Clinical presentation and management of patients with primary hyperparathyroidism in Italy.

PURPOSE: Evaluation of the phenotype of primary hyperparathyroidism (PHPT), adherence to International Guidelines for parathyroidectomy (PTx), and rate of surgical cure. METHOD: From January 2014-January 2016, we performed a prospective, multicenter study in patients with newly diagnosed PHPT. Biochemical and instrumental data were collected at baseline and during 1-year follow-up. RESULTS: Over the first year we enrolled 604 patients (age 61 ± 14 years), mostly women (83%), referred for further evaluation and treatment advice. Five hundred sixty-six patients had sporadic PHPT (93.7%, age 63 ± 13  years), the remaining 38 (6.3%, age 41 ± 17  years) had familial PHPT. The majority of patients (59%) were asymptomatic. Surgery was advised in 281 (46.5%). Follow-up data were available in 345 patients. Eighty-seven of 158 (55.1%) symptomatic patients underwent PTx. Sixty-five (53.7%) of 121 asymptomatic patients with at least one criterion for surgery underwent PTx and 56 (46.3%) were followed without surgery. Negative parathyroid imaging studies predicted a conservative approach [symptomatic PHPT: OR 18.0 (95% CI 4.2-81.0) P < 0.001; asymptomatic PHPT: OR 10.8, (95% CI 3.1-37.15) P < 0.001). PTx was also performed in 16 of 66 (25.7%) asymptomatic patients without surgical criteria. Young age, serum calcium concentration, 24 h urinary calcium, positive parathyroid imaging (either ultrasound or MIBI scan positive in 75% vs. 16.7%, P = 0.001) were predictors of parathyroid surgery. Almost all (94%) of patients were cured by PTx. CONCLUSIONS: Italian endocrinologists do not follow guidelines for the management of PHPT. Negative parathyroid imaging studies are strong predictors of a non-surgical approach. PTx is successful in almost all patients.

The basal to total insulin ratio in outpatients with diabetes on basal-bolus regimen.

OBJECTIVE: To evaluate the basal/total ratio of daily insulin dose (b/T) in outpatients with diabetes type 1 (DM1) and type 2 (DM2) on basal-bolus regimen, by investigating whether there is a relationship with HbA1c and episodes of hypoglycemia. METHODS: Multicentric, observational, cross-sectional study in Italy. Adult DM1 (n = 476) and DM2 (n = 541) outpatients, with eGFR >30 mL/min/1.73 m2, on a basal-bolus regimen for at least six months, were recruited from 31 Italian Diabetes services between March and September 2016. Clinicaltrials.govID: NCT03489031. RESULTS: Total daily insulin dose was significantly higher in DM2 patients (52.3 ± 22.5 vs. 46 ± 20.9 U/day), but this difference disappeared when insulin doses were normalized for body weight. The b/T ratio was lower than 0.50 in both groups: 0.46 ± 0.14 in DM1 and 0.43 ± 0.15 in DM2 patients (p = 0.0011). The b/T was significantly higher in the patients taking metformin in both groups, and significantly different according to the type of basal insulin (Degludec, 0.48 in DM1 and 0.44 in DM2; Glargine, 0.44 in DM1 and 0.43 in DM2; Detemir, 0.45 in DM1 and 0.39 in DM2). The b/T ratio was not correlated in either group to HbA1c or incidence of hypoglycemia (<40 mg/dL, or requiring caregiver intervention, in the last three months). In the multivariate analysis, metformin use and age were independent predictors of the b/T ratio in both DM1 and DM2 patients, while the type of basal insulin was an independent predictor only in DM1. CONCLUSION: The b/T ratio was independent of glycemic control and incidence of hypoglycemia.

Treatment of peripheral arterial disease in diabetes: a consensus of the Italian Societies of Diabetes (SID, AMD), Radiology (SIRM) and Vascular Endovascular Surgery (SICVE).

Diabetic foot (DF) is a chronic and highly disabling complication of diabetes. The prevalence of peripheral arterial disease (PAD) is high in diabetic patients and, associated or not with peripheral neuropathy (PN), can be found in 50% of cases of DF. It is worth pointing out that the number of major amputations in diabetic patients is still very high. Many PAD diabetic patients are not revascularised due to lack of technical expertise or, even worse, negative beliefs because of poor experience. This despite the progress obtained in the techniques of distal revascularisation that nowadays allow to reopen distal arteries of the leg and foot. Italy has one of the lowest prevalence rates of major amputations in Europe, and has a long tradition in the field of limb salvage by means of an aggressive approach in debridement, antibiotic therapy and distal revascularisation. Therefore, we believe it is appropriate to produce a consensus document concerning the treatment of PAD and limb salvage in diabetic patients, based on the Italian experience in this field, to share with the scientific community.

