Dino Casarotto

Surgical Pathology of primary cardiac and pericardial tumors

OBJECTIVE Retrospective study of surgical pathology experience on cardiac and pericardial tumors at the University of Padua in the era of immunohistochemistry and endomyocardial biopsy. METHODS In the period 1970-1995, we studied 125 bioptic primary neoplasms: specimens were obtained from surgical resection in 116 cases, heart transplantation in 3, pericardiectomy in 3, endomyocardial biopsy in 2 and thoracoscopic biopsy in 1. Tumor histotype was established by light microscopy and more recently by immuno-histochemistry, using a large panel of antibodies, through avidin-biotin peroxidase method, against factor VIII-related antigen, ulex-europaeus, desmin, myoglobin, muscle-specific actin, smooth muscle-specific actin, vimentin, cytokeratins, leukocytic common antigen, neurofilaments and S100-protein. RESULTS One hundred and thirteen were benign neoplasms: myxoma was the most frequent (87 cases) followed by pericardial cyst (8), endocardial papilloma (5), fibroma (3), rhabdomyoma (3), hematic cyst (2), teratoma (2), hemangioma (1), celothelioma (1) and lipoma (1). Malignancy was diagnosed in 12 cases, and consisted of pericardial mesothelioma (3), myxosarcoma (3), angiosarcoma (2), fibrosarcoma (2) and leiomyosarcoma (2); 4 of them were intracavitary atrial masses and were supposed to be atrial myxoma on the clinical ground. Differential diagnosis included endocardial thrombosis (10), metastasis of concealed extracardiac tumors (5), echinococcosis (3), and Loefflers fibroplastic endocarditis (3). In 4 cases, cardiac mass histotype was defined without thoracotomy, through endomyocardial (3) and thoracoscopic (1) biopsy. CONCLUSIONS A large spectrum of cardiac tumors is observed in the surgical pathology practice. Although the diagnosis of cardiac masses is easily attainable by routine imaging techniques, differential diagnosis between primary and secondary tumors, malignant and benign forms, and non neoplastic masses, is achievable only by a thorough microscopic study of surgical resections. The role of the cardiac pathologist is becoming crucial as in other fields of oncology.

Reoperations for acute prosthetic thrombosis and pannus: an assessment of rates, relationship and risk.

OBJECTIVE Mechanical valvular prostheses have the advantage of longevity but carry a risk of thrombosis which is dependant on valve design, materials and host-related interface. While pannus is common to both biologic and mechanical valves, acute prosthetic thrombosis is mostly a complication of mechanical valves; therefore we investigated to find rates and risk of these obstructive complications. METHODS Between 1/1/70 and 31/12/97, 2680 patients received at least one mechanical prosthesis in the aortic or mitral or tricuspid position and a total of 3014 operations were performed. Follow-up included 18523 years and was 98% complete. Incidence rates, Kaplan-Meier estimates, modeling of the hazard and multivariate analysis in the hazard domain were used in the analysis. RESULTS Overall survival was 76%, 64%, 51%, 38.5% and 29% at 5, 10, 15, 20 and 25 years, respectively. It was significantly better in aortic than in mitral than in double prosthesis. 290 patients received a single reoperation, 37 a second, six a third and one a fourth reoperation. Two-hundred and fifty-one of these reoperations were exclusively due to malfunction of mechanical prosthesis, nine to malfunction of both mechanic and biologic prostheses. Most frequent reoperative indications was dehiscence (133), pannus (48) and thrombosis (29). The linearized rate of reoperations for pannus was 0.24%/patient per year, for valvular thrombosis 0.15%/patient per year. The shape of the thrombotic hazard was constant (at random) and the relative risk 12 times higher for tricuspid prosthesis, seven times higher for mitral prosthesis. Multivariate analysis controlling for prosthetic position, age, sex and prosthetic size, showed a 67% risk reduction with larger prosthesis (>27 mm), a 69% risk reduction with the Sorin tilting disk prosthesis and an 83% risk reduction with the bileaflet prosthesis. Pannus hazard shows a delayed exponential rise and was two times higher in tricuspid and three times higher in mitral position. Multivariate analysis showed a 50% risk reduction with larger prosthesis, an 11 times higher hazard of old (caged-disk, caged ball) prosthesis and a three times higher hazard of Lillehei-Kaster prosthesis. Reoperation for thrombosis has a 62% perioperative (30 days) survival compared to 92% survival of pannus reoperation. CONCLUSIONS Mechanical valves have a low incidence of reoperation, mostly for prosthetic dehiscence. Pannus development is the next frequent complication increasing with time since implant, therefore in this series it was related to old valvular models and tilting disk prosthesis, with longer follow-up. Acute thrombosis occurs significantly earlier than pannus formation. Despite shorter follow-up we are therefore confident that bileaflet prostheses are less prone to this complication and pannus is a rare early etiologic factor. Thrombosis has very high operative risk as compared to pannus, justifying the present trend to thrombolysate selected cases.

