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E Arbustini

Publications and source records attributed to E Arbustini.

At least 37 records · Page 2Linked to original sources
PubMed2001

Evidence-based diagnosis of familial non-X-linked dilated cardiomyopathy. Prevalence, inheritance and characteristics.

AIMS: To assess the prevalence of familial non-X-linked dilated cardiomyopathy, to diagnose early asymptomatic cases evaluate inheritance and characterize clinical phenotypes. METHODS AND RESULTS: We screened 472 relatives of 104 consecutive patients diagnosed with dilated cardiomyopathy; males with X-linked dilated cardiomyopathy were excluded based on systematic immunohistochemical and molecular analysis. Relatives underwent clinical examination, electrocardiography, echocardiography and serum creatine-phosphokinase determination. Twenty-six index patients (25%) had familial disease: four youths (< or = 20 years) had rapidly progressive outcome and underwent emergency transplantation. In a sib-pair, the onset was with atrioventricular block. Inheritance was autosomal dominant in 15, undetermined in seven (four sib-pairs); mitochondrial DNA pathological mutations were found in four. The screening identified 23 newly diagnosed relatives in the familial group. Transplantation (P = 0.04) and atrial fibrillation (P = 0.04) were more frequent, and left bundle branch block (P = 0.04) less frequent in index patients with familial than in those with non-familial disease. Several non-affected relatives had instrumental abnormalities potentially useful as pre-clinical markers: their prevalence was similar in both groups. CONCLUSIONS: The prevalence of familial, non X-linked dilated cardiomyopathy was 25%. The immediate benefits of screening family members of index patients was early diagnosis in unaware symptomless affected relatives.

Adult↗
PubMed2001

Correlation between high frequency intravascular ultrasound and histomorphology in human coronary arteries.

OBJECTIVE: To test the efficacy of high frequency intravascular ultrasound (IVUS) transducers in identifying lipid/necrotic pools in atherosclerotic plaques. METHODS: 40 MHz transducers were used for in vitro IVUS assessment of 12 arterial segments (10 coronary and two carotid arteries, dissected from five different necropsy cases). IVUS acquisition was performed at 0.5 mm/s after ligature of the branching points to generate a closed system. Lipid/necrotic areas were defined by IVUS as large echolucent intraplaque areas surrounded by tissue with higher echodensity. To obtain histopathological sections corresponding to IVUS cross sections, vessels were divided into consecutive 3 mm long segments using the most distal recorded IVUS image as the starting reference. Samples were then fixed with 10% buffered formalin, processed for histopathological study, serially cut, and stained using the Movat pentacrome method. RESULTS: 122 sections were analysed. Lipid pools were observed by histology in 30 sections (25%). IVUS revealed the presence of lipid pools in 19 of these sections (16%; sensitivity 65%, specificity 95%). CONCLUSIONS: In vitro assessment of lipid/necrotic pools with high frequency transducers was achieved with good accuracy. This opens new perspectives for future IVUS characterisation of atherosclerotic plaques.

Aged↗
PubMed2001

Healing of acute myocarditis with left ventricular assist device: morphological recovery and evolution to the aspecific features of dilated cardiomyopathy.

Dilated cardiomyopathy may result from an acute myocarditis. Little is reported in vivo documenting the progression from the acute inflammatory disease to the healing phase. We describe the consecutive light and electron microscopy studies performed on five myocardial sample series in a 47-year-old female patient who was referred to our hospital with acute myocarditis. She was sustained with left ventricular assist device (LVAD) for 63 days, and then she died of cerebral hemorrhage. The first three consecutive endomyocardial biopsies (days 2, 4, 36 from onset) documented the acute and early healing phase of the inflammatory disease. In the last two biopsies (days 50 and 64 from onset) active inflammation and myocyte necrosis were absent. The histopathological features were those commonly observed in most patients diagnosed with dilated cardiomyopathy, namely myocyte hypertrophy, nuclear size and shape irregularities, and interstitial fibrosis. Overall, the myocyte morphology significantly improved and LVAD support likely contributed to the structural recovery. The major conclusions to be drawn from this case are: 1) the aspecific pathologic findings of dilated cardiomyopathy patients may result from an acute myocardial inflammation; 2) immediate endomyocardial biopsy in patients with clinically diagnosed myocarditis minimizes the risk of missing the diagnosis of inflammatory disease; to this aim a precise definition of "early onset" is especially needed; 3) LVAD support may contribute to the morphological recovery of severely damaged myocytes.

