Italian guidelines for the management of adult individuals with overweight and obesity and metabolic comorbidities that are resistant to behavioral treatment.

AIM: This guideline (GL) is aimed at providing a clinical practice reference for the management of adult patients with overweight or obesity associated with metabolic complications who are resistant to lifestyle modification. METHODS: Surgeons, endocrinologists, gastroenterologists, psychologists, pharmacologists, a general practitioner, a nutritionist, a nurse and a patients' representative acted as multi-disciplinary panel. This GL has been developed following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A systematic review and network meta-analysis was performed by a methodologic group. For each question, the panel identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for clinical practice recommendations. Consensus on the direction (for or against) and strength (strong or conditional) of recommendations was reached through a majority vote. RESULTS: The present GL provides recommendations about the role of both pharmacological and surgical treatment for the clinical management of the adult patient population with BMI > 27 kg/m2 and < 40 kg/m2 associated with weight-related metabolic comorbidities, resistant to lifestyle changes. The panel: suggests the timely implementation of therapeutic interventions in addition to diet and physical activity; recommends the use of semaglutide 2.4 mg/week and suggests liraglutide 3 mg/day in patients with obesity or overweight also affected by diabetes or pre-diabetes; recommends semaglutide 2.4 mg/week in patients with obesity or overweight also affected by non-alcoholic fatty liver disease; recommends semaglutide 2.4 mg/week as first-line drug in patients with obesity or overweight that require a larger weight loss to reduce comorbidities; suggests the use of orlistat in patients with obesity or overweight also affected by hypertriglyceridemia that assume high-calorie and high-fat diet; suggests the use of naltrexone/bupropion combination in patients with obesity or overweight, with emotional eating; recommends surgical intervention (sleeve gastrectomy, Roux-en-Y gastric bypass, or metabolic gastric bypass/gastric bypass with single anastomosis/gastric mini bypass in patients with BMI ≥ 35 kg/m2 who are suitable for metabolic surgery; and suggests gastric banding as a possible, though less effective, surgical alternative. CONCLUSION: The present GL is directed to all physicians addressing people with obesity-working in hospitals, territorial services or private practice-and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.

Increased myocardial GRP94 amounts during sustained atrial fibrillation: a protective response?

BACKGROUND: Structural and phenotypic changes of cardiomyocytes characterize atrial fibrillation. We investigated whether changes in the glucose-regulated protein GRP94, which is essential for cell viability, occur in the presence of chronic atrial fibrillation. METHODS AND RESULTS: Samples of fibrillating atrial myocardium obtained from both goat and human hearts were analyzed for GRP94 expression by an immunologic approach. In goats, atrial fibrillation was induced and maintained for 2, 4, 8, and 16 weeks. After 16 weeks of atrial fibrillation, cardioversion was applied and followed by 8 weeks of sinus rhythm. GRP94 levels doubled in goat atrial myocytes after 4 to 16 weeks of fibrillation with respect to normal atria and returned to control levels in atrial myocardium of cardioverted goats. Immunohistochemical analyses confirm that GRP94 increase occurred within cardiomyocytes. Significantly, increased levels of GRP94 were also observed in samples from human fibrillating atria. In the absence of signs of myocyte irreversible damage, the GRP94 increase in fibrillating atria is comparable to GRP94 levels observed in perinatal goat myocardium. However, calreticulin, another endoplasmic reticulum protein highly expressed in perinatal hearts, does not increase in fibrillating atria, whereas inducible HSP70, a cytoplasm stress protein that is expressed in perinatal goat hearts at levels comparable to those observed in the adult heart, shows a significant increase in chronic fibrillating atria. CONCLUSIONS: Our data demonstrate a large, reversible increase in GRP94 in fibrillating atrial myocytes, which may be related to the appearance of a protective phenotype.

Skin cancer in heart transplant recipients: risk factor analysis and relevance of immunosuppressive therapy.

