Expression of natriuretic peptide in ventricular myocardium of failing human hearts and its correlation with the severity of clinical and hemodynamic impairment.

Atrial natriuretic peptide (ANP) was immunohistochemically investigated in (1) right ventricular endomyocardial biopsy specimens from 87 apparently healthy donor hearts taken from victims of cerebral accidents; (2) 1 normal heart not suitable for transplantation (HBsAg carrier); (3) right ventricular endomyocardial biopsy specimens from 151 patients with dilated cardiomyopathy (DC); and (4) 57 explanted hearts, 26 with DC and 31 with ischemic heart disease. No ANP immunoreactivity was found in normal ventricles. Failing hearts showed ventricular positivity in 31% of the DC biopsy series, in 61% of the left ventricles, and in 30% of the right ventricles of the explanted heart series. An endoepicardial gradient was observed, because ANP positivity was greater and more extensive in the subendocardial layers. Ultrastructural studies were performed on biopsy specimens from 10 normal hearts and 132 DC biopsy samples. No ANP-storing granules were found in biopsy samples of normal ventricles, whereas ANP granules were seen in 15 of 132 (11.4%) DC cases. In parallel immunoblotting, investigation showed the same 13 kDa band protein in 1 normal atrium as well as in 8 failing atria and ventricles. ANP immunoreactivity was positively correlated with higher New York Heart Association functional classes as well as with higher left ventricular end-diastolic pressure (p less than 0.005), end-diastolic volume (p less than 0.005) and end-diastolic volume index (p less than 0.005). In conclusion, apparently healthy ventricles do not show ANP immunoreactivity, whereas failing ventricles do. ANP expression seems to be independent of the underlying disease, but positively related to the clinical status and the degree of left ventricular impairment and dilatation.

Expression of proliferating cell markers in normal and diseased human hearts.

Proliferating cell nuclear antigen (PCNA) myocyte expression and histopathologic features related to its occurrence were investigated in normal and diseased hearts of adult humans using both immunohistochemical and Western blotting techniques. Ki67 Western blotting was also performed in the same samples used for PCNA blotting. Two hundred seventy-one endomyocardial biopsies, and 15 adult, 1 embryonic and 2 fetal hearts were studied. The biopsies were from normal donor hearts (n = 71), patients with cardiomyopathy and myocarditis (n = 64), and patients with transplantation with (n = 106) and without (n = 30) acute rejection of any grade. The 15 hearts were from 1 heart donor, and from patients with cardiomyopathy (n = 5), valvular heart disease (n = 2), ischemic heart disease (n = 4), amyloidosis (n = 1) and transplantation with acute rejection (n = 2). The PCNA labeling index was plotted against myocyte hypertrophy, inflammatory infiltrates and binucleation index. The PCNA labeling index ranged from 2 to 9% in embryonic and fetal hearts. PCNA was expressed by 1 to 2% of myocyte nuclei in 12% of normal heart biopsies, 1 to 5% of myocyte nuclei in 28% of cardiomyopathy and myocarditis biopsies, and by up to 8% of myocyte nuclei in 53% of biopsies of patients with transplantation, independently of the presence and degree of acute rejection. In the latter biopsies and in myocarditis, some inflammatory cells also showed PCNA expression. PCNA positive myocytes were both mono- and binucleated, and there was no correlation between binucleation and PCNA labeling indexes. Ki67 and PCNA blotting confirmed immunohistochemical results.(ABSTRACT TRUNCATED AT 250 WORDS)

Pregnancy in heart transplant recipients.

The aim of this report is to present data from Italian cardiac transplant centers assessing pregnancy after cardiac transplantation. Our retrospective survey included 10 pregnancies occurring in 7 patients during January 1991 to February 2002. Eight pregnancies were completed successfully and 2 abortions were reported (frequency rate 20%). No complications were observed during pregnancy or after delivery. Of 8 infants studied, 6 (75%) were born at term and 2 (25%) pre-term. One baby presented congenital talipes valgus. Pediatric development was uneventful. The data from the literature and our series show that a multidisciplinary approach is mandatory. The course of pregnancy is usually normal and the maternal and fetal outcomes are usually favorable. Although no fetal malformations have been reported, prolonged follow-up of these infants is required.

