Driving forces in the origins of life.

What were the physico-chemical forces that drove the origins of life? We discuss four major prebiotic 'discoveries': persistent sampling of chemical reaction space; sequence-encodable foldable catalysts; assembly of functional pathways; and encapsulation and heritability. We describe how a 'proteins-first' world gives plausible mechanisms. We note the importance of hydrophobic and polar compositions of matter in these advances.

Nuclear shadowing in the holographic framework.

The nucleon structure function F2(N) computed in a holographic framework can be used to describe nuclear deep inelastic scattering effects provided that a rescaling of the Q2 momentum and of the IR hard-wall parameter z0 is made. The ratios RA=F2(A)/F2(N) can be obtained in terms of a single rescaling parameter λA for each nucleus. The resulting ratios agree with the experiment in a wide range of the shadowing region.

Criteria for histopathologic diagnosis of aortic disease consensus statement from the SIAPEC-IAP study group of "cardiovascular pathology" in collaboration with the association for Italian cardiovascular pathology.

Nowadays, the histopathological study of surgical specimens is an essential part of the diagnostic work-up in aortic disease, and not only in characterizing the neoplastic forms. Despite increasing clinico-therapeutic complexity of aortic pathology, the criteria for histopathological diagnosis have not been properly updated over the years, with the result that we find inconsistent terminology and little standardization of diagnostic criteria. In light of this consideration, the SIAPeC-IAP Study Group of "Cardiovascular Pathology", in collaboration with the Association for Italian Cardiovascular Pathology, has created this consensus document, with the aim of defining the features of histopathological substrates in the main non-neoplastic aortopathies (atherosclerotic, "degenerative"/non inflammatory, and inflammatory) and of systematizing diagnostic criteria even for the rare tumours of the aorta and pulmonary artery. The principal aims of the project are defining histopathological diagnostic criteria, standard nomenclature and classification, methodology and reporting of histopathological study and handling of aortic specimens. In addiction, some current issues and new knowledge emerging from basic aortic research are debated, with the aim of promoting a "modern" and up-to-date view of aortic pathology.

Ultrastructural pathology of pediatric myocardium in acute ischemia: bioptic study before and after treatment with cardioplegic solution.

Protecting the myocardium from the risk of acute ischemia during heart surgery is still an unsolved problem; the problem is even more open and more pressing in pediatric heart surgery. To meet this greater risk it is advisable to use a cardioplegic solution with a composition that is better suited to the particular morphofunctional conditions of the myocardium in the child, i.e., a solution offering greater protection. To this purpose the authors experimented with Celsior cardioplegic solution during heart surgery in children to evaluate the efficacy compared to the standard St. Thomas solution. In this comparative study 15 children were treated with Celsior cardioplegic solution and 15 others with St. Thomas cardioplegic solution. Each patient underwent 2 biopsies of the myocardium, the first before cardioplegic treatment and the second immediately after reperfusion. In both groups, focal lesions involving both the cardiomyocytes and the vascular-stromal structures were randomly found. The former had undergone a necrotic-regressive process with changes in the myofibrils and the mitochondria. The vascular-stromal structures showed changes in the permeability of the capillary endothelia, with interstitial edema. The results show the lesions to be similar in the 2 groups both on a quality and quantitative level.

Desmin-free cardiomyocytes and myocardial dysfunction in end stage heart failure.

