Search PubMed⌕ Search

Biomedical subjects

Gaetano Thiene

Publications and source records attributed to Gaetano Thiene.

At least 55 records · Page 3Linked to original sources
PubMed2005

C2 is superior to C0 as predictor of renal toxicity and rejection risk profile in stable heart transplant recipients.

To assess whether cyclosporine A (CsA) 2-h peak (C2) is superior to trough levels (C0) for Neoral dose monitoring in heart transplantation (HT), we studied 928 C0-C2 paired determinations from 313 stable HT patients (257 male, aged 50 +/- 14 years at HT, follow-up 6.9 +/- 4 years), on a C0-based regimen. Our target C0 levels (ng/ml) were 150-400 (first 3 months), 150-300 (4-12 months), 100-250 (>12 months). Mean C0 and C2 levels were 268 +/- 80 and 1031 +/- 386, respectively (first 3 months); 230 +/- 49 and 955 +/- 239 (4-12 months); 157 +/- 53 and 745 +/- 236 (>12 months). For patients within the target C0, the corresponding C2 were 600-1500 (first 3 months), 600-1300 (4-12 months), 400-1100 (>12 months). C2 correlated with C0 (r = 0.64, P = 0.0001). C2 correlated better with CsA dose than C0 (r = 0.41, P = 0.0001 vs. r = 0.33, P = 0.0001). Between patients, CsA dose varied by a factor of 9.3; the C/dose ratio varied by a factor of 8.5 for C2 and of 15.6 for C0. Patients with higher C2 (>740) had higher severe rejection score at 2 years (P = 0.02) than patients with lower C2. This did not apply to C0. Both C2 and C0 correlated with blood urea (r = -0.18, P = 0.0001; r = -0.12, P = 0.0002) and creatinine (r = -0.19, P = 0.0004; r = -0.19, P = 0.0001 respectively). By logistic regression higher C2 (>740) was associated with higher total severe rejection score at 2 years (P = 0.006). C2 showed better correlation with CsA dose, renal function, rejection profile and less variability between patients than C0. C2 may improve CsA-based immunosuppression in HT.

Cyclosporine↗
PubMed2005

Abnormal total ejection isovolume index as early noninvasive marker of chronic rejection in heart transplantation.

Abnormally high myocardial performance index (MPI) is a Doppler-derived marker of combined systolic and diastolic left ventricular (LV) dysfunction. To identify early stage allograft dysfunction by MPI, we studied 154 long-term heart transplantation (HT) recipients (131 male, aged 51 +/- 13 years at HT, mean follow up 8.4 +/- 3.5 years), with normal left ventricular ejection fraction (LVEF) and free from acute rejection (AR), and 25 normals (13 male, aged 39 +/- 16 years). Rejection score (RS) on endomyocardial biopsy was calculated in the first year. MPI was prolonged (0.45 +/- 0.18 vs. 0.28 +/- 0.10, P = 0.0001) in patients and directly related with mean time from HT (P = 0.001), higher cumulative dosages of cyclosporine at 3 months (P = 0.01), 6 months (P = 0.03), 1 year (P = 0.02), 3 years (P = 0.04) and with cumulative dosage of methylprednisolone at 1 year (P = 0.002). The index was inversely related with mean age at HT (P = 0.002) and tended to be directly related with RS at 1 year (P = 0.05). Thus, MPI is abnormal in long-term HT recipients with normal LVEF. Its direct relation with time from HT as well as immunosuppressive load suggests an early stage of graft dysfunction because of chronic rejection. Extended prospective studies are warranted to clarify its potential role as a negative prognostic marker in HT.

Adult↗
PubMed2005

Biological versus mechanical aortic prosthesis? A nineteen-year comparison in a propensity-matched population.

