Stress-induced cardiomyopathy (takotsubo cardiomyopathy) after liver transplantation-report of two cases.

Cardiac complications after liver transplantation are a common cause of death. Stress-induced cardiomyopathy, also called takotsubo cardiomyopathy, is a special form of cardiomyopathy that is precipitated by a stress situation. It can occur after a surgical procedure that results in acute heart failure. Herein we have presented 2 cases of reversible stress-induced cardiac dysfunction early in the period after liver transplantation. Before surgery, cardiac evaluation was normal, with both patients classified as low risk for cardiovascular events during the proposed procedure. Both patients experienced cardiac arrest after graft reperfusion with return of spontaneous circulation after resuscitation. Their early periods after transplantation were characterized by cardiogenic shock secondary to important ventricular dysfunction requiring vasoactive drugs. Subsequent investigations excluded coronary disease. The diagnosis of takotsubo cardiomyopathy was established based on the clinical features and ancillary tests, particularly echocardiography showing apical ballooning. In both cases, ventricular function recovered completely. In conclusion, stress-induced cardiomyopathy, an underestimated cause of heart complications, should be considered as a possible cause of cardiac failure in liver transplant patients.

Validation of a cutoff value on echo Doppler analysis to replace right heart catheterization during pulmonary hypertension evaluation in heart transplant candidates.

BACKGROUND: Heart transplantation (OHT) has traditionally been contraindicated in the presence of severe pulmonary hypertension (PH), as detected by right heart catheterization. Noninvasive methods are still not reliably accurate to make this evaluation. OBJECTIVES: Determine the efficacy of echo Doppler analysis for the diagnosis of severe PH. METHODS: One hundred thirty patients (mean age = 42 +/- 15 years, 82 men) showed severe left ventricular dysfunction (mean ejection fraction = 29 +/- 12%; functional class III-IV). We excluded patients with atrial fibrillation, heart failure secondary to congenital disease, and valvulopathy. The pulmonary parameters defined as severe PH were: systolic pulmonary artery pressure (sPAP) >or= 60 mm Hg; a mean transpulmonary gradient >or= 15; or pulmonary vascular resistance >or= 5 Wood units. Patients underwent a right heart catheterization using a Swan-Ganz catheter to measure hemodynamic parameters and to noninvasively estimate right-sided pressures from spectral Doppler recordings of tricuspid regurgitation velocity (right ventricular systolic pressure [RVsP]). A Pearson correlation of sPAP was obtained with RVsP by; the sensitivity of RVsP for the diagnosis of PH was determined by a receiver operating characteristic (ROC) curve. RESULTS: A good correlation between sPAP and RVsP was obtained by Pearson correlation analysis (r = 0.64; 95% confidence interval [CI] 0.50-0.75; P < .001). The ROC curve analysis showed a sensitivity of 100%, a specificity of 37.2%, (95% CI 0.69-0.83, P < .0001) of a RVsP < 45 mm Hg (cutoff) on the exclusion of severe PH. CONCLUSIONS: The cutoff of RVsP < 45 mm Hg, on noninvasive echo Doppler evaluation of PH is an efficient method to replace invasive heart catheterization in OHT candidates.

Dobutamine stress echocardiography in heart transplant recipients' evaluation: the role of reinnervation.

INTRODUCTION: Orthotopic heart transplantation renders the recipient denervated. This remodeling of the intrinsic cardiac nervous system should be taken in account during functional evaluation for allograft coronary artery disease. Dobutamine stress echocardiography (DSE) has been used to detect patients at greater risk. The aim of this study was to determine whether patients with various autonomic response levels, and supposed reinnervation patterns, show the same response to DSE. METHODS: We studied 20 patients who had survived more than 5 years after orthotopic heart transplantation. All patients underwent a Holter evaluation. We considered patients with low variability to be those with less than a 40-bpm variation from the lowest to highest heart rate, so-called "noninnenervated" (group NI). Patients who had 40-bpm or more variation were considered to show high variability and called "reinnervated" (group RI). After that, all patients performed an ergometric test and DSE. RESULTS: Groups were defined as NI (n = 9) and RI (n = 11). Ergometric tests confirmed this response with NI patients showing less variability when compared to RI patients (P = .0401). During DSE, patients showed similar median heart rate responses according to the dobutamine dose. Spearmen correlation showed r = 1.0 (P = .016). CONCLUSIONS: DES was effective to reach higher heart rates, probably related to catecholamine infusion. These findings may justify a better response when evaluating cardiac allograft vasculopathy in heart transplant patients.

Recovery of renal function in heart transplantation patients after conversion from a calcineurin inhibitor-based therapy to sirolimus.