BACKGROUND: The frequency of skin tumors of all types and specifically of squamous cell carcinoma (SCC) is increased in heart transplantation (HT), but the predisposing risk factors are controversial. METHODS AND RESULTS: We studied 300 patients (age 49+/-15 years, 258 men, mean follow-up 4.6 years, follow-up range 1 month to 12 years) who were receiving standard double (cyclosporin plus azathioprine) or triple (cyclosporin plus azathioprine plus prednisone) therapy. The first-year rejection score was calculated for endomyocardial biopsy samples (International Society for Heart and Lung Transplantation grade 0=0, 1A=1, 1B=2, 2=3, 3A=4, 3B=5, and 4=6) and used as an indirect marker of the level of immunosuppression. Multivariate analysis (Cox regression) included age at HT, sex, skin type, first-year rejection score, presence of warts and solar keratosis, lifetime sunlight exposure, and first-year cumulative dose of steroids. The incidence of skin tumors of all types increased from 15% after 5 years to 35% after 10 years after HT according to life-table analysis. Age at HT of >50 years (P:=0.03, RR=5.3), skin type II (P:=0.05, RR=2.6), rejection score of 19 (P:=0.003, RR=5.7), solar keratosis (P:=0.001, RR=6.9), and lifetime sunlight exposure of >30 000 hours (P:=0.0003, RR=7.6) were risk factors for SCC. CONCLUSIONS: Older age at HT, light skin type, solar keratosis, greater sunlight exposure, and high rejection score in the first year were independently associated with an increased risk of SCC. The progressive increase in cancer frequency during follow-up and the association with high rejection scores suggest that both the length and level of immunosuppression may be relevant. Because cumulative immunosuppressive load is cumbersome to calculate, a high rejection score in the first year may provide a useful predictor for patients at risk.

Hancock II porcine bioprosthesis: excellent durability at intermediate-term follow-up.

OBJECTIVES: This study aimed to assess the clinical performance and durability of a new generation of porcine valve, the Hancock II bioprosthesis, at intermediate-term follow-up. BACKGROUND: Standard porcine bioprostheses undergo progressive structural deterioration, mainly due to cusp and commissural calcification, affecting durability and requiring reoperation. The Hancock II bioprosthesis, which is currently undergoing clinical investigation, is made from a porcine aortic valve treated with a calcium-retarding agent (sodium dodecyl sulfate [T6]), which should delay onset of calcification and increase durability. METHODS: From May 1983 to December 1992, we used the Hancock II bioprothesis in aortic (59 patients), mitral (101 patients) and mitral-aortic (25 patients), valve replacement procedures. Postoperative follow-up ranged from 0.1 to 8.7 years (mean [+/- SD] 4.5 +/- 2.6 years) and was 100% complete. Freedom from major postoperative events was calculated at 7 years for patients with aortic valve replacement and at 8 years for those with mitral and mitral-aortic valve replacement. RESULTS: The actuarial survival rate was 48 +/- 10%, 76 +/- 3% and 63 +/- 6%; freedom from valve-related mortality was 91 +/- 4%, 94 +/- 2% and 89 +/- 6%; freedom from thromboembolism was 80 +/- 11%, 90 +/- 2% and 79 +/- 7%; and freedom from reoperation was 100%, 97 +/- 1% and 89 +/- 6% after aortic, mitral and mitral-aortic valve replacement, respectively. No structural valve deterioration occurred. CONCLUSIONS: At intermediate-term follow-up the Hancock II bioprosthesis showed excellent durability in all positions. However, the effectiveness of anticalcification treatment must be assessed with longer follow-up studies.

Extracorporeal photochemotherapy as adjuvant treatment of heart transplant recipients with recurrent rejection.

Recurrent rejection is an uncommon, severe complication after heart transplantation that is associated with a poor long-term prognosis. Photopheresis (ECP), a new form of extracorporeal photo-chemotherapy used for the treatment of cutaneous T cell lymphoma and several autoimmune diseases, has also been used for prevention and treatment of acute rejection in heart transplant recipients. It seems to induce specific suppression of both cellular and humoral rejection. In this study, we evaluated whether ECP added to standard therapies allowed better control of rejection and reduction of conventional immunosuppressive drugs in patients with repeated rejection episodes. Eight heart transplant recipients (6 men and 2 women, mean age 48 yr), with recurrent rejection were treated with ECP for 6 months. Endomyocardial biopsies (EMB) were performed monthly. As a result of treatment, 7 patients on ECP experienced a reduction of the number and severity of rejection episodes. The fraction of EMB negative for rejection increased from 13 to 41%, whereas the fraction of specimens with multifocal and/or diffuse moderate lymphocytes infiltration (grades 3A and 3B) decreased from 41 to 21%. ECP allowed reductions of daily immunosuppressive therapy: prednisone by 44% (16.9 vs. 9.4 mg), cyclosporine by 21% (366 vs. 291 mg), and azathioprine by 29% (137 vs. 97 mg). No major side effects were observed. We conclude that, although the number of patients is small, the use of ECP was safe and associated with improved control of recurrent rejection. This allowed tapering of immunosuppressive drugs, which was particularly useful in two patients with insulin-dependent diabetes and one with sternal wound osteomyelitis.

