L-arginine and Its Derivatives Correlate with Exercise Capacity in Patients with Advanced Heart Failure.

Methylated arginine metabolites interrupt nitric oxide synthesis, which can result in endothelium dysfunction and inadequate vasodilation. Since little is known about the dynamics of arginine derivatives in patients with heart failure (HF) during physical exercise, we aimed to determine this as well as its impact on the patient outcomes. Fifty-one patients with HF (left ventricle ejection fraction-LVEF ≤ 35%, mean 21.7 ± 5.4%) underwent the cardiopulmonary exercise test (CPET). Plasma concentrations of L-arginine, citrulline, ornithine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) were measured before and directly after CPET. All patients were followed for a mean of 23.5 ± 12.6 months. The combined endpoint was: any death, urgent heart transplantation, or urgent LVAD implantation. L-arginine concentrations increased significantly after CPET (p = 0.02), when ADMA (p = 0.01) and SDMA (p = 0.0005) decreased. The parameters of better exercise capacity were positively correlated with post-CPET concentration of L-arginine and inversely with post-CPET changes in ADMA, SDMA, and baseline and post-CPET SDMA concentrations. Baseline and post-CPET SDMA concentrations increased the risk of endpoint occurrence (HR 1.02, 95% CI 1.009-1.03, p = 0.04 and HR 1.02, 95% CI 1.01-1.03, p = 0.02, respectively). In conclusion, in patients with HF, extensive exercise is accompanied by changes in arginine derivatives that can reflect endothelium function. These observations may contribute to the explanation of the pathophysiology of exercise intolerance in HF.

Heart Transplantation and Risk of Cardiac Vasculopathy Development: What Factors Are Important?

BACKGROUND The aim of this study was to find the main risk factors for development of cardiac allograft vasculopathy (CAV), especially factors identified before the surgical procedure and factors related to the recipient profile and the medical history of the donor. MATERIAL AND METHODS There were 147 patients who had heart transplantation (HT) included in this study: mean age was 45.8±15.3 years. All study patients had coronary angiography after HT. Analyzed risk factors were: non-immunologic recipient risk factors (age of transplantation, smoking, hypertension, lipids, diabetes, obesity and weight gain after HT), immunologic recipient risk factors (acute cellular rejection (ACR), acute humoral rejection (AMR), cytomegalovirus (CMV) episodes), and donor-related risk factors (age, sex, catecholamine usage, ischemic time, compatibility of sex and blood groups, cause of death, cardiac arrest). RESULTS CAV was recognized in 48 patients (CAV group); mean age 53.6±13.6 years. There were 99 patients without CAV (nonCAV group); mean age 48.3±15.5 years. A univariate Cox analysis of the development of coronary disease showed statistical significance (p<0.05) for baseline high-density lipid (HDL), ACR, AMR, CMV, and donor age. Multivariate Cox regression model confirmed that only baseline HDL, episodes of ACR, donor age, and CMV infection are significant for the frequency of CAV after HT. CONCLUSIONS Older donor age is highly associated with CAV development. Older donor age and low level of HDL in heart recipients with the strongest influence of immunologic risk factors (ACR, CMV infection) were linked with development of CAV.

Incidence of malignancies in cardiac allograft recipients - a single-center experience.

BACKGROUND: Most of the available data suggest that the risk of malignancy in solid organ recipients is higher than in the general population. In Poland, the prevalence rate for malignancy in the general population is about 1.02%. MATERIAL AND METHODS: At out Outpatient Clinic for patients after heart transplantation we analyzed all 324 patients transplanted from 1987-2011 for the presence of malignancies. The end-point of the analysis was determined by malignancy diagnosis, patient death, or end of the observation period (December 12, 2011). RESULTS: We detected 31 malignancies in 29 of 324 patients (8.95%). In 2 patients we found 2 types of malignancies. The dominant type of malignancy was pulmonary carcinoma, diagnosed in 11/29 (37.93%) patients. Skin carcinoma was recognized in 7 patients (24.14%). Fourteen (48.3%) patients died (12 men and 2 women): 5 of them in the course of pulmonary carcinoma (35.7%), 3 of skin carcinoma (21.4), 3 in the course of lymphoma, 1 in the course of renal carcinoma, 1 in the course of stomach carcinoma, 1 of colorectal carcinoma, and 1 of prostatic carcinoma. CONCLUSIONS: The risk of malignancy development is many times higher for HT patients than in the general population. The high incidence rate for pulmonary carcinoma in the analyzed group of patients was most likely related to smoking before transplantation and continuation of smoking after the procedure in the case of patients who received immunosuppressive therapy.

Usefulness of dual-source computed tomography for the evaluation of coronary arteries in heart transplant recipients.

BACKGROUND: Heart transplant recipients require serial assessment of coronary arteries due to a risk of cardiac allograft vasculopathy or atherosclerosis. Currently available non-invasive imaging methods are of a limited value for the detection of coronary stenoses, and thus invasive coronary angiography (ICA) is recommended. AIM: We evaluated diagnostic accuracy and clinical usefulness of dual-source computed tomography (DSCT) as a potential alternative to ICA for the detection of coronary stenoses. METHODS: DSCT was performed in 20 consecutive heart transplant recipients (15 males, mean age 47.5 years) who were scheduled for ICA. Exclusion criteria included renal dysfunction with creatinine clearance <45 mL/min and lack of patient consent. All examinations were performed using a first generation dual-source scanner and a retrospectively ECG-gated protocol. Data sets were routinely reconstructed in best-systolic and best-diastolic phases. We evaluated presence of a >50% stenosis in a vessel with a diameter of >1.0 mm, image quality of each segment, and radiation dose delivered to the patient. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were calculated in per segment, per vessel, and per patient analyses, with ICA considered the reference method. RESULTS: All DSCT and ICA examinations were diagnostic and performed without any complications. Mean heart rate was 85 bpm (range 63-114), and was stable in 85% of patients. Significant stenoses (>50%) were diagnosed by DSCT in 4 of the 287 segments, and these findings were confirmed by ICA in 2 segments. Sensitivity, specificity, and diagnostic accuracy were: (1) in the per segment analysis, 100%, 99%, and 99%, respectively, for the left coronary artery; and 100% each for the right coronary artery; (2) 100%, 97%, and 97%, respectively, in the per vessel analysis; and (3) 100%, 94%, 95%, respectively, in the per patient analysis. In diastolic reconstructions, right coronary segments were significantly more commonly nondiagnostic than left coronary segments (25% vs. 11.5%, p = 0.003). In contrast, right coronary segments showed better quality than left coronary segments in systolic reconstructions (63.5% vs. 42.2%, p <0.001). Mean effective radiation dose was 12.7 (range 5.4-18.7) mSv. CONCLUSIONS: DSCT is a clinically useful alternative to invasive coronary angiography for excluding significant coronary stenoses in heart transplant recipients. The negative predictive value of this modality is very high. Sensitivity, specificity and diagnostic accuracy is acceptably high. Imaging of coronary arteries in patients with high heart rates in technically feasible, but require modifications of routine exam protocol. Using of modern prospectively ECG-triggered protocols is not reccommended.