Biopsy↗
PubMed2001

[The Genetic Area of the ANMCO. Family history in modern cardiology: cardiomyopathies -- Part II].

The family history plays an important role in the cardiomyopathy setting. Cardiomyopathies are defined as familial when at least two members of the family are proven as affected. Given that the definition of familial cardiomyopathy has to be evidence-based, the familial forms have to be identified and documented. Detailed family pedigrees are obtained by interviewing patients and relatives and examining all clinical and pathological reports. Then, the clinical non-invasive screening of relatives is proposed, and performed in all informed and consenting relatives. All patients diagnosed with cardiomyopathy are potentially affected by familial forms, until relatives are proven to be unaffected. A few exceptions could be for syndromic disorders for which the phenotypes provide certainty elements/signs analogous to those observed in the proband. Key points for family history interpretation are the phenotype at onset, the time of onset, the presence/absence of coronary risk factors (such as diabetes and hypertension) and concomitant diseases. Special attention has to be paid to neuromuscular disorders that represent a wide heterogeneous issue in which cardiac involvement (cardiomyopathy, arrhythmias and conduction defects) could be the first manifestation of the disease. Based on rigorous investigation, the information derived for each family will provide useful data for present and future management of the family members, and for future research in the field of cardiomyopathies.

Heart Diseases↗
PubMed2001

[ANMCO genetic area. Significance of family history in cardiology--Part III].

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.

Cardiology↗
PubMed2000

Immunohistochemical characterization of coronary thrombi in allograft vascular disease.

BACKGROUND: Coronary thrombosis is a frequent complication of allograft vascular disease (AVD) in cardiac transplant recipients. No data are available on thrombus composition in these hearts. METHODS: The present study aimed at characterizing thrombus components in coronary arteries from transplanted hearts with AVD, using single and double immunostain with anti-gpIIb-IIIa, anti-fibrin, and anti-endothelial antibodies. The pathologic series consists of 55 grafts survived longer than 2 months, and obtained from 55 patients deceased (n=44) or undergone repeat transplantation (n=11). RESULTS: Mural thrombi were found in multiple segments of 75 of 440 total coronary vessels (17%) (recent in 33, organizing in 28, and organized in 14), whereas occlusive thrombi were found in 19 vessels (8 recent and 11 with multichannel pattern of organization). Recent and thin mural thrombi were mostly constituted of CD41a- and CD61-positive platelets; the amount of fibrin progressively increased with the increase of thrombus size. In organizing mural thrombi, gpIIb-IIIa immunostain was still present. Fibrin was the only identifiable thrombus component in old mural thrombi embedded within the intimal lesions. Recent occlusive thrombi immunoreacted both with anti-CD41a and anti-CD61 and with anti-fibrin antibodies, whereas organized occlusive thrombi with multichannel pattern exclusively immunoreacted with anti-fibrin antibodies. Double immunostain showed that mural thrombi were stratified on de-endothelized arterial segments. CONCLUSIONS: Thrombus composition is related to both type and "age" of thrombus, with platelets as the early and major components of mural microthrombi at one end of the spectrum, and fibrin as the dominant component of occlusive thrombi at the other end.

Adult↗
PubMed2000

Genetics of idiopathic dilated cardiomyopathy.

