Clinical Focus

  • Cardiovascular Disease

Honors & Awards

  • Scientist Development Grant Recipient, American Heart Association (2014-2017)
  • Early Investigator Grant Program Award Recipient, The Marfan Foundation (2014-2015)
  • Alderman Award for Excellence in Clinical Research, Stanford University (2011)
  • Dean?s Fellowship Award, Stanford University (2010)
  • Women in Cardiology Trainee Award for Excellence, American Heart Association (2010)

Education & Certifications

  • Fellowship:Stanford University (2013) CA
  • Residency:University of Michigan Medical Center (2008) MI
  • Medical Education:Dartmouth Medical School (2005) NH
  • Fellowship:Stanford University (2001) CA
  • Board Certification: Echocardiography, National Board of Echocardiography (2013)
  • Board Certification: Cardiovascular Disease, American Board of Internal Medicine (2012)
  • Board Certification: Internal Medicine, American Board of Internal Medicine (2008)
  • Fellow, Stanford University School of Medicine, Multimodality Cardiovascular Imaging (2013)
  • Fellow, Stanford University School of Medicine, Cardiovascular MRI (2013)
  • Fellow, Stanford University School of Medicine, Cardiovascular Medicine (2011)
  • Resident, University of Michigan Hospitals, Internal Medicine Training Program (2008)
  • Intern, University of Michigan Hospitals, Internal Medicine Training Program (2006)
  • MD, Dartmouth Medical School, Medicine (2005)
  • BS, University of California, Berkeley, Bioengineering, chemical engineering (2000)


Graduate and Fellowship Programs


All Publications

  • Relationship between Echocardiographic and Magnetic Resonance Derived Measures of Right Ventricular Size and Function in Patients with Pulmonary Hypertension JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Shiran, H., Zamanian, R. T., McConnell, M. V., Liang, D. H., Dash, R., Heidary, S., Sudini, N. L., Wu, J. C., Haddad, F., Yang, P. C. 2014; 27 (4): 405-412


    Transthoracic echocardiographic (TTE) imaging is the mainstay of clinical practice for evaluating right ventricular (RV) size and function, but its accuracy in patients with pulmonary hypertension has not been well validated.Magnetic resonance imaging (MRI) and TTE images were retrospectively reviewed in 40 consecutive patients with pulmonary hypertension. RV and left ventricular volumes and ejection fractions were calculated using MRI. TTE areas and indices of RV ejection fraction (RVEF) were compared.The average age was 42 ± 12 years, with a majority of women (85%). There was a wide range of mean pulmonary arterial pressures (27-81 mm Hg) and RV end-diastolic volumes (111-576 mL), RVEFs (8%-67 %), and left ventricular ejection fractions (26%-72%) by MRI. There was a strong association between TTE and MRI-derived parameters: RV end-diastolic area (by TTE imaging) and RV end-diastolic volume (by MRI), R(2) = 0.78 (P < .001); RV fractional area change by TTE imaging and RVEF by MRI, R(2) = 0.76 (P < .001); and tricuspid annular plane systolic excursion by TTE imaging and RVEF by MRI, R(2) = 0.64 (P < .001). By receiver operating characteristic curve analysis, an RV fractional area change < 25% provided excellent discrimination of moderate systolic dysfunction (RVEF < 35%), with an area under the curve of 0.97 (P < .001). An RV end-diastolic area index of 18 cm(2)/m(2) provided excellent discrimination for moderate RV enlargement (area under the curve, 0.89; P < .001).Echocardiographic estimates of RV volume (by RV end-diastolic area) and function (by RV fractional area change and tricuspid annular plane systolic excursion) offer good approximations of RV size and function in patients with pulmonary hypertension and allow the accurate discrimination of normal from abnormal.

