New index for assessing the chronotropic response in patients with end-stage liver disease who are undergoing dobutamine stress echocardiography.

The inability to achieve 85% of the maximum predicted heart rate (MPHR) on dobutamine stress echocardiography (DSE) is defined as chronotropic incompetence and is a predictor of major cardiac events after orthotopic liver transplantation (OLT). The majority of patients with end-stage liver disease (ESLD) receive beta-blockers for the prevention of variceal bleeding. In these patients, it is impossible to determine whether chronotropic incompetence is secondary to cirrhosis-related autonomic dysfunction or is merely a beta-blocker effect. We evaluated the usefulness of the maximum achieved heart rate (MAHR) and the heart rate reserve (HRR) in the detection of chronotropic incompetence in ESLD patients on beta-blocker therapy before DSE. We also evaluated the usefulness of a new index, the modified heart rate reserve (MHRR), in diagnosing chronotropic incompetence and predicting major cardiovascular adverse events after OLT. The study population consisted of 284 ESLD patients. The mean values of MAHR (expressed as a percentage of 85% of MPHR) and HRR were significantly lower for patients on beta-blockers versus patients off beta-blockers [97.1% versus 101.6% (t = 5.01, P < 0.001) and 71.7% versus 77.3% (t = 4.03, P < 0.001), respectively], whereas the values of MHRR were similar in patients on beta-blockers and patients off beta-blockers [102.3% versus 102.1% (t = 0.04, P = 0.97)]. A regression analysis showed a significant association of MAHR (P < 0.001) and HRR (P < 0.001) with beta-blockers, whereas MHRR was not associated with beta-blocker treatment (P = 0.92). MAHR and HRR were found to have no value for diagnosing chronotropic incompetence in ESLD patients. MHRR was not affected by beta-blocker therapy. Patients who developed heart failure (HF) and myocardial infarction (MI) after OLT had significantly lower MHRR values according to pretransplant DSE. MHRR was significantly associated with the subsequent development of HF (P = 0.01) and MI (P = 0.01) after OLT. MHRR may be useful for the determination of the target heart rate for stress testing, the diagnosis of chronotropic incompetence, and the prediction of adverse cardiac events after OLT.

Hepatitis status, child-pugh classification, and serum AFP levels predict survival in patients treated with transarterial embolization for unresectable hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) represents one of the most prevalent cancers worldwide. Most patients are not surgical candidates, and transarterial embolization (TAE) has been used to treat patients with unresectable HCC. The purpose of this study was to identify factors that predict survival in patients treated with TAE at a Western medical center. Review of a prospective database identified 345 patients treated for HCC at University Hospital (Newark, NJ) between July 1998 and July 2004. Of these patients, 109 patients underwent TAE. Eleven of these patients were subsequently treated surgically and excluded from this study. Of the remaining 98 patients, demographic data and laboratory values were analyzed to predict survival by univariate and multivariate analysis. Several factors, including hepatitis status, Child-Pugh classification, serum alpha fetoprotein levels <500 ng/ml, bilirubin <2.0 mg/dl, prothrombin time <16 seconds, platelet count <200 x 10(9)/l, albumin >3.5 gm/dl, and multiple treatments, predicted survival by univariate analysis. Serum alpha fetoprotein levels, Child-Pugh classification, and hepatitis status were found by multivariate analysis to independently predict survival. These factors may help to select patients with unresectable HCC who might benefit from TAE.

Ischemic preconditioning in deceased donor liver transplantation: a prospective randomized clinical trial of safety and efficacy.

