Noninvasive Liver Assessment in Adult Patients With Fontan Circulation Using Acoustic Radiation Force Impulse Elastography and Hepatic Magnetic Resonance Imaging.

BACKGROUND: Patients who have undergone the Fontan procedure are at risk of developing hepatic dysfunction. However, broad recommendations regarding liver monitoring are limited. The purpose of this study was to characterize the frequency of liver disease in adult Fontan patients using multimodality imaging (hepatic magnetic resonance imaging [MRI], acoustic radiation force impulse [ARFI] elastography, or hepatic ultrasound). METHODS: In a prospective cross-sectional analysis of adult patients palliated with a Fontan procedure, hepatic MRI, ARFI, and hepatic ultrasound were used to assess for liver disease. The protocol compared (1) varying prevalence of liver disease based on each imaging technique, (2) agreement between different techniques, and (3) association between noninvasive imaging diagnosis of liver disease and clinical variables, including specific liver disease biomarkers. RESULTS: Thirty-seven patients were enrolled. The ARFI results showed high wave propagation velocity in 35 patients (94.6%). All patients had some abnormality in the hepatic MRI. Specifically, 8 patients (21.6%) showed signs of chronic liver disease, 10 patients (27%) had significant liver fibrosis, and 27 patients (73%) had congestion. No correlation was found between liver stiffness measured as propagation velocity and hepatic MRI findings. Only 7 patients had an abnormal hepatic ultrasound study. CONCLUSIONS: There is an inherent liver injury in adult Fontan patients. Signs of liver disease were observed in most patients by both hepatic MRI and ARFI elastography but not by ultrasound imaging. Increased liver stiffness did not identify specific disease patterns from MRI, supporting the need for multimodality imaging to characterize liver disease in Fontan patients.

High-Bandpass Filters in Electrocardiography: Source of Error in the Interpretation of the ST Segment.

Introduction. Artifactual variations in the ST segment may lead to confusion with acute coronary syndromes. Objective. To evaluate how the technical characteristics of the recording mode may distort the ST segment. Material and Method. We made a series of electrocardiograms using different filter configurations in 45 asymptomatic patients. A spectral analysis of the electrocardiograms was made by discrete Fourier transforms, and an accurate recomposition of the ECG signal was obtained from the addition of successive harmonics. Digital high-pass filters of 0.05 and 0.5 Hz were used, and the resulting shapes were compared with the originals. Results. In 42 patients (93%) clinically significant alterations in ST segment level were detected. These changes were only seen in "real time mode" with high-pass filter of 0.5 Hz. Conclusions. Interpretation of the ST segment in "real time mode" should only be carried out using high-pass filters of 0.05 Hz.

Sympathetic reinnervation 1 year after heart transplantation, assessed using iodine-123 metaiodobenzylguanidine imaging.

Complete allograft denervation occurs during heart transplantation (HT). Partial ventricular sympathetic reinnervation that may develop after transplantation can be measured using iodine-123 meta iodobenzylguanidine (MIBG) uptake. Previous studies have suggested that reinnervation is likely to be a slow process, only occurring after 1 year posttransplantation. However, the reinnervation prevalence at 1 year after HT remains unknown. This study sought to determine sympathetic reinnervation measured by MIBG at 12 months after surgery. We performed serial cardiac MIBG imaging in 45 cardiac transplant recipients, including 32 males and 13 females, early (2 months) and late (12 months) after the operation. The intensity of myocardial MIBG uptaken was quantified by heart-to-mediastinum ratios (HMR). Reinnervation was considered when the HMR was >1.3. HMR was significantly higher at 12 months: 1.16 ± 0.10 at 2 vs 1.30 ± 0.15 at 12 months (P < .001). Eighteen (40%) of 45 subjects developed visible cardiac MIBG uptake at 1 year after transplantation with HMR >1.3. In conclusion, partial sympathetic reinnervation increases with time after HT; it was seen in 40% of patients at 1 year after the operation.

Can we accept donors who have suffered a resuscitated cardiac arrest?

