Bio

Clinical Focus


  • Pulmonary Hypertension
  • Critical Care
  • Pulmonary Disease

Academic Appointments


Honors & Awards


  • Teaching Award for the Division of Pulmonary and Critical Care Medicine, Department of Medicine, Stanford University Medical Center (2011)
  • Clinical Fellowship in Pulmonary Vascular Disease, Vera Moulton Wall Center, Stanford University Medical Center (2008-2009)
  • David E. Rogers Memorial Research Award, NY Presbyterian Hospital-Cornell (2005)
  • National Institutes of Health Pre-Doctoral Intramural Training Award, National Human Genome Research Institute (1997-1998)

Professional Education


  • Fellowship:New York Presbyterian Hospital Weill Cornell (06/30/2008) NY
  • Board Certification: Critical Care Medicine, American Board of Internal Medicine (2008)
  • Residency:New York Presbyterian Hospital Weill Cornell (2005) NY
  • Internship:New York Presbyterian Hospital Weill Cornell (2003) NY
  • Fellowship:Stanford University (2009) CA
  • Board Certification: Pulmonary Disease, American Board of Internal Medicine (2007)
  • Board Certification: Internal Medicine, American Board of Internal Medicine (2005)
  • Medical Education:University of Pennsylvania School of Medicine (2002) PA
  • B.S., Yale University, Biology (1997)

Research & Scholarship

Current Research and Scholarly Interests


Drugs and toxins-associated pulmonary arterial hypertension, clinical outcomes research, acute kidney injury in pulmonary arterial hypertension

Publications

Journal Articles


  • A case of recurrent pericardial constriction presenting with severe pulmonary hypertension. Pulmonary circulation Brunner, N. W., Ramachandran, K., Kudelko, K. T., Sung, Y. K., Spiekerkoetter, E., Yang, P. C., Zamanian, R. T., Perez, V. d. 2013; 3 (2): 436-439

    Abstract

    Chronic constrictive pericarditis (CP) is a relatively rare condition in which the pericardium becomes fibrotic and noncompliant, eventually resulting in heart failure due to impaired ventricular filling. The only curative treatment is pericardiectomy. Classically, CP does not usually cause severe pulmonary hypertension. When attempting to differentiate CP from restrictive cardiomyopathy, the presence of severely elevated pulmonary arterial pressure is used as a diagnostic criterion ruling against CP. We present a case of proven recurrent pericardial constriction following pericardiectomy presenting with severe pulmonary hypertension.

    View details for DOI 10.4103/2045-8932.114780

    View details for PubMedID 24015347

  • Safety and Efficacy of Transition from Systemic Prostanoids to Inhaled Treprostinil in Pulmonary Arterial Hypertension AMERICAN JOURNAL OF CARDIOLOGY Perez, V. A., Rosenzweig, E., Rubin, L. J., Poch, D., Bajwa, A., Park, M., Jain, M., Bourge, R. C., Kudelko, K., Spiekerkoetter, E., Liu, J., Hsi, A., Zamanian, R. T. 2012; 110 (10): 1546-1550

    Abstract

    Pulmonary arterial hypertension (PAH) is a disease characterized by increased pulmonary pressures and chronic right heart failure. Therapies for moderate and severe PAH include subcutaneous (SQ) and intravenous (IV) prostanoids that improve symptoms and quality of life. However, treatment compliance can be limited by severe side effects and complications related to methods of drug administration. Inhaled prostanoids, which offer the advantage of direct delivery of the drug to the pulmonary circulation without need for invasive approaches, may serve as an alternative for patients unable to tolerate SQ/IV therapy. In this retrospective cohort study we collected clinical, hemodynamic, and functional data from 18 clinically stable patients with World Health Organization group I PAH seen in 6 large national PAH centers before and after transitioning to inhaled treprostinil from IV/SQ prostanoids. Before transition 15 patients had been receiving IV or SQ treprostinil (mean dose 73 ng/kg/min) and 3 patients had been on IV epoprostenol (mean dose 10 ng/kg/min) for an average duration of 113 ± 80 months. Although most patients who transitioned to inhaled treprostinil demonstrated no statistically significant worsening of hemodynamics or 6-minute walk distance, a minority demonstrated worsening of New York Heart Association functional class over a 7-month period. In conclusion, although transition of patients from IV/SQ prostanoids to inhaled treprostinil appears to be well tolerated in clinically stable patients, they should remain closely monitored for signs of clinical decompensation.