BACKGROUND AND AIM OF THE STUDY: The choice of aortic valve substitutes remains controversial. Malfunction and systemic valve complications affect the results of mechanical and tissue valves. Two devices--the Sorin Monocast (tilting disk) valve and the Hancock Standard valve were compared, the study aim being to determine whether the valve model is a marker or a causal influence of poor outcome after aortic valve replacement (AVR). METHODS: Between January 1970 and January 1984, patients aged < 70 years and operated on for aortic valve disease were selected. A total of 379 patients received either Sorin (group S) valves (n = 213; median age 51 years) or Hancock Standard (group HcK) valves (n = 192; median age 50 years) (p = NS). Total follow up was 2,471 patient-years (pt-yr) for group S and 2,368 pt-yr for group HcK. Follow up was 98% complete; median duration was 15 pt-yr for group S and 13.2 pt-yr for group HcK. Propensity matching for available patient intrinsic and operative risk factors was ultimately used to investigate whether biological or mechanical valve models impact upon outcome after aortic valve surgery. Patient survival was analyzed according to the 'intention to treat' principle. RESULTS: The 30-day mortality was 7.5% for group S and 10.9% for group HcK (p = NS). The 19-year Kaplan-Meier freedom from valve-related mortality was 84% (group S) and 82% (group HcK) (p = NS), while overall survival was 42% (group S) and 35% (group HcK) (p = NS). Structural valve deterioration (SVD) was the major cause of reoperation in the HcK group. The 19-year freedom from all valve-related complications was 43% (group S) versus 19% (group HcK) (p = 0.0001). By propensity score, 61% of the valve replacements (247/405) were perfectly matched for available risk factors, with an equal distribution of risk covariates. When SVD and reoperation due to SVD were excluded, survival and freedom from all valve-related complications of the matched patients were identical between the prostheses under comparison. CONCLUSION: In this relatively young population, the Sorin valve showed a significantly lower valve-related complication rate than the Hancock Standard valve. The latter valve showed a significantly increasing rate of reoperation due to SVD, and thereby a relative inadequacy for use in younger patients. When analyzed according to an 'intention to treat' principle, the 19-year survival and freedom from valve-related complications of patients with the same propensity score for selection of either valve type were similar.

Adolescent↗
PubMed2004

Intramyocyte detection of Epstein-Barr virus genome by laser capture microdissection in patients with inflammatory cardiomyopathy.

BACKGROUND: The causal role of Epstein-Barr virus (EBV) in inflammatory cardiomyopathy (IC) is still unclear, because this virus is present in latently infected circulating B lymphocytes in 90% of adults. Laser capture microdissection (LCM) has been applied on endomyocardial biopsy samples from patients with IC to assess the presence of EBV genome in separately dissected lymphocytes and myocytes. METHODS AND RESULTS: Among 142 patients with cardiac dilation and dysfunction and a histological and immunohistochemical diagnosis of myocarditis, 44 had a myocardial viral infection detected by polymerase chain reaction on frozen endomyocardial biopsy samples. In 9 of them, the virus detected was EBV. LCM was performed on 5-microm-thick paraffin sections of EBV-infected hearts. Lymphocytes and myocytes were microdissected and analyzed separately by polymerase chain reaction analysis on DNA extracted from the collected cells. Blood and myocardial samples from patients with positive and negative serology for EBV were used as controls. EBV genome was detected in myocytes but not in infiltrating lymphocytes of patients, nor in myocardial samples from controls. Despite full conventional antifailure therapy, a progressive cardiac dilation and dysfunction was documented in patients with EBV-related IC at a mean of 31+/-14 months of follow-up. CONCLUSIONS: Intramyocyte detection of EBV can be obtained by LCM in up to 6.3% of patients with IC. This supports a cytopathic EBV role and suggests the opportunity for an antiviral/immunomodulatory therapy.

Adult↗
PubMed2004

Distal protection with a filter device during coronary stenting in patients with stable and unstable angina.

BACKGROUND: Filter protection after percutaneous coronary intervention (PCI) is now available to prevent distal embolization. The aims of this study were (1) to evaluate the microembolization phenomenon during procedures of stent implantation in native coronary arteries of patients with stable and unstable angina, (2) to assess the amount and characteristics of the debris captured by the Angioguard, and (3) to investigate the relation between clinical and angiographic variables and pathological data. METHODS AND RESULTS: Elective coronary stenting with the use of a protective filter was attempted in 39 consecutive coronary artery lesions with >60% stenosis (mean, 67.6+/-8.79%). Debris was present in 75.6% of the filters. Particle size ranged from 47.16 to 2503.48 microm (mean, 518.83+/-319.61 microm) in the major axis. Particles >300 microm were found in 24 of 28 filters with debris (85.7%), and particles >1000 microm were present in 10 of 28 filters (35.7%). Patients with unstable angina had greater particles (mean maximum longitudinal diameter, 1098.33+/-714.3 microm) than those with stable angina (412.91+/-453 microm; P<0.001). The presence of unstable angina (OR, 65; CI, 1.2 to 3420; P=0.03) and age >67 years (OR, 42; CI, 1 to 1698; P=0.04) were found to be the only independent predictors of embolic particle size. CONCLUSIONS: By limiting embolization, protective devices may prevent a number of potentially unfavorable events, thereby improving outcome. Our data support the use of these devices, especially in lesions with higher embolic potential, such as those occurring in older patients and in those with unstable angina.