INTRODUCTION AND AIMS: The shortage of donor organs has prompted increased acceptance of hearts from donors with more comorbidities. With increasing frequency, hearts are being offered from patients who have undergone a resuscitated cardiac arrest (RCA). Our aim was to compare the rate of complications in the postoperative and follow-up periods, depending on whether the transplanted organ came from a donor who had undergone an RCA. MATERIALS AND METHODS: We included all 604 heart transplantations (HTs) performed in our center from 1987 to 2009, including 25 recipients who received an organ from a donor who had undergone RCA. We considered RCA to be an in-hospital cardiac arrest that was resuscitated from the onset, with a duration of <30 minutes, and with total recovery of cardiac and hemodynamic function. We analyzed ischemia time, incidence of acute graft failure (AGF), intubation period, recovery room stay, and long-term survival. The statistical methods were Student t and chi-square tests. RESULTS: There were no differences in baseline characteristics, except that patients in the RCA group were younger (47±13 vs 51±11 years; P=.50). There were also no differences between the RCA group and the other patients in ischemia time (151±50 vs 154±53 minutes; P=.826), incidence of AGF (33% vs 24.7%; P=.311), hours of intubation (76±204 vs 72±249; P=.926), days of recovery room stay (6±7 vs 8±6; P=.453), or survival after HT (53±54 vs 53±52 months; P=.982). CONCLUSIONS: Patients receiving a heart from a patient with an in-hospital RCA and subsequent hemodynamic stability have a similar outcomes to other HT patients.

Normalization of the heart rate response to exercise 6 months after cardiac transplantation.

INTRODUCTION: Heart transplant recipients show an abnormal heart rate (HR) response to exercise due to complete cardiac denervation after surgery. They present elevated resting HR, minimal increase in HR during exercise, with maximal HR reached during the recovery period. The objective of this study was to study the frequency of normalization of the abnormal HR in the first 6 months after transplantation. MATERIALS AND METHODS: We prospectively studied 27 heart transplant recipients who underwent treadmill exercise tests at 2 and 6 months after heart transplantation (HT). HR responses to exercise were classified as normal or abnormal, depending on achieving all of the following criteria: (1) increased HR for each minute of exercise, (2) highest HR at the peak exercise intensity, and (3) decreased HR for each minute of the recovery period. The HR response at 2 months was compared with the results at 6 months post-HT. RESULTS: At 2 months post-HT, 96.3% of the patients showed abnormal HR responses to exercise. Four months later, 11 patients (40.7%) had normalized HR responses (P<.001), which also involved a significant decrease in the time to achieve the highest HR after exercise (124.4±63.8 seconds in the first test and 55.6±44.6 seconds in the second). A significant improvement in exercise capacity and chronotropic competence was also shown in tests performed at 6 months after surgery. CONCLUSIONS: We observed important improvements in HR responses to exercise at 6 months after HT, which may represent early functional cardiac reinnervation.

Mortality from renal dysfunction in heart transplant patients: creatinine versus glomerular filtration rate.

INTRODUCTION: One of the most common, significant problems after heart transplantation (HT) is the development of renal dysfunction. In recent years, the glomerular filtration rate (GFR) has replaced the serum creatinine as the standard parameter for its determination. Our objective was to analyze which renal function parameter (creatinine or GFR) at 1 year after HT better classified patients who will die during follow-up. PATIENTS AND METHODS: The study included 316 consecutive HT patients surviving at least 1 year after transplantation. Creatinine and GFR were determined by the Modification of Diet in Renal Disease Study (MDRD4) equation. Mortality during the follow-up was analyzed to compare both parameters using receiver operating characteristic curves. RESULTS: Over a mean follow-up of 6±3 years, 97 patients died (30.7%). At 1 year after HT, the patients who succumbed displayed a significantly higher mean creatinine value (1.63±0.65 vs 1.41±0.64 mg/dL; P=.004) and a more decreased GFR (53.8 vs 60.8 mL/min/1.73 m2; P=.006). Both groups had the same area under the curve, 0.61 (95% confidence interval: 0.54-0.68; P=.002). CONCLUSION: Among our population, GFR calculated by the abbreviated MDRD4 equation did not provide any additional prognostic value to serum creatinine at 1 year after HT to predict long-term mortality.

Post-heart transplant tumors: chronology and impact on survival.