Cardiac lithomyxoma.

Among 102 consecutive cardiac myxomas, 10 (10%) showed heavy calcification both on gross inspection and on x-ray examination. Mineralization was partial in 6 patients (mean age 56.8 years) and massive stone-like in 4 (mean age 70 years); relevant histologic findings in patients with partial calcification were Gamma-Gandy bodies in 5, cartilaginous and bone metaplasia in 2, and aspecific calcium deposits in 1. All were incidental findings either at autopsy or during clinical investigation.

Left ventricular rupture following mitral valve replacement with a Hancock bioprosthesis.

A rare complication of mitral valve replacement with the Hancock bioprosthesis was observed in three patients presenting with prevalent mitral stenosis and normally-sized left ventricular cavity. In the patients, a deep erosion of the left ventricular free wall was present which evolved into cardiac rupture in one of them. The laceration is ascribed to the friction between a prosthetic strut and the myocardium; a disproportion between the "high-profile" device and the left ventricular chamber is suggested to explain this complication, which may be avoided by employing a "low-profile" prosthesis.

Mitral and aortic valve replacement in valvular rheumatoid heart disease.

Specific endocarditis involving the aortic and mitral valves in a patient with peripheral rheumatoid arthritis is reported. The patient underwent prosthetic replacement of both valves. Typical rheumatoid nodules were detected histologically in the valvular tissues.

Donor shortage in heart transplantation. Is extension of donor age limits justified?

Chronic shortage of donor organs for heart transplantation led us to extend donor age limits. To verify the effectiveness of such a policy we have compared the results of heart transplantation in 45 patients with donors more than 40 years of age (group 1) with those of 72 patients older than 50 years of age who had heart transplantation with younger donors (group 2) between November 1985 and December 1992. The two groups were comparable in terms of mean recipient age, recipient and donor sex, and indication for heart transplantation. Mean donor age was 46 +/- 4 years (range 41 to 59 years) in group 1 and 23 +/- 7 years (range 8 to 39 years) in group 2 (p < 0.001). In group 1 cerebrovascular accidents were more common as the cause of donor death (60% versus 16%, p = 0.001), and no difference was found in ischemic time (144 +/- 47 minutes versus 140 +/- 48 minutes, p = not significant). There were 6 early (< 30 days) deaths in group 1 (13%) and 10 in group 2 (14%; p = not significant). Fatal acute graft failure was more prevalent, but not significantly so, in group 1 (10% versus 5.5%, p = not significant). Mean follow-up was 29 +/- 20 months (range 3 to 78 months) in group 1 and 30 +/- 20 months (range 3 to 80 months) in group 2 (p = not significant). At 5 years actuarial survival was 80% +/- 6% in both groups with comparable graft performance at echocardiographic and hemodynamic control studies. A significant difference was found in freedom from any type of coronary artery abnormality between group 1 (49% +/- 13%) and group 2 (77% +/- 8%) at 5 years (p < 0.05); however, freedom from coronary stenotic lesions only was similar. Major conduction disturbances have occurred more frequently in patients of group 1 (37% versus 12%; p = 0.003) without any difference in the need for permanent pacing. Donors older than 40 years of age can be accepted for heart transplantation with early and long-term results comparable with those obtained with younger donors. The impact of a higher incidence of coronary abnormalities on late performance of older grafts must be assessed at longer follow-up. Our results indicate that, because of the current organ shortage, extension of donor age limits is justified, even up to the sixth decade of life in selected cases.

