Elizabeth B Juneman

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Chapters

• Juneman, E. B. (2014). Non-Cardiac Findings on Echocardiography. In Questions, Tips and Tricks for the Echocardiography Boards..

Journals/Publications

• , G. I., Joseph, P., Roy, A., Lonn, E., Störk, S., Floras, J., Mielniczuk, L., Rouleau, J. L., Zhu, J., Dzudie, A., Balasubramanian, K., Karaye, K., AlHabib, K. F., Gómez-Mesa, J. E., Branch, K. R., Makubi, A., Budaj, A., Avezum, A., Wittlinger, T., , Ertl, G., et al. (2023). Global Variations in Heart Failure Etiology, Management, and Outcomes. JAMA, 329(19), 1650-1661.
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  Most epidemiological studies of heart failure (HF) have been conducted in high-income countries with limited comparable data from middle- or low-income countries.
• Acharya, D., Kazui, T., Al Rameni, D., Acharya, T., Betterton, E., Juneman, E., Loyaga-Rendon, R., Lotun, K., Shetty, R., & Chatterjee, A. (2023). Aortic valve disorders and left ventricular assist devices. Frontiers in cardiovascular medicine, 10, 1098348.
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  Aortic valve disorders are important considerations in advanced heart failure patients being evaluated for left ventricular assist devices (LVAD) and those on LVAD support. Aortic insufficiency (AI) can be present prior to LVAD implantation or develop during LVAD support. It is usually a progressive disorder and can lead to impaired LVAD effectiveness and heart failure symptoms. Severe AI is associated with worsening hemodynamics, increased hospitalizations, and decreased survival in LVAD patients. Diagnosis is made with echocardiographic, device assessment, and/or catheterization studies. Standard echocardiographic criteria for AI are insufficient for accurate diagnosis of AI severity. Management of pre-existing AI includes aortic repair or replacement at the time of LVAD implant. Management of AI on LVAD support is challenging with increased risks of repeat surgical intervention, and percutaneous techniques including transcatheter aortic valve replacement are assuming greater importance. In this manuscript, we provide a comprehensive approach to contemporary diagnosis and management of aortic valve disorders in the setting of LVAD therapy.
• Chinyere, I. R., Hutchinson, M., Moukabary, T., Koevary, J. W., Juneman, E. B., Goldman, S., & Lancaster, J. (2020). Modulating the Infarcted Ventricle’s Refractoriness with an Epicardial Biomaterial.. Journal of Investigative Medicine.
• Hernandez, A., Andres, B., Jagadish, P. S., Oskouie, S., Acharya, T., Juneman, E., & Acharya, D. (2023). Steroid-Responsive Fulminant Lymphocytic Myocarditis Mimicking Giant-Cell Myocarditis. The American journal of medicine, 136(11), e220-e221.
• Shah, S. J., Borlaug, B. A., Chung, E. S., Cutlip, D. E., Debonnaire, P., Fail, P. S., Gao, Q., Hasenfuß, G., Kahwash, R., Kaye, D. M., Litwin, S. E., Lurz, P., Massaro, J. M., Mohan, R. C., Ricciardi, M. J., Solomon, S. D., Sverdlov, A. L., Swarup, V., van Veldhuisen, D. J., , Winkler, S., et al. (2022). Atrial shunt device for heart failure with preserved and mildly reduced ejection fraction (REDUCE LAP-HF II): a randomised, multicentre, blinded, sham-controlled trial. Lancet (London, England), 399(10330), 1130-1140.
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  Placement of an interatrial shunt device reduces pulmonary capillary wedge pressure during exercise in patients with heart failure and preserved or mildly reduced ejection fraction. We aimed to investigate whether an interatrial shunt can reduce heart failure events or improve health status in these patients.
• Soomro, Q. H., Anand, S. T., Weisbord, S. D., Gallagher, M. P., Ferguson, R. E., Palevsky, P. M., Bhatt, D. L., Parikh, C. R., Kaufman, J. S., , P. T., & , P. T. (2022). The Relationship between Rate and Volume of Intravenous Fluid Administration and Kidney Outcomes after Angiography. Clinical journal of the American Society of Nephrology : CJASN, 17(10), 1446-1456.
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  Contrast-associated AKI may result in higher morbidity and mortality. Intravenous fluid administration remains the mainstay for prevention. There is a lack of consensus on the optimal administration strategy. We studied the association of periprocedure fluid administration with contrast-associated AKI, defined as an increase in serum creatinine of at least 25% or 0.5 mg/dl from baseline at 3-5 days after angiography, and 90-day need for dialysis, death, or a 50% increase in serum creatinine.
• Chinyere, I. R., Moukabary, T., Hutchinson, M. D., Lancaster, J. J., Juneman, E., & Goldman, S. (2021). Progression of infarct-mediated arrhythmogenesis in a rodent model of heart failure. American journal of physiology. Heart and circulatory physiology, 320(1), H108-H116.
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  Heart failure (HF) post-myocardial infarction (MI) presents with increased vulnerability to monomorphic ventricular tachycardia (mmVT). To appropriately evaluate new therapies for infarct-mediated reentrant arrhythmia in the preclinical setting, chronologic characterization of the preclinical animal model pathophysiology is critical. This study aimed to evaluate the rigor and reproducibility of mmVT incidence in a rodent model of HF. We hypothesize a progressive increase in the incidence of mmVT as the duration of HF increases. Adult male Sprague-Dawley rats underwent permanent left coronary artery ligation or SHAM surgery and were maintained for either 6 or 10 wk. At end point, SHAM and HF rats underwent echocardiographic and invasive hemodynamic evaluation. Finally, rats underwent electrophysiologic (EP) assessment to assess susceptibility to mmVT and define ventricular effective refractory period (ERP). In 6-wk HF rats ( = 20), left ventricular (LV) ejection fraction (EF) decreased ( < 0.05) and LV end-diastolic pressure (EDP) increased ( < 0.05) compared with SHAM ( = 10). Ten-week HF ( = 12) revealed maintenance of LVEF and LVEDP ( > 0.05), ( > 0.05). Electrophysiology studies revealed an increase in incidence of mmVT between SHAM and 6-wk HF ( = 0.0016) and ERP prolongation ( = 0.0186). The incidence of mmVT and ventricular ERP did not differ between 6- and 10-wk HF ( = 1.0000), ( = 0.9831). Findings from this rodent model of HF suggest that once the ischemia-mediated infarct stabilizes, proarrhythmic deterioration ceases. Within the 6- and 10-wk period post-MI, no echocardiographic, invasive hemodynamic, or electrophysiologic changes were observed, suggesting stable HF. This is the necessary context for the evaluation of experimental therapies in rodent HF. Rodent model of ischemic cardiomyopathy exhibits a plateau of inducible monomorphic ventricular tachycardia incidence between 6 and 10 wk postinfarction.
• Chinyere, I. R., Moukabary, T., Hutchinson, M., Koevary, J. W., Paulino, L., Juneman, E., Goldman, S., & Lancaster, J. (2021). Localized Ventricular effective Refractory period Prolongation with an Epicardial Biomaterial. Journal of Investigative Medicine, 69(2), 364-370.
• Gupta, A., Fei, Y. D., Kim, T. Y., Xie, A., Batai, K., Greener, I., Tang, H., Ciftci-Yilmaz, S., Juneman, E., Indik, J. H., Shi, G., Christensen, J., Gupta, G., Hillery, C., Kansal, M. M., Parikh, D. S., Zhou, T., Yuan, J. X., Kanthi, Y., , Bronk, P., et al. (2021). IL-18 mediates sickle cell cardiomyopathy and ventricular arrhythmias. Blood, 137(9), 1208-1218.
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  Previous reports indicate that IL18 is a novel candidate gene for diastolic dysfunction in sickle cell disease (SCD)-related cardiomyopathy. We hypothesize that interleukin-18 (IL-18) mediates the development of cardiomyopathy and ventricular tachycardia (VT) in SCD. Compared with control mice, a humanized mouse model of SCD exhibited increased cardiac fibrosis, prolonged duration of action potential, higher VT inducibility in vivo, higher cardiac NF-κB phosphorylation, and higher circulating IL-18 levels, as well as reduced voltage-gated potassium channel expression, which translates to reduced transient outward potassium current (Ito) in isolated cardiomyocytes. Administering IL-18 to isolated mouse hearts resulted in VT originating from the right ventricle and further reduced Ito in SCD mouse cardiomyocytes. Sustained IL-18 inhibition via IL-18-binding protein resulted in decreased cardiac fibrosis and NF-κB phosphorylation, improved diastolic function, normalized electrical remodeling, and attenuated IL-18-mediated VT in SCD mice. Patients with SCD and either myocardial fibrosis or increased QTc displayed greater IL18 gene expression in peripheral blood mononuclear cells (PBMCs), and QTc was strongly correlated with plasma IL-18 levels. PBMC-derived IL18 gene expression was increased in patients who did not survive compared with those who did. IL-18 is a mediator of sickle cell cardiomyopathy and VT in mice and a novel therapeutic target in patients at risk for sudden death.
• Alpert, J. S., & Juneman, E. B. (2020). We Will Never Give Up. The American journal of medicine, 133(10), 1111-1112.
• Chinyere, I. R., Hutchinson, M., Moukabary, T., Koevary, J. W., Juneman, E., Goldman, S., & Lancaster, J. J. (2020). Modulating the Infarcted Ventricle's Refractoriness with an Epicardial Biomaterial. Journal of investigative medicine : the official publication of the American Federation for Clinical Research.