BACKGROUND: Renal failure is the most important comorbidity in patients with heart transplantation, it is associated with increased mortality. The major cause of renal dysfunction is the toxic effects of calcineurin inhibitors (CNI). Sirolimus, a proliferation signal inhibitor, is an imunossupressant recently introduced in cardiac transplantation. Its nonnephrotoxic properties make it an attractive immunosuppressive agent for patients with renal dysfunction. In this study, we evaluated the improvement in renal function after switching the CNI to sirolimus among patients with new-onset kidney dysfunction after heart transplantation. METHODS: The study included orthotopic cardiac transplant (OHT) patients who required discontinuation of CNI due to worsening renal function (creatinine clearance < 50 mL/min). We excluded subjects who had another indication for initiation of sirolimus, that is, rejection, malignancy, or allograft vasculopathy. The patients were followed for 6 months. The creatinine clearance (CrCl) was estimated according to the Cockcroft-Gault equation using the baseline weight and the serum creatinine at the time of introduction of sirolimus and 6 months there after. Nine patients were included, 7 (78%) were males and the overall mean age was 60.1 +/- 12.3 years and time since transplantation 8.7 +/- 6.1 years. The allograft was beyond 1 year in all patients. There was a significant improvement in the serum creatinine (2.98 +/- 0.9 to 1.69 +/- 0.5 mg/dL, P = .01) and CrCl (24.9 +/- 6.5 to 45.7 +/- 17.2 mL/min, P = .005) at 6 months follow-up. CONCLUSION: The replacement of CNI by sirolimus for imunosuppressive therapy for patients with renal failure after OHT was associated with a significant improvement in renal function after 6 months.

Cardiomyopathy, adult valve disease and heart failure in South America.

Continued assessment of temporal trends in mortality and epidemiology of specific cardiovascular diseases in South America is needed to provide a scientific basis for rational allocation of the limited healthcare resources and introduction of strategies to reduce risk and predict the future burden of cardiovascular disease. The epidemiology of cardiomyopathies, adult valve disease and heart failure (HF) in South America is reviewed here. Diseases of the circulatory system are the main cause of death based on data from about 50% of the South American population. Among the cardiovascular causes of death, cerebrovascular disease is predominant followed by ischaemic heart disease, other heart diseases and hypertensive disease. Of note, cerebrovascular disease is the main cause of death in women, and race also influenced cardiovascular mortality rates. HF is the most important cardiovascular reason for admission to hospital due to cardiovascular disease of ischaemic, idiopathic dilated cardiomyopathic, valvular, hypertensive and chagasic aetiologies. Also, mortality due to HF is high, especially owing to Chagas' disease. HF and aetiologies associated with HF are responsible for 6.3% of deaths. Rheumatic fever is the leading cause of valvular heart disease. The findings have important public health implications because the allocation of healthcare resources, and strategies to reduce the risk of HF should also consider controlling Chagas' disease and rheumatic fever in South American countries.

[Headache in a pediatric emergency department]. / La cefalea in pronto soccorso pediatrico.

INTRODUCTION: Headache, a very frequent symptom in pediatrics, can severely affect the child and his family's life quality, representing an important reason of access to a Pediatric Emergency Department. From a clinical point of view, it is useful to subdivide headaches in primary and secondary ones. As far as the primary ones are concerned, the common migraine without aura is recognised as the most frequent in the child, while the most recurrent among the second ones are due to infective processes, and they represent 57% of the patients admitted to ED for headache with acute onset. MATERIALS AND METHODS: We analyzed data collected from June 2000 to December 2006, at the Pediatric Emergency Department of Institute "G. Gaslini" Genoa, concerning the admissions of patients with headache, with particular attention to the necessity of coming up with a clinical and diagnostical path. RESULTS: During the study, there have been 228.255 admissions, 2.214 of which with a diagnosis of discharge from ED of headache (55% males, 45% females). After triage, 14,3% has been evaluated as white code, 74,3% as green one, 10,8% as yellow one and 0,6% as red code. Final outcome of these patients has been hospitalization for 38%, OBI for 8%, home or ambulatory control for 54%. CONCLUSIONS: The accesses to ED for headache are increasing. Better information of the family is needed, with coordination among territorial structures and clinic management in ED.

Optimization of emergency department management of infants with bronchiolitis.

