[show abstract][hide abstract] ABSTRACT: Objectives To test the diagnostic impact of the non-invasive rescreening of relatives of index patients consecutively diagnosed as having dilated cardiomyopathy. Background The aim of rescreening asymptomatic healthy relatives of DCM patients is to diagnose newly affected subjects and evaluate the predictive significance of the instrumental abnormalities found at the first screening. Methods and results Two hundred and three healthy relatives of 73 consecutive index patients with DCM (18 with familial disease at first screening) underwent rescreening involving a clinical examination, electro- and echocardiography, and biochemical tests a median of 29.3 months after the first screening. Seven relatives had developed the diagnostic criteria for DCM during the screening–rescreening interval. Of the 24 healthy relatives with left ventricular end-diastolic diameter enlargement and normal function at the first screening, nine had normalised, seven showed persistent enlargement, three had worsened, and five had developed the disease criteria at rescreening. Of the three relatives with atrioventricular block at the first screening, one had developed DCM. Finally, one of the relatives with normal echocardiographic and electrocardiographic results at the first screening, had developed the disease. Three of the newly diagnosed subjects came from families with evidence-based familial DCM, and four from families with what was defined as sporadic DCM at the first screening. Conclusions Medium-term rescreening of the relatives of DCM patients can identify a significant number of newly affected patients (3.5%).
[show abstract][hide abstract] ABSTRACT: Endomyocardial biopsy (EMB) is currently the standard method to diagnose acute graft rejection. However, considering the potential complications of this procedure, a noninvasive marker of rejection would be an ideal alternative or at least a helpful adjunct to posttransplant management. We measured myoglobin (Myo), creatine kinase MB mass (CK-MBm), troponin T (cTnT), serum amyloid A (SAA), and C-reactive protein (CRP) in 57 patients (mean age 37.5 years) who underwent orthotopic heart transplantation for end-stage cardiac failure between January and December 2001.Endomyocardial biopsies were performed routinely after surgery and histologically diagnosed rejection was graded according to the criteria of the International Society of Heart and Lung Transplantation. Concomittant with the biopsies, blood samples were drawn from the coronary sinus (central blood samples) and from a peripheral vein (peripheral blood samples) to assay biochemical markers. Among 149 EMB evaluated, 87 were negative (grade 0); 28 showed grade 1a rejection; 26 showed grade 1b; and 8 showed grade > 1b (2 were grade 2, 6 were grade 3a). Grades 0 and 1a were considered to be negative, while grades 1b and >1b were considered positive indicating potential acute graft rejection. cTnT, Myo, CK-MBm, SAA, and CRP levels were measured in 149 central blood samples and 149 peripheral blood samples. Myo and CK-MBm did not show significant changes. cTnT seems to be a potentially useful addition to the EMB results, while SAA and CRP showed variations with respect to EMB grade both in central and peripheral samples.
[show abstract][hide abstract] ABSTRACT: Background Patients with chronic heart failure syndrome may develop a myopathy contributing to muscle wasting and exercise intolerance. Little is known about skeletal muscle pathology in patients with dilated cardiomyopathy (DCM). Aims To correlate skeletal muscle biopsy (SMB) findings with endomyocardial biopsy (EMB) and clinical/functional data in DCM patients. Methods and results SMBs and EMBs were morphometrically and morphologically analysed in 30 consecutive patients aged 40.7±14 years (16–63), including 25 in NYHA classes I and II. Four had familial DCM. Serum creatine-phosphokinase (sCPK) was normal in 23 and slightly increased in seven. All the SMBs showed morphological (including non-recurrent changes different from those in the EMBs) and morphometric changes, with atrophic fibres in all cases (atrophy factor >150 in six NYHA II patients) and necrotic fibres in three. The SMBs of two patients with EMB-proven myocarditis showed inflammation. Plotting the morphometric factors against age at symptom onset, age at diagnosis, follow-up, clinical outcome, ejection fraction and sCPK levels showed that only sCPK >180 mU/ml correlated with atrophy factor. Conclusions The use of SMB in DCM patients documents some aspecific subclinical muscle damage that is unrelated to the functional class and duration of the DCM. However, this information does not contribute to identify the aetiology or managing the disease.
