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Background. Superimposed acute right ventricular dysfunction in the setting of preexisting pulmonary hypertension is a nearly fatal complication after heart transplantation. The optimal treatment modality remains a matter of debate. Recently, sildenafil citrate, a nonselective pulmonary vasodilator, has gained popularity in the treatment of pulmonary hypertension in transplant candidates. Methods. Herein we have presented a series of 13 patients in whom sildenafil was used to treat right ventricular dysfunction and pulmonary hypertension as detected by transesophageal echocardiography and Swan-Ganz right heart catheterization after heart transplant. Their characteristics were mean age 49 11.4 years; 38.4% with previous cardiac procedures, 30.8% status I, basal pulmonary vascular resistance index 10.4 4.6 WoodU, mean transpulmonary gradient 18.7 5.4 mmHg. In addition to conventional inodilator support, we administered 1 to 3 mg per kilogram of sildenafil. Complete hemodynamic measurements were obtained before and after the institution of the therapy and at 1-month follow-up. Results. Within the first 72 hours, acute right ventricular dysfunction resolved in all cases without untoward side effects or significant systemic impact. Sildenafil significantly decreased the transpulmonary gradient and pulmonary vascular resistance index relative to baseline values; 5.6 1.82 versus 10.4 4.6 WU, (P .05), 13.5 3.4 mm Hg versus 18.7 5.4 mm Hg (P .05), respectively. Improved indices of right ventricular function were observed on echocardiographic monitoring. After 1 month, sildenafil treatment was discontinued. Conclusion. Management of acute right ventricular dysfunction in heart transplant recipients with pulmonary hypertension using sildenafil proved safe and effective.

Cryptococcosis primarily occurs in patients with impaired immune response. While pulmonary and/or cerebral involvement are more often described, there is limited experience of its presence in other sites. We present a case of hepatic cryptococcosis with possible pulmonary involvement in a 54-year-old male heart transplant recipient. Two months after heart transplantation, he developed a persistent, moderate dyspnea with fever and signs of liver damage. Diagnosis was made with liver biopsy for a concurrent reactivation of chronic hepatitis B virus (HBV) infection already present before transplant. Along with a mild chronic HBV hepatitis with fibrosis, we observed sinusoidal dilation and groups of bright, rounded, colorless cells with a central nucleus suggestive of cryptococci. Periodic acid–Schiff stain clearly showed encapsulated yeasts, which supported the diagnosis. Cryptococcal antigen was positive in serum and negative in the cerebrospinal fluid. Computed tomography scan of the chest demonstrated a mild interstitial infiltrate. The patient promptly responded to reduction of immunosuppressive therapy and antifungal treatment with amphotericin B lipid complex and flucytosine followed by maintenance treatment with fluconazole. Cryptococcosis should always be considered in the differential diagnosis in immunocompromised hosts with dyspnea and signs of extrapulmonary involvement. Diagnosis of extrapulmonary and extraneural cryptococcosis is difficult and often fortuitous; a histopathological examination of tissues involved is probably warranted.

Results after isolated aortic valve replacement with bileaflet prostheses in patients over 70 years old were reviewed. One-hundred-twenty-eight elderly patients were operated on between January 1988 and January 2000. Patients with associated heart disease were excluded from the study. Preoperative data, early and late postoperative mortality, all valve related complications and data concerning anticoagulation status were recorded. Hospital mortality was 9.3%. Mean follow-up time was 60.98±2.23 months. Twelve-year actuarial survival was 69.6±0.08%. Valve related and anticoagulation related complication rates (0.8% and 1.6% respectively) and actuarial freedom (99±0.009 both) were low, as well as the mean interval between consecutive INR checks (18.39±1.90 days) and the mean INR value (2.17±0.135). Late echocardiographic results showed low postoperative mean transprosthetic gradients (15.48±0.94). Bileaftlet prostheses in the elderly can achieve excellent results with a low incidence of anticoagulation related complications and low risk of reoperation. Older age can no longer be considered a contraindication to bileaftlet prosthesis implant.