    View details for DOI 10.1016/j.amjcard.2012.07.012

    View details for Web of Science ID 000311523900026

  • Airway Management and Perioperative Decision Making in the Patient With Severe Pulmonary Hypertension Who Requires Emergency Noncardiac Surgery JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Maxwell, B. G., Pearl, R. G., Kudelko, K. T., Zamanian, R. T., Hill, C. C. 2012; 26 (5): 940-944

    View details for DOI 10.1053/j.jvca.2012.06.018

    View details for Web of Science ID 000309020900031

    View details for PubMedID 22943790

  • The Intersection of Genes and Environment Development of Pulmonary Arterial Hypertension in a Patient With Hereditary Hemorrhagic Telangiectasia and Stimulant Exposure CHEST Ayala, E., Kudelko, K. T., Haddad, F., Zamanian, R. T., Perez, V. d. 2012; 141 (6): 1598-1600

    Abstract

    Pulmonary arterial hypertension (PAH) is a rare complication of hereditary hemorrhagic telangiectasia (HHT). The triggers that promote the development of PAH in HHT remain poorly understood. We present the case of a 45-year-old woman with decompensated right-sided heart failure secondary to newly diagnosed PAH. The clinical diagnosis of HHT was confirmed on the basis of recurrent spontaneous epistaxis, multiple typical mucocutaneous telangiectasia, and the presence of pulmonary arteriovenous malformation. There was also a suggestive family history. The patient was discovered to have active and extensive stimulant abuse in addition to HHT. We concluded that there may be a temporal relationship between exposure to stimulants and development of PAH in a host with underlying gene mutation. This case highlights the paradigm of PAH development after environmental exposure in a genetically susceptible host.

    View details for DOI 10.1378/chest.11-1402

    View details for Web of Science ID 000305039300054

    View details for PubMedID 22670022

  • Characteristics and Outcome After Hospitalization for Acute Right Heart Failure in Patients With Pulmonary Arterial Hypertension CIRCULATION-HEART FAILURE Haddad, F., Peterson, T., Fuh, E., Kudelko, K. T., Perez, V. D., Skhiri, M., Vagelos, R., Schnittger, I., Denault, A. Y., Rosenthal, D. N., Doyle, R. L., Zamanian, R. T. 2011; 4 (6): 692-699

    Abstract

    Although much is known about the risk factors for poor outcome in patients hospitalized with acute heart failure and left ventricular dysfunction, much less is known about the syndrome of acute heart failure primarily affecting the right ventricle (acute right heart failure).By using Stanford Hospital's pulmonary hypertension database, we identified consecutive acute right heart failure hospitalizations in patients with PAH. We used longitudinal regression analysis with the generalized estimating equations method to identify factors associated with an increased likelihood of 90-day mortality or urgent transplantation. From June 1999 to September 2009, 119 patients with PAH were hospitalized for acute right heart failure (207 episodes). Death or urgent transplantation occurred in 34 patients by 90 days of admission. Multivariable analysis identified a higher respiratory rate on admission (>20 breaths per minute; OR, 3.4; 95% CI, 1.5-7.8), renal dysfunction on admission (glomerular filtration rate <45 mL/min per 1.73 m2; OR, 2.7; 95% CI, 1.2-6.3), hyponatremia (serum sodium ?136 mEq/L; OR, 3.6; 95% CI, 1.7-7.9), and tricuspid regurgitation severity (OR, 2.5 per grade; 95% CI, 1.2-5.5) as independent factors associated with an increased likelihood of death or urgent transplantation.These results highlight the high mortality after hospitalizations for acute right heart failure in patients with PAH. Factors identifiable within hours of hospitalization may help predict the likelihood of death or the need for urgent transplantation in patients with PAH.

