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Biomedical subjects

Gaetano Thiene

Publications and source records attributed to Gaetano Thiene.

At least 19 recordsLinked to original sources
PubMed2006

Relevance of apoptosis in influencing recovery of hibernating myocardium.

BACKGROUND: Hibernating myocardium (HM) is viable but dysfunctional myocardium which can recover following revascularization. Myocyte necrosis is virtually absent in HM; however, cellular loss may take place by apoptosis, although this is controversial. AIM: To assess the presence of apoptosis and its relevance in HM. METHODS: During coronary artery by-pass surgery (CABG), 21 patients underwent transmural biopsy in the dysfunctional left anterior descending artery tributary area of the left ventricle (LV), with kinetic recovery at follow-up, thus fulfilling the HM criteria. All patients underwent echocardiographic follow-up at 12 months. All biopsies were evaluated by light microscopy, electron microscopy (EM), and molecular analysis. RESULTS: All biopsies were structurally altered, showing increased fibrosis and myocytes with variable size. Myocyte dedifferentiation was not detected by immunohistochemistry or EM. On stepwise linear regression, 1 year LVEF was predicted by the apoptotic index (beta=-0.973, p=0.002), the normotrophic cell percentage (beta=0.449, p=0.038), and mean fibrosis (beta=-0.412, p=0.51). CONCLUSIONS: Our biopsy study detected a wide range of morphological substrate heterogeneity in HM with degenerative features. We have demonstrated for the first time in humans that myocyte apoptosis is an important phenomenon in HM, negatively influencing LV functional recovery after CABG.

Apoptosis↗
PubMed2006

Hybrid cardiomyocytes derived by cell fusion in heterotopic cardiac xenografts.

Cardiomyocytes expressing host markers, such as the Y chromosome in sex-mismatched transplants, have been described in human allografts, suggesting that circulating cells can contribute to cardiac regeneration. It has not been established, however, whether host-derived cardiomyocytes result from transdifferentiation of stem cells or cell fusion. To address this issue, we used heterotopic heart xenografts and looked for markers of donor and recipient cells. Golden Syrian hamsters or transgenic mice expressing nuclear beta-galactosidase under the control of the cardiac troponin I promoter served as organ donors, while GFP+ transgenic rats were used as recipients. GFP+ cells, including abundant CD-45+ inflammatory cells and rare undifferentiated cells expressing early cardiac markers (GATA-4 or MEF2C), were found in xenografts harvested two weeks after surgery. In addition, rare GFP+ mature cardiomyocytes were found in 7 of 8 hamster xenografts and 6 of 6 mouse xenografts. The proportion of these cells was very low (0.0001% to 0.0344% in hamster xenografts) but similar to the one observed in control rat heart allografts. Without exception, all GFP+ cardiomyocytes also expressed donor markers, i.e., hamster membrane antigens or lacZ, so they must derive from cell fusion, not transdifferentiation.

Animals↗
PubMed2006

Trends in sudden cardiovascular death in young competitive athletes after implementation of a preparticipation screening program.

CONTEXT: A nationwide systematic preparticipation athletic screening was introduced in Italy in 1982. The impact of such a program on prevention of sudden cardiovascular death in the athlete remains to be determined. OBJECTIVE: To analyze trends in incidence rates and cardiovascular causes of sudden death in young competitive athletes in relation to preparticipation screening. DESIGN, SETTING, AND PARTICIPANTS: A population-based study of trends in sudden cardiovascular death in athletic and nonathletic populations aged 12 to 35 years in the Veneto region of Italy between 1979 and 2004. A parallel study examined trends in cardiovascular causes of disqualification from competitive sports in 42,386 athletes undergoing preparticipation screening at the Center for Sports Medicine in Padua (22,312 in the early screening period [1982-1992] and 20,074 in the late screening period [1993-2004]). MAIN OUTCOME MEASURES: Incidence trends of total cardiovascular and cause-specific sudden death in screened athletes and unscreened nonathletes of the same age range over a 26-year period. RESULTS: During the study period, 55 sudden cardiovascular deaths occurred in screened athletes (1.9 deaths/100,000 person-years) and 265 sudden deaths in unscreened nonathletes (0.79 deaths/100,000 person-years). The annual incidence of sudden cardiovascular death in athletes decreased by 89% (from 3.6/100,000 person-years in 1979-1980 to 0.4/100,000 person-years in 2003-2004; P for trend < .001), whereas the incidence of sudden death among the unscreened nonathletic population did not change significantly. The mortality decline started after mandatory screening was implemented and persisted to the late screening period. Compared with the prescreening period (1979-1981), the relative risk of sudden cardiovascular death in athletes was 0.56 in the early screening period (95% CI, 0.29-1.15; P = .04) and 0.21 in the late screening period (95% CI, 0.09-0.48; P = .001). Most of the reduced mortality was due to fewer cases of sudden death from cardiomyopathies (from 1.50/100,000 person-years in the prescreening period to 0.15/100,000 person-years in the late screening period; P for trend = .002). During the study period, 879 athletes (2.0%) were disqualified from competition due to cardiovascular causes at the Center for Sports Medicine: 455 (2.0%) in the early screening period and 424 (2.1%) in the late screening period. The proportion of athletes who were disqualified for cardiomyopathies increased from 20 (4.4%) of 455 in the early screening period to 40 (9.4%) of 424 in the late screening period (P = .005). CONCLUSIONS: The incidence of sudden cardiovascular death in young competitive athletes has substantially declined in the Veneto region of Italy since the introduction of a nationwide systematic screening. Mortality reduction was predominantly due to a lower incidence of sudden death from cardiomyopathies that paralleled the increasing identification of athletes with cardiomyopathies at preparticipation screening.