Cell composition of the human pulmonary valve : A comparative study with the aortic valve : The VESALIO* project

BACKGROUND Cell populations present in human semilunar valves have not been investigated thoroughly. The aim of this study was to characterize the cell phenotypes in pulmonary valve leaflets (PVL) in comparison with aortic (AVL) valve leaflets. METHODS AVL and PVL were dissected from hearts (n = 4) harvested from transplanted patients. Leaflets were processed for immunocytochemistry analysis and Western blotting procedures using a panel of monoclonal antibodies specific for cytoskeletal/contractile antigens. RESULTS The fibrosa and the ventricularis layers of AVL had a higher cellularity than PVL. In PVL and AVL most cells were reactive for vimentin and nonmuscle (NM) myosin, though vimentin-positive cells were more abundant in AVL than in PVL. Sparse cells positive to anti-smooth muscle (SM) alpha-actin, calponin, and anti-SM myosin antibodies were found only at the outer edge of fibrosa. In Western blotting, AVL and PVL extracts were shown to be equally reactive for vimentin, SM alpha-actin, and NM myosin, whereas both valves were negative for SM myosin and SM22. CONCLUSIONS Three distinct cell phenotypes have been identified in both valves: fibroblasts, myofibroblasts, and fetal-type SM cells whose distribution is specifically related to the valve layers. Although PVL and AVL cell populations differ quantitatively, some minor qualitative differences exist for vimentin and NM myosin distribution. These data are essential for studies aimed at repopulating valve scaffolds by using tissue engineering technology.

Endothelin-1 and its mRNA in the wall layers of human arteries ex vivo.

BACKGROUND The participation of endothelin-1 (ET-1) in the control of vascular tone in humans has been questioned, on the basis of the finding of subthreshold immunoreactive (ir) ET-1 plasma levels. However, because most ET-1 is secreted abluminally, it might attain a higher concentration in the tunica media than in plasma. Furthermore, evidence indicates that vascular smooth muscle cells (VSMCs) can synthesize ET-1 on stimulation in vitro. We therefore looked for irET-1 in the different layers of the wall of human arteries, including renal, gastric, and internal thoracic artery wall, obtained ex vivo from consenting patients with coronary artery disease and/or high blood pressure undergoing surgery, as well as from young organ donors. METHODS AND RESULTS We performed immunohistochemistry with specific anti-ET-1 and anti-vWF antibodies followed by detection with an avidin-biotin complex ultrasensitive kit. The presence of preproET-1 and human endothelin-converting enzyme-1 (hECE-1) mRNA was also investigated by reverse transcription-polymerase chain reaction in homogenates of vessel wall, including preparations deprived of both endothelium and adventitia, and in isolated VSMCs. We detected irET-1 in the endothelium of all arteries and in the tunica media of internal thoracic artery from most patients with coronary artery disease. PreproET-1 and hECE-1 mRNA was also detected in VSMCs isolated from these vessels. irET-1 and irvWF staining in endothelium and tunica media was measured by use of microscope-coupled computer-assisted technology. Significant correlations between the amount of irET-1 in the tunica media and mean blood pressure (P<0.05), total serum cholesterol (P<0.05), and number of atherosclerotic sites (P<0.001) were found. Thus, in organ donors, irET-1 was detectable almost exclusively in endothelial cells, whereas in patients with coronary artery disease and/or arterial hypertension, sizable amounts of irET-1 were detectable in the tunica media of different types of arteries. In addition, VSMCs isolated from these vessels coexpressed the preproET-1 and hECE-1 genes. CONCLUSIONS Collectively, these findings are consistent with the contention that endothelial damage occurs in most patients with atherosclerosis and/or hypertension and that ET-1 is synthesized in VSMCs of these patients.

