Bio

Clinical Focus


  • Heart Transplantation
  • RIght Heart Failure
  • Cardiology

Academic Appointments


Administrative Appointments


  • Director Biomarker and Phenotypic Core Laboratory, Cardiovascular Institute (2013 - Present)
  • Task Force member, WHO Pulmonary Hypertension Committee (2013 - Present)

Honors & Awards


  • Faculty Teacher Award, Montreal University (2004)
  • Governor's General Medal of Excellence, Goverment of Canada (1992)
  • Dean's Honours List, University of Montreal (2000-2004)

Professional Education


  • Board Certification: Cardiology, Royal College of Physicians and Surgeons (2004)
  • Fellowship:Stanford University School of Medicine (2007) CA
  • Fellowship:Montreal Heart Institute (2004) Canada
  • Residency:Montreal University Medical Center (2001) Canada
  • Internship:University of Montreal/Sacre-Coeur Hospital (1999) Canada
  • Board Certification: Internal Medicine, Royal College of Physicians and Surgeons (2003)
  • Medical Education:University of Montreal (1998) Canada

Teaching

Graduate and Fellowship Programs


Publications

Journal Articles


  • Experimental Models of Right Heart Failure: A Window for Translational Research in Pulmonary Hypertension SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE Guihaire, J., Bogaard, H. J., Flecher, E., Noly, P., Mercier, O., Haddad, F., Fadel, E. 2013; 34 (5): 689-699

    Abstract

    The right ventricle (RV) faces major changes in loading conditions associated with cardiovascular and pulmonary vascular disorders. Despite major pharmacological advances since the last decade, pulmonary arterial hypertension remains a deadly disease mainly secondary to the development of right ventricular failure (RVF). Several experimental models of RVF have been developed over the past three decades providing a particular insight in RV pathophysiology. Mechanisms involved in the transition from RV adaptive hypertrophy to maladaptive remodeling and failure in conditions of chronic RV pressure or volume overload are of a great interest but not yet completely understood. Further investigations are needed to find new therapeutic approaches for RVF. Current animal models and emerging concepts of translational RV research will be detailed in this review.

    View details for DOI 10.1055/s-0033-1355444

    View details for Web of Science ID 000324401900013

    View details for PubMedID 24037635

  • Effects of Intracoronary CD34(+) Stem Cell Transplantation in Nonischemic Dilated Cardiomyopathy Patients 5-Year Follow-Up CIRCULATION RESEARCH Vrtovec, B., Poglajen, G., Lezaic, L., Sever, M., Domanovic, D., Cernelc, P., Socan, A., Schrepfer, S., Torre-Amione, G., Haddad, F., Wu, J. C. 2013; 112 (1): 165-173

    Abstract

    CD34+ transplantation in dilated cardiomyopathy was associated with short-term improvement in left ventricular ejection fraction and exercise tolerance.We investigated long-term effects of intracoronary CD34+ cell transplantation in dilated cardiomyopathy and the relationship between intramyocardial cell homing and clinical response.Of 110 dilated cardiomyopathy patients, 55 were randomized to receive CD34+ stem cell transplantation (SC group) and 55 received no cell therapy (controls). In the SC group, CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and cells were injected in the artery supplying segments with the greatest perfusion defect. At baseline, 2 groups did not differ in age, sex, left ventricular ejection fraction, or N-terminal B-type natriuretic peptide levels. At 5 years, stem cell therapy was associated with increased left ventricular ejection fraction (from 24.3 ± 6.5% to 30.0 ± 5.1%; P=0.02), increased 6-minute walk distance (from 344 ± 90 m to 477 ± 130 m; P<0.001), and decreased N-terminal B-type natriuretic peptide (from 2322 ± 1234 pg/mL to 1011 ± 893 pg/mL; P<0.01). Left ventricular ejection fraction improvement was more significant in patients with higher myocardial homing of injected cells. During follow-up, 27 (25%) patients died and 9 (8%) underwent heart transplantation. Of the 27 deaths, 13 were attributed to pump failure and 14 were attributed to sudden cardiac death. Total mortality was lower in the SC group (14%) than in controls (35%; P=0.01). The same was true of pump failure (5% vs. 18%; P=0.03), but not of sudden cardiac death (9% vs. 16%; P=0.39).Intracoronary stem cell transplantation may be associated with improved ventricular function, exercise tolerance, and long-term survival in patients with dilated cardiomyopathy. Higher intramyocardial homing is associated with better stem cell therapy response.

    View details for DOI 10.1161/CIRCRESAHA.112.276519

    View details for Web of Science ID 000313053000021

    View details for PubMedID 23065358

  • Sudden death in myotonic dystrophy NEW ENGLAND JOURNAL OF MEDICINE Vrtovec, B., Haddad, F. 2008; 359 (15): 1628-1628

    View details for Web of Science ID 000259903100022

    View details for PubMedID 18846683

  • Twenty-year survivors of heart transplantation at Stanford University AMERICAN JOURNAL OF TRANSPLANTATION Deuse, T., Haddad, F., Pham, M., Hunt, S., Valantine, H., BATES, M. J., Mallidi, H. R., Oyer, P. E., Robbins, R. C., Reitz, B. A. 2008; 8 (9): 1769-1774

    Abstract

    Human heart transplantation started 40 years ago. Medical records of all cardiac transplants performed at Stanford were reviewed. A total of 1446 heart transplantations have been performed between January 1968 and December 2007 with an increase of 1-year survival from 43.1% to 90.2%. Sixty patients who were transplanted between 1968 and 1987 were identified who survived at least 20 years. Twenty-year survivors had a mean age at transplant of 29.4 +/- 13.6 years. Rejection-free and infection-free 1-year survivals were 14.3% and 18.8%, respectively. At their last follow-up, 86.7% of long-term survivors were treated for hypertension, 28.3% showed chronic renal dysfunction, 6.7% required hemodialysis, 10% were status postkidney transplantation, 13.3% were treated for diabetes mellitus, 36.7% had a history of malignancy and 43.3% had evidence of allograft vasculopathy. The half-life conditional on survival to 20 years was 28.1 years. Eleven patients received a second heart transplant after 11.9 +/- 8.0 years. The most common causes of death were allograft vasculopathy (56.3%) and nonlymphoid malignancy (25.0%). Twenty-year survival was achieved in 12.5% of patients transplanted before 1988. Although still associated with considerable morbidity, long-term survival is expected to occur at much higher rates in the future due to major advances in the field over the past decade.

    View details for DOI 10.1111/j.1600-6143.2008.02310.x

    View details for Web of Science ID 000258401700004

    View details for PubMedID 18557718

  • The changing face of heart transplantation JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Hunt, S. A., Haddad, F. 2008; 52 (8): 587-598

    Abstract

    It has been 40 years since the first human-to-human heart transplant performed in South Africa by Christiaan Barnard in December 1967. This achievement did not come as a surprise to the medical community but was the result of many years of early pioneering experimental work by Alexis Carrel, Frank Mann, Norman Shumway, and Richard Lower. Since then, refinement of donor and recipient selection methods, better donor heart management, and advances in immunosuppression have significantly improved survival. In this article, we hope to give a perspective on the changing face of heart transplantation. Topics that will be covered in this review include the changing patient population as well as recent advances in transplantation immunology, organ preservation, allograft vasculopathy, and immune tolerance.