    View details for DOI 10.1161/CIRCHEARTFAILURE.110.949933

    View details for Web of Science ID 000297166100008

    View details for PubMedID 21908586

  • Pulmonary Hypertension Associated With Left Heart Disease: Characteristics, Emerging Concepts, and Treatment Strategies PROGRESS IN CARDIOVASCULAR DISEASES Haddad, F., Kudelko, K., Mercier, O., Vrtovec, B., Zamanian, R. T., Perez, V. D. 2011; 54 (2): 154-167

    Abstract

    Left heart disease (LHD) represents the most common causes of pulmonary hypertension (PH). Whether caused by systolic or diastolic dysfunction or valvular heart disease, a hallmark of PH associated with LHD is elevated left atrial pressure. In all cases, the increase in left atrial pressure causes a passive increase in pulmonary pressure. In some patients, a superimposed active component caused by pulmonary arterial vasoconstriction and vascular remodeling may lead to a further increase in pulmonary arterial pressure. When present, PH is associated with a worse prognosis in patients with LHD. In addition to local abnormalities in nitric oxide and endothelin production, gene modifiers such as serotonin polymorphisms may be associated with the pathogenesis of PH in LHD. Optimizing heart failure regimens and corrective valve surgery represent the cornerstone of the treatment of PH in LHD. Recent studies suggest that sildenafil, a phosphodiesterase-5 inhibitor, is a promising agent in the treatment of PH in LHD. Unloading the left ventricle with circulatory support may also reverse severe PH in patients with end-stage heart failure allowing candidacy to heart transplantation.

    View details for DOI 10.1016/j.pcad.2011.06.003

    View details for Web of Science ID 000294880400009

    View details for PubMedID 21875514

  • Incidence, Correlates, and Consequences of Acute Kidney Injury in Patients With Pulmonary Arterial Hypertension Hospitalized With Acute Right-Side Heart Failure JOURNAL OF CARDIAC FAILURE Haddad, F., Fuh, E., Peterson, T., Skhiri, M., Kudelko, K. T., Perez, V. D., Winkelmayer, W. C., Doyle, R. L., Chertow, G. M., Zamanian, R. T. 2011; 17 (7): 533-539

    Abstract

    Though much is known about the prognostic influence of acute kidney injury (AKI) in left-side heart failure, much less is known about AKI in patients with pulmonary arterial hypertension (PAH).We identified consecutive patients with PAH who were hospitalized at Stanford Hospital for acute right-side heart failure. AKI was diagnosed according to the criteria of the Acute Kidney Injury Network. From June 1999 to June 2009, 105 patients with PAH were hospitalized for acute right-side heart failure (184 hospitalizations). AKI occurred in 43 hospitalizations (23%) in 34 patients (32%). The odds of developing AKI were higher among patients with chronic kidney disease (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.8-8.5), high central venous pressure (OR 1.8, 95% CI 1.1-2.4, per 5 mm Hg), and tachycardia on admission (OR 4.3, 95% CI 2.1-8.8). AKI was strongly associated with 30-day mortality after acute right-side heart failure hospitalization (OR 5.3, 95% CI 2.2-13.2).AKI is relatively common in patients with PAH and associated with a short-term risk of death.

    View details for DOI 10.1016/j.cardfail.2011.03.003

    View details for Web of Science ID 000292368500002

    View details for PubMedID 21703524

  • Drugs and toxins-associated pulmonary arterial hypertension: lessons learned and challenges ahead. International journal of clinical practice. Supplement de Jesus Perez, V., Kudelko, K., Snook, S., Zamanian, R. T. 2011: 8-10

    Abstract

    Since the identification of the link between pulmonary arterial hypertension (PAH) and exposure to certain drugs and toxins nearly fifty years ago, the expanding landscape of available pharmaceuticals and illicit drugs is further fueling this association. While some causative agents in drugs and toxins associated PAH (D&T-APAH) have been identified, little is known about the exact biology and clinical implications of the disease. In this review, we discuss the historical evidence that links PAH with exposure to anorexinogens, cocaine, and methamphetamines and concentrate on what is known about potential pathogenesis, clinical manifestations, and current management. We conclude that future research should focus on studies looking at clinical outcome and susceptibility factors.