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  Patients diagnosed with heart failure with reduced ejection fraction (HFrEF) are at increased risk of monomorphic ventricular tachycardia (VT) and ventricular fibrillation. The presence of myocardial fibrosis provides both anatomical and functional barriers that promote arrhythmias in these patients. Propagation of VT in a reentrant circuit depends on the presence of excitable myocardium and the refractoriness of the circuit. We hypothesize that myocardial refractoriness can be modulated surgically in a model of HFrEF, leading to decreased susceptibility to VT.Male Sprague-Dawley rats were infarcted via permanent left coronary artery ligation. At 3 weeks post-infarction, engineered grafts composed of human dermal fibroblasts cultured into a polyglactin-910 biomaterial were implanted onto the epicardium to cover the area of infarction. Three weeks post-graft treatment, all rats underwent a terminal electrophysiologic study to compare monophasic action potential electroanatomic maps and susceptibility to inducible monomorphic VT.HFrEF rats (n=29) demonstrated a longer (p=0.0191) ventricular effective refractory period (ERP) and a greater (p=0.0394) VT inducibility compared with sham (n=7). HFrEF rats treated with the graft (n=12) exhibited no change in capture threshold (p=0.3220), but had a longer ventricular ERP (p=0.0029) compared with HFrEF. No statistically significant change in VT incidence was found between HFrEF rats treated with the graft and untreated HFrEF rats (p=0.0834).Surgical deployment of a fibroblast-containing biomaterial in a rodent ischemic cardiomyopathy model prolonged ventricular ERP as measured by programmed electrical stimulation. This hypothesis-generating study warrants additional studies to further characterize the antiarrhythmic or proarrhythmic effects of this novel surgical therapy.
• Juneman, E. B. (2020). Leading the Compassionate Charge. Circulation. Heart failure, 13(4), e007085.
• Lancaster, J., Goldman, S., Juneman, E. B., Koevary, J. W., Moukabary, T., Hutchinson, M., & Chinyere, I. R. (2020). Modulating the Infarcted Ventricle’s Refractoriness with an Epicardial Biomaterial.. Journal of Investigative Medicine.
• Morris, C. C., Stroud, S. C., Golconda, U., Gregoire, S. A., & Juneman, E. B. (2020). Orthotopic Heart Transplant Recipient with Enteric-coated Mycophenolate Sodium (Myfortic) Induced Colitis. The American journal of case reports, 21, e920235.
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  BACKGROUND Mycophenolic acid is an immunosuppressive drug commonly used in solid organ transplantation to prevent acute and chronic allograft rejection. There are 2 common preparations of mycophenolic acid including mycophenolate mofetil (Cellcept), and enteric-coated mycophenolate sodium (Myfortic) which was developed to reduce the high rate of gastrointestinal side effects seen with Cellcept. Cases of mycophenolate mofetil induced colitis have been described in solid organ transplant patients and rarely in heart transplant patients, but enteric-coated mycophenolate sodium induced colitis is very rare and has not been reported in heart transplant patients. CASE REPORT A 66-year old male with an orthotopic heart transplant was admitted with diarrhea. The patient was on an immunosuppression regimen including mycophenolate mofetil for 10 weeks post-transplantation until complaining of soft stools and bloating. At this time, he was switched to enteric-coated mycophenolate sodium. At week 11 post-transplantation, the patient was admitted to the hospital with worsening diarrhea. Extensive workup was unrevealing. Colonoscopy with biopsy showed features of mycophenolic acid induced colitis. Enteric coated mycophenolate sodium was discontinued, and the patient's diarrhea markedly improved over the next 48 hours. The patient had no signs of colitis or solid organ rejection at 7-month follow up appointment. CONCLUSIONS Although a diagnosis of exclusion, enteric-coated mycophenolate sodium induced colitis should be considered in the differential of an orthotopic heart transplant patient with diarrhea as discontinuing the medication can improve symptoms and avoid costly workups, however, patients should be monitored closely for signs of rebound rejection.
• Avery, R., Ebong, I., Skaria, R., Day, K., Miller, C., Juneman, E., Oliva, I., Friedman, M., Maltais, S., & Khalpey, Z. (2019). Preoperative Risk Stratification of Right Ventricular Function Utilizing Cardiac Magnetic Resonance Imaging Compared With Echocardiographic and Hemodynamic Parameters. ASAIO journal (American Society for Artificial Internal Organs : 1992).
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  Accurate right ventricle functional analysis prior to mechanical circulatory support continues to be valuable for preoperative stratification of patients at risk for developing right ventricular (RV) failure. While cardiac magnetic resonance imaging (CMR) remains the gold standard, CMR is limited by availability and patient-specific contraindications. Further investigation of other imaging modalities would be beneficial as it may serve as a surrogate to identifying RV systolic dysfunction. A single-center, retrospective study including 29 patients with advanced heart failure was performed. All patients underwent ventricular functional analysis with both CMR and echocardiography, and 19 patients underwent right heart catheterization. Predictability with multimodal assessment of RV function was determined using logistic regression methods. Of the 29 participants, 10 had severe RV dysfunction. Tricuspid annular plane of systolic excursion was a modest predictor of RV dysfunction with odd ratio (OR) of 0.07 (0.01-0.72) and c-statistic of 0.79. Invasive hemodynamic measurement of cardiac index by thermodilution method was also predictive of RV dysfunction but failed to reach statistical significance (OR of 0.03,
• Chinyere, I. R., Hutchinson, M., Moukabary, T., Lancaster, J., Goldman, S., & Juneman, E. (2019). Monophasic action potential amplitude for substrate mapping. American journal of physiology. Heart and circulatory physiology, 317(4), H667-H673.
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  Although radiofrequency ablation has revolutionized the management of tachyarrhythmias, the rate of arrhythmia recurrence is a large drawback. Successful substrate identification is paramount to abolishing arrhythmia, and bipolar voltage electrogram's narrow field of view can be further reduced for increased sensitivity. In this report, we perform cardiac mapping with monophasic action potential (MAP) amplitude. We hypothesize that MAP amplitude (MAPA) will provide more accurate infarct sizes than other mapping modalities via increased sensitivity to distinguish healthy myocardium from scar tissue. Using the left coronary artery ligation Sprague-Dawley rat model of ischemic heart failure, we investigate the accuracy of in vivo ventricular epicardial maps derived from MAPA, MAP duration to 90% repolarization (MAPD), unipolar voltage amplitude (UVA), and bipolar voltage amplitude (BVA) compared with gold standard histopathological measurement of infarct size. Numerical analysis reveals discrimination of healthy myocardium versus scar tissue using MAPD ( = 0.0158) and UVA ( < 0.001, = 21). MAPA and BVA decreased between healthy and border tissue ( = 0.0218 and 0.0015, respectively) and border and scar tissue ( = 0.0037 and 0.0094, respectively). Contrary to our hypothesis, BVA mapping performed most accurately regarding quantifying infarct size. MAPA mapping may have high spatial resolution for myocardial tissue characterization but was quantitatively less accurate than other mapping methods at determining infarct size. BVA mapping's superior utility has been reinforced, supporting its use in translational research and clinical electrophysiology laboratories. MAPA may hold potential value for precisely distinguishing healthy myocardium, border zone, and scar tissue in diseases of disseminated fibrosis such as atrial fibrillation. Monophasic action potential mapping in a clinically relevant model of heart failure with potential implications for atrial fibrillation management.
• Goldman, S., Chinyere, I. R., Daugherty, S. L., Juneman, E., Koevary, J. W., & Lancaster, J. J. (2019). Abstract 500: Progression of Chronic Ischemia-Mediated Arrhythmogenesis in a Rat Model of Heart Failure. Circulation Research, 125(Suppl_1). doi:10.1161/res.125.suppl_1.500
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  Background: Worldwide, the prevalence of heart failure (HF) is increasing and HF patients are living longer. Chronic ischemic HF presents with increased vulnerability to ventricular tachycardia and...
• Lancaster, J. J., Sanchez, P., Repetti, G. G., Juneman, E., Pandey, A. C., Chinyere, I. R., Moukabary, T., LaHood, N., Daugherty, S. L., & Goldman, S. (2019). Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Patch in Rats With Heart Failure. The Annals of thoracic surgery, 108(4), 1169-1177.
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  To treat chronic heart failure (CHF), we developed a robust, easy to handle bioabsorbable tissue-engineered patch embedded with human neonatal fibroblasts and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). This patch was implanted on the epicardial surface of the heart covering the previously infarcted tissue.
• Lancaster, J., Sanchez, P., Repetti, G., Juneman, E. B., Pandey, A., Royal Chinyere, I., Moukabary, T., LaHood, N., Daugherty, S., & Goldman, S. (2019). Human Induced Pluripotent Stem Cell Derived Cardiomyocyte Patch in Rats with Heart Failure.. Annals Thoracic Surgery, 1169-1177. doi:https://doi.org/10.1016/j.athoracsur.2019.03.099
• Metra, M., Teerlink, J. R., Cotter, G., Davison, B. A., Felker, G. M., Filippatos, G., Greenberg, B. H., Pang, P. S., Ponikowski, P., Voors, A. A., Adams, K. F., Anker, S. D., Arias-Mendoza, A., Avendaño, P., Bacal, F., Böhm, M., Bortman, G., Cleland, J. G., Cohen-Solal, A., , Crespo-Leiro, M. G., et al. (2019). Effects of Serelaxin in Patients with Acute Heart Failure. The New England journal of medicine, 381(8), 716-726.
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  Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure.
• Bounthavong, M., Juneman, E. B., Reed, K. L., & Wei, R. (2018). 459: Sonographically measured inferior vena caval diameter in response to different maternal positions in pregnancy. American Journal of Obstetrics and Gynecology, 218(1), S277. doi:10.1016/j.ajog.2017.10.395
• Brilakis, E. S., Edson, R., Bhatt, D. L., Goldman, S., Holmes, D. R., Rao, S. V., Shunk, K., Rangan, B. V., Mavromatis, K., Ramanathan, K., Bavry, A. A., Garcia, S., Latif, F., Armstrong, E., Jneid, H., Conner, T. A., Wagner, T., Karacsonyi, J., Uyeda, L., , Ventura, B., et al. (2018). Drug-eluting stents versus bare-metal stents in saphenous vein grafts: a double-blind, randomised trial. Lancet (London, England), 391(10134), 1997-2007.
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  Few studies have examined the efficacy of drug-eluting stents (DES) for reducing aortocoronary saphenous vein bypass graft (SVG) failure compared with bare-metal stents (BMS) in patients undergoing stenting of de-novo SVG lesions. We assessed the risks and benefits of the use of DES versus BMS in de-novo SVG lesions.
• Chinyere, I. R., Moukabary, T., Goldman, S., & Juneman, E. (2018). Electrical and mechanical alternans during ventricular tachycardia with moderate chronic heart failure. Journal of Electrocardiology, 51(1), 33-37.