Bronchiolitis is the most common lower respiratory tract infection in infants < 2 years of age; in the last decades both incidence and hospitalization rate had increased, thus increasing sanitary burden. From November 2006 to March 2007, an experimental protocol was followed in the Emergency Department at G. Gaslini Children's Hospital, Genoa, Italy, which attempted to optimise the management of patients with bronchiolitis and to reduce the overall hospitalization rate therefore admitting only those patients with severe illness. All clinical evaluations of the patients were obtained administering a score (Bronchiolitis Clinical Score - BCS), to quantify both initial severity of illness and response to treatment. All patient were at first treated with inhaled epinephrine, supplemented with or substituted by other drugs, if needed, according to clinical evolution. Moreover, strict admission and discharge criteria were defined, taking into consideration the BCS, response to treatment and the presence of risk factors for severe disease, attempting to increase the role of the Short Stay Unit (SSU). The outcome evaluated were the percentage of patients discharged, admitted and managed through the SSU respectively, the length of stay and the readmission rate after discharge; data collected were then compared to that regarding patients with bronchiolitis presented at the ED from November 2005 to March 2006. Our data showed an increasing of both discharged patients (37.5% vs 25.22%) and patients managed through the SSU (25.83% vs 19.57%) and a related decrease of hospitalization (36.67% vs 55.22%); no significative difference was observed regarding the readmission rate between the two populations. We also observed a statistically significant reduction of the length of stay in the study population (2.07 +/- 2.56 vs 2.84 +/- 3.25, p = 0.005). In conclusion, the protocol proposed showed to be useful in optimizing the ED management of the patient with bronchiolitis, being able to safely reduce both admission rate and lenght of stay.

Protein and m-RNA expression of farnesyl-transferases, RhoA and RhoB in rat liver hepatocytes: action of perillyl alcohol and vitamin A in vivo.

We analysed the action, in rats in vivo, of the protein isoprenylation inhibitor perillyl alcohol (POH) and that of vitamin A, alone or in association, on m-RNA and protein expression of farnesyltransferases (FTases alpha and beta subunits) and their protein substrates RhoA and RhoB, in isolated hepatocytes. Combined administration of POH and vitamin A induced a sharp decrease in FTase alpha protein after 96 h, suggesting an involvement not only of farnesyltransferases but also of geranylgeranyltransferases, which share the FTase alpha protein. FTase beta protein did not decrease. POH plus vitamin A, in contrast with POH or vitamin A alone, induced a decrease in RhoB protein, probably because of different cleavages. No modification was observed in RhoA protein. Vitamin A alone increased RhoB m-RNA and protein expression. As one of the functions of RhoB is cell polarisation, these data support our previous hypothesis of a polarised transport of vitamin A from hepatocytes to hepatic stellate cells. As the behaviours of m-RNAs and proteins in this study were often different, cytoplasmic metabolic pathways must be considered for the parameters studied. The behaviour of Rho B, which is thought to have an antioncogene function, is discussed in view of its isoprenylated forms in the membranes. These preliminary findings stress the need, when studying the association of two isoprenoids in cancer therapy, to consider normal as well as tumour-bearing animals.

Organochlorine residues in human adipose and hepatic tissues from autopsy sources in northern Italy.

Organochlorine compounds have been analyzed in human samples from residents of Genoa, a city in Northern Italy. Twenty-eight specimens of adipose tissue from 17 males and 11 females deceased from accidental causes in March and April 1989 were examined. In 12 of the 17 males, liver tissue specimens were also analyzed. DDE was the major organochlorine pesticide (OCP) found in all human adipose tissues (395 +/- 264 ng/g); additional OCPs found in our series of human subjects with an occurrence greater than 80% included p,p-DDT (64 +/- 31 ng/g), lindane (104 +/- 93 ng/g), and beta-BHC (213 +/- 260 ng/g). Statistical analysis showed positive correlation of DDE and p,p-DDT with age with an annual increase of 7 ng/yr and 0.9 ng/yr, respectively. No statistically significant differences were found for OCPs concentration between sexes. In DDE to sigma DDT (o,p-DDT + p,p-DDT + o,p-TDE + p,p-TDE) ratio changed in the last two decades from 0.95 (1966) to 5.2. Significant correlation was found between paired liver-adipose tissues concentrations of DDE and p,p-DDT (1:2 ratio). No correlation was found between age of subjects and the DDE to sigma DDT ratio. This study indicates that the ban on DDT use as a pesticide has been largely effective in Liguria, as supported by the lower concentrations of the compound in youngsters and the increase in the DDE to sigma DDT ratio with time. However, other data, such as the lack of correlation between age of subject and the DDE to sigma DDT ratio, indicate that intake of minimal amounts of DDT may have taken place even recently. This intake could depend on contamination of food imported from abroad or on illegal, or incorrect, use of these compounds in Italy.

Propionyl-L-carnitine: a new compound in the metabolic approach to the treatment of effort angina.

