Does hyperuricemia predict adverse clinical outcome while awaiting heart transplantation?

164

Abstracts

infections were seen in 15 patients. Toxicity correlated with high SRL levels. Conclusion: SRL is a useful alternative immunosuppressant to standard CI therapy in the difficult clinical setting of significant renal impairment post LTx & HTx. At the doses used, and in combination with other agents, excellent rejection prophylaxis was achieved. In future, lowering the SRL dose and corresponding levels may avoid the leucopaenia and infection noted to be particularly problematic in the LTx setting. 44 CLINICAL VALUE OF BRAIN NATRIURETIC PEPTIDE FOR CANDIDATE SELECTION BEFORE CARDIAC TRANSPLANTATION J. Koglin, S. Pehlivanli, M. Schwaiblmair, M. Vogeser, P. Cremer, W. Von Scheidt, Universitaetsklinikum Grosshadern, University of Munich, Munich, Germany With increasing waiting lists for cardiac transplantation, risk stratification of the individual clinical course of chronic heart failure of potential candidates is a critical part in the candidate selection process. Using a prospective study design, we assessed the value of brain natriuretic pepetide (BNP) to identify heart failure patients with an increased risk of deterioration of their functional status. Furthermore, we examined the relation of BNP and various clinical characteristics incorporated in the Heart Failure Survival Score already clinically established for risk stratification and candidate selection. In 78 patients referred to our heart failure outpatient clinic, plasma BNP levels were compared with the results of the Heart Failure Survival Score. To assess the prognostic power of BNP, the clinical course of this cohort (assessed as improvement, stabilization or deterioration based on history and examination) was monitored for a median follow-up period of 398 days. At study entry, plasma BNP and Heart Failure Survival Score showed a significant correlation (r⫽-0.706, p⬍0.0001). During follow-up, Kaplan Meier estimates of freedom from clinical events differed significantly for patients above and below to the 75th percentile concentration of plasma BNP (107.5 pg/ml; p⬍0.0001). Changes in plasma BNP were significantly related to changes in limitations of physical activity as demonstrated by logistic regression (c2⫽24.9, p⬍0.0001). Proportional hazard analysis confirmed BNP as a powerful predictor of deterioration of the functional status (p⬍0.0001). This prognostic information was as powerful as that derived from the multivariable Heart Failure Survival Score. Patients with high levels of BNP had a substantially higher probability of deterioration of their functional status or death compared to those with only moderately increased levels. Hence, measurement of plasma BNP levels might provide a useful screening tool to preselect potential candidates for transplantation and reduce the need and frequency for more expensive prognostic work-up in patients with advanced CHF. 45 RELATIONSHIP BETWEEN PEAK EXERCISE OXYGEN CONSUMPTION AND QTC IN PATIENTS WITH ADVANCED HEART FAILURE F. Boccalandro, A. Yepes, A. Velasco, C.D. Thomas, M. Bologna, B. Richartz, B. Radovancevic, Texas Heart Institute, Houston, TX, USA

The Journal of Heart and Lung Transplantation February 2001 Background: In heart transplant candidates, peak exercise oxygen consumption (MVO2) may predict survival. Moreover, in patients with a left ventricular assist system (LVAS), the QTc is a predictor of survival. This suggests that the QTc may indicate the degree of systemic metabolic compromise rather than the degree of isolated myocardial dysfunction. We undertook this study to determine if the MVO2 inversely correlates with the QTc and to examine the relationship between these parameters and mortality. Methods: QTc, MVO2, and clinical, laboratory, echocardiographic, and hemodynamic parameters were collected for 298 class III and IV heart transplant candidates between April 1993 and April 2000. Patients were followed until the end of the study, until they received a heart transplant, or until they died (mean, 4.3⫾1.8 years). We excluded patients who had a previous heart transplant, an LVAS, renal failure, a pacemaker, or medications affecting QTc. The correlation between QTc and MVO2 was analyzed with Pearson’s correlation coefficient and a 2-tailed Student t test for significance. Patients not undergoing transplantation were stratified by MVO2 to study the relationship between QTc and mortality. Results: 233 patients completed the study; 208 (88%) were men (mean age, 50⫾10 years). The mean ejection fraction was 10⫾9%, with a mean cardiac index of 2.06⫾0.7 L/min/m2. Of the 154 patients (67%) who underwent transplantation, 71 (47%) died before study completion. When these patients were stratified by MVO2, the mortality was higher in the groups with a lower MVO2 and longer mean QTc (Table); there were no differences in medical regimen or in serum electrolytes. A significant inverse correlation was found between the QTc and the MVO2 (r ⫽0.70; P ⬍0.001). Conclusion: In patients with advanced heart failure, the QTc has an inverse correlation with the MVO2. A lower MVO2 and longer QTc correlate with a worse outcome in this population, which suggests a possible role for QTc in the assessment of heart failure severity. MVO2 (mL/kg/min)

