Papers by Hannah Valantine
Transplantation, 2003
Endothelial injury plays a central role in the pathophysiologic mechanisms underlying cardiac all... more Endothelial injury plays a central role in the pathophysiologic mechanisms underlying cardiac allograft vasculopathy (CAV). Although the accelerated course of CAV and its localization to the allograft support an important role for the alloimmune response, there is considerable evidence implicating lipoprotein abnormalities, metabolic disturbances, viral infections, and systemic inflammation in the process. This multifactorial basis for CAV may be put into a pathophysiologic context in which endothelial cell injury is the triggering event that initiates and drives the proliferative and fibrotic processes characteristic of CAV. In the transplant setting, endothelial cell injury is induced by multiple factors, including brain death, ischemia-reperfusion, alloimmune responses, and viral infections. Once initiated, propagation of the proliferative processes that ultimately lead to vascular occlusion is enhanced by the abnormal metabolic environment of elevated lipoproteins and insulin resistance encountered in most patients. This review examines the evidence for the role of potential triggers of endothelial injury in the pathophysiology of CAV and discusses the central role of the nitric oxide pathway in the disease process.
Journal of Heart and Lung Transplantation, 2004
Cardiovascular disease post-transplant, particularly ischemic heart disease, is a significant pro... more Cardiovascular disease post-transplant, particularly ischemic heart disease, is a significant problem for all transplant recipients. The major risk factors-smoking, obesity, diabetes, dyslipidemia and hypertension-are often more prevalent in heart transplant populations than in the general population. One of the main risk factors influencing graft loss and patient survival is cardiac allograft vasculopathy (CAV). Because CAV affects between 30% and 60% of cardiac transplant recipients within 5 years of surgery, prevention is a key focus for cardiac transplant teams today. CAV is caused by both immunologic mechanisms (e.g., acute rejection and anti-HLA antibodies) and non-immunologic mechanisms relating to the transplant itself or the recipient (e.g., donor age, hypertension, hyperlipidemia and pre-existing diabetes) or to the side effects often associated with immunosuppression with calcineurin inhibitors or corticosteroids (e.g., cytomegalovirus infection, nephrotoxicity and new-onset diabetes after transplantation). The calcineurin inhibitors, cyclosporine and tacrolimus, effectively prevent acute rejection, but do not prevent the development of CAV. CAV prevention will require a combined approach of new adjunct immunosuppressant agents (e.g., the proliferation signal inhibitors) and reduction in cardiovascular risk. Hypertension, hyperlipidemia and diabetes are also associated with the immunosuppression required to prevent organ rejection. Some studies have shown that hypertension is present more frequently in cyclosporine-treated patients than in tacrolimus-treated patients and that tacrolimus may be associated with a more favorable lipid profile. On the other hand, tacrolimus may be more diabetogenic than cyclosporine with current data suggesting a trend but no statistically significant supporting evidence. New-onset diabetes after transplantation is at times difficult to manage and may be an important determinant along with hypertension and hyperlipidemia of ischemic heart disease, cerebrovascular disease and peripheral vascular disease. The choice of calcineurin inhibitor for an immunosuppressive regimen in heart transplantation should consider the associated relative cardiovascular risks. J Heart Lung Transplant 2004;23:S187-93.
New England Journal of Medicine, 2010
Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardi... more Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant. However, this procedure is uncomfortable, and there are risks associated with it. Gene-expression profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy.
Journal of Heart and Lung Transplantation, 2008
Journal of Heart and Lung Transplantation, 2003
Background: Long-term survival after heart transplantation is common in the cyclosporine era. How... more Background: Long-term survival after heart transplantation is common in the cyclosporine era. However, there are few data documenting pre-transplant/perioperative factors predictive of truly long-term survival (Ͼ10 years). The purpose of this study is to identify factors associated with 10-year survival after heart transplantation.