    View details for DOI 10.1016/j.echo.2013.12.011

    View details for Web of Science ID 000334315700006

  • Unexplained Double-Chambered Left Ventricle Associated with Contracting Right Ventricular Aneurysm and Right Atrial Enlargement ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES Finocchiaro, G., Murphy, D., Pavlovic, A., Haddad, F., Shiran, H., Sinagra, G., Ashley, E. A., Knowles, J. W. 2014; 31 (3): E80-E84

    View details for DOI 10.1111/echo.12467

    View details for Web of Science ID 000332346700003

  • Unexplained double-chambered left ventricle associated with contracting right ventricular aneurysm and right atrial enlargement. Echocardiography (Mount Kisco, N.Y.) Finocchiaro, G., Murphy, D., Pavlovic, A., Haddad, F., Shiran, H., Sinagra, G., Ashley, E. A., Knowles, J. W. 2014; 31 (3): E80-4


    In this article, we describe a double-chambered left ventricle (LV) associated with a functional right ventricular (RV) aneurysm and right atrial (RA) enlargement in an asymptomatic 24-year-old woman with a family history of sudden cardiac death. We will discuss the differential diagnosis, genetic testing and possible prognostic implications.

    View details for DOI 10.1111/echo.12467

    View details for PubMedID 24299065

  • Aortic wall thickness: an independent risk factor for aortic dissection? journal of heart valve disease Shiran, H., Odegaard, J., Berry, G., Miller, D. C., Fischbein, M., Liang, D. 2014; 23 (1): 17-24


    Aortic aneurysm size is known to portend a higher likelihood of aortic complications in patients with connective tissue disorders (CTD), but other objective tools are needed to determine which patients are at greatest risk of dissection, especially those which reflect the structural integrity and strength of the aortic wall.The aortic wall pathology was evaluated in CTD patients with and without acute aortic dissection to identify parameters that affect the risk of dissection. A retrospective review was performed of aneurysm pathology from patients with Marfan syndrome (MFS; n = 53) without dissection undergoing prophylactic aortic root surgery, and acute type A aortic dissection patients (AAAoD; n = 16). Patients without a cardiovascular cause of death (n = 19) served as controls. The minimal aortic medial wall thickness was measured, and medial myxoid degeneration (MMD) and the degree of elastin loss and fragmentation were graded.The mean minimal aortic wall thickness was 1,625 +/- 364 microm in controls, and 703 +/- 256 microm and 438 +/- 322 microm for MFS and AAAoD patients, respectively. Aortic root diameters did not correlate with aortic wall thickness. A comparison of aortic medial thickness showed that the media was significantly thinner among acute dissection patients than either elective surgical patients (p = 0.02) or controls (p < 0.001). Aortic size, degree of MMD, and elastin loss did not vary significantly between CTD patients.A diminished aortic wall medial thickness may be linked to aortic dissection. High-resolution imaging techniques in the future may lead to the morphological assessment of aortic medial wall thickness in vivo becoming a reality which, in theory, could provide a more refined risk prognostication for acute aortic dissection.

    View details for PubMedID 24779324

  • Comparison of Aortic Root Diameter to Left Ventricular Outflow Diameter Versus Body Surface Area in Patients With Marfan Syndrome AMERICAN JOURNAL OF CARDIOLOGY Shiran, H., Haddad, F., Miller, D. C., Liang, D. 2012; 110 (10): 1518-1522


    Aortic root dilation is important in the diagnosis of familial aortic syndromes, such as Marfan syndrome, and an important risk factor for aortic complications, such as dissection or rupture. Transthoracic echocardiography reliably measures the absolute aortic root size; however, the degree of abnormality of the measurement requires correction for the expected normal aortic root size for each patient. The expected normal size is currently predicted according to the body surface area (BSA) and age. However, the correlation between root size and BSA is imperfect, particularly for older patients. A potential exists to improve the diagnosis and treatment of patients with aortic disease, with an improved estimation of normal aortic root size. A reference size derived from within the cardiovascular system has been hypothesized to provide a more direct correlation with the aortic root size. Images from the Stanford echocardiography database were reviewed, and measurements of the aortic root and internal dimensions were performed in a control cohort (n = 150). The measurements were repeated in adult patients with Marfan syndrome (n = 70) on serial echocardiograms (145 total studies reviewed). Of the 150 control patients, excellent correlation was found between the aortic root and left ventricular outflow tract diameters, r(2) = 0.67, and r(2) = 0.34 with BSA (p <0.0001, for both). More importantly, using the left ventricular outflow tract to predict the normal aortic root size, instead of the BSA and age, improved the diagnostic accuracy of aortic root measurements for diagnosing Marfan syndrome. In conclusion, an internal cardiovascular reference, the left ventricular outflow tract diameter, can improve the diagnosis of aortic disease and might provide a better reference for the degree of abnormality.