The effects of propionyl-L-carnitine on exercise tolerance of 12 patients with stable exertional angina were assessed in a double-blind, placebo-controlled, cross-over protocol using serial exercise tests. Compared to placebo, propionyl-L-carnitine significantly increased total work from 514 +/- 199 to 600 +/- 209 W (P less than 0.05) (17%) and prolonged exercise time and time to ischemic threshold from 515 +/- 115 to 565 +/- 109 sec (P less than 0.05) (10%) and from 375 +/- 102 to 427 +/- 93 sec (P less than 0.01) (14%), respectively. ST segment depression at the highest common work level was significantly reduced from 0.19 +/- 0.08 to 0.15 +/- 0.08 mV (P less than 0.05) (21%). No significant changes in heart rate, systolic blood pressure, and rate-pressure product at rest, at the highest common work level, on appearance of the ischemic threshold, or at peak exercise were observed after propionyl-L-carnitine treatment. No side effects were observed under propionyl-L-carnitine treatment. This study shows that propionyl-L-carnitine can significantly improve exercise tolerance in patients with stable angina. Our data seem to confirm that propionyl-L-carnitine most likely exerts its protective action via the metabolic pathway.

Evaluation of pentisomide on stable ventricular premature beats. Comparison with placebo.

Pentisomide, a new class I anti-arrhythmic drug, was compared to placebo in 50 hospitalized patients with frequent (greater than 30 h-1) and stable ventricular premature beats (VPB) (variation less than 50% between two preliminary and one placebo 24-h Holter recordings). All patients underwent a single-dose acute oral testing followed by a short-term testing with 300 mg t.i.d. for 4 days and then by a 4-day placebo period. For the studied population, a 56.4% reduction of simple VPB and a 98.8% decrease of couplets and runs were the minimum required to define the drug efficacy and to exclude spontaneous variability, using the linear regression analysis. Pentisomide was found effective in 27 (54%) of the 50 patients after the acute test and in 23 (46%) after the short-term test. The drug induced a mild increase of PR and QRS intervals, while QTc, heart rate, blood pressure and ejection fraction showed no significant variations. Subjective tolerability was excellent.

[Efficacy and length of action of a slow-release formulation of isosorbide-5-mononitrate in stable effort angina]. / Efficacia e durata d'azione di una formulazione a lento rilascio di isosorbide-5-mononitrato nell'angina da sforzo stabile.

This double-blind randomized placebo-controlled study was designed to evaluate the acute effects of orally administered slow-release isosorbide-5-mononitrate (SR IS-5-MN) in 12 patients with chronic stable angina. After a prestudy screening to assess the reproducibility of exercise response, the patients entered the study lasting 5 days. On the first and fourth day of the trial, each patient underwent a bicycle exercise test 4, 8 and 24 hours after acute administration of SR IS-5-MN 50 mg or placebo. Statistic analysis of the results was performed using a 2-way analysis of variance for cross-over design. Compared to placebo, 4 hours after administration, SR IS-5-MN prolonged the exercise time from 525 +/- 162 s to 685 +/- 207 s (p less than 0.05; 30%) and - 1mm time from 437 +/- 147 s to 562 +/- 219 (p less than 0.05; 29%). After 8 hours SR IS-5-MN prolonged the exercise time from 510 +/- 145 s to 615 +/- 189 s (p:ns; 21%), and - 1mm time from 415 +/- 128 s to 522 +/- 205 s (p less than 0.05; 26%). No significant changes were observed 24 hours after SR IS-5-MN administration. The maximal rate-pressure product was significantly increased by SR IS-5-MN 4 hours after administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective evaluation of gallopamil in patients with chronic stable angina. Exercise testing, Holter monitoring, cross-sectional echocardiography and plasma levels.

In this double-blind, randomized placebo-controlled study the effects of two dosages of gallopamil on exercise tolerance were evaluated in 12 patients with stable effort angina. After a pre-study screening aimed at assessing the reproducibility of the exercise response, the patients entered the study which consisted of three 7-day consecutive periods during which placebo or gallopamil 50 mg t.i.d. or gallopamil 75 mg t.i.d. were administered according to a randomized sequence. 24-hour Holter monitoring and cross-sectional echocardiography were performed on the 6th and 7th day of each treatment period, respectively. On the 7th day of each treatment period, patients underwent an exercise test 2 and 8 h after the last administration of gallopamil or placebo. Blood samples for plasma gallopamil concentrations were taken just before each exercise test. The results were analysed using a three-way analysis of variance; intergroup differences were evaluated by the Newman-Keuls test. At 2 h, 11 patients with placebo and three with gallopamil experienced angina; both dosages of gallopamil significantly prolonged exercise time and -1 mm time and also reduced ST segment depression and the rate-pressure product at submaximal workload. No significant change in the rate-pressure product was observed either on the appearance of 1 mm ST depression or at peak exercise. At 8 h, 11 patients with placebo and gallopamil 50 mg t.i.d. and 10 with gallopamil 75 mg t.i.d. experienced angina; although exercise time was significantly prolonged by both dosages of gallopamil, the increase in -1 mm time and reduction of ST segment depression at submaximal workload did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)