Associate Professor of Medicine (Cardiovascular Medicine) at the Stanford University Medical Center

Publications

  • Stem Cell-Derived Exosomes Protect Astrocyte Cultures From in vitro Ischemia and Decrease Injury as Post-stroke Intravenous Therapy FRONTIERS IN CELLULAR NEUROSCIENCE Sun, X., Jung, J., Arvola, O., Santoso, M. R., Giffard, R. G., Yang, P. C., Stary, C. M. 2019; 13
  • Myocardial viability of the peri-infarct region measured by T1 mapping post manganese-enhanced MRI correlates with LV dysfunction INTERNATIONAL JOURNAL OF CARDIOLOGY Tada, Y., Heidary, S., Tachibana, A., Zaman, J., Neofytou, E., Dash, R., Wu, J. C., Yang, P. C. 2019; 281: 8–14
  • MICROVESICLES LARGER THAN 200NM RESCUE CARDIOMYOCYTES FROM DOXORUBICIN INJURY IN A PATIENT-SPECIFIC MODEL OF ANTHRACYCLINE INDUCED CARDIOMYOPATHY O'Brien, C., Shi, L., Ozgun, M., Vaskova, E., Santoso, M., Jung, J., Ikeda, G., Demirci, U., Yang, P. ELSEVIER SCIENCE INC. 2019: 688
  • Whole-heart coronary MR angiography using a 3D cones phyllotaxis trajectory MAGNETIC RESONANCE IN MEDICINE Malave, M. O., Baron, C. A., Addy, N., Cheng, J. Y., Yang, P. C., Hu, B. S., Nishimura, D. G. 2019; 81 (2): 1092–1103

    View details for DOI 10.1002/mrm.27475

    View details for Web of Science ID 000462086300030

  • Myocardial viability of the peri-infarct region measured by T1 mapping post manganese-enhanced MRI correlates with LV dysfunction. International journal of cardiology Tada, Y., Heidary, S., Tachibana, A., Zaman, J., Neofytou, E., Dash, R., Wu, J. C., Yang, P. C. 2019

    Abstract

    BACKGROUND: Manganese-enhanced MRI (MEMRI) detects viable cardiomyocytes based on the intracellular manganese uptake via L-type calcium-channels. This study aimed to quantify myocardial viability based on manganese uptake by viable myocardium in the infarct core (IC), peri-infarct region (PIR) and remote myocardium (RM) using T1 mapping before and after MEMRI and assess their association with cardiac function and arrhythmogenesis.METHODS: Fifteen female swine had a 60-minute balloon ischemia-reperfusion injury in the LAD. MRI (Signa 3T, GE Healthcare) and electrophysiological study (EPS) were performed 4 weeks later. MEMRI and delayed gadolinium-enhanced MRI (DEMRI) were acquired on LV short axis. The DEMRI positive total infarct area was subdivided into the regions of MEMRI-negative non-viable IC and MEMRI-positive viable PIR. T1 mapping was performed to evaluate native T1, post-MEMRI T1, and delta R1 (R1post-R1pre, where R1 equals 1/T1) of each territory. Their correlation with LV function and EPS data was assessed.RESULTS: PIR was characterized by intermediate native T1 (1530.5 ± 75.2 ms) compared to IC (1634.7 ± 88.4 ms, p = 0.001) and RM (1406.4 ± 37.9 ms, p < 0.0001). Lower post-MEMRI T1 of PIR (1136.3 ± 99.6 ms) than IC (1262.6 ± 126.8 ms, p = 0.005) and higher delta R1 (0.23 ± 0.08 s-1) of PIR than IC (0.18 ± 0.09 s-1, p = 0.04) indicated higher myocardial manganese uptake of PIR compared to IC. Post-MEMRI T1 (r = -0.57, p = 0.02) and delta R1 (r = 0.51, p = 0.04) of PIR correlated significantly with LVEF.CONCLUSIONS: PIR is characterized by higher manganese uptake compared to the infarct core. In the subacute phase post-IR, PIR viability measured by post-MEMRI T1 correlates with cardiac function.

    View details for PubMedID 30739802

  • Defining genotype-phenotype relationships in patients with hypertrophic cardiomyopathy using cardiovascular magnetic resonance imaging. PloS one Miller, R. J., Heidary, S., Pavlovic, A., Schlachter, A., Dash, R., Fleischmann, D., Ashley, E. A., Wheeler, M. T., Yang, P. C. 2019; 14 (6): e0217612