[show abstract][hide abstract] ABSTRACT: Mutations of the LMNA gene encoding the lamin A and C nuclear envelope proteins cause an autosomal dominant form of dilated cardiomyopathy (DCM) with atrioventricular block (AVB). The aim of this study was to investigate ultrastructural nuclear membrane changes by conventional electron microscopy and protein expression by immuno-electron microscopy in the heart of patients with DCM and AVB due to LMNA gene mutations. Four immunohistochemical techniques were used: pre-embedding and post-embedding in Epon-Araldite resin and London Resin White (LRW), with and without silver enhancement. Parallel light microscopy immunohistochemistry studies were performed. Conventional electron microscopy showed a loss of integrity of the myocyte nuclei with blebs of the nuclear membrane, herniations and delamination of the nuclear lamina and nuclear pore clustering. Post-embedding LRW was the most informative technique for morphology and immuno-labelling. Immuno-labelling was almost absent in the nuclear envelope of patients with LMNA gene mutations, but intensely present in controls. The loss of labelling selectively affected myocyte nuclei; the endothelial cell nuclei were immunostained in patients and controls. Light immunohistochemistry confirmed the results. These findings confirm the hypothesis that LMNA gene defects are associated with a loss of protein expression in the selective compartment of non-cycling myocyte nuclei.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 12/2003; 443(5):664-71. · 2.68 Impact Factor
[show abstract][hide abstract] ABSTRACT: AIMS: To investigate celiac disease (CD) and related co-morbidity in patients with familial and sporadic cardiomyopathy and in their relatives. METHODS AND RESULTS: We screened anti-human-tissue-transglutaminase (IgA and IgG anti-h-tTG) and anti-endomysial antibodies (AEAs) in 238 consecutive adult patients with inherited or sporadic dilated cardiomyopathy (DCM), 418 relatives, and 2000 healthy blood donors. HLADQ2-DQ8 was tested in tTG-positive subjects. The IgA-tTG-positive patients with cardiomyopathy underwent duodenal biopsy. Twenty-six subjects were tTG-positive: five DCM patients (2.1%), two of 28 (7.1%) and three of 390 (0.7%) relatives with and without echocardiographic abnormalities respectively, and 16 controls (0.8%). Twenty-two of 26 subjects were AEA-positive, and 25 HLA-positive. Of the five patients with cardiomyopathy and biopsy-proven CD, four suffered iron-deficiency anaemia. Two CD-positive DCM patients and two tTG-positive relatives were from families with inherited disease in which CD did not co-segregate with DCM. CONCLUSIONS; The higher prevalence of CD in patients with sporadic or inherited DCM, and of tTG-positive serology in relatives with echocardiographic abnormalities, suggests that immune-mediated mechanisms are active in subsets of patients/families. However, gluten intolerance cannot be considered causative since CD seems to be associated but not co-segregated with DCM in familial cases.
European Heart Journal 09/2003; 24(15):1455-61. · 14.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: In this study we assessed functional changes (motility and absorption) of intestinal allografts in a large-animal model of orthotopic small bowel transplantation in swine. Studies were performed on non-rejecting animals in the early and late stages after transplantation and after induction of different grades of acute rejection. Immunosuppression consisted of oral FK506 and mycophenolate mofetil. In each study group we regulated drug administration, in terms of dosage and timing, in order to induce different grades of acute rejection or to prevent it. Migrating myoelectrical complexes were recorded in fasting animals so that motility could be assessed. Mucosal biopsy of the allograft and D-xylose absorption tests were performed on the same day as the motility study. In the early stages following intestinal transplantation, we observed in non-rejecting animals a slightly increased graft motility and a marked carbohydrate malabsorption. Recovery of the carbohydrate absorption capacity occurs within 2 months, but the persistence of diarrhea leads to partial malabsorption and to a lack of normal weight gain. Motility reduction correlates with the grade of acute rejection and becomes significant at a later stage, when rejection is severe. Allograft carbohydrate absorption, on the contrary, is markedly reduced in all rejecting pigs, irrespective of the grade of rejection. In summary, the early functional impairment of non-rejecting animals has multifactorial causes due to surgery and immunosuppression (drug toxicity), and its occurrence suggests the need for specific guidelines for clinical early postoperative enteral feeding. The functional studies adopted here are helpful in defining the grade of functional impairment with or without acute rejection; however, they are not useful for early detection of ongoing acute rejection of the small bowel graft.
Transplant International 06/2003; 16(5):327-35. · 3.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: The transversal distribution of coronary atherosclerotic plaques (AP) (myocardial vs pericardial) affects vessel remodelling. The aim of this study was to define the impact of transversal lesion distribution on vessel remodelling in proximal and distal coronary segments using a 3D intravascular ultrasound (IVUS) reconstruction.