Circulating BRAFV600E in the diagnosis and follow-up of differentiated papillary thyroid carcinoma.

CONTEXT: Cell-free nucleic acids circulating in plasma are considered a promising noninvasive tool for cancer monitoring. BRAF(V600E) mutation in cell-free DNA (cfDNA) could represent an appropriate marker for papillary thyroid carcinoma (PTC). OBJECTIVE: Our aim is to investigate the role of BRAF(V600E)-mutated allele in cfDNA as a marker for the diagnosis and follow-up of PTC. STUDY DESIGN: BRAF(V600E) allele was detected and quantified by an allele-specific real-time quantitative PCR assay in plasma from 103 patients affected by nodular goiter. As control populations, we enrolled 49 healthy subjects and 16 patients with non-nodular thyroid diseases. RESULTS: The percentage of circulating BRAF(V600E) was significantly different between patients and controls and throughout different cytological categories of ultrasound-assisted fine-needle aspiration. Patients with a histopathological diagnosis of PTC showed a higher percentage of circulating BRAF(V600E) (P = .035) compared to those with benign histology. In 19 patients, a second blood draw, taken 3-6 months after surgery, showed a lower percentage of BRAF(V600E) in cfDNA than the presurgical sample (P < .001). The diagnostic performance of circulating BRAF(V600E) was assessed by receiver operating characteristic curve analysis resulting in an area under the curve of 0.797. A cutoff value was chosen corresponding to maximum specificity (65%) and sensitivity (80%). On this basis, we evaluated the predictive value of BRAF(V600E) in Thy 3 patients with a resulting positive predictive value of 33% and a negative predictive value of 80%. CONCLUSIONS: The results of the present study provide encouraging data supporting the possibility to take advantage of circulating BRAF(V600E) in the management of PTC.

A simple ultrasound score for the identification of candidates to fine needle aspiration of thyroid nodules.

BACKGROUND: Cytological examination of fine needle aspirates (FNA) is the standard procedure for discriminating potentially malignant thyroid nodules to be referred to surgery. In a fraction of cases, ultrasound (US) examination could provide information theoretically sufficient to avoid FNA, when typical US features suggesting malignancies are lacking. AIM: The aim of this study was to construct a simple US score predicting malignant nodules so as to reduce the number of unnecessary FNA. SUBJECTS AND METHODS: In a series of 1632 consecutive patients undergoing US-guided FNA (1812 nodules), echostructure, echogenicity, margins, halo, microcalcification, and vascularization were assessed. RESULTS: At multivariate analysis, the following parameters showed a strong predictive value for positive cytology (Thy 4 and Thy 5, suspicious and diagnostic for malignancy, respectively, according to the Thyroid British Association): solid echostructure, irregular margins and hypoechogenicity [adjusted odd ratio (OR) 5.13 (1.58-16.66), 3.03 (1.70-5.39), 2.05 (1.17-3.57), respectively]. A 10-point Thyroid Risk Ultrasound Score (TRUS) was constructed on the basis of the adjusted OR. A TRUS≥6 identified malignant nodules with sensitivity and specificity of 73% and 65%, respectively. Among the patients with follicular lesions (Thy 3) and final diagnosis of carcinoma, about 65% had a TRUS≥6.0. CONCLUSIONS: The sensitivity of TRUS, although higher than that of other scores, could still be insufficient for the identification of patients who could avoid FNA in routine clinical practice, whereas its predictive value for Thy 3 lesions deserves further investigations.

Perioperative optic neuropathy following off-pump coronary artery bypass grafting.

Visual loss from ischemic perioperative optic neuropathy (PON) rarely occurs during the postoperative period of patients undergoing cardiac surgery. Since the first description, PON has been associated with cardiopulmonary bypass (CPB), being some CPB-related complications and epiphenomena considered the causes of such terrible complication. In particular, the risk for micro-embolization during aortic cannulation and clamping, the CPB-related inflammatory response, the hemodilution and the hypothermia during CPB could be responsible of PON. However, some cases of PON still remain idiopathic. We report here a very rare case of PON following off-pump surgery in a patient with severe coronary disease and multiorgan comorbidities. The case reported opens the debate on the potential mechanisms underlying PON, other than cardiopulmonary bypass.