Although new models of bileaflet valves with improved orifice have been devised, aortic valve replacement with 19mm prostheses still raises concerns about long term effects of residual transprosthetic gradient. We reviewed our experience with 19 mm standard model St Jude prostheses in 68 patients operated on between January 1983 and December 1995. Clinical late assessment was performed to evaluate the incidence of valve related complications. Postoperative echocardiography was performed to evaluate hemodynamic performance of the prostheses. Mean body surface area was 1.66±0.14m2. Late postoperative peak gradient was 53.85±7.16 mmHg; mean gradient was 34.80±5.55 mm Hg; effective orifice area was 1.93±0.05 cm2. Thirteen-year actuarial survival has been 90.89 ± 0.6%; thirteen-year freedom from embolism 89.41 ± 0.7% and freedom from hemorrhage 98.25 ± 0.02%. No case of prosthetic endocarditis, thrombosis, or reoperation was observed during follow-up.

Advanced heart failure is becoming an increasing cause of mortality and morbidity in a large number of patients. Heart transplantation is the treatment of choice for many selected patients in this group. According to the clinical status at the time of transplant, patients may have a different outcome related to the early survival, while the late results are similar and not affected by the patient’s initial clinical status. All surviving patients showed recovery of kidney function as soon the cardiac output was restored to normal values. High urine output was present in a large number of patients in the early postoperative period. However, in severely ill patients with cardiac index 2, diuretic resistance and mortality were higher.

Objectives. Cytomegalovirus (CMV) disease often represents a serious complication that promotes opportunistic infections in heart transplant recipients. In this study we evaluated the impact of preemptive gancylovir therapy, guided by pp65 antigenemia on the morbidity associated with viral reactivation. Patients and methods. We have performed a CMV infection surveillance program since March 1999, with antigenemia pp65 determinations weekly for the first 2 months biweekly in the third months, and monthly to the sixth month. Patients with pp65 antigenemia value 10 positive cells per 2 10 5 polymorphonuclear cells (PMN) were treated with intravenous gancyclovir followed by 1 month of oral gancyclovir. Results. Among the 107 patients who underwent the virological monitoring, 80 were pp65 antigenemia-positive with preemptive therapy administered in 48 cases. Five patients displayed symptomatic CMV disease (4.7% vs 18% rate in the period of 1988 to 1998 before the introduction of virologic monitoring; P .01). We observed only one case of gancyclovir-resistant pneumonia which was successfully treated with foscarnet. CMV recurrence in 10 patients required a second cycle of gancyclovir treatment. Our experience included 13 opportunistic infections (12.7%) with 11 antigenemia-positive. Conclusions. Preemptive therapy drastically reduces the incidence of CMV disease and the associated morbidity. Compared to universal prophylaxis, this approach may avoid unnecessary pharmacologic treatment in more than 50% of transplant recipients. Indeed, preemptive therapy does not fully prevent CMV disease, because it may manifest at the first antigenemia determination, and furthermore may select gancyclovir-resistant strains.

