Zhang, K. Y. 2024; 10 (9): e1696

  Abstract

  Combined heart liver transplant (CHLT) continues to gain attention as a surgical treatment for patients with end-stage heart and liver disease but remains rare. We present our institutional longitudinal experience with up to 14 y of follow-up, focused on long-term outcomes in CHLT recipients.We conducted a single-institutional, retrospective review from January 1, 2010, to December 31, 2023, including 7 patients ages 7-17 y who underwent CHLT.Most patients were surgically palliated via Fontan procedure pretransplant (n = 6), and all had evidence of advanced fibrosis or cirrhosis before transplant. The 30-d mortality was 14.3% (n = 1, multiorgan failure). During the follow-up period, 1 patient developed acute heart rejection which required treatment and 2 developed acute liver rejection. In all cases, rejection was successfully treated. Two patients developed acute heart rejection which did not require treatment (grade 1R). No patients developed chronic or refractory rejection. No patients developed allograft coronary artery vasculopathy.CHLT remains a rarely performed treatment for pediatric patients with end-stage heart and liver disease, but our long-term data suggest that this treatment strategy should be considered more frequently.

  View details for DOI 10.1097/TXD.0000000000001696

  View details for PubMedID 39165490

  View details for PubMedCentralID PMC11335332

• Heart-Liver Transplantation Utilizing the En Bloc Technique: A Single-Center Experience Over Two Decades. The Journal of thoracic and cardiovascular surgery Mullis, D. M., Garrison, A., Heng, E., Zhu, Y., Elde, S., Nilkant, R., Boyd, J., Hiesinger, W., Lee, A., Shudo, Y., Gallo, A., Bonham, C. A., Woo, Y. J., MacArthur, J. W. 2024

  Abstract

  Combined heart-liver transplantation (CHLT) is a definitive therapy reserved for patients with concomitant heart failure and advanced liver disease. A limited number of centers perform CHLT, and even fewer use the en bloc implantation technique. This study 1) reviews clinical outcomes and immunoprotective effects following CHLT, and 2) describes our institution's experience of over two decades using the en bloc technique.All patients who underwent CHLT at our institution between January 2003 and July 2023 were identified. Recipient and donor characteristics, operative details, and clinical outcomes were assessed. Kaplan-Meier analysis was performed to evaluate survival following CHLT.A total of 20 patients underwent CHLT using the en bloc technique at our institution between January 2003 and July 2023. At a median follow-up of 3.8 years for patients who survived the perioperative period (n=18), estimated survival at 1- and 5-years was 94% and 75%, respectively. There was 100% freedom from acute moderate rejection, acute severe rejection, and chronic rejection in all patients. No patients required re-transplantation due to rejection.CHLT is a definitive therapy reserved for patients with multi-organ dysfunction. At our institution, the en bloc technique is the preferred operative approach, as it minimizes cardiac insult, requires fewer anastomoses, minimizes cold ischemia time, and allows for rapid correction of coagulopathy. Overall survival for this cohort is excellent. Episodes of acute rejection were rarely observed, providing further support that the liver may serve an immunoprotective role in multi-organ transplantation.

  View details for DOI 10.1016/j.jtcvs.2024.08.031

  View details for PubMedID 39187122

• Long-Term Outcomes After Lung Transplantation in Children With Intellectual Disabilities. Pediatric transplantation Lee, J. Y., Mullis, D. M., Zawadzki, R. S., Nilkant, R., Kuhan, S., Kidambi, S., Sharir, A., Ma, M. 2024; 28 (5): e14807

  Abstract

  The United Network for Organ Sharing (UNOS) started recording data on intellectual disability status in 2008. This study aimed to characterize the long-term outcomes for children with intellectual disabilities (IDs) undergoing lung transplantation.All pediatric patients (under 18 years old) undergoing bilateral lung transplantation were identified using the UNOS database. The patients were grouped into the following categories: no cognitive delay, possible cognitive delay, and definite cognitive delay. The primary endpoint was graft survival at 3-year posttransplantation. Multivariate Cox proportional hazards modeling was used to estimate the independent effect of cognitive disability on graft survival.Five hundred four pediatric patients who underwent lung transplantation between March 2008 and December 2022 were retrospectively analyzed. 59 had a definite cognitive delay (12%), 23 had a possible delay (5%), and 421 had no delay (83%). When comparing these three groups, there was no significant difference in 60-day graft survival (p = 0.4), 3-year graft survival (p = 0.6), 3-year graft survival for patients who survived at least 60-day posttransplantation (p = 0.9), distribution of causes of death (p = 0.24), nor distribution treatment of rejection within 1-year posttransplantation (p = 0.06).Intellectual disability does not impact long-term outcomes after bilateral lung transplantation. Intellectual disability should not be a contraindication to bilateral lung transplantation on the basis of inferior graft survival.