The study group included 70 lesions located in the left anterior descending artery within 5mm of the septal take-off, and imaged using 3D-IVUS. The take-off of the septal branch was used to divide the plaque into a myocardial and pericardial surface. The IVUS index of vessel remodelling was calculated as: [narrowest external elastic membrane (EEM) site cross-sectional area (CSA)-reference EEM CSA)/reference EEM CSAx100]. The lesions with an intermediate vessel remodelling index (between -25% and +15%) were excluded from analysis.
Of the 38 APs with a pericardial distribution, 34 (89%) showed positive remodelling (P<0.001). The distal lesions had a positive vessel remodelling index regardless of transversal plaque distribution. At multivariate analysis, pericardial distribution and the distal location of AP were the only independent variables predictive of positive remodelling.
The transversal distribution of atherosclerotic plaque affects vessel remodelling in left anterior descending coronary lesions, probably because of an extravascular splinting effect. Distal lesions usually show positive remodelling regardless of transversal plaque distribution.
European Heart Journal 03/2003; 24(4):329-36. · 14.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: Patients with pulmonary hypertension develop intimal plaques in large pulmonary arteries.
To test the hypothesis that the composition of such plaques differs depending on whether the aetiology of the disease is thromboembolic or hypertensive.
Chronic thromboembolic and plexogenic pulmonary hypertension (primary and secondary (Eisenmenger syndrome)) were investigated. These are spontaneous human models and were used to examine the independent role of thrombus and hypertension in plaque composition.
A national tertiary referral centre for lung transplantation and pulmonary thromboendoarterectomy.
Thirty nine patients with chronic thromboembolic pulmonary hypertension who had undergone thromboendoarterectomy (n = 32) or lung transplantation (n = 7), 28 with plexogenic diseases (nine primary and 19 Eisenmenger), and three with Eisenmenger syndrome complicated by thromboembolic events.
The lung and thromboendoarterectomy samples were sectioned, stained with Movat pentachrome, and immunostained with antibodies for fibrin, platelets, inflammatory cells, smooth muscle cells, and erythrocyte membrane glycophorin A.
Composition of the plaques affecting large pulmonary arteries.
Two types of intimal lesion were distinguished in chronic thromboembolic pulmonary hypertension: fibrous plaques with angioneogenesis; and core-rich atherosclerotic plaques with pultaceous cores largely consisting of glycophorin immunoreactive material, with cholesterol clefts (61.5%), CD68 positive macrophages (84.6%), T lymphocytes (87%), and calcification (46.1%). The samples from the patients with Eisenmenger syndrome and thromboembolic complications had similar characteristics, whereas those from patients with uncomplicated primary pulmonary hypertension had core-free fibrous plaques, spotted with macrophages and T lymphocytes.
Chronic thromboembolic pulmonary hypertension is associated with atherosclerotic plaques with glycophorin-rich pultaceous cores, and plexogenic pulmonary hypertension with fibrous plaques. Thromboembolic material thus plays a critical role in the formation of pultaceous cores, of which erythrocyte membrane derived glycophorin is a major component.
[show abstract][hide abstract] ABSTRACT: Statins appear to have beneficial effects on fibrous cap stabilisation but their effects on plaque thrombogenicity have not been reported. To evaluate the thrombogenicity of human carotid plaques before and after atorvastatin treatment, 59 patients with bilateral carotid stenosis eligible for two-step carotid endoarterectomy (CEA) were randomly assigned to atorvastatin, 20 mg/day, or placebo. Histological and immunohistochemical analyses, Tissue Factor (TF), Tissue Factor Pathway Inhibitor (TFPI) antigens (Ag) and TF activity were determined in endoarterectomy specimens obtained at baseline and after treatment. Mean TFAg and TFPIAg levels from plaques removed at the first CEA were 55 +/- 56 and 32 +/- 26 pg/mg. After placebo, TFAg and TFPIAg content was higher in the second than the first CEA. Plaques removed at the second CEA from atorvastatin-treated patients had a lower macrophage content than plaques at the first CEA. TFAg and TFPIAg levels, and TF activity in plaques after atorvastatin treatment were lower (respectively 29, 18% and 56%) than after placebo. These findings indicate that atorvastatin reduce the inflammatory/thrombotic phenotype of carotid plaque, suggesting that these drugs may indeed have a beneficial effect on cerebrovascular events.
