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Biomedical subjects

Elisa Carniel

Publications and source records attributed to Elisa Carniel.

10 recordsLinked to original sources
PubMed2006

Cardiomyopathy, familial dilated.

Dilated cardiomyopathy (DCM) is a heart muscle disease characterized by ventricular dilatation and impaired systolic function. Patients with DCM suffer from heart failure, arrhythmia, and are at risk of premature death. DCM has a prevalence of one case out of 2500 individuals with an incidence of 7/100,000/year (but may be under diagnosed). In many cases the disease is inherited and is termed familial DCM (FDC). FDC may account for 20-48% of DCM. FDC is principally caused by genetic mutations in FDC genes that encode for cytoskeletal and sarcomeric proteins in the cardiac myocyte. Family history analysis is an important tool for identifying families affected by FDC. Standard criteria for evaluating FDC families have been published and the use of such criteria is increasing. Clinical genetic testing has been developed for some FDC genes and will be increasingly utilized for evaluating FDC families. Through the use of family screening by pedigree analysis and/or genetic testing, it is possible to identify patients at earlier, or even presymptomatic stages of their disease. This presents an opportunity to invoke lifestyle changes and to provide pharmacological therapy earlier in the course of disease. Genetic counseling is used to identify additional asymptomatic family members who are at risk of developing symptoms, allowing for regular screening of these individuals. The management of FDC focuses on limiting the progression of heart failure and controlling arrhythmia, and is based on currently accepted treatment guidelines for DCM. It includes general measures (salt and fluid restriction, treatment of hypertension, limitation of alcohol intake, control of body weight, moderate exercise) and pharmacotherapy. Cardiac resynchronization, implantable cardioverter defibrillators and left ventricular assist devices have progressively expanding usage. Patients with severe heart failure, severe reduction of the functional capacity and depressed left ventricular ejection fraction have a low survival rate and may require heart transplant.

Cardiomyopathy, Dilated↗
PubMed2005

Alpha-myosin heavy chain: a sarcomeric gene associated with dilated and hypertrophic phenotypes of cardiomyopathy.

BACKGROUND: Mutations in the beta-myosin heavy-chain (betaMyHC) gene cause hypertrophic (HCM) and dilated (DCM) forms of cardiomyopathy. In failing human hearts, downregulation of alphaMyHC mRNA or protein has been correlated with systolic dysfunction. We hypothesized that mutations in alphaMyHC could also lead to pleiotropic cardiac phenotypes, including HCM and DCM. METHODS AND RESULTS: A cohort of 434 subjects, 374 (134 affected, 214 unaffected, 26 unknown) belonging to 69 DCM families and 60 (29 affected, 30 unaffected, 1 unknown) in 21 HCM families, was screened for alphaMyHC gene (MYH6) mutations. Three heterozygous MYH6 missense mutations were identified in DCM probands (P830L, A1004S, and E1457K; 4.3% of probands). A Q1065H mutation was detected in 1 of 21 HCM probands and was absent in 2 unaffected offspring. All MYH6 mutations were distributed in highly conserved residues, were predicted to change the structure or chemical bonds of alphaMyHC, and were absent in at least 300 control chromosomes from an ethnically similar population. The DCM carrier phenotype was characterized by late onset, whereas the HCM phenotype was characterized by progression toward dilation, left ventricular dysfunction, and refractory heart failure. CONCLUSIONS: This study suggests that mutations in MYH6 may cause a spectrum of phenotypes ranging from DCM to HCM.

Cardiomyopathy, Dilated↗
PubMed2005

Thymopoietin (lamina-associated polypeptide 2) gene mutation associated with dilated cardiomyopathy.

Thymopoietin or TMPO (indicated by its alternative gene symbol, LAP2, in this work) has been proposed as a candidate disease gene for dilated cardiomyopathy (DCM), since a LAP2 product associates with nucleoplasmic lamins A/C, which are encoded by the DCM gene LMNA. We developed a study to screen for genetic mutations in LAP2 in a large collection of DCM patients and families. A total of 113 subjects from 88 families (56 with familial DCM (FDC) and 32 with sporadic DCM) were screened for LAP2 mutations using denaturing high-performance liquid chromatography and sequence analysis. We found a single putative mutation affecting the LAP2alpha isoform in one FDC pedigree. The mutation predicts an Arg690Cys substitution (c.2068C>T; p.R690C) located in the C-terminal domain of the LAP2alpha protein, a region that is known to interact with lamin A/C. RT-PCR, Western blot analyses, and immunolocalization revealed low-level LAP2alpha expression in adult cardiac muscle, and localization to a subset of nuclei. Mutated Arg690Cys LAP2alpha expressed in HeLa cells localized to the nucleoplasm like wild-type LAP2alpha, with no effect on peripheral and nucleoplasmic lamin A distribution. However, the in vitro interaction of mutated LAP2alpha with the pre-lamin A C-terminus was significantly compromised compared to the wild-type protein. LAP2 mutations may represent a rare cause of DCM. The Arg690Cys mutation altered the observed LAP2alpha interaction with A-type lamins. Our finding implicates a novel nuclear lamina-associated protein in the pathogenesis of genetic forms of dilated cardiomyopathy.