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  A chronic heart failure (CHF) rat underwent epicardial programmed electrical stimulation (PES). Ventricular tachycardia (VT) developed during PES. Mechanical alternans was noted despite fixed tachycardia cycle length. Anti-tachycardia pacing attempts initiated a second VT that generated pulse intermittently and then degenerated into pulseless VT with electrical alternans.To our knowledge electrical and mechanical alternans have not been recorded in animal models of CHF during VT. The distinct events of mechanical alternans and electrical alternans may be indicative of progressively worsened calcium handling in the compromised cardiomyocytes.Although ion channel differences between rodents and humans exist, this work attempts to demonstrate this rat model's usefulness in understanding cardiac electrophysiology in CHF.
• Weisbord, S. D., Gallagher, M., Jneid, H., Garcia, S., Cass, A., Thwin, S. S., Conner, T. A., Chertow, G. M., Bhatt, D. L., Shunk, K., Parikh, C. R., McFalls, E. O., Brophy, M., Ferguson, R., Wu, H., Androsenko, M., Myles, J., Kaufman, J., Palevsky, P. M., & , P. T. (2018). Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine. The New England journal of medicine, 378(7), 603-614.
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  Intravenous sodium bicarbonate and oral acetylcysteine are widely used to prevent acute kidney injury and associated adverse outcomes after angiography without definitive evidence of their efficacy.
• Avery, R. J., Cook, J. L., Juneman, E. B., Kazui, T., Khalpey, Z. I., Lick, S. D., Singh, S., Smith, R. G., Suryanarayana, P. G., & Sweitzer, N. K. (2017). (1349) - A Minimaly Invasive Left Ventricular Asssist Device Surgical Appraoch Is More Durable at Protecting Right Ventricular Function Than a Full Sternotomy. Journal of Heart and Lung Transplantation, 36(4), S440-S441. doi:10.1016/j.healun.2017.01.1261
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  To evaluate the effect of surgical approach (median full sternotomy (MS), upper hemisternotomy and minithoracotomy (UHM)) on right ventricular (RV) function after left ventricular assist device (LAVD) implantation.
• Avery, R. J., Cook, J. L., Juneman, E. B., Kazui, T., Khalpey, Z. I., Lick, S. D., Smith, R. G., Suryanarayana, P. G., & Sweitzer, N. K. (2017). (1351) – Minimally Invasive Off Pump HVAD Placement in Redo Patients: Is It a Better Approach?. Journal of Heart and Lung Transplantation, 36(4), S441. doi:10.1016/j.healun.2017.01.1263
• Avery, R. J., Cook, J. L., Juneman, E. B., Kazui, T., Khalpey, Z. I., Lick, S. D., Smith, R. G., Suryanarayana, P. G., & Sweitzer, N. K. (2017). (1353) – Minimally Invasive Off-Pump HVAD vs Full Sternotomy On-Pump LVAD Placement: A Better Option?. Journal of Heart and Lung Transplantation, 36(4), S442. doi:10.1016/j.healun.2017.01.1265
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  To evaluate short-term clinical outcomes of HVAD (HeartWare®) off-pump placement with upper ministernotomy and minithoracotomy compared to on pump LVAD implant with median sternotomy.
• Chinyere, I. R., Goldman, S. A., Juneman, E., Koevary, J. W., & Lancaster, J. J. (2017). 247 - Cardiac Grafts Engineered Fromvhuman Ipsc Ventricular Pure or Heterogeneous Cardiomyocytes Display Synchronousand Spontaneous Contraction and Reduces Ventricular Tachycardia in Rats with Chronic Heart Failure. Journal of Cardiac Failure, 23(8), S90. doi:10.1016/j.cardfail.2017.07.262
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  Background: Twenty six million people worldwide are diagnosed with chronic heart failure (CHF). With only 5000 heart transplants performed annually, the prognosis for these individuals is poor and new therapeutic options are needed. Previously we have described a cardiac engineered graft comprised of human induced pluripotent stem cell (iPSC) derived cardiomyocytes co-cultured with fibroblasts in a bio-absorbable mesh. While this work is exciting, few studies to date have examined comparatively the therapeutic benefits of different cardiac populations. In the present study we engineered grafts generated with either hiPSC derived heterogeneous cardiac myocytes (hetCMs) or ventricular pure myocyte (VMs) populations to compare functional outcomes in a rat model of CHF. Methods: Cardiac grafts were generated with hetCMs or VMs (Axiogenesis) by co-culture into a 3D bioabsorbable mesh with human dermal fibroblasts. The hetCMs contain 60% ventricular, 40% atrial and nodal-like cardiomyocytes. The VMs contain 90% ventricular and 10% atrial cardiomyocytes. Grafts were evaluated in culture out to 6 days. Adult male Sprague-Dawley rats underwent permanent left coronary artery ligation and were randomized to Sham, CHF or graft treatment. Hemodynamic pressure measurements were performed at 6 weeks post-ligation with Millar solid state micromanometer pressure catheters. Ventricular tachycardia (VT) induction studies were performed at study endpoint (3 weeks after implant) to evaluate VT susceptibility using methods developed in the laboratory. Results: Both HetCM and VM generated cardiac grafts displayed synchronous and spontaneous contractions after 48 hrs in culture and maintained an average contraction rate of 67 ± 6 (hetCM) and 71 ± 9 (VM) beats per minute (n = 10 per group). Implantation of HetCM and VM grafts statistically (P < .05) improved EDP 45% vs 14% and resulted in decreased susceptibility of VT induction 54% vs 65% respectively (n = 10). Conclusion: Cardiac grafts engineered with hetCMs or VMs and implanted in a rat CHF model can lower LV EDP in-vivo while decreasing susceptibility of induced VT. This approach raises the possibility that iPSC derived engineered grafts may be used as a treatment for VT in patients with CHF.
• Chinyere, I. R., Goldman, S., Juneman, E. B., Koevary, J., Lancaster, J. J., & Mohran, S. E. (2017). Abstract 344: Cardiac Grafts Engineered From Human Induced Pluripotent Stem Cell Ventricular Pure or Heterogeneous Cardiomyocytes Display Synchronous and Spontaneous Contraction and Reduce Ventricular Tachycardia in Rats with Chronic Heart Failure. Circulation Research, 121(suppl_1). doi:10.1161/res.121.suppl_1.344
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  Background: Twenty six million people worldwide are diagnosed with chronic heart failure (CHF). With only 5000 heart transplants performed annually, the prognosis for the remaining individuals is poor and new therapeutic options are needed. Previously we have described a cardiac engineered graft comprised of human induced pluripotent stem cell (iPSC) derived cardiomyocytes co-cultured with fibroblasts in a bio-absorbable mesh. Few studies to date have examined comparatively the therapeutic benefits of different cardiac populations. In the present study we engineered grafts generated with either hiPSC derived heterogeneous cardiac myocytes (hetCMs) or ventricular pure myocyte (VMs) populations to compare functional outcomes in a rat model of CHF. Methods: Cardiac grafts were generated with hetCMs or VMs (Axiogenesis) by co-culture into a 3D bioabsorbable mesh with human dermal fibroblasts. The hetCMs contain 60% ventricular, 40% atrial and nodal-like cardiomyocytes. The VMs contain 90% ventricular and 10% atrial cardiomyocytes. Grafts were evaluated in culture out to 6 days. Adult male Sprague-Dawley rats underwent permanent left coronary artery ligation and were randomized to Sham, CHF or graft treatment. Hemodynamic pressure measurements were performed at 6 weeks post-ligation with Millar solid state micromanometer pressure catheters. Ventricular tachycardia (VT) induction studies were performed at study endpoint (3 weeks after implant) to evaluate VT susceptibility using methods developed in the laboratory. Results: Both HetCM and VM generated cardiac grafts displayed synchronous and spontaneous contractions after 48hrs in culture and maintained an average contraction rate of 67±6 (hetCM) and 71±9 (VM) beats per minute (n=10 per group). Implantation of HetCM and VM grafts lowered (p
• Chinyere, I., Chu, M., Goldman, S., Gregorio, C., Hutchinson, M., Juneman, E., Lancaster, J., Moukabary, T., Novak, S., Weigand, K., & Witte, R. (2017). Abstract 86: Mapping and Inducing Ventricular Tachycardia in Cardiomyopathic Animal Models. Circulation Research, 121(suppl_1). doi:10.1161/res.121.suppl_1.86
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  Introduction: In the United States, one in three deaths is attributed to cardiovascular disease (CVD). With CVD, sudden cardiac death is a common cause of mortality, specifically by way of ventricular tachycardia (VT) and ventricular fibrillation. We propose the application of our custom software to evaluate the electrophysiologic (EP) properties of animal models of ischemic and non-ischemic dilated cardiomyopathies. Methods: Adult male Sprague-Dawley rats with left coronary artery ligation and adult male and female transgenic Fragile X cardiomyopathic mice were sedated with Inactin and Isoflurane, respectively, and underwent hemodynamic measurements and/or EP testing. Using a PowerLab system and LabChart software, three-lead electrocardiograms were recorded. Using a pressure catheter, hemodynamic parameters were calculated. Using a concentric microelectrode (World Precision Inc.), a clinical EP catheter (Bard Inc.), and custom MATLAB software, local epicardial monophasic action potentials (MAP) and local epicardial voltages were recorded. Using custom MATLAB software for programmed electrical stimulation (PES), VT was induced epicardially with a clinically-accepted drivetrain. Animals underwent eight equidistant ‘S1’ stimulations followed by a premature ‘S2’ stimulation. The S2 stimulation was decreased by 5 milliseconds until loss of capture, indicating the effective refractory period. Sustained ventricular tachycardia (sVT) has been defined as more than fifteen consecutive premature ventricular contractions. Results: The chronic heart failure (CHF) rats had documented hemodynamic heart failure with elevated LV EDPs, and decreased EFs. Mapping and PES was performed on the two groups of rats, namely CHF and Sham-operated. In the CHF group, 71% (27/39) of the rats exhibited sVT, while 0% (0/10) of the Sham-operated rats exhibited sVT. Mapping was also performed on the two groups of mice, namely Wild-Type and Fragile X. Conclusions: We have performed clinically-relevant EP studies in CHF rats and in Fragile X dilated cardiomyopathic mice. These EP studies demonstrate our ability to evaluate and validate the phenotypes of animal models of cardiomyopathies and demonstrate the potential to evaluate the effectiveness of new therapies.