Myocardial protection in diabetics with left main stem disease: which is the best strategy?

AIM: Diabetes mellitus is a well known risk factor for extensive coronary disease. The optimal route for cardioplegia administration in patients with severe ischaemic heart disease undergone surgery, especially with left main stem disease (LMSD) is still under debate. Aim of the study is to compare 2 different strategies of myocardial protection in diabetics with LMSD. METHODS: Between January 2000 and June 2003 90 consecutive patients with type II diabetes mellitus and LMSD undergoing isolated myocardial revascularization were divided into 2 groups according to the route of cardioplegia delivery: antegrade in 45 patients (group A), antegrade followed by intermittent retrograde in 45 (group B). ECG, Troponin I, MB-CPK, MB-CPK mass were performed at 12, 24, 48, and 72 hours postoperatively. Echocardiography was performed preoperatively and before hospital discharge. RESULTS: Groups were homogeneous in preoperative and intraoperative variables, apart from higher incidence of unstable angina and longer cardiopulmonary bypass time in Group B and hypertension in Group A. Hospital deaths, in intensive care units (ITU) stay, perioperative acute myocardial infarction, intra-aortic balloon pump support, postoperative recovery of left ventricle ejection fraction and wall motion score index were similar in both groups. In hospital stay proved shorter in group B (p=0.002), whereas postoperative atrial fibrillation was higher in group A (p<0.001), as postoperative inotropic support (p=0.006). Troponin I proved significantly higher in group A from the 12 degrees to the 72 degrees postoperative hour (p<0.0001). CONCLUSIONS: Despite major in hospital end-points did not differ with strategy of cardioplegia administration, combined route of intermittent blood cardioplegia allows better biochemical and perioperative results in diabetics with LMSD.

The risk of stroke following CABG: one possible strategy to reduce it?

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

Myocardial protection with insulin cardioplegia: who can really benefit?

AIM: The aim of the study was to evaluate the effects on myocardial protection of insulin-enriched warm blood cardioplegia (IWBC) in coronary artery bypass grafting (CABG) and in subgroups of patients with associated cardiac co-morbidities. METHODS: Between May 2000 and December 2002, 268 consecutive patients underwent CABG with warm blood cardioplegia (group A) or IWBC (10 UI/L) (group B). Hospital outcome, ECG, echocardiography and biochemical markers of ischemia were compared. Differences between subgroups of patients with unstable angina (UA), ventricular hypertrophy (VH) and diabetes were assessed. RESULTS: Hospital mortality, incidence of postoperative myocardial infarction and low output syndrome, IABP requirement, postoperative atrial fibrillation, in-hospital and in-ITU stay, postoperative recovery of left ventricular function and enzyme leakage did not show differences between the 2 groups; inotropic support was lower in IWBC. Moreover, patients with UA and IWBC showed a lower troponin I (TnI) (12 h: 0.82+/-0.57 ng/mL vs 2.56+/-1.18, P < 0.0001; 24 h: 0.71+/-0.64 vs 2.16+/-1.52, P < 0.0001; 48 h: 0.69+/-1.13 vs 1.79+/-1.43, P = 0.001; 72 h: 0.44+/-0.83 vs 1.01+/-1.02, P = 0.001), lower incidence of atrial fibrillation (4.2% versus 60.6%; P < 0.0001) and intraoperative defibrillation (0% versus 27.3%; P = 0.007). Furthermore, patients with VH treated with IWBC showed lower level of TnI (12 h: 0.41+/-0.32 ng/mL vs 2.93+/-0.67, P < 0.0001; 24 h: 0.37+/-0.45 vs 2.40+/-1.28, P < 0.0001; 48 h: 0.22+/-0.18 vs 1.95+/-1.33, P < 0.0001; 72 h: 0.12+/-0.12 vs 1.31+/-1.56, P < 0.0001), lower atrial fibrillation (6.5% vs 48%, P < 0.0001) and ventricular defibrillation (0% vs 20%, P = 0.011). CONCLUSIONS: Insulin addiction to blood cardioplegia does not show any benefit in the global population and in diabetics; nevertheless, better myocardial protection can be demonstrated in patients with unstable angina and left ventricular hypertrophy.