    View details for DOI 10.1111/j.1742-1241.2010.02606.x

    View details for PubMedID 21176010

  • [ABSTRACT] Reassessing vasoreactivity in patients with pulmonary arterial hypertension (PAH) over time shows both loss as well as gain in vasoreactivity. Am. J. Respir. Crit. Care Med. Spiekerkoetter E, Hsi A, De Jesus Perez V, Liu J, Saito S, Kudelko K, Zamanian RT 2011; 183: A5747
  • [ABSTRACT] Product of heart rate recovery and six minute walk distance as a predictor of outcomes in pulmonary arterial hypertension Am. J. Respir. Crit. Care Med. Zamanian RT, Spiekerkoetter E, Hsi A, de Jesus Perez V, Saito S, Haddad F, Kudelko K 2011; 183: A5935
  • [ABSTRACT] Change in hemoglobin-adjusted diffusion capacity for carbon monoxide as a marker of mortality in pulmonary hypertension Am J Respir Crit Care Med Saito S, Kudelko K, Skhiri M, Hsi A, Deal J, De Jesus Perez V, Spiekerkoetter E, Haddad F, Zamanian RT. 2011; 183: A5948
  • Epoprostenol-associated pneumonitis: diagnostic use of a T-cell proliferation assay. journal of heart and lung transplantation Kudelko, K. T., Nadeau, K., Leung, A. N., Liu, J., Haddad, F., Zamanian, R. T., de Jesus Perez, V. 2010; 29 (9): 1071-1075

    Abstract

    We describe a case of severe drug-induced interstitial pneumonitis in a woman with idiopathic pulmonary arterial hypertension receiving epoprostenol confirmed by a drug T-cell proliferation assay. Proliferation assays were completed in our patient and in a healthy control. Isolated T cells were incubated with CD3-depleted peripheral blood mononuclear cells and then stimulated to proliferate with (3)H-thymidine in the presence of epoprostenol, other prostanoid analogs, and controls. A significant (p < 0.001) T-cell proliferation response occurred in our patient in the presence of epoprostenol alone. There was a trend towards an increased T-cell response to treprostinil but this was statistically insignificant. There was no significant T-cell response to the diluent alone, normal saline, iloprost, or alprostadil. There was no significant proliferation to any drug in the healthy control. Hence, a drug T-cell proliferation assay confirmed that epoprostenol can rarely incite a profound inflammatory response in the pulmonary interstitium.