Cell characterization of porcine aortic valve and decellularized leaflets repopulated with aortic valve interstitial cells: the VESALIO project (vitalitate exornatum succedaneum aorticum labore ingenioso obtenibitur)

BACKGROUND Heart valve bioprostheses for cardiac valve replacement are fabricated by xeno- or allograft tissues. Decellularization techniques and tissue engineering technologies applied to these tissues might contribute to the reduction in risk of calcification and immune response. Surprisingly, there are few data on the cell phenotypes obtained after cellularizing these naturally-derived biomaterials in comparison to those expressed in the intact valve. METHODS Aortic valve interstitial cells (VIC) were used to repopulate the corresponding valve leaflets after a novel decellularization procedure based on the use of ionic and nonionic detergents. VIC from leaflet microexplants at the third passage were utilized to repopulate the decellularized leaflets. Intact, decellularized and repopulated valve leaflets and cultured VIC were examined by immunocytochemical procedures with a panel of antibodies to smooth muscle and nonmuscle differentiation antigens. Intact and cellularized leaflets were also investigated with Western blotting and transmission electron microscopy, respectively. RESULTS Myofibroblasts and smooth muscle cells (SMC) were mostly localized to the ventricularis of the leaflet whereas fibroblasts were dispersed unevenly. Cultured VIC were comprised of myofibroblasts and fibroblasts with no evidence of endothelial cells and SMC. Two weeks after VIC seeding into decellularized leaflets, grafted cells were found penetrating the bioscaffold. The immunophenotypic and ultrastructural properties of the grafted cells indicated that a VIC heterogeneous mesenchymal cell population was present: fibroblasts, myofibroblasts, SMC, and endothelial cells. CONCLUSIONS VIC seeding on detergent-treated valve bioscaffolds has the cellular potential to reconstruct a viable aortic valve.

Repair of tetralogy of Fallot in the first six months of life: Transatrial versus transventricular approach

BACKGROUND This report describes our experience with primary correction of tetralogy of Fallot in infants. METHODS Fifty-one consecutive infants younger than 6 months underwent primary correction of tetralogy of Fallot between January 1978 and October 1994. Mean age at repair was 4.2 months. Four were neonates. Correction was accomplished through a right ventriculotomy in the first consecutive 22 patients (43%; group A); since 1991, a combined transatrial-transpulmonary approach was used in 29 consecutive patients (57%; group B). A transannular patch was necessary in 33 infants (65%) 16 of group A (73%) and 17 of group B (59%). RESULTS There was one early death from possible left anterior descending coronary artery distortion in group A and no deaths in group B. Two patients required early reoperation for systemic-to-pulmonary artery collateral ligation (postoperative day 6) and permanent pacemaker implantation (postoperative day 30). There were no late deaths. All 50 survivors are currently asymptomatic and in New York Heart Association class I. Three patients required late reoperations 36 months, 30 months, and 13 months after repair for (1) subaortic stenosis and dysfunctioning dysplastic mitral valve, (2) residual pulmonary artery branch stenosis, and (3) residual right ventricular outflow obstruction. Four patients underwent balloon dilation and stent insertion (1 patient) for peripheral pulmonary artery stenosis 1.5 year to 12 years (mean, 5 years) after initial repair. Actuarial freedom from need for reintervention at 4 years was 78.4% in group A and 85.7% in group B. Two-dimensional and Doppler echocardiographic follow-up studies showed a residual mild to moderate pulmonary artery branch stenosis in 4 patients in group A, and a recurrent subaortic stenosis in 1 patient in group A. Right ventricular peak systolic pressure was less than 40 mm hg in all but 3 asymptomatic patients who had a residual pulmonary artery branch stenosis. Right ventricular end-systolic and end-diastolic volumes showed larger volumes and reduced ejection fraction in group A compared with group B. CONCLUSIONS This limited experience with repair of tetralogy of Fallot in patients less than 6 months of age demonstrates that the transatrial-transventricular approach is possible in neonates and young infants with a very low mortality and morbidity and also a low incidence of residual lesions. Follow-up echocardiographic data suggest that right ventricular function is better preserved in those patients who underwent the transatrial-transpulmonary repair.

