Michel T. Corban

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Chapters

• Lerman, A., & Corban, M. (2021). Coronary endothelial and microvascular function testing. In The Mayo Clinic Cardiac Catheterization Laboratory. doi:10.1007/978-3-030-79329-6_9
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  Mayo Clinic Cardiac Catheterization Laboratory's role in understanding the pathophysiology, establishing the diagnosis, predicting the prognosis, and advancing treatment of coronary endothelial dysfunction has been, and in fact remains, crucial. Following Robert F. Furchgott's 1986 historic announcement on the major role of endothelium-derived nitric oxide (NO) in regulation of vascular tone, Mayo Clinic researchers demonstrated that the functional and structural integrity of the vascular endothelium is not only important to maintain balance between circulating endothelium-derived vasodilator and vasoconstrictor molecules but also confers protection against arterial atherosclerosis and thrombosis. Acetylcholine catheter-based evaluation protocol of coronary epicardial and microvascular endothelial function was initiated in 1994 as part of an NIH grant and approved for clinical practice in 1997. In 1994, the Mayo Endothelial Database - world's current largest invasive database of coronary endothelial and microvascular function assessment - enrolled its first patient. In a series of subsequent cutting-edge high-impact studies between 1997 and 2000, our lab demonstrated the association between coronary endothelial and microvascular dysfunction, myocardial ischemia, and increased risk of severe adverse cardiovascular events. Since 2001, we have investigated new therapeutic options for coronary endothelial dysfunction that either constitute current mainstay clinical therapy for this challenging disease entity, such statins and L-arginine, or cornerstone early studies of potentially promising investigational therapies such as endothelin-1 antagonists and most recently autologous intracoronary CD34+ cell therapy. In 2018, we were among the first to introduce and advance the concept of endothelial dysfunction as a systemic disease with not only cardiac but also numerous extracardiac clinical manifestations.
• AbdelWahab, A., Aras, K., Arora, R., Azeem, L., Berger, R. D., Blankenship, J. C., Boink, G. J., Bolignano, D., Boucek, D., Brügmann, T., Bushi, D., Chen, S. W., Christoffels, V. M., Corban, M., Regazzoli, D., Dash, D., Dávid, R., Vries, A. A., Devalla, H. D., , Donahue, J. K., et al. (2020). Contributors. In Emerging Technologies for Heart Diseases. doi:10.1016/b978-0-12-813704-8.00050-4
• Corban, M. T., El-sabbagh, A., Hajj, S. E., Prasad, A., & Raphael, C. E. (2020). Emerging therapies in coronary balloon angioplasty, stenting, and bioabsorbable scaffolds. In Emerging Technologies for Heart Diseases. Academic Press. doi:10.1016/B978-0-12-813704-8.00024-3
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  Abstract Mortality from coronary artery disease, the leading cause of death globally, has been on the decline. Percutaneous coronary intervention, performed for over 40 years, has been a major contributor to this favorable trend, together with advances in surgical revascularization, adjunctive pharmacotherapy and risk factor modification. In this chapter, we provide an overview of percutaneous coronary interventions, focusing on the iterative development of devices that have facilitated treatment of increasingly complex coronary lesions, lower complication rates and increase procedural success. We review emerging technologies in percutaneous coronary interventions with their specific applications and advantages, including specialty angioplasty balloons for modifying calcific and fibrotic lesions, novel drug-eluting stents with improves safety profile, deliverability and designs to treat bifurcations, bioresorbable scaffolds that hold the promise of restoring vessel architecture as well as robotic percutaneous coronary intervention to tackle operator radiation exposure and orthopedic injuries related to wearing protective aprons, and the emerging use of 3D printing.

Journals/Publications

• Tryon, D., Corban, M. T., Alkhouli, M., Prasad, A., Raphael, C. E., Rihal, C. S., Reeder, G. S., Lewis, B., Albers, D., Gulati, R., & Lerman, A. (2024). Coronary Sinus Reducer Improves Angina, Quality of Life, and Coronary Flow Reserve in Microvascular Dysfunction. JACC. Cardiovascular interventions.
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  Coronary microvascular dysfunction (CMD) is a common cause of angina with no obstructive coronary artery disease (ANOCA), and effective treatment options are limited.
• Ahmad, A., Corban, M., Moriarty, J. P., Rosedahl, J., Gulati, R., Rihal, C. S., Prasad, A., Sara, J. D., Toya, T., Horst, I. t., Lerman, L. O., Borah, B. J., & Lerman, A. (2023). CORONARY REACTIVITY ASSESSMENT REDUCED HEALTHCARE-ASSOCIATED COST OF PATIENTS PRESENTING WITH ANGINA AND NON-OBSTRUCTIVE CORONARY ARTERY DISEASE. Circ Cardiovasc Interv .. doi:10.1016/s0735-1097(23)01213-5
• Kolimas, A., Beverly, J. K., Kashif, M., Acharya, T., Vangala, A. S., & Corban, M. (2023). Abstract 18714: Myocardial Infarction With Non-Obstructive Coronary Artery Disease in a Young Woman - The Cardinal Role of Coronary Reactivity Testing in Unveiling the Underlying Etiology. Circulation. doi:10.1161/circ.148.suppl_1.18714
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  43-year old female presented to the emergency department with substernal chest pain. She had similar symptoms years ago without obstructive CAD on coronary angiogram and was diagnosed with myocarditis. Presenting ECG revealed new anterolateral T wave inversions (Fig 1), and high-sensitivity troponins peaked at 322 ng/L consistent with NSTEMI. TTE was significant for global hypokinesis of the left ventricle with a reduced ejection fraction of 35 to 40%. Invasive coronary angiogram showed no obstructive CAD or spontaneous coronary artery dissection however there was reduced flow in the mid to distal LAD raising suspicion for endothelial and microvascular dysfunction. Contrast-enhanced cardiac MRI showed myocardial edema in the anterior and anteroseptal walls with elevated myocardial T1 and T2 values, and early enhancement post gadolinium administration showed an acute LAD territorial infarct (Fig 2). Findings were consistent with myocardial infarction with non-obstructive coronary artery disease (MINOCA). She was started on carvedilol for empiric treatment of coronary artery spasm and microvascular dysfunction, along with aspirin and atorvastatin. Losartan was added for heart failure management. Outpatient invasive coronary reactivity testing showed severe epicardial (70% vasoconstriction) and microvascular (80% decrease in coronary blood flow) endothelial dysfunction in response to acetylcholine (Fig 3 and Fig 4) as underlying etiology of recent MINOCA. CFR was normal. L-arginine (NO precursor) was added to the medical regimen. Patient has not had recurrence of chest pain or ACS at 1 year follow-up and LVEF normalized on repeat echocardiogram. This case shows the importance of cardiac MRI in confirming the diagnosis of MINOCA in patients with no obstructive CAD, and the crucial role of coronary reactivity testing in diagnosing and treating severe coronary endothelial dysfunction, which is aligned with the AHA/ACC MINOCA consensus document.
• Prasad, M., Corban, M., Godo, S., Ben‐Ami, J., Nardi, V., Toya, T., Gulati, R., Rihal, C. S., Lerman, L. O., & Lerman, A. (2023). SERUM URIC ACID, CORONARY PLAQUE CHARACTERISTICS, AND LONG-TERM MORTALITY AFTER PERCUTANEOUS CORONARY INTERVENTION. JACC: Uric Acid in Cardiovascular and Renal Health. doi:10.1016/s0735-1097(23)01723-0
• Srinivasan, S., Jagadish, P. S., Kashif, M., & Corban, M. (2023). DOUBLE TROUBLE: ENDOTHELIAL DYSFUNCTION WITHIN A HEMODYNAMICALLY SIGNIFICANT MYOCARDIAL BRIDGE. JACC: Complex Clinical Cases. doi:10.1016/s0735-1097(23)03733-6
• Ajmal, M., Shenoy, S., Hung, O. Y., Lee, K. S., & Corban, M. (2022). RIGHT CORONARY ARTERY ATHEROTHROMBOSIS MIMICKING SPONTANEOUS CORONARY ARTERY DISSECTION: MYSTERY SOLVED BY INTRACORONARY OPTICAL COHERENCE TOMOGRAPHY. JACC: Diagnosis and Treatment of Carotid Artery Disease. doi:10.1016/s0735-1097(22)03804-9
• Akhiyat, N., Lasho, T., Ganji, M., Toya, T., Shi, C., Chen, X., Corban, M., Braggio, E., Ahmad, A., Keith, S., Lerman, L. O., Mrinal, P., & Lerman, A. (2022). CLONAL HEMATOPOIESIS OF INDETERMINATE POTENTIAL IS ASSOCIATED WITH FUTURE CARDIOVASCULAR EVENTS IN PATIENTS WITH EARLY VASCULAR AGING. JACC: Vascular Medicine. doi:10.1016/s0735-1097(22)02751-6
• Corban, M. T., Toya, T., Albers, D., Sebaali, F., Lewis, B. R., Bois, J., Gulati, R., Prasad, A., Best, P. J., Bell, M. R., Rihal, C. S., Prasad, M., Ahmad, A., Lerman, L. O., Solseth, M. L., Winters, J. L., Dietz, A. B., & Lerman, A. (2022). IMPROvE-CED Trial: Intracoronary Autologous CD34+ Cell Therapy for Treatment of Coronary Endothelial Dysfunction in Patients With Angina and Nonobstructive Coronary Arteries. Circulation research, 130(3), 326-338.
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  Coronary endothelial dysfunction (CED) causes angina/ischemia in patients with nonobstructive coronary artery disease (NOCAD). Patients with CED have decreased number and function of CD34+ cells involved in normal vascular repair with microcirculatory regenerative potential and paracrine anti-inflammatory effects. We evaluated safety and potential efficacy of intracoronary autologous CD34+ cell therapy for CED.
• Henry, T. D., Bairey Merz, C. N., Wei, J., Corban, M. T., Quesada, O., Joung, S., Kotynski, C. L., Wang, J., Lewis, M., Schumacher, A. M., Bartel, R. L., Takagi, H., Shah, V., Lee, A., Sietsema, W. K., Losordo, D. W., & Lerman, A. (2022). Autologous CD34+ Stem Cell Therapy Increases Coronary Flow Reserve and Reduces Angina in Patients With Coronary Microvascular Dysfunction. Circulation. Cardiovascular interventions, 15(2), e010802.
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  Coronary microvascular dysfunction results in angina and adverse outcomes in patients with evidence of ischemia and nonobstructive coronary artery disease; however, no specific therapy exists. CD34+ cell therapy increases microvasculature in preclinical models and improves symptoms, exercise tolerance, and mortality in refractory angina patients with obstructive coronary artery disease. The objective of this research was to evaluate the safety, tolerability, and efficacy of intracoronary CD34+ cell therapy in patients with coronary microvascular dysfunction.