Cardiomyopathy, Dilated↗
PubMed2004

Familial hypertrophic cardiomyopathy: clinical features, molecular genetics and molecular genetic testing.

Hypertrophic cardiomyopathy is a Mendelian disease characterized by cardiac hypertrophy. It has a prevalence of 1:500 individuals and is the most common cause of sudden death in the young. Other complications include heart failure and the need for heart transplantation. Hypertrophic cardiomyopathy is due to sarcomeric gene mutations, however, phenocopies with myocardial hypertrophy can be due to triplet-repeat syndromes (Friedreich ataxia and myotonic dystrophy), mitochondrial and metabolic diseases. In a peculiar form associated with Wolf-Parkinson-White syndrome, the disease is caused by mutations in the gamma2 regulatory subunit of the AMP-activated protein kinase gene, leading to a glycogen storage cardiomyopathy. In spite of the growing knowledge about the molecular basis of hypertrophic cardiomyopathy, very little is still known about the genotype-phenotype correlations and their clinical implications. In this review, the clinical and molecular genetics of hypertrophic cardiomyopathy are described.

Animals↗
PubMed2004

[How the natural history of dilated cardiomyopathy has changed. Review of the Registry of Myocardial Diseases of Trieste].

Dilated cardiomyopathy (DCM), a heart muscle disease characterized by ventricular dilation and dysfunction, is a leading cause of mortality and morbidity. In the present paper we will consider the main results of studies on the natural history of DCM in 581 consecutive patients prospectively enrolled and systematically followed in the Heart Muscle Disease Registry of Trieste in the last 25 years. In the last decades prognosis of DCM significantly improved over time, mainly as a consequence of optimized treatment with ACE-inhibitors and beta-blockers. However, a strong heterogeneity of prognosis was observed among patients both in familial and sporadic cases. Early diagnosis and treatment allowed to recognize two distinct subgroups, one with a rapidly progressive downhill course, high mortality and urgent indication to heart transplantation, another with a more favorable outcome. Long-term optimized treatment with ACE-inhibitors (in 90% of cases) and beta-blockers (in 87% of cases) was associated with a remarkable clinical improvement in 50% of patients and apparent "healing" in 16% of cases. A systematic and accurate echocardiographic follow-up showed in these cases a significant improvement of the left ventricular ejection fraction (LVEF) with "reverse remodeling", frequently associated with a decrease of severity of functional mitral regurgitation and regression of the restrictive filling pattern. The response to optimal treatment showed a strong relation to long-term outcome. The 8-year transplant-free survival, starting from the evaluation at 2 years, was 31% in patients with persistent NYHA class III-IV, 64% in NYHA class I-II and LVEF < or = 40%, 83% in NYHA class I-II and LVEF > 40% and 94% in patients with apparent "healing" (p < 0.0001). Long-term follow-up showed a significant clinical progression of the disease in 33% of cases, independently of the initial clinical response to treatment. Predictive factors of a favorable response to beta-blocker treatment associated with ACE-inhibitors were a history of mild hypertension, an early diagnosis and treatment and the presence of sinus tachycardia. The risk of sudden death was increased particularly in patients with long-term persistent or progressive left ventricular dilation and dysfunction. A rigorous pharmacological approach (optimization of beta-blockers, withdrawal or decrease of dosage of digitalis), and selective non-pharmacological strategy (automated implantable cardioverter-defibrillators for primary prevention in high-risk patients) are potentially effective to decrease the incidence of sudden death during long-term follow-up. In conclusion, the Heart Muscle Disease Registry of Trieste gave us in the last 25 years new insights into the natural history of DCM, underlying the importance of a rigorous and systematic approach both at clinical presentation and during long-term follow-up on optimized medical treatment.

Arrhythmias, Cardiac↗
PubMed2004

[The natural history of dilated cardiomyopathy: a review of the Heart Muscle Disease Registry of Trieste].