Surgical removal of a left atrial myxoma during pregnancy.

Successful removal of a left atrial myxoma in a pregnant woman has not been previously reported. The patient postoperatively had an uncomplicated pregnancy, delivering at term a normal, healthy baby.

Long-term results of mitral commissurotomy.

Between January 1968 and December 1989, 280 patients underwent conservative surgical treatment for pure mitral stenosis. Closed commissurotomy was utilized in 134 patients, with a mean age of 38 +/- 11 years and a mean valve area of 1.0 +/- 0.29 cm2. Open commissurotomy was performed in 146 older patients (mean age 44 +/- 11 years) with a mean valve area of 0.9 +/- 0.3 cm2. The perioperative mortality was 3% in closed procedures and 3.4% in open procedures. Surviving patients were evaluated by questionnaires or phone interviews, and 129 patients were examined by two-dimensional echocardiography with the purpose of analyzing long-term results. Follow-up was 95% complete (Grunkemeier-Starr method), with a median of 18 years in patients with closed commissurotomy and 6.6 years in patients with open commissurotomy. The actuarial survival at 21 years was 60.8% (70% confidence limits 55% to 66%) in patients having closed commissurotomies and 60.6% (70% confidence limits 49% to 71%) at 22 years in patients having open commissurotomies. The "effective palliation" rate, defined by clinical and echocardiographic criteria, was 47% at 15 years and 15% at 20 years. We conclude that mitral commissurotomy is the procedure of choice in pure mitral valve stenosis and should be applied early. When performed in patients aged less than 40 years, a 78% (70% confidence limits 72% to 84%) survival at 18 years and 67% "effective palliation" at 15 years were observed. The closed valvotomy results of our study support the present trend toward use of percutaneous balloon valvotomy.

Pulmonary atresia, intact ventricular septum, and Ebstein anomaly of the tricuspid valve. Anatomic and surgical considerations.

Pulmonary atresia with intact ventricular septum is a disorder that involves the whole right ventricle. An associated Ebstein deformity of the tricuspid valve is found in 10% of the cases, further complicating the anatomy and the function of the right ventricle. From January 1966 to December 1990, pulmonary atresia, intact ventricular septum, and Ebstein deformity of the tricuspid valve were observed in 11 cases in our institution; four of them were necropsy findings and the remaining seven were patients treated surgically. Of the latter, two were boys and five were girls (age range 1 day to 18 days). Two patients were managed by pulmonary valvotomy, three by systemic-pulmonary artery shunt, and two had a combination of the two. Operative mortality was 57%. Eight hearts were available for morphologic study. All had viscero-atrial situs solitus, D-loop ventricular structure, and normally related great arteries. A correlation between the degree of tricuspid valve dysplasia and right ventricular cavity size was observed in all. Furthermore, in five cases the anterior leaflet of the tricuspid valve obstructed the right ventricle at the ostium infundibuli level. In two of our surgical patients, a protruding anterior tricuspid valve leaflet was identified and excised and both patients survived. Ebstein anomaly of the tricuspid valve further complicates surgical management and outcome of pulmonary atresia and intact ventricular septum. Potential obstruction at the ostium infundibuli level should always be considered during repair. Various degrees of right ventricular inlet dysplasia, always present in this complex, may contraindicate an anatomic correction. In these cases a modified Fontan-type procedure should be considered as a valid surgical option.

Aortic valve replacement with pulmonary homografts. Early experience.