• Chinyere, I., Moukabary, T., Goldman, S., & Juneman, E. B. (2017). . Electrical and Mechanical Alternans during Ventricular Tachycardia with Moderate Chronic Heart Failure. Journal of Electrocardiography. doi:doi.org/10.1016/j.jelectrocard.2017.09.002
• Cosgrove, R. H., Avery, R. J., Basken, R. L., Cook, J. L., Hewlett, D. A., Juneman, E. B., Kazui, T., Khalpey, Z. I., Lick, S. D., Smith, R. G., Suryanarayana, P. G., & Sweitzer, N. K. (2017). (1293) - D-dimer as a Prognostic Indicator for Survival or Death in Mechanical Circulatory Support Device Patients. Journal of Heart and Lung Transplantation, 36(4), S421. doi:10.1016/j.healun.2017.01.1205
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  To investigate the utility of measuring D-dimer levels as a harbinger of mortality in mechanical circulatory support (MCS) patients. The delineation of an additional biomarker to help guide therapy and may provide some insight into physiology.
• Juneman, E. B., Goldman, S., Moukabary, T., & Chinyere, I. (2017). Electrical and Mechanical Alternans during Ventricular Tachycardia with Moderate Chronic Heart Failure. Journal of Electrocardiography. doi:doi.org/10.1016/j.jelectrocard.2017.09.002
• Pandey, A. C., Lancaster, J. J., Harris, D. T., Goldman, S., & Juneman, E. (2017). Cellular Therapeutics for Heart Failure: Focus on Mesenchymal Stem Cells. Stem cells international, 2017, 9640108.
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  Resulting from a various etiologies, the most notable remains ischemia; heart failure (HF) manifests as the common end pathway of many cardiovascular processes and remains among the top causes for hospitalization and a major cause of morbidity and mortality worldwide. Current pharmacologic treatment for HF utilizes pharmacologic agents to control symptoms and slow further deterioration; however, on a cellular level, in a patient with progressive disease, fibrosis and cardiac remodeling can continue leading to end-stage heart failure. Cellular therapeutics have risen as the new hope for an improvement in the treatment of HF. Mesenchymal stem cells (MSCs) have gained popularity given their propensity of promoting endogenous cellular repair of a myriad of disease processes via paracrine signaling through expression of various cytokines, chemokines, and adhesion molecules resulting in activation of signal transduction pathways. While the exact mechanism remains to be completely elucidated, this remains the primary mechanism identified to date. Recently, MSCs have been incorporated as the central focus in clinical trials investigating the role how MSCs can play in the treatment of HF. In this review, we focus on the characteristics of MSCs that give them a distinct edge as cellular therapeutics and present results of clinical trials investigating MSCs in the setting of ischemic HF.
• Pandey, A. C., Lancaster, J. J., Harris, D., Goldman, S., & Juneman, E. B. (2017). Cellular Therapeutics for Heart Failure: Focus on Mesenchymal Stem Cells. Stem Cell International, 2017, 12. doi:doi.org/10.1155/2017/9640108
• Sanchez, P., Lancaster, J. J., Weigand, K., Mohran, S. E., Goldman, S., & Juneman, E. (2017). Doppler Assessment of Diastolic Function Reflect the Severity of Injury in Rats With Chronic Heart Failure. Journal of cardiac failure, 23(10), 753-761.
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  For chronic heart failure (CHF), more emphasis has been placed on evaluation of systolic as opposed to diastolic function. Within the study of diastology, measurements of left ventricular (LV) longitudinal myocardial relaxation have the most validation. Anterior wall radial myocardial tissue relaxation velocities along with mitral valve inflow (MVI) patterns are applicable diastolic parameters in the differentiation between moderate and severe disease in the ischemic rat model of CHF. Myocardial tissue relaxation velocities correlate with traditional measurements of diastolic function (ie, hemodynamics, Tau, and diastolic pressure-volume relationships).
• Sanchez, P., Lancaster, J., Weigand, K., Mohran, S. A., Goldman, S., & Juneman, E. B. (2017). Doppler Assessment of Diastolic Function Reflect the Severity of Injury in Rats With Chronic Heart Failure.. Journal of Cardiac Failure. doi:10.1016/j.cardfail.2017.08.446
• Weigand, K., Witte, R., Moukabary, T., Chinyere, I., Lancaster, J., Pierce, M. K., Goldman, S., & Juneman, E. (2017). In vivo Electrophysiological Study of Induced Ventricular Tachycardia in Intact Rat Model of Chronic Ischemic Heart Failure. IEEE transactions on bio-medical engineering, 64(6), 1393-1399.
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  The objective of this study was to define the clinical relevance of in vivo electrophysiologic (EP) studies in a rat model of chronic ischemic heart failure (CHF).
• Avery, R., Chinyere, I., Daugherty, S., Goldman, S., Jokerst, C., Juneman, E., Kim, S., Kim, B. N., Lancaster, L. D., Lancaster, J. J., & Larson, B. (2016). Abstract 205: Feasibility and Testing of a Human Induced Pluripotent Stem Cell Derived Cardiac Patch in a Pre-clinical Swine Model of CHF. Circulation Research, 119(suppl_1). doi:10.1161/res.119.suppl_1.205
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  Introduction: Previously we have demonstrated that a tissue engineered heart patch comprised of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) and fibroblasts improves both left ventricular (LV) systolic and diastolic function in a rat model of CHF. In this study we tested the feasibility of upscaling cardiac patch size and surgical deployment in a swine model of CHF to test clinical utility. Methods: Four male Gottingen mini swine 20-25kg and three domestic swine 50-60kg were infarcted using percutaneous methods. Embolizing coils were deployed via catheter distal to the first diagonal branch of the left anterior descending (LAD) coronary artery and animals recovered for 4 weeks. Cardiac patches engineered with bio absorbable polygalactin-910 knitted mesh, dermal fibroblasts and hiPSC-CMs were cultured and implanted on the infarcted epicardium 4 weeks after MI. Cardiac magnetic resonance imaging was performed at baseline, 4 and 8 weeks post MI. All swine were implanted with continuous event recorders to acquire surface electrocardiogram during the entire study. In addition quality of life and functional capacity were assessed through video monitoring and treadmill exertion testing respectively. Infarct size was determined through 2,3,5-triphenyltetrazolium chloride staining. Results: LAD occlusion resulted in a significant (P
• Chinyere, I., Weigand, K., Moukabary, T., Witte, R. S., Lancaster, J. J., Goldman, S., & Juneman, E. (2016). Abstract 71: Model of Induced Ventricular Tachycardia and Cardiac Electrophysiological Mapping. Circulation Research, 119(suppl_1). doi:10.1161/res.119.suppl_1.71
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  Introduction: We have developed a computer user interface able to provide prescribed programmed electrical stimulation (PES) to induce sustained-ventricular tachycardia (VT) in rats with chronic heart failure (CHF). We propose this program to examine the cardiac electrophysiology (EP) properties and arrhythmogenic potential in varying disease models and as a method of evaluating drug safety in an intact animal. Methods: Using custom MATLAB software developed in our laboratory, we performed monophasic action potential (MAP) recordings and initiated protocols to induce sustained-VT through right ventricular epicardium PES outputs. Studies were performed in adult male Sprague-Dawley rats (N=22) six weeks after left coronary artery ligation under anesthesia and open chest. Results: CHF was verified by standard hemodynamic and echocardiographic parameters as is standard in our laboratory. In the CHF group, 71% (10/14) of the rats exhibited sustained-VT in response to PES versus 0% (0/8) of Sham rats. MAP recordings taken prior-to and during VT induction provided examples of localized activity for arrhythmia mechanisms such as delayed afterdepolarizations. Mechanical alternans, electrical alternans, intermittent pulse generations, and pulseless electrical activity were all observed in this model. EP data analysis showed a decreased (p
• Chinyere, I., Weigand, K., Moukabary, T., Witte, R. S., Lancaster, J., Goldman, S., & Juneman, E. B. (2016). Model of Induced Ventricular Tachycardia and Cardiac Electrophysiological Mapping. Circulation Research, 119(Supl 1), A 71.
• Hernandez, C. A., Reed, K. L., Juneman, E. B., & Cohen, W. R. (2016). Changes in Sonographically Measured Inferior Vena Caval Diameter in Response to Fluid Loading in Term Pregnancy. Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine, 35(2), 389-94.
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  The purpose of this study was to determine whether the inferior vena caval (IVC) diameter is influenced by intravascular volume changes in pregnancy.
• Lancaster, J. J., Repetti, G. G., Pandey, A. C., Weigand, K., Bahl, J. J., Juneman, E., & Goldman, S. (2016). Abstract 360: Implantation of an Induced Pluripotent Stem Cell Derived Cardiomyocyte Tissue Engineered Patch Improves Left Ventricular Function and Electro-mechanical Coupling in Rats With Heart Failure. Circulation Research, 119(suppl_1). doi:10.1161/res.119.suppl_1.360
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  Background: Chronic Heart Failure (CHF) is the leading cause of hospital readmissions and mortality in the US. Here we report the effects of surgically delivering a human bioengineered patch of human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs) and fibroblasts on left ventricular (LV) function in rats with CHF. We evaluate improvements in LV systolic and diastolic function, electromechanical coupling and gene expression after patch implantation. Methods: Adult male Sprague-Dawley rats underwent left coronary artery ligation and were randomized to Sham (N = 8), CHF (N = 8–21), and CHF+hiPSC-CM patch (N = 20–24). Heterogeneous hiPSC-CMs were seeded and co-cultured onto a vicryl matrix embedded with human dermal fibroblasts. Echocardiography was performed at 3 and 6 weeks post-randomization. Hemodynamic pressure measurements were performed at 6 weeks post-ligation with Millar solid state micromanometer pressure catheters. Open chest Electrophysiologic (EP) mapping was performed at 6 weeks post ligation. Gene expression was evaluated through qRT-PCR. Results: 48 hours into culture hiPSC-CMs patches displayed synchronized and spontaneous contractions which developed in robustness over time. At maximal robustness, contractions were visualized across the full thickness of the construct. Contractions were recorded at 36 ± 5 beats BPM. Three weeks after patch implantation (6 weeks post ligation) the hiPSC-CM patch decreased (P < .05) LV EDP (45%), Tau (29%), E/e‘ (23%) and increased (P < .05), e’/a' (36%) with trending improvements in EF (14%) and e' (20%). EP studies show electro-mechanical coupling between the patch and the native myocardium with normal activation through the patch and increases (P < .05) voltage amplitude in CHF versus hiPSC-CM patch treated rats (1 ± 0.5 mV vs 6 ± 1.5mV). Rats treated with the hiPSC-CM patch showed significant (P < .05) fold expression of Cx43 (3.3), ANG-1 (13.63), VEGF (3.8), βMYH7 (6.4) and IGF-1 (22.9) versus control. Conclusion: Cardiac patch implantation with hiPSC derived cardiomyocytes is an effective and feasible method of treating CHF with improvements in systolic function, diastolic function, and electro-mechanical coupling in rats with CHF.