Thrombosis and Haemostasis 08/2002; 88(1):41-7. · 6.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: We evaluated the role of electron microscopy and immuno-electron microscopy studies on abdominal fat fine-needle biopsy samples in diagnosis and characterization of cardiac amyloidosis. The series consists of 15 patients with echocardiographic evidence of "restrictive cardiomyopathy" suspected to be due to amyloidosis. Patients underwent: clinical examination, electrocardiography, 2-D and Doppler echocardiography, immunofixation of serum and urine for detection of monoclonal immunoglobulins, and abdominalfat biopsies that were investigated with polarized light (Congo red), electron and immuno-electron microscopy using specific antibodies to kappa and lambda light chains, apolipoprotein A1, serum amyloid A (SAA), and transthyretin (TTR). Ultrastructural study of abdominal fat samples identified amyloid deposits in 15/15 cases. Immuno-electron microscopy specifically stained amyloid fibrils with antibodies anti-lambda (n = 8), -kappa (n = 2), -apolipoprotein A1 (n = 2) and -TTR (n = 3). Immuno-electron microscopy revealed TTR immuno-labelling in 2 patients with accidental monoclonal components, and a A reaction in I patient without monoclonal components. TTR and apolipoprotein A1 positive cases carried missense mutations in the corresponding genes. Our results demonstrate that amyloid deposits are present in the abdominalfat of patients suspected to have cardiac amyloidosis and that immuno-electron microscopy was able to characterize the amyloid protein in all cases.
[show abstract][hide abstract] ABSTRACT: Several proteins share the property of conforming as antiparallel beta-sheets, and forming insoluble amyloid fibrils that deposit in the interstitium of organs/tissues and cause systemic amyloidosis. Cardiac involvement is frequent and constitutes a major predictor of poor outcome. Its typical phenotype is that of restrictive cardiomyopathy. The biochemical classification of the amyloidogenic proteins provides the bases for innovative therapeutic approaches. Primary systemic amyloidosis (AL) is a protein conformation disorder in which monoclonal immunoglobulin light chains (kappa or lambda) produced by clonal plasma cells, are deposited as amyloid in kidneys, heart, liver, and other organs. The recent evidence that chemotherapy reduces or even eradicates the amyloidogenic clone with consequent functional improvement of the affected organs raises new hopes for a treatment, whose key of success is early diagnosis. Heart transplantation can be proposed in patients < 60 years of age in association with autologous stem cell transplantation. In serum amyloid A amyloidosis, fibrils are constituted of the acute phase serum amyloid A protein that is produced in excess in chronic inflammatory diseases such as familial mediterranean fever, autoimmune disorders and chronic infections. The strategy is to treat the underlying inflammatory disease, but new molecules inhibiting amyloid formation and promoting amyloid resorption are facing the clinical scenario and trials are in progress. In transthyretin (TTR) amyloidosis, the non-senile forms are autosomal dominant diseases caused by defective proteins synthesized by mutated TTR genes (more than 70 known mutations with different genotype-phenotype correlations). The treatment is based on transplantation of the TTR-producing liver; exceptionally, liver plus heart or kidney are transplanted. Apolipoprotein A1 amyloidosis is an inherited autosomal dominant disease that benefits from the transplantation of the most impaired organs, usually heart, liver or kidney, either single or combined. The diagnosis of apolipoprotein A1 and TTR amyloidosis relies on positive family history, immunocharacterization of the amyloid fibrils in a tissue biopsy, gene defect detection and absence of light chains in serum and urines. Vice versa, non-familial primary amyloidoses are diagnosed when kappa or lambda light chains are identified with immunofixation in serum or urines. Tissue studies provide the gold standard for the diagnosis and immunocharacterization of amyloid protein. Heart involvement is diagnosed with a multiparametric approach that includes clinical, electrocardiographic and echocardiographic evaluation. The fine-needle biopsy of the periumbilical fat is the preferral procedure for amyloid detection and immunocharacterization of amyloid protein. This approach excludes, with a few exceptions, the need of endomyocardial biopsy.
Italian heart journal. Supplement: official journal of the Italian Federation of Cardiology 07/2002; 3(6):590-7.
[show abstract][hide abstract] ABSTRACT: In Italy, typical HFE mutations account for only 64% of the cases with overt hereditary hemochromatosis (HH), and a common HFE-unrelated disease was hypothesized.
One thousand and fifty potential blood donors were screened by iron tests, C282Y and H63D HFE mutation analysis in a region in North Italy. Subjects with repeated fasting transferrin saturation of 45% or more and no secondary iron overload were defined as probands with idiopathic iron overload. To assess the inheritance of iron overload, relatives of probands were screened.