Objective This retrospective single-center report sought to evaluate the relation of immunosuppressive regimen with the incidence and characteristics of cytomegalovirus (CMV) infection from 1999 to 2003. Patients and methods Immunosuppression consisted of cyclosporine microemulsion (Neoral), azathioprine (AZA), and prednisolone associated with either thymoglobulin or ATG high-dosage induction from 1999 to 2000 (AZA, 64 patients [AZA-Thymo = 38 patients and AZA-ATG 26 patients]), or cyclosporine microemulsion (Neoral), mycophenolate mofetil (MMF), and prednisolone with low-dose thymoglobulin induction from 2001 onward (n = 52 patients). Ganciclovir preemptive therapy was guided by pp65 antigenemia monitoring without CMV prophylaxis. Results The study groups were homogeneous with respect to major perioperative risk factors. Comparing the two AZA subgroups no difference emerged as to percentage of pp65 antigenemia-positive, preemptively treated patients reflecting CMV disease incidence and relapses. AZA-Thymo patient showed significantly shorter time to first positive pp65-antigenemia and higher viral load (AZA-Thymo vs AZA-ATG, P = .004 and P = .009). The two subgroups did not differ with regard to incidence of rejection, superinfection, and graft coronary disease. By shifting from AZA to MMF no difference emerged as to incidence and characteristics of CMV infections, but there was a significant reduction in acute rejection and superinfection (AZA vs MMF P = .001 and P = .008). Conclusions The distinct immunological properties of thymoglobulin versus ATG significantly altered the pattern of CMV expression. MMF with reduced-dose induction did not engender a higher CMV morbidity.

Objective: Stroke remains a devastating complication of coronary artery bypass grafting (CABG): we evaluated whether a more aggressive diagnostic and therapeutic approach can reduce its incidence. Methods: Between January 1998 and January 2002, 1388 consecutive patients underwent isolated on pump CABG with blood cardioplegia. Among the first 627 patients (Group A), Echo-Doppler study (DS) was performed only in selected patients (58) with history of cerebrovascular disease (CVD) and/or carotid bruit; in 761 patients (Group B), DS was performed routinely. Carotid endarterectomy (CEA) was performed in 45 patients in Group A associated to CABG during cardiopulmonary bypass (CPB) and in 90 patients in Group B under local anaesthesia before CABG. Brain CT scan was performed in all cases with postoperative neurological symptoms. Results: The two groups were homogeneous for age, sex, associated diseases, history of CVD, number of graft and CPB time. There were no differences in terms of hospital mortality between Group A (22/627: 3.5%) and Group B (21/761: 2.75%); p = 0.5. Postoperative stroke was observed in 24/627 (3.82%) patients of Group A and in 2/761 (0.26%) of Group B ( p < 0.001). Hospital mortality for stroke was higher in Group A (12/627: 1.91%) than in Group B (0/761; p < 0.001) as well as the incidence of non-fatal stroke (Group A 12/627: 1.91% versus Group B 2/761: 0.26% p = 0.006). Conclusions: Preoperative DS, performed in all cases of CABG, followed by CEA under local anaesthesia in patients with critical carotid stenosis reduces the incidence of postoperative stroke.

This prospective randomized study compared the effects in heart transplant recipients of thymoglobulin and ATG, two rabbit polyclonal antithymocyte antibodies available for induction therapy. Among 40 patients (29 men and 11 women, mean age: 40.7 +/- 14 years) undergoing orthotopic heart transplantation, 20 were randomly allocated to receive induction with thymoglobulin (group A) and 20 to ATG-fresenius (group B). Comparisons between the two groups included early posttransplant (6 months) incidence of acute rejection episodes (grade/= 1B), bouts of steroid-resistant rejection, time to first rejection, survival, graft atherosclerosis, infections, and malignancies. The study groups displayed similar preoperative and demographic variables. No significant difference was found with regard to actuarial survival (P =.98), freedom from rejection (P =.68), number of early rejections1B (P =.67), mean time to first early cardiac rejection (P =.13), number of steroid-resistant rejections (P =.69). Cytomegalovirus reactivations were more frequent among group A (65%) than group B (30%; P =.028). New infections due to cytomegalovirus occurred only in group A (four patients; 20%; P =.05). No cases of malignancies were observed at a mean follow-up of 32.8 +/- 8.9 months. Although thymoglobulin and ATG showed equivalent efficacy for rejection prevention, they have different immunological properties. In particular, thymoglobulin seems to be associated with a significantly higher incidence of cytomegalovirus disease/reactivation.