• Lancaster, J., Chinyere, I., Kim, B. N., Daugherty, S., Kim, S., Jokerst, C., Avery, R., Larson, B., Lancaster, L. D., Juneman, E. B., & Goldman, S. (2016). . Feasibility and Testing of a Human Induced Pluripotent Stem Cell Derived Cardiac Patch in a Pre-clinical Swine Model of CHF. Circulation Research, 119(Supl 1), A 205.
• Lancaster, J., Pandey, A., Weigand, K., Bahl, J., Juneman, E. B., & Goldman, S. (2016). Implantation of an induced pluripotent stem cell derived cardiomyocyte tissue engineered patch improves left ventricular function and electromechanical coupling in rats with heart failure. Journal of Cardiac Failure, 22(8), S 123. doi:http://dx.doi.org/10.1016/j.cardfail.2016.06.383
• Mohran, S., Lancaster, J. J., Sanchez, P., Goldman, S., & Juneman, E. (2016). Abstract 48: Differentiation of Moderate and Severe Ischemic Heart Failure by Invasive and Non-invasive Assessments of Diastolic Function in a Rat Model of Chronic Heart Failure. Circulation Research, 119(suppl_1). doi:10.1161/res.119.suppl_1.48
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  Background: This work is designed to determine if specific left ventricle (LV) pressure-volume relations, hemodynamic, and echo derived parameters of diastolic function are able to separate severe from moderate CHF in rats with left coronary artery occlusion. Hypothesis: Echocardiographic indices of diastolic function, end-diastolic pressure (EDP), dead volume, stiffness constants (k), and pressure volume relations predict the severity of CHF in infarcted rats. Methods: Male Sprague Dawley rats (N=14) were randomized to undergo left coronary artery ligation or sham operation. Echocardiography was performed at 3 and 6 weeks post coronary ligation. The rats were categorized into moderate or severe CHF according to their LVEDP at 6 weeks post ligation. Invasive hemodynamic measurements with solid state micro manometer pressure catheters as well as diastolic pressure-volume relation values were obtained at the 6 week end point. Results: Moderate and severe CHF rats had significantly (P
• Mohran, S., Lancaster, J., Sanchez, P., Goldman, S., & Juneman, E. B. (2016). Differentiation of Moderate and Severe Ischemic Heart Failure by Invasive and Non-invasive Assessments of Diastolic Function in a Rat Model of Chronic Heart Failure. Circulation Research, 119(Supl 1), A48.
• Bahl, J. J., Goldman, S., Juneman, E., Lahood, N., Lancaster, J. J., Moukabary, T., Pandey, A., Sanchez, P., Weigand, K., Bahl, J. J., Goldman, S., Juneman, E., Lahood, N., Lancaster, J. J., Moukabary, T., Pandey, A. C., Sanchez, P., & Weigand, K. (2015). Abstract 425: Induced Pluripotent Stem Cell Derived Cardiomyocyte Tissue Engineered Scaffold Improves Left Ventricular Function and Electro-Mechanical Coupling in Rats with Heart Failure. Circulation Research, 117(suppl_1). doi:10.1161/res.117.suppl_1.425
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  Background: Chronic Heart Failure (CHF) is the leading cause of hospital readmissions in the United States. It may result from systolic or diastolic dysfunction, which often coexists. Here we report the effects of delivering human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs) via a bioengineered patch on left ventricular function in rats with CHF. Methods: Adult male Sprague-Dawley rats underwent left coronary artery ligation and were randomized to Sham, CHF, and hiPSC-CM patch. High purity human hiPSC-CMs were obtained from Cellular Dynamics International, seeded and co-cultured onto a vicryl matrix embedded with human dermal fibroblasts. Echocardiography was performed at 3 and 6 weeks post-randomization. Hemodynamic pressure measurements were performed at 6 weeks post-ligation with Millar solid state micromanometer catheters. Open chest Electrophysiologic (EP) mapping was performed at 6 weeks post ligation. Results: Patches constructed with hiPSC-CMs displayed synchronized and spontaneous contractions within 48hrs of culture which developed in robustness over time. At maximal robustness, contractions were visualized across the full thickness of the construct. Contractions were recorded at 36+5 beats BPM. Three weeks after implantation, the hiPSC-CM patch decreased LV EDP (45%), Tau (29%), E/e’ (23%) and increased, EF (14%), e’ (20%), and e’/a’ (36%) versus CHF. EP studies show electro-mechanical coupling between the patch and the native myocardium with normal activation through the patch and increases (P
• Chu, M., Novak, S. M., Cover, C., Wang, A. A., Chinyere, I. R., Juneman, E., Zarnescu, D. C., Wong, P. K., & Gregorio, C. (2018). Increased Cardiac Arrhythmogenesis Associated with Gap Junction Remodeling with Upregulation of RNA Binding Protein FXR1. Circulation.
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  Background -Gap junction remodeling is well established as a consistent feature of human heart disease involving spontaneous ventricular arrhythmia. The mechanisms responsible for gap junction remodeling that include alterations in the distribution of, and protein expression within, gap junctions are still debated. Studies reveal that multiple transcriptional and post-transcriptional regulatory pathways are triggered in response to cardiac disease, such as those involving RNA-binding proteins. The expression levels of Fragile X mental retardation autosomal homolog 1 (FXR1), an RNA-binding protein, are critical to maintain proper cardiac muscle function; however, the connection between FXR1 and disease is not clear. Methods -To identify the mechanisms regulating gap junction remodeling in cardiac disease, we sought to identify: the functional properties of FXR1 expression, direct targets of FXR1 in human left ventricle dilated cardiomyopathy (DCM) biopsy samples and mouse models of DCM through BioID proximity assay and RNA immunoprecipitation, how FXR1 regulates it targets through RNA stability and luciferase assays, and functional consequences of altering the levels of this important RNA binding protein through the analysis of cardiac-specific FXR1 knockout mice and mice injected with 3xMyc-FXR1 adeno-associated virus. Results -FXR1 expression is significantly increased in tissue samples from human and mouse models of DCM via western blot analysis. FXR1 associates with intercalated discs and integral gap junction proteins Cx43, Cx45 and ZO-1 were identified as novel mRNA targets of FXR1 using a BioID proximity assay and RNA immunoprecipitation. Our findings show FXR1 is a multifunctional protein involved in translational regulation and stabilization of its mRNA targets in heart muscle. Additionally, introduction of 3xMyc-FXR1 via adeno-associated virus into mice leads to redistribution of gap junctions and promotes ventricular tachycardia showing functional significance of FXR1 upregulation observed in DCM. Conclusions -In DCM, increased FXR1 expression appears to play an important role in disease progression by regulating gap junction remodeling. Together this study provides a novel function of FXR1 namely that it directly regulates major gap junction components, contributing to proper cell-cell communication in the heart.
• Desai, A. A., Dherange, P., Juneman, E., Lee, K. S., Lee, J. Z., Low, S., Suryanarayana, P., & Yun, S. (2015). Abstract 16722: Comparison of Tricuspid Annular Plane Systolic Excursion to Fractional Area Change for Evaluation of Right Ventricular Systolic Function: Systematic Review and Meta-analysis. Circulation, 132(suppl_3). doi:10.1161/circ.132.suppl_3.16722
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  Introduction: Right ventricular (RV) systolic function is prognostically important, but its assessment by echocardiography remains challenging. Tricuspid annular plane systolic excursion (TAPSE) and fractional area change (FAC) have been evaluated as echocardiographic indices for RV ejection fraction (RVEF), but their correlation with the gold-standard cardiac magnetic resonance imaging (CMRI) remains unclear. The aim of this meta-analysis is to pool and compare data from all studies that evaluated reliability of TAPSE and FAC in comparison to CMRI-derived RVEF. Hypothesis: We assessed the hypothesis that FAC is superior to TAPSE as an echocardiographic index for measurement of RV systolic function. Methods: A systematic literature search of 4493 potentially relevant citations from PubMed, and EMBASE databases yielded 25 eligible studies. The means of TAPSE and FAC, CMRI-derived RVEF, and correlation coefficients were pooled from each study for analysis. Results: A total of 25 studies were included in the final analysis, with a total of 1,858 patients who underwent 2D-echocardiography and cardiac MRI. FAC, compared to TAPSE, exhibited numerically superior correlation to CMRI RVEF (R2 = 0.63, and R2 = 0.15 respectively). Subgroup analysis revealed that FAC’s correlation was also numerically superior in patients with reduced right ventricular ejection fraction of less than 45% (R2 = 0.4 and R2 = 0.17, respectively). In patients with pulmonary hypertension (PH), TAPSE and FAC had mean correlation coefficients of 0.57±0.1 and 0.60±0.13, and were not statistically different (p=0.85). Conclusions: FAC is superior to TAPSE as an echocardiographic index for measurement of RV systolic function, even in patients with reduced right ventricular ejection fraction, but not in patients with PH. The adaptation to increased afterload of PH likely culminates in distinct and asymmetric patterns of RV dysfunction, which are not well assessed by FAC or TAPSE.
• Dherange, P., Desai, A. A., Juneman, E., Lee, K. S., Lee, J., Low, S., Suryanarayana, P., & Yun, S. (2015). Abstract 16722: Comparison of Tricuspid Annular Plane Systolic Excursion to Fractional Area Change for Evaluation of Right Ventricular Systolic Function: Systematic Review and Meta-analysis. Circulation.
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  Introduction: Right ventricular (RV) systolic function is prognostically important, but its assessment by echocardiography remains challenging. Tricuspid annular plane systolic excursion (TAPSE) an...
