BACKGROUND In recent years a syndrome characterized by hypotension, acidosis, and vasodilatation, which we have designated HAV syndrome, has been reported to occur more frequently after heart transplantation (HT), but its pathogenesis is unknown. METHODS We analyzed consecutive patients undergoing HT between January 1994 and June 1998 (aged 50 +/- 8 years; 87% male; 40% African American; ischemia time, 190 +/- 20 minutes; given triple immunosuppression without anti-lymphocyte antibodies) in 2 groups: 38 (54%) who developed HAV (systemic vascular resistance < or = 800 dines x sec x cm(-5) and serum bicarbonate < or = 20 mEq/liter) and 32 (46%) who did not. To identify causes of HAV, we compared 113 pre-HT donor and recipient variables, 28 peri-HT variables, and 46 post-HT variables between groups. We used Mann-Whitney, Fisher exact, and chi-squared tests to compare variables and to determine significance. RESULTS Univariate analysis showed that HAV patients had significantly greater recipient and donor weight (p = 0.000007 and 0.0017, respectively), longer ischemia times (p = 0.0052), pre-HT use of beta-blockers (p = 0.009), and longer waiting times for HT (p = 0.018). African-American patients had less HAV than Caucasians (p = 0.047). Patients with pre-HT mechanical circulatory assistance had less HAV than pharmacologically treated patients (p = 0.014). Multivariate analysis showed that recipient (p = 0.0004) and donor weight (p = 0.0394) and ischemia time (p = 0.0015) independently predicted HAV and correlated with HAV severity. Deaths at < or =30 days of HT occurred more in patients with (33%) than in those without (15%) HAV. CONCLUSIONS (1) Hypotension, acidosis, and vasodilatation after HT are associated with high mortality. (2) Recipient and donor weights and ischemia time are independent risk factors for HAV. (3) Pre-HT mechanical circulatory assistance and African-American race confer protection against HAV. (4) Because HAV risk factors can be altered, prevention may be possible. Further study is needed to identify the cellular and humoral mediators of HAV.