    View details for DOI 10.1016/j.amjcard.2012.06.062

    View details for Web of Science ID 000311523900021

    View details for PubMedID 22858189

  • Correlates of Delayed Recognition and Treatment of Acute Type A Aortic Dissection The International Registry of Acute Aortic Dissection (IRAD) CIRCULATION Harris, K. M., Strauss, C. E., Eagle, K. A., Hirsch, A. T., Isselbacher, E. M., Tsai, T. T., Shiran, H., Fattori, R., Evangelista, A., Cooper, J. V., Montgomery, D. G., Froehlich, J. B., Nienaber, C. A. 2011; 124 (18): 1911-U82


    In acute aortic dissection, delays exist between presentation and diagnosis and, once diagnosed, definitive treatment. This study aimed to define the variables associated with these delays.Acute aortic dissection patients enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and January 2007 were evaluated for factors contributing to delays in presentation to diagnosis and in diagnosis to surgery. Multiple linear regression was performed to determine relative delay time ratios (DTRs) for individual correlates. The median time from arrival at the emergency department to diagnosis was 4.3 hours (quartile 1-3, 1.5-24 hours; n=894 patients) and from diagnosis to surgery was 4.3 hours (quartile 1-3, 2.4-24 hours; n=751). Delays in acute aortic dissection diagnosis occurred in female patients; those with atypical symptoms that were not abrupt or did not include chest, back, or any pain; patients with an absence of pulse deficit or hypotension; or those who initially presented to a nontertiary care hospital (all P<0.05). The largest relative DTRs were for fever (DTR=5.11; P<0.001) and transfer from nontertiary hospital (DTR=3.34; P<0.001). Delay in time from diagnosis to surgery was associated with a history of previous cardiac surgery, presentation without abrupt or any pain, and initial presentation to a nontertiary care hospital (all P<0.001). The strongest factors associated with operative delay were prolonged time from presentation to diagnosis (DTR=1.35; P<0.001), race other than white (DTR=2.25; P<0.001), and history of coronary artery bypass surgery (DTR=2.81; P<0.001).Improved physician awareness of atypical presentations and prompt transport of acute aortic dissection patients could reduce crucial time variables.

    View details for DOI 10.1161/CIRCULATIONAHA.110.006320

    View details for Web of Science ID 000296593800013

    View details for PubMedID 21969019

  • Humanitarian use devices/humanitarian device exemptions in cardiovascular medicine CIRCULATION Kaplan, A. V., Harvey, E. D., Kuntz, R. E., Shiran, H., Robb, J. F., Fitzgerald, P. 2005; 112 (18): 2883-2886


    The Second Dartmouth Device Development Symposium held in October 2004 brought together leaders from the medical device community, including clinical investigators, senior representatives from the US Food and Drug Administration, large and small device manufacturers, and representatives from the financial community to examine difficult issues confronting device development. The role of the Humanitarian Use Device/Humanitarian Device Exemption (HUD/HDE) pathway in the development of new cardiovascular devices was discussed in this forum. The HUD/HDE pathway was created by Congress to facilitate the availability of medical devices for "orphan" indications, ie, those affecting <4000 individuals within the United States each year. The HUD/HDE pathway streamlines the approval process and permits less well-characterized devices to enter the market. HDE approval focuses primarily on issues of safety and scientific soundness and does not require demonstration of efficacy. In the 7 years since the first device was approved in 1997, a total of 35 HDEs have been granted (23 devices, 6 diagnostic tests). As the costs to gain regulatory approval for commonly used devices increase, companies often seek alternative ways to gain market access, including the HUD/HDE pathway. For a given device, there may be multiple legitimate and distinct indications, including indications that meet the HUD criteria. Companies must choose how and when to pursue each of these indications. The consensus of symposium participants was for the HUD/HDE pathway to be reserved for true orphan indications and not be viewed strategically as part of the clinical development plan to access a large market.