The increasing use of the aortic homograft as aortic valve substitute and the limited availability of donor valves prompted us to consider the pulmonary homograft as an alternative substitute for aortic valve replacement. The aim of our study is to compare the ultrastructural and biomechanical properties of pulmonary homograft leaflets with those of their aortic counterpart and to present the early results of using the pulmonary homograft for aortic valve replacement. Light and transmission electron microscopy have shown that pulmonary homograft leaflets are thinner than the aortic with a lesser content of elastic tissue in the ventricularis layer. However there were no substantial differences in the ultrastructure. Uniaxial tensile tests were done on 69 cusps from human pulmonary and aortic valves using an Instron testing machine. The strain at 200 KPa was found to be similar for both pulmonary and aortic leaflets (8.20% +/- 2.87% versus 8.98% +/- 1.90%) cut circumferentially. Radial strips appear to be more extensible in pulmonary leaflets than in aortic (32.6% +/- 7.5% and 28.6% +/- 11.1%, respectively). The ultimate tensile strength for circumferential strips was found to be similar for both aortic and pulmonary valves (1460 +/- 857 kPa versus 1450 +/- 689 kPa), but there was relatively little difference between the radial strips (295 +/- 95 kPa versus 252 +/- 104 kPa). A total of 123 patients whose ages ranged between 13 and 78 years received either fresh antibiotic sterilized or cryopreserved pulmonary homografts for aortic valve replacement. The pulmonary homograft was inserted in place of the patient's diseased aortic valve by using one of two different techniques: freehand in the subcoronary position or as a "short cylinder" inside the aortic root. There was three hospital deaths (2.43%; 70% confidence limits = 1.08% to 4.83%). Cumulative follow-up was 184 patient-years (range 1 to 39 months). All surviving patients have been followed up with serial color flow Doppler echocardiography. There were no late deaths. Actuarial late survival was 97.5% (70% confidence limits = 95.7% to 98.6%) at 3 years. Four patients (2.2%/pt-yr) underwent reoperation because of severe aortic regurgitation (1, 4, 12, and 15 months after the operation) because of technical problems (mismatch in size between the pulmonary homograft and aortic anulus) in three patients and probably because of graft rejection in one patient. At 3 years the actuarial rate of freedom from reoperation was 95.5% (70% confidence limits = 92.7% to 97.3%). Mild aortic regurgitation has been detected in three patients (2.6%). No patients incurred thromboembolic episodes or infective endocarditis.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical evaluation of St Jude Medical Hemodynamic Plus versus standard aortic valve prostheses: The Italian multicenter, prospective, randomized study.

OBJECTIVE: Hemodynamic and clinical performances of 21-mm and 23-mm St Jude Medical Hemodynamic Plus aortic valves (St Jude Medical, Inc, St Paul, Minn) were compared with those of 21-mm and 23-mm St Jude Medical standard cuff aortic valves in the first such multicenter, prospective, randomized study. Hemodynamic Plus valves are mechanical, bileaflet prostheses suitable for the small aortic anulus. METHODS: Patients with 21-mm and 23-mm anulus diameters were randomized to receive either a Hemodynamic Plus or a standard cuff valve. Postoperatively and at 6 months after the operation, patients underwent 2-dimensional Doppler echocardiography. Ejection fraction, cardiac output, peak gradient, mean gradient, effective orifice area, effective area index, and performance index were calculated. Postoperative and 6-month echocardiographic measurements and their variations across observation times were analyzed statistically. RESULTS: Of the 140 patients enrolled, 5 died at operation and 1 died of aortic dissection during the follow-up period. Eight patients were lost to follow-up. A total of 125 patients completed the study. In 1 patient a sewing cuff escaped intraoperatively. At 6 months the 21-mm and 23-mm Hemodynamic Plus valves showed significantly lower peak gradients and mean gradients than those of the 21-mm and 23-mm standard cuff valves. The 21-mm Hemodynamic Plus valves had gradients similar to those of the 23-mm Hemodynamic Plus valves. The effective orifice area did not differ significantly between the Hemodynamic Plus and standard cuff valves at either measurement. No valve mismatch was found in the 4 groups of patients. A more enhanced decrease of peak gradients and mean gradients and a more enhanced increase of effective orifice areas, effective area indices, and performance indices were found across observation times for patients with Hemodynamic Plus valves compared with those with standard cuff valves. CONCLUSIONS: Clinical hemodynamic performances of 21-mm and 23-mm St Jude Medical Hemodynamic Plus valves correspond closely with those of standard cuff valves, and gradients are substantially better than those of standard cuff valves of the same diameter. Therefore, use of this valve may minimize the need for aortic anulus enlargement. Early follow-up results with the Hemodynamic Plus valves were excellent, although more time is required to confirm this outcome.

Evolution of focal moderate (International Society for Heart and Lung Transplantation grade 2) rejection of the cardiac allograft.