Adolescent↗
PubMed2006

Ultrastructural evidence of intercalated disc remodelling in arrhythmogenic right ventricular cardiomyopathy: an electron microscopy investigation on endomyocardial biopsies.

AIMS: The ultrastructural features of the myocardium in arrhythmogenic right ventricular cardiomyopathy (ARVC) have not been systematically investigated so far. The recent discovery of gene mutations encoding intercalated disc proteins prompted us to perform a transmission electron microscopy study on endomyocardial biopsies. METHODS AND RESULTS: Twenty-one ARVC probands who fulfilled the international Task Force diagnostic criteria underwent right ventricular endomyocardial biopsy and screening of desmosome (D) protein encoding genes. Myocyte intercalated discs were analysed by transmission electron microscope and the data were compared with those of 10 controls and 10 patients with idiopathic dilated cardiomyopathy. Extensive fibro-fatty replacement with a residual myocardium of 59+/-23% was found in ARVC biopsy samples. Pathogenic D gene mutations were identified in 10 (48%): desmoglein-2 in four, desmoplakin in three and plakophilin-2 in three. Mean D length and D percent length of intercalated disc were significantly higher, D number was significantly lower and D gap was widened in ARVC. Moreover, abnormally located D in 75%, abnormal small junctions in 52%, and pale internal plaques in 32% of ARVC patients were found in the presence of a normal intercalated disc convolution index. CONCLUSION: The ultrastructural evidence of intercalated discs remodelling in ARVC, together with the positive screening of D protein encoding genes in half of probands, are in keeping with an intercellular junction cardiomyopathy.

Adult↗
PubMed2006

Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention.

Classifications of heart muscle diseases have proved to be exceedingly complex and in many respects contradictory. Indeed, the precise language used to describe these diseases is profoundly important. A new contemporary and rigorous classification of cardiomyopathies (with definitions) is proposed here. This reference document affords an important framework and measure of clarity to this heterogeneous group of diseases. Of particular note, the present classification scheme recognizes the rapid evolution of molecular genetics in cardiology, as well as the introduction of several recently described diseases, and is unique in that it incorporates ion channelopathies as a primary cardiomyopathy.

American Heart Association↗
PubMed2006

Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive myocardial atrophy with fibrofatty replacement. The recent identification of causative mutations in plakoglobin, desmoplakin (DSP), and plakophilin-2 (PKP2) genes led to the hypothesis that ARVC is due to desmosomal defects. Therefore, desmoglein-2 (DSG2), the only desmoglein isoform expressed in cardiac myocytes, was screened in subjects with ARVC. METHODS AND RESULTS: In a series of 80 unrelated ARVC probands, 26 carried a mutation in DSP (16%), PKP2 (14%), and transforming growth factor-beta3 (2.5%) genes; the remaining 54 were screened for DSG2 mutations by denaturing high-performance liquid chromatography and direct sequencing. Nine heterozygous DSG2 mutations (5 missense, 2 insertion-deletions, 1 nonsense, and 1 splice site mutation) were detected in 8 probands (10%). All probands fulfilled task force criteria for ARVC. An endomyocardial biopsy was obtained in 5, showing extensive loss of myocytes with fibrofatty tissue replacement. In 3 patients, electron microscopy investigation was performed, showing intercalated disc paleness, decreased desmosome number, and intercellular gap widening. CONCLUSIONS: This is the first investigation demonstrating DSG2 gene mutations in a significant number of ARVC-unrelated probands. Cardiac phenotype is characterized clinically by typical ARVC features with frequent left ventricular involvement and morphologically by fibrofatty myocardial replacement and desmosomal remodeling. The presence of mutations in desmosomal encoding genes in 40% of cases confirms that many forms of ARVC are due to alterations in the desmosome complex.