Evolving practice patterns in heart transplantation: a single-center experience over 15 years.

This analysis is a retrospective characterization of evolving patterns in donor and recipient risk factors for early and late outcomes (survival and freedom from rejection) along with determinants of hospital and 1-year mortality after heart transplantation over a 15-year experience in a single center. Profiles and outcomes were evaluated for procedures performed between 1988 and 1995 (group A, n = 105) versus 1996 and 2003 (group B, n = 218). The following parameters were considered: pretransplant diagnosis, recipient age UNOS status, donor age, total postretrieval ischemic time, donor/recipient size match, and degree of myocardial necrosis at biopsy. Recipients in group B were significantly more compromised as demonstrated by UNOS status (11.4% vs 19.3%; P =.05) and pretransplant pulmonary vascular resistance (2.3 +/- 1.5 vs 3.1 +/- 1.5; P =.04). Marginal donors were more frequently used for group B procedures (21.9% vs 47.7%; P <.0001). Outcomes were significantly more favorable among group B patients in terms of hospital mortality (18.1% vs 10.6%; P =.046), and 1- and 5-year actuarial survival (72.4% vs 83.4%, 60% vs 73.3%, respectively; P =.006). Analysis of the causes of death disclosed a significant reduction in fatal events due to graft failure and acute rejection in group B. No difference emerged with regard to actual freedom from acute rejection. Determinants of hospital mortality were pretransplant diagnosis, UNOS status, donor age, and cardioplegic solution. Transplant era, recipient age, infectious episodes, and ischemic necrosis at biopsy were risk factors for 1-year mortality. We conclude that despite extensive usage of marginal donors and selection of worse candidates, significantly better outcomes were achieved due to improvements in global management strategies.

Midterm results of a prospective randomized comparison of two different rabbit-antithymocyte globulin induction therapies after heart transplantation.

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

Initial clinical and hemodynamic experience with Edwards MIRA mechanical bileaflet valve.

AIM: An enhanced bileaflet valve, the Edwards MIRA feminine Mechanical Valve became available in 1998. Favorable hydrodynamic features and a redesigned sewing ring encouraged us to implant this device in indicated patients. Hemodynamics and clinical performance parameters were evaluated. METHODS: Between February 1998 and October 1999, 338 patients (171 males, 167 females) underwent native valve replacement with a MIRA prosthesis. Mean age 56.6+/-13.6 years, 320 patients were in NYHA class III/IV. Sixty-seven patients had echocardiographic examinations. Standard cardiopulmonary bypass was employed utilizing institutionally accepted implantation techniques. Aortic valve replacement was performed in 163 patients, mitral valve replacement in 134 patients, 35* double valve replacements and 1 triple valve replacement. RESULTS: Follow-up is 98% complete. Mean follow-up is 6.9+/-3.3 months (178.2 patient years). There were no operative deaths. Four early deaths were seen (1.18%). Late deaths reported in 12 patients. Linearized rate of late mortality was 6.7% per patient year (ppy). Overall actuarial survival at 13 months is 92.2%. Mean gradients and Effective Orifice Areas (EOA's) are comparable to other bileaflet valves. Linearized rates for valve-related complications was 4.49% ppy. Only 5 transient thromboembolic events (TE = 2.81% ppy) and 3 non-structural valve dysfunction events (NSVD = 1.68%) were seen. No reports of bleeding events, prosthetic endocarditis, valve thrombosis or structural valve deterioration. One patient required mitral valve reoperation for perivalvular leak. CONCLUSIONS: Short-term hemodynamic and clinical results are comparable to other bileaflet valves. The sewing ring is non-obstructive, compliant with smoother needle penetration. Early clinical results are encouraging, follow-up should be continued.

Pilot study on prevention of lung injury during surgery for type A acute aortic dissection: no evident improvements with celsior flushing through the pulmonary artery.