• Goldman, S., Harris, D., Juneman, E., Lancaster, J., Pandey, A. C., Goldman, S., Goldman, S. A., Harris, D. T., Juneman, E., Lancaster, J. J., & Pandey, A. C. (2015). Abstract 151: Cell-based Therapies for Heart Failure: Changes in Cytokine Expression From Mesenchymal Stem Cells and Induced Pluripotent Stem Cell Derived Cardiomyocytes. Circulation Research, 117(suppl_1). doi:10.1161/res.117.suppl_1.151
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  Mesenchymal stem cells (MSCs) use paracrine signaling to modulate the cellular microenvironment via expression of cytokines, chemokines, and adhesion molecules to aid and promote endogenous repair. Induced pluripotent stem cell derived cardiomyocyte (iPSC-CMs) and mesenchymal stem cells (MSCs) together may play a synergistic role in changing the microenvironment milieu to allow for endogenous cellular repair through paracrine signaling. Cytokine expression is involved in the progression of heart failure (HF). Using a rat model of HF, cell based therapies with a fibroblast embedded patch only, iPSC-CM patch, and MSCs via tail vein (IV) or intracardiac injections (IC) to the left ventricle (LV) were administered, and RNA was subsequently isolated, and real-time polymerase chain reaction (PCR) was performed for analysis of gene expression. Evaluation of gene expression revealed significant increases in the expression of connexin 43 with iPSC-CMs (p
• Gupta, A., Gupta, G., Kim, T. Y., Shi, G., Weigand, K., Batai, K., Fleming, I., Kanady, J., Rutledge, C., Nair, N., Groth, J., Juneman, E. B., Goldman, S., Indik, J. H., Hillery, C., Garcia, J. G., Machado, R. F., Kittles, R., Dudley, S. C., , Choi, B., et al. (2018). IL-18 is a novel mediator of prolonged QTc and ventricular arrhythmias associated with Sickle Cell Disease. Proceedings of the National Academy of Sciences.
• Bahl, J. J., Goldman, S., Juneman, E., Lancaster, J. J., Sanchez, P., Weigand, K., Bahl, J. J., Goldman, S., Juneman, E., Lancaster, J. J., Sanchez, P., & Weigand, K. (2014). Abstract 9: Development And Testing Of A Human Induced Pluripotetent Stem Cell Derived Cardiac Scaffold. Circulation Research, 115(suppl_1). doi:10.1161/res.115.suppl_1.9
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  Introduction: Cell-based regenerative therapies hold promise in providing treatment strategies for heart failure. Previous work from our laboratory has shown that tissue engineered cardiac constructs enhance improvements in cardiac function by providing structural and nutrient support, potentially aiding in transplanted cell survival, integration and re-population of injured tissues. Our current studies focus on the development and testing of second-generation cardiac constructs utilizing high purity human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs). Methods: High purity hiPSC-CMs were seeded and co-cultured onto a vicryl matrix embedded with biologically active human dermal fibroblasts. The hiPSC-CM constructs were maintained at 37°C and 5% CO2. Patches were constructed maintained as described for both in vitro and in vivo evaluation. Patches for in vivo evaluation were seeded, cultured and implanted onto the rat heart 3 weeks after left coronary artery ligation to assess improvements in LV function. Patches prepared for in vitro evaluation were seeded and cultured 1-10 days. Results: Patches constructed with hiPSC-CMs displayed synchronized and spontaneous contractions within 48hrs of culture which developed in robustness over time. At maximal robustness, contractions were visualized across the full thickness of the construct. Contractions were recorded at 36+5 beats BPM. In addition hiPSC-CM constructs respond to electrical stimulation with increased rate of contraction while maintaining their synchrony. Post pacing, the hiPSC-CM constructs return to their intrinsic rhythm. Conclusion: These findings show that high purity hiPSC-CMs can be seeded and co-cultured onto a vicryl and fibroblast construct in manner permitting adhesion and electromechanical coupling of the hiPSC-CMs to form a fully contractile construct. This is supported by the observation that the hiPSC-CMs contract spontaneously and in a synchronized manner in a directional fashion.
• Khan, M. F., Gottesman, S., Boyella, R., & Juneman, E. (2014). Gemcitabine-induced cardiomyopathy: a case report and review of the literature. Journal of medical case reports, 8, 220.
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  Newly developed antineoplastic drugs have resulted in improvements in morbidity and mortality from many forms of cancers. However, some of these new chemotherapeutic agents have potentially lethal side effects, which are now being exposed with their widespread use. Gemcitabine is a nucleoside analog, which is a commonly used agent for various solid organ malignancies. Phase 1 and 2 trials with gemcitabine did not show significant risk for cardiotoxicity; however, with its widespread clinical use over the last decade, a few cases of cardiotoxicity related to gemcitabine use have been reported. Cardiomyopathy after the use of gemcitabine monotherapy is extremely rare; and only one such case has been reported in detail previously.
• Lancaster, J. J., Juneman, E., Arnce, S. A., Johnson, N. M., Qin, Y., Witte, R., Thai, H., Kellar, R. S., Ek Vitorin, J., Burt, J., Gaballa, M. A., Bahl, J. J., & Goldman, S. (2014). An electrically coupled tissue-engineered cardiomyocyte scaffold improves cardiac function in rats with chronic heart failure. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 33(4), 438-45.
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  Varying strategies are currently being evaluated to develop tissue-engineered constructs for the treatment of ischemic heart disease. This study examines an angiogenic and biodegradable cardiac construct seeded with neonatal cardiomyocytes for the treatment of chronic heart failure (CHF).
• Gheorghiade, M., Böhm, M., Greene, S. J., Fonarow, G. C., Lewis, E. F., Zannad, F., Solomon, S. D., Baschiera, F., Botha, J., Hua, T. A., Gimpelewicz, C. R., Jaumont, X., Lesogor, A., Maggioni, A. P., & , A. I. (2013). Effect of aliskiren on postdischarge mortality and heart failure readmissions among patients hospitalized for heart failure: the ASTRONAUT randomized trial. JAMA, 309(11), 1125-35.
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  Hospitalizations for heart failure (HHF) represent a major health burden, with high rates of early postdischarge rehospitalization and mortality.
• Juneman, E. B., Arsanjani, R., Thai, H., Lancaster, J., Madwed, J., & Goldman, S. (2013). Development of a Novel Sodium-Hydrogen Exchanger Inhibitor for Heart Failure. Journal of Cardiology and Vascular Medicine..
• Juneman, E. B., Maggioni, A. P., Greene, S. J., Fonarow, G. C., Bohm, M., Zannad, F., Solomon, S. D., Lewis, E. F., Baschiera, F., Hua, T. A., Gimpelewicz, C. R., Lesogor, A., & Gheorghiade, M. (2013). ASTRONAUT Investigators and Coordinators. Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial. European Heart Journal, 34(40), 3117 -3127.
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  http://eurheartj.oxfordjournals.org/content/34/40/3117
• Maggioni, A. P., Greene, S. J., Fonarow, G. C., Böhm, M., Zannad, F., Solomon, S. D., Lewis, E. F., Baschiera, F., Hua, T. A., Gimpelewicz, C. R., Lesogor, A., Gheorghiade, M., & , A. I. (2013). Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial. European heart journal, 34(40), 3117-27.
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  The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM).
• Nguyen, J., Juneman, E., & Movahed, M. R. (2013). The value of β-blockers administration during recovery phase of dobutamine stress echocardiography: a review. Echocardiography (Mount Kisco, N.Y.), 30(6), 723-9.
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  Dobutamine stress echocardiography (DSE) is a successful technique for detection of ischemia in patients with suspected coronary artery disease (CAD). There are some data that administration of β-blocker after peak infusion of dobutamine can improve sensitivity. The goal of this manuscript is to review the current literature in regard to the mechanism and accuracy of post-dobutamine β-blocker administration for ischemia detection. In this review, we present 2 case reports followed by detailed review of the literature.
• Tanaka, T. D., Lancaster, J. J., Juneman, E., Bahl, J. J., & Goldman, S. (2013). Clenbuterol plus granulocyte colony-stimulating factor regulates stem/progenitor cell mobilization and exerts beneficial effect by increasing neovascularization in rats with heart failure. Journal of cardiac failure, 19(7), 503-8.
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  Treatment of beta2-adrenergic receptor agonists with myeloid cytokines, such as granulocyte colony-stimulating factor (G-CSF) has been reported to enhance stem/progenitor cell mobilization and proliferation in ischemic myocardium. However, whether the combination therapy of G-CSF and clenbuterol (Clen) contributes to improved left ventricular (LV) function remains uncertain. We investigated whether this combination therapy induced bone marrow-derived stem/progenitor cell mobilization, neovascularization, and altered LV function after acute myocardial infarction (MI).
• Bakaeen, F. G., Sethi, G., Wagner, T. H., Kelly, R., Lee, K., Upadhyay, A., Thai, H., Juneman, E., Goldman, S., & Holman, W. L. (2012). Coronary artery bypass graft patency: residents versus attending surgeons. The Annals of thoracic surgery, 94(2), 482-8; discussion 488.
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  Data are limited regarding the patency of coronary artery bypass grafts performed by residents versus attending surgeons.
• Farkouh, M. E., Domanski, M., Sleeper, L. A., Siami, F. S., Dangas, G., Mack, M., Yang, M., Cohen, D. J., Rosenberg, Y., Solomon, S. D., Desai, A. S., Gersh, B. J., Magnuson, E. A., Lansky, A., Boineau, R., Weinberger, J., Ramanathan, K., Sousa, J. E., Rankin, J., , Bhargava, B., et al. (2012). Strategies for multivessel revascularization in patients with diabetes. The New England journal of medicine, 367(25), 2375-84.
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  In some randomized trials comparing revascularization strategies for patients with diabetes, coronary-artery bypass grafting (CABG) has had a better outcome than percutaneous coronary intervention (PCI). We sought to discover whether aggressive medical therapy and the use of drug-eluting stents could alter the revascularization approach for patients with diabetes and multivessel coronary artery disease.
• Juneman, E. B., Saleh, L., Lancaster, J. J., Thai, H. M., Markham, B., & Goldman, S. (2012). The effects of poloxamer-188 on left ventricular function in chronic heart failure after myocardial infarction. Journal of cardiovascular pharmacology, 60(3), 293-8.