• Kolimas, A., Ajmal, M., Avila, D. D., Kotagiri, R., Kazui, T., Moynahan, K., & Corban, M. (2022). Abstract 14522: Infective Mitral Valve Endocarditis in an Immunocompetent Patient Caused by Lactobacillus Species Transmitted by Intranasal Cocaine Use. Circulation. doi:10.1161/circ.146.suppl_1.14522
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  A 59-year-old male with controlled DM2, HTN, tobacco abuse, and remote MSSA bacteremia secondary to longstanding intranasal cocaine use (never IV drug user) presented to the ER with acute onset of left leg pain. He was in extreme distress and examination showed a cold left leg with absent extremity pulses. Cardiac assessment was notable for an apical systolic murmur. Magnetic resonance angiography (MRA) of the leg revealed a thrombotic occlusion of the left common femoral artery extending into the popliteal artery prompting emergent successful femoral artery thrombectomy and compartment fasciotomy. An intraoperative TEE revealed mobile echodensities on the anterior and posterior MV leaflets with severe eccentric mitral regurgitation (MR) [Figure1]. Blood and thrombectomy debris cultures yielded Lactobacillus acidophilus vs. gasseri species. Further workup showed multiple small embolic infarcts on MRA head and chronic sinusitis on CT sinuses, while CT chest, abdomen and pelvis were unremarkable. He received IV ampicillin for 1 week with bacterial clearance, followed by bioprosthetic mitral valve replacement. Gram stain of the mitral valve revealed gram positive rods, cultures grew Lactobacillus species, and histopathology confirmed the presence of infective endocarditis. The patient completed 7 weeks of penicillin G intravenously with clinical recovery. Lactobacillus acidophilus and gasseri are normal flora of the human oral cavity, gastrointestinal and genitourinary tracts. Lactobacillus endocarditis is rare and has been identified in only 0.05-0.4% of endocarditis cases. Infections primarily affect the immunocompromised, but to the best of our knowledge this is the first case of Lactobacillus mitral valve endocarditis presenting with concomitant acute limb ischemia with infected thromboembolic debris in an immunocompetent individual with the suspected inciting event being intranasal cocaine use causing trauma to the nasal vasculature.
• Martín, A. E., Ajmal, M., Cendrowski, E., Giesler, D., Iacobini, J., Acharya, D., Corban, M., & Lee, K. S. (2022). IN-VITRO EFFECT OF SHOCKWAVE INTRAVASCULAR LITHOTRIPSY ON CORONARY DRUG-ELUTING STENT POLYMER VISUALIZED BY SCANNING ELECTRON MICROSCOPY. JACC: Clinical Studies on Coronary Stents and Revascularization. doi:10.1016/s0735-1097(22)01657-6
• Ozcan, I., Toya, T., Corban, M. T., Ahmad, A., Loeffler, D., Morse, D., Lerman, L. O., Kushwaha, S. S., & Lerman, A. (2022). Circulating progenitor cells are associated with plaque progression and long-term outcomes in heart transplant patients. Cardiovascular research, 118(7), 1703-1712.
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  Circulating progenitor cells (CPCs) play a role in vascular repair and plaque stability, while osteocalcin (OC) expressing CPCs have been linked to unstable plaque and adverse cardiovascular outcomes. However, their role in cardiac allograft vasculopathy (CAV) has not been elucidated. This cohort study aimed to investigate the contribution of CPCs on CAV progression and cardiovascular events after heart transplantation.
• Park, H. W., Corban, M., Toya, T., Ahmad, A., Ozcan, I., Lerman, L., & Lerman, A. (2022). Impact of invasive aortic pulse pressure on coronary microvascular endothelial-independent dysfunction and on mortality in non-obstructive coronary artery disease. Open heart, 9(1).
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  Pulse pressure (PP), a raw index of arterial stiffness, is inversely related to coronary microvascular function, even among patients with non-obstructive coronary artery disease (CAD), as per non-invasive studies. We aimed to determine whether invasive aortic PP is associated with coronary microvascular endothelial dysfunction (CMED) and/or coronary microvascular endothelial independent dysfunction (CMEID) in patients with non-obstructed CAD.
• Takamatsu, C., Ibrahim, R., Corban, M. T., Klewer, S. E., & Seckeler, M. D. (2022). Abstract 11712: Transcatheter Reconstruction of Right Ventricular Outflow Tract After Severe External Compression by a Pseudoaneurysm in an Adult With Tetralogy of Fallot. Circulation, 146(Suppl_1). doi:10.1161/circ.146.suppl_1.11712
• Ahmad, A., Corban, M. T., & Lerman, A. (2021). Contrast fractional flow reserve vs adenosine fractional flow reserve: The impact of discordant results. International journal of cardiology, 328, 59-60.
• Ahmad, A., Corban, M. T., Kushwaha, S. S., Lerman, L. O., Lerman, A., Ozcan, I., & Toya, T. (2021). PERIPHERAL ENDOTHELIAL DYSFUNCTION IS ASSOCIATED WITH CARDIAC ALLOGRAFT VASCULOPATHY PROGRESSION. Journal of the American College of Cardiology, 77(18), 573. doi:10.1016/s0735-1097(21)01932-x
• Ahmad, A., Corban, M. T., Toya, T., Attia, Z. I., Noseworthy, P. A., Lopez-Jimenez, F., Cohen, M. S., Sara, J. D., Ozcan, I., Lerman, L. O., Kapa, S., Friedman, P. A., & Lerman, A. (2021). Coronary Microvascular Dysfunction and the Risk of Atrial Fibrillation From an Artificial Intelligence-Enabled Electrocardiogram. Circulation. Arrhythmia and electrophysiology, 14(8), e009947.
• Ahmad, A., Corban, M. T., Toya, T., Verbrugge, F. H., Sara, J. D., Lerman, L. O., Borlaug, B. A., & Lerman, A. (2021). Coronary microvascular dysfunction is associated with exertional haemodynamic abnormalities in patients with heart failure with preserved ejection fraction. European journal of heart failure, 23(5), 765-772.
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  This study uniquely explored the relationship between coronary microvascular function and exercise haemodynamics using concurrent invasive testing.
• Ahmad, A., Shelly-Cohen, M., Corban, M. T., Murphree, D. H., Toya, T., Sara, J. D., Ozcan, I., Lerman, L. O., Friedman, P. A., Attia, Z. I., & Lerman, A. (2021). Machine learning aids clinical decision-making in patients presenting with angina and non-obstructive coronary artery disease. European heart journal. Digital health, 2(4), 597-605.
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  The current gold standard comprehensive assessment of coronary microvascular dysfunction (CMD) is through a limited-access invasive catheterization lab procedure. We aimed to develop a point-of-care tool to assist clinical guidance in patients presenting with chest pain and/or an abnormal cardiac functional stress test and with non-obstructive coronary artery disease (NOCAD).
• Ahmad, A., Toya, T., Corban, M., Ӧzcan, I., Sara, J. D., Lerman, L. O., & Lerman, A. (2021). Abstract 14465: Sex Has an Effect on the Relationship Between Intracoronary Acetylcholine and Coronary Blood Flow. Circulation.
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  Introduction: The endothelium controls coronary blood flow (CBF) by regulating microvascular tone, which is an important index of microcirculatory health. The difference in vasomotor response of th...
• Albers, D., Bell, M. R., Best, P. J., Bois, J. P., Corban, M. T., Dietz, A. B., Gulati, R., Lerman, L. O., Lerman, A., Prasad, M., Prasad, A., Rihal, C. S., Sebaali, F., Solseth, M. L., Toya, T., & Winters, J. L. (2021). INTRACORONARY AUTOLOGOUS CD34+ CELL THERAPY FOR TREATMENT OF CORONARY ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH ANGINA AND NON-OBSTRUCTIVE CORONARY ARTERIES: IMPROVE-CED TRIAL. Journal of the American College of Cardiology, 77(18), 3409. doi:10.1016/s0735-1097(21)04763-x
• Corban, M. T., Prasad, A., Gulati, R., Lerman, L. O., & Lerman, A. (2021). Sex-specific differences in coronary blood flow and flow velocity reserve in symptomatic patients with non-obstructive disease. EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology, 16(13), 1079-1084.
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  Reduced coronary flow velocity reserve (CFVR) is associated with adverse cardiovascular outcomes. Whether CFVR and coronary blood flow (CBF) are similar in men and women with chest pain and non-obstructive CAD remains unknown. We hypothesised sex differences in CFVR and CBF.
• Corban, M. T., Toya, T., Ahmad, A., Lerman, L. O., Lee, H. C., & Lerman, A. (2021). Atrial Fibrillation and Endothelial Dysfunction: A Potential Link?. Mayo Clinic proceedings, 96(6), 1609-1621.
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  Atrial fibrillation (AF) is the most common cardiac arrhythmia, and coronary atherosclerosis is the leading cause of death in the United States and worldwide. Endothelial dysfunction is the earliest clinically detectable form of atherosclerosis. Control of shared AF and coronary atherosclerosis risk factors improves both AF-free survival and vascular endothelial function. Decades of AF research have yielded fundamental insight into AF pathophysiology, but current pharmacological and catheter-based invasive AF therapies have limited long-term efficacy and substantial side effects, possibly because of incomplete understanding of underlying complex AF pathophysiology. We hereby discuss potential mechanistic links between endothelial dysfunction and AF (risk-factor-associated systemic inflammation and oxidative stress, myocardial ischemia, common gene variants, vascular shear stress, and fibroblast growth factor-23), explore a potential new vascular dimension to AF pathophysiology, highlight a growing body of evidence supporting an association between systemic vascular endothelial dysfunction, AF, and stroke, and discuss potential common effective therapies.
• Liu, H., Xie, G., Huang, W., Liu, J., Zhao, N., Corban, M. T., Lerman, A., Wu, Y., & Wang, H. (2021). Rationale and design of a multicenter, randomized, patients-blinded two-stage clinical trial on effects of endothelial function test in patients with non-obstructive coronary artery disease (ENDOFIND). International journal of cardiology, 325, 16-22.
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  Abnormal peripheral and coronary endothelial function has been associated with increased risk of major adverse cardiovascular events (MACE) in cross-sectional retrospective and observational studies. However, prognostic value of routine clinical evaluation, diagnosis and treatment of endothelial dysfunction on incident MACE in patients with non-obstructive coronary artery disease (NOCAD) remains unknown. Endothelial Function Guided Management in Patients with NOCAD (ENDOFIND) is a multicenter, randomized, patients-blinded, parallel-controlled, two-stage clinical trial evaluating the impact of routine clinical peripheral endothelial function testing on initiation and/or intensification of cardiovascular preventive therapies in Stage I, and on the risk of MACE in Stage II in patients with NOCAD. One thousand participants with NOCAD on clinically indicated coronary computed tomography or invasive angiography will be enrolled and randomized 1:1, after baseline peripheral endothelial function evaluation, to either endothelial function guided treatment group or standard of care control group. In Stage I, patients will be followed for 12 months and primary outcome will be the proportion of patients receiving prescriptions for cardiovascular evidence-based lipid, blood pressure and glucose lowering medications at the clinic visit immediately after endothelial function evaluation. Secondary outcomes are change in endothelial function measured as reactive hyperemia index and patients' adherence to evidence-based medications in 12 months. Study will be extended into Stage II where sample size and follow up duration will be reevaluated to ensure statistical power, and primary outcome will be incident MACE. ENDOFIND is proof-of-concept clinical trial of a disruptive endothelial function guided clinical intervention with potential benefits to NOCAD patients. CONDENSED ABSTRACT: ENDOFIND is a proof-of-concept clinical trial of a disruptive endothelial function guided clinical intervention with potential benefits to patients with no obstructive coronary artery disease (NOCAD). It is a multicenter, randomized, patients-blinded, parallel controlled two-stage clinical trial to evaluate the impact of routine clinical peripheral endothelial function testing on initiation and/or intensification of cardiovascular disease preventive therapies in Stage I, and on the risk of MACE in Stage II.
• Mahowald, M. K., Corban, M. T., Eleid, M. F., & Nishimura, R. A. (2021). Alcohol Septal Ablation for Hypertrophic Cardiomyopathy Through an Anomalous Septal Perforator Off the Right Cusp. JACC. Cardiovascular interventions, 14(12), e129-e130.
• Ozcan, I., Toya, T., Corban, M. T., Ahmad, A., Lerman, L. O., Kushwaha, S. S., & Lerman, A. (2021). Peripheral microvascular dysfunction is associated with plaque progression and adverse long-term outcomes in heart transplant patients. ESC heart failure, 8(6), 5266-5274.
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  Cardiac allograft vasculopathy (CAV) is the major cause of increased morbidity and mortality after heart transplantation. Peripheral endothelial dysfunction (PED) is associated with early atherosclerosis and future risk of major adverse cardiovascular events (MACE) in non-heart transplant population. We aimed to investigate the association of PED with future MACE, and plaque progression assessed by intravascular ultrasound (IVUS) after heart transplantation.