    View details for DOI 10.1016/j.jacc.2008.05.020

    View details for Web of Science ID 000258394000001

    View details for PubMedID 18702960

  • Right ventricular function in cardiovascular disease, Part II - Pathophysiology, clinical importance, and management of right ventricular failure CIRCULATION Haddad, F., Doyle, R., Murphy, D. J., Hunt, S. A. 2008; 117 (13): 1717-1731
  • Right ventricular function in cardiovascular disease, part I - Anatomy, physiology, aging, and functional assessment of the right ventricle CIRCULATION Haddad, F., Hunt, S. A., Rosenthal, D. N., Murphy, D. J. 2008; 117 (11): 1436-1448
  • Right ventricular myocardial performance index predicts perioperative mortality or circulatory failure in high-risk valvular surgery JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Haddad, F., Denault, A. Y., Couture, P., Cartier, R., Pellerin, M., Levesque, S., Lambert, J., Tardif, J. 2007; 20 (9): 1065-1072

    Abstract

    The prognostic value of right ventricular myocardial performance index (RVMPI) and right ventricular fractional area change (RVFAC) in mitral or aortic valve surgery has not been well described. The main objective of this study is to assess the prognostic value of RVMPI and RVFAC in predicting postoperative mortality or circulatory failure.RVMPI and RVFAC were prospectively measured after induction of anesthesia using transesophageal echocardiography in 50 consecutive patients undergoing corrective mitral or aortic valve surgery. Univariate and multivariate analyses were performed for the primary clinical end point of in-hospital mortality or circulatory failure.In the study population, the mean age was 67 +/- 9 years. The primary end point occurred in 17 patients (34%); three patients died, and 14 patients presented signs of circulatory failure. Multivariate regression analysis identified RVMPI and RVFAC as variables of prognostic significance.Preoperative RVMPI and RVFAC could have an incremental value in predicting postoperative mortality and morbidity in valvular heart surgery. Future studies are needed to validate these results in a larger population.

    View details for DOI 10.1016/j.echo.2007.02.017

    View details for Web of Science ID 000249454900006

    View details for PubMedID 17566702

  • CD34(+) Stem Cell Therapy in Nonischemic Dilated Cardiomyopathy Patients. Clinical pharmacology & therapeutics Vrtovec, B., Poglajen, G., Sever, M., Lezaic, L., Socan, A., Haddad, F., Wu, J. C. 2013; 94 (4): 452-458

    Abstract

    Recent trends indicate that patients with nonischemic dilated cardiomyopathy represent the largest subpopulation of heart failure patients with a significant need for alternative treatment modalities. Similar to patients with ischemic cardiomyopathy, patients with nonischemic dilated cardiomyopathy have been found to have myocardial regions with flow abnormalities, which may represent targets for neoangiogenic therapies. CD34(+) stem cells might contribute to the formation of new blood vessels from existing vascular structures in ischemic tissues by the direct incorporation of injected cells into the newly developing vasculature or by the production and secretion of angiogenic cytokines. This review summarizes the long-term clinical effects and potential underlying mechanisms of CD34(+) cell therapy in patients with nonischemic dilated cardiomyopathy.Clinical Pharmacology & Therapeutics (2013); 94 4, 452-458. doi:10.1038/clpt.2013.134.

    View details for DOI 10.1038/clpt.2013.134

    View details for PubMedID 23903668

  • Granulocyte colony-stimulating factor therapy is associated with a reduced incidence of acute rejection episodes or allograft vasculopathy in heart transplant recipients. Transplantation proceedings Vrtovec, B., Haddad, F., Pham, M., Deuse, T., Fearon, W. F., Schrepfer, S., Leon, S., Vu, T., Valantine, H., Hunt, S. A. 2013; 45 (6): 2406-2409

    Abstract

    We evaluated the potential effects of granulocyte colony-simulating factor (G- CSF) on the incidence of rejection and allograft vasculopathy in heart transplant recipients.Of 247 patients undergoing heart transplantation from 2000 to 2007, 52 (21%) developed leukopenia (white blood cell [WBC] <2.5 × 10(9)cells/L) in the absence of active infection, rejection, or malignancy. In 24 (46%) patients a clinical decision was made to treat the leukopenia with G-CSF (G-CSF group), and 28 (54%) Patients received no G-CSF (non-GCSF group). Patients followed up for 1 year after the period of leukopenia were assessed for allograft vasculopathy and acute rejection incidence.At baseline, the G-CSF group and the non-GCSF group did not differ in age, gender, race, heart failure etiology, creatinine, left ventricular ejection fraction (LVEF) or immunosupressive regimen. During 1-year follow-up there were no deaths in the G-CSF group, and 1 death in the non-GCSF group (P = .34). The incidence of rejection or progressive allograft vasculopathy was lower in the G-CSF group when compared with the non-GCSF group (2 [8%] vs 15 [53%]; P < .01). Multivariate analysis identified both prior rejection episodes and G-CSF therapy as factors associated with the combined end-point of rejection or progressive allograft vasculopathy (odds ratio [OR] = 7.89 [1.67-37.2] and OR = 0.09 [0.02-0.52], respectively).G-CSF therapy appears to be associated with a decreased incidence of acute rejection episodes or allograft vasculopathy in heart transplant recipients, suggesting a potential immunomodulatory effect of G-CSF.

    View details for DOI 10.1016/j.transproceed.2013.01.106

    View details for PubMedID 23953556

  • Race differences in ventricular remodeling and function among college football players. American journal of cardiology Haddad, F., Peter, S., Hulme, O., Liang, D., Schnittger, I., Puryear, J., Gomari, F. A., Finocchiaro, G., Myers, J., Froelicher, V., Garza, D., Ashley, E. A. 2013; 112 (1): 128-134

    Abstract

    Athletic training is associated with increases in ventricular mass and volume. Recent studies have shown that left ventricular mass increases proportionally in white athletes with a mass/volume ratio approaching unity. The objective of this study was to compare the proportionality in ventricular remodeling and ventricular function in black versus white National Collegiate Athletic Association Division I football players. From 2008 to 2011, football players at Stanford University underwent cardiovascular screening with a 12-point history and physical examination, electrocardiography, and focused echocardiography. Compared with white players, black players had on average higher left ventricular mass indexes (77 ± 11 vs 71 ± 11 g/m(2), p = 0.009), higher mass/volume ratios (1.18 ± 0.16 vs 1.06 ± 0.09 g/ml, p <0.001), and higher QRS vector magnitudes (3.2 ± 0.7 vs 2.7 ± 0.8, p = 0.002). Black race had an odds ratio of 14 (95% confidence interval 5 to 42, p <0.001) for a mass/volume ratio >1.2. Mass/volume ratio was inversely related to early diastolic tissue Doppler velocity e' (r = -0.50, p <0.001) but not to QRS vector magnitude (r = 0.065, p = 0.034). With regard to systolic indexes, there was no significant difference in the left ventricular ejection fraction, velocity of circumferential shortening, and isovolumic acceleration. In conclusion, black college football players exhibit more concentric ventricular remodeling, lower early diastolic annular velocities, and increased ventricular voltage compared with white players. Ventricular mass increases proportionally to volume in white players but not in black players.

    View details for DOI 10.1016/j.amjcard.2013.02.065

    View details for PubMedID 23602691

  • Relation of B-Type Natriuretic Peptide Level in Heart Failure to Sudden Cardiac Death in Patients With and Without QT Interval Prolongation AMERICAN JOURNAL OF CARDIOLOGY Vrtovec, B., Knezevic, I., Poglajen, G., Sebestjen, M., Olcrajsek, R., Haddad, F. 2013; 111 (6): 886-890

    Abstract

    Increased levels of B-type natriuretic peptide (BNP) are associated with prolongation of the action potential in ventricular myocardium. We investigated the relation of a BNP increase, QT interval, and sudden cardiac death (SCD) in the presence of heart failure (HF). We enrolled 398 patients with HF, New York Heart Association class III or IV, and left ventricular ejection fraction <40%. At baseline and after 3 months, we measured BNP and the QT interval. A BNP increase was defined as a change in BNP of ≥+10%. The QTc interval was calculated using the Bazett formula. QTc interval prolongation was defined as a change in QTc of ≥+10%. The patients were followed up for 1 year. During a 3-month period, BNP increased significantly in 53% of the patients (group 1) and did not in 47% (group 2). During the same period, the QTc interval was more prolonged in group 1 (+44 ± 12 ms) than in group 2 (+7 ± 6 ms; p = 0.01). During 1 year of follow-up, 20 patients died suddenly (SCD), 16 from pump failure. Although the SCD rates did not differ between the 2 groups (5.7% in group 1 vs 4.2% in group 2, p = 0.53), they were significantly greater in the patients in group 1 with QTc interval prolongation ≥+10% (13.8%, p <0.001). The Kaplan-Meier-derived SCD-free survival rates were 2.9 times greater in patients without QTc interval prolongation than in those with prolonged QTc (p <0.001). QTc interval prolongation was an independent correlate of SCD (p = 0.006), but BNP increase was not (p = 0.32). In conclusion, a BNP increase in patients with HF was associated with an increased risk of SCD only in patients with QTc interval prolongation.