FK506 effectiveness in reducing acute rejection after heart transplantation: a prospective randomized study.

BACKGROUND: Tacrolimus (FK506) has recently become available clinically as an alternative to cyclosporine-based immunosuppression. This study reports the middle-term results of a prospective, randomized trial that compared FK506 with cyclosporine-based immunosuppression in heart transplant recipients. METHODS: Twenty-five consecutive patients were randomized at a 2:1 ratio into two groups, one of which received FK506 (15 patients), the other cyclosporine (10 patients). Both groups received similar concomitant immunosuppression. The patients were followed up for 12 months. The following outcome parameters were analyzed: survival, rejection and infection rate, lymphocyte subsets, new-onset diabetes, renal and hepatic function, hypertension, right-sided heart catheterization data, graft coronary artery disease, and neurologic side effects. RESULTS: The mortality rate (two patients) in the FK506 group was 13% versus 0% in the cyclosporine group (p = NS). The two deaths were the consequences of early infections and higher doses of FK506. From the outset, the FK506 group presented a lower prevalence of acute rejection, a lower requirement for rejection treatments and a higher incidence of infections. Accordingly, we reduced overall immunosuppression for the last seven patients in the FK506 group; the decrease in FK506 and prednisone dosage led to a decrease in the early infection rate without an increase in the rejection rate. There was no difference between the two groups in diabetes incidence, renal and hepatic function, right-sided heart catheterization data, or coronary angiograms. Hypertension was less frequent and milder in the FK506 group. CONCLUSIONS: This experience suggests that FK506 can be safely used in heart transplantation. It can decrease the frequency of rejection episodes. Low-dose administration allows a lower infection rate without an increase in rejection. With a protocol of delayed starting and low dosing, side effects such as renal toxicity, hypertension, and neurologic toxicity seem to be unlikely. Further studies are needed to establish the exact dosage and therapeutic levels of the drug.

Histopathologic and molecular profile of human cytomegalovirus infections in patients with heart transplants.

From November 1985 to December 1990, 2,552 endomyocardial biopsy specimens from 209 heart transplant patients were studied. Forty-four (21%) patients developed 45 episodes of major human cytomegalovirus infection (HCMV). Human cytomegalovirus infection was primary in 13 of 44 patients. Thirty-one patients developed episodes of recurrent major infection. One patient had both primary and recurrent infections. Conventional histopathologic and immunohistochemical study, in situ hybridization, and polymerase chain reaction were used to diagnose HCMV myocardial involvement on corresponding endomyocardial biopsy specimens performed during infection. Conventional morphologic study showed typical viral inclusion bodies in four biopsy specimens. Two cases had myocyte HCMV localization with necrotizing myocarditis, whereas two had endothelial cell involvement without any inflammatory reaction. In these four biopsy specimens, immunohistochemistry showed a higher number of infected cells than that recognized by conventional histopathologic study. In situ hybridization detected infected cells with no evidence of cytopathic effect. Polymerase chain reaction gave HCMV amplification products in two additional biopsy specimens otherwise interpreted as moderate and mild rejection, respectively. Therefore, 6 biopsies showed HCMV myocardial involvement (6 of 45; 13.3%): all were from patients with primary HCMV infection (6 of 13; 46%). None of 32 major recurrent infections showed any myocardial involvement. In conclusion, our study is the first to demonstrate that myocardial HCMV involvement preferentially occurs in primary infection and HCMV endothelial localization can be free from inflammatory reaction, whereas HCMV myocyte localization leads to necrotizing myocarditis. Polymerase chain reaction has a higher diagnostic sensitivity than in situ hybridization. However, polymerase chain reaction findings of HCMV DNA on otherwise negative endomyocardial biopsy specimens remains of questionable significance because polymerase chain reaction-positive biopsy samples do not necessarily indicate tissue infection. It is impossible to determine whether amplified sequences derive from circulating leukocytes or from tissue cells.