Surgical closure of apical ventricular septal defects through a right ventricular apical infundibulotomy.

BACKGROUND We present a new understanding of the anatomic position of apical ventricular septal defects and its surgical relevance. These defects occur between the left ventricular apex and the infundibular apex, rather than between the left and right ventricular apices. Often a sizable apical recess, the infundibular apex lies anteriorly and inferiorly to the moderator band and is the most leftward part of the right ventricle. METHODS Four patients (2 boys and 2 girls) with a mean age of 109 days (range, 48 to 217 days) underwent patch closure through an apical infundibulotomy, which allowed complete visualization of the muscular apical ventricular septal defect. RESULTS There were no early or late deaths at operation. No significant residual shunt at ventricular level was detected by postoperative two-dimensional and Doppler echocardiography. Intraoperative comparison of right atrial and pulmonary arterial blood samples showed a difference of less than 5%. At a mean follow-up of 18 months, all the patients are asymptomatic and growing well. CONCLUSIONS The successful outcome of these 4 patients indicates that surgical closure of apical ventricular septal defects can be achieved safely and completely in early infancy through a limited right ventricular apical infundibulotomy. Long-term follow-up of these and similar patients is needed to provide further evaluation of this approach.

Prosthetic replacement of the tricuspid valve: biological or mechanical?

BACKGROUND Incidence of tricuspid prosthesis replacement was 1.9% of all valvular operations performed between June 6, 1966 and April 18, 1996. Many series report similar figures, but institutional experience is limited and the consensus on treatment modalities is lacking. METHODS One hundred tricuspid operations were performed on 83 patients (46 female). A primary operation was performed in 64 cases, 13 patients had one previous operation, 4 patients had two previous operations, and 2 patients had three previous operations. Seventeen patients required a tricuspid prosthetic valve rereplacement. There were 2 emergent and 17 urgent operations. The New York Heart Association class was IV in 13 patients (mean pulmonary artery pressure, 41 mm Hg), III in 66 patients (mean pressure, 38 mm Hg), and II in 21 patients. The most frequent operation was simultaneous replacement of the mitral and tricuspid valve (41 patients). Seventy biological and 30 mechanical prostheses were used. Total follow-up time was 613 years, mean 7.4 years (median 4.2 years), with a maximum of 27.8 years, and was 92% complete. RESULTS Operative mortality was 24%. Survival was 0.54 (0.48 to 0.59, n = 39) at 5 years, 0.38 (0.32 to 0.44, n = 27) at 10 years, 0.31 (0.25 to 0.36, n = 19) at 15 years, 0.29 (0.23 to 0.34, n = 11) at 20 years, and 0.17 (0.098 to 0.26, n = 3) at 25 years. Early mortality was increased from higher New York Heart Association class (hazard ratio = 2.2), congenital disease (hazard ratio = 6.9), and valvuloplasty failure (hazard ratio = 4.3). The constant risk phase (4%/patient-year) after 2 years was enhanced by older operative age (hazard ratio = 1.4). Prosthetic type had no independent effect. Biological prostheses were at risk for 300 years and had a reoperation incidence of 4.7%/ patient-year (14 events); mechanical prosthesis were at risk for 137 years with a rate of 2.2%/patient-year (3 events) (p = 0.21). Three valve thromboses were observed in old-design mechanical prosthesis. Bioprosthetic degeneration showed a steeper rate after 7 years. CONCLUSIONS This study does not show a clear superiority of biological versus mechanical prostheses. In the long run survival with mechanical prostheses could be superior, given the high rate of bioprosthetic degeneration after 7 years.