Our aim was to evaluate the desmin content in the myocardial tissue of patients with end-stage heart failure of ischaemic origin and to assess its role on cardiac function. We studied 18 explanted hearts from patients transplanted for end-stage heart failure due to ischaemic cardiomyopathy (ICM). Control myocardial tissue was obtained from the cardiac biopsies of six women with breast cancer taken prior to commencing chemotherapy with anthracyclines, four male donors for heart transplantation and two autoptic hearts from patients who died due to non-cardiac events. Myocardial tissue, obtained from the left ventricle (remote zone from infarcted area), was analyzed by light and confocal immunochemistry (desmin) microscopy. The desmin content of myocardial tissue was obtained by real-time PCR. Cardiac function was evaluated by echocardiographic and right heart catheterization data, obtained before heart transplantation. Confocal microscopy evaluation showed a significant decrease in the number of desmin-positive myocytes (P<0.01) in ICM hearts compared to controls. At real-time PCR evaluation, there was a reduction (P<0.01) in desmin content in the ICM patients compared to controls. A negative correlation was found between desmin-free cardiomyocytes and ejection fraction (EF) (r=-0.834; P<0.02) on echocardiogram. A negative relationship (r=-0.688) was also found between desmin-negative myocytes and capillary wedge pressure. In conclusion, the myocardial tissue of patients with end-stage heart failure of ischaemic origin, shows a decreased number in desmin-positive myocytes at immunochemistry evaluation compared to normal individuals. This deficiency in cytoskeletal intermediate filament content is associated with reduced cardiac function.

Gene expression and morphological changes in surgically injured carotids of spontaneously hypertensive rats.

The expression profiles of genes involved in cell proliferation, differentiation and programmed death were investigated in carotids of spontaneously hypertensive rats (SHR) treated with a model of surgical injury that mimics events occurring during arterial grafts, endarterectomy and organ transplantation. The mRNA level of the c-myc, angiotensin II receptor 1 (AT1), Rb/p105, Rb2/p130, Bcl-2 and Bax-alpha genes was assessed by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) technique at different times up to 48 h after injury, while the morphological changes were evaluated 30 days after injury. The proliferation marker c-myc increases almost immediately, peaks after 4 h and returns to basal levels after 24 h; the AT1 receptor mRNA reaches its maximal level 48 h after injury. The level of cell cycle exit markers Rb/p105 and Rb2/p130 gradually decreases after injury. The apoptosis marker Bcl-2/Bax-alpha ratio shows a significant reduction only 4 h after injury, resuming the initial value after 24 and 48 h. Morphological analysis reveals that surgical injury in SHR induces adventitial and medial constrictive remodeling changes rather than intima proliferation as in balloon angioplasty. Both molecular and histological data show substantial differences with respect to normotensive rats.

Medial degeneration does not involve uniformly the whole ascending aorta: morphological, biochemical and clinical correlations.

OBJECTIVE: To investigate whether and how the severity of medial degeneration (MD) lesions varies along the circumference of the dilated intrapericardial aorta. METHODS: Two groups of aortic wall specimens, respectively harvested 1cm distal to the non-coronary (NC) sinus (right postero-lateral wall) and to the right coronary sinus (anterior wall) in 22 patients undergoing surgery for dilatation of the intrapericardial aorta associated with aortic valve disease, were separately sent for pathology, morphometry and ultrastructural examination. MD lesions found at histology were classified into three degrees of severity. MD mean degree and morphometric findings in postero-lateral ('NC') and anterior ('coronary') specimens were compared by paired t-test. Correlation between degree of aortic dilatation at echocardiography and severity of MD was assessed separately for each of the two groups of specimens. After the preliminary results of the morphological study, we decided to send the specimens for biochemical investigation of protein electrophoretic patterns. This was performed in the last seven patients of this series. RESULTS: At histology, MD was found in all cases. A higher mean MD degree was found in the NC group (2.59+/-0.50 versus 1.59+/-0.67 in the coronary group; P<0.001). At morphometry, normal smooth muscle cells in the NC specimens were significantly reduced (P=0.012) and the length (P=0.011) and number (P=0.015) of elastic fibres reduced and increased, respectively. Correlation between aortic ratio and MD degree was significant in the NC specimens (P<0.001), not in the coronary ones (P=0.227). Quantitative differences between coronary and NC proteins from the same patient and between coronary proteins from different patients were found at electrophoresis. However, at this stage of the study, the sample was too small to allow for the identification of proteins involved in those differences. CONCLUSIONS: MD lesions in dilated intrapericardial aorta are more severe in the right postero-lateral wall area, likely due to haemodynamic stress asymmetry.