    View details for DOI 10.1016/j.amjcard.2012.11.041

    View details for Web of Science ID 000316537700019

  • ST-Elevation Myocardial Infarction Following Heart Transplantation as an Unusual Presentation of Coronary Allograft Vasculopathy: A Case Report TRANSPLANTATION PROCEEDINGS Peter, S., HULME, O., Deuse, T., Vrtovec, B., Fearon, W. F., Hunt, S., Haddad, F. 2013; 45 (2): 787-791

    Abstract

    The presentation, mechanisms, and incidence of ST elevation myocardial infarction (STEMI) in heart transplant recipients have been characterized only to a limited degree in the current literature. Herein, we present a unique case of STEMI years after heart transplantation with a focus on the salient features of its diagnosis and interventions. We also provide a review of the epidemiology of this phenomenon.A 33-year-old woman who was status post cardiac transplantation for dilated cardiomyopathy presented to the clinic with mild nonspecific fatigue and concern after having noticed relative bradycardia compared with her posttransplantation baseline heart rate. Electrocardiogram (ECG) showed junctional rhythm and inferior ST elevations, likely reflecting nodal ischemia. Troponins were grossly positive and echocardiogram showed marked right ventricular dysfunction.Successful percutaneous coronary intervention (PCI) with aspiration thrombectomy and drug-eluting stent placement was emergently performed. The heart's rhythm soon returned to sinus tachycardia. Right ventricular wall-motion abnormalities resolved. The patient suffered no clinical sequelae of her STEMI.This case illustrated that "classic" symptoms of STEMI may not occur at all in the setting of heart transplantation. To our knowledge, this is the first case of posttransplantation STEMI presenting as asymptomatic bradycardia, and highlights the importance of maintaining high clinical suspicion for ischemia in transplant recipients with subtle changes. In reviewing the epidemiology of this case, we locate and bundle different types of studies that have directly or indirectly looked at STEMI in heart transplantation. For a variety of putative pathophysiological reasons, STEMI is indeed a rare manifestation of the common transplant phenomenon of coronary artery vasculopathy (CAV).

    View details for DOI 10.1016/j.transproceed.2012.08.021

    View details for Web of Science ID 000316772500055

    View details for PubMedID 23498821

  • Perioperative right ventricular dysfunction CURRENT OPINION IN ANESTHESIOLOGY Denault, A. Y., Haddad, F., Jacobsohn, E., Deschamps, A. 2013; 26 (1): 71-81

    Abstract

    To evaluate new information on the importance of right ventricular function, diagnosis and management in cardiac surgical patients.There is growing evidence that right ventricular function is a key determinant in survival in cardiac surgery, particularly in patients with pulmonary hypertension. The diagnosis of this condition is helped by the use of specific hemodynamic parameters and echocardiography. In that regard, international consensus guidelines on the echocardiographic assessment of right ventricular function have been recently published. New monitoring modalities in cardiac surgery such as regional near-infrared spectroscopy can also assist management. Management of right ventricular failure will be influenced by the presence or absence of myocardial ischemia and left ventricular dysfunction. The differential diagnosis and management will be facilitated using a systematic approach.The use of right ventricular pressure monitoring and the publications of guidelines for the echocardiographic assessment of right ventricular anatomy and function allow the early identification of right ventricular failure. The treatment success will be associated by optimization of the hemodynamic, echocardiographic and near-infrared spectroscopy parameters.

    View details for DOI 10.1097/ACO.0b013e32835b8be2

    View details for Web of Science ID 000312953900012

    View details for PubMedID 23235519

  • Stem cell therapy in patients with heart failure. Methodist DeBakey cardiovascular journal Vrtovec, B., Poglajen, G., Haddad, F. 2013; 9 (1): 6-10

    Abstract

    Heart failure results from injury to the myocardium from a variety of causes, including ischemic and nonischemic etiologies. Severe heart failure carries a 50% 5-year mortality rate and is responsible for more than one-third of cardiovascular deaths in the United States.1 Heart failure progression is accompanied by activation of neurohormonal and cytokine systems as well as a series of adaptive changes within the myocardium, collectively referred to as left ventricular remodelling. The unfavorable alterations may be categorized broadly into changes that occur in the cardiac myocytes and changes that occur in the volume and composition of the extracellular matrix.2 Since remodelling in heart failure is progressive and eventually becomes detrimental, the majority of treatment strategies are aimed at stopping or reversing this process. Although medical management, cardiac resychronization therapy, and long-term or destination mechanical circulatory support have been successful in this regard, a considerable number of patients still progress to end-stage heart failure with limited therapeutic options. For these patients, stem cell therapies are being investigated as a safe treatment strategy for decreasing cardiac remodelling on top of conventional medical and device treatment.

    View details for PubMedID 23518819

  • Right-ventricular failure following left ventricle assist device implantation CURRENT OPINION IN CARDIOLOGY Patlolla, B., Beygui, R., Haddad, F. 2013; 28 (2): 223-233

    Abstract

    To review recent insights on right-ventricular failure (RVF) following left-ventricular assist device (LVAD) implantation.Even with the availability of new generation continuous mechanical assist devices, RVF after implantation of LVAD is still associated with high morbidity and mortality. Recent studies have tried to better define the risk of RVF using combined clinical scores and measures of right-ventricular function or strain. Small exploratory studies have also investigated the role of pulmonary vasodilators and phosphodiesterase inhibitors in selected patients receiving LVAD implantation.Measure of right-ventricular function could improve the risk stratification of RVF following LVAD implantation. Future multicenter studies are needed to validate right-ventricular risk scores and to develop evidence-guided preventive and therapeutic strategies.

    View details for DOI 10.1097/HCO.0b013e32835dd12c

    View details for Web of Science ID 000314811800018

    View details for PubMedID 23337895

  • 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

    Abstract

    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

  • Clinical and Functional Correlates of Early Microvascular Dysfunction After Heart Transplantation CIRCULATION-HEART FAILURE Haddad, F., Khazanie, P., Deuse, T., Weisshaar, D., Zhou, J., Nam, C. W., Vu, T. A., Gomari, F. A., Skhiri, M., Simos, A., Schnittger, I., Vrotvec, B., Hunt, S. A., Fearon, W. F. 2012; 5 (6): 759-768

    Abstract

    Microvascular dysfunction is emerging as a strong predictor of outcome in heart transplant recipients. At this time, the determinants and consequences of early microvascular dysfunction are not well established. The objective of the study was to determine the risk factors and functional correlates associated with early microvascular dysfunction in heart transplant recipients.Sixty-three heart transplant recipients who had coronary physiology assessment, right heart catheterization, and echocardiography performed at the time of their first annual evaluation were included in the study. Microvascular dysfunction was assessed using the recently described index of microcirculatory resistance. The presence of microvascular dysfunction, predefined by an index of microcirculatory resistance >20, was observed in 46% of patients at 1 year. A history of acute rejection and undersized donor hearts were associated with microvascular dysfunction at 1 year, with odds ratio of 4.0 (1.3-12.8) and 3.6 (1.2-11.1), respectively. Patients with microvascular dysfunction had lower cardiac index (3.1±0.7 versus 3.5±0.7 L/min per m(2); P=0.02) and mild graft dysfunction measured by echocardiography-derived left and right myocardial performance indices ([0.54±0.09 versus 0.43±0.09; P<0.01] and [0.47±0.14 versus 0.32±0.05; P<0.01], respectively). Microvascular dysfunction was also associated with a higher likelihood of death, graft failure, or allograft vasculopathy at 5 years after transplant (hazard ratio, 2.52 [95% CI, 1.04-5.91]).A history of acute rejection during the first year and smaller donor hearts were identified as risk factors for early microvascular dysfunction. Microvascular dysfunction assessed using index of microcirculatory resistances at 1 year was also associated with worse graft function and possibly worse clinical outcomes.