Patients

Deaths

%

QTc (ms)

⬍10 11-15 16-20 ⬎20

20 68 50 16

16 33 18 4

80 48 36 25

592.15(⫾30.4) 446.61(⫾20.7) 423.07(⫾19.2) 411.25(⫾13.1)

46 DOES HYPERURICEMIA PREDICT ADVERSE CLINICAL OUTCOME WHILE AWAITING HEART TRANSPLANTATION? P.A. Uber, M.R. Mehra, M.H. Park, H. Ventura, R.L. Scott, Ochsner Cardiomyopathy and Heart Transplant Center, New Orleans, LA, USA Background: Xanthine oxidase is associated with free radical generation and stimulation of inflammatory mediators implicated in the progression of chronic heart failure. We hypothesized that hyperuricemia, a reflection of xanthine oxidase activity, might allow prognostic discrimination in severe heart failure. Methods and Results: The study cohort consisted of 143 severe heart failure patients(52⫾11 years,EF 20⫾9%,80% men, 74% caucasian, follow-up 12-72 months)awaiting heart transplantation between Jan 1993 and Dec 1998. We assessed the utility of uric acid levels (ⱖ 7.5 versus ⬍ 7.5 mg/dl)at the time of listing, in

The Journal of Heart and Lung Transplantation Volume 20, Number 2

Abstracts

these ambulatory and stable patients for predicting the composite end point of hospitalization or death. A Cox proportional hazards model was constructed and hyperuricemia (ⱖ 7.5 mg/dl)emerged as the most important predictor (␹ 2 17, p 0.0007), along with NYHA class IV (␹2 9,p 0.001)and Male sex (␹2 4, p 0.03). No significant prognostic utility of peak aerobic capacity, hemodynamics, nor other metabolic variables was noted, including diuretic dose and renal function. See Table Conclusions: This investigation provides evidence for the clinical prognostic utility of hyperuricemia(independent of diuretic use or renal dysfunction)in heart transplant candidates, and provides insight into the possible pathophysiological role of xanthine oxidase associated oxidative stress in determining disease progression in severe chronic heart failure. Whether this finding represents a marker or a therapeutic target remains to be elucidated.

Uric Acid ⱖ 7.5 Uric Acid ⬍ 7.5 p value

LVEF%

Serum Creatinine

Diuretic Dose

Bilirubin

Event Free

19⫾7 21⫾11 ns

1.2⫾0.3 1.1⫾0.3 ns

96⫾59 81⫾70 ns

1.1⫾0.6 1.0⫾0.6 ns

68% 81% 0.0007

47 DOES HDL-CHOLESTEROL LEVEL PREDICT CLINICAL OUTCOME IN ADVANCED HEART FAILURE? M.R. Mehra, P.A. Uber, M.H. Park, R.L. Scott, R.V. Milani, Ochsner Clinic, New Orleans, LA, USA Background: High Density Lipoproteins (HDL) are known to interact with cytokine induced adhesion cell molecule elucidation and in influencing the generation of prostacyclin via cyclooxygenase stimulation, both pathophysiological events that are implicated in the natural history of chronic heart failure. Methods: We sought to evaluate the prognostic impact of HDL levels on disease progression in severe heart failure by prospectively examining 132 patients listed for heart transplantation between January 1993 and December 1998 (52⫾11 years, 80%men, 79% Caucasian, 60% ischemic etiology, follow-up 551⫾264 days). The relationship of HDL levels (HDL ⬍ 33mg/dl (n⫽47) versus ⱖ 33mg/dl (n⫽85)) with the primary composite end point of hospitalizations or death was examined. Results: Univariate analysis of selected variables is shown in the table. Survival analysis, using a Cox proportional hazards model, revealed reduced HDL(⬍33mg/dl) as the most powerful independent predictor of worsening disease progression (␹2 19, p⫽0.0001) in concert with black race (␹2 4, p⫽0.04), New York Heart Association class IV (␹2 10, p⫽0.01), while female sex was found to be protective (␹2 5, p⫽0.02). No significance was noted with regard to ventricular geometry or function, hemodynamics, peak aerobic capacity, or use of lipid lowering therapy. Conclusion: This is the first investigation to demonstrate that low HDL levels are strongly predictive of clinical worsening in severe heart failure. Whether this finding represents a mere risk marker or a potential therapeutic target, remains to be elucidated. HDL HDL ⬍ 33 HDL ⱖ 33 p value