Objective: Postoperative respiratory failure is a frequent and serious complication in patients with type A acute aortic dissection. Experimental evidence suggests that pulmonary artery perfusion using hypothermic protective solutions helps prevent lung injury. The aim of this pilot prospective study was to evaluate the effect of pulmonary artery flushing during selective cerebral perfusion (SCP) on lung function. Methods: Twenty patients referred for acute type A aortic dissection, who were free from preoperative respiratory dysfunction, were assigned prospectively and alternately to two treatment groups. Pulmonary flushing was performed during SCP in group P (10 patients), while conventional Kazui technique was applied in group N (10 patients). Lung perfusion consisted of single-shot hypothermic pulmonary artery flush with Celsior. Lung function was evaluated by intubation time, scoring of chest radiograms at 12 hours after CPB, and PaO 2 /FiO 2 assessed from immediately before surgery to 72 hours after termination of cardiopulmonary bypass. Results: Incidence of pre, intra and post operative determinants of lung dysfunction proved homogeneous in both groups. Lung oxygenation function showed a marked post operative decline followed by a slow improvement in both groups. Analysis of respiratory ratios did not disclose significant differences even though the flushed group had a better performance in all study patients. The incidence of prolonged ventilator support (longer than 72 hours) (30% vs 20%, p=NS) and severity of x-ray pulmonary infiltrate score were comparable (mean score 1.7±0.71 vs 1.6±0.68, p=NS). Conclusions: Pulmonary artery flushing with Celsior solution does not seem to provide an effective preservation of lung function. (Int J Artif Organs 2003; 26: 1032-8)

Objectives: To analyse circulating concentrations of advanced glycation end products (AGEs) in patients with severe congestive heart failure (CHF) and after heart transplantation; to identify the potential contribution of kidney function to plasma AGE concentrations; and to determine whether AGE concentrations and parameters of oxidative stress are interrelated.Methods and results: Circulating N-epsilon-(carboxymethyl) lysine (CML) and AGE associated fluorescence (AGE-Fl), lipid peroxidation, and glomerular filtration rate (GFR) were measured in a cross sectional study of 22 patients with advanced CHF, 30 heart transplant recipients, and 20 healthy controls. Compared with the controls, the CHF patients had decreased CML (mean(SEM) 467.8 (20.0) ng/ml v 369.3 (22.3) ng/ml, p

Basal lamina (BL) is a crucial mechanical and functional component of blood vessels, constituting a sensor of extracellular microenvironment for endothelial cells and pericytes. Recently, an abnormality in the process of matrix microfibrillar component remodeling has been advocated as a mechanism involved in the development of aortic dilation. We focused our attention on BL composition and organization and studied some of the main components of the Extracellular Matrix such as Tenascin, Laminins, Fibronectin, type I, III and IV Collagens. We used surgical fragments from 27 patients, submitted to operation because of aortic root aneurysm and 5 normal aortic wall specimens from heart donors without any evidence for aneurysmal or atherosclerotic diseases of the aorta. Two samples of aortic wall were harvested from each patient, proximal to the sino-tubular junction at the aortic convexity and concavity. Each specimen was processed both for immunohistochemical examination and molecular biology study. We compared the convexity of each aortic sample with the concavity of the same vessel, and both of them with the control samples. The synthesis of mRNA and the levels of each protein were assessed, respectively, by RT-PCR and Western Blot analysis. Immunohistochemistry elucidated the organization of BL, whose composition was revealed by molecular biology. All pathological samples showed a wall thinner than normal ones. Basal lamina of the aortic wall evidentiated important changes in the tridimensional arrangement of its major components which lost their regular arrangement in pathological specimens. Collagen 1, Laminin alpha 2 chain and Fibronectin amounts decreased in pathological samples, while type IV Collagen and Tenascin synthesis increased. Consistently with the common macroscopic observation that ascending aorta dilations tend to expand asymmetrically, with prevalent involvement of the vessel convexity and relative sparing of the concavity, Collagen type IV is more evident in the concavity and Tenascin in the convexity.