• Toya, T., Ahmad, A., Corban, M. T., Ӧzcan, I., Sara, J. D., Sebaali, F., Escaned, J., Lerman, L. O., & Lerman, A. (2021). Risk Stratification of Patients With NonObstructive Coronary Artery Disease Using Resistive Reserve Ratio. Journal of the American Heart Association, 10(11), e020464.
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  Background Resistive reserve ratio (RRR), or the ratio of baseline to hyperemic microvascular resistance, has prognostic implications in predicting clinical outcomes in patients with obstructive coronary artery disease. However, its value in patients with angina or ischemia with nonobstructive coronary artery disease is unknown. Methods and Results We included 1692 patients with nonobstructive coronary artery disease who underwent invasive coronary vasoreactivity testing. Abnormal coronary flow reserve (CFR, the ratio of hyperemic and baseline resting flow velocities) and RRR were defined as
• Toya, T., Ahmad, A., Corban, M., Sara, J. D., Ӧzcan, I., Lerman, L. O., & Lerman, A. (2021). Abstract 10441: Sex-Specific Decline in Coronary Flow Reserve with Aging. Circulation. doi:10.1161/circ.144.suppl_1.10441
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  Introduction: Coronary vasomotor response is different between males and females. Overall, females have lower coronary flow reserve (CFR) than males due to higher baseline coronary flow than males. Hypothesis: Sex has an essential role in the interaction between age and CFR. Methods: We included 668 patients with nonobstructive coronary artery disease who underwent invasive coronary vasoreactivity testing using intracoronary incremental doses of adenosine (18-72 μg). Changes in CFR (hyperemic flow velocity/baseline flow velocity) with aging were separately analyzed between males (N=207, mean age 53±13 years) and females (N=461, mean age 54±12 years). We further divided patients by age of 53 which is average age of menopause. Results: In males, CFR decreased with aging in younger patients
• Toya, T., Corban, M. T., Park, J. Y., Ahmad, A., Ӧzcan, I., Sebaali, F., Sara, J. D., Gulati, R., Lerman, L. O., & Lerman, A. (2021). Prognostic impact and clinical outcomes of coronary flow reserve and hyperaemic microvascular resistance. EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology, 17(7), 569-575.
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  Most studies dichotomise indices of coronary microvascular function to assess their prognostic values.
• Toya, T., Ozcan, I., Corban, M. T., Sara, J. D., Marietta, E. V., Ahmad, A., Horwath, I. E., Loeffler, D. L., Murray, J. A., Lerman, L. O., & Lerman, A. (2021). Compositional change of gut microbiome and osteocalcin expressing endothelial progenitor cells in patients with coronary artery disease. PloS one, 16(3), e0249187.
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  Osteogenic endothelial progenitor cells (EPCs) contribute to impaired endothelial repair and promote coronary artery disease (CAD) and vascular calcification. Immature EPCs expressing osteocalcin (OCN) has been linked to unstable CAD; however, phenotypic regulation of OCN-expressing EPCs is not understood. We hypothesized that gut-microbiome derived pro-inflammatory substance, trimethylamine N-oxide (TMAO) might be associated with mobilization of OCN-expressing EPCs. This study aimed to investigate the association between dysbiosis, TMAO, and circulating mature and immature OCN-expressing EPCs levels in patients with and without CAD. We included 202 patients (CAD N = 88; no CAD N = 114) who underwent assessment of EPCs using flow cytometry and gut microbiome composition. Mature and immature EPCs co-staining for OCN were identified using cell surface markers as CD34+/CD133-/kinase insert domain receptor (KDR)+ and CD34-/CD133+/KDR+ cells, respectively. The number of observed operational taxonomy units (OTU), index of microbial richness, was used to identify patients with dysbiosis. The number of immature OCN-expressing EPCs were higher in patients with CAD or dysbiosis than patients without. TMAO levels were not associated with circulating levels of OCN-expressing EPCs. The relative abundance of Ruminococcus gnavus was moderately correlated with circulating levels of immature OCN-expressing EPCs, especially in diabetic patients. Gut dysbiosis was associated with increased levels of TMAO, immature OCN-expressing EPCs, and CAD. The relative abundance of Ruminococcus gnavus was correlated with immature OCN-expressing EPCs, suggesting that the harmful effects of immature OCN-expressing EPCs on CAD and potentially vascular calcification might be mediated by gut microbiome-derived systemic inflammation.
• Ӧzcan, I., Toya, T., Cohen‐Shelly, M., Ahmad, A., Corban, M., Noseworthy, P. A., Kapa, S., Lerman, L. O., Attia, Z. I., Friedman, P. A., Kushwaha, S. S., & Lerman, A. (2021). Artificial intelligence derived age algorithm after heart transplantation. Eur Heart J Digit Health.. doi:10.1093/eurheartj/ehab724.2272
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  Abstract Background An artificial intelligence (AI) algorithm detecting age from 12-lead ECG has been suggested to signal “physiological age” of the individual. Importantly, increased physiological age gauged by an increased difference between ECG-age and chronological age has been associated with higher risk of cardiac events in non-transplant population. Purpose We sought to investigate the validity of the AI-derived ECG-age algorithm in patients who underwent heart transplantation and its relationship to major adverse cardiovascular events (MACE). Methods A total of 489 consecutive patients who had undergone heart transplantation in our institution between 1994 and 2018 were studied. AI-ECG age was calculated by a previously-trained artificial intelligence (AI) algorithm using a 12-lead ECG per patient. ECGs used in the training process of the algorithm were excluded. The average of the ECG-ages within one year before and one year after heart transplantation was used to represent pre- and post-transplant ECG-ages. MACE was defined as any incidence of revascularization, re-transplantation, and death. Results Pre-transplant ECG-age (mean 63±10 years) correlated significantly with recipient chronological age (mean 50±13 years, r=0.57, p
• Ahmad, A., Corban, M. T., Toya, T., Sara, J. D., Lerman, B., Park, J. Y., Lerman, L. O., & Lerman, A. (2020). Coronary Microvascular Endothelial Dysfunction in Patients With Angina and Nonobstructive Coronary Artery Disease Is Associated With Elevated Serum Homocysteine Levels. Journal of the American Heart Association, 9(19), e017746.
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  Background Elevated levels of serum homocysteine, via impaired nitric oxide production, and coronary microvascular dysfunction are associated with increased risk of major adverse cardiovascular events. However, whether serum homocysteine levels and coronary microvascular endothelial dysfunction (CMED) are linked remains unknown. Methods and Results This study included 1418 patients with chest pain or an abnormal functional stress test and with nonobstructive coronary artery disease (
• Corban, M. T., Godo, S., Burczak, D. R., Noseworthy, P. A., Toya, T., Lewis, B. R., Lerman, L. O., Gulati, R., & Lerman, A. (2020). Coronary Endothelial Dysfunction Is Associated With Increased Risk of Incident Atrial Fibrillation. Journal of the American Heart Association, 9(8), e014850.
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  Background Coronary artery disease risk factors are associated with atrial fibrillation (AF) and coronary endothelial dysfunction (CED). We hypothesized that CED is associated with increased risk of incident AF among patients with chest pain and nonobstructive coronary artery disease. Methods and Results Three hundred patients with chest pain, nonobstructive coronary artery disease, and no history of AF underwent intracoronary acetylcholine infusion for evaluation of baseline epicardial (decrease in mid-left anterior descending coronary artery diameter in response to acetylcholine) and microvascular (34 mL/m) left atrial volume index (odds ratio, 3.87; 95% CI, 1.60-9.11) were independent predictors of incident AF. Conclusions Patients with normal coronary endothelial function, as compared with those with CED and similar AF risk factors, have significantly lower incidence of AF on long-term follow-up. The potential mechanistic link between vascular dysfunction and AF development warrants further investigation.
• Corban, M. T., Kim, T., Lee, G., Rihal, C. S., Lerman, A., Bae, J. H., Kim, K. H., Kwon, T. G., Lee, M. S., Seo, Y. H., & Song, I. G. (2020). Ten-year clinical outcomes of an intermediate coronary lesion; prognosis and predictors of major adverse cardiovascular events.. International journal of cardiology, 299, 26-30. doi:10.1016/j.ijcard.2019.06.076
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  The natural history of intermediate coronary lesions (30 to 70% angiographic stenosis) and the prognostic predictors in predicting very long-term clinical outcomes is unknown..Patients (n = 82, mean 60 years old) with intermediate non-culprit coronary lesions (NCL, n = 86), evaluated by virtual histology-intravascular ultrasound (VH-IVUS), were followed for 10 years. Major adverse cardiovascular events (MACE; all-cause death, myocardial infarction, stroke, and revascularization) were collected over follow-up period and stratified by culprit lesion (CL)-related, NCL-related and indeterminate/unrelated to CL or NCL lesions. NCL-related MACE was further stratified into intermediate and minimal NCL-related events..Twenty two (25.6%) out of 86 intermediate NCL were associated with MACE in 20/82 (24.4%) study patients. Ten-year cumulative intermediate NCL-related MACE rate was twice (25.6% vs. 12.8%) compared to treated culprit lesion (CL)-related MACE. Ten-year cumulative revascularization rate of the intermediate NCL lesions was similar (17.4% vs. 15.1%) to those of CL, but higher than that of minimal (stenosed
• Corban, M. T., Lerman, L. O., & Lerman, A. (2020). Endothelin-1 in coronary microvascular dysfunction: a potential new therapeutic target once again. European heart journal, 41(34), 3252-3254.
• Corban, M. T., Widmer, R. J., Cilluffo, R., Kazeck, M. A., Lennon, R. J., Lerman, L. O., & Lerman, A. (2020). The effect of polyphenol-rich chardonnay seed supplements on peripheral endothelial function. European journal of nutrition, 59(8), 3723-3734.
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  Peripheral endothelial dysfunction (PED) is associated with major adverse cardiovascular events. Similar to cardio-protective Mediterranean diet, Chardonnay seeds are rich in polyphenols, fibers, and grape seed oil. In this randomized double-blinded trial, we investigated safety and incremental benefit of Chardonnay seed polyphenols-rich (PR), compared to polyphenols-free (PF), supplements on PED.
• El-Am, E. A., Corban, M. T., Pollak, A. W., Lerman, A., & Ammash, N. M. (2020). A Challenging Combination: Anomalous Left Anterior Descending Coronary Artery, Myocardial Bridging, and Endothelial Dysfunction. Frontiers in cardiovascular medicine, 7, 57.
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  50 years old female patient with a medical history of hypertension presented to the clinic with chest pain, palpitations, and dyspnea on exertion of 2 years duration. Extensive workup in search of the culprit etiology of her chest pain revealed a challenging combination of an anomalous left anterior descending artery with myocardial bridging and endothelial dysfunction. She was treated medically with long acting nitrates, L-arginine and calcium channel blockers, and remains asymptomatic after 12 months of follow up.