Journal of Heart and Lung Transplantation, 2006
Background: Investigating changes in coronary physiology that occur after cardiac transplantation... more Background: Investigating changes in coronary physiology that occur after cardiac transplantation has been challenging. Simultaneous and independent assessment of the epicardial artery by measuring fractional flow reserve (FFR) and of the microvasculature by calculating the index of microvascular resistance (IMR) with a single coronary pressure wire may be useful.
Transplantation, 1995
... 2 Sources of support: Heather Ross is a Sobey Fellow from the Dalhousie Medical Research Foun... more ... 2 Sources of support: Heather Ross is a Sobey Fellow from the Dalhousie Medical Research Foundation, Canada. Hannah Valan-tine is supported by NIH Grant No. ... Am J Med 1994; 96: 497. 13. Pannuti C, Gingrich R, Pfaller MA, Kao C, Wenzel RP. ...
Transplantation, 2006
Anticytomegalovirus (CMV) prophylaxis prevents the acute disease but its impact on subclinical in... more Anticytomegalovirus (CMV) prophylaxis prevents the acute disease but its impact on subclinical infection and allograft outcome is unknown. We sought to determine whether CMV prophylaxis administered for three months after heart transplant would improve patient outcomes. This prospective cohort study of 66 heart transplant recipients compared aggressive CMV prophylaxis (n = 21, CMV hyperimmune globulin [CMVIG] plus four weeks of intravenous ganciclovir followed by two months of valganciclovir); with standard prophylaxis (n = 45, intravenous ganciclovir for four weeks). Prophylaxis was based on pretransplant donor (D) and recipient (R) CMV serology: R-/D+ received aggressive prophylaxis; R+ received standard prophylaxis. Outcome measures were: CMV infection assessed by DNA-polymerase chain reaction on peripheral blood polymorphonuclear leukocytes, acute rejection, and cardiac allograft vascular disease (CAV) assessed by intravascular ultrasound. All patients completed one year of follow-up. RESULTS.: CMV infection was subclinical in all but four patients (two in each group). Aggressively treated patients had a lower incidence of CMV infection (73 +/- 10% vs. 94 +/- 4%; P = 0.038), and an independent reduced relative risk for acute rejection graded > or =3A (relative risk [95% CI] = 0.55 [0.26-0.96]; P = 0.03), as compared with the standard prophylaxis group. Aggressively prophylaxed patients also showed a slower progression of CAV, in terms of coronary artery lumen loss (lumen volume change=-21 +/- 13% vs. -10+/-14%; P = 0.05); and vessel shrinkage (vessel volume change = -15 +/- 11% vs. -3 +/- 18%; P = 0.03). Prolonged (val)ganciclovir plus CMVIG reduces viral levels, acute rejection, and allograft vascular disease, suggesting a role for chronic subclinical infection in the pathophysiology of the most common diseases affecting heart transplant recipients.
Journal of The American College of Cardiology, 2005
We sought to assess the validity of first-year intravascular ultrasound (IVUS) data as a surrogat... more We sought to assess the validity of first-year intravascular ultrasound (IVUS) data as a surrogate marker for long-term outcome after heart transplantation. BACKGROUND Cardiac allograft vasculopathy (CAV) is a major impediment to long-term graft survival. Intravascular ultrasound is more sensitive than coronary angiography and detects intimal thickening (early CAV) in the coronary arteries of the donor heart. Single-center studies have suggested first-year IVUS results might be a surrogate marker for long-term outcome.
Liver Transplantation, 2001
Patients with end-stage liver disease and coronary artery disease (CAD) being considered for orth... more Patients with end-stage liver disease and coronary artery disease (CAD) being considered for orthotopic liver transplantation (OLT) present a difficult dilemma. The availability of multiple screening tests and newer treatment options for CAD prompted this review. Recent data suggest that the prevalence of CAD in patients with cirrhosis is much greater than previously believed and likely mirrors or exceeds the prevalence rate in the healthy population. The morbidity and mortality of patients with CAD who undergo OLT without treatment are unacceptably high, making identification of patients with CAD before OLT an important consideration. Patients with documented CAD or major clinical predictors of CAD should undergo cardiac catheterization before OLT. Those with advanced CAD not amenable to interventional therapy or with poor cardiac function are not candidates for OLT. Dobutamine stress echocardiogram appears to be an excellent means of screening patients with intermediate or minor clinical predictors of CAD before OLT. Patients found to have mild or moderate CAD should be aggressively treated medically and, if necessary and feasible based on hepatic reserve, by percutaneous or, less likely, surgical intervention pre-OLT to correct obstructive coronary lesions. Prospective studies regarding optimal screening strategies for the presence of CAD and the indications, timing, and outcomes of interventional therapy in patients with advanced cirrhosis are lacking and much needed. (Liver Transpl 2001;7:755-761.)