Heart transplantation without informed consent: discussion of a case.

OBJECTIVE: To discuss informed consent to heart transplantation in the case of an intensive care unit (ICU) patient: relatives' informed consent was refused by the patient himself whose cognitive ability appeared to be reasonable for the purpose. SETTING: ICU of a university teaching hospital. PATIENT: A 62-year-old man who underwent myocardial revascularization had in the immediate post-operative hemodynamic instability, continuous serious arrhythmias, ventilatory support, fentanyl infusion. Heart transplantation could be the only chance for his survival. INVENTION: Heart transplantation. RESULTS: Despite patient's refusal, we decided to hold the relative's consent as valid, and transplantation was accordingly performed, to the subsequent satisfaction of the patient. CONCLUSIONS: Our decision was based on two beliefs: (1) the severity of the patient's clinical condition may have impaired his cognitive abilities; (2) the very same conditions may mask impairment and certainly make reliable assessment of cognition and judgment impossible. This being so, the preservation of life assumes priority.

Successful treatment of aortic dissection after heterotopic heart transplantation.

Heterotopic heart transplantation is a valid option when there is a large donor-recipient size mismatch. However, the presence of the diseased native heart can jeopardize the medium-term and long-term outcome. The problems stemming from this most commonly described in the literature are thromboembolism, angina, and arrhythmias. In this report, we describe the case of a type A aortic dissection in the native aorta that occurred 30 months after heterotopic heart transplantation and the surgical technique successfully applied for its repair. We also discuss some of the alternative techniques.

Emergency and elective cardiac retransplantation.

Among 265 patients transplanted at our Institution, 7 underwent cardiac retransplantation. There were five emergency retransplantations, the indication being graft failure in one case and acute rejection in four cases. Two patients, retransplanted because of acute rejection, had a positive panel reactivity antibody and a negative donor crossmatch. In the rejection cases immunosuppression was enhanced by perioperative plasmapheresis and a postoperative 1-month course of cyclophosphamide. In two cases emergency retransplantations were successfully performed despite a highly positive prospective crossmatch. Two patients underwent elective retransplantations for chronic rejection 12 and 41 months, respectively, after the primary transplants. The overall early and late survival rates are 71% and 57%, respectively, with a mean follow-up of 48.5 months. The early and late mortality for elective retransplantation is zero. Our experience confirms both the high operative risk for emergency retransplantation and the excellent results for elective retransplantation. The use of plasmapheresis and cyclophosphamide allowed us to undertake retransplantation successfully in 2 cases with positive donor crossmatch. Both hyperimmunized patients in our series were retransplanted because of irreversible acute rejection despite a negative crossmatch with the primary donor. The meaning of negative crossmatch in patients with preformed cytotoxic antibodies is therefore questionable.

Different results of cardiac transplantation in patients with ischemic and dilated cardiomyopathy.

We retrospectively analyzed 275 consecutive transplanted patients, dividing them into group A (128 patients) affected by ischemic cardiomyopathy and group B (147 patients) affected by dilated cardiomyopathy. The difference in demographic, clinical and hemodynamic preoperative and postoperative data between the groups was studied; group A patients presented at transplantation with a less compromised hemodynamic picture, requiring inotrope infusion and mechanical assistance less frequently. The influence of etiology on early postoperative complications was also analyzed: group A patients needed postoperative mechanical assistance, inotrope, infusion and prolonged mechanical ventilation more often, therefore requiring a longer stay in the intensive care unit (ICU). Hospital mortality was twice as high in group A. The older age of group A patients per se did not influence these results significantly. The long-term follow-up was then studied with particular attention to parenchymal functions, hemodynamics, coronary artery disease, metabolic and surgical complications, and survival. The complication rate was higher in group A, with more severe hypertension and higher cholesterol levels at 1 year, a higher prevalence of accelerated coronary artery disease (CAD) and a more frequent onset of insulin-dependent diabetes. Surgical and vascular complications were also more frequent. The final result was a better 5-year actuarial survival rate for group B patients. Donor and recipient ages at the time of transplant did not influence this result. We conclude that ischemic patients, even if they are transplanted in better condition and operated more electively, have a more critical early and long-term postoperative course and a worse survival rate. These findings are not explained by advanced age, but could be due to the impact of atherosclerosis and metabolic impairments associated with ischemic disease.