INTRODUCTION AND AIMS: Tumors are the second leading cause of death beyond the first year heart transplantation (HT). The aim of our study was to establish a chronology for the occurrence and the impact on overall survival of de novo neoplasms after HT. MATERIALS AND METHODS: We included 597 patients undergoing HT from January 1987 to December 2008. De novo tumors were classified into groups: Kaposi's sarcoma, melanoma, epidermoid skin carcinoma, other skin tumors, lung neoplasms, bladder tumors, prostate adenocarcinoma, digestive tumors, lymphomas, and other tumors. We based the study on the median value and interquartile range of the tumors to estimate their occurrence. Survival rates were calculated using Kaplan-Meier curves and the log-rank tests. We included only patients with survivals beyond 1 year after HT. RESULTS: A total of 109 tumors developed during the follow-up. There were no differences in the survival of patients who lived more than 1 year regarding the development or not of a tumor (155±8 vs 179±6 months; P=.177). CONCLUSIONS: The incidence of tumor occurrence after HT was high (18.25%). There were several periods in which the occurrence of certain tumors was more frequent, while other periods appeared to be tumor-free. As most tumors were skin cancers, their impact on overall survival was low.

Preliminary results of a prospective randomized study of cyclosporine versus tacrolimus in the development of cardiac allograft vasculopathy at 1 year after heart transplantation.

INTRODUCTION AND AIMS: Cardiac allograft vasculopathy (CAV) is the leading cause of death after the first year post-heart transplantation (HT). Numerous factors have been implicated in the development of CAV. The aim of this prospective randomized study was to assess the impact of cyclosporine (CsA) and tacrolimus (Tac) on the development of CAV. MATERIALS AND METHODS: From November 2006 to October 2008, 49 HT patients in our center were randomized to receive CsA or Tac. The additional treatment for all patients consisted of daclizumab induction and maintenance treatment with mycophenolate mofetil (1 g/12 hours) and steroids (withdrawal was not attempted). Thirteen patients died before coronary arteriography plus intravascular ultrasound of the left anterior descending artery was performed at 1 year after HT. Hence, the final number of patients included was 36 (18 per group). We considered significant CAV to be the presence of intimal proliferation>1 mm and/or>0.5 mm in 180°. The statistical methods were Student t and chi-square tests. RESULTS: There were no differences in baseline characteristics between the two groups. Nor were there significant differences in maximum intimal proliferation between the groups (CsA 0.65±0.29 vs Tac 0.82±0.51 mm; P=.292) or in the development of significant CAV when both criteria were combined (CsA 31.6% vs Tac 38.9%; P=.642). CONCLUSIONS: One year after HT, no differences were detected in the development of significant CAV according to the type of calcineurin inhibitor used when combined with daclizumab induction and maintenance treatment with mycophenolate mofetil and steroids.

Exercise tolerance after beta blockade in recent cardiac transplant recipients.

OBJECTIVE: Exercise capacity has been shown to be reduced among cardiac transplant recipients. This observation is directly connected to both the transplanted heart's dependence on circulating catecholamines and the abnormal sympathoadrenal response to exercise in these patients. Taking into account this background, there is reluctance to use beta-blockers after heart transplantation. Nevertheless, this point remains controversial. Our aim was to examine exercise tolerance after an oral dose of atenolol early after cardiac transplantation. MATERIALS AND METHODS: Eighteen nonrejecting, otherwise health, cardiac transplant recipients were included in this study at a mean of 61.9 +/- 25.6 days after surgery; 13 were men. Patients performed controlled exercise to a symptom-limited maximum before and 2 hours after taking an oral dose of atenolol. Heart rate, blood pressure, exercise time, and metabolic equivalent units (METS) were recorded at rest as well as during and after exercise. We compared results depending on taking atenolol. RESULTS: Resting (101.7 +/- 14.5 vs 84 +/- 12.4 bpm; P = .001) and peak heart rates (128.5 +/- 12.9 vs 100.7 +/- 16 bpm; P = .001) were significantly higher before than after beta blockade. Resting systolic blood pressure was slightly higher before compared with after beta blockade (129.3 +/- 23.6 vs 122.2 +/- 20.3 mm Hg; P = .103). However, there was neither a significant difference in the length of exercise (3.17 +/- 1.96 vs 3.40 +/- 2.48 minutes; P = .918) nor in the estimated oxygen consumption (METS; 5.07 +/- 1.8 vs 5.31 +/- 2.2; P = .229). Furthermore, no patient reported a greater degree of tiredness after beta blockade. CONCLUSIONS: This study showed little adverse effect on exercise tolerance by beta blockade in recently transplanted patients. Atenolol seemed to be safe in this context.

Effect of circulatory assistance on premature death and long-term prognosis.