Unusual manifestation of vertebral osteoid osteoma: case report.

We report the case of a 64 year-old man with a clinical history suggesting a low thoracic-cord involvement, in which an unexpected vertebral osteoid osteoma was discovered. The patient underwent MRI of the thoraco-lumbar spine, which included sagittal and axial T1-weighted images, and sagittal double-echo T2-weighted images. Subsequently, CT scan was carried out with 2-mm-thick axial sections, aimed at T10 vertebra. Magnetic resonance imaging disclosed an extra-axial mass at T10 level. Computed tomography scan suggested an osteoid osteoma of the tenth thoracic vertebra, involving the lamina with marked sclerosis and prevalently endocanalar extension. Histology following surgical resection confirmed the diagnosis. In the reported case CT scan provided the correct pre-operative diagnosis of osteoid osteoma despite its unusual clinical--anamnestic presentation. Magnetic resonance imaging was useful in establishing the relationship of the neoplasm with the spinal cord.

Asymmetric medial degeneration of the intrapericardial aorta in aortic valve disease.

BACKGROUND: A geometrical and functional asymmetry in the normal aortic root has been recently demonstrated. Whether the distribution of medial degeneration (MD) within the wall of the dilated ascending aorta in adult patients reflects such asymmetry, still has to be assessed. METHODS: Nineteen patients with fibrocalcific aortic valve disease and dilatation of the intrapericardial aorta, without clinical signs and familiar history of primary elastic connective tissue disorders, underwent surgery. Biopsies (57 specimens) were taken in each patient from three areas of the ascending aortic wall distal to the three sinuses of Valsalva. MD lesions found at histology in each specimen were classified in three degrees. Comparisons were made between the three sites as to distribution of the three degrees and between one site and the other two as to incidence of the highest degree. RESULTS: A mild degree of MD was found in 26 specimens (45.6%), moderate in 14 (24.6%), severe in 17 (29.8%). The distribution of the three degrees of MD changes was significantly different between one of the three studied wall areas and the other two (P<0.001): a significantly greater incidence of the highest degree of involvement in the aortic wall distal to the non-coronary sinus than in the wall areas corresponding to the coronary sinuses was found (P<0.001). CONCLUSIONS: MD lesions in dilated intrapericardial aorta are more severe in the wall area distal to the non-coronary sinus, likely due to haemodynamic stress asymmetry.

Lipoma of the heart: a case report.

Lipomas of the heart are rare (only 0.5% according to the Armed Forces Institute of Pathology series) and their diagnosis is often difficult because they are asymptomatic; in fact, in contrast to lipomatous hypertrophy, lipomas are usually found on the epicardial surfaces of the atria or ventricles. In our case, the lipoma was located in both atria and was attached to the interatrial septum involving also the right pulmonary veins, the inferior vena cava and the right phrenic nerve. At histology, the tumor was composed only of mature adipose tissue with entrapped myocytes and vessels. The combination of computed tomography and transesophageal echocardiography allowed a precise diagnosis in terms of the localization and tissue characterization of the tumor.

Determinants and prognostic value of ischemic necrosis in early biopsies following heart transplant.

To evaluate the impact of early ischemic necrosis (IN) on the early and late outcome of heart transplantation, we reviewed our 11-year experience. Between January 1988 and June 1999, 207 heart transplants were performed in 205 patients (174 male and 31 female). Criteria for donor and recipient selection, and protocols for postoperative immunosuppression and rejection monitoring have remained unchanged over this period. Three different cardioplegic solutions were employed in graft preservation: St. Thomas Hospital solution in the earliest 31 cases (15%), University of Wisconsin solution in 96 cases (46.4%), and Celsior solution in the last 80 cases (38.6%). All patients who underwent at least one endomyocardial biopsy (176 patients) were divided into two groups according to the findings of IN within the early 3 postoperative months (group A, 49 patients with IN; group B, 127 patients without IN). The following variables were estimated in each group: donor and recipient age, ischemic time, type of cardioplegia, late mortality for cardiac causes, incidence of grade >2 rejection within the first 6 postoperative months, late incidence of grade >2 rejection, late incidence of NYHA class >II. No significant difference was found in any parameter between the two groups, except for the type of cardioplegic solution. A significantly higher incidence of ischemic necrosis in hearts preserved with St. Thomas solution was found (P < 0.001). Although pathology findings show that extracellular solutions carried a higher risk of early IN, no associated significant impairment in terms of late survival and event-free rate was observed in recipients with early IN.