Familial dilated cardiomyopathy (DCM) should be an "evidence-based" diagnosis derived from clinical and echocardiographic screening of informed and consenting relatives of index patients, and on the examination of clinical reports for deceased relatives. Most familial dilated cardiomyopathy pedigrees show an autosomal pattern of inheritance. Very few of them are X-linked and matrilinear. Autosomal recessive inheritance is difficult to be assessed in an evidence-based setting. By linkage analysis, several loci, but no disease gene, have been identified. At present, few cases of familial dilated cardiomyopathy can benefit of a molecular diagnosis. The diagnosis of dystrophin defect-related dilated cardiomyopathy is important for patients and families, especially for carrier detection. These patients present X-linked inheritance, dominant cardiac involvement and raised levels of serum creatine phosphokinase. Defects of the glycoprotein complex associated to dystrophin (DAG) are rare skeletal muscle diseases with possible cardiac involvement. Mitochondrial diseases, both pure cardiomyopathies and multiorgan syndromes involving the heart, are associated to defects of mitochondrial DNA genes or of nuclear genes coding for mitochondrial proteins. Barth's syndrome develops in male children with granulocytopenia, dilated cardiomyopathy, and methylglutaconic aciduria. Cardiomyopathies with atrioventricular block are observed in hemochromatosis, Emery-Dreifuss syndrome, desmin storage disease, and in isolated familial dilated cardiomyopathy. Actin defects were recently identified in 2 unrelated patients with familial dilated cardiomyopathy. Desmin defects were also recently identified in 1 familial dilated cardiomyopathy. The overall knowledge, although in progression, is still limited. Clinical family screening identifies familial forms, preclinical cases, and inheritance pattern. By candidate gene screening, the molecular diagnosis can be provided for dystrophin, DAG, mitochondrial DNA, actin and desmin gene defects.

Adult↗
PubMed2000

Intravascular ultrasound insights into plaque composition.

UNLABELLED: Previous studies correlating histomorphology with 20-30 MHz-derived intravascular ultrasound (IVUS) images showed that IVUS provides to some extent qualitative information on plaque composition. IVUS imaging proved to define calcifications with high sensitivity and specificity but was found to be less accurate in the assessment of soft components. Nevertheless previous studies on atherosclerotic plaque characterization were limited by use of low-frequency transducers that did not define accurately soft components. Our goal was to test the effectiveness of high frequency IVUS transducers in the identification of lipid/necrotic pools in atherosclerotic plaques. METHODS: Forty MHz transducers were used for in vitro IVUS assessment of 12 arterial segments (10 coronary arteries and 2 carotid arteries dissected from 5 different autopsy cases). IVUS acquisition was performed at a 0.5 mm/s speed after ligature of the branching points to generate a closed system. Lipid necrotic areas were defined by IVUS as large echolucent intraplaque areas surrounded by tissue with higher echodensity. To obtain histopathologic sections corresponding to IVUS cross sections, vessels were divided into consecutive 3 mm-long segments using the most distal recorded IVUS image as the starting reference. Then, samples were fixed with 10% buffered formalin, processed for histopathologic study, serially cut, and stained with the Movat penthacrome method. RESULTS: One hundred twenty-two sections were analyzed. Lipid pools were observed by histology in 30 cross sections (25%). IVUS revealed the presence of lipid pools in 19 of 122 cross sections with a sensitivity and specificity of 67% and 94%, respectively. CONCLUSIONS: High frequency transducers accurately identify lipid/necrotic pools and open new perspectives on future IVUS characterization of atherosclerotic plaques.

Arteriosclerosis↗
PubMed2000

Prevalence and characteristics of dystrophin defects in adult male patients with dilated cardiomyopathy.

OBJECTIVES: To assess the prevalence of dystrophin defects in dilated cardiomyopathy (DCM) in male patients and to formulate investigation strategies for their identification. BACKGROUND: Dystrophin defects presenting with predominant or exclusive cardiac involvement may be clinically indistinguishable from "idiopathic" DCM. Diagnosis may be missed, unless specifically investigated. METHODS: Clinical and biochemical evaluation, right ventricular endomyocardial biopsy (EMB), light and electron microscopic and immunohistochemical studies of biopsy samples, six multiplex and two single polymerase chain reactions for 38 exons and automated sequencing of exon 9 and muscle promoter-exon 1 were undertaken in 201 consecutive male patients presenting with DCM, with (n = 14) and without (n = 187) increased serum creatine phosphokinase (sCPK). RESULTS: Dystrophin defects were identified in 13 of the 201 patients (6.5%, age 16-50). Family history was positive in four patients. Serum CPK levels were increased in 11 of 13 patients. Light microscopy examination of EMB was uninformative; ultrastructural study showed multiple membrane defects. Dystrophin immunostain was abnormal. Eight patients, all older than 20, had deletions affecting midrod domain, normal or mildly increased CPK and better outcome than the five remaining cases all younger than 20, with more than five-fold increase of sCPK. Two of these latter had proximal and rod-domain deletions. Sisters of two patients were diagnosed as noncarriers with microsatellite analysis. CONCLUSIONS: Although the overall prevalence of dystrophin defects in our consecutive DCM male series is low (6.5%), immunohistochemical and molecular studies are essential to identify protein and gene defects; screening studies are justified to define prevalence, clinical profile and genotype-phenotype correlation.