    View details for DOI 10.1016/j.healun.2010.04.023

    View details for PubMedID 20627625

  • [ABSTRACT] Characteristics of patients with drugs and toxins-associated pulmonary arterial hypertension: a clinical and outcomes perspective Am. J. Respir. Crit. Care Med. Snook S, Kudelko K, Spiekerkoetter E, De Jesus Perez V, Haddad F, Doyle R, Zamanian RT 2009; 179: A4923
  • The Finland-United States Investigation of Non-Insulin-Dependent Diabetes Mellitus Genetics (FUSION) study. I. An autosomal genome scan for genes that predispose to type 2 diabetes AMERICAN JOURNAL OF HUMAN GENETICS Ghosh, S., Watanabe, R. M., Valle, T. T., Hauser, E. R., Magnuson, V. L., Langefeld, C. D., Ally, D. S., Mohlke, K. L., Silander, K., Kohtamaki, K., Chines, P., Balow, J., Birznieks, G., Chang, J., Eldridge, W., Erdos, M. R., Karanjawala, Z. E., Knapp, J. I., Kudelko, K., Martin, C., Morales-Mena, A., Musick, A., Musick, T., Pfahl, C., Porter, R., Rayman, J. B., Rha, D., Segal, L., Shapiro, S., Sharaf, R., Shurtleff, B., So, A., Tannenbaum, J., Te, C., Tovar, J., Unni, A., Welch, C., Whiten, R., Witt, A., Blaschak-Harvan, J., Douglas, J. A., Duren, W. L., Epstein, M. P., Fingerlin, T. E., Kaleta, H. S., Lange, E. M., Li, C., McEachin, R. C., Stringham, H. M., Trager, E., White, P. P., Eriksson, J., Toivanen, L., Vidgren, G., NYLUND, S. J., Tuomilehto-Wolf, E., Ross, E. H., Demirchyan, E., Hagopian, W. A., Buchanan, T. A., Tuomilehto, J., Bergman, R. N., Collins, F. S., Boehnke, M. 2000; 67 (5): 1174-1185

    Abstract

    We performed a genome scan at an average resolution of 8 cM in 719 Finnish sib pairs with type 2 diabetes. Our strongest results are for chromosome 20, where we observe a weighted maximum LOD score (MLS) of 2.15 at map position 69.5 cM from pter and secondary weighted LOD-score peaks of 2.04 at 56.5 cM and 1.99 at 17.5 cM. Our next largest MLS is for chromosome 11 (MLS = 1.75 at 84.0 cM), followed by chromosomes 2 (MLS = 0.87 at 5.5 cM), 10 (MLS = 0.77 at 75.0 cM), and 6 (MLS = 0.61 at 112.5 cM), all under an additive model. When we condition on chromosome 2 at 8.5 cM, the MLS for chromosome 20 increases to 5.50 at 69.0 cM (P=.0014). An ordered-subsets analysis based on families with high or low diabetes-related quantitative traits yielded results that support the possible existence of disease-predisposing genes on chromosomes 6 and 10. Genomewide linkage-disequilibrium analysis using microsatellite marker data revealed strong evidence of association for D22S423 (P=.00007). Further analyses are being carried out to confirm and to refine the location of these putative diabetes-predisposing genes.

    View details for Web of Science ID 000165091600015

    View details for PubMedID 11032783

  • The Finland-United States Investigation of Non-Insulin-Dependent Diabetes Mellitus Genetics (FUSION) study. II. An autosomal genome scan for diabetes-related quantitative-trait loci AMERICAN JOURNAL OF HUMAN GENETICS Watanabe, R. M., Ghosh, S., Langefeld, C. D., Valle, T. T., Hauser, E. R., Magnuson, V. L., Mohlke, K. L., Silander, K., Ally, D. S., Chines, P., Blaschak-Harvan, J., Douglas, J. A., Duren, W. L., Epstein, M. P., Fingerlin, T. E., Kaleta, H. S., Lange, E. M., Li, C., McEachin, R. C., Stringham, H. M., Trager, E., White, P. P., Balow, J., Birznieks, G., Chang, J., Eldridge, W., Erdos, M. R., Karanjawala, Z. E., Knapp, J. I., Kudelko, K., Martin, C., Morales-Mena, A., Musick, A., Musick, T., Pfahl, C., Porter, R., Rayman, J. B., Rha, D., Segal, L., Shapiro, S., Sharaf, R., Shurtleff, B., So, A., Tannenbaum, J., Te, C., Tovar, J., Unni, A., Welch, C., Whiten, R., Witt, A., Kohtamaki, K., Ehnholm, C., Eriksson, J., Toivanen, L., Vidgren, G., NYLUND, S. J., Tuomilehto-Wolf, E., Ross, E. H., Demirchyan, E., Hagopian, W. A., Buchanan, T. A., Tuomilehto, J., Bergman, R. N., Collins, F. S., Boehnke, M. 2000; 67 (5): 1186-1200