OBJECTIVE: Postoperative respiratory failure is a frequent and serious complication in patients with type A acute aortic dissection. Experimental evidence suggests that pulmonary artery perfusion using hypothermic protective solutions helps prevent lung injury. The aim of this pilot prospective study was to evaluate the effect of pulmonary artery flushing during selective cerebral perfusion (SCP) on lung function. METHODS: Twenty patients referred for acute type A aortic dissection, who were free from preoperative respiratory dysfunction, were assigned prospectively and alternately to two treatment groups. Pulmonary flushing was performed during SCP in group P (10 patients), while conventional Kazui technique was applied in group N (10 patients). Lung perfusion consisted of single-shot hypothermic pulmonary artery flush with Celsior. Lung function was evaluated by intubation time, scoring of chest radiograms at 12 hours after CPB, and PaO2/FiO2 assessed from immediately before surgery to 72 hours after termination of cardiopulmonary bypass. RESULTS: Incidence of pre, intra and post operative determinants of lung dysfunction proved homogeneous in both groups. Lung oxygenation function showed a marked post operative decline followed by a slow improvement in both groups. Analysis of respiratory ratios did not disclose significant differences even though the flushed group had a better performance in all study patients. The incidence of prolonged ventilator support (longer than 72 hours) (30% vs 20%, p = NS) and severity of x-ray pulmonary infiltrate score were comparable (mean score 1.7 +/- 0.71 vs 1.6 +/- 0.68, p = NS). CONCLUSIONS: Pulmonary artery flushing with Celsior solution does not seem to provide an effective preservation of lung function.

Surgical injury of rat arteries: genetic control of the remodelling process.

OBJECTIVES: Remodelling and restenosis are complex biological processes responsible for bypass and percutaneous transluminal coronary angioplasty failures which are likely to affect many hundreds of genes. We evaluated the effectiveness of topically applied antisense oligonucleotides in reducing the translation of the messenger RNA for the transcription factor c-myc and in reducing stenosis. METHODS: Surgery was performed under sterile conditions; 60 Wistar-Kyoto male rats were anaesthetized by ketamine. The carotid arteries were isolated through a median incision in the anterior neck region. At the same point, 0.5 mm longitudinal incisions were performed. Haemostasis was obtained by an adventitial 8.0 stitch. Thirty animals were given 150 microg of c-myc antisense oligonucleotide (Group A) while the other 30 animals received 150 microg of c-myc control sense oligonucleotide (Group B). Oligo molecules were locally applied through 100 microl of 20% pluronic gel. Rats were sacrificed at 30 days; carotid arteries were explanted and stained. Qualitative histological analysis was performed in all cases; serial sections were made every 25 micro in seven consecutive rats for each group. Morphometric analysis was also performed, luminal and medial area values recorded and the ratio between the two areas calculated. Data from each animal were compared with the corresponding contralateral carotid artery and expressed as mean+/-standard deviation. Statistical comparison between the two groups was carried out by one-way ANOVA text. RESULTS: Qualitative histological analysis showed marked remodelling with complete disarray of vessel wall, neointima accumulation and evidence of elastic fibres in the adventitia of all animals of Group B versus Group A. Morphometric analysis showed a significant reduction in the lumen area in Group A animals together with increased values of the medial area versus Group B animals. In addition, the ratio between the lumen and medial area was significantly higher in Group A than in Group B (2.61+/-0.18 versus 1.14+/-0.33, P<0.0001). CONCLUSIONS: c-myc antisense oligonucleotides applied intraoperatively can reduce post-operative stenosis.

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.

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.

Infective endocarditis of native cardiac valves: 22 years' surgical experience.

BACKGROUND AND AIM OF THE STUDY: Most previous studies on surgery for endocarditis included cases of both prosthetic and native valve endocarditis (NVE), which clearly differ in their course and prognosis. METHODS: Between February 1979 and July 2000, 199 patients underwent surgical treatment for NVE. The native valve was replaced in 185 patients, and repaired in 14. Correlations between previous heart disease and site of NVE, site and etiology, site and embolism, and etiology and extracardiac infection were analyzed. Viability of echocardiography to identify NVE features was compared with surgical inspection. Risk factors for hospital, late mortality and recurrence were assessed by multivariate analysis, including preoperative, operative and postoperative variables. RESULTS: Streptococci were found in 52 cases (26.1%), mostly spreading from splanchnic (n = 10) and cutaneous (n = 9) infections; Staphylococci were found in 43 cases (21.6%), mostly from cutaneous foci (n = 20). Tricuspid valve endocarditis was due to Staphylococcus sp. in all documented cases (11/15; p <0.001), while Streptococcus sp. predominated in the mitral (p = 0.026) position. Echocardiography was reliable in identifying anatomic features of NVE, except for periannular abscess (13 versus 31 found at surgery; p <0.001). Hospital mortality was 6% (n = 12): preoperative NYHA class IV (p = 0.034) and emergency surgery (p = 0.001) were significant predictors of mortality. Average follow up was 57.2+/-4.4 months and was 96.3% complete. There were 27 late deaths (15%). Actuarial survival was 75.7% at 10 years and 60.3% at 20 years. Low social status (p = 0.022), diabetes mellitus (p = 0.003), fever at time of surgery (p = 0.041) and persistent postoperative fever (p = 0.0002) were predictors for late mortality. Endocarditis recurred in 28 patients (15.5%), with 74.1% freedom at 10 years and 68.7% at 20 years. Drug abuse (p = 0.001), mitral endocarditis (p = 0.002), positive blood cultures (p = 0.0003), homograft implantation (p = 0.0012) and persistent postoperative fever (p <0.0001) were significant predictors for recurrence. CONCLUSION: Preoperative conditions of patients with NVE significantly affect early and long-term outcomes. Prognosis is worsened by delayed diagnosis and operation during the active septic process.