Adolescent↗
PubMed2000

Epidemiology of desmin and cardiac actin gene mutations in a european population of dilated cardiomyopathy.

AIMS: Although dilated cardiomyopathy is the most frequent form of cardiomyopathy, its aetiology is still poorly understood. In about 20-30% of cases the disease is familial with a large predominance of autosomal dominant transmission. Ten different chromosomal loci have been described for autosomal dominant forms of dilated cardiomyopathy. Only two genes have been associated with pure forms (without myopathy and/or conduction disorders) of the disease, the cardiac actin and the desmin genes. Our aim was to determine the proportion of dilated cardiomyopathy affected individuals carrying a mutation in one of these two genes. METHODS AND RESULTS: We performed (1) a systematic polymerase chain reaction-SSCP-sequencing screening of the coding sequences of cardiac actin on DNA samples from 43 probands of dilated cardiomyopathy families and 43 sporadic cases; (2) a systematic polymerase chain reaction-SSCP-sequencing screening of the coding sequences of desmin combined with a search for the described missense mutation (Ile451Met) by restriction fragment length polymorphism analysis on DNA samples from 41 probands of dilated cardiomyopathy families and 22 sporadic cases. CONCLUSION: None of the patients presents a mutation in any of these two genes. Consequently, the proportion of European dilated cardiomyopathy affected individuals bearing a mutation in (1) the cardiac actin gene is less than 1.2%, (2) the desmin gene is less than 1.6%.

Actins↗
PubMed2000

Enteroviral infection causing fatal myocarditis and subclinical myopathy.

UNLABELLED: Enteroviral RNA detection in myocarditis and dilated cardiomyopathy is rare. Enteroviral particles and RNA have recently been identified in patient's skeletal muscle, suggesting that skeletal more than heart muscle hosts the virus in chronic infection. Enteroviral RNA and virus-like particles were found in the myocardium and in the skeletal muscle of two patients with fatal myocarditis: a 39 year old man who died five days after the onset of febrile flu; and a 49 year old woman, assisted for 50 days with a left ventricular assist device, who then died from cerebral haemorrhage. Automated sequencing, alignment, and sequence comparison confirmed the enteroviral origin of polymerase chain reaction products and excluded contamination. These findings agree with prior observations of enteroviral localisation in the skeletal muscle of patients with dilated cardiomyopathy, and further support the hypothesis that skeletal rather than heart muscle may host the virus and serve as a reservoir in cardiomyopathies related to chronic infection. KEYWORDS: enterovirus; myocarditis; viral particles; skeletal muscle

Adult↗
PubMed2000

Identificaiton of chlamydia penumoniae DNA in caroitd plaques.

Chlamydia pneumoniae (CP) is a bacterium that in recent years has been investigated as an etiologic agent for atherosclerosis. It is a ubiquitous microorganism that has been isolated in various regions of the vascular system and its prevalence is about 10% in the patient population. This study involved a group of 43 patients (27 men, 16 women, mean age 68 years) who underwent carotid endarterectomy. About 9.3% of the patients yielded plaques that tested positive for the DNA genome of Chlamydia pneumoniae.

Aged↗
PubMed2000

Percutaneous transluminal coronary revascularization in women: higher risk of dissection and need for stenting.