Dilated cardiomyopathy (DCM), a heart muscle disease characterized by ventricular dilation and dysfunction, is a leading cause of mortality and morbidity. In the present paper we will consider the main results of studies on the natural history of DCM in 581 consecutive patients prospectively enrolled and systematically followed in the Heart Muscle Disease Registry of Trieste in the last 25 years. In the last decades prognosis of DCM significantly improved over time, mainly as a consequence of optimized treatment with ACE-inhibitors and beta-blockers. However, a strong heterogeneity of prognosis was observed among patients both in familial and sporadic cases. Early diagnosis and treatment allowed to recognize two distinct subgroups, one with a rapidly progressive downhill course, high mortality and urgent indication to heart transplantation, another with a more favorable outcome. Long-term optimized treatment with ACE-inhibitors (in 90% of cases) and beta-blockers (in 87% of cases) was associated with a remarkable clinical improvement in 50% of patients and apparent "healing" in 16% of cases. A systematic and accurate echocardiographic follow-up showed in these cases a significant improvement of the left ventricular ejection fraction (LVEF) with "reverse remodeling", frequently associated with a decrease of severity of functional mitral regurgitation and regression of the restrictive filling pattern. The response to optimal treatment showed a strong relation to long-term outcome. The 8-year transplant-free survival, starting from the evaluation at 2 years, was 31% in patients with persistent NYHA class III-IV, 64% in NYHA class I-II and LVEF < or = 40%, 83% in NYHA class I-II and LVEF > 40% and 94% in patients with apparent "healing" (p < 0.0001). Long-term follow-up showed a significant clinical progression of the disease in 33% of cases, independently of the initial clinical response to treatment. Predictive factors of a favorable response to beta-blocker treatment associated with ACE-inhibitors were a history of mild hypertension, an early diagnosis and treatment and the presence of sinus tachycardia. The risk of sudden death was increased particularly in patients with long-term persistent or progressive left ventricular dilation and dysfunction. A rigorous pharmacological approach (optimization of beta-blockers, withdrawal or decrease of dosage of digitalis), and selective non-pharmacological strategy (automated implantable cardioverter-defibrillators for primary prevention in high-risk patients) are potentially effective to decrease the incidence of sudden death during long-term follow-up. In conclusion, the Heart Muscle Disease Registry of Trieste gave us in the last 25 years new insights into the natural history of DCM, underlying the importance of a rigorous and systematic approach both at clinical presentation and during long-term follow-up on optimized medical treatment.

Adult↗
PubMed2004

Idiopathic dilated cardiomyopathy: prognostic significance of electrocardiographic and electrophysiologic findings in the nineties.

BACKGROUND: With the exception of a few cases such as aborted sudden cardiac death, sustained ventricular tachycardia, and syncope of unexplained origin, there is no consensus on the clinical findings identifying patients with idiopathic dilated cardiomyopathy with an increased risk of sudden cardiac death or malignant ventricular arrhythmias. METHODS: To verify whether electrocardiographic and arrhythmologic features could be useful for prognostic stratification, 78 consecutive patients with an invasive diagnosis of idiopathic dilated cardiomyopathy, but without symptomatic ventricular arrhythmias, were enrolled in a prospective study. Signal-averaged ECG, 24 to 48 hour ECG monitoring and electrophysiologic study were performed at the time of diagnosis to identify arrhythmogenic predictors of outcome. Transplant-free and arrhythmic event-free survival was evaluated on the basis of initial parameters. RESULTS: During a mean follow-up of 85 months, 9 patients died (6 of sudden cardiac death and 3 of congestive heart failure), 10 patients underwent cardiac transplantation for refractory heart failure, and 3 presented with sustained ventricular tachycardia. The independent predictors for death and cardiac transplantation were an HV interval > 55 ms and the combination of frequent repetitive ventricular ectopics with a poor left ventricular function. A strong index of arrhythmic events proved to be the association of a prolonged HV interval with a wide (> 110 ms) QRS complex (odds ratio 4.53, 95% confidence interval 1.57-13.04, p < 0.005). CONCLUSIONS: An accurate measurement of the HV interval and QRS duration at baseline evaluation may add prognostic information in patients with idiopathic dilated cardiomyopathy. In our experience, abnormal values of both parameters identified a group of patients with a very high risk of late occurring arrhythmic events.

Adolescent↗
PubMed2004

Fatal myocarditis: morphologic and clinical features.