Journal of The American College of Cardiology, 1995
The purpose of this study was to quantify the severity of transplant coronary artery disease and ... more The purpose of this study was to quantify the severity of transplant coronary artery disease and to assess lesion characteristics early and up to 15 years after heart transplantation by using intracoronary ultrasound. Intravascular ultrasound has the ability to measure the components of the arterial wall and has been shown to be a sensitive method for detection of transplant coronary artery disease. A total of 304 intracoronary ultrasound studies were performed in 174 heart transplant recipients at baseline and up to 15 (mean 3.3 +/- 0.2) years after transplantation. Mean intimal thickness and an intimal index were calculated, and lesion characteristics (eccentricity, calcification) were assessed for all coronary sites imaged (mean 3.0 +/- 0.1 sites/study). The Stanford classification was used to grade lesion severity. Compared with findings in patients studied at baseline (< 2 months after transplantation, n = 50), mean intimal thickness (0.09 +/- 0.02 vs. 0.16 +/- 0.02 mm, p < 0.01), intimal index (0.07 +/- 0.01 vs. 0.14 +/- 0.02, p < 0.01) and mean severity class (1.5 +/- 0.2 vs. 2.3 +/- 0.2, p < 0.01) were significantly higher at year 1 (n = 52) after transplantation. Thereafter, all three variables further increased over time and reached highest values between years 5 and 15. Calcification of lesions was detected in 2% to 12% of studies up to 5 years after transplantation, with a significant increase to 24% at years 6 to 10 (p < 0.05). Severity of transplant coronary artery disease appeared to progress with time after transplantation in this cross-sectional study. This characteristic was most prominent during the 1st 2 years after transplantation, whereas calcification of plaques occurred to a significant extent only later in the process. These data may serve as a reference for comparison of intravascular ultrasound findings in other studies of patients with transplant coronary artery disease.
Journal of Heart and Lung Transplantation, 2004
Background: Truly long term survival post heart transplantation has become increasingly frequent ... more Background: Truly long term survival post heart transplantation has become increasingly frequent over the past two decades.
Journal of Heart and Lung Transplantation, 2001
Background: Tricuspid regurgitation (TR) is common after heart transplantation. However, the inci... more Background: Tricuspid regurgitation (TR) is common after heart transplantation. However, the incidence of severe TR and the incidence of symptoms after echocardiographic diagnosis of severe TR have not been documented. The purpose of this study is to determine the incidence of severe TR and its clinical significance in the heart transplant population.
American Journal of Cardiology, 1989
To charade&e the clinical and patho&ic fe&ures of acute myocardial infarction (AMI) in car&c tran... more To charade&e the clinical and patho&ic fe&ures of acute myocardial infarction (AMI) in car&c transplant recipients, 22 Stanford patients who had 2Sdoarmentedinfarctsatameanof3.66years after transplantation were revlewed. Symptoms included chest pain (2), arm pain , weakness (16), dyspmea(ll)adpalpitations(8).Three~s wem dinii silent, detected only as new electrocadiographic changes duling routlne follow-up. of 18 patknts hosphlized with symptoms, only 7 had ekctmcardiographk changes of typical Q-wave AMI; 5 had nonspedfic ST-segment changes and 2 had ne docmwnted changes. Two had oid Q waves.