• Ganji, M., Lasho, T., Toya, T., Akhiyat, N., Shi, C., Chen, X., Braggio, E., Ahmad, A., Corban, M., Stewart, A. F., Lerman, L. O., Patnaik, M. M., & Lerman, A. (2020). Elevated expression of clonal hematopoiesis of indeterminate potential in patients with coronary endothelial dysfunction is associated with future cardiovascular events. Research Gate: Endothelial Dysfunction. doi:10.21203/rs.3.rs-75002/v1
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  Abstract Aims We aimed to test the hypothesis that the presence of clonal hematopoiesis of indeterminate potential (CHIP) in peripheral blood cells is associated with coronary endothelial dysfunction, enhanced inflammatory markers, and major adverse cardiovascular events (MACE). Methods and results We compared targeted next generation sequencing (35 CHIP related genes) between patients with coronary endothelial dysfunction (n = 123) and controls (n=65). Coronary endothelial dysfunction was defined by ≥ 20% decrease in coronary artery diameter (CAD) or ≤ 50% increase in coronary blood flow (CBF) in response to acetylcholine injection compared to baseline. Plasma cytokine levels of Interleukin (IL)-6 and IL-8 were also assessed. Patients were subsequently followed for 12.2 ± 4.3 years. Clonal hematopoiesis relevant gene mutations were found in 1 individual in normal endothelial function group (1.5%) and 11 cases in endothelial dysfunction group (9.3%) (p = 0.04). Additionally, CHIP mutations were associated with an increased risk of MACE (OR = 4.08, P = 0.04). Mutations in ASXL1, DNMT3A and TET2 in the endothelial dysfunction group were also associated with increased levels of IL-6 and IL-8 ( P = 0.001, P = 0.003; respectively). Conclusion The current study demonstrates a high frequency of CHIP in patients with coronary endothelial dysfunction as well as an association between mutations in three most common epigenetic regulator genes and increased levels of IL-6 and IL-8. Therefore it infers a probable relationship between CHIP, endothelial dysfunction and cardiovascular adverse events.
• Hebbel, R. P., Wei, P., Milbauer, L., Corban, M. T., Solovey, A., Kiley, J., Pattee, J., Lerman, L. O., Pan, W., & Lerman, A. (2020). Abnormal Endothelial Gene Expression Associated With Early Coronary Atherosclerosis. Journal of the American Heart Association, 9(14), e016134.
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  Background We examined feasibility of a unique approach towards gaining insight into heritable risk for early atherosclerosis: surveying gene expression by endothelial cells from living subjects. Methods and Results Subjects aged
• Koh, J. S., Hung, O. Y., Eshtehardi, P., Kumar, A., Rabah, R., Raad, M., Kumar, S., Chaudhry, S., Gupta, S., Hosseini, H., Brilakis, E., Corban, M., Sabbak, N., Burnett, G. M., Liu, C., Mehta, P. K., Quyyumi, A. A., & Samady, H. (2020). Microvascular Assessment of Ranolazine in Non-Obstructive Atherosclerosis: The MARINA Randomized, Double-Blinded, Controlled Pilot Trial. Circulation. Cardiovascular interventions, 13(12), e008204.
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  Microvascular dysfunction is known to play a key role in patients with angina and nonobstructive coronary artery disease. We investigated the impact of ranolazine among patients with angina and nonobstructive coronary artery disease.
• Koh, J. S., Hung, O. Y., Eshtehardi, P., Kumar, A., Rabah, R., Raad, M., Kumar, S., Chaudhry, S., Sk, G., Hosseini, H., Brilakis, E. S., Corban, M., Sabbak, N., Burnett, G. M., Liu, C., Mehta, P. K., Quyyumi, A. A., & Samady, H. (2020). Microvascular Assessment of Ranolazine in Non-Obstructive Atherosclerosis. Circulation Cardiovascular Interventions. doi:10.1161/circinterventions.119.008204
• Lerman, A., Ahmad, A., Corban, M., Toya, T., Park, J. Y., & Lerman, L. O. (2020). ASSOCIATION OF SERUM HOMOCYSTEINE LEVEL AND CORONARY MICROVASCULAR ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH ANGINA AND NON-OBSTRUCTIVE CORONARY ARTERY DISEASE. J Am Heart Assoc .. doi:10.1016/s0735-1097(20)31905-7
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  Both high levels of serum-homocysteine (sHcy), via impaired nitric-oxide production, and coronary microvascular endothelial dysfunction (CMED) are each associated with increased risk of major adverse cardiovascular events (MACE). However, the relationship between sHcy levels and CMED remains unknown
• Lerman, A., Park, J., Corban, M., Toya, T., & Ahmad, A. (2020). IMPACT OF RESTING CORONARY MICROVASCULAR RESISTANCE AND HYPEREMIC CORONARY FLOW RESERVE ON MORTALITY IN PATIENTS WITH ANGINA AND NON-OBSTRUCTIVE CORONARY ARTERY DISEASE. JACC: Interventional Cardiology. doi:10.1016/s0735-1097(20)31747-2
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  The aim of this study is to evaluate the impact of resting coronary microvascular resistance (MR) and coronary flow reserve (CFR) on mortality. 1,643 patients with angina and non-obstructive coronary artery disease who underwent invasive assessment of coronary physiology between January 1996 and
• Lerman, A., Toya, T., Sara, J. D., Lerman, B., Ahmad, A., Corban, M., & Lerman, L. O. (2020). PLASMA HOMOCYSTEINE LEVEL IS ASSOCIATED WITH PERIPHERAL MICROVASCULAR ENDOTHELIAL DYSFUNCTION. JACC: Diagnosis and Treatment of Carotid Artery Disease. doi:10.1016/s0735-1097(20)32897-7
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  Hyperhomocysteinemia has been proposed as an important cardiovascular risk factor. However, little is known about the association between homocysteine (Hcy) levels and peripheral microvascular endothelial dysfunction (MED). This study included patients who underwent non-invasive microvascular
• Prasad, M., Corban, M. T., Henry, T. D., Dietz, A. B., Lerman, L. O., & Lerman, A. (2020). Promise of autologous CD34+ stem/progenitor cell therapy for treatment of cardiovascular disease.. Cardiovascular research, 116(8), 1424-1433. doi:10.1093/cvr/cvaa027
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  CD34+ cells are haematopoietic stem cells used therapeutically in patients undergoing radiation or chemotherapy due to their regenerative potential and ability to restore the haematopoietic system. In animal models, CD34+ cells have been associated with therapeutic angiogenesis in response to ischaemia. Several trials have shown the potential safety and efficacy of CD34+ cell delivery in various cardiovascular diseases. Moreover, Phase III trials have now begun to explore the potential role of CD34+ cells in treatment of both myocardial and peripheral ischaemia. CD34+ cells have been shown to be safe and well-tolerated in the acute myocardial infarction (AMI), heart failure, and angina models. Several studies have suggested potential benefit of CD34+ cell therapy in patients with coronary microvascular disease as well. In this review, we will discuss the therapeutic potential of CD34+ cells, and describe the pertinent trials that have used autologous CD34+ cells in no-options refractory angina, AMI, and heart failure. Lastly, we will review the potential utility of autologous CD34+ cells in coronary endothelial and microvascular dysfunction.
• Sara, J., Corban, M., Prasad, M., Prasad, A., Gulati, R., Lerman, L., & Lerman, A. (2020). Prevalence of myocardial bridging associated with coronary endothelial dysfunction in patients with chest pain and nonobstructive coronary artery disease. EuroIntervention, 15(14). doi:10.4244/EIJ-D-18-00920
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  Aims: Myocardial bridging (MB), characterised by the epicardial coronary vessel diving into the myocardium, is present in up to one third of adults and is associated with angina and acute coronary syndromes. MB is accompanied by altered blood flow mechanics and regional changes in wall sheer stress. The purpose of this study was to determine the association between myocardial bridging and coronary endothelial dysfunction. Methods and results: Patients presenting with chest pain and found to have non-obstructive CAD (stenosis
• Toya, T., Corban, M. T., Imamura, K., Bois, J. P., Gulati, R., Oh, J. K., Lerman, L. O., & Lerman, A. (2020). Coronary perivascular epicardial adipose tissue and major adverse cardiovascular events after ST segment-elevation myocardial infarction. Atherosclerosis, 302, 27-35.
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  Perivascular epicardial adipose tissue (pEAT) plays a key role in the progression of atherosclerosis, plaque rupture, and thrombosis. However, the relationship between pEAT and prognosis after revascularization of ST-segment elevation myocardial infarction (STEMI) is unknown. This study aimed to investigate the relationship between pEAT thickness and prognosis after STEMI.
• Toya, T., Corban, M., Marrietta, E., Horwath, I., Lerman, L., Murray, J., & Lerman, A. (2020). Coronary artery disease is associated with an altered gut microbiome composition. Implications of gut microbiome on coronary artery disease, 15(1). doi:10.1371/journal.pone.0227147
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  Alteration of gut microbiome composition has been linked to cardiovascular diseases. To identify specific bacterial communities associated with coronary artery diseases (CAD), we conducted a case-control study with 53 advanced CAD patients and 53 age-, sex-, race-, and BMI-matched controls. V3-V5 regions of the 16S rDNA from the fecal gut material were analyzed to compare the gut microbiome composition between CAD patients and controls. The alpha diversity, including Chao-1, Shannon-index, and the number of observed taxonomy units were significantly decreased in CAD patients indicating, decreased richness and evenness of gut microbiome. Among 23 different abundant taxa at the genus level, 12 taxa belonged to Lachnospiraceae family, which are known to produce butyrate. Further, we identified five taxa which showed more than two log-fold changes with maximum proportion >0.002, including Ruminococcus gnavus, Lachnospiraceae anaerosporobacter, Lachnospiraceae NK4B4 group, Lachnospiraceae UCG-004, and Ruminococcus gauvreauii. After adjustment for coronary risk factors (diabetes mellitus and dyslipidemia), decreased relative abundance of Lachnospiraceae NK4B4 group and Ruminococcus Gauvreauii and increased relative abundance of Ruminococcus gnavus were associated with the presence of advanced CAD. The observed differences in taxa between CAD patients and controls in this study may provide insight into the link between the gut microbiome and CAD.
• Toya, T., Sara, J. D., Lerman, B., Ahmad, A., Taher, R., Godo, S., Corban, M. T., Lerman, L. O., & Lerman, A. (2020). Elevated plasma homocysteine levels are associated with impaired peripheral microvascular vasomotor response. International journal of cardiology. Heart & vasculature, 28, 100515.
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  Hyperhomocysteinemia (HHcy) has been proposed as an important cardiovascular risk factor (cRF). However, little is known about the association between plasma homocysteine levels and peripheral microvascular endothelial dysfunction (PMED), which is an integrated index of vascular health.
• Toya, T., Sara, J., Corban, M., Taher, R., Godo, S., Herrmann, J., Lerman, L., & Lerman, A. (2020). Assessment of peripheral endothelial function predicts future risk of solid-tumor cancer. Eur J Prev Cardiol ., 27(6). doi:10.1177/2047487319884246
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  Aims: Cardiovascular health metrics predict the risk not only of cardiovascular diseases but also of several types of cancers. Microvascular endothelial dysfunction can predict future cardiovascular adverse events, but the predictive value of microvascular endothelial dysfunction for future risk of solid-tumor cancer has not been characterized. Methods: A total of 488 patients who underwent microvascular endothelial function assessment using reactive hyperemia peripheral arterial tonometry were included in this study. Microvascular endothelial dysfunction was defined as a reactive hyperemia peripheral arterial tonometry index ≤2.0. Results: Of 221 patients with a baseline reactive hyperemia peripheral arterial tonometry index ≤2.0, 21 patients (9.5%) were diagnosed with incident solid-tumor cancer during follow-up, whereas of 267 patients with a baseline reactive hyperemia peripheral arterial tonometry index >2.0, 10 patients (3.7%) were diagnosed with incident solid-tumor cancer during follow-up (p = 0.009). Patients with a reactive hyperemia peripheral arterial tonometry index ≤2.0 had lower solid-tumor cancer-free survival compared to patients with a reactive hyperemia peripheral arterial tonometry index >2.0 (log-rank p = 0.017) (median follow-up 6.0 (3.0–9.1) years). Cox proportional hazard analyses showed that a reactive hyperemia peripheral arterial tonometry index ≤2.0 predicted the incidence of solid-tumor cancer, with a hazard ratio of 2.52 (95% confidence interval 1.17–5.45; p = 0.019) after adjusting for age, sex, and coronary artery disease, 2.83 (95% confidence interval 1.30–6.17; p = 0.009) after adjusting for diabetes mellitus, hypertension, smoking status, and body mass index >30 kg/m2, 2.79 (95% confidence interval 1.21–6.41; p = 0.016) after adjusting for fasting plasma glucose, systolic blood pressure, smoking status (current or former), and body mass index, and 2.43 (95% confidence interval 1.10–5.34; p = 0.028) after adjusting for Framingham risk score. Conclusion: Microvascular endothelial dysfunction, as defined by a reactive hyperemia peripheral arterial tonometry index ≤2.0, was associated with a greater than two-fold increased risk of solid-tumor cancer. Microvascular endothelial dysfunction may be a useful marker to predict the future risk of solid-tumor cancer, in addition to its known ability to predict cardiovascular disease. Further research is necessary to develop adequate cancer screening strategies for patients with microvascular endothelial dysfunction.