[Peritoneal cystic mesothelioma. A clinical case and review of the literature]. / Mesotelioma cistico peritoneale. Caso clinico e revisione della letteratura.

Multicystic peritoneal mesothelioma is an extremely rare benign neoplastic disease with high tendency to recur locally, but no tendency to malignancy. Correct diagnosis can be made with histopathologic examination and always with immunohistochemical and ultrastructural evaluation. A case in a twenty-eight-year-old woman is reported and the anatomo-clinical characteristics of multicystic peritoneal mesothelioma from sixty-nine cases described in the literature are specified, discussing the management of this disease and emphasizing the importance of a nondemolitive approach.

[Pathology of heart transplantation.(Morphological study of 1246 endomyocardial biopsies from 167 transplanted hearts). Causes of early, intermediate, and late deaths]. / Patologia del trapianto cardiaco. (Studio morfologico di 1246 biopsie endomiocardiche (BEM) da 167 trapianti cardiaci). Cause di mortalità precoce, intermedia e tardiva.

From January 1988 through October 1997, 167 cardiac transplants were performed. 1246 endomyocardial biopsies (EMBs) from 138 cardiac allograft recipients were investigated and graded according to the Working Formulation (WF) criteria. The specimens were inadequate in 44 EMBs (3.5%), while 598 (48%) showed no rejection. The grade of rejection was: mild (grade 1A and 1B) in 531 EMBs (42.6%), mild/moderate (grade 2) in 38 (3.1%), and moderate (grade 3A and 3B) in 35 (2.8%). The indications for transplantation were: dilated cardiomyopathy (46.1%); ischemic disease (37.1%); valvular disease (12%); hypertrophic cardiomyopathy (1.8%); myocarditis (1.2%); congenital cardiopathy (0.6%), restrictive cardiomyopathy (0.6%) and chronic rejection (0.6%). The most reliable histologic feature of acute rejection was the myocyte necrosis or damage in presence of pironinophilic mononuclear cell infiltrate, so our protocol requires multifocal or diffuse myocyte damage (rejection grade 3A and 3B) to perform an additional treatment, which was required in 35 cases (2.8%). An intermediate grade mild/moderate 2, was introduced from the WF to classify the EMBs in which the myocyte necrosis was scant or not clear; this grade in our series generally resolves without any additional treatment; in order to monitor the rejection another EMB was performed 5 days after in these patients. The EMBs showed also the following lesions other than acute rejection: Quilty A (79 patients; 57.25%), Quilty B (24 pts; 17.39%), early ischemic necrosis (43 pts; 31.15%) and late ischemic necrosis (5 pz; 3.62%). Quilty B and late ischemic necrosis were correlated with acute rejection (grade 2), furthermore the patients with graft vascular disease showed 3 or more episodes of acute rejection. These findings confirm the relationship between acute and chronic rejection. Furthermore, a relationship between chronic rejection (4 pts) and infection from hepatitis C (antibodies positive 3 pts/4) and cytomegalovirus (antibodies positive 4 pts/4) was found in our series. In the follow-up period (117 months), a 30.72% death rate was recorded; the main causes of death were: early failure of the transplanted heart (30 pts) in 4 of them associated with pulmonary hypertension, infections (6 pts), sudden death (4 pts), graft's vasculopathy (4 pts), acute pancreatitis (1 pts) pulmonary embolism (1 pts), lung (1 pts) and ovary (1 pts) carcinoma, acute rejection (1 pts), others (2 pts). In the early period (< 1 month), the most frequent cause of death was the early failure of the transplanted heart, while in the late period (> 1 year) the chronic rejection following by sudden death and tumours. The actuarial survival curve drops to 83.13% after the first post-operative month, abates to 75.30 at the end of the first year, and progressively decreases to 70.48% at the end of the fifth follow-up year. The mortality rate was 38.7% in pts transplanted for ischemic disease and 24.7% for dilated cardiomyopathy. Cardioplegia seems to play an important role in the success of the heart transplant.