    View details for DOI 10.1161/CIRCHEARTFAILURE.111.962787

    View details for Web of Science ID 000313580100023

    View details for PubMedID 22933526

  • Pulmonary Hypertension A Stage for Ventricular Interdependence? JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Hsia, H. H., Haddad, F. 2012; 59 (24): 2203-2205

    View details for DOI 10.1016/j.jacc.2011.12.049

    View details for Web of Science ID 000304932500011

    View details for PubMedID 22676941

  • 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

  • Diagnosis and management of pulmonary hypertension associated with left ventricular diastolic dysfunction. Pulmonary circulation Perez, V. A., Haddad, F., Zamanian, R. T. 2012; 2 (2): 163-169

    Abstract

    Pulmonary hypertension (PH) is commonly seen in patients who present with left ventricular diastolic dysfunction (LVDD) and is considered a marker of poor prognosis. While PH in this setting is thought to result from pulmonary venous congestion, there is a subset of patients in which pulmonary pressures fail to improve with appropriate management of diastolic heart failure and go on to develop a clinical picture similar to that of patients with pulmonary arterial hypertension (PAH). Despite the utility of Doppler echocardiography and exercise testing in the initial evaluation of patients with suspected PH-LVDD, the diagnosis can only be confirmed using right heart catheterization. Management of PH-LVDD centers on both optimizing fluid management and afterload reduction to reducing left ventricular diastolic pressures and also increase pulmonary venous return. To date, there is no clear evidence that addition of PH-specific drugs can improve clinical outcomes, and their use should only be considered in the setting of clinical trials. In conclusion, PH-LVDD remains a challenging clinical entity that complicates the management of left ventricular dysfunction and significantly contributes to its morbidity and mortality. Determination of the optimal diagnostic and treatment strategies for this form of PH should be the goal of future studies.

    View details for DOI 10.4103/2045-8932.97598

    View details for PubMedID 22837857

  • Cardiac Paraganglioma: Diagnostic and Surgical Challenges JOURNAL OF CARDIAC SURGERY Huo, J. L., Choi, J. C., DeLuna, A., Lee, D., Fleischmann, D., Berry, G. J., Deuse, T., Haddad, F. 2012; 27 (2): 178-182

    Abstract

    Primary cardiac paragangliomas are rare extra-adrenal tumors. Though they account for less than 1% of all primary cardiac tumors, they are considerable sources of morbidity and mortality. In this case review, we discuss the challenges associated with the diagnosis and management of cardiac paragangliomas.

    View details for DOI 10.1111/j.1540-8191.2011.01378.x

    View details for Web of Science ID 000302172800009

    View details for PubMedID 22273468

  • Endothelial progenitor cells in cardiovascular disease and chronic inflammation: from biomarker to therapeutic agent BIOMARKERS IN MEDICINE Grisar, J. C., Haddad, F., Gomari, F. A., Wu, J. C. 2011; 5 (6): 731-744

    Abstract

    The discovery of endothelial progenitor cells in the 1990s challenged the paradigm of angiogenesis by showing that cells derived from hematopoietic stem cells are capable of forming new blood vessels even in the absence of a pre-existing vessel network, a process termed vasculogenesis. Since then, the majority of studies in the field have found a strong association between circulating endothelial progenitor cells and cardiovascular risk. Several studies have also reported that inflammation influences the mobilization and differentiation of endothelial progenitor cells. In this review, we discuss the emerging role of endothelial progenitor cells as biomarkers of cardiovascular disease as well as the interplay between inflammation and endothelial progenitor cell biology. We will also review the challenges in the field of endothelial progenitor cell-based therapy.

    View details for DOI 10.2217/BMM.11.92

    View details for Web of Science ID 000298488200005

    View details for PubMedID 22103609

  • 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

  • Effects of Intracoronary Stem Cell Transplantation in Patients With Dilated Cardiomyopathy JOURNAL OF CARDIAC FAILURE Vrtovec, B., Poglajen, G., Sever, M., Lezaic, L., Domanovic, D., Cernelc, P., Haddad, F., Torre-Amione, G. 2011; 17 (4): 272-281

    Abstract

    We investigated clinical effects of intracoronary transplantation of CD34+ cells in patients with dilated cardiomyopathy (DCM).Of 55 patients with DCM, 28 were randomized to CD34+ transplantation (SC group), and 27 patients did not receive stem cell therapy (controls). In the SC group, peripheral blood CD34+ cells were mobilized by granulocyte-colony stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and CD34+ cells were injected in the coronary artery supplying the segments with reduced viability.At baseline, the 2 groups did not differ in age, gender, left ventricular ejection fraction (LVEF), or NT-proBNP levels. At 1 year, stem cell therapy was associated with an increase in LVEF (from 25.5 ± 7.5% to 30.1 ± 6.7%; P = .03), an increase in 6-minute walk distance (from 359 ± 104 m to 485 ± 127 m; P = .001), and a decrease in NT-proBNP (from 2069 ± 1996 pg/mL to 1037 ± 950 pg/mL; P = .01). The secondary endpoint of 1-year mortality or heart transplantation was lower in patients receiving SC therapy (2/28, 7%) than in controls (8/27, 30%) (P = .03), and SC therapy was the only independent predictor of outcome on multivariable analysis (P = .04).Intracoronary stem cell transplantation could lead to improved ventricular remodeling, better exercise tolerance and potentially improved survival in patients with DCM.

    View details for DOI 10.1016/j.cardfail.2010.11.007

    View details for Web of Science ID 000289318500002

    View details for PubMedID 21440864

  • Stress-induced cardiomyopathy associated with a transfusion reaction: A case of potential crosstalk between the histaminic and adrenergic systems EXPERIMENTAL & CLINICAL CARDIOLOGY Zhou, J. Q., Choe, E., Ang, L., Schnittger, I., Rockson, S. G., Tremmel, J. A., Haddad, F. 2011; 16 (1): 30-32

    Abstract

    The adrenergic and histaminergic systems have been reported to have analogous effects on the heart. A case of transient ventricular dysfunction with echocardiographic findings characteristic of stress-induced cardiomyopathy (also known as takotsubo cardiomyopathy) in a patient who had an urticarial transfusion reaction is described. The effect of histamine on ventricular function and its interaction with the adrenergic system are discussed.

    View details for Web of Science ID 000300518800008

    View details for PubMedID 21523205

  • The concept of ventricular reserve in heart failure and pulmonary hypertension: an old metric that brings us one step closer in our quest for prediction CURRENT OPINION IN CARDIOLOGY Haddad, F., Vrtovec, B., Ashley, E. A., Deschamps, A., Haddad, H., Denault, A. Y. 2011; 26 (2): 123-131

    Abstract

    Ventricular reserve is emerging a strong predictor of outcome in heart failure and cardiovascular disease. Ventricular reserve is the term used to describe the extent of increase or change in ventricular function that occurs during exercise or pharmacological stress (typically with dobutamine).The interest in ventricular reserve lies in its ability to assess viability in coronary artery disease, to predict clinical outcome and response to therapy in patients with heart failure and to screen patients for early cardiovascular disease.In this paper, we will review the emerging role of ventricular reserve in heart failure and pulmonary hypertension. We will also explore the mechanisms involved in the pathophysiology of impaired ventricular reserve and discuss future directions of research in the field.