Heterotopic heart transplantation: a single-centre experience.

INTRODUCTION: Orthotopic heart transplantation (OHTx) represents the therapy of choice for end-stage heart disease not treatable with medical or conservative surgical approach. Heterotopic heart transplantation (HHTx) is a surgical procedure in which the graft is connected to the native heart in a parallel fashion and it was especially employed in precyclosporine era. The aim of this paper is to present our experience with HHTx. METHODS: From November 1985 till May 2003, 713 heart transplanted patients included 12 (1.7%) received HHTx. Eleven were male, mean age was 50.7 +/- 5.8 years. Five patients suffered from dilated cardiomyopathy and seven from ischemic cardiomyopathy. Indication for HHTx was: a body size mismatch in 11 cases and availability of a marginal organ in one case. RESULTS: Mean ischemic time was 149 +/- 48 minutes and mean cross-clamp time was 82.3 +/- 19.1 minutes. In four cases left ventricle aneurysm resection was associated with HHTx. Hospital mortality was 8.3% (one patient due to multiorgan failure). The actuarial survival rates were 92% and 64% at 1 and 5 years, respectively. The causes of death were: liver cancer, liver cirrosis, aortic dissection, cerebrovascular accident, and chronic rejection. CONCLUSIONS: In our experience, HHTx survival rate is comparable to OHTx. Because of the scarcity of donors, use of an undersized or marginal graft is a valid option to increase the number of transplanted patients. The major disadvantages of HHTx are the need for anticoagulant therapy, the more difficult hemodynamic and immunologic follow-up, and the presence of the diseased native heart.

Heart transplantation in patients with amyloidosis: single-center experience.

INTRODUCTION: Amyloidosis is a systemic disease. Heart transplantation in this subset of patients is contraindicated by the majority of authors. In our center, patients with heart failure due to amyloidosis have been evaluated for cardiac transplantation since 1991. The aim of this study was to analyze the outcome of these patients waiting for transplant and the effectiveness of this therapy. MATERIALS AND METHODS: Since 1991, eight patients affected by amyloidosis have been evaluated and enrolled on the waiting list for transplant: five affected by AL lambda type; two by APO A1; and one by TTR. Four were transplanted, three died waiting for a donor (two from cardiac failure, one from sudden death), and one has been recently transplanted after 17 months on waiting list. RESULTS: Since 1985, 713 patients underwent heart transplantation in our center, five of whom were affected by amyloidosis (0.7%). Two are still alive (60 and 41 months) without evidence of cardiac amyloidotic infiltration. One patient recently underwent a combined heart-liver transplantation. Two patients died after the intervention: one sudden death after 23 months with amyloidotic infiltration of transplanted heart, and one multiple organ failure (MOF) due to progression of the systemic disease. CONCLUSIONS: Despite the small size of the group preventing us from drawing definitive conclusion, heart transplantation may prevent therapy to arrest organ damage in patients with isolated cardiac involvement. Cardiac events are the main cause of death. Patients must be followed-up for evolution of systemic disease. The midterm survival is encouraging.

The role of surgery in the treatment of post-infarction ventricular tachycardia. A 5 year experience.

