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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.
Methodist DeBakey cardiovascular journal 01/2013; 9(1):6-10.
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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.
The American journal of cardiology 12/2012; · 3.58 Impact Factor
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François Haddad,
Prateeti Khazanie,
Tobias Deuse,
Dana Weisshaar,
Jessica Zhou,
Chang Wook Nam,
Thu A Vu,
Fatemeh A Gomari,
Mehdi Skhiri,
Ana Simos,
Ingela Schnittger,
Bojan Vrotvec,
Sharon A Hunt,
William F Fearon
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ABSTRACT: BACKGROUND: -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 risk factors and functional correlates associated with early microvascular dysfunction in heart transplant recipients. METHODS AND RESULTS: -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 (IMR). The presence of microvascular dysfunction, pre-defined by an IMR > 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 an OR=4.0 (1.3-12.8) and OR=3.6 (1.2-11.1), respectively. Patients with microvascular dysfunction had lower cardiac index (3.1 ± 0.7 vs. 3.5 ± 0.7 L/min/m(2), p=0.02), and mild graft dysfunction measured by echocardiography-derived left and right myocardial performance indices [(0.54 ± 0.09 vs. 0.43 ± 0.09, p< 0.01) and (0.47 ± 0.14 vs. 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 post transplant (hazard ratio of 2.52, 95% confidence interval between 1.04 and 5.91). CONCLUSIONS: -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 IMR at 1 year was also associated with worse graft function and possibly worse clinical outcomes.
Circulation Heart Failure 08/2012; · 6.29 Impact Factor
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ABSTRACT: In patients with congenital heart disease, the right heart may support the pulmonary or the systemic circulation. Several congenital heart diseases primarily affect the right heart including Tetralogy of Fallot, transposition of great arteries, septal defects leading to pulmonary vascular disease, Ebstein anomaly and arrhythmogenic right ventricular cardiomyopathy. In these patients, right ventricular dysfunction leads to considerable morbidity and mortality. In this paper, our objective is to review the mechanisms and management of right heart failure associated with congenital heart disease. We will outline pearls and pitfalls in the management of congenital heart disease affecting the right heart and highlight recent advances in the field.
Journal of clinical & experimental cardiology. 06/2012; 8(10):1-11.
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François Haddad,
Tyler Peterson,
Eric Fuh,
Kristina T Kudelko,
Vinicio de Jesus Perez,
Mehdi Skhiri,
Randall Vagelos,
Ingela Schnittger,
Andre Y Denault,
David N Rosenthal,
Ramona L Doyle,
Roham T Zamanian
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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.
Circulation Heart Failure 09/2011; 4(6):692-9. · 6.29 Impact Factor
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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.
Journal of cardiac failure 07/2011; 17(7):533-9. · 3.25 Impact Factor
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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.
Journal of cardiac failure 04/2011; 17(4):272-81. · 3.25 Impact Factor
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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.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 09/2010; 29(9):1071-5. · 3.54 Impact Factor
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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.
Revista Espa de Cardiologia 04/2010; 63(4):451-71. · 2.53 Impact Factor
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François Haddad,
Tobias Deuse,
Michael Pham,
Prateeti Khazanie,
Fernando Rosso,
Helen Luikart,
Hannah Valantine,
Sebastian Leon,
Thu A Vu,
Sharon A Hunt,
Philip Oyer,
Jose G Montoya
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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.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 10/2009; 29(3):306-15. · 3.54 Impact Factor
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François Haddad,
Patrick Fisher,
Michael Pham,
Gerald Berry,
Dana Weisshaar,
Suman Kuppahally,
Bojan Vrtovec,
Tobias Deuse,
Sean Virani,
William Fearon,
Hannah Valantine,
Sharon Hunt
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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.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 05/2009; 28(4):312-9. · 3.54 Impact Factor
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Vivian W Tsai,
Joshua Cooper,
Hasan Garan,
Andrea Natale,
Leon M Ptaszek,
Patrick T Ellinor,
Kathleen Hickey,
Ross Downey,
Paul Zei,
Henry Hsia,
Paul Wang,
Sharon Hunt, François Haddad,
Amin Al-Ahmad
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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.
Circulation Heart Failure 05/2009; 2(3):197-201. · 6.29 Impact Factor
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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.
Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 04/2009; 22(5):523-9. · 2.98 Impact Factor
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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.
Anesthesia and analgesia 03/2009; 108(2):407-21. · 3.08 Impact Factor
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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.
Anesthesia and analgesia 03/2009; 108(2):422-33. · 3.08 Impact Factor
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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.
Journal of the American College of Cardiology 09/2008; 52(8):587-98. · 14.16 Impact Factor
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Circulation 05/2008; 117(13):1717-31. · 14.74 Impact Factor
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Circulation 04/2008; 117(11):1436-48. · 14.74 Impact Factor
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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.
Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 10/2007; 20(9):1065-72. · 2.98 Impact Factor
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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.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 08/2007; 26(7):745-9. · 3.54 Impact Factor