The overall frequency of probands with idiopathic iron overload was 3.43% (95% confidence interval, 2.32 to 4.52). Of these, 8.4% had genotypes associated with HH (compound heterozygous for H63D/C282Y or homozygous for H63D HFE mutations), and 91.6% had atypical genotypes: 47.2% were heterozygous for C282Y or H63D HFE mutations, and 44.4% had wild type/wild type genotype. A family history of iron overload was proven in 33.3% of probands with atypical genotypes (1.04% of the overall population). Pedigree analysis excluded linkage of heterozygous HFE mutations with iron overload (cumulative lod score 2.41) and documented a recessive non-HLA-linked locus accounting for iron overload in wild type/wild type genotypes. None of the probands had clinical signs of iron accumulation; in males, serum ferritin positively correlated with age (r=0.63, p<0.01), and the regression model predicted a serum ferritin of 700 ng/mL at the age of 58.
In Northern Italy an HFE-unrelated, mild idiopathic iron overload is highly prevalent. A recessive locus accounts for iron overload in at least 1.04% of the overall population.
[show abstract][hide abstract] ABSTRACT: The definition of familial dilated cardiomyopathy (DCM) is clinically based on the presence, in the same family, of at least two members proven as affected. The prevalence of familial forms is about 25-30%. The approach to define the prevalence of familial diseases and to identify asymptomatic subjects is based on a clinical, non-invasive screening of family members of consecutive index patients. Familial DCM is commonly inherited as autosomal dominant trait; less frequently it is autosomal recessive, X-linked or matrilinear. The disease is clinically and genetically heterogeneous. Genes causally linked to this phenotype include dystrophin, dystrophin-associated glycoproteins, actin, desmin, beta-miosin heavy chain, cardiac troponin T, and mitochondrial DNA genes, mostly transfer RNAs. A peculiar phenotype is DCM associated with atrioventricular block, an autosomal dominant disorder that is causally linked to lamin A/C gene defects in a high proportion of cases. Although the knowledge on molecular genetics of DCM is progressively increasing, at present, the number of molecular diagnoses that can be provided to patients is limited to a few X-linked, autosomal dominant and matrilinear DCMs (overall, about 10% of DCMs). The new clinical approach to familial DCM studies, based on the screening of family members, will bring to the cardiologist's attention both patients and relatives, with extension of the clinical evaluation to subjects who are still healthy. On the other hand, molecular genetists will face a complex molecular field, for both high heterogeneity and poor phenotypical specificity. Therefore, interdisciplinary clinical and research projects are especially needed, hopefully coordinated by scientific societies.
Italian heart journal. Supplement: official journal of the Italian Federation of Cardiology 05/2002; 3(4):386-93.
[show abstract][hide abstract] ABSTRACT: Encouraging results in transplantation of other solid organs led to investigation of the use of tacrolimus in lung transplantation as a salvage immunosuppressant in persistent acute rejection.
The incidence and severity of acute rejection and the number of steroid pulses were analyzed in 20 lung recipients who were converted from a cyclosporine- to a tacrolimus-based immunosuppressive regimen because of refractory biopsy-proven acute rejection.
Tacrolimus was started 12.0 +/- 13.0 months after transplantation, and the mean follow-up was 25.0 +/- 13.7 months. After shifting to tacrolimus, a significant decline was observed in both the number of acute rejections per patient (3.0 +/- 1.56 to 0.85 +/- 1.14, p < 0.0001), and the incidence of acute rejection per 100 patient-days (1.52 +/- 0.99 to 0.14 +/- 0.21, p < 0.0001). Furthermore, the average histologic grade of rejection decreased from 1.9 +/- 0.8 to 0.4 +/- 0.5 (p < 0.0001). Methylprednisolone pulses similarly decreased from 1.9 +/- 1.3/patient to 0.3 +/- 0.7/patient (p < 0.0001). During cyclosporine immunosuppression, the mean forced expiratory volume in 1 second decreased to 84.4% +/- 13.3% of individual best value. The average lung function parameters were stable 3 months after the change of medication, and then began to improve. After an average follow-up of 36.5 +/- 19.2 months, 2 patients have developed bronchiolitis obliterans syndrome (one has Stage 1 and one has Stage 3).
Conversion to a tacrolimus-based immunosuppressive regimen for refractory acute lung rejection is associated with reduced incidence and severity of acute rejection episodes, steroid sparing, and stabilization or improvement of pulmonary function.