The purpose of this report is to present a 5 year experience in electrophysiologically guided surgical treatment of post-infarction ventricular tachycardia (VT) in a consecutive series of 39 patients. In every case the arrhythmia was not responsive to pluripharmacological therapy. The diagnostic steps included preoperative endocardial, intraoperative epi- and endocardial mapping, automatically carried out when possible. Surgical techniques were: classic Guiraudon's encircling endocardial ventriculotomy (EEV), partial EEV, endocardial resection (ER), cryoablation or combined procedures. The hospital mortality was of 4 patients (10%). During the follow-up period (1-68 mo), 4 patients (11%) died of cardiac non-VT related causes. Among the survivors, 90% are in sinus rhythm. The authors consider electrophysiologically guided surgery a safe and reliable method for the treatment of post-infarction VT and suggest more extensive indications. They stress the importance of automatic mapping in pleomorphic and non-sustained VT, and the necessity of tailoring the surgical technique to the characteristics of each case.

[Aneurysms of the coronary arteries. Apropos of a case of bilateral aneurysm successfully treated by surgery]. / Gli aneurismi delle arterie coronarie. A proposito di un caso di aneurisma bilaterale operato con successo.

Successful surgical management of multiple aneurysms of the coronary arteries by means of an aorto-coronary by-pass was later followed by equal success in the treatment of a double aneurysm of the carotid siphon. The literature appears not to contain any previous report of such an association. The pathogenesis, complications and therapeutic management of this uncommon branch of coronary pathology are discussed.

Pneumocystis carinii pneumonia in heart transplant recipients.

Seven cases of Pneumocystis carinii pneumonia (PCP) (two in 1988, three in 1989, one in 1990 and one in 1991) have been observed in a group of 241 heart transplant recipients transplanted in Pavia, Italy, from November 1985 through December 1991. Median time to onset of symptoms was 100 days after transplantation (range 59-333 days). Diagnosis was achieved in all patients by cytological examination of bronchoalveolar lavage (BAL) fluid and/or transbronchial biopsy. Clinical and roentgenographic features were remarkably similar in all PCP-affected heart transplant recipients. A dry, persistent hacking cough associated with dyspnoea was consistently observed. Fever ranged from 37.6 to 39.4 degrees C, median leukocyte count and median arterial oxygen saturation (SaO2) values were 7,300/mm3 (range 3,000-16,000/mm3) and 61% (range 49.3-93%), respectively. Median CD4+ count at the onset of symptoms was 211/mm3 (range 28-739/mm3). The only patient experiencing a recurrence of PCP had a CD4+ cell count of 28/mm3 at the end of treatment with trimethoprim-sulfamethoxazole (TMP-SMX). In all patients human cytomegalovirus was isolated from BAL fluids; however, treatment with TMP-SMX alone (20 mg/kg/day of TMP) was consistently followed by a complete recovery.

Emergency heart retransplantation with a positive donor crossmatch.

We report a case of one patient who underwent emergency retransplantation with a highly positive donor crossmatch. Standard immunosuppression was integrated by the addition of plasma exchange during extracorporeal circulation, polyclonal IgG, and cyclophosphamide for the first 30 days. After transplantation the clinical outcome was normal; immunosuppression induced a complete disappearance of the donor-specific antibody. In spite of the heavy immunosuppression, we did not observe any infectious complications. We suggest that a greater immunosuppression established soon after the transplant and adjusted on the basis of immunological monitoring may allow a heart transplant with a positive crossmatch.

[Aortic aneurysms as complication of bacterial endocarditis. Report of two cases (author's transl)]. / Gli aneurismi iuxtaorifiziali aortici di origine batterica. A proposito di due osservazioni personali.

The authors report on two cases, one of supravalvular aortic aneurysm and one of subvalvular aortic aneurysm. Both patients suffered from bacterial endocarditis of the aortic valve, superimposed on previous rheumatic valvular disease. The authors believe that such aneurysms represent typical though rare complication of bacterial endocarditis of the aortic valve. Subvalvular aneurysms should be the consequence of the systolic stress acting on the myocardial wall involved by endocarditis, whereas supravalvular aneurysms could result from the jet-lesion through the affected valve.