Faculty Bibliography

OBJECTIVES/OBJECTIVE:We hypothesized that higher plasma levels of von Willebrand factor (vWF) and reduced ristocetin cofactor activity (RCA)/vWF ratios at baseline and follow-up would be associated with an increased risk of death in patients with pulmonary arterial hypertension (PAH). BACKGROUND:Endothelial injury and dysfunction cause increased vWF levels in patients with cardiovascular disease. Increased vWF is associated with a higher risk of death in patients with coronary artery disease, congestive heart failure, and ARDS. In PAH, vWF is elevated and functions abnormally, resulting in reduced platelet binding. The ability of vWF to bind platelets is reflected by RCA. METHODS:We performed a retrospective cohort study of 66 PAH patients who underwent initial evaluation at our center from January 1994 to June 2002. The primary outcome was death or lung transplantation. RESULTS:vWF level was directly associated with Factor VIII activity, RCA, fibrinogen, and prothrombin time (p < or = 0.01). vWF levels at baseline and follow-up were associated with the risk of death (hazard ratio [HR] per 50% increase, 1.4; 95% confidence interval [CI], 1.1 to 1.8 [p = 0.02]; and HR per 50% increase, 1.5; 95% CI, 1.1 to 2.0 [p = 0.011]; n = 48, respectively). RCA/vWF ratios were not associated with outcome. These results were unaffected by adjustment for demographics, baseline hemodynamics, laboratory results, or PAH therapy in multivariate analyses. CONCLUSIONS:Increased vWF levels at baseline and follow-up are associated with worse survival in patients with PAH; however, RCA/vWF ratios are not. The hemostatic effects of vWF do not account for these findings. This suggests that endothelial injury and dysfunction may persist despite treatment and may impact on disease course. Therapies that target endothelial injury may therefore improve outcomes for patients with PAH.

Idiopathic pulmonary arterial hypertension (PAH) is a rare disease with a poor prognosis. New therapies have improved the outcome of this condition; accordingly, the factors that determine outcome may have changed. We aimed to identify determinants of survival in a cohort of consecutive patients with PAH: which was idiopathic, familial, or associated with anorexigen use. We performed a retrospective cohort study of 84 consecutive patients with PAH who underwent initial evaluation at our center from January 1994 to June 2002. The primary outcome was death or lung transplantation. Survival at 1, 3, and 5 [corrected] years was 87%, 75%, and 61%, respectively. Multivariate analysis showed that being of African-American or Asian descent was associated with an increased risk of death. Warfarin use was associated with a reduced risk of death. Higher serum albumin and cardiac index and acute vasoreactivity were independently associated with improved survival. These data suggest that the determinants of outcome have changed. Race is identified as a new risk factor, which may be attributable to biologic or socioeconomic differences. Cardiac function and acute reactivity of the pulmonary vascular bed remain strong independent predictors of outcome.

BACKGROUND: This study examines the relationship between functional capacity, left ventricular diastolic function, and myocardial perfusion reserve (MPR) in patients with left ventricular hypertrophy (LVH). METHODS: We studied 16 patients with LVH and 10 controls. Functional capacity was assessed by cardiopulmonary exercise, MPR by positron emission tomography, and left ventricular diastolic function by echo-Doppler. RESULTS: Functional capacity and MPR were significantly lower in the patients. Functional capacity correlated positively with MPR and left ventricular diastolic function. CONCLUSIONS: Diminished functional capacity in patients with hypertension-induced LVH is related to the impairment in MPR and left ventricular diastolic function.

BACKGROUND: Previous studies have shown that the risk of major cardiovascular events at 1 year is less than 1% in patients with normal myocardial stress perfusion study results. However, the racial distribution of patients enrolled in these studies is not known. Hence, the prognostic value of normal stress perfusion study results in black patients is not well established. Our objective was to determine the incidence of major cardiovascular events in black patients with normal stress perfusion study results over a 12-month period. METHODS AND RESULTS: We searched the nuclear cardiology database at our institution for all black patients who had normal stress perfusion study results between January 1990 and December 1996. We excluded patients with a history of coronary revascularization, valvular heart disease, cardiomyopathy, congenital heart disease, left bundle branch block, or pre-excitation syndrome. Patients were followed up for at least 12 months from the time of inclusion. A total of 592 patients were enrolled and were followed up for 18 +/- 6 months (mean +/- SD). Of these, 388 underwent treadmill exercise testing, 155 underwent dipyridamole stress testing, and the remainder underwent dobutamine stress testing. Perfusion studies were performed in all patients with thallium 201 single photon emission computed tomography imaging. During the follow-up period, 11 cardiac deaths and 7 myocardial infarctions (MIs) occurred. The incidence of cardiac deaths was 1.2% per year, and that of nonfatal MIs was 0.8% per year. The total incidence of major cardiovascular events was 2% per year. In patients who underwent treadmill exercise testing, the incidence of major cardiovascular events was 1% per year. Performance of a pharmacologic stress test and a prior MI were significantly associated with death or nonfatal MI (P <.05). CONCLUSIONS: The overall incidence of major cardiovascular events in black patients after normal exercise perfusion study results were obtained was low (1%). However, black patients who had normal perfusion study results but underwent pharmacologic stress testing or had a history of MI were at intermediate risk. These patients require close surveillance for major cardiovascular events.