• Ӧzcan, I., Toya, T., Corban, M., Ahmad, A., Loeffler, D., Ostlie, H., Kushwaha, S., Lerman, L. O., & Lerman, A. (2020). Abstract 15245: Cd34+ Progenitor Cells in the Progression of Cardiac Allograft Vasculopathy. Circulation. doi:10.1161/circ.142.suppl_3.15245
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  Introduction: CD34+ progenitor cells play a role in vascular repair and plaque stability. However, their role in cardiac allograft vasculopathy (CAV), vessel remodeling, and changes in plaque morphology is incompletely understood. Hypothesis: We hypothesized that decreased levels of baseline CD34+ progenitor cells would be associated with Intravascular Ultrasound (IVUS)-defined vulnerable plaque characteristics and CAV progression. Methods: In heart transplant patients undergoing annual IVUS, CD34+ cells were counted in peripheral blood using flow cytometry, on the same day as baseline IVUS. Gray-scale and virtual-histology IVUS were used to evaluate vessel size, plaque burden, and plaque composition (fibrous, fibrofatty, necrotic core, calcific). Positive remodeling was defined as expansion of external elastic membrane area on follow-up. Patients were divided into two groups by the median of the change (Δ) in necrotic core volume over the subsequent 3 years. Results: A total of 55 patients (mean age 52±15 years, 65% males) were included. Median time after transplant was 4.2 years at baseline. Average vessel area at baseline and three years were 15.8±4.6 and 15.3±5.4 mm, respectively (p=0.32). Twenty-four patients (44%) who showed positive remodeling at follow-up, compared to those who did not, had lower levels of baseline CD34+ progenitor cells (absolute count per 100,000 counts, 980 [690, 1460]) vs. 665 [438, 1015], p=0.02) (Fig. 1A). Patients with greater than median (>1.96 mm3) Δnecrotic core volume, as compared to those with below median Δ, also had lower baseline CD34+ cells (705 [483, 998] vs. 1180 [660, 1620] per 100,000 counts, p=0.04) (Fig. 1B). Conclusions: Lower levels of CD34+ progenitor cells are associated with long-term positive coronary vascular remodeling and increased plaque necrotic core volume in patients who underwent allograft heart transplant. This study supports the notion that circulating CD34+ progenitor cells play a role in CAV.
• Ӧzcan, I., Toya, T., Corban, M., Ahmad, A., Loeffler, D., Ostlie, H., Kushwaha, S., Lerman, L. O., & Lerman, A. (2020). Abstract 15260: Higher Levels of Osteoblast-lineage Cells Are Associated With Cardiac Allograft Vasculopathy Progression. Circulation. doi:10.1161/circ.142.suppl_3.15260
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  Introduction: Cardiac allograft vasculopathy (CAV) is a major determinant of long term graft survival. Endothelial progenitor cells (EPC) expressing osteocalcin (OC) have been linked to atherosclerosis. However, little is known regarding bone-forming osteoblast-lineage (OL) cells, and their role in atherosclerosis and CAV. Methods: Heart transplant patients undergoing serial Intravascular Ultrasound (IVUS) and progenitor cell studies were included in the study. OL cells, defined as cells positive for alkaline phosphatase (AP) and OC, were counted using flow cytometry on the day of baseline IVUS. A follow up IVUS was done 3 years later. Gray-scale and virtual-histology IVUS were used to evaluate vessel size, plaque burden, and plaque composition (fibrous, fibrofatty, necrotic core, calcified). Patients were divided into two groups by the median change (Δ) in necrotic core volume and plaque volume over 3 years. Results: A total of 55 patients (mean age 52±15 years, 65% males) were included. At baseline, median time after transplant was 4.2 years. Average vessel area at baseline and three years were 15.8 ±4.6 and 15.3 ±5.4 mm2, respectively (p=0.32). However, 24/55 patients (44%) had positive remodeling. The number of OL cells was positively correlated with Δvessel (r=0.36, p=0.01) and Δlumen areas. (r=0.30, p=0.02). Patients with greater Δplaque volume and Δnecrotic core volume had higher OL cell levels compared to those with below medians (Δplaque volume: 95 [30,348] vs. 30 [10, 90] OL per 100,000 counts, p=0.01; Δnecrotic core volume: 95 [22.5, 320] vs. 30 [10, 90] OL per 100,000 counts, p=0.03) (Fig. 1A and 1B). Conclusions: The number of OL cells in heart transplant patients correlates with positive vascular remodeling, accompanied by increased lumen area over 3 months. Furthermore, patients with unstable plaque features had higher OL cells, suggesting a possible role in pathologic plaque progression.
• Albadri, A., Eshtehardi, P., Hung, O. Y., Bouchi, Y., Khawaja, S., Mercado, K., Corban, M. T., Mehta, P. K., Shaw, L. J., & Samady, H. (2019). Coronary Microvascular Dysfunction Is Associated With Significant Plaque Burden and Diffuse Epicardial Atherosclerotic Disease.. JACC. Cardiovascular interventions, 12(15), 1519-1520. doi:10.1016/j.jcin.2019.05.003
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  Approximately 50% of patients with signs and symptoms of ischemia who undergo elective coronary angiography have no obstructive coronary epicardial atherosclerotic disease (CAD) [(1)][1]. However, two-thirds of these patients have evidence of coronary microvascular dysfunction (CMD) [(2)][2]. CMD
• Bae, J., Corban, M., Seo, Y. H., Kim, T., Lee, G., Rihal, C. S., & Lerman, A. (2019). Abstract 14104: Ten-Year Clinical Outcomes of Intermediate Coronary Lesion; Prognosis and Predictors of Major Adverse Cardiovascular Events. Circulation.
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  Introduction: The natural history of intermediate coronary lesions (30 to 70% angiographic stenosis) and the prognostic predictors in predicting very long-term clinical outcomes is unknown. Methods...
• Chen, Y. J., Corban, M., Wackel, P. L., Dorn, C. S., Dearani, J. A., & Sinak, L. J. (2019). Intramyocardial Hematoma After Radiofrequency Catheter Ablation. Circulation Journal: Atrial Fibrillation. doi:10.1253/circj.cj-18-0550
• Corban, M., Lerman, L., & Lerman, A. (2019). Endothelial dysfunction cardiovascular disease pathophysiology hidden in plain sight. Arterioscler Thromb Vasc Biol ., 39(7). doi:10.1161/ATVBAHA.119.312836
• Corban, M., Noseworthy, P. A., Lerman, L. O., & Lerman, A. (2019). 100.65 Abnormal Coronary Reactivity is Associated With Atrial Fibrillation Development: Is Atrial Fibrillation a Vascular Disease?. JACC: Interventions. doi:10.1016/j.jcin.2019.01.079
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  Coronary artery disease (CAD) risk factors are associated with atrial fibrillation (AF) and impaired endothelial function. We hypothesized that an abnormal coronary reactivity test (Abn-CRT) is associated with AF in patients with non-obstructive CAD. Three hundred patients with chest pain, non-
• Corban, M., Widmer, R. J., Kazeck, M., Lerman, L. O., & Lerman, A. (2019). SAFETY AND EFFICACY OF CHARDONNAY SEED SUPPLEMENTS IN IMPROVING PERIPHERAL VASCULAR HEALTH: A DOUBLE-BLINDED RANDOMIZED CONTROLLED TRIAL. JACC: Health Benefits of Nut Consumption. doi:10.1016/s0735-1097(19)32726-3
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  Peripheral endothelial dysfunction (PED) is associated with major adverse cardiovascular events. Similar to Mediterranean diet, Chardonnay seeds are rich in antioxidants, fiber, and mono-(MUFA)/poly-(PUFA) unsaturated fatty-acids. In a randomized double-blinded controlled trial we investigated the
• Fortin, S., Nkomo, V. T., Barillas-Lara, M. I., Assaf, Y., Bonikowske, A. R., Corban, M., Carta, K. G., Allison, T. G., & Brala, D. (2019). UTILITY OF CARDIOPULMONARY EXERCISE TESTING IN PATIENTS WITH ASYMPTOMATIC SEVERE AORTIC STENOSIS. JACC: Valvular Heart Disease. doi:10.1016/s0735-1097(19)32563-x
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  Indications for aortic valve replacement (AVR) in patients with asymptomatic severe AS (ASAS) are currently not well defined ObjectiveTo investigate the potential role of cardiopulmonary exercise testing (CPX) for identifying candidates for AVR in ASAS We reviewed CPX tests from November 2007-April
• Godo, S., Corban, M., Toya, T., Gulati, R., Lerman, L. O., & Lerman, A. (2019). CORONARY MICROVASCULAR ENDOTHELIAL DYSFUNCTION IS ASSOCIATED WITH ADVANCED CORONARY PLAQUE CHARACTERISTICS IN PATIENTS WITH EARLY CORONARY ATHEROSCLEROSIS. JACC: Interventional Cardiology. doi:10.1016/s0735-1097(19)32028-5
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  This study tested the hypothesis that coronary microvascular endothelial dysfunction (CMED) is associated with epicardial atherosclerotic coronary artery disease (CAD). 149 patients with chest pain, found to have angiographically normal coronary arteries or nonobstructive CAD (
• Merz, C. N., Henry, T. D., Wei, J., Corban, M., Joung, S., Kotynski, C., Lewis, M., Schumacher, A. M., Bartel, R. L., Sietsema, W. K., Losordo, D. W., & Lerman, A. (2019). Abstract 15864: Clinical Trial of Autologous CD34 Cell Therapy for Treatment of Coronary Microvascular Dysfunction in Patients With Angina and Non-Obstructive Coronary Arteries. Circulation.
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  Background: Coronary microvascular dysfunction (CMD) has been shown to result in ischemia and cause angina and is linked to adverse clinical outcomes. Thus, CMD may serve as the underlying mechanis...