Late complications of heart transplantation: an 11-year experience.

Advances in donor and recipient selection and postoperative management of patients undergoing a heart transplant have improved survival after cardiac transplantation; nevertheless, late complications are still the main cause of mortality. Between January 1988 and March 1999, 200 heart transplants and 2 retransplants were performed at our Institution. The actuarial survival rate was 84.45% at 1 month, 75.22% at 1 year, and 69.48% at 5 years. One-hundred forty-five patients reached at least 6 months of follow-up. In this group of patients we reviewed all available pathological specimens from endomyocardial biopsies, autopsies, and hearts retrieved at retransplantation. The most frequent late complications have been: malignancies (9 patients), allograft coronary artery disease (ACAD) (6 patients), and infections (6 patients). All patients with ACAD had serological evidence of cytomegalovirus (CMV) infection and 5 of them (83.3%) of hepatitis C virus (HCV) infection. Squamous cell lung carcinoma and Kaposi's sarcoma were the most frequent neoplasms (3 patients). Twenty-six out of 145 patients died during the follow-up: sudden death occurred in 10 patients (38.46%), infections caused death in 6 patients (23.08%). ACAD in 4, and cancer in 4. Causes and rates of late mortality in patients with a cardiac transplant differ from those of early mortality. Development of infections, ACAD, or cancer is associated with a high late mortality rate. A striking correlation has been found between ACAD and HCV and/or CMV positivity. suggesting that such viruses may play a role in the development of vascular late complications in transplanted hearts.

Causes of late failure after heart transplantation: a ten-year survey.

BACKGROUND: Little is known about the causes of death of heart transplant recipients who survive long-term. METHODS: The pathologic and clinical records of 97 patients who underwent heart transplantation in Italy from 1985 to 1995 and died (85 of 97) or underwent retransplantation (12 of 97) at least 2 years after transplantation were surveyed. Graft failures were classified as late (occurring between 2 and 5 years after transplantation) and belated (more than 5 years). RESULTS: Graft vasculopathy was the single most common cause of death (40.0%) and the only cause of late retransplantation. Tumors ranked second (23.5% of deaths), but the expected non-Hodgkin's lymphomas and Kaposi's sarcoma were accompanied by a high number of lung cancers (especially metastasizing adenocarcinomas). They were followed by the emergence or recurrence of pretransplantation diseases (9.4%), fatal infections (exclusively bacterial) (4.7%), the development of transmissible diseases (viral hepatitis and acquired immunodeficiency syndrome, 4.7%), and late acute rejection (2.3%). The distribution of failures differed in the late and belated periods: death and organ loss proportions for graft vasculopathy, respectively, fell and rose from the late to the belated period; some types of malignancy and fatal acute rejection were never observed in the belated period, whereas the emergence of pretransplantation diseases prevailed in the belated period. Graft vasculopathy was more frequent and tumors were less frequent among patients undergoing transplantation for ischemic heart disease. CONCLUSIONS: The reasons why heart transplant recipients die or undergo retransplantation, respectively, in the late and belated periods slightly differ from one another and are widely different than in short-term survivors.

Obstruction of mechanical mitral prostheses: analysis of pathologic findings.