The Journal of Heart and Lung Transplantation 04/2002; 21(4):435-9. · 5.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to verify whether or not the clinical profile could be helpful in diagnosing myocarditis in patients with recent-onset (< 6 months) heart failure, suspected myocarditis and a biopsy-proven diagnosis.
From March 1998 to December 2000, 118 patients underwent a complete clinical, hemodynamic, echocardiographic and laboratory examination and a diagnostic endomyocardial biopsy in our Department; among them, 28 patients were admitted with clinically suspected myocarditis; in 9, the diagnosis was confirmed by the histopathologic findings.
At the time of presentation, patients with biopsy-proven myocarditis showed early in-hospital admission (median 6 vs 69 days) with fever, a higher sinus rate and a significantly lower systolic blood pressure. Left ventricular dilation was observed in the non-myocarditis group only (left ventricular end-diastolic diameter 65.0 +/- 8.9 vs 52.6 +/- 5.8 mm); right ventricular function, as assessed by evaluation of the tricuspid annulus plane systolic excursion (TAPSE) and the right ventricular ejection fraction (RVEF) were found to be significantly lower in the myocarditis group (TAPSE 14.2 +/- 3.6 vs 20.3 +/- 7.0 mm; RVEF 21.3 +/- 11.1 vs 30.3 +/- 11.5%). Only patients with biopsy-proven myocarditis had an increase in serum creatine kinase and inflammatory markers (erythrocyte sedimentation rate and white blood cell count). Three cases had a clinical presentation of fulminant myocarditis showing marked increases in the serum levels of creatine kinase and inflammatory markers, and severely compromised right ventricular function and cardiac index.
At univariate analysis, an early onset, fever, tachycardia, hypotension, a reduced right ventricular function, increased creatine kinase, erythrocyte sedimentation rate and white blood cell count were predictive of myocarditis. In patients with recent-onset heart failure, the clinical, laboratory and echocardiographic profiles can suggest, but not prove, a diagnosis of myocarditis.
Italian heart journal: official journal of the Italian Federation of Cardiology 04/2002; 3(3):188-93.
[show abstract][hide abstract] ABSTRACT: We investigated the prevalence of lamin A/C (LMNA) gene defects in familial and sporadic dilated cardiomyopathies (DCM) associated with atrioventricular block (AVB) or increased serum creatine-phosphokinase (sCPK), and the corresponding changes in myocardial and protein expression.
It has been reported that familial DCM, associated with conduction disturbances or variable myopathies, is causally linked to LMNA gene defects.
The LMNA gene and myocardial ultrastructural and immunochemical changes were analyzed in 73 cases of DCM (49 pure, 15 with AVB [seven familial, eight sporadic], 9 with increased sCPK), four cases of familial AVB and 19 non-DCM heart diseases. The normal controls included eight heart donor biopsies for tissue studies and 107 subjects for LMNA gene studies.
Five novel LMNA mutations (K97E, E111X, R190W, E317K, four base pair insertion at 1,713 cDNA) were identified in five cases of familial autosomal dominant DCM with AVB (5/15: 33%). The LMNA expression of the myocyte nuclei was reduced or absent. Western blot protein analyses of three hearts with different mutations showed an additional 30-kDa band, suggesting a degrading effect of mutated on wild-type protein. Focal disruptions, bleb formation and nuclear pore clustering were documented by electron microscopy of the myocyte nuclear membranes. None of these changes and no mutations were found in the nine patients with DCM and increased sCPK or in the disease and normal controls.
The LMNA gene mutations account for 33% of the DCMs with AVB, all familial autosomal dominant. Increased sCPK in patients with DCM without AVB is not a useful predictor of LMNA mutation.
Journal of the American College of Cardiology 04/2002; 39(6):981-90. · 14.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: This is a proposal for collecting the family history throughout a guided form to be given to the patient when awaiting for ambulatory examination or hospital admission, before meeting the cardiologist. In this form, the patient is asked to make an effort in order to focus on his family history (diseases, signs, symptoms, medications, etc.) at least for parents, sibs, and off-springs. A nurse should be committed to give the form to the patient, making him sure that the incomplete filling does not limit the quality of the diagnostic and therapeutic work-up. Thanks to the guided form, the patient concentrates the attention on his family history, eventually consulting the relatives before being examined. The form opens stating that all data are potentially helpful, but none is essential for diagnosis and treatment. This new approach to the family history could support clinicians in having helpful news, only deepening information that seems to be more relevant for the diagnosis.
Italian heart journal. Supplement: official journal of the Italian Federation of Cardiology 07/2001; 2(6):640-6.