• Corban, M. T. (2018). A DISAPPEARING ACT: NOW YOU SEE IT, NOW YOU DON’T. FIT Clinical Decision Making. doi:10.1016/s0735-1097(18)32774-8
• Corban, M., Alothman, O. W., Martin, W., Gerber, T. C., Casanegra, A. I., Oh, J. K., & Reeder, G. S. (2018). NEITHER HERE NOR THERE: INTRA-CARDIAC THROMBUS IN TRANSIT WEDGED IN A PATENT FORAMEN OVALE. JACC: Diagnosis and Management of Cardiac Tumors. doi:10.1016/s0735-1097(18)32820-1
• Corban, M., Lerman, L., & Lerman, A. (2018). Coronary Microvasculature: Are the Small and the Mighty Cross-Talking With the Epicardial Vessels?. JACC Cardiovasc Interv, 11(20). doi:10.1016/j.jcin.2018.07.059
• Corban, M., Lerman, L., & Lerman, A. (2018). Ubiquitous yet unseen: Microvascular endothelial dysfunction beyond the heart. Eur Heart J., 39(46). doi:10.1093/eurheartj/ehy576
• Corban, M., Prasad, A., Nesbitt, L., Loeffler, D., Herrmann, J., Lerman, L. O., & Lerman, A. (2018). Local Production of Soluble Urokinase Plasminogen Activator Receptor and Plasminogen Activator Inhibitor‐1 in the Coronary Circulation Is Associated With Coronary Endothelial Dysfunction in Humans. AHA: Role of Matrix Metalloproteinases in Cancer and Physiology. doi:10.1161/jaha.118.009881
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  Background Soluble urokinase plasminogen activator receptor (su PAR ) is a proinflammatory biomarker associated with immune activation and fibrinolysis inhibition. Plasminogen activator inhibitor ( PAI ‐1) is associated with excessive fibrin accumulation, thrombus formation, and atherosclerosis. The relationship between cross‐coronary su PAR and PAI ‐1 production and endothelial dysfunction remains unknown. Methods and Results Seventy‐nine patients (age 53±10 years, 75% women) with angina and normal coronary arteries or mild coronary artery disease (20% after acetylcholine) and mircovascular endothelial dysfunction (coronary blood flow change
• Corban, M., Prasad, A., Nesbitt, L., Loeffler, D., Lerman, L. O., & Lerman, A. (2018). CORONARY PLASMINOGEN ACTIVATOR INHIBITOR-1 RELEASE IS ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION. Journal of the American College of Cardiology. doi:10.1016/s0735-1097(18)31785-6
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  Plasminogen activator inhibitor (PAI-1), a potent inhibitor of fibrinolysis, is associated with excessive fibrin accumulation, thrombus formation, and atherosclerosis. Endothelial dysfunction (ED) occurs early in the pathophysiology of atherosclerotic coronary artery disease (CAD). We hypothesized
• Corban, M., Prasad, A., Nesbitt, L., Loeffler, D., Lerman, L. O., & Lerman, A. (2018). CORONARY SOLUBLE UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR RELEASE IS A BIOMARKER OF ENDOTHELIAL-DEPENDENT MICROVASCULAR DYSFUNCTION. JACC: Interventional Cardiology. doi:10.1016/s0735-1097(18)31717-0
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  Soluble Urokinase Plasminogen Activator Receptor (suPAR) is a pro-inflammatory biomarker associated with immune activation and fibrinolysis inhibition. suPAR, coronary epicardial endothelial dysfunction (ED) and endothelial-dependent microvascular dysfunction (MD) have been associated with adverse
• Khorramirouz, R., Corban, M., Yang, S. W., Lewis, B. R., Bois, J. P., Foley, T. A., Lerman, L. O., Herrmann, J., Oh, J. K., & Lerman, A. (2018). Microvascular obstruction in non-infarct related coronary arteries is an independent predictor of major adverse cardiovascular events in patients with ST segment-elevation myocardial infarction. International Journal of Cardiology. doi:10.1016/j.ijcard.2018.08.020
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  Background Coronary microvascular obstruction (MVO) in infarct-related artery (IRA) territory has been associated with worse cardiovascular outcomes in patients presenting with ST-segment elevation myocardial infarction. However, the prognostic value of non-IRA MVO in this patient population remains unknown. Methods and results One hundred ninety nine patients presenting to our institution with STEMI were enrolled. All patients underwent primary percutaneous coronary intervention per institutional STEMI protocol followed by a cardiac MRI within 1 week of presentation and the IRA and non-IRA MVO segments were determined. All cause death, recurrent myocardial infarction, hospitalization for heart failure, and ventricular tachycardia were counted as major adverse cardiovascular events (MACE). Patients with non-IRA MVO had lower composite MACE free survival at 6 months (HR 2.15, 95% CI, 1.06–4.35; p = 0.029) compared to those without non-IRA MVO. In a sub-analysis of patients with multi vessel disease (MVD), patients with non-IRA MVO also had lower composite MACE-free survival at 6 months as compared to those without non-IRA MVO (HR 2.47, 95% CI, 1.02–5.97; p = 0.037). Non-IRA MVO continued to be predictive of MACE in a cox proportional hazards model adjusting for additional prognostic factors using inverse probability weighting (p = 0.007). Non-IRA MVO was more prevalent in patients with LAD culprit vessel STEMI rather than those with RCA or Circumflex culprit vessels (p < 0.001). Conclusions Patients presenting with STEMI and non-IRA MVO have significantly lower MACE free survival at 6 months as compared to those without non-IRA MVO.
• Kumar, A., Hung, O. Y., Eshtehardi, P., Thompson, E., Sternheim, D., Sk, G., Chandran, K., Molony, D., Piccinelli, M., Lefieux, A., Corban, M., McDaniel, M., Quyyumi, A. A., Gogas, B. D., Giddens, D. P., Veneziani, A., & Samady, H. (2018). CRT-500.04 Lower Wall Shear Stress and Clinical Risk Factors are Associated with Endothelial Dysfunction in Patients with Non-Obstructive Coronary Artery Disease. JACC: Atherosclerosis. doi:10.1016/j.jcin.2018.01.131
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  We hypothesized that wall shear stress (WSS) has incremental value over cardiovascular risk factors for predicting severe endothelial dysfunction (EDFx) in patients with non-obstructive coronary artery disease (CAD). WSS was calculated in each 0.5 mm thick coronary segment in 44 patients with CAD
• Kumar, A., Hung, O., Piccinelli, M., Eshtehardi, P., Corban, M., Sternheim, D., Yang, B., Lefieux, A., Molony, D., Thompson, E., Zeng, W., Bouchi, Y., Gupta, S., Hosseini, H., Raad, M., Ko, Y., Liu, C., McDaniel, M., Gogas, B., , Douglas, J., et al. (2018). Low Coronary Wall Shear Stress Is Associated With Severe Endothelial Dysfunction in Patients With Nonobstructive Coronary Artery Disease. JACC: Cardiovascular Interventions, 11(20). doi:10.1016/j.jcin.2018.07.004
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  Objectives: This study investigated the relationship between low wall shear stress (WSS) and severe endothelial dysfunction (EDFx). Background: Local hemodynamic forces such as WSS play an important role in atherogenesis through their effect on endothelial cells. The study hypothesized that low WSS independently predicts severe EDFx in patients with coronary artery disease (CAD). Methods: Forty-four patients with CAD underwent coronary angiography, fractional flow reserve, and endothelial function testing. Segments with >10% vasoconstriction after acetylcholine (Ach) infusion were defined as having severe EDFx. WSS, calculated using 3-dimensional angiography, velocity measurements, and computational fluid dynamics, was defined as low (2.5 Pa). Results: Median age was 52 years, 73% were women. Mean fractional flow reserve was 0.94 ± 0.06. In 4,510 coronary segments, median WSS was 3.67 Pa. A total of 24% had severe EDFx. A higher proportion of segments with low WSS had severe EDFx (71%) compared with intermediate WSS (22%) or high WSS (23%) (p < 0.001). Segments with low WSS demonstrated greater vasoconstriction in response to Ach than did intermediate or high WSS segments (−10.7% vs. −2.5% vs. +1.3%, respectively; p < 0.001). In a multivariable logistic regression analysis, female sex (odds ratio [OR]: 2.44; p = 0.04), diabetes (OR: 5.01; p = 0.007), and low WSS (OR: 9.14; p < 0.001) were independent predictors of severe EDFx. Conclusions: In patients with nonobstructive CAD, segments with low WSS demonstrated more vasoconstriction in response to Ach than did intermediate or high WSS segments. Low WSS was independently associated with severe EDFx.
• Lerman, A., Khorramirouz, R., Corban, M., Yang, S., Bois, J. P., Lerman, L. O., & Oh, J. K. (2018). NON INFARCT RELATED ARTERY MICROVASCULAR OBSTRUCTION IS A PREDICTOR OF PERSISTENT DIASTOLIC DYSFUNCTION IN PATIENTS PRESENTING WITH ST ELEVATION MYOCARDIAL INFARCTION. JACC: Recommendations for Cardiac Chamber Quantification by Echocardiography. doi:10.1016/s0735-1097(18)32187-9
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  Diastolic dysfunction (DD) is associated with myocardial ischemia and left ventricular (LV) remodeling after myocardial infarction”. We hypothesized that patients presenting with STEMI and non-infarct-related (IRA) MVO will develop worse DD on long term follow-up post primary percutaneous
• Sara, J. D., Corban, M., Lerman, L. O., & Lerman, A. (2018). MYOCARDIAL BRIDGING IS ASSOCIATED WITH CORONARY ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH CHEST PAIN AND NON-OBSTRUCTIVE CORONARY ARTERY DISEASE. JACC: Congenital Coronary Artery Anomalies and Their Management. doi:10.1016/s0735-1097(18)30677-6
• Sara, J. D., Corban, M., Prasad, M., Prasad, A., Lerman, L. O., & Lerman, A. (2018). TCT-400 Prevalence of Myocardial Bridging Associated with Coronary Endothelial Dysfunction in Patients with Chest Pain and Non-Obstructive Coronary Artery Disease. JACC: Congenital Coronary Artery Anomalies and Their Management. doi:10.1016/j.jacc.2018.08.1559
• Sara, J. D., Corban, M., Prasad, M., Widmer, R. J., Lerman, L. O., & Lerman, A. (2018). 1344Myocardial bridging is associated with coronary endothelial dysfunction in patients with chest pain and non-obstructive coronary artery disease. European Heart Journal. doi:10.1093/eurheartj/ehy565.1344
• Sternheim, D., Thompson, E., Kumar, A., Hung, O. Y., Piccinelli, M., Molony, D., Eshtehardi, P., Corban, M., Sk, G., Chandran, K., Lefieux, A., Ko, Y., McDaniel, M., Gogas, B. D., Quyyumi, A. A., Giddens, D. P., Veneziani, A., & Samady, H. (2018). CRT-300.08 Coronary Vessels with Larger Contiguous Regions of Low Wall Shear Stress Have More Endothelial Dysfunction. JACC: Physiologic Lesion Assessment. doi:10.1016/j.jcin.2018.01.125
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  Impaired endothelial function (EFx) is associated with atherosclerosis. We hypothesized that a higher number of contiguous coronary samples with low wall shear stress (WSS) is associated with more endothelial dysfunction. A total of 44 patients with non-obstructive coronary artery disease (CAD) (
• Corban, M., Duarte‐García, A., McBane, R. D., Matteson, E. L., Lerman, L. O., & Lerman, A. (2017). Antiphospholipid Syndrome. Journal of the American College of Cardiology. doi:10.1016/j.jacc.2017.02.058
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  Antiphospholipid syndrome (APS) is an autoimmune disease characterized by venous thromboembolism, arterial thrombosis, and obstetric morbidities in the setting of persistently positive levels of antiphospholipid antibodies measured on 2 different occasions 12 weeks apart. Patients with APS are at increased risk for accelerated atherosclerosis, myocardial infarction, stroke, and valvular heart disease. Vascular endothelial cell dysfunction mediated by antiphospholipid antibodies and subsequent complement system activation play a cardinal role in APS pathogenesis. Improved understanding of their pathogenic function could help in the risk stratification of patients with APS and provide new molecular therapeutic targets.