BACKGROUND: Autopsy studies report a frequency of myocarditis ranging from 0.11 to 5.5% in the general population, reaching almost 50% in selected groups. Myocarditis is often undiagnosed and the incidence of fatal course myocarditis has never been evaluated. The aim of our study was to assess the frequency of fatal course myocarditis in a consecutive series of autopsies and to describe the clinical, histological and morphologic features of the disease. METHODS: From January 1, 1995 to January 31, 1996, 2560 autopsies were performed, and 143 cases of active myocarditis were diagnosed (5.6%). RESULTS: In 39 cases (1.5%; 12 males; 4/39 aged < or = 35 years) active myocarditis was identified as the final cause of death. Only in 1 case was myocarditis suspected ante-mortem. The histological pattern was lymphocytic in 64% of cases. A mixed inflammatory infiltration was found in 33% and a granulomatous infiltration in 3%. In 49% of cases myocarditis was localized in both ventricles and the interventricular septum. The clinical presentation of myocarditis was heart failure in 18/39 patients (46%), cardiac arrest in 4/39 patients (10%) and syncope and chest pain in 1/39 patient (3%). The mean creatine phosphokinase levels were 890 +/- 2742 IU/I (assessed in 11/39 patients, 28%) but they were increased only in 7/39 (18%). ECG (performed in 29/39 patients, 74%) showed sinus rhythm in 16/39 patients (55%, > 100 b/min in 41%), atrioventricular or interventricular conduction defects in 10/39 patients (34%) and a pathological Q wave in 4/39 patients (14%). At echocardiography (performed in 7/39 patients, 18%), right and/or left ventricular dysfunction was found to be present in 5 cases (71%) and a pericardial effusion in 4 cases (57%). CONCLUSIONS: Myocarditis is underdiagnosed ante-mortem. A high index of clinical suspicion is mandatory for prompt diagnosis and treatment of this fatal disease seen also in the young.

Adolescent↗
PubMed2003

Natural history of dilated cardiomyopathy due to lamin A/C gene mutations.

OBJECTIVES: We examined the prevalence, genotype-phenotype correlation, and natural history of lamin A/C gene (LMNA) mutations in subjects with dilated cardiomyopathy (DCM). BACKGROUND: Mutations in LMNA have been found in patients with DCM with familial conduction defects and muscular dystrophy, but the clinical spectrum, prognosis, and clinical relevance of laminopathies in DCM are unknown. BACKGROUND: A cohort of 49 nuclear families, 40 with familial DCM and 9 with sporadic DCM (269 subjects, 105 affected), was screened for mutations in LMNA using denaturing high-performance liquid chromatography and sequence analysis. Bivariate analysis of clinical predictors of LMNA mutation carrier status and Kaplan-Meier survival analysis were performed. RESULTS: Mutations in LMNA were detected in four families (8%), three with familial (R89L, 959delT, R377H) and one with sporadic DCM (S573L). There was significant phenotypic variability, but the presence of skeletal muscle involvement (p < 0.001), supraventricular arrhythmia (p = 0.003), conduction defects (p = 0.01), and "mildly" DCM (p = 0.006) were predictors of LMNA mutations. The LMNA mutation carriers had a significantly poorer cumulative survival compared with non-carrier DCM patients: event-free survival at the age of 45 years was 31% versus 75% in non-carriers. CONCLUSIONS: Mutations in LMNA cause a severe and progressive DCM in a relevant proportion of patients. Mutation screening should be considered in patients with DCM, in particular when clinical predictors of LMNA mutation are present, regardless of family history.

Amino Acid Sequence↗
PubMed2003

Usefulness of exercise test in selected patients coming to the emergency department for acute chest pain.

BACKGROUND: The management of patients with acute chest pain is a common and difficult challenge for clinicians. In our emergency department (ED) a systematic protocol that involves the use of the exercise test for the management of patients with chest pain of suspected cardiac origin is presently running. The aim of the present study was to evaluate the feasibility of such a test in this setting, in terms of the safety and satisfactory follow-up of these patients discharged home. METHODS: Patients with chest pain lasting < or = 24 hours, aged > 18 years, without a history of trauma or of any other evident medical cause of chest pain and without high-risk characteristics were included in the present study. These patients, defined as low-risk patients for acute coronary events on admission, were evaluated in the ED area and submitted to serial ECG and blood sampling for the determination of the creatine kinase-MB mass and troponin I serum levels on admission and at 6 and 12 hours after admission. A symptom-limited maximal exercise was performed in the patients with a negative clinical observation and typical chest pain or atypical chest pain but multiple coronary risk factors. RESULTS: In the year 2000, 1370 patients were evaluated in the ED for chest pain. In 150 (11%) an exercise test was performed. The test was positive in 24 patients (16%). The criteria for a positive test were only clinical in 3 patients, only ECG in 13 patients, and both in 8 patients. Inconclusive tests were observed in 27 patients (18%) and the test was negative in 99 patients (66%). There were no complications during the exercise test. At a median follow-up of 237 days (range 11-443 days), 11 clinical events were recorded (4 acute coronary syndromes and 7 revascularization procedures). Patients with a non-negative exercise test had a significantly shorter event-free survival (p < 0.005). CONCLUSIONS: The exercise test performed in selected patients coming to the ED with acute chest pain is safe and useful for further risk assessment.

Acute Disease↗