  View details for DOI 10.1111/petr.14807

  View details for PubMedID 38923151

• Diversifying cardiac intensive care unit models: Successful example of an operating surgeon-led unit. JTCVS open Choi, P. S., Pines, K. C., Swaminathan, A., Nilkant, R., Mendez, M. A., He, H., Woo, Y. J., Martin, B. 2023; 16: 524-531

  Abstract

  Objective: The intensivist-led cardiovascular intensive care unit model is the standard of care in cardiac surgery. This study examines whether a cardiovascular intensive care unit model that uses operating cardiac surgeons, cardiothoracic surgery residents, and advanced practice providers is associated with comparable outcomes.Methods: This is a single-institution review of the first 400 cardiac surgery patients admitted to an operating surgeon-led cardiovascular intensive care unit from 2020 to 2022. Inclusion criteria are elective status and operations managed by both cardiovascular intensive care unit models (aortic operations, valve operations, coronary operations, septal myectomy). Patients from the surgeon-led cardiovascular intensive care unit were exact matched by operation type and 1:1 propensity score matched with controls from the traditional cardiovascular intensive care unit using a logistic regression model that included age, sex, preoperative mortality risk, incision type, and use of cardiopulmonary bypass and circulatory arrest. Primary outcome was total postoperative length of stay. Secondary outcomes included postoperative intensive care unit length of stay, 30-day mortality, 30-day Society of Thoracic Surgeons-defined morbidity (permanent stroke, renal failure, cardiac reoperation, prolonged intubation, deep sternal infection), packed red cell transfusions, and vasopressor use. Outcomes between the 2 groups were compared using chi-square, Fisher exact test, or 2-sample t test as appropriate.Results: A total of 400 patients from the surgeon-led cardiovascular intensive care unit (mean age 61.2±12.8years, 131 female patients [33%], 346 patients [86.5%] with European System for Cardiac Operative Risk Evaluation II <2%) and their matched controls were included. The most common operations across both units were coronary artery bypass grafting (n=318, 39.8%) and mitral valve repair or replacement (n=238, 29.8%). Approximately half of the operations were performed via sternotomy (n=462, 57.8%). There were 3 (0.2%) in-hospital deaths, and 47 patients (5.9%) had a 30-day complication. The total length of stay was significantly shorter for the surgeon-led cardiovascular intensive care unit patients (6.3 vs 7.0days, P=.028), and intensive care unit length of stay trended in the same direction (2.5 vs 2.9days, P=.16). Intensive care unit readmission rates, 30-day mortality, and 30-day morbidity were not significantly different between cardiovascular intensive care unit models. The surgeon-led cardiovascular intensive care unit was associated with fewer postoperative red blood cell transfusions in the cardiovascular intensive care unit (P=.002) and decreased vasopressor use (P=.001).Conclusions: In its first 2years, the surgeon-led cardiovascular intensive care unit demonstrated comparable outcomes to the traditional cardiovascular intensive care unit with significant improvements in total length of stay, postoperative transfusions in the cardiovascular intensive care unit, and vasopressor use. This early success exemplifies how an operating surgeon-led cardiovascular intensive care unit can provide similar outcomes to the standard-of-care model for patients undergoing elective cardiac surgery.

  View details for DOI 10.1016/j.xjon.2023.09.040

  View details for PubMedID 38204639

• Mesenchymal stem cell-derived extracellular vesicles for the treatment of acute rejection in pediatric and adult bowel transplant. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Levitte, S., Zhang, K. Y., Guevara-Tique, A. A., Ganguly, A., Dulken, B. W., Nilkant, R., Rigmaiden, M., Kumari, R., Khlifi, K., Thakor, A. S., Bonham, C. A. 2023

  Abstract

  Mesenchymal stem cells are under investigation as a novel therapy to treat solid organ transplant rejection. However, significant hurdles have limited their use in humans. Mesenchymal stem cell-derived extracellular vesicles address many of these shortcomings but have not been investigated clinically. Here we report our experience treating two patients with graft rejection and inflammation following bowel transplant using mesenchymal stem cell-derived extracellular vesicles.

  View details for DOI 10.1016/j.ajt.2023.10.019

  View details for PubMedID 39491097