Adolescent↗
PubMed2006

Exercise and the risk of sudden cardiac death.

Sports activity may precipitate acute fatalities in both adults and young competitive athletes with concealed heart diseases. However, the risk-benefit ratio of physical exercise differs among these two age groups. In adolescents and young adults, competitive physical exercise is associated with a significant increase of the risk of sudden death. Sports is not "per se" cause of the enhanced mortality in this age group; rather, it acts as a trigger of cardiac arrest in those athletes who are affected by silent cardiovascular conditions, mostly cardiomyopathy, premature coronary artery disease and congenital coronary anomalies, which predispose to life-threatening ventricular arrhythmias during physical exercise. In adults, on the other hand, physical activity can be regarded as a "two-edged sword": vigorous exertion increases the incidence of acute coronary events in individuals who did not exercise regularly, whereas habitual physical activity reduces the overall risk of myocardial infarction and sudden coronary death by preventing development of coronary artery disease and progression of coronary atherosclerotic lesions.

Adolescent↗
PubMed2006

Commissural dehiscence: a rare and peculiar cause of porcine valve structural deterioration.

OBJECTIVE: Calcification is the main cause of structural valve deterioration; however, other causes of failure have been identified, and among them, dehiscence of a commissure from the stent has been reported in several models of porcine valves. The aim of this study was to analyze the rate and mode of occurrence of this complication in first- and second-generation porcine bioprosthetic explants. METHODS: Among 586 porcine xenografts explanted and analyzed at the Institute of Pathological Anatomy of the University of Padua, 17 (2.9%) have been replaced for incompetence because of commissural dehiscence. All these explants were in the mitral position, with the exception of a Carpentier-Edwards supra-annular aortic valve prosthesis. RESULTS: Dehiscence was observed in 9 (1.9%) of 455 Hancock standard explants, in 1 (3.2%) of 31 Hancock II, in 3 (8.6%, 2 standard and 1 supra-annular) of 35 Carpentier-Edwards, in 1 (2.4%) of 42 Bioimplants, and in 3 (50%) of 6 Xenotech after a mean time function of 157 +/- 50, 156, 96 +/- 29, 143, and 130 +/- 8 months, respectively. Dehiscence was the sole cause of incompetence in 6 cases. An impending commissural dehiscence caused by blood creeping was observed in one case. This might be an explanation for the dehiscence other than excessive trimming of the aortic wall. CONCLUSIONS: Commissural dehiscence is an uncommon and peculiar mode of failure of porcine valves implanted in the mitral position and was observed earlier and more frequently with Carpentier-Edwards porcine explants (P < .05). We speculate that pericardial strip protection of the suture between the Dacron fabric and porcine aortic wall, as used in the Biocor porcine valve, might prevent this complication.

Aged↗
PubMed2006

Evidence of mitigated calcification of the Mosaic versus Hancock Standard valve xenograft in the mitral position of young sheep.

OBJECTIVES: Durability remains the main problem of all bioprosthetic valves, and calcification is the major cause of failure. New tissue treatment processes are expected to reduce mineralization. A comparative animal study was undertaken to evaluate the behavior of a new-generation porcine bioprosthesis in contrast with a first-generation porcine bioprosthesis. The primary goal was to evaluate the efficacy of alpha-amino-oleic acid as an anticalcification treatment. METHODS: Seventeen Targhee sheep (aged 4.5-7 months) had a mitral valve replacement with a Mosaic or Hancock Standard. The animals were followed up to 20 weeks (144.1 +/- 4.0 days vs 144.3 +/- 8.2 days) and then euthanized as scheduled. After gross examination, the explants were radiographed for the presence of calcification. The central portions were preserved for histologic examination, and the remainder of the sample was analyzed for quantitative calcium content by atomic absorption spectroscopy. RESULTS: Four Mosaic sheep were excluded because of perioperative surgical mortality. The remaining 13 were enrolled in the study (9 Mosaic and 4 Hancock Standard). The mean calcium content was 1.97 +/- 2.21 microg/mg tissue weight for Mosaic versus 8.36 +/- 4.12 microg/mg for Hancock Standard valves (P < .01). Mild fibrous tissue overgrowth and fibrinous lining were observed regardless the xenograft type. CONCLUSIONS: The low level of calcification in the Mosaic versus Hancock Standard xenografts confirms the efficacy of alpha-amino-oleic acid treatment in mitigating mineralization. A longer durability is expected with the clinical use of the Mosaic porcine valve.

