First Report of a Successful Pregnancy in an Everolimus-Treated Heart-Transplanted Patient: Neonatal Disappearance of Immunosuppressive Drugs.

The use of everolimus (EVL) as primary immunosuppression is steadily increasing in heart transplantation (HTx) patients. Limited data currently exist in kidney transplantation, but there is no report of EVL use during pregnancy after HTx and its pharmacokinetics in the newborn. We report a case of an unplanned pregnancy discovered at 21 weeks of gestation in a female HTx patient aged 40 years treated with EVL and cyclosporine (CyA). Because pregnancy was advanced, immunosuppression therapy was left unchanged. At 36 weeks, a healthy infant was delivered. At birth, CyA blood levels were lower in the neonate, but EVL concentrations in maternal and neonatal umbilical blood were similar. Amniotic fluid concentrations were undetectable for both drugs. In the newborn, EVL was measurable at 5 days after birth, whereas CyA disappeared within 2 days. Cord blood displayed a normal count of B and T cells and CD4, CD8 and natural killer cell populations. At birth, both mother and newborn displayed the same blood levels of EVL; therefore, a filter effect of the placenta may be hypothesized for CyA but not for EVL. No immediate complications were observed with this pregnancy.

Outcome of patients listed for heart transplantation after a failed surgical ventricular restoration procedure.

Patients with end-stage ischemic cardiomyopathy (IHD) and left ventricular (LV) dilatation are increasingly treated by means of surgical ventricular restoration (SVR). In some patients, SVR can delay heart transplantation (HTX). We retrospectively analyzed our experience, trying to ascertain whether HTX after a failed SVR (fSVR) carried a greater mortality risk. Since 1985, we performed 742 HTX. Since June 1999, 133 IHD patients were listed for HTX. We assigned them to 3 groups: (A) not a redo (n=54); (B) redo after coronary artery bypass grafting (n=54); and (C) redo after fSVR (n=25). Respectively, 37, 33, and 12 patients underwent HTX with in-hospital mortality after HTX of 4/37 (10.8%), 12/33 (36.4%), and 2/12 (16.7%). Mortality on the list was 9/54 (16.7%), 11/54 (20.4%), and 7/25 (28.0%) respectively. Removal from the list occurred in 4, 5, and 2 patients, and 4, 5, and 4 patients are still awaiting HTX, respectively. In group C, the mean time from SVR to HTX list was 45.6+/-43.3 months, and list mortality occurred after 5.83+/-5.81 months. In-hospital mortality in both patients of group C was due to the occurrence of multisystem organ failure; 10/12 were extubated after 19.3+/-9.6 hours and discharged from the intensive care unit after 3.9+/-1.6 days. The recorded complications were: 3 acute renal failure, 1 pericardial effusion, and 2 episodes of acute rejection. Since only 5/25 patients with fSVR had undergone SVR at our institution, we cannot establish which patients were really eligible for HTX at the time of SVR. Our experience showed that patients listed for HTX displayed a high list mortality, but that HTX after a failed SVR did not seem to have a poorer outcome than HTX after previous conventional CABG.

Possible role of everolimus in improving renal function in long-term heart transplantation.

Patient survival after heart transplantation has improved dramatically since the availability of calcineurine inhibitor (CNIs); the number of long-term patients is progressively increasing. However, in these patients, nephrotoxicity of CNIs has been largely responsible for the progressive development of renal dysfunction. Since impaired renal function is an important issue that reduces long-term patient survival, it is important to develop strategies to improve renal function while maintaining immunologic safety to preserve graft function. Everolimus is an mTOR inhibitor sirolimus analogue, that has proved, to be highly efficacious to prevent acute myocardial rejection and reduce the severity of cardiac allograft vasculopathy in de novo HTx patients. There is reasonable evidence that, in long term heart transplanted patients, renal function may improve when everolimus is administered associated with a progressive reduction of CNIs. So far there is no evidence to identify which patient may benefit from this therapeutic approach. Indeed everolimus alone may be equally effective to prevent rejection and improve renal function when CNIs are completely discontinued, but data are still lacking on the risks, dosages and side effects of this type of immunosuppression. Ongoing clinical studies will provide further guidance about the possibility to halt or reduce the progression of renal impairment in long term heart transplant patients.

Doppler velocimetry in superior vena cava provides useful information on the right circulatory function in patients with congestive heart failure.

