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1.
Transpl Infect Dis ; 12(3): 258-60, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20015115

ABSTRACT

Pulmonary complications are not infrequent after heart transplantation. Kaposi sarcoma is a vascular tumor that can involve the skin as well as visceral organs. We describe a case of visceral and cutaneous Kaposi sarcoma that presented with diffuse bilateral pulmonary infiltration and breathlessness 6 month after heart transplantation. Following modulation of the immunosuppressive regimen and addition of chemotherapy, the patient had an excellent response and has had an uneventful 1-year follow-up.


Subject(s)
Heart Transplantation/adverse effects , Lung Neoplasms/etiology , Sarcoma, Kaposi/etiology , Skin Neoplasms/etiology , Herpesvirus 8, Human/classification , Herpesvirus 8, Human/genetics , Herpesvirus 8, Human/isolation & purification , Humans , Lung/pathology , Lung Neoplasms/pathology , Lung Neoplasms/virology , Male , Middle Aged , Sarcoma, Kaposi/pathology , Sarcoma, Kaposi/virology , Skin Neoplasms/pathology , Skin Neoplasms/virology
2.
Pacing Clin Electrophysiol ; 29(12): 1326-33, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17201838

ABSTRACT

BACKGROUND: His Bundle (HB) pacing is a valid alternative to right ventricular pacing for patients with preserved His-ventricle conduction who are candidates for permanent stimulation. Permanent pacing in the HB area enables Selective HB pacing (SHBP) or para-Hisian pacing (PHP) to be achieved. The aim of our study was to draw up a set of easy criteria to differentiate and validate the two kinds of stimulations according to the pacing output and the ECG/EKG signals. METHODS AND RESULTS: From February to July 2005, 17 patients eligible for a pacemaker (PM) procedure underwent implantation with the Medtronic SelectSecure lead (Medtronic, Minneapolis, MN, USA) screwed into the HB area.SHBP was defined when the intrinsic QRS was equal, in both duration and morphology, to the paced QRS, the His-Ventricular (H-V) interval was equal to Pace-Ventricular interval (Vp-V) and, at low output, only the HB was captured, while increasing the output resulted in both the HB and right ventricular (RV) being captured (widening of QRS at high output). Conversely, PHP was defined when the intrinsic QRS differed from the paced one, either in morphology or in duration and, at high output, both the RV and HB were captured (non-SHBP), while decreasing the output resulted in losing HB capture (widening of QRS at low output). According to these criteria, SHBP was