Risk predictors of paroxysmal atrial fibrillation following aortic valve replacement.

BACKGROUND: Atrial fibrillation (AF) is the most frequently encountered arrhythmic complication associated with cardiac surgery. The aim of this paper was to identify the clinical predictors of AF occurrence following aortic valve replacement. METHODS: Three hundred and two patients were included in this study and divided into two groups according to the absence (SR group, 243 patients, mean age 55.6 +/- 15 years) or the evidence (AF group, 59 patients, mean age 63.8 +/- 11 years) of post-aortic valve replacement AF. Sixty-five perioperative variables (37 preoperative, 8 intraoperative and 20 postoperative) were considered. RESULTS: Post-aortic valve replacement paroxysmal AF occurred in 59 out of 302 patients (19%). At univariate analysis, post-aortic valve replacement AF was associated with advanced age, left atrial enlargement, preoperative episodes of paroxysmal AF, the use of a warm blood cardioplegic solution and normothermia, administration of inotropic agents, prolonged assisted ventilation but also with postoperative acidosis, electrolyte imbalance and atrioventricular and intraventricular conduction disorders. Stepwise forward multivariate logistic regression analysis identified age (p = 0.002, odds ratio--OR 1.04), left atrial enlargement (p = 0.004, OR 2.6), a prior history of paroxysmal AF (p = 0.0003, OR 10.9), and postoperative electrolyte imbalance (p = 0.01, OR 2.3) as independent correlates of AF, whereas the use of hypothermia appeared to be a protective factor (p = 0.0004, OR 0.26). CONCLUSIONS: According to our findings, post-aortic valve replacement AF seems to be associated with well-defined anatomical and electrical substrates generated by advanced age, increased left atrial dimensions, and a possible electrical remodeling consequent to prior repetitive episodes of paroxysmal AF. On these grounds, external factors such as postoperative electrolyte imbalance might enhance atrial ectopic activity and trigger postoperative sustained tachyarrhythmias, while the use of hypothermia might allow for better protection of the atrial myocardium against intraoperative ischemia.

Recurrent infective endocarditis: a multivariate analysis of 21 years of experience. arenzul@tin.it.

BACKGROUND: To evaluate which variables predict recurrence of endocarditis after surgical treatment, we reviewed our 21-year experience. METHODS: Between January 1979 and May 2000, 308 consecutive valve replacement procedures for infective endocarditis were performed in 271 patients. Univariate and multivariate time-related analyses were performed to retrospectively evaluate the role of the following variables in the development of recurrent postoperative endocarditis: gender, site of endocarditis, previous valve disease, drug abuse, diabetes, positive valve/blood cultures, sepsis, perivalvular involvement, previous embolic events, type of replacement device, and persistent postoperative fever. RESULTS: Clinical and echocardiographic follow-up was 97.36% complete, mean follow-up time was 53.2+/-3.4 months. Recurrent endocarditis developed in 58 cases (22.5%). Variables predicting recurrence were prosthetic endocarditis (p = 0.00001), positive valve culture (p = 0.0039), and persistence of fever at the seventh postoperative day (p = 0.000001). CONCLUSIONS: Correct protocols of antibiotic therapy guided by microbiology may reduce the incidence of recurrent endocarditis to allow for surgery on sterile tissues and to prevent prosthetic infection. Recurrence rate is not affected by the choice of valve substitute, but can be prevented by complete surgical debridement.