BACKGROUND: Although flow velocities curves recorded with pulsed-wave Doppler in systemic vein are known to provide functional data on the right circulatory function, little information is available on the relationship between right heart filling dynamics and right ventricular function. METHODS: Consecutive patients with chronic heart failure due to severe systolic left ventricular dysfunction and in sinus rhythm underwent echocardiography and right heart catheterization. In the initial part of the study, the hemodynamic correlates of different flow velocity patterns recorded into the superior vena cava were evaluated in 120 patients. The accuracy of the prediction of different right heart hemodynamic profiles by means of the different venous flow patterns was then prospectively tested in a subsequent series of 86 patients. RESULTS: The venous flow pattern was closely related to right heart hemodynamics. A normal Doppler pattern identified patients with normal right heart hemodynamics (sensitivity 86%, specificity 78%); a "predominant systolic wave" pattern identified patients with a reduced thermodilution-derived right ventricular ejection fraction (< 30%) and normal or slightly elevated right atrial pressure (< or = 8 mmHg) (sensitivity 69%, specificity 81%); a "predominant diastolic wave" pattern identified patients with a reduced right ventricular ejection fraction (< 3 0%) and elevated right atrial pressure (> 8 mmHg) (sensitivity 52%, specificity 95%). The observed and the predicted hemodynamic profiles turned out to be concordant in 80% of patients. CONCLUSIONS: The analysis of the flow velocity pattern into the superior vena cava is a useful tool to estimate the extent of the right circulatory impairment in patients with congestive heart failure.

Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure.

OBJECTIVES: We sought a better understanding of the coupling between right ventricular ejection fraction (RVEF) and pulmonary artery pressure (PAP), as it might improve the accuracy of the prognostic stratification of patients with heart failure. BACKGROUND: Despite the long-standing view that systolic function of the right ventricle (RV) is almost exclusively dependent on the afterload that this cardiac chamber must confront, recent studies claim that RV function is an independent prognostic factor in patients with chronic heart failure. METHODS: Right heart catheterization was performed in 377 consecutive patients with heart failure. RESULTS: During a median follow-up period of 17 +/- 9 months, 105 patients died and 35 underwent urgent heart transplantation. Pulmonary artery pressure and thermodilution-derived RVEF were inversely related (r = 0.66, p < 0.001). However, on Cox multivariate survival analysis, no interaction between such variables was found, and both turned out to be independent prognostic predictors (p < 0.001). It was found that RVEF was preserved in some patients with pulmonary hypertension, and that the prognosis of these patients was similar to that of the patients with normal PAP. In contrast, when PAP was normal, reduced RV function did not carry an additional risk. CONCLUSIONS: These observations emphasize the necessity of combining the right heart hemodynamic variables with a functional evaluation of the RV when trying to define the individual risk of patients with heart failure.

[Role of intersphincter resection among the surgical options for cancer of the distal rectum]. / Il ruolo della resezione intersfinterica fra le opzioni chirurgiche per il cancro del retto distale.

The surgical treatment of low rectal cancer has yet to be standardised. The aims of the study were to define the curative role of intersphincteric resection and to evaluate its indications and functional results through a retrospective clinical experience. From 1988 to 2000, out of 783 operations for primary rectal cancers (resectability rate 96%; restorative resections 83% and APR 10%) an intersphincteric resection was performed in 48 patients (31 male, 17 female, average age 62) for tumours located at a mean distance of 4.5 cm from the anal verge. Clinical stage: 27 T3 (56.3%), 12 T2, 5 T4 and 4 T1. All the operations were rated R0. TME with N-S, endo-anal distal transection and manual colo-anal anastomosis with a protective stoma were systematically performed. The mean follow-up was 46 months (range: 12-80). Functional results were evaluated with a prospective standardised questionnaire. There was no hospital mortality (30 days). The total morbidity rate was 22% with anastomotic leakage (clinical or X-ray evidence) in 12.5%. Four anal stenoses needed dilatation. Only one local recurrence six years after operation (2.1%). Nine patients died of systemic metastases within 3 years of surgery; the others are still alive and disease-free. Minor faecal incontinence with frequency and urgency occurred in 68.7% of cases at 3 months after protective stoma closure and in 37.5% after 6 months. After one year continence was good in 85.4% of survivors. Only one case required a permanent stoma for poststenotic total incontinence. The best functional results were achieved by colonic pouch reconstruction. For selected low rectal cancers (T2/T3) without voluntary sphincter infiltration, intersphincteric resection is safe and effective for oncological and functional purposes. The procedure requires accuracy in dissecting the anorectal junction. Preoperative radiotherapy may increase the indications for intersphincteric resection as well as the availability of a disease-free margin. A manual colo-anal anastomosis with colonic pouch interposition is strongly recommended.

Prognostic usefulness of the tricuspid annular plane systolic excursion in patients with congestive heart failure secondary to idiopathic or ischemic dilated cardiomyopathy.