BACKGROUND: Patients undergoing urgent heart transplantation (HT) have a poorer prognosis and more long-term complications. The objective of this study was to compare the preoperative course in patients undergoing urgent HT according to the need for preoperative intra-aortic balloon counterpulsation (IABP). MATERIALS AND METHODS: We studied 102 consecutive patients including 23 patients with IABP who underwent urgent HT between January 2000 and September 2006. We excluded patients who received combination transplants, those who underwent repeat HT, and pediatric patients who underwent HT. The statistical methods used were the t test for quantitative variables and the chi(2) test for qualitative variables. A logistic regression model was constructed to assess the possible relationship between IABP and other variables on premature death within 30 days after HT. RESULTS: Mean (SD) patient-age was 50 (10) years. No significant differences were observed in baseline characteristics between the IABP and the non-IAPB groups. The IABP patient group had higher rates of acute graft failure (45.5% vs 35.4%; P = .46) and premature death (18.8% vs 14.8%; P = .67) and shorter long-term survival (40.6 [34.9] vs 54.5 [43.7] mo; P = .30). Multivariate analysis demonstrated no association between the need for IABP and increased frequency of premature death. CONCLUSIONS: Use of IABP is not associated with premature or late death. We recommend use of IABP in patients with acute decompensated heart failure to stabilize them before HT.

Effect of hypertension, diabetes, and smoking on development of renal dysfunction after heart transplantation.

BACKGROUND: Renal dysfunction is a serious problem after heart transplantation (HT). The objective of this study was to determine the cardiovascular risk factors associated with medium- to long-term dysfunction after HT. MATERIALS AND METHODS: We studied 247 consecutive patients who underwent HT between January 2000 and September 2006 who survived for at least 6 months. We excluded patients receiving combination transplants, those undergoing repeat HT, and pediatric patients undergoing HT. Mean (SD) follow-up was 72 (42) months. We defined renal dysfunction as serum creatinine concentration greater than 1.4 mg/dL during follow-up. Patients were considered to be smokers if they had smoked during the six months before HT, to have hypertension if they required drugs for blood pressure control, and to have diabetes if they required insulin therapy. Statistical tests included the t test and the chi(2) tests. We performed Cox regression analysis using significant or nearly significant values in the univariate analysis. RESULTS: Mean (SD) age of the patients who underwent HT was 52 (10) years, and 217 (87.9%) were men. Renal dysfunction was detected during follow-up in 135 (54.5%) patients. The significant variables at univariate analysis were smoking (61.4% vs. 43.2%; P = .01) and previous renal dysfunction (94.1% vs 52.7%; P = .001). Nearly significant variables were the presence of hypertension before HT (63.8% vs 51.1%; P = .09) and after HT (58.2% vs 44.8%; P = .082). At multivariate analysis, pre-HT smoking and previous renal dysfunction were significant correlates (P = .04 and P = .01, respectively). CONCLUSIONS: Renal dysfunction is common after HT. In our analysis, the best predictors were pre-HT dysfunction and smoking. Less important factors were advanced age and post-HT hypertension.

Influence of traditional cardiovascular risk factors in the recipient on the development of cardiac allograft vasculopathy after heart transplantation.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the leading cause of death heart transplant (HT) recipients after the first year. We assessed the influence of cardiovascular risk factors (CVRFs) in HT recipients on the development of CAV after 1 year of follow-up. MATERIALS AND METHODS: From 2001 to 2005, we studied 72 patients who received a HT and survived for at least 1 years. All patients underwent coronary arteriography and intravascular ultrasonography at 1 year after HT. Cardiac allograft vasculopathy was defined as intimal proliferation of 0.5 mm or more. The analyzed CVRFs were age, sex, body mass index, diabetes mellitus, hypertension, dyslipidemia, and smoking. We also considered the heart disease that was the reason for HT. The statistical tests used in the univariate analysis were the t and chi(2) tests. Logistic regression was performed with the variables obtained at univariate analysis. RESULTS: Mean (SD) recipient age at HT was 51 (9) years. Eighty patients (90.5%) were men. Dyslipidemia was significantly associated with a greater incidence of CAV at 1 year (68.3% vs 41.9%; P = .03). Ischemia, as opposed to all other causes, was also significantly associated with CAV (69.4% vs 44.4%; P = .03). Older age, hypertension, smoking history, and high body mass index were associated with a higher incidence of CAV, albeit without statistical significance. At multivariate analysis, dyslipidemia was the most significant CVRF (P = .045) for the development of CAV. CONCLUSIONS: Recipient dyslipidemia is a risk factor for the development of CAV in HT. The remaining traditional CVRFs are more weakly associated with CAV. After HT close monitoring of recipients with pretransplantation CVRFs is essential for early detection of CAV.