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  Poloxamer-188 (P-188) is a biological membrane sealant that prevents the unregulated entry of Ca into cardiomyocytes and has been shown to have the ability to act as a membrane-repair agent in isolated cardiac myocytes. The purpose of this study was to determine if treatment with P-188 would improve left ventricular (LV) function in a rat chronic heart failure (CHF) model.
• Juneman, E., Saleh, L., Thai, H., Goldman, S., & Movahed, M. R. (2012). Successful coronary angiography with adequate image acquisition using a combination of gadolinium and a power injector in a patient with severe iodine contrast allergy. Experimental and clinical cardiology, 17(1), 17-9.
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  A history of severe allergic reaction to iodine contrast leading to anaphylactic shock presents a dilemma in patients requiring cardiac catheterization. As an alternative, gadolinium has been an interesting and potentially useful agent. However, gadolinium produces poor image quality and has been associated with significant arrhythmias in small case series. Furthermore, there is no consensus about the maximal allowable dose that can be administered to a patient. In the present report, a successful combination of gadolinium contrast with a power injector that produced adequate image quality in a patient with severe allergy to iodine contrast is described. The case was complicated by the occurrence of ventricular fibrillation when damping occurred during injection of contrast into the right coronary artery. This complication has been reported previously with intracoronary gadolinium injection. The report is followed by a brief literature review.
• Thal, S., Boyella, R., Arsanjani, R., Thai, H., Juneman, E., Movahed, M. R., & Goldman, S. (2012). Unusual combination of holt-oram syndrome and persistent left superior vena cava. Congenital heart disease, 7(4), E46-9.
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  Holt-Oram (HO) is a syndrome characterized by congenital cardiovascular malformations, specifically atrial and ventricular septal defects, and skeletal abnormalities of the upper limbs bones. Associations of HO cardiac disorders with other congenital cardiac malformations, specifically persistent left superior vena cava (PLSVC) are rarely reported and its real incidence is unknown. We present a case of this unusual combination in a patient undergoing cardiac resynchronization therapy (CRT) device implant.
• Bahl, J., Goldman, S., Johnson, N., Juneman, E., Lancaster, J., Bahl, J. J., Goldman, S. A., Johnson, N. M., Juneman, E., & Lancaster, J. J. (2011). Abstract P020: A Bioengineered Neonatal Cardiomyocyte Scaffold Promotes Cell Survival and Improves Left Ventricular Function in Rats with Heart Failure. Circulation Research, 109(suppl_1). doi:10.1161/res.109.suppl_1.ap020
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  Background: Cell-based regenerative therapies hold promise as a new treatment for heart failure. Tissue engineered scaffolds used for cell delivery enhance potential improvements in cardiac function by providing the structural and nutrient support for transplanted cell survival, integration, and re-population of injured tissues. Previously, our laboratory reported improvements in left ventricular (LV) function in rats with chronic heart failure (CHF) after placement of a neonatal cardiomyocyte (NCM) seeded 3-dimensional fibroblast construct (3DFC). In brief, 3 weeks after implantation of the NCM-3DFC, LV function improves by increasing (p
• Goldman, S., Sethi, G. K., Holman, W., Thai, H., McFalls, E., Ward, H. B., Kelly, R. F., Rhenman, B., Tobler, G. H., Bakaeen, F. G., Huh, J., Soltero, E., Moursi, M., Haime, M., Crittenden, M., Kasirajan, V., Ratliff, M., Pett, S., Irimpen, A., , Gunnar, W., et al. (2011). Radial artery grafts vs saphenous vein grafts in coronary artery bypass surgery: a randomized trial. JAMA, 305(2), 167-74.
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  Arterial grafts are thought to be better conduits than saphenous vein grafts for coronary artery bypass grafting (CABG) based on experience with using the left internal mammary artery to bypass the left anterior descending coronary artery. The efficacy of the radial artery graft is less clear.
• Kellar, R. S., Lancaster, J. J., Thai, H. M., Juneman, E., Johnson, N. M., Byrne, H. G., Stansifer, M., Arsanjani, R., Baer, M., Bebbington, C., Flashner, M., Yarranton, G., & Goldman, S. (2011). Antibody to granulocyte macrophage colony-stimulating factor reduces the number of activated tissue macrophages and improves left ventricular function after myocardial infarction in a rat coronary artery ligation model. Journal of cardiovascular pharmacology, 57(5), 568-74.
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  Granulocyte macrophage colony-stimulating factor (GM-CSF) promotes infarct expansion and inappropriate collagen synthesis in a myocardial infarction (MI). This study was designed to determine if treatment with anti-GM-CSF will inhibit macrophage migration, preserve function, and limit left ventricular (LV) remodeling in the rat coronary artery ligation model. Treatment with a monoclonal antibody to GM-CSF (5 mg/kg) was initiated 24 hours before coronary artery ligation and continued every 3 days for 3 weeks. Left coronary arteries of rats were ligated, animals were recovered, and cardiac function was evaluated 3 weeks postligation. Tissue samples were processed for histochemistry. Anti-GM-CSF treatment increased LV ejection fraction (37 ± 3% vs 47 ± 5%) and decreased LV end systolic diameter (0.75 ± 0.12 vs 0.59 ± 0.05 cm) with no changes in LV systolic pressure (109 ± 4 vs 104 ± 5 mm Hg), LV end diastolic pressure (22 ± 4 vs 21 ± 2 mm Hg), LV end diastolic diameter (0.96 ± 0.04 vs 0.92 ± 0.05 cm), or the time constant of LV relaxation tau (25.4 ± +2.4 vs 22.7 ± 1.4 milliseconds) (P < 0.05). Significantly lower numbers of tissue macrophages and significant reductions in infarct size were found in the myocardium of antibody-treated animals (81 ± 21.24 vs 195 ± 31.7 positive cells per 0.105 mm, compared with controls. These findings suggest that inhibition of macrophage migration may be beneficial in the treatment of heart failure after MI.
• Kowey, P. R., Crijns, H. J., Aliot, E. M., Capucci, A., Kulakowski, P., Radzik, D., Roy, D., Connolly, S. J., & Hohnloser, S. H. (2011). Efficacy and safety of celivarone, with amiodarone as calibrator, in patients with an implantable cardioverter-defibrillator for prevention of implantable cardioverter-defibrillator interventions or death: the ALPHEE study. Circulation, 124(24), 2649-60.
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  Celivarone is a new antiarrhythmic agent developed for the treatment of ventricular arrhythmias. This study investigated the efficacy and safety of celivarone in preventing implantable cardioverter-defibrillator (ICD) interventions or death.
• Saleh, L., Juneman, E., & Movahed, M. R. (2011). The use of gadolinium in patients with contrast allergy or renal failure requiring coronary angiography, coronary intervention, or vascular procedure. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions, 78(5), 747-54.
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  Coronary artery angiography remains an important procedure for the assessment of coronary arteries. It requires injection of iodinated contrast for the opacification of coronary arteries. Severe allergy to iodine contrast and renal insufficiency are two main problems with iodine-based contrast media. Gadolinium (Gd) has different chemical structure with no cross reactivity with iodine-based contrast media in patients with iodine allergy. The use of Gd is commonly used in contrast-enhanced magnetic resonance imaging for image enhancement, making it a potential alternative in patients in whom iodine is contraindicated. The aim of this manuscript is to review the available literature on the use of Gd in patients with contraindication to iodine contrast due to allergy or in patients with severe renal failure requiring coronary or vascular procedures.
• Lancaster, J., Juneman, E., Hagerty, T., Do, R., Hicks, M., Meltzer, K., Standley, P., Gaballa, M., Kellar, R., Goldman, S., & Thai, H. (2010). Viable fibroblast matrix patch induces angiogenesis and increases myocardial blood flow in heart failure after myocardial infarction. Tissue engineering. Part A, 16(10), 3065-73.
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  This study examines a viable biodegradable three-dimensional fibroblast construct (3DFC) in a model of chronic heart failure. The viable fibroblasts, cultured on a vicryl mesh, secrete growth factors that stimulate angiogenesis.
• Bebbington, C. R., Bebbington, C., Byrne, H. G., Goldman, S. A., Johnson, N. M., Juneman, E., Kellar, R. S., Lancaster, J. J., Stansifer, M., Thai, H. M., & Yarranton, G. T. (2009). Abstract 4740: Antibody to Granulocyte-Macrophage Colony-Stimulating Factor Reduces the Number of Activated Tissue Macrophages and Improves Left Ventricular Function Following Myocardial Infarction in a Rat Coronary-Artery Ligation Model. Circulation, 120.
• Thai, H. M., Juneman, E., Lancaster, J., Hagerty, T., Do, R., Castellano, L., Kellar, R., Williams, S., Sethi, G., Schmelz, M., Gaballa, M., & Goldman, S. (2009). Implantation of a three-dimensional fibroblast matrix improves left ventricular function and blood flow after acute myocardial infarction. Cell transplantation, 18(3), 283-95.
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  This study was designed to determine if a viable biodegradable three-dimensional fibroblast construct (3DFC) patch implanted on the left ventricle after myocardial infarction (MI) improves left ventricular (LV) function and blood flow. We ligated the left coronary artery of adult male Sprague-Dawley rats and implanted the 3DFC at the time of the infarct. Three weeks after MI, the 3DFC improved LV systolic function by increasing (p < 0.05) ejection fraction (37 +/- 3% to 62 +/- 5%), increasing regional systolic displacement of the infarcted wall (0.04 +/- 0.02 to 0.11 +/- 0.03 cm), and shifting the passive LV diastolic pressure volume relationship toward the pressure axis. The 3FDC improved LV remodeling by decreasing (p < 0.05) LV end-systolic and end-diastolic diameters with no change in LV systolic pressure. The 3DFC did not change LV end-diastolic pressure (LV EDP; 25 +/- 2 vs. 23 +/- 2 mmHg) but the addition of captopril (2mg/L drinking water) lowered (p < 0.05) LV EDP to 12.9 +/- 2.5 mmHg and shifted the pressure-volume relationship toward the pressure axis and decreased (p < 0.05) the LV operating end-diastolic volume from 0.49 +/- 0.02 to 0.34 +/- 0.03 ml. The 3DFC increased myocardial blood flow to the infarcted anterior wall after MI over threefold (p < 0.05). This biodegradable 3DFC patch improves LV function and myocardial blood flow 3 weeks after MI. This is a potentially new approach to cell-based therapy for heart failure after MI.