    View details for DOI 10.1097/HCO.0b013e3283437485

    View details for Web of Science ID 000287189400008

    View details for PubMedID 21297465

  • Right ventricular failure: a novel era of targeted therapy. Current heart failure reports Banerjee, D., Haddad, F., Zamanian, R. T., Nagendran, J. 2010; 7 (4): 202-211

    Abstract

    There now is strong evidence to recognize the pivotal role of the right ventricle (RV) in heart disease and to establish it as a unique and separate entity than the left ventricle (LV). Here, we summarize the differences between the two ventricles, the diagnosis of RV failure, and the management of acute and chronic RV failure. We review the indices derived by echocardiography used to measure RV function, and novel biomarkers that may play a role diagnosing and prognosticating in RV-specific disease. There are new novel therapies that specifically target the RV in disease. For example, phosphodiesterase type 5 inhibitors improve contractility of the hypertrophied RV while sparing the normal LV in pulmonary arterial hypertension. The metabolism of the hypertrophied RV is another area for therapeutic exploitation by metabolic modulation. We also suggest future potential molecular targets that may be unique to the RV because they are upregulated in RV hypertrophy greater than in LV hypertrophy.

    View details for DOI 10.1007/s11897-010-0031-7

    View details for PubMedID 20890792

  • 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., Perez, V. D. 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 Web of Science ID 000281494800016

  • Review of Heart-Lung Transplantation at Stanford ANNALS OF THORACIC SURGERY Deuse, T., Sista, R., Weill, D., Tyan, D., Haddad, F., Dhillon, G., Robbins, R. C., Reitz, B. A. 2010; 90 (1): 329-337

    Abstract

    Long-term survival after heart-lung transplantation was first achieved in 1981 at Stanford and a total of 217 heart-lung transplantations had been performed by June 2008. This review summarizes Stanford's cumulative experience with heart-lung transplantation, demonstrates the progress that has been made, and discusses past and persistent problems. Diagnostic tools and treatment options for infectious diseases and rejection have changed and patient survival markedly improved over the almost three decades. Eight patients lived longer than 20 years. Further options to treat infections and strategies to control bronchiolitis obliterans syndrome, the main causes of early and long-term mortality, respectively, are required to achieve routine long-term survival.

    View details for DOI 10.1016/j.athoracsur.2010.01.023

    View details for Web of Science ID 000278998400070

    View details for PubMedID 20609821

  • Risk Factors Predictive of Right Ventricular Failure After Left Ventricular Assist Device Implantation AMERICAN JOURNAL OF CARDIOLOGY Drakos, S. G., Janicki, L., Horne, B. D., Kfoury, A. G., Reid, B. B., Clayson, S., Horton, K., Haddad, F., Li, D. Y., Renlund, D. G., Fisher, P. W. 2010; 105 (7): 1030-1035

    Abstract

    Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation appears to be associated with increased mortality. However, the determination of which patients are at greater risk of developing postoperative RVF remains controversial and relatively unknown. We sought to determine the preoperative risk factors for the development of RVF after LVAD implantation. The data were obtained for 175 consecutive patients who had received an LVAD. RVF was defined by the need for inhaled nitric oxide for >/=48 hours or intravenous inotropes for >14 days and/or right ventricular assist device implantation. An RVF risk score was developed from the beta coefficients of the independent variables from a multivariate logistic regression model predicting RVF. Destination therapy (DT) was identified as the indication for LVAD implantation in 42% of our patients. RVF after LVAD occurred in 44% of patients (n = 77). The mortality rates for patients with RVF were significantly greater at 30, 180, and 365 days after implantation compared to patients with no RVF. By multivariate logistic regression analysis, 3 preoperative factors were significantly associated with RVF after LVAD implantation: (1) a preoperative need for intra-aortic balloon counterpulsation, (2) increased pulmonary vascular resistance, and (3) DT. The developed RVF risk score effectively stratified the risk of RV failure and death after LVAD implantation. In conclusion, given the progressively growing need for DT, the developed RVF risk score, derived from a population with a large percentage of DT patients, might lead to improved patient selection and help stratify patients who could potentially benefit from early right ventricular assist device implantation.

    View details for DOI 10.1016/j.amjcard.2009.11.026

    View details for Web of Science ID 000276576200023

    View details for PubMedID 20346326

  • Evidence-Based Management of Right Heart Failure: a Systematic Review of an Empiric Field REVISTA ESPANOLA DE CARDIOLOGIA Skhiri, M., Hunt, S. A., Denault, A. Y., Haddad, F. 2010; 63 (4): 451-471

    Abstract

    In recent years, several studies have shown that right ventricular function is an important predictor of survival in patients with congenital heart disease, pulmonary hypertension or left heart failure. Our understanding of right heart failure has improved considerably over the last two decades. In this review article, our objective was to provide a critical summary of the evidence underlying the management of right heart failure. A systematic review of the literature was performed using PubMed and the latest issue of the Cochrane Central Register of Controlled Trials to identify studies conducted between January 1975 and January 2010. The literature search encompassed observational studies, randomized controlled trials and meta-analyses. The evidence underlying the use of beta-blockade, angiotensin-converting enzyme inhibitors, inhaled nitric oxide, hydralazine, warfarin, and resynchronization therapy in right heart failure was systematically reviewed. Emerging new therapies, such as metabolic modulators, and the pearls and pitfalls of managing right heart failure are also discussed in the article.

    View details for Web of Science ID 000276217300011

    View details for PubMedID 20334811

  • Changing trends in infectious disease in heart transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Haddad, F., Deuse, T., Pham, M., Khazanie, P., Rosso, F., Luikart, H., Valantine, H., Leon, S., Vu, T. A., Hunt, S. A., Oyer, P., Montoya, J. G. 2010; 29 (3): 306-315

    Abstract

    During the past 25 years, advances in immunosuppression and the use of selective anti-microbial prophylaxis have progressively reduced the risk of infection after heart transplantation. This study presents a historical perspective of the changing trends of infectious disease after heart transplantation.Infectious complications in 4 representative eras of immunosuppression and anti-microbial prophylaxis were analyzed: (1) 38 in the pre-cyclosporine era (1978-1980), (2) 72 in the early cyclosporine era (1982-1984), where maintenance immunosuppression included high-dose cyclosporine and corticosteroid therapy; (3) 395 in the cyclosporine era (1988-1997), where maintenance immunosuppression included cyclosporine, azathioprine, and lower corticosteroid doses; and (4) 167 in the more recent era (2002-2005), where maintenance immunosuppression included cyclosporine and mycophenolate mofetil.The overall incidence of infections decreased in the 4 cohorts from 3.35 episodes/patient to 2.03, 1.35, and 0.60 in the more recent cohorts (p < 0.001). Gram-positive bacteria are emerging as the predominant cause of bacterial infections (28.6%, 31.4%, 51.0%, 67.6%, p = 0.001). Cytomegalovirus infections have significantly decreased in incidence and occur later after transplantation (88 +/- 77 days, pre-cyclosporine era; 304 +/- 238 days, recent cohort; p < 0.001). Fungal infections also decreased, from an incidence of 0.29/patient in the pre-cyclosporine era to 0.08 in the most recent era. A major decrease in Pneumocystis jiroveci and Nocardia infections has also occurred.The overall incidence and mortality associated with infections continues to decrease in heart transplantation and coincides with advances in immunosuppression, the use of selective anti-microbial prophylaxis, and more effective treatment regimens.