BACKGROUND: The pathologic and echocardiographic findings observed in 87 patients with mitral valve obstruction were reviewed to ascertain the incidence of pannus formation versus that of thrombosis, the relationship between the two, and the time to the occurrence of pannus versus the time to thrombosis. METHODS: Pannus morphology (concentric or eccentric), its location on the valve (atrial, ventricular, atrioventricular), and the presence and relationship of associated thrombi (atrial, ventricular, atrioventricular) were analyzed. The times between valve replacement and the occurrence of obstruction were also compared. RESULTS: There were 10 caged-ball valves, 65 tilting-disc valves, and 12 bileaflet valves. Seventy-two patients underwent prosthetic replacement, and 15 underwent thrombolysis. Pannus alone was found in 27, pannus and thrombus in 39, and thrombus alone in 21. Primary thrombosis occurred earlier than pannus formation (p = 0.04); this was true for patients with bileaflet valves (p = 0.006) and those with tilting-disc valves (p = 0.04). Pannus was atrial in 19.7% (13/66), ventricular in 21.2% (14/66), and atrioventricular in 59.1% (39/66). Pannus morphology was concentric in 22.7% (15/66) and eccentric in 77.3% (51/66). Atrial secondary thrombi occur more often in patients with atrioventricular pannus (p = 0.04). Eight patients had reobstruction; this was caused by pannus formation in 5 and by thrombosis in 3. Five underwent reoperation, and 3 underwent thrombolysis. Reobstruction occurred earlier than the first event. CONCLUSIONS: The frequency of pannus formation is much higher than that of thrombus formation, but thrombosis is of earlier onset than pannus formation. Thrombosis is due to the deposition of clots on the prosthesis, and a pannus occurs as the result of an inflammatory reaction developing on both valve surfaces.

Non-inflammatory aortic root disease and floppy aortic valve as cause of isolated regurgitation: a clinico-morphologic study.

A clinico-morphologic study was performed on 1120 patients who underwent aortic valve replacement at the Department of Medical and Surgical Cardiology, 2nd University Medical School of Naples, Naples, Italy, from January 1981 through December 1991. In 69 cases the aortic valve was incompetent due to a non-inflammatory aortic root disease such as myxomatous infiltration of the cusps and or aortic root dilatation. Among these patients males were prevalent (male/female ratio = 2.2). The mean age was 37 +/- 7.5 years. A floppy mitral valve was diagnosed in 16 cases while in one a left atrial myxoma was found. The patients were divided into 3 groups: Group 1-29 patients with aortic root dilatation and normal cusps; Group 2-25 patients with aortic root dilatation and myxomatous infiltration of aortic cusps (floppy aortic valve); and Group 3-15 patients with floppy aortic valve and undilated aortic root. At the gross examination the cusps of the patients in Groups 2 and 3 were redundant, thin, soft and gelatinous. The histology showed myxomatous infiltration with disruption of the fibrous layer. In patients with aortic root dilatation the histology of the aortic root fragments showed a cystic medial necrosis. Deep correlation was found between the root dilatation and the grade of aortic wall cystic medial necrosis. Cusp's diastasis was the cause of aortic regurgitation in patients with aortic root dilatation, while cusp prolapse caused aortic incompetence in presence of the floppy aortic valve and undilated aortic root.(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical pathology of the aortic valve: gross and histological findings in 1120 excised valves.

From January 1981 through December 1991, 1120 consecutive aortic valves were surgically explanted and their gross anatomy and histology studied at our university. Rheumatic disease (65%), dystrophic calcific valvular disease (23%), noninflammatory disease of the aortic root and/or floppy aortic valve (6.3%), and endocarditis (5.4%) were the causes of valve dysfunction. Among the total population the male sex predominated. The male to female ratio was 2.4 in the group with dystrophic calcific valvular disease and 1.6 in the group with bacterial endocarditis. The mean age was 37 ± 7.5 years in the group with non-inflammatory disease of the aortic root and/or aortic cusps. In the group with dystrophic calcific valvular disease, the mean age was 62 ± 6.3 years. Among the 1120 patients, 717 (64.03%) underwent surgery for aortic stenotic-incompetence, 250 (22.25%) for isolated aortic stenosis, and 153 (13.72%) for isolated aortic incompetence. In 449 cases (40.13%) a mitral pathology was associated. Chronic rheumatic aortic disease usually caused stenotic insufficiency (92.8%). Dystrophic calcific aortic disease caused pure stenosis in 84.8% of the cases. Among these, 46 patients (18.4%) had a congenitally bicuspidal aortic valve. Pure aortic incompetence was caused by noninflammatory aortic root and/or cusp disease in 44% of patients, infective endocarditis in 40%, and rheumatic disease in 16%. Patients with noninflammatory aortic root and/or cusp disease were divided into three groups: 29 patients with aortic root dilatation and normal cusps, 25 patients with aortic root dilatation and mixomatous infiltration of aortic cusps (floppy aortic valve), and 15 patients with floppy aortic valve and normal aortic root. Aortic incompetence was caused by cusp retraction caused by chronic rheumatic disease, cusp perforation or tears caused by infective endocarditis, and cusp prolapse for floppy aortic valve. Cusp diastasis has been the cause of aortic incompetence in patients with dilated aortic root. In patient with floppy aortic valve caused by the fibrous lamina disarray, the cusps prolapsed toward the left ventricle, causing valve regurgitation.