• Thal, S., Thai, H., Juneman, E., & Goldman, S. (2008). Coronary sinus diverticulum complicating CRT device implantation. Pacing and clinical electrophysiology : PACE, 31(9), 1184-5.
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  Coronary sinus diverticula are rare findings usually associated with the presence of accessory pathways. We report the case of a 74-year-old man, who underwent cardiac resynchronization therapy (CRT) device implant. Coronary sinus diverticulum was an incidental finding while attempting to subselectively cannulate the coronary sinus for left ventricle lead implant. The case was able to be completed without complications.
• Rough, S., Juneman, E. B., & Fain, M. (2007). Aldosterone Receptor Antagonists Therapy in Older Heart Failure Patients: Another Look. Arizona Geriatric Society Journal, 12(2), 10-13.
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  Aldosterone Receptor Antagonists Therapy in Older Heart Failure Patients: Another Look. Arizona Geriatric Society Journal 2007;12(2):10-13
• Goldman, S., Castellano, L., Do, R., Gaballa, M. A., Juneman, E., & Thai, H. M. (2006). 89 IMPLANTATION OF A FIBROBLAST PATCH IMPROVES LEFT VENTRICULAR SYSTOLIC FUNCTION AND PREVENTS REMODELING AFTER MYOCARDIAL INFARCTION.. Journal of Investigative Medicine, 54(1), S95.1-S95. doi:10.2310/6650.2005.x0004.88
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  Background Tissue engineering is a novel method to restore myocardial function in ischemic heart disease. One technique is to apply a biologically active graft onto the infarcted region (IR) of the left ventricle (LV). The effects of a fibroblast patch (3DFC) placement on the IR of the LV on systolic/diastolic function in a coronary artery ligation (CAL) model of heart failure were evaluated. Methods CAL to induce myocardial infarction (MI) is performed on Sprague-Dawley rats. The 3DFC patch is placed on the IR. Echos were done at 3 weeks. Hemodynamics was measured. LV regional systolic displacement (SD), LV ejection fraction (LVEF), LV fractional shortening (FS), and LV pressure/diameter relaxation curves were obtained. Results 3DFC patch placement improved (p Summary Implantation of a fibroblast mesh on the IR of the LV improved LV systolic function. The patch also prevented LV dilation and normalized LV diastolic function post MI. Our data illustrate the future potential of using a biologically active graft in the treatment of ischemic heart failure.
• Thai, H., Castellano, L., Juneman, E., Phan, H., Do, R., Gaballa, M. A., & Goldman, S. (2006). Pretreatment with angiotensin receptor blockade prevents left ventricular dysfunction and blunts left ventricular remodeling associated with acute myocardial infarction. Circulation, 114(18), 1933-9.
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  This study was designed to determine the effects of pretreatment with an angiotensin receptor blocker on left ventricular (LV) function and remodeling during acute myocardial infarction (MI).
• Goldman, S., Castellano, L., Gaballa, M. A., Johnson, N. M., Juneman, E., Phan, H., & Thai, H. M. (2005). 105 ALTERATIONS IN REGIONAL WALL STRAIN, ENOS AND MICROTUBULIN CONCENTRATIONS SIGNALING LEFT VENTRICULAR REMODELING OCCUR IMMEDIATELY AFTER ACUTE MYOCARDIAL INFARCTION. Journal of Investigative Medicine, 53(1), S95.6-S95. doi:10.2310/6650.2005.00005.104
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  Background Left ventricular (LV) remodeling after myocardial infarction (MI) leads to heart failure (HF). While alterations in LV wall strain are seen in the infarcted regions (IR), it is unclear if this also affects the non-infarcted regions (NIR) of the LV. Additionally, while LV tissue eNOS and constituitive microtubulin (CM) are altered in chronic HF, it is unknown what happens to these biomarkers acutely. We evaluated changes in LV wall strain; myocardial eNOS and CM acutely post MI. Methods LV wall motion of Sprague Dawley rats (N = 10) was analyzed by echocardiography at several time points after MI. Hemodynamic measurements were obtained via a Millar catheter. Alterations in myocardial contraction (δ strain) are measured via M-mode echocardiography. CM and eNOS were determined via immunoblot techniques. Results Systolic blood pressure decreased (P ≤ 0.05) acutely post MI (127.1 ± 6.1 vs 101.7± 10.1 mmHg). LV end diastolic pressure increased (P≤0.05) acutely after MI (5.8 ± 0.5 vs. 19.9 ± 2.0 mmHg). These changes were accompanied by a decrease (P≤ 0.05) in LV dP/dt after MI (7106 ± 520 vs. 4671± 350, mmHg/sec). δ strain was decreased in the anterior IR immediately (0.15 ± 0.04 vs 0.1 ± 0.02 mm, P ≤ 0.01); similarly δ strain was also decreased in the posterior NIR starting at 1 minute (0.17 ± 0.02 vs 0.1 ± 0.02 mm, P ≤ 0.01). A decrease in eNOS was seen with both the IR and NIR of the LV (20.8± 3.8 intensity unit (IU)/50 μg of tissue vs 11.1 ± 3.3 IU/50 μg, P = 0.04) and (26.7 ± 4.8 vs 8.14 ± 1.6 IU/50 μg, P = 0.002), respectively after MI. Conversely, CM was increased in both IR and NIR of the LV (10.3 ± 2.4 IU/25 μg vs 26.2 ± 4.6 IU/25 μg, P = 0.0005) and (9.3 ± 1.8 vs 18.5 ± 3.7 IU/25 μg, P = 0.003), respectively. Conclusion Decreases in δ strain occurred in both IR and NIR of the LV acutely after MI. This is accompanied by alterations in eNOS and CM levels throughout the LV immediately after MI. Our data demonstrate that physical and biomarkers signaling LV remodeling occur immediately after MI, rather than over time.
• Goldman, S., Castellano, L., Dahiya, R., Do, B. Q., Gaballa, M. A., Juneman, E., & Thai, H. M. (2004). 232 REGIONAL WALL STRESS IN THE NON-INFARCTED MYOCARDIUM IS INCREASED AFTER ACUTE MYOCARDIAL INFARCTION.. Journal of Investigative Medicine, 52(Suppl 1), S119.6-S119. doi:10.1136/jim-52-suppl1-232
• Goldman, S., Castellano, L., Gaballa, M. A., John, J., Juneman, E., Kim, F. C., Meredith, K. G., Thai, H. M., & Tran, T. D. (2004). 231 SEVERITY OF DIASTOLIC DYSFUNCTION AS A DETERMINANT OF LEFT ATRIAL SIZE.. Journal of Investigative Medicine, 52(Suppl 1), S119.5-S119. doi:10.1136/jim-52-suppl1-231
• Goldman, S., Gaballa, M. A., Juneman, E. B., Mitchell, B., Pierce, M. K., Shinde, A. A., & Thai, H. M. (2004). 227 SEVERE LEFT VENTRICULAR DYSFUNCTION AND ADVANCED AGE ARE NOT ASSOCIATED WITH INCREASED IMPLANTABLE CARDIOVERTER DEFIBRILLATOR DISCHARGES IN PATIENTS WITH SUDDEN CARDIAC DEATH TREATED WITH AMIODARONE.. Journal of Investigative Medicine, 52(Suppl 1), S119.1-S119. doi:10.1136/jim-52-suppl1-227
• Shinde, A. A., Juneman, E. B., Mitchell, B., Pierce, M. K., Gaballa, M. A., Goldman, S., & Thai, H. (2003). Shocks from pacemaker cardioverter defibrillators increase with amiodarone in patients at high risk for sudden cardiac death. Cardiology, 100(3), 143-8.
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  The efficacy of amiodarone used in combination with a pacemaker cardioverter defibrillator (PCD) to decrease episodes of ventricular tachycardia and subsequent PCD shocks is not clear. We examined a retrospective registry of 82 patients with PCD implantation to define the efficacy of amiodarone treatment. We compared patients treated with amiodarone (for 24 consecutive months without interruption) versus no amiodarone. In patients treated with amiodarone there was a 3-fold increase (p = 0.02) in PCD shocks; in patients not on beta-blockers, amiodarone resulted in a 6-fold increase (p < 0.05) in PCD shocks. Patients with a left ventricular ejection fraction >30% on amiodarone and patients

Presentations

• Lee, J. Z., Low, S., Yun, S., Dherange, P., Desai, A., Juneman, E. B., Lee, K. S., & Suryanarayana, P. (2016, November). Comparison of Tricuspid Annular Plane Systolic Excursion to Fractional Area Change for Evaluation of Right Ventricular Systolic Function: Systematic Review and Meta-analysis. American Heart Association Scientific Sessions. Orlando, FL: American Heart Association.

Poster Presentations

• Chinyere, I. R., Weigand, K., Moukabary, T., Witte, R. S., Chu, M., Novak, S., Hutchinson, M., Lancaster, J., Gregorio, C. C., Goldman, S., & Juneman, E. B. (2018, spring). Mapping and Inducing Ventricular Tachycardia in Cardiomyopathic Animal Models. Circ Res. San Antonio, TX: 2018 Circ Res 121:A86.
• Kazui, T., Kazui, T., Lick, S. D., Lick, S. D., Avery, R., Avery, R., Juneman, E. B., Juneman, E. B., Cook, J., Cook, J., Sweitzer, N. K., Sweitzer, N. K., Khalpey, Z. I., & Khalpey, Z. I. (2017, Oct). Minimally invasive off-pump HVAD vs full sternotomy on-pump LVAD placement: comparison of clinical outcomes. The 2017 ISMCS Conference. Tucson: ISMCS.
• Kazui, T., Lick, S. D., Avery, R., Juneman, E. B., Cook, J., Sweitzer, N. K., & Khalpey, Z. I. (2017, Oct). The effectiveness of minimally invasive off pump HVAD placement in redo patients. The 2017 ISMCS Conference. Tucson: ISMCS.
• Lancaster, J., Koevary, J. W., Chinyere, I. R., Juneman, E. B., & Goldman, S. (2017, Summer). Cardiac Grafts Engineered from human iPSC Ventricular Pure or Heterogeneous Cardiomyocytes Display Synchronous Spontaneous Contraction and Reduces Ventricular Tachycardia in Rats with Chronic Heart Failure. J Cardiac Failure. Dallas, TX.