    Abstract

    HCM is the most common inherited cardiomyopathy. Historically, there has been poor correlation between genotype and phenotype. However, CMR has the potential to more accurately assess disease phenotype. We characterized phenotype with CMR in a cohort of patients with confirmed HCM and high prevalence of genetic testing.Patients with a diagnosis of HCM, who had undergone contrast-enhanced CMR were identified. Left ventricular mass index (LVMI) and volumes were measured from steady-state free precession sequences. Late gadolinium enhancement (LGE) was quantified using the full width, half maximum method. All patients were prospectively followed for the development of septal reduction therapy, arrhythmia or death.We included 273 patients, mean age 51.2 ± 15.5, 62.9% male. Of those patients 202 (74.0%) underwent genetic testing with 90 pathogenic, likely pathogenic, or rare variants and 13 variants of uncertain significance identified. Median follow-up was 1138 days. Mean LVMI was 82.7 ± 30.6 and 145 patients had late gadolinium enhancement (LGE). Patients with beta-myosin heavy chain (MYH7) mutations had higher LV ejection fraction (68.8 vs 59.1, p<0.001) than those with cardiac myosin binding protein C (MYBPC3) mutations. Patients with MYBPC3 mutations were more likely to have LVEF < 55% (29.7% vs 4.9%, p = 0.005) or receive a defibrillator than those with MYH7 mutations (54.1% vs 26.8%, p = 0.020).We found that patients with MYBPC3 mutations were more likely to have impaired ventricular function and may be more prone to arrhythmic events. Larger studies using CMR phenotyping may be capable of identifying additional characteristics associated with less frequent genetic causes of HCM.

    View details for DOI 10.1371/journal.pone.0217612

    View details for PubMedID 31199839

  • Whole-heart coronary MR angiography using a 3D cones phyllotaxis trajectory. Magnetic resonance in medicine Malave, M. O., Baron, C. A., Addy, N. O., Cheng, J. Y., Yang, P. C., Hu, B. S., Nishimura, D. G. 2018

    Abstract

    PURPOSE: To develop a 3D cones steady-state free precession sequence with improved robustness to respiratory motion while mitigating eddy current artifacts for free-breathing whole-heart coronary magnetic resonance angiography.METHOD: The proposed sequence collects cone interleaves using a phyllotaxis pattern, which allows for more distributed k-space sampling for each heartbeat compared to a typical sequential collection pattern. A Fibonacci number of segments is chosen to minimize eddy current effects with the trade-off of an increased number of acquisition heartbeats. For verification, phyllotaxis-cones is compared to sequential-cones through simulations, phantom studies, and in vivo coronary scans with 8 subjects using 2D image-based navigators for retrospective motion correction.RESULTS: Simulated point spread functions and moving phantom results show less coherent motion artifacts for phyllotaxis-cones compared to sequential-cones. Assessment of the right and left coronary arteries using reader scores and the image edge profile acutance vessel sharpness metric indicate superior image quality and sharpness for phyllotaxis-cones.CONCLUSION: Phyllotaxis 3D cones results in improved qualitative image scores and coronary vessel sharpness for free-breathing whole-heart coronary magnetic resonance angiography compared to standard sequential ordering when using a steady-state free precession sequence.

    View details for PubMedID 30370941

  • Rationale and Design of the SENECA (StEm cell iNjECtion in cAncer survivors) Trial AMERICAN HEART JOURNAL Bolli, R., Hare, J. M., Henry, T. D., Lenneman, C. G., March, K. L., Miller, K., Pepine, C. J., Perin, E. C., Traverse, J. H., Willerson, J. T., Yang, P. C., Gee, A. P., Lima, J. A., Moye, L., Vojvodic, R. W., Sayre, S. L., Bettencourt, J., Cohen, M., Ebert, R. F., Simari, R. D., Cardiovasc Cell Therapy Res 2018; 201: 54–62

    Abstract

    SENECA (StEm cell iNjECtion in cAncer survivors) is a phase I, randomized, double-blind, placebo-controlled study to evaluate the safety and feasibility of delivering allogeneic mesenchymal stromal cells (allo-MSCs) transendocardially in subjects with anthracycline-induced cardiomyopathy (AIC).AIC is an incurable and often fatal syndrome, with a prognosis worse than that of ischemic or nonischemic cardiomyopathy. Recently, cell therapy with MSCs has emerged as a promising new approach to repair damaged myocardium.The study population is 36 cancer survivors with a diagnosis of AIC, left ventricular (LV) ejection fraction ≤40%, and symptoms of heart failure (NYHA class II-III) on optimally-tolerated medical therapy. Subjects must be clinically free of cancer for at least two years with a ≤ 30% estimated five-year risk of recurrence. The first six subjects participated in an open-label, lead-in phase and received 100 million allo-MSCs; the remaining 30 will be randomized 1:1 to receive allo-MSCs or vehicle via 20 transendocardial injections. Efficacy measures (obtained at baseline, 6 months, and 12 months) include MRI evaluation of LV function, LV volumes, fibrosis, and scar burden; assessment of exercise tolerance (six-minute walk test) and quality of life (Minnesota Living with Heart Failure Questionnaire); clinical outcomes (MACE and cumulative days alive and out of hospital); and biomarkers of heart failure (NT-proBNP).This is the first clinical trial using direct cardiac injection of cells for the treatment of AIC. If administration of allo-MSCs is found feasible and safe, SENECA will pave the way for larger phase II/III studies with therapeutic efficacy as the primary outcome.