• Corban, M., Pollak, A. W., Lerman, A., & Ammash, N. M. (2017). CHEST PAIN IN A PATIENT WITH ANOMALOUS LEFT ANTERIOR DESCENDING CORONARY ARTERY, MYOCARDIAL BRIDGING AND VASOCONSTRICTION: IDENTIFICATION OF THE CULPRIT ETIOLOGY AND MANAGEMENT OF A CHALLENGING COMBINATION. Front Cardiovasc Med .. doi:10.1016/s0735-1097(17)35628-0
• Corban, M., Sabbagh, A. E., Chedid, V., & Sinak, L. J. (2017). PROMPT RECOGNITION AND INTERVENTION FOR CARDIAC TAMPONADE SECONDARY TO GASTRO-PERICARDIAL FISTULA: A SUCCESSFUL HEART TEAM EFFORT. JACC: Spontaneous Pneumomediastinum in COVID-19 Patients. doi:10.1016/s0735-1097(17)35534-1
• Corban, M., Shah, N., & Anavekar, N. S. (2017). DIAGNOSIS OF MYOTONIC DYSTROPHY TYPE 1 IN A PATIENT PRESENTING WITH STRESS-INDUCED CARDIOMYOPATHY: IMPORTANCE OF OBTAINING FAMILY HISTORY AND HAVING A LOW THRESHOLD OF SUSPICION. JACC: FIT Clinical Decision Making. doi:10.1016/s0735-1097(17)35754-6
• Eshtehardi, P., Brown, A., Bhargava, A., Costopoulos, C., Hung, O., Corban, M., Hosseini, H., Gogas, B., Giddens, D., & Samady, H. (2017). High wall shear stress and high-risk plaque: an emerging concept. International Journal of Cardiovascular Imaging, 33(7). doi:10.1007/s10554-016-1055-1
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  In recent years, there has been a significant effort to identify high-risk plaques in vivo prior to acute events. While number of imaging modalities have been developed to identify morphologic characteristics of high-risk plaques, prospective natural-history observational studies suggest that vulnerability is not solely dependent on plaque morphology and likely involves additional contributing mechanisms. High wall shear stress (WSS) has recently been proposed as one possible causative factor, promoting the development of high-risk plaques. High WSS has been shown to induce specific changes in endothelial cell behavior, exacerbating inflammation and stimulating progression of the atherosclerotic lipid core. In line with experimental and autopsy studies, several human studies have shown associations between high WSS and known morphological features of high-risk plaques. However, despite increasing evidence, there is still no longitudinal data linking high WSS to clinical events. As the interplay between atherosclerotic plaque, artery, and WSS is highly dynamic, large natural history studies of atherosclerosis that include WSS measurements are now warranted. This review will summarize the available clinical evidence on high WSS as a possible etiological mechanism underlying high-risk plaque development.
• Khorramirouz, R., Corban, M., Yang, S., Bois, J. P., Foley, T. A., Lerman, L. O., & Lerman, A. (2017). Abstract 20300: Microvascular Obstruction in Non Infarct Related Coronary Arteries in an Independent Predictor of Major Adverse Cardiovascular Events in ST Segment Elevation Myocardial Infarction Patients. Circulation.
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  Background: Coronary microvascular disease has been associated with increased myocardial ischemia and adverse cardiovascular events (MACE). The prognostic value of non-infarct-related coronary arte...
• Lee, S., Sandesara, P. B., Eshtehardi, P., Hayek, S. S., Tahhan, A. S., Hung, O. Y., Corban, M., Rabah, R., Gandhi, R. V., Hosseini, H., Chand, N., Gogas, B. D., Shaw, L. J., Quyyumi, A. A., & Samady, H. (2017). P1771Soluble urokinase plasminogen activator receptor and vulnerable plaque: high suPAR is associated with larger coronary plaque necrotic core and dense calcium in non-obstructive coronary artery disease. European Heart Journal. doi:10.1093/eurheartj/ehx502.p1771
• Corban, M., Hung, O., Mekonnen, G., Eshtehardi, P., Eapen, D., Rasoul-Arzrumly, E., Al Kassem, H., Manocha, P., Ko, Y., Sperling, L., Quyyumi, A., & Samady, H. (2016). Elevated levels of serum fibrin and fibrinogen degradation products are independent predictors of larger coronary plaques and greater plaque necrotic core. Circulation Journal, 80(4). doi:10.1253/circj.CJ-15-0768
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  Background: Co-existence of vulnerable plaque and pro-thrombotic state may provoke acute coronary events. It was hypothesized that elevated serum levels of fibrin and fibrinogen degradation products (FDP) are associated with larger total plaque and necrotic core (NC) areas. Methods and Results: Seventy-five patients presenting with stable anginal symptoms (69%) or stabilized acute coronary syndrome (ACS; 31%), and found to have non-obstructive coronary artery disease (CAD) with a fractional flow reserve >0.8, were studied. Invasive virtual histology intravascular ultrasound (VH-IVUS) was performed in 68 LAD arteries, 6 circumflex arteries, and 1 right coronary artery. Serum FDP levels were measured using ELISA technique. Plaque volumetrics and composition were assessed in each VH-IVUS frame and averaged. The median age of patients was 56 (47–63) years; 52% were men and 23% had diabetes. The average length of coronary artery studied was 62 mm. After adjustment for systemic risk factors, medications, CRP levels and ACS, male gender (P
• Eshtehardi, P., Hung, O. Y., Bouchi, Y., Zhang, W., Corban, M., Gandhi, R., Hosseini, H., Gogas, B. D., Mehta, P. K., Shaw, L. J., Quyyumi, A. A., & Samady, H. (2016). Abstract 15369: Patients With Coronary Microvascular Dysfunction Have High Plaque Burden and Diffuse Epicardial Atherosclerotic Disease on Intravascular Ultrasound. Circulation.
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  Background: Coronary microvascular dysfunction (CMD) often coexists with epicardial atherosclerotic coronary artery disease (CAD). Although CMD has been implicated as a marker of early or diffuse C...
• Eshtehardi, P., Hung, O. Y., Corban, M., Timmins, L. H., Molony, D., Ahn, S. G., Gogas, B. D., Bouchi, Y., Zhang, W., Sebaali, F., Joshi, U., Suh, J., Giddens, D. P., & Samady, H. (2016). ELEVATED HYPEREMIC MICROVASCULAR RESISTANCE IS ASSOCIATED WITH LOWER CORONARY WALL SHEAR STRESS IN PATIENTS WITH NON-OBSTRUCTIVE CORONARY ARTERY DISEASE. JACC: ACC.I2 Interventional Cardiology. doi:10.1016/s0735-1097(16)30367-9
• Hung, O., Molony, D., Corban, M., Rasoul-Arzrumly, E., Maynard, C., Eshtehardi, P., Dhawan, S., Timmins, L., Piccinelli, M., Ahn, S., Gogas, B., McDaniel, M., Quyyumi, A., Giddens, D., & Samady, H. (2016). Comprehensive assessment of coronary plaque progression with advanced intravascular imaging, physiological measures, and wall shear stress: A pilot double-blinded randomized controlled clinical trial of nebivolol versus atenolol in nonobstructive coronary artery disease. Journal of the American Heart Association, 5(1). doi:10.1161/JAHA.115.002764
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  Background-We hypothesized that nebivolol, a β-blocker with nitric oxide-mediated activity, compared with atenolol, a β-blocker without such activity, would decrease oxidative stress and improve the effects of endothelial dysfunction and wall shear stress (WSS), thereby reducing atherosclerosis progression and vulnerability in patients with nonobstructive coronary artery disease. Methods and Results-In this pilot double-blinded randomized controlled trial, 24 patients treated for 1 year with nebivolol 10 mg versus atenolol 100 mg plus standard medical therapy underwent baseline and follow-up coronary angiography with assessments of inflammatory and oxidative stress biomarkers, microvascular function, endothelial function, and virtual histology intravascular ultrasound. WSS was calculated from computational fluid dynamics. Virtual histology intravascular ultrasound segments were assessed for vessel volumetrics and remodeling. There was a trend toward more low-WSS segments in the nebivolol cohort (P=0.06). Low-WSS regions were associated with greater plaque progression (P < 0.0001) and constrictive remodeling (P=0.04); conversely, high-WSS segments demonstrated plaque regression and excessive expansive remodeling. Nebivolol patients had decreased lumen and vessel areas along with increased plaque area, resulting in more constrictive remodeling (P=0.002). There were no significant differences in biomarker levels, microvascular function, endothelial function, or number of thin-capped fibroatheromas per vessel. Importantly, after adjusting for β-blocker, low-WSS segments remained significantly associated with lumen loss and plaque progression. Conclusion-Nebivolol, compared with atenolol, was associated with greater plaque progression and constrictive remodeling, likely driven by more low-WSS segments in the nebivolol arm. Both β-blockers had similar effects on oxidative stress, microvascular function, and endothelial function.
• Mekonnen, G., Corban, M., Hung, O. Y., Eshtehardi, P., Eapen, D. J., Al-Kassem, H., Rasoul–Arzrumly, E., Gogas, B. D., McDaniel, M., Pielak, T., Thorball, C. W., Sperling, L., Quyyumi, A. A., & Samady, H. (2015). Plasma soluble urokinase-type plasminogen activator receptor level is independently associated with coronary microvascular function in patients with non-obstructive coronary artery disease. Science Direct: Atherosclerosis. doi:10.1016/j.atherosclerosis.2014.12.025
• Timmins, L., Gupta, D., Corban, M., Molony, D., Oshinski, J., Samady, H., & Giddens, D. (2015). Co-localization of Disturbed Flow Patterns and Occlusive Cardiac Allograft Vasculopathy Lesion Formation in Heart Transplant Patients. Cardiovascular Engineering and Technology, 6(1). doi:10.1007/s13239-014-0198-2
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  Cardiac allograft vasculopathy (CAV) is one of the leading causes of morbidity and morality in orthotopic heart transplant (HTx) patients. While disturbed flow patterns have been linked to the spatial localization of atherosclerosis, the role of hemodynamics in CAV development has not been examined. HTx patients (n = 5) requiring percutaneous coronary intervention (PCI) for a focal, epicardial lesion were studied. Angiographic images were retrospectively obtained from baseline (i.e., in the presence of no observed disease) and follow-up catheterizations (i.e., at the time of PCI; 12.4 ± 2.6 years post-HTx). Patient-specific computational models were created from baseline images. Computational fluid dynamic techniques were employed to quantify the hemodynamic environment, which was expressed as normalized time-averaged WSS (TAWSSnorm; measure of temporal WSS magnitude) and normalized WSS angle deviation (WSSADnorm; measure of instantaneous WSS vector oscillation) values. Baseline hemodynamic and follow-up angiographic data were co-registered to investigate the association between WSS and subsequent occlusive CAV lesion location. Results indicate a high degree of co-localization between baseline low WSS data and follow-up occlusive CAV lesion. Local minima in TAWSSnorm were located 2.5 ± 0.6 mm from the site of PCI. Furthermore, local maxima in WSSADnorm were located 3.9 ± 0.7 mm from the site of PCI. In 3 patients, the occlusive lesion formed in a region that was subjected to both low and oscillatory WSS at baseline. There was discernable spatial co-localization between baseline disturbed flow patterns and follow-up CAV lesions requiring PCI. These results suggest a role of fluid mechanics in the development of focal, flow-limiting CAV lesions.