The prognostic value of ultrasound evaluation of right ventricular (RV) performance in patients with congestive heart failure (CHF) is still a matter of investigation. We studied 140 consecutive patients with chronic CHF and a left ventricular ejection fraction <35%. All patients underwent a complete echocardiographic evaluation that systematically included the measurement of the tricuspid annular plane systolic excursion (TAPSE). During a follow-up period of 24 +/- 14 months, 45 patients died and 7 underwent emergency heart transplantation. At the multivariate survival analysis (Cox regression model) backward stepwise selection identified a prognostic model with 2 parameters: New York Heart Association (NYHA) class III or IV and TAPSE < or =14 mm (p <000). In a subgroup of 97 patients in sinus rhythm in whom mitral inflow Doppler variables could be measured, survival was further analyzed according to a model in which the significant parameters were included in the same order as usually used in routine clinical practice: clinical variables first, left ventricular function data second, mitral Doppler variables third, and indexes of right ventricular (RV) function last. TAPSE < or =14 mm added significant (p <0.03) prognostic information to NYHA class III or IV, left ventricular ejection fraction of <20%, and mitral deceleration time of < 125 ms. In conclusion, in patients with CHF, TAPSE adds significant prognostic information to the NYHA clinical classification, to the echocardiographic evaluation of left ventricular function, and to mitral Doppler variables. Furthermore, the measurement of TAPSE is easy to obtain in all patients, irrespective of heart rate and rhythm.

Value of right ventricular ejection fraction in predicting short-term prognosis of patients with severe chronic heart failure.

BACKGROUND: The prognosis of chronic heart failure has been studied extensively, but factors predicting short-term outcome in patients with severe chronic heart failure are still poorly defined, and the current indications for heart transplantation as a treatment for end-stage heart failure need on objective analysis. METHODS: Purpose of the study was to identify the determinants of short-term prognosis in a group of 142 consecutive ambulatory patients (mean age 49.8 +/- 11 years). Referred for heart transplantation because of severe chronic heart failure, the patients were admitted with left ventricular ejection fraction markedly depressed and had had symptoms in spite of an optimal standardized medical therapy for at least 1 month. Baseline clinical and instrumental evaluation included right-sided heart catheterization with a flow-directed multilumen thermodilution catheter, which enables determination of pressures, cardiac output, right ventricular volumes, and ejection fraction. RESULTS: Most patients were in New York Heart Association class III (61%) and IV (24%), and the hemodynamic profile was characterized by mean left ventricular ejection fraction of 20.2% +/- 6%, cardiac index of 2.13 +/- 0.6 l/min/m2, pulmonary capillary wedge pressure of 23.1 +/- 11 mm Hg, right atrial pressure of 7.9 +/- 6 mm Hg, right ventricular ejection fraction of 23.2% +/- 12.4%. During a mean follow-up of 11.1 +/- 9.4 months, 33 patients underwent transplantation (23.4%), 41 died (28.8%), and 68 were still alive (47.8%). There was a substantial overlap in left ventricular ejection fraction between patients divided on the basis of outcome, whereas right ventricular ejection fraction was significantly lower in patients who died or underwent transplantation. Cox multivariate analysis showed three independent prognostic variables: cause (p = 0.03), heart failure score (p = 0.001), and right ventricular ejection fraction (p = 0.000). Short-term survival (10 months) was significantly (p = 0.000) different in patients with > or = 24% or < 24% right ventricular ejection fraction. Statistical analysis identified right ventricular ejection fraction as the single variable to be highly correlated with an increased risk of early death. CONCLUSIONS: This study suggests that right ventricular function is a crucial determinant of short-term prognosis in severe chronic heart failure. Statistical analysis identified right ventricular ejection fraction, determined by thermodilution during right-sided heart catheterization, as the single most important predictor of short-term prognosis in a large cohort of patients who had symptoms in spite of a standardized, optimized, multipharmacologic treatment. The variable allows a useful risk stratification in patients with severe chronic heart failure and uniformly depressed left ventricular ejection fraction and provides guidance in the assessment of indications and timing for transplantation.

[Ileal stenosis caused by chronic granulomatous inflammation secondary to a foreign body simulating Crohn disease]. / Stenosi ileale da flogosi granulomatosa cronica da corpo estraneo simulante morbo di Crohn.

A case of ileal stenosis due to foreign body induced chronic granulomatous inflammation simulating Crohn's disease with onset on an ileo-ileostomy carried out 23 years before due to iatrogenic rupture of ileal loop following clandestine abortion is reported. After noting the problem of attributing to the foreign body alone responsibility for the stenosis, the hypothesis that it might have been an acute occurrence of Crohn's disease or the expression of an association of Crohn's disease and granulomatous inflammation due to surgical material is advanced. This for the moment is the only plausible cause. It is concluded that for accurate nosological classification and, therefore, definitive clinical diagnosis, prolonged clinical control of the patient is indispensable.

[Spontaneous hemoperitoneum caused by hemorrhage and the rupture of pancreatic pseudocysts]. / L'emoperitoneo spontaneo da emorragia e rottura di pseudocisti pancreatica.

Two cases of haemoperitoneum due to haemorrhage and rupture of pancreatic pseudocyst in the peritoneal cavity are reported. After mentioning the exceptional nature of this complication in pancreatic pathology, the particular features of these cases are stressed, stress being laid particularly on the usefulness of echography which should be preferred to selective angiography for the usual reasons of speed of execution and harmlessness of the examination which can be carried out at the bedside if a portable echography unit is available.