    View details for PubMedID 29910056

  • Rationale and Design of the CONCERT-HF Trial (Combination of Mesenchymal and c-kit(+) Cardiac Stem Cells As Regenerative Therapy for Heart Failure) CIRCULATION RESEARCH Bolli, R., Hare, J. M., March, K. L., Pepine, C. J., Willerson, J. T., Perin, E. C., Yang, P. C., Henry, T. D., Traverse, J. H., Mitrani, R. D., Khan, A., Hernandez-Schulman, I., Taylor, D. A., DiFede, D. L., Lima, J. C., Chugh, A., Loughran, J., Vojvodic, R. W., Sayre, S. L., Bettencourt, J., Cohen, M., Moye, L., Ebert, R. F., Simari, R. D., Cardiovasc Cell Therapy Res 2018; 122 (12): 1703–15

    Abstract

    Autologous bone marrow mesenchymal stem cells (MSCs) and c-kit+ cardiac progenitor cells (CPCs) are 2 promising cell types being evaluated for patients with heart failure (HF) secondary to ischemic cardiomyopathy. No information is available in humans about the relative efficacy of MSCs and CPCs and whether their combination is more efficacious than either cell type alone.CONCERT-HF (Combination of Mesenchymal and c-kit+ Cardiac Stem Cells As Regenerative Therapy for Heart Failure) is a phase II trial aimed at elucidating these issues by assessing the feasibility, safety, and efficacy of transendocardial administration of autologous MSCs and CPCs, alone and in combination, in patients with HF caused by chronic ischemic cardiomyopathy (coronary artery disease and old myocardial infarction).Using a randomized, double-blinded, placebo-controlled, multicenter, multitreatment, and adaptive design, CONCERT-HF examines whether administration of MSCs alone, CPCs alone, or MSCs+CPCs in this population alleviates left ventricular remodeling and dysfunction, reduces scar size, improves quality of life, or augments functional capacity. The 4-arm design enables comparisons of MSCs alone with CPCs alone and with their combination. CONCERT-HF consists of 162 patients, 18 in a safety lead-in phase (stage 1) and 144 in the main trial (stage 2). Stage 1 is complete, and stage 2 is currently randomizing patients from 7 centers across the United States.CONCERT-HF will provide important insights into the potential therapeutic utility of MSCs and CPCs, given alone and in combination, for patients with HF secondary to ischemic cardiomyopathy.URL: http://www.clinicaltrials.gov. Unique identifier: NCT02501811.

    View details for PubMedID 29703749

  • MANGANESE-ENHANCED T1 MAPPING IN MYOCARDIAL INFARCTION: VALIDATION WITH F-18-FDG PET/MR Spath, N. B., Tavares, A., Gray, G. A., Dweck, M. R., Newby, D. E., Yang, P. C., Jansen, M. A., Semple, S. I. BMJ PUBLISHING GROUP. 2018: A9
  • EXOSOMES PRODUCED BY HUMAN AMNIOTIC MESENCHYMAL STEM CELL-DERIVED INDUCED PLURIPOTENT STEM CELLS MODULATE IMMUNE RESPONSE IN MURINE MYOCARDIAL INJURY MODEL Jang, A., Seo, H., Bornstaedt, D., Jung, J., Vaskova, E., Yang, P. ELSEVIER SCIENCE INC. 2018: 82
  • PLEIOTROPIC EFFECTS OF THE EXOSOMES FROM IPSC-DERIVATIVES IN RESTORING INJURED MYOCARDIUM Vaskova, E., Tada, Y., von Bornstaedt, D., Woo, Y., Yang, P. ELSEVIER SCIENCE INC. 2018: 80
  • EXOSOMAL MIR-106A-363 CLUSTER FROM THE HYPOXIC HUMAN IPSC-DERIVED CARDIOMYOCYTES RESTORE THE ISCHEMIC MYOCARDIUM Jung, J., Tada, Y., Bornstaedt, D., Wahlquist, C., Mercola, M., Woo, Y., Yang, P. ELSEVIER SCIENCE INC. 2018: 14
  • Circulating Biomarkers to Identify Responders in Cardiac Cell therapy (vol 7, 4419, 2017) SCIENTIFIC REPORTS Jokerst, J. V., Cauwenberghs, N., Kuznetsova, T., Haddad, F., Sweeney, T., Hou, J., Rosenberg-Hasson, Y., Zhao, E., Schutt, R., Bolli, R., Traverse, J. H., Pepine, C. J., Henry, T. D., Schulman, I. H., Moye, L., Taylor, D. A., Yang, P. C. 2018; 8: 4257

    Abstract

    A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

    View details for PubMedID 29511207

  • Induced Pluripotent Stem Cell (iPSC)-Derived Exosomes for Precision Medicine in Heart Failure CIRCULATION RESEARCH Yang, P. C. 2018; 122 (5): 661–63

    View details for PubMedID 29496797