BACKGROUND: In the absence of clinical evidence of cardiac allograft rejection, it is still poorly defined whether the International Society for Heart and Lung Transplantation biopsy grade 2 (e.g., focal moderate rejection) should be treated. Aim of the present study was to retrospectively investigate the evolution of focal moderate rejection, diagnosed during the first postoperative year in patients who had undergone orthotopic heart transplantation. METHODS: A retrospective analysis was conducted on 256 International Society for Heart and Lung Transplantation grade 2 biopsies from 110 orthotopic heart transplantations; 125 episodes occurred within the first 3 months (group 1), 131 later (group 2). For each grade 2 diagnosis, two biopsies, one immediately before and one after, were analyzed and classified as follows: lower (grade 0 or 1), equal (grade 2), or higher (grade 3 or 4). RESULTS: Evolution of grade 2 rejection was to a lower grade in 66% of cases, an equal grade in 16.8%, and a higher grade in 17.2%, with differences between group 1 and 2 (higher: 25% versus 10%, respectively, p = 0.005). Episodes which progressed into higher grades occurred earlier compared with those which persisted or resolved (9.2 +/- 8.6 weeks versus 20.0 +/- 15.6, p < 0.001). Five-year actuarial survival and incidence of graft coronary disease were similar in patients whose conditions progressed and those whose conditions did not. However, left ventricular ejection fraction at 1 and 2 years was lower in patients whose conditions progressed compared with those whose conditions persisted or resolved (56% +/- 4% versus 66% +/- 2%, p = 0.004; 56% +/- 10% versus 64% +/- 8%, p = 0.02, respectively). CONCLUSIONS: Progression of grade 2 rejection occurred in a minority of cases and did not affect 5-year survival or incidence of coronary disease, but its relationship with long-term cardiac allograft dysfunction warrants further investigation.

Sulfinpyrazone reduces cyclosporine levels: a new drug interaction in heart transplant recipients.

BACKGROUND: Management of cyclosporine (CsA)-associated hyperuricemia in heart transplantation (HT) is difficult. Because of the myelotoxicity of combined allopurinol and azathioprine, we tested sulfinpyrazone. METHODS: We studied 120 HT recipients (109 men; mean age at HT, 52+/-10 years). All had received allopurinol for at least 6 months, which was stopped for 1 month before initiation of sulfinpyrazone. Mean follow-up from HT to onset of sulfinpyrazone (200 mg/day) was 59+/-41 months. We stopped the drug after 6+/-2 months. We compared CsA level and daily dose, serum creatinine, blood urea, and uric acid at onset and before interruption of sulfinpyrazone and, as control, in the last 6 months of allopurinol. RESULTS: Mean uricemia decreased with allopurinol (0.58+/-0.12 vs. 0.41+/-0.07 mmol/liter, p = 0.0001) as well as with sulfinpyrazone (0.51+/-0.13 vs. 0.40+/-0.12 mmol/liter, p = 0.0001). Mean creatinine increased (171+/-42 and 164+/-35 micromol/liter, p = 0.01) with allopurinol, whereas it tended to decrease with sulfinpyrazone (160+/-35 and 154+/-48 micromol/liter, p = NS). Mean urea did not change with allopurinol (14+/-5 vs. 15+/-7 mmol/liter, p = NS), but fell with sulfinpyrazone (14.01+/-5 vs. 12.60 +/-5 mmol/liter, p = 0.0004). Mean CsA levels were constant with allopurinol (193+/-73 vs. 188+/-65 ng/ml, p = NS), although CsA dose was slightly reduced (2.7+/-0.8 vs. 2.6+/-0.8 mg/kg/day, p = 0.007). Conversely, CsA levels dropped with sulfinpyrazone (183+/-89 vs. 121 +/-63 ng/ml, p = 0.0001) despite an increase in CsA daily dose (2.6 +/-0.9 vs. 2.8+/-0.9 mg/kg/day, p = 0.0001). Two subjects were treated for acute rejection. We observed no other side effects. In HT recipients sulfinpyrazone, as an alternative to allopurinol, is effective in achieving metabolic control of hyperuricemia. However, this drug reduced CsA levels, thus the risk of rejection is present.

Discordance between pre and post cardiac transplant diagnosis: implications for pre- and postoperative decision making.