    Abstract

    Type 2 diabetes mellitus is a complex disorder encompassing multiple metabolic defects. We report results from an autosomal genome scan for type 2 diabetes-related quantitative traits in 580 Finnish families ascertained for an affected sibling pair and analyzed by the variance components-based quantitative-trait locus (QTL) linkage approach. We analyzed diabetic and nondiabetic subjects separately, because of the possible impact of disease on the traits of interest. In diabetic individuals, our strongest results were observed on chromosomes 3 (fasting C-peptide/glucose: maximum LOD score [MLS] = 3.13 at 53.0 cM) and 13 (body-mass index: MLS = 3.28 at 5.0 cM). In nondiabetic individuals, the strongest results were observed on chromosomes 10 (acute insulin response: MLS = 3.11 at 21.0 cM), 13 (2-h insulin: MLS = 2.86 at 65.5 cM), and 17 (fasting insulin/glucose ratio: MLS = 3.20 at 9.0 cM). In several cases, there was evidence for overlapping signals between diabetic and nondiabetic individuals; therefore we performed joint analyses. In these joint analyses, we observed strong signals for chromosomes 3 (body-mass index: MLS = 3.43 at 59.5 cM), 17 (empirical insulin-resistance index: MLS = 3.61 at 0.0 cM), and 19 (empirical insulin-resistance index: MLS = 2.80 at 74.5 cM). Integrating genome-scan results from the companion article by Ghosh et al., we identify several regions that may harbor susceptibility genes for type 2 diabetes in the Finnish population.

    View details for Web of Science ID 000165091600016

    View details for PubMedID 11032784

  • Type 2 diabetes: Evidence for linkage on chromosome 20 in 716 Finnish affected sib pairs PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Ghosh, S., Watanabe, R. M., Hauser, E. R., Valle, T., Magnuson, V. L., Erdos, M. R., Langefeld, C. D., Balow, J., Ally, D. S., Kohtamaki, K., Chines, P., Birznieks, G., Kaleta, H. S., Musick, A., Te, C., Tannenbaum, J., Eldridge, W., Shapiro, S., Martin, C., Witt, A., So, A., Chang, J., Shurtleff, B., Porter, R., Kudelko, K., Unni, A., Segal, L., Sharaf, R., Blaschak-Harvan, J., Eriksson, J., Tenkula, T., Vidgren, G., Ehnholm, C., Tuomilehto-Wolf, E., Hagopian, W., Buchanan, T. A., Tuomilehto, J., Bergman, R. N., Collins, F. S., Boehnke, M. 1999; 96 (5): 2198-2203

    Abstract

    We are conducting a genome scan at an average resolution of 10 centimorgans (cM) for type 2 diabetes susceptibility genes in 716 affected sib pairs from 477 Finnish families. To date, our best evidence for linkage is on chromosome 20 with potentially separable peaks located on both the long and short arms. The unweighted multipoint maximum logarithm of odds score (MLS) was 3.08 on 20p (location, chi = 19.5 cM) under an additive model, whereas the weighted MLS was 2.06 on 20q (chi = 57 cM, recurrence risk,lambda(s) = 1. 25, P = 0.009). Weighted logarithm of odds scores of 2.00 (chi = 69.5 cM, P = 0.010) and 1.92 (chi = 18.5 cM, P = 0.013) were also observed. Ordered subset analyses based on sibships with extreme mean values of diabetes-related quantitative traits yielded sets of families who contributed disproportionately to the peaks. Two-hour glucose levels in offspring of diabetic individuals gave a MLS of 2. 12 (P = 0.0018) at 9.5 cM. Evidence from this and other studies suggests at least two diabetes-susceptibility genes on chromosome 20. We have also screened the gene for maturity-onset diabetes of the young 1, hepatic nuclear factor 4-a (HNF-4alpha) in 64 affected sibships with evidence for high chromosomal sharing at its location on chromosome 20q. We found no evidence that sequence changes in this gene accounted for the linkage results we observed.

    View details for Web of Science ID 000078956600071

    View details for PubMedID 10051618

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