American Journal of Cardiology, 1989
Journal of Heart and Lung Transplantation, 2005
on behalf of the Mycophenolate Mofetil Cardiac Study Investigators
Transplantation, 1996
This study examined the hypothesis that immunologic factors are the major correlates of coronary ... more This study examined the hypothesis that immunologic factors are the major correlates of coronary artery intimal thickening and luminal stenosis. The study population included 116 adult heart transplant recipients with a mean age of 44.7 +/- 12.0 years (89 men and 27 women) undergoing annual coronary angiography and intracoronary ultrasound 3.4 +/- 2.7 (range, 1.0-14.6) years after transplantation. Mean intimal thickness was obtained from several distinct sites along the left anterior descending and/or left circumflex coronary artery by intracoronary ultrasound. Coronary artery stenosis defined by angiography was classified as mild (< 30% luminal stenosis), moderate (> or = 30-70% luminal stenosis), or severe (> 70% luminal stenosis or diffuse pruning of distal vessels). Prevalence of any transplant coronary artery disease (TxCAD) was 85% by intracoronary ultrasound and 15% by angiography. By multiple regression analysis, only average fasting plasma triglyceride level (P < 0.006) and average weight (P < 0.007) were significantly correlated with severity of intimal thickening (R = 0.54, P < 0.0001). Donor age (P < 0.006) and average fasting plasma triglyceride level (P < 0.009) were significantly correlated with stenosis by angiography. Correlation of multiple immunologic and metabolic factors with intimal thickness by univariate analysis suggests a multifactorial etiology for TxCAD. Among the multiple univariate correlates of TxCAD, higher fasting plasma triglyceride levels and body weight are the only independent correlates of TxCAD. The absence of acute rejection as an independent predictor of intimal thickening suggests that mechanisms beyond those mediating typical cellular rejection should be targeted for advancing our understanding of Tx-CAD.
Transplantation, 1998
Background. After heart transplantation, 1-year and 5-year survival rates are 79% and 63%, respec... more Background. After heart transplantation, 1-year and 5-year survival rates are 79% and 63%, respectively, with rejection, infection, and allograft coronary artery disease accounting for the majority of deaths. Mycophenolate mofetil (MMF), an inhibitor of the de novo pathway for purine biosynthesis, decreases rejection in animals and in human renal transplantation.
Transplantation, 2001
Cytomegalovirus (CMV) disease was previously shown to be unaltered by a 28-day course of ganciclo... more Cytomegalovirus (CMV) disease was previously shown to be unaltered by a 28-day course of ganciclovir compared with placebo in seronegative recipients of hearts from seropositive donors (D+/R-). This study tests the hypothesis that a combination of ganciclovir plus CMV hyperimmune globulin (CMVIG) is more effective than ganciclovir alone for preventing acute CMV illness and its long-term sequelae. The study population receiving CMVIG (n=80) included 27 heart transplant recipients (D+/R-) and 53 heart-lung and lung transplant recipients (R+ and/or D+). Each group was matched with historical controls who underwent transplantation within the preceding 2-3 years. Outcome measures compared were as follows: 3-year incidence of CMV disease; fungal infection; acute rejection; survival; rates and severity of transplant coronary artery disease (in heart patients) defined by intimal thickness (ultrasound) and coronary artery stenosis (angiographic); and incidence and death from obliterative bronchiolitis defined by pathological criteria on endobronchial biopsy specimens (in heart-lung/lung patients). Patients treated with CMVIG had a higher disease-free incidence of CMV, lower rejection incidence, and higher survival rate compared with the patients treated with ganciclovir alone. The coronary artery intimal thickness and the prevalence of intimal thickening were lower in the patients receiving CMVIG. Heart-lung and lung transplant patients treated with CMVIG had lower incidences of obliterative bronchiolitis and death from obliterative bronchiolitis and longer survival compared with the patients treated with ganciclovir alone. CMVIG plus ganciclovir seems to be more effective that ganciclovir alone for preventing the sequelae of CMV infection. A prospective randomized study is required to confirm these observations.
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Papers by Hannah Valantine