Immediate causes of death in short-term surviving heart transplant recipients.

From 1985 to 1992, 1068 cardiac transplants have been performed in the Italian units. The immediate causes of death of 142 of the 148 orthotopic cardiac transplantation recipients who died within the first 6 postoperative months were surveyed. Deaths were grouped into three periods: perioperative (⩽1 month, 68.3%), early (>1 ⩽3 months, 23.2%), and advanced (>3 ⩽6 months, 8.5%). Acute graft failure (arising from the ischemic damage to the donor heart, from surgical problems, from severe pulmonary hypertension, or from multiorgan failure) accounted for 49% of perioperative deaths and, along with noncardiac emergencies (23% of perioperative deaths), was significantly more frequent in this period than in the subsequent ones. The dissection of thoracic arteries was responsible for 4% of postoperative deaths, occurring exclusively among patients transplanted for ischemic or valvular heart disease. In the early and advanced periods, untreatable acute rejection (13%) and fatal infections (38%), mostly saprophytic, were significantly more frequent. Ischemic heart damage secondary to graft vasculopathy already caused 26% of deaths between the fourth and sixth months after transplantation. Some diseases, such as acute rejection, had the same frequency as both underlying disease and immediate cause of death. On the contrary, graft failure is more common as primary disease, leading to death also through noncardiac complications and saprophytic infections. Bacterial infections have the same frequency as both prime and immediate cause of death, viral infections are more common as primary disease, and the opposite is true for saprophytic infections.

When and why do heart transplant recipients die? A 7 year experience of 1068 cardiac transplants.

This mortality study deals with the 1068 heart transplants (1054 patients) performed in Italian Units from November 1985 to April 1992. The death rate was 19.7% and the actuarial survival was 89% at 1 month, 83% at 1 year and 74% at 6.5 years. Recipients who died had been less often transplanted for dilated cardiomyopathy, were older (44.1 vs. 41.7 years) and more often male (84.5 vs. 72.7%). Analysis of the causes of death was restricted to orthotopic transplantations (1029/1068 procedures, 195/208 deaths). Deaths were grouped within four intervals: peri-operative (< or = 1 month, 50.0% of deaths), early (> 1 month < or = 3 months, 17.2%), intermediate (> 3 months < or = 2 years, 22.6%) and late (> 2 years, 10.2%). The prime causes of death were mostly postoperative graft failure (whose effects brought about 64% of peri-operative deaths, 28% of early and 7% of intermediate deaths), post-operative complications (10% of peri-operative deaths), acute rejection (10% of total deaths, distributed in all the periods), graft arteriopathy (6% of early, 36% of intermediate and 58% of late deaths), infections (17% of deaths, occurring in all periods but late) and malignant tumours (7% of deaths), lymphomas being the first to occur and Kaposi's sarcoma occurring only in the intermediate period. Repeat transplantation had a poor outcome (death rate 71.4%), two-thirds of the re-transplanted patients' deaths being due to early graft failure and a third to late relapsing graft vasculopathy.