    View details for DOI 10.1016/j.healun.2009.08.018

    View details for Web of Science ID 000276005200013

    View details for PubMedID 19853478

  • New insights for the diagnosis and management of right ventricular failure, from molecular imaging to targeted right ventricular therapy CURRENT OPINION IN CARDIOLOGY Haddad, F., Ashley, E., Michelakis, E. D. 2010; 25 (2): 131-140

    Abstract

    Despite the recognition of a critical role of the right ventricle (RV) in many aspects of cardiovascular medicine, there has been surprisingly little interest in right ventricular-targeted imaging and therapeutic approaches. Compared with the left ventricle, the RV has a different embryologic origin, undergoes a dramatic change during the transition from the fetal to the adult circulation and normally operates in a low resistance or impedance arterial system. Here, we review new insights on the pathophysiology, assessment and management of right ventricular failure.Our understanding of the mechanisms underlying right ventricular failure has improved. As in the left ventricle, decrease in alpha-myosin heavy chain and a switch towards glycolysis from fatty acid oxidation is observed in the stressed RV, but the key question remains unanswered: why is the RV so much more vulnerable to failure upon afterload increase compared with the left ventricle? In assessing the RV, it is becoming increasingly important to consider the RV and pulmonary artery as a unit. New therapies that could specifically target the RV, such as metabolic modulators and phosphodiesterase type 5 inhibitors, are now being considered.A better understanding of the molecular mechanisms of right ventricular failure will lead to the development of new strategies for the diagnosis and management of right ventricular failure. Right ventricular-targeted therapies are needed in a number of diseases in which only the RV fails.

    View details for DOI 10.1097/HCO.0b013e328335febd

    View details for Web of Science ID 000274797100010

    View details for PubMedID 20130456

  • The Efficacy of Implantable Cardioverter-Defibrillators in Heart Transplant Recipients Results From a Multicenter Registry CIRCULATION-HEART FAILURE Tsai, V. W., Cooper, J., Garan, H., Natale, A., Ptaszek, L. M., Ellinor, P. T., Hickey, K., Downey, R., Zei, P., Hsia, H., Wang, P., Hunt, S., Haddad, F., Al-Ahmad, A. 2009; 2 (3): 197-201

    Abstract

    Sudden cardiac death among orthotopic heart transplant recipients is an important mechanism of death after cardiac transplantation. The role for implantable cardioverter-defibrillators (ICDs) in this population is not well established. This study sought to determine whether ICDs are effective in preventing sudden cardiac death in high-risk heart transplant recipients.We retrospectively analyzed the records of all orthotopic heart transplant patients who had ICD implantation between January 1995 and December 2005 at 5 heart transplant centers. Thirty-six patients were considered high risk for sudden cardiac death. The mean age at orthotopic heart transplant was 44+/-14 years, the majority being male (n=29). The mean age at ICD implantation was 52+/-14 years, whereas the average time from orthotopic heart transplant to ICD implant was 8 years +/-6 years. The main indications for ICD implantation were severe allograft vasculopathy (n=12), unexplained syncope (n=9), history of cardiac arrest (n=8), and severe left ventricular dysfunction (n=7). Twenty-two shocks were delivered to 10 patients (28%), of whom 8 (80%) received 12 appropriate shocks for either rapid ventricular tachycardia or ventricular fibrillation. The shocks were effective in terminating the ventricular arrhythmias in all cases. Three (8%) patients received 10 inappropriate shocks. Underlying allograft vasculopathy was present in 100% (8 of 8) of patients who received appropriate ICD therapy.Use of ICDs after heart transplantation may be appropriate in selected high-risk patients. Further studies are needed to establish an appropriate prevention strategy in this population.

    View details for DOI 10.1161/CIRCHEARTFAILURE.108.814525

    View details for Web of Science ID 000269161600007

    View details for PubMedID 19808340

  • Angina Associated With Left Main Coronary Artery Compression in Pulmonary Hypertension JOURNAL OF HEART AND LUNG TRANSPLANTATION Perez, V. A., Haddad, F., Vagelos, R. H., Fearon, W., Feinstein, J., Zamanian, R. T. 2009; 28 (5): 527-530

    Abstract

    Chest pain is a common complaint in patients with pulmonary arterial hypertension (PAH). Left main coronary artery (LMCA) compression by an enlarged pulmonary artery trunk (PAT) has been associated with angina, but appropriate diagnostic and treatment approaches remain poorly defined. We present two cases of angina caused by LMCA compression from an enlarged pulmonary artery, one of which also presented with new, severe left ventricular systolic dysfunction attributed to myocardial ischemia. Diagnosis of LMCA stenosis was made via coronary angiography followed by computed tomography-gated coronary angiography (CT-CA), which confirmed pulmonary artery enlargement as the source of extrinsic compression. Restoring LMCA patency with percutaneous intervention and/or aggressive treatment of pulmonary hypertension led to significant improvement in angina, cardiac function and quality of life. Given the negative impact on cardiac function, prompt diagnosis and treatment of extrinsic LMCA compression should be considered a priority.

    View details for DOI 10.1016/j.healun.2008.12.008

    View details for Web of Science ID 000266171400021

    View details for PubMedID 19416787

  • A Novel Non-Invasive Method of Estimating Pulmonary Vascular Resistance in Patients With Pulmonary Arterial Hypertension JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Haddad, F., Zamanian, R., Beraud, A., Schnittger, I., Feinstein, J., Peterson, T., Yang, P., Doyle, R., Rosenthal, D. 2009; 22 (5): 523-529

    Abstract

    The assessment of pulmonary vascular resistance (PVR) plays an important role in the diagnosis and management of pulmonary arterial hypertension (PAH). The main objective of this study was to determine whether the noninvasive index of systolic pulmonary arterial pressure (SPAP) to heart rate (HR) times the right ventricular outflow tract time-velocity integral (TVI(RVOT)) (SPAP/[HR x TVI(RVOT)]) provides clinically useful estimations of PVR in PAH.Doppler echocardiography and right-heart catheterization were performed in 51 consecutive patients with established PAH. The ratio of SPAP/(HR x TVI(RVOT)) was then correlated with invasive indexed PVR (PVRI) using regression and Bland-Altman analysis. Using receiver operating characteristic curve analysis, a cutoff value for the Doppler equation was generated to identify patients with PVRI > or = 15 Wood units (WU)/m2.The mean pulmonary arterial pressure was 52 +/- 15 mm Hg, the mean cardiac index was 2.2 +/- 0.6 L/min/m2, and the mean PVRI was 20.5 +/- 9.6 WU/m2. The ratio of SPAP/(HR x TVI(RVOT)) correlated very well with invasive PVRI measurements (r = 0.860; 95% confidence interval, 0.759-0.920). A cutoff value of 0.076 provided well-balanced sensitivity (86%) and specificity (82%) to determine PVRI > 15 WU/m2. A cutoff value of 0.057 increased sensitivity to 97% and decreased specificity to 65%.The novel index of SPAP/(HR x TVI(RVOT)) provides useful estimations of PVRI in patients with PAH.

    View details for DOI 10.1016/j.echo.2009.01.021

    View details for Web of Science ID 000266091400017

    View details for PubMedID 19307098

  • Right Ventricular Dysfunction Predicts Poor Outcome Following Hemodynamically Compromising Rejection JOURNAL OF HEART AND LUNG TRANSPLANTATION Haddad, F., Fisher, P., Pham, M., Berry, G., Weisshaar, D., Kuppahally, S., Vrtovec, B., Deuse, T., Virani, S., Fearon, W., Valantine, H., Hunt, S. 2009; 28 (4): 312-319

    Abstract

    Hemodynamically compromising rejection (HCR) is a major cause of mortality and morbidity after heart transplantation. Right ventricular (RV) function is a strong predictor of outcome in patients with heart failure and myocarditis. The objective of the current study is to determine whether RV dysfunction predicts event-free survival in patients with HCR.Medical records of 548 heart transplant patients followed at Stanford University between January 1998 and January 2007 were reviewed. HCR was defined as a rejection episode requiring hospitalization for heart failure. Univariate and multivariate analyses were performed to identify risk factors for death or retransplantation at 1 year.HCR occurred in 71 patients (12.9%). Death or retransplantation at 1 year occurred in 28 patients (39%). Univariate analysis identified non-cellular rejection (odds ratio [OR] = 3.20, p = 0.021), the need for inotropic support (OR = 4.80, p = 0.007), RV dysfunction (OR = 4.63, p = 0.006), left ventricular ejection fraction (OR = 0.941, p = 0.031) and acute renal failure (OR = 3.82, p = 0.010) as predictors of death or retransplantation at 1 year. Multivariate analysis identified RV dysfunction (OR = 4.80, p = 0.007) and the need for inotropic support (OR = 5.00, p = 0.009) as predictors of death or retransplantation at 1 year.In the modern era of immunosuppression, HCR remains a major complication after heart transplantation. RV dysfunction was identified as a novel risk factor for death or retransplantation following HCR.