• Corban, M., Eshtehardi, P., Suo, J., McDaniel, M., Timmins, L., Rassoul-Arzrumly, E., Maynard, C., Mekonnen, G., King, S., Quyyumi, A., Giddens, D., & Samady, H. (2014). Combination of plaque burden, wall shear stress, and plaque phenotype has incremental value for prediction of coronary atherosclerotic plaque progression and vulnerability. Atherosclerosis, 232(2). doi:10.1016/j.atherosclerosis.2013.11.049
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  Aims: Large plaque burden, certain phenotypes, and low wall shear stress (WSS) are associated with adverse outcomes and high WSS with development of plaque vulnerability. We aimed to investigate the incremental value of the combination of plaque burden, WSS and plaque phenotype for prediction of coronary atherosclerotic plaque progression and vulnerability. Methods: Twenty patients with CAD underwent baseline and 6-month follow-up coronary virtual histology-intravascular ultrasound (VH-IVUS) and computational fluid dynamics modeling for calculation of WSS. Low WSS was defined as 40% and low WSS had significantly greater change in plaque area at follow-up (+0.68±1.05mm2), compared to segments with plaque burden >40% without low WSS (-0.28±1.32mm2) or segments with low WSS and plaque burden ≤40% (+0.05±0.71mm2) (p=0.047). Among plaque phenotypes, pathologic intimal thickening (PIT) had the greatest increase in necrotic core (NC) area (p=0.06) and greatest decrease in fibro-fatty (FF) area (p60%, PIT, or high WSS, those with a combination of plaque burden >60%, PIT, and high WSS developed greater increase in NC area (p=0.002), greater decrease in FF (p=0.004) and fibrous areas (p
• Corban, M., Hung, O., Timmins, L., & Samady, H. (2014). Reply: Myocardial bridging. Journal of the American College of Cardiology, 64(20). doi:10.1016/j.jacc.2014.09.009
• Corban, M., Eshtehardi, P., & Samady, H. (2013). Fractional flow reserve for the assessment of complex multivessel disease in a patient after hybrid coronary revascularization. Catheterization and Cardiovascular Interventions, 81(7). doi:10.1002/ccd.24605
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  We present a case of a 43-year-old woman with history of hybrid coronary revascularization [endoscopic atraumatic coronary artery bypass (ACAB)] of left internal mammary artery (LIMA) to the left anterior descending artery (LAD) and stent implantation in right coronary artery (RCA), who presented 6 years later with recurrent atypical angina. Coronary angiography revealed patent LIMA to LAD and RCA stent, with a new lesion in an obtuse marginal artery and significant progression of disease in the proximal/mid LAD proximal to LIMA touchdown. To further evaluate the hemodynamic significance of these new disease segments, the patient underwent fractional flow reserve (FFR) assessment of the left coronary system with subsequent stent implantation in the proximal/mid LAD. This case illustrates (1) the critical value of FFR assessment in determining the ischemia provoking lesions in this post ACAB patient with complex multivessel coronary artery disease; and (2) the accelerated progression of atherosclerosis in bypassed segments as compared to segments proximal to stents. © 2012 Wiley Periodicals, Inc.
• Corban, M., Eshtehardi, P., Eapen, D. J., Rasoul–Arzrumly, E., Kassem, H. A., Manocha, P., Patel, A. D., Sikora, S., Mekonnen, G., Hassanyar, M. R., Sperling, L., Quyyumi, A. A., & Samady, H. (2013). ELEVATED LEVELS OF FIBRIN DEGRADATION PRODUCTS IS AN INDEPENDENT PREDICTOR OF INTRAVASCULAR ULTRASOUND–DEFINED FEATURES OF PLAQUE VULNERABILITY IN PATIENTS WITH CORONARY ARTERY DISEASE. JACC: TCT@ACC-I2: Invasive And Interventional Cardiology. doi:10.1016/s0735-1097(13)61785-4
• Eshtehardi, P., Corban, M., Suo, J., Piccinelli, M., Timmins, L. H., Passerini, T., Rasoul–Arzrumly, E., McDaniel, M., Mekonnen, G., Quyyumi, A. A., Veneziani, A., Giddens, D. P., & Samady, H. (2013). HIGHER CORONARY WALL SHEAR STRESS IS ASSOCIATED WITH GREATER IMPAIRMENT IN MICROVASCULAR FUNCTION IN PATIENTS WITH NON–OBSTRUCTIVE CORONARY ARTERY DISEASE. JACC: TCT@ACC-I2: Invasive And Interventional Cardiology. doi:10.1016/s0735-1097(13)61843-4
• Corban, M., & Samady, H. (2012). Wall shear stress and evolution of coronary atherosclerosis: An emerging intravascular imaging modality. Interventional Cardiology, 4(2). doi:10.2217/ica.12.9
• Corban, M., Eshtehardi, P., McDaniel, M., Suo, J., Dhawan, S. S., Maynard, C., Timmins, L. H., Quyyumi, A. A., Giddens, D. P., & Samady, H. (2012). TCT-22 Combination of High Wall Shear Stress, Plaque Burden, and Plaque Phenotype has Incremental Value for Prediction of Increased Plaque Vulnerability in Patients with Coronary Artery Disease. JACC: Clinical Studies on Coronary Stents and Revascularization. doi:10.1016/j.jacc.2012.08.028
• Corban, M., Eshtehardi, P., McDaniel, M., Suo, J., Dhawan, S. S., Maynard, C., Timmins, L. H., Rasoul–Arzrumly, E., Quyyumi, A. A., Giddens, D. P., & Samady, H. (2012). TCT-265 Combination of Large Plaque Burden and Low Wall Shear Stress Results in Greater Progression of Coronary Atherosclerosis than Low Wall Shear Stress Alone in Patients with Coronary Artery Disease. JACC: Clinical Studies on Coronary Stents and Revascularization. doi:10.1016/j.jacc.2012.08.289
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  than the low peak hs-CRP group. A multivariate logistic regression model revealed that high peak hs-CRP levels correlated with the presence of ruptured plaque and microchannel (odds ratio 5.19, P 0.01 and odds ratio 4.18, P 0.01, respectively). Conclusions: High peak hs-CRP was associated with the presence of ruptured plaque and neovascularization, suggesting that elevation of hs-CRP during admission may reflect greater plaque vulnerability in the setting of NSTEACS.
• Corban, M., Piccinelli, M., Timmins, L. H., Passerini, T., Eshtehardi, P., Nanjundappa, R. P., Rasoul–Arzrumly, E., McDaniel, M., Oshinski, J. N., Quyyumi, A. A., Veneziani, A., Giddens, D. P., & Samady, H. (2012). Abstract 17758: Lower Coronary Wall Shear Stress is Associated with Endothelial Dysfunction in Patients with Non-Obstructive Coronary Artery Disease. Circulation.
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  Background: Both low wall shear stress (WSS) and endothelial dysfunction have been associated with various stages of coronary atherosclerosis. However, the relationship between WSS and endothelial ...
• Dhawan, S. S., Nanjundappa, R. P., Eshtehardi, P., Corban, M., Golub, L., Timmins, L. H., McDaniel, M., Quyyumi, A. A., & Samady, H. (2012). IMPAIRED CORONARY MICROVASCULAR FUNCTION IS ASSOCIATED WITH FEATURES OF PLAQUE VULNERABILITY. JACC: Acute Coronary Syndromes. doi:10.1016/s0735-1097(12)60409-4
• Dhawan, S., Corban, M., Nanjundappa, R., Eshtehardi, P., McDaniel, M., Kwarteng, C., & Samady, H. (2012). Coronary microvascular dysfunction is associated with higher frequency of thin-cap fibroatheroma. Atherosclerosis, 223(2). doi:10.1016/j.atherosclerosis.2012.05.034
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  Objective: Both coronary microvascular dysfunction and epicardial plaque vulnerability have been associated with adverse cardiovascular outcomes. However, whether microvascular dysfunction is a predictor of plaque vulnerability is not known. We hypothesized that microvascular dysfunction is associated with greater systemic inflammation and is a predictor of virtual histology-intravascular ultrasound (VH-IVUS)-defined coronary thin-cap fibroatheromas. Methods: Invasive physiologic assessment and VH-IVUS were performed and serum high-sensitivity C-reactive protein (hs-CRP) was measured in 51 patients with non-obstructive CAD [fractional flow reserve (FFR). ≥. 0.75]. Microvascular dysfunction was defined as coronary flow velocity reserve (CFVR).
• Eshtehardi, P., McDaniel, M., Dhawan, S. S., Binongo, J., Krishnan, S., Golub, L., Corban, M., Raggi, P., Quyyumi, A. A., & Samady, H. (2012). Effect of intensive atorvastatin therapy on coronary atherosclerosis progression, composition, arterial remodeling, and microvascular function.. J Invasive Cardiol ..
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  There is a discrepancy between the marked reduction in adverse events with statins and their modest effect on atheroma regression. We hypothesized that, in a Western population, high-dose atorvastatin will result in alterations in coronary atheroma composition, phenotype, and microvascular function.Serial coronary radiofrequency intravascular ultrasound (VH-IVUS), coronary flow reserve (CFR), and hyperemic microvascular resistance (HMR) were performed at baseline and after 6 months of treatment with 80 mg atorvastatin in 20 patients with moderate coronary artery disease (CAD). For each VH-IVUS frame (n = 2249), changes in total plaque atheroma, composition, and phenotype (pathological intimal thickening, fibrotic plaque, fibroatheroma), and serial remodeling were assessed.Total serum cholesterol decreased from 186.0 mg/dL (interquartile range [IQR], 168.0 to 212.5 mg/dL) to 139.0 mg/dL (IQR, 124.3 to 151.3 mg/dL). Percent atheroma volume did not change significantly (-0.5% [IQR, -2.8% to 3.7%]; P=.90) and serial remodeling analysis demonstrated 40% constrictive, 24% incomplete, and 36% expansive patterns. There was a trend toward lower percent fibrous tissue (-3.47 ± 1.78%; P=.07) and percent fibro-fatty tissue (-2.52 ± 1.24%; P=.06) and increase in percent necrotic core (+2.74 ± 1.65%; P=.11) and percent dense calcium (+1.99 ± 0.81; P=.02), which translated into significantly less pathological intimal thickening (4% vs 12%; P
• Eshtehardi, P., McDaniel, M., Suo, J., Dhawan, S. S., Timmins, L. H., Binongo, J., Golub, L., Corban, M., Finn, A. V., Oshinski, J. N., Quyyumi, A. A., Giddens, D. P., & Samady, H. (2012). Association of Coronary Wall Shear Stress With Atherosclerotic Plaque Burden, Composition, and Distribution in Patients With Coronary Artery Disease. J Am Heart Assoc .. doi:10.1161/jaha.112.002543
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  Extremes of wall shear stress (WSS) have been associated with plaque progression and transformation, which has raised interest in the clinical assessment of WSS. We hypothesized that calculated coronary WSS is predicted only partially by luminal geometry and that WSS is related to plaque composition.Twenty-seven patients with coronary artery disease underwent virtual histology intravascular ultrasound and Doppler velocity measurement for computational fluid dynamics modeling for WSS calculation in each virtual histology intravascular ultrasound segment (N=3581 segments). We assessed the association of WSS with plaque burden and distribution and with plaque composition. WSS remained relatively constant across the lower 3 quartiles of plaque burden (P=0.08) but increased in the highest quartile of plaque burden (P
• Davis, J., Smith, M., Crooks, P., Corban, M., Morrison, L., Panizza, B., Coman, W. B., & Moss, D. (2005). Regulatory T cells localise in nasopharyngeal carcinoma (NPC) tumours. The University of Queensland.

Presentations

• Corban, M. (2024, September). Endothelial Dysfunction. University of Arizona - Medicine Grand Rounds. Banner University Medical Center.
• Corban, M. (2023, August). Cath Practicum. Fellows Conference. Tucson, AZ: Sarver Heart Center, University of Arizona.
• Corban, M. (2023, February). Angio practicum. Fellows Conference. Tucson, AZ: Sarver Heart Center, University of Arizona.
• Corban, M. (2023, October). Coronary Physiology  Part 1. Fellows Conference. Tucson, AZ: Sarver Heart Center, University of Arizona.

Poster Presentations

• Ajmal, M., Kubba, S., Lee, K. S., Lerman, A., & Corban, M. (2022, November). Abstract 11774: Heart Failure with Preserved Ejection Fraction Secondary to Coronary Endothelial Dysfunction and Microvascular Disease. American Heart Association Scientific Sessions 2022. Chicago, IL.
• Kazui, T., Kotagiri, R., Avila, D., Corban, M., Moynahan, K. F., Kolimas, A., & Muhammad, A. (2022, November). Infective endocarditis of the mitral valve in an immunocompetent patient caused by lactobacillus species. American Heart Association Scientific Sessions 2022. Chicago: AHA.
• Seckeler, M., Klewer, S. E., Corban, M., Ibrahim, R., & Takamatsu, C. (2022, November). Transcatheter reconstruction of right ventricular outflow tract after severe external compression by a pseudoaneurysm in an adult with tetralogy of Fallot. American Heart Association 2022 Scientific Sessions. Chicago, IL.