Aged↗
PubMed2004

An echocardiographic survey of primary school children for bicuspid aortic valve.

Primary school students (817 apparently healthy 10-year olds) were screened by transthoracic 2-dimensional echocardiography to assess for the prevalence of bicuspid aortic valve. Bicuspid aortic valve was found in 0.5% of cases, with a higher prevalence in males than females (0.75% vs 0.24%), and was significantly associated with aortic root enlargement compared with children who had tricuspid aortic valves.

Aortic Valve↗
PubMed2004

Arrhythmogenic right ventricular cardiomyopathy causing sudden cardiac death in boxer dogs: a new animal model of human disease.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary familial heart muscle disease associated with substantial cardiovascular morbidity and risk of sudden death. Efforts to discern relevant pathophysiological mechanisms have been impaired by lack of a suitable animal model. METHODS AND RESULTS: ARVC was diagnosed in 23 boxer dogs (12 male; 9.1+/-2.3 years old). Clinical events alone or in combination included sudden death (n=9; 39%), ventricular arrhythmias of suspected right ventricular (RV) origin (n=19; 83%), syncope (n=12, 52%), and heart failure (n=3; 13%). Right ventricular enlargement or aneurysms occurred in 10 (43%). Striking histopathological abnormalities were present in each boxer dog but not in controls, including severe RV myocyte loss with replacement by fatty (n=15, 65%) or fibrofatty (n=8, 35%) tissue. Focal fibrofatty lesions were also present in both atria (n=8) and the left ventricle (LV) (n=11). Fatty replacement occupied substantially greater RV wall area in ARVC dogs than controls (40.4+/-18.8% versus 13.8+/-3.4%, respectively) (P<0.001); residual myocardium was correspondingly reduced (56.6+/-19.2% versus 84.8+/-3.8% in controls) (P<0.001). MRI demonstrated bright anterolateral and/or infundibular RV myocardial signals, confirmed as fat by histopathology. Myocarditis appeared in the RV (n=14, 61%) and LV (n=16, 70%) and in each dog with sudden death, but not in controls. Familial transmission was evident in 10 of the 23. CONCLUSIONS: We describe a novel, spontaneous, and genetically transmitted animal model of ARVC associated with sudden death in the boxer dog, closely resembling the human disease. This model may aid in understanding the pathogenic mechanisms of ARVC.

Animals↗
PubMed2004

Cardiomyopathies: is it time for a molecular classification?

Primary myocardial diseases have always attracted the interest of the scientific community because of their obscure aetiopathogenesis. For years there was a confusion and controversy over their definition and classification. The 1995 WHO classification led to major advancements such as the introduction of a unified terminology, the official recognition of novel entities (arrhythmogenic right ventricular and idiopathic restrictive cardiomyopathies) and the definitive clarification that inflammatory heart disease has to be regarded as a cardiomyopathy. However, according to the new definition of cardiomyopathies as diseases of the myocardium associated with cardiac dysfunction, they should include not only forms with depressed contractility and impaired diastolic function, but also conduction and rhythm disturbances and enhanced arrhythmogenicity. Moreover, the recent development of molecular genetics, with the discovery of a genetic background in several forms previously defined of unknown origin, raises the need of a debate on a possible classification based on genomics.

Cardiomyopathies↗
PubMed2004

Remodeling of myocyte gap junctions in arrhythmogenic right ventricular cardiomyopathy due to a deletion in plakoglobin (Naxos disease).