BACKGROUND: Even though success rates of percutaneous transluminal coronary angioplasty (PTCA) are influenced by gender, women are at higher risk for adverse procedural events. Plaque dissection has been demonstrated to cause more adverse cardiac events during PTCA in the female gender than the male, but it is not clear how much it could influence stent implantation and procedural complications in the stent era. This study sought to evaluate whether the prevalence of dissection is equal in men and women with similar vessel size, which factors are associated with the risk of this complication and whether stenting has modified the immediate outcome. METHODS: Three hundred thirty-nine lesions were studied in 100 consecutive women and 128 men with a vessel diameter < or = 3.5 mm, who underwent PTCA in our catheterization laboratory between March 1998 and March 1999. RESULTS: Procedural success rates were similar in the two groups (93.9% women vs 97.6% men). Complications were one coronary artery bypass graft and five acute myocardial infarctions. In the group of women, however, there was a significant increase in the incidence of plaque dissection during the procedure (37.9 vs 21.7%, p = 0.001), with consequent increased need for stenting (70.4 vs 52.2%, p < 0.05) to achieve adequate final results. Moreover, dissection was strongly associated (p = 0.03) with procedural complications. Multivariate analysis of the whole patient cohort showed the risk of dissection to be associated only with the female gender (p = 0.009), diabetes (p = 0.029), and type C lesion morphology (p = 0.019). CONCLUSIONS: Women are at higher risk of plaque dissection, which is associated with adverse procedural events and an increased need for stenting.

Aged↗
PubMed1999

Stem cell factor is localized in, released from, and cleaved by human mast cells.

Stem cell factor (SCF) is the most important cytokine regulating human mast cell growth and functions. The immunogold technique showed SCF in the secretory granules of skin mast cells and in lung parenchymal mast cells (HLMC). Immunoreactive SCF (iSCF) was detected in cell lysates of HLMC, but not in basophils; iSCF and histamine were detected in supernatants of HLMC 3 min after challenge with anti-FcepsilonRI or anti-IgE, and iSCF in supernatants rapidly declined after 30 min, whereas histamine remained unchanged for 120 min. HPLC and electrospray mass spectrometry (ES/MS) analysis of recombinant human SCF1-166 (18,656. 9 +/- 0.9 Da) treated with chymase showed a polypeptide of 17,977.1 +/- 0.6 Da and a minor component of 697.4 +/- 0.1 Da generated by specific cleavage at Phe159. SCF1-166 and SCF1-159 similarly activated HLMC, potentiated anti-IgE-induced activation of these cells, and stimulated HLMC chemotaxis. SCF159-166 had no effect on mast cells. Western blot analysis of supernatants of anti-IgE-activated HLMC incubated with recombinant human SCF1-166 showed that SCF1-166 was rapidly cleaved to SCF1-159 and SCF1-144. Experiments with supernatants of anti-IgE-activated HLMC incubated with SCF1-166 yielded similar results. In conclusion, SCF is stored in mast cell secretory granules and is immunologically released by human mast cells. SCF1-166 is rapidly and specifically cleaved to SCF1-159 by chymase, which retains its biological effect on mast cells. SCF is also cleaved by other proteases to several SCF species whose possible biological activities remain to be established.

Adolescent↗
PubMed1999

Apoptosis in heart failure: release of cytochrome c from mitochondria and activation of caspase-3 in human cardiomyopathy.

Apoptosis has been shown to contribute to loss of cardiomyocytes in cardiomyopathy, progressive decline in left ventricular function, and congestive heart failure. Because the molecular mechanisms involved in apoptosis of cardiocytes are not completely understood, we studied the biochemical and ultrastructural characteristics of upstream regulators of apoptosis in hearts explanted from patients undergoing transplantation. Sixteen explanted hearts from patients undergoing heart transplantation were studied by electron microscopy or immunoblotting to detect release of mitochondrial cytochrome c and activation of caspase-3. The hearts explanted from five victims of motor vehicle accidents or myocardial ventricular tissues from three donor hearts were used as controls. Evidence of apoptosis was observed only in endstage cardiomyopathy. There was significant accumulation of cytochrome c in the cytosol, over myofibrils, and near intercalated discs of cardiomyocytes in failing hearts. The release of mitochondrial cytochrome c was associated with activation of caspase-3 and cleavage of its substrate protein kinase C delta but not poly(ADP-ribose) polymerase. By contrast, there was no apparent accumulation of cytosolic cytochrome c or caspase-3 activation in the hearts used as controls. The present study provides in vivo evidence of cytochrome c-dependent activation of cysteine proteases in human cardiomyopathy. Activation of proteases supports the phenomenon of apoptosis in myopathic process. Because loss of myocytes contributes to myocardial dysfunction and is a predictor of adverse outcomes in the patients with congestive heart failure, the present demonstration of an activated apoptotic cascade in cardiomyopathy could provide the basis for novel interventional strategies.

Animals↗