A correct clinical diagnosis in end-stage patients undergoing cardiac transplantation may have important prognostic and therapeutic implications. A retrospective clinico-pathologic study was carried out in 257 patients who had undergone cardiac transplantation at the University of Padua. A discrepancy between clinical and pathological diagnosis was found in 20 cases (8%). Among 126 patients with the clinical diagnosis of dilated cardiomyopathy, seven were found eventually to have ischemic heart disease (IHD), five myocarditis, one arrhythmogenic right ventricular cardiomyopathy (ARVC), and one non-compacted myocardium. Among the 87 patients with clinical diagnosis of IHD, three turned out to be dilated cardiomyopathy and one granulomatous myocarditis. Among the 10 patients with the clinical diagnosis of hypertrophic-restrictive cardiomyopathy, one had ARVC and one had cardiac fibroma. Altogether, only 24.5% underwent endomyocardial biopsy (EMB) and 75% coronary angiography before transplantation. Missed diagnosis of myocarditis occurred in patients in whom EMB was not carried out. EMB and coronary angiography might be indicated routinely in patients with apparent dilated cardiomyopathy, before proceeding to cardiectomy.

Repair of aortico-left ventricular tunnel originating from the left aortic sinus.

We report on a case of an 11-year-old asymptomatic child with aortico-left ventricular tunnel arising from the left aortic sinus. Preoperative transesophageal echocardiography showed a dilated aortic root with mild aortic valve incompetence and demonstrated the course of the tunnel, which originated from the left coronary sinus entering the outlet portion of the left ventricular outflow tract. Patch closure of the aortic end of the tunnel eliminated left ventricular volume overload with immediate marked reduction of cardiomegaly. At 10-month follow-up the child is asymptomatic and receiving no oral medications. Control two-dimensional Doppler echocardiography shows trivial central aortic valve incompetence.

Demand dynamic cardiomyoplasty: mechanograms prove incomplete transformation of the rested latissimus dorsi.

BACKGROUND: In dynamic cardiomyoplasty, standard stimulation produces high fatigue resistance but also undesirable dynamic characteristics of the latissimus dorsi (LD). Based on results of intermittent stimulation in animals we introduced demand stimulation, a lighter regimen of LD activity-rest stimulation, and the mechanogram, a noninvasive method to determine the contractile characteristics of LD wrap. METHODS: Surgery and standard stimulation was according to the technique of Carpentier and Chachques, demand stimulation and LD wrap mechanogram were as we previously described. The LD contraction is synchronized to heart systole by mechanogram and echocardiography, and extent of transformation by tetanic fusion frequency analysis. A total of 22 patients were studied to date. Data for the 8 subjects who attained 6-month follow-up are reported. Four of them were lightly stimulated from the conditioning period, whereas 4 others were converted to light and then demand stimulation after years of standard stimulation. Patients were followed up with respect to survival, functional class, hospital admission rate, medication used, cardiopulmonary exercise testing, and LD wrap mechanography. RESULTS: Latissimus dorsi wrap slowness reverses by the activity-rest regimen, even after years of standard stimulation (Tetanic fusion frequency of 11 +/- 2 Hz after standard stimulation vs 30 +/- 3 Hz after demand regimen, p < 0.0001). After demand dynamic cardiomyoplasty there are no deaths. Quality of life is substantially improved with significant reduction of heart failure symptoms (New York Heart Association class: preoperative 3.0 +/- 0.0, post-demand dynamic cardiomyoplasty 1.5 +/- 0.2, p < 0.0001). In the subgroup of patients lightly stimulated from LD conditioning, exercise capacity tends to increase over preoperative values more than 2 years after operation (VO2 max: preoperative 12.3 +/- 0.7 vs 16.6 +/- 1.7 post-demand dynamic cardiomyoplasty, p = 0.05). CONCLUSIONS: Demand stimulation and mechanography of the LD wrap are safe procedures that could offer long-term benefits of dynamic cardiomyoplasty to patients with pharmacologically intractable heart failure.

Cell composition of the human pulmonary valve: a comparative study with the aortic valve--the VESALIO Project. Vitalitate Exornatum Succedaneum Aorticum labore Ingegnoso Obtinebitur.

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.