OBJECTIVES: We tested the hypothesis that defective interactions between adhesion junctions and the cytoskeleton caused by the plakoglobin mutation in Naxos disease lead to remodeling of gap junctions and altered expression of the major gap junction protein, connexin43. BACKGROUND: Naxos disease, a recessive form of arrhythmogenic right ventricular cardiomyopathy, is associated with a high incidence of arrhythmias and sudden cardiac death. Naxos disease is caused by a mutation in plakoglobin, a protein that links cell-cell adhesion molecules to the cytoskeleton. METHODS: Myocardial expression of connexin43 and other intercellular junction proteins was characterized in 4 patients with Naxos disease. Immunohistochemistry was performed in all 4 patients, and immunoblotting and electron microscopy were performed in 1 patient who died in childhood before overt arrhythmogenic right ventricular cardiomyopathy had developed. RESULTS: Connexin43 expression at intercellular junctions was reduced significantly in both right and left ventricles in all patients with Naxos disease. Electron microscopy revealed smaller and fewer gap junctions interconnecting ventricular myocytes. Mutant plakoglobin was expressed but failed to localize normally at intercellular junctions. Localization of N-cadherin, alpha- and beta-catenins, plakophilin-2, desmoplakin-1, and desmocollin-2 at intercalated disks appeared normal. CONCLUSIONS: Remodeling of gap junctions occurs early in Naxos disease, presumably because of abnormal linkage between mechanical junctions and the cytoskeleton. Gap junction remodeling may produce a coupling defect which, combined with the subsequent development of pathologic changes in myocardium, could contribute to a highly arrhythmogenic substrate and enhance the risk of sudden death in Naxos disease.

Adult↗
PubMed2004

Hemodynamic and clinical outcomes with the Biocor valve in the aortic position: an 8-year experience.

OBJECTIVES: The aim of this study was to analyze the 8-year experience, survival, prosthetic complications, and hemodynamics of patients who received the Biocor valve, a new-generation tissue valve, in the aortic position. METHODS: From May 1992 through May 2001, 257 consecutive patients (129 women and 128 men; mean age, 75 +/- 6 years; age range, 45-91 years) received 258 aortic Biocor porcine prostheses. One female patient who received 2 Biocor valves in the aortic position during 2 consecutive operations was entered twice in the statistical analysis. Twelve (4.6%) patients had previous aortic valve operations. Preoperatively, 82 (32%) patients were in New York Heart Association functional class III or IV. Associated surgical procedures included coronary artery bypass grafting in 56 (21.7%) patients, aortic annular enlargement or aortoplasty in 20 (8%) patients, and others in 8 (3%) patients. Echocardiography was performed in the majority of long-term survivors (91.6%). Follow-up included 1215 patient-years and was 100% complete, with a median time of 5 patient-years (range, 0.4-10.5 years). RESULTS: There were 16 (6.2%) early deaths. According to a univariate analysis, New York Heart Association functional class III or IV, concomitant procedures, ejection fractions of less than 40%, and urgent operations were identified as significant perioperative risk factors. At follow-up, 75 patients died; 8-year actuarial Kaplan-Meier survival was 48% +/- 5%. At 8 years, the actuarial freedom from valve-related death was 92% +/- 2.6%, the freedom from thromboembolism was 93% +/- 2%, the freedom from anticoagulant-related hemorrhage was 95% +/- 2%, the freedom from endocarditis was 99% +/- 0.6%, the freedom from paravalvular leak was 96% +/- 1.5%, the freedom from all valve-related complications was 78% +/- 4.5%, and the freedom from structural valve deterioration was 95% +/- 3.7%. At 8 years, the actuarial freedom from structural valve deterioration was 89% +/- 10% and 95.8% +/- 4% in patients younger and older than 65 years, respectively. At 10 years, in patients older than 65 years, the actual freedom from structural valve deterioration was 97.9% +/- 2.1%, and the freedom from reoperation was 97% +/- 1.3%. New York Heart Association status was I or II in 90% of patients at the end of follow-up. The mean echocardiographic follow-up time was 4.6 +/- 2 years. By using Doppler echocardiography, the peak and mean transprosthetic gradients were determined to be 30.8 +/- 9.3 mm Hg and 16.6 +/- 5.3 mm Hg, respectively. Mean mass/volume ratio and left ventricular end-diastolic volume were 1.37 +/- 0.17 g/mL and 63.4 +/- 22.6 mL/m(2), respectively. The majority of patients showed a persistent left ventricular hypertrophy. CONCLUSION: The Biocor is an effective bioprosthesis with a low incidence of valve-related complications comparable with that of other second-generation bioprostheses. This stented porcine prosthesis provides satisfactory results in terms of hemodynamics, valve durability, and freedom from reoperation.

Aged↗