Repair of congenital mitral valve dysplasia in infants and children: is it always possible?

OBJECTIVES Surgical management of congenital malformation of the mitral valve (MV) in the pediatric age group remains a therapeutic challenge for the wide spectrum of the morphological abnormalities and the high incidence of associated cardiac anomalies. We reviewed our experience so as to assess whether MV conservative surgery is always advisable and its results are superior to MV replacement. METHODS Thirty-four consecutive children (20 male and 14 female) with a mean age of 5.9 years (range 45 days-18 years) treated surgically for congenital MV disease between January 1987 and June 1999. Four patients (11.7%) were under 12 months of age, while 21 patients (62%) were younger than 5 years. Twenty-two patients presented with MV incompetence (or prevalent incompetence), while 12 presented with stenosis (or prevalent stenosis). Associated cardiac lesions were present in 22 patients (62.8%). RESULTS Mitral valve reconstruction was possible in all. There were no operative deaths. Three patients required reoperation for MV restenosis (a re-repair in one and MV replacement with mechanical prosthesis in two) 4 months, 27 months and 5.6 years after repair with no operative deaths. There was only one late death for prosthetic valve thrombosis. Follow-up data reveal that the 33 surviving patients are asymptomatic and well 4 months-12 years (mean 72 months) after surgery. At 12 years, actuarial survival and freedom from reoperation are 96.8 and 85.9%, respectively. Echocardiography performed in all of them shows no or mild incompetence or stenosis in 26 (78%), while residual moderate MV incompetence persists in six. CONCLUSIONS Our experience indicates that MV reconstructive procedures in infants and children with congenital MV dysplasia may be effective and reliable with low mortality and low incidence of reoperation rate. Mitral valve repair should always be attempted, especially in infants, despite the frequent severity of MV dysplasia, to avoid the drawbacks of the currently available prostheses.

Double crisscross sternal wiring and chest wound infections: a prospective randomized study.

OBJECTIVE We sought to assess the efficiency of 2 different sternal wiring techniques in preventing deep sternal wound infection or sternal instability. METHODS Seven hundred patients were randomized to 2 different groups according to chest-closure techniques. Three hundred fifty patients who underwent a peristernal double crisscross wire closure were included in group X, whereas 350 patients who underwent a standard transsternal closure were included in group T. After sternal closure, the technique for wound suturing was the same for both groups, namely triple-layer sutures up to the intracutaneous skin. All data were prospectively collected and entered in our institute database. RESULTS The 2 groups of patients were comparable for sex, age, preoperative risk factors, and operative procedures. The overall mortality rate was 4.3% in group X and 4.6% in group T. Postoperative morbidity and mortality were comparable between the 2 groups, unlike for sternal wound complications. None of the patients included in group X had superficial or deep wound complications, whereas in group T 7 (2%) patients presented with a superficial sternal wound infection, 6 (1.7%) presented with a deep chest wound infection with sternal instability requiring re-exploration (P <.05), and 3 presented with a sternal instability caused by sternum disruption without infection. Among patients with deep wound infection and sternal instability, 1 patient died, resulting in a mortality rate of 16.7%. CONCLUSIONS The peristernal double crisscross wiring technique achieved a greater sternal stability, resulting in a lower incidence of wound infection in association with triple-layer closure of suprasternal tissues.