    View details for DOI 10.1016/j.healun.2008.12.023

    View details for Web of Science ID 000265042300003

    View details for PubMedID 19332256

  • Diabetes Does Not Affect Ventricular Repolarization and Sudden Cardiac Death Risk in Patients with Dilated Cardiomyopathy PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Vrtovec, B., Fister, M., Poglajen, G., Starc, V., Haddad, F. 2009; 32: S146-S150

    Abstract

    We studied the effects of diabetes on ventricular repolarization parameters and sudden cardiac death in patients with dilated cardiomyopathy (DCM).We enrolled 132 consecutive patients in New York Heart Association (NYHA) heart failure functional classes II or III and left ventricular ejection fraction <40% without evidence of coronary artery disease. In 45 patients (34%), diabetes was diagnosed according to standard criteria (study group), and the remaining 87 (66%) had no diabetes (controls). All patients underwent a 5-minute high-resolution electrocardiogram recording for determination of QT variability (QTV) index and were followed for 1 year thereafter.At baseline, the two groups did not differ in age, gender, left ventricular ejection fraction, NYHA functional class, or plasma brain natriuretic peptide levels. Similarly, QTV index did not differ between the study group (-0.51 +/- 0.55) and controls (-0.48 +/- 0.51; P = 0.48). During follow-up, 18 patients (14%) died of cardiac causes. Of the 18 deaths, eight were attributed to heart failure, and 10 to sudden cardiac death. Mortality was higher in the study group (10/45, 20%) than in controls (8/87, 10%) (P = 0.03). The same was true of the heart failure mortality (6/45 [13%] vs 2/87 [2%], P = 0.01), but not of the sudden cardiac death rate (3/45 [7%] vs 7/87 [8%], P = 0.78). By multiple variable analyses, diabetes predicted total and heart failure mortality, and a high QTV predicted sudden cardiac death.Diabetes appears to increase the risk of heart failure in patients with DCM without affecting ventricular repolarization parameters and sudden cardiac death risk.

    View details for Web of Science ID 000266562900034

    View details for PubMedID 19250080

  • The Right Ventricle in Cardiac Surgery, a Perioperative Perspective: II. Pathophysiology, Clinical Importance, and Management ANESTHESIA AND ANALGESIA Haddad, F., Couture, P., Tousignant, C., Denault, A. Y. 2009; 108 (2): 422-433

    Abstract

    The importance of right ventricular (RV) function in cardiovascular disease and cardiac surgery has been recognized for several years. RV dysfunction has been shown to be a significant prognostic factor in cardiac surgery and heart transplantation. In the first article of this review, key features of RV anatomy, physiology, and assessment were presented. In this second part, we review the pathophysiology, clinical importance, and management of RV failure in cardiac surgery.

    View details for DOI 10.1213/ane.0b013e31818d8b92

    View details for Web of Science ID 000262590000005

    View details for PubMedID 19151265

  • The Right Ventricle in Cardiac Surgery, a Perioperative Perspective: I. Anatomy, Physiology, and Assessment ANESTHESIA AND ANALGESIA Haddad, F., Couture, P., Tousignant, C., Denault, A. Y. 2009; 108 (2): 407-421

    Abstract

    The importance of right ventricular (RV) function in cardiovascular disease and cardiac surgery has been recognized for several years. RV dysfunction has been shown to be a significant prognostic factor in heart failure, congenital heart disease, valvular disease, and cardiac surgery. In the first of our two articles, we will review key features of RV anatomy, physiology, and assessment. In the first article, the main discussion will be centered on the echographic assessment of RV structure and function. In the second review article, pathophysiology, clinical importance, and management of RV failure in cardiac surgery will be discussed.

    View details for DOI 10.1213/ane.0b013e31818f8623

    View details for Web of Science ID 000262590000004

    View details for PubMedID 19151264

  • Outcome in cardiac recipients of donor hearts with increased left ventricular wall thickness AMERICAN JOURNAL OF TRANSPLANTATION Kuppahally, S. S., Valantine, H. A., Weisshaar, D., Parekh, H., Hung, Y. Y., Haddad, F., Fowler, M., Vagelos, R., Perlroth, M. G., Robbins, R. C., Hunt, S. A. 2007; 7 (10): 2388-2395

    Abstract

    The ongoing shortage of donors for cardiac transplantation has led to a trend toward acceptance of donor hearts with some structural abnormalities including left ventricular hypertrophy. To evaluate the outcome in recipients of donor hearts with increased left ventricular wall thickness (LVWT), we retrospectively analyzed data for 157 cardiac donors and respective recipients from January 2001 to December 2004. There were 47 recipients of donor heart with increased LVWT >or=1.2 cm, which constituted the study group and 110 recipients of a donor heart with normal LVWT < 1.2 cm that formed the control group. At 3 +/- 1.5 years, recipient survival was lower (50% vs. 82%, p = 0.0053) and incidence of allograft vasculopathy was higher (50% vs. 22%, p = 0.05) in recipients of donor heart with LVWT > 1.4 cm as compared to LVWT 1.4 cm (p = 0.003), recipient preoperative ventricular assist device (VAD) support (p = 0.04) and bypass time > 150 min (p = 0.05) were predictors of reduced survival. Our results suggest careful consideration of donor hearts with echocardiographic evidence of increased LVWT in the absence of hypovolemia, because they may be associated with poorer outcomes; such hearts should potentially be reserved only for the most desperately ill recipients.

    View details for DOI 10.1111/j.1600-6143.2007.01930.x

    View details for Web of Science ID 000249167000022

    View details for PubMedID 17845572

  • Management strategies for patients with pulmonary hypertension in the intensive care unit CRITICAL CARE MEDICINE Zamanian, R. T., Haddad, F., Doyle, R. L., Weinacker, A. B. 2007; 35 (9): 2037-2050

    Abstract

    Pulmonary hypertension may be encountered in the intensive care unit in patients with critical illnesses such as acute respiratory distress syndrome, left ventricular dysfunction, and pulmonary embolism, as well as after cardiothoracic surgery. Pulmonary hypertension also may be encountered in patients with preexisting pulmonary vascular, lung, liver, or cardiac diseases. The intensive care unit management of patients can prove extremely challenging, particularly when they become hemodynamically unstable. The objective of this review is to discuss the pathogenesis and physiology of pulmonary hypertension and the utility of various diagnostic tools, and to provide recommendations regarding the use of vasopressors and pulmonary vasodilators in intensive care.We undertook a comprehensive review of the literature regarding the management of pulmonary hypertension in the setting of critical illness. We performed a MEDLINE search of articles published from January 1970 to March 2007. Medical subject headings and keywords searched and cross-referenced with each other were: pulmonary hypertension, vasopressor agents, therapeutics, critical illness, intensive care, right ventricular failure, mitral stenosis, prostacyclin, nitric oxide, sildenafil, dopamine, dobutamine, phenylephrine, isoproterenol, and vasopressin. Both human and animal studies related to pulmonary hypertension were reviewed.Pulmonary hypertension presents a particular challenge in critically ill patients, because typical therapies such as volume resuscitation and mechanical ventilation may worsen hemodynamics in patients with pulmonary hypertension and right ventricular failure. Patients with decompensated pulmonary hypertension, including those with pulmonary hypertension associated with cardiothoracic surgery, require therapy for right ventricular failure. Very few human studies have addressed the use of vasopressors and pulmonary vasodilators in these patients, but the use of dobutamine, milrinone, inhaled nitric oxide, and intravenous prostacyclin have the greatest support in the literature. Treatment of pulmonary hypertension resulting from critical illness or chronic lung diseases should address the primary cause of hemodynamic deterioration, and pulmonary vasodilators usually are not necessary.