EF %

Bilirubin

Sodium

PVR

Survival

20⫾8 21⫾11 ns

1.2⫾.9 0.7⫾0.4 ns

135⫾6 137⫾4 0.01

2.4⫾.8 1.7⫾.8 0.003

69% 83% 0.0006

165

48 PREDICTING A PATIENT’S WAITING TIME TO HEART TRANSPLANT IN THE UK. F.M. Seeney1, J. Mahler1, L. Sharples2, J. Parameshwar2, 1UK Transplant, Bristol, United Kingdom; 2Papworth Hospital, Cambridge, United Kingdom Background: Patients accepted for heart transplantation face an uncertain wait. Knowledge of the expected waiting time for each 3candidate can help patients and clinicians to discuss management. This study aimed to: identify factors influencing waiting time, estimate patient-specific waiting times, produce software for use in clinical practice and evaluate the accuracy of the software. Methods: Data on 1165 adult patients, listed for a first heart transplant in one of 7 UK centres during the period 1990 to 1997 were analysed. All UK patients are registered on the UK National Transplant Database at listing (NTxD) and deaths, removals from the list and transplants are notified to the NTxD. A multiple variable survival model was used to access the predictive value of: patient sex, age at listing, blood group, weight, height, primary diagnosis, CMV status at listing, number of previous heart transplants received and time already spent on the active waiting list. The analysis was stratified by centre to produce centre specific waiting times as well as National estimates. Software was developed which reports the chances of receiving a transplant within 3, 6, 9 and 12 months depending on patient characteristics. An additional 247 registrations were used to test the accuracy of the software. Results: The following factors were identified as influential factors: blood group, weight, height, primary disease and the current time spent on the active waiting list. Using the additional 247 listings, at 3 months post-listing 59% of patients were no longer waiting, of which 47% were predicted correctly by the model - by 12 months, 93% were no longer waiting, of which 83% were predicted correctly. Conclusions: Desktop software, based on readily available patient data, has been developed which predicts the chance of receiving donor hearts by 3, 6, 9 and 12 months after listing. 49 INDIRECT ALLORESPONSES ARE MORE PRONOUNCED IN NON-REJECTING LUNG THAN HEART ALLOGRAFTS S.A. Webber, C. Bentlejeweski, G.J. Boyle, Y. Law, P. Bowman, S.A. Miller, S. Gribar, A. Fitzsimmons, K. McCurry, S. Murali, B. Griffith, A. Zeevi, University of Pittsburgh, Pittsburgh, PA, USA Background and Aims: The indirect pathway of allorecognition is characterized by recipient alloreactive T cells recognizing donor peptide antigen presented by MHC Class II molecules on self APC’s. Evidence is accruing that chronic rejection (CR) may be mediated by indirect allorecognition. We compared the indirect response in heart and lung allografts during quiescence (i.e. no evidence of acute/CR). Methods: Limiting dilution analysis (LDA) was performed to quantify the frequency of peripheral blood T helper cells reactive toward donor peptides corresponding to the hypervariable regions of the mismatched donor DR antigens. PBMC were cultured with rIL-2 (7 days) and then incubated with self irradiated APC’s and the relevant synthetic allopeptides. Proliferation was assessed at 48 hours using 3H-thymidine and quantified by LDA. Lower limit of sensitivity is 1.5 cells/million PBMC. Blood (n⫽132) was collected at time of biopsy (Bx) from 63 pts (49