    View details for DOI 10.1161/CIRCULATIONAHA.105.553701

    View details for Web of Science ID 000232988900020

    View details for PubMedID 16267261

  • A novel orthotopic tumor model to study growth factors and oncogenes in hepatocarcinogenesis CLINICAL CANCER RESEARCH Yao, X. M., Hu, J. F., Daniels, M., Yien, H. F., Lu, H. Q., Sharan, H., Zhou, X. J., Zeng, Z. L., Li, T., Yang, Y. W., Hoffman, A. R. 2003; 9 (7): 2719-2726


    An orthotopic xenograft tumor model of hepatocellular carcinoma was created by injection of Hep 3B cells directly into the liver parenchyma of nude mice. Tumors were localized primarily in the injected lobe of the liver, beginning from the third week after tumor cell implantation. Thereafter, tumors grew rapidly, and animals usually died from hepatocellular carcinoma within 2 months. Insulin-like growth factor II, an embryonic growth factor and mitogen, is overexpressed in these tumors at both mRNA and protein levels. Oncogenes, such as c-myc, c-fos, and c-jun, are also up-regulated in this model. alpha-Fetal protein can be detected shortly after implantation and correlates with tumor growth, and measurement of serum alpha-fetal protein serves as an early biomarker to monitor the effect of antitumor therapy. Using this model, we have shown that inhibition of insulin-like growth factor II expression by a short methylated oligonucleotide prolongs survival. This in situ tumor model thus provides a fast, reliable, and reproducible means to study the therapeutic effect of inhibitors of growth factors and oncogenes in liver cancer.

    View details for Web of Science ID 000184108700045

    View details for PubMedID 12855652

  • A methylated oligonucleotide inhibits IGF2 expression and enhances survival in a model of hepatocellular carcinoma JOURNAL OF CLINICAL INVESTIGATION Yao, X. M., Hu, J. F., Daniels, M., Shiran, H., Zhou, X. J., Yan, H. F., Lu, H. Q., Zeng, Z. L., Wang, Q. X., Li, T., Hoffman, A. R. 2003; 111 (2): 265-273


    IGF-II is a mitogenic peptide that has been implicated in hepatocellular oncogenesis. Since the silencing of gene expression is frequently associated with cytosine methylation at cytosine-guanine (CpG) dinucleotides, we designed a methylated oligonucleotide (MON1) complementary to a region encompassing IGF2 promoter P4 in an attempt to induce DNA methylation at that locus and diminish IGF2 mRNA levels. MON1 specifically inhibited IGF2 mRNA accumulation in vitro, whereas an oligonucleotide (ON1) with the same sequence but with nonmethylated cytosines had no effect on IGF2 mRNA abundance. MON1 treatment led to the specific induction of de novo DNA methylation in the region of IGF2 promoter hP4. Cells from a human hepatocellular carcinoma (HCC) cell line, Hep 3B, were implanted into the livers of nude mice, resulting in the growth of large tumors. Animals treated with MON1 had markedly prolonged survival as compared with those animals treated with saline or a truncated methylated oligonucleotide that did not alter IGF2 mRNA levels in vitro. This study demonstrates that a methylated sense oligonucleotide can be used to induce epigenetic changes in the IGF2 gene and that inhibition of IGF2 mRNA accumulation may lead to enhanced survival in a model of HCC.

    View details for DOI 10.1172/JCI200315109

    View details for Web of Science ID 000180672900018

    View details for PubMedID 12531883

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