Animals↗
PubMed2006

Endovascular treatment of in-stent restenosis after carotid artery stenting: immediate and midterm results.

PURPOSE: To evaluate the immediate and midterm outcome and analyze the debris captured after repeat endovascular intervention for the treatment of in-stent restenosis after carotid artery stenting (CAS). METHODS: Thirty-one consecutive patients (27 men; mean age 63.7+/-13.0 years, range 53- 81) underwent repeat endovascular intervention (balloon angioplasty and provisional stenting) for the treatment of 32 in-stent restenoses following CAS. RESULTS: Procedural success was achieved in all patients. An additional stent was implanted in 10 (31%) cases. No procedural complication was observed. Filter analysis was performed in 17 (53%) procedures; on 12 (71%), macroscopically visible material was captured. The histomorphometric analysis performed on 6 (19%) filters showed fibrin nets entrapping erythrocytes, leucocytes, platelets, and in 2 cases, fibrous hypercellular tissue fragments. At 30 days and during follow-up (mean 17+/-5 months), no deaths, transient ischemic attacks, or strokes were observed. In 1 (3.1%) patient, asymptomatic recurrence of ISR was found on Doppler ultrasonography and successfully treated with balloon angioplasty. CONCLUSION: Repeat endovascular intervention using balloon angioplasty with provisional stenting and routine cerebral protection appears to be a feasible, safe, and clinically effective strategy for the treatment of in-stent restenosis after CAS.

Aged↗
PubMed2006

Does sports activity enhance the risk of sudden cardiac death?

Vigorous physical exercise may precipitate acute fatalities in both adults and young competitive athletes with concealed heart diseases. However, the risk-benefit ratio of physical exercise differs among these two age groups. In adults, physical activity can be regarded as a 'double-edged sword': vigorous exertion increases the incidence of acute coronary events in individuals who did not exercise regularly, whereas habitual physical activity reduces the overall risk of myocardial infarction and sudden coronary death by preventing development and progression of atherosclerotic coronary artery disease. On the other hand, in adolescents and young adults sports activity is associated with a significant increase of the risk of sudden death. Sport is not per se the cause of the enhanced mortality in this age group; rather, it acts as a trigger of cardiac arrest in those athletes who are affected by silent cardiovascular conditions, mainly cardiomyopathy, premature coronary artery disease and congenital coronary anomalies, which predispose to life-threatening ventricular arrhythmias during physical exercise.

Arrhythmias, Cardiac↗
PubMed2005

Effects of long-term administration of high-dose recombinant human antithrombin in immunosuppressed primate recipients of porcine xenografts.

BACKGROUND: Fibrin deposition is central to the acute humoral rejection process occurring in the presence of consumptive coagulopathy when pig organs are transplanted into primates. METHODS: To assess whether strategies aimed at preventing fibrin formation may extend xenograft survival, we administered high daily doses of recombinant human antithrombin (rhAT) (500 U/kg twice daily) to obtain both anticoagulant and anti-inflammatory effects in immunosuppressed primate recipients of porcine kidneys. RESULTS: Some degree of consumptive coagulopathy developed in both rhAT-treated (n=3) and untreated (n=3) primates. No major differences in the coagulation parameters analyzed were observed between the 2 groups. Similarly, no difference in survival was seen between rhAT-treated (20.6+/-4 days; range: 15-23 days) and untreated animals (17.3+/-11.6 days; range: 7-30 days), although the rhAT-treated primates had a higher bleeding tendency. Despite the high daily dose of rhAT, considerable fibrin deposition was observed in the graft as early as 2 weeks after transplantation. CONCLUSIONS: These results suggest that a high daily dose of rhAT fails to influence survival or prevent fibrin formation and deposition in the graft in our pig-to-primate model. However, the potential role of rhAT administered in combination with heparins or other clotting inhibitor concentrates in this model remains to be determined.

Animals↗