    View details for DOI 10.1097/01.CCM.0000280433.74246.9E

    View details for Web of Science ID 000249038700005

    View details for PubMedID 17855818

  • Active bacterial myocarditis: A case report and review of the literature JOURNAL OF HEART AND LUNG TRANSPLANTATION Haddad, F., Berry, G., Doyle, R. L., Martineau, P., Leung, T., Racine, N. 2007; 26 (7): 745-749

    Abstract

    Bacterial myocarditis (BM) is an uncommon cause of infectious myocarditis. BM is usually seen in the context of overwhelming sepsis or as part of a specific bacterial syndrome. The definitive diagnosis of bacterial myocarditis requires biopsy or morphologically proven active myocarditis with evidence of bacterial invasion or positive tissue cultures. The management of bacterial myocarditis consists of aggressive and early antibiotic or anti-toxin treatment, appropriate hemodynamic support, and treatment of arrhythmias or mechanical complications. We present a case of acute Listeria monocytogenes myocarditis in an immunocompetent patient and highlight the challenges in the diagnosis and treatment of bacterial myocarditis.

    View details for DOI 10.1016/j.healun.2007.04.010

    View details for Web of Science ID 000248195700014

    View details for PubMedID 17613408

  • Pulmonary nocardiosis in a heart transplant patient: Case report and review of the literature JOURNAL OF HEART AND LUNG TRANSPLANTATION Haddad, F., Hunt, S. A., Perlroth, M., Valantine, H., Doyle, R., Montoya, J. 2007; 26 (1): 93-97

    Abstract

    Pulmonary infection with Nocardia is an uncommon but serious infection found in immunocompromised patients. We describe a rapidly progressive pulmonary nocardiosis in a heart transplant patient. We then review the common clinical features of Nocardia infection in transplant recipients, outlining the challenges in its diagnosis and management. We also review the differences between Pneumocystis jiroveci prophylaxis regimens with respect to concomitant prophylaxis of Nocardia and other opportunistic infections.

    View details for DOI 10.1016/j.healun.2006.11.002

    View details for Web of Science ID 000243950900015

    View details for PubMedID 17234524

  • Inhaled milrinone: a new alternative in cardiac surgery? Seminars in cardiothoracic and vascular anesthesia Denault, A. Y., Lamarche, Y., Couture, P., Haddad, F., Lambert, J., Tardif, J., Perrault, L. P. 2006; 10 (4): 346-360

    Abstract

    The administration of milrinone through inhalation has been studied in only a few animal and human studies. Compared to the intravenous administration, inhaled milrinone has been shown to reduce pulmonary artery pressure without systemic hypotension. Therefore, this approach could represent an alternative to nitric oxide. This current state of knowledge of intravenous and inhaled milrinone is presented and summarized.

    View details for PubMedID 17200091

  • Giant coronary aneurysms in heart transplantation: an unusual presentation of cardiac allograft vasculopathy JOURNAL OF HEART AND LUNG TRANSPLANTATION Haddad, F., Perez, M., Fleischmann, D., Valantine, H., Hunt, S. A. 2006; 25 (11): 1367-1370

    Abstract

    Cardiac allograft vasculopathy is a leading cause of death during long-term follow-up of heart transplant recipients. We report 2 cases of cardiac allograft vasculopathy associated with giant coronary aneurysms. To our knowledge, these are the first reported cases of spontaneous giant coronary aneurysms in heart transplant recipients.

    View details for DOI 10.1016/j.healun.2006.07.006

    View details for Web of Science ID 000242222100015

    View details for PubMedID 17097503

  • Left and right ventricular diastolic dysfunction as predictors of difficult separation from cardiopulmonary bypass CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE Denault, A. Y., Couture, P., Buithieu, J., Haddad, F., Carrier, M., Babin, D., Levesque, S., Tardif, J. 2006; 53 (10): 1020-1029

    Abstract

    As the evaluation of diastolic function can be complex in the setting of a busy cardiac operating room, its assessment may benefit from an algorithmic approach using transesophageal echocardiography. We developed a diagnostic algorithm which was then applied in a series of cardiac surgery patients to determine whether moderate to severe left ventricular diastolic dysfunction (LVDD) and right ventricular diastolic dysfunction (RVDD) can predict difficult separation from cardiopulmonary bypass (DSB).An algorithm using pulsed-wave Doppler interrogation of the mitral and tricuspid valve, the pulmonary and hepatic venous flow, and tissue Doppler interrogation of the mitral and tricuspid annulus was developed. The study was divided in two phases involving two groups of patients undergoing cardiac surgery. In phase I, echocardiographic evaluations of patients (n = 74) were used to test the reproducibility of the algorithm and to evaluate inter-observer variability using Cohen's kappa values which were calculated in three specific periods. In phase II, the algorithm was applied to a second group of patients (validation group, n = 179) to explore its prognostic significance. The primary end-point in phase II was DSB.In phase I, the kappa coefficients for LVDD and RVDD algorithms were 0.77 and 0.82, respectively. In phase II, moderate or severe degrees of LVDD were observed in 29 patients (16%) and moderate to severe RVDD was observed in 18 patients (10%) before cardiac surgery. Both moderate and severe LVDD (P = 0.017) and RVDD (P = 0.049) before surgery were observed more frequently in patients with DSB.Moderate and severe LVDD and RVDD can be identified with very good reproducibility, and both degrees of diastolic dysfunction are associated with DSB.

    View details for Web of Science ID 000241350900012

    View details for PubMedID 16987858

  • Dynamic right ventricular outflow tract obstruction in cardiac surgery JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Denault, A. Y., Chaput, M., Couture, P., Hebert, Y., Haddad, F., Tardif, J. 2006; 132 (1): 43-49

    Abstract

    Right ventricular outflow tract obstruction can be a cause of hemodynamic instability but it has not been described in non-congenital cardiac surgery.The prevalence of right ventricular outflow tract obstruction was retrospectively studied in 670 consecutive patients undergoing cardiac surgery. Significant right ventricular outflow tract obstruction was diagnosed if the right ventricular systolic to pulmonary artery peak gradient was more than 25 mm Hg. The diagnosis was based on measurement of the right ventricular and pulmonary artery systolic pressure through the paceport and distal opening of the pulmonary artery catheter. To further validate the prevalence and the importance of right ventricular outflow tract obstruction, 130 patients were prospectively studied over a 12-month period.In the retrospective cohort, 6 patients (1%) undergoing various types of cardiac surgical procedures were found to have significant dynamic right ventricular outflow tract obstruction with a mean gradient of 31 +/- 4 mm Hg (26 to 35 mm Hg). In the prospective study significant dynamic right ventricular outflow tract obstruction was identified in 5 patients (4%) (average peak: 37 +/- 15 mm Hg; range: 27 to 60 mm Hg). The typical transesophageal echocardiography finding was end-systolic obliteration of the right ventricular outflow tract. In patients with significant dynamic right ventricular outflow tract obstruction, hemodynamic instability was present in 10/11 patients (91%).Right ventricular outflow tract obstruction is easily diagnosed using the paceport of the pulmonary artery catheter and should be considered as a potential cause of hemodynamic instability especially when transesophageal echocardiography reveals systolic right ventricular cavity obliteration.

    View details for DOI 10.1016/j.jtcvs.2006.03.014

    View details for Web of Science ID 000238522000011

    View details for PubMedID 16798301

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