Ischemic preconditioning (IPC) has the potential to decrease graft injury and morbidity after liver transplantation. We prospectively investigated the safety and efficacy of 5 minutes of IPC induced by hilar clamping in local deceased donor livers randomized 1:1 to standard (STD) recovery (N = 28) or IPC (N = 34). Safety was assessed by measurement of heart rate, blood pressure, and visual inspection of abdominal organs during recovery, and efficacy by recipient aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT], both measured in U/L), total bilirubin, and international normalized ratio of prothrombin time (INR) after transplantation. IPC performed soon after laparotomy did not cause hemodynamic instability or visceral congestion. Recipient median AST, median ALT, and mean INR, in STD vs. IPC were as follows: day 1 AST 696 vs. 841 U/L; day 3 AST 183 vs. 183 U/L; day 1 ALT 444 vs. 764 U/L; day 3 ALT 421 vs. 463 U/L; day 1 INR 1.7 +/- .4 vs. 2.0 +/- .8; and day 3 INR 1.3 +/- .2 vs. 1.4 +/- .3; all P > .05. No instances of nonfunction occurred. The 6-month graft and patient survival STD vs. IPC were 82 vs. 91% and median hospital stay was 10 vs. 8 days; both P > .05. In conclusion, deceased donor livers tolerated 5 minutes of hilar clamping well, but IPC did not decrease graft injury. Further trials with longer periods of preconditioning such as 10 minutes are needed.

Racial discrepancies in the outcome of patients with hepatocellular carcinoma.

HYPOTHESIS: There is a marked variation in the outcome of patients with hepatocellular carcinoma with respect to race and ethnicity. Rates among African American and Hispanic individuals are elevated as compared with those among white individuals. DESIGN: Retrospective review of a prospective database. Demographic information, clinical staging, and other defining factors, including the absence or presence of hepatitis, cirrhosis, and alcohol abuse, were analyzed by patient interviews and review of the medical record. SETTING: Urban tertiary referral teaching hospital. PATIENTS: Patients diagnosed as having hepatocellular carcinoma between July 1997 and June 2003 (N = 264). Main Outcome Measure Overall survival rates. RESULTS: Based on multivariate analysis, race was identified as an independent predictor of survival. While there was no difference in the distribution of patient or tumor characteristics between the 2 groups, African American/Hispanic patients had a 5-year survival rate of 12%, which was significantly lower than that of white patients (50%; P = .001). CONCLUSIONS: This study demonstrates a significant discrepancy in overall survival of African American/Hispanic patients as compared with that of white patients. The reason for this difference cannot be explained by patient or tumor characteristics or completely by treatment allocation. These data suggest that there may be socioeconomic, biological, and/or cultural determinants contributing to this observed difference in outcome.

Donors with cardiac arrest: improved organ recovery but no preconditioning benefit in liver allografts.

BACKGROUND: Historically, organ recovery rates in donors with cardiac arrest (CA) have been low, presumably from hemodynamic instability. We hypothesized that donor resuscitation has improved hemodynamic stability and organ recovery in CA donors, and that CA triggers ischemic preconditioning (IP) in liver grafts. METHODS: A total of 131 donor pairs with and without CA were matched in age, gender, and year of recovery. Hemodynamic stability was determined by vasopressor use. Abdominal and thoracic organs recovered and livers transplanted were compared between the groups. Liver graft function, injury, and IP benefit were examined by comparing liver chemistries after transplantation and postperfusion biopsies between recipients of grafts from both groups (n=40 each). RESULTS: Hemodynamic stability was similar in both groups, but recovery of thoracic organs was significantly lower in CA versus non-CA donors (35 vs. 53%, P<0.01). On the other hand, recovery rates of three or more abdominal organs from CA donors approached those of non-CA donors (77 vs. 87%, not significant). Although significantly fewer livers were transplanted from CA donors (69 vs. 85%, P<0.01), posttransplantation graft function and injury parameters were similar between the two groups, and CA did not appear to trigger IP. CONCLUSION: Compared with historical data, cardiovascular stability and abdominal organ recovery rates have improved considerably in CA donors. Liver grafts from CA donors function similarly to grafts from non-CA donors with no IP from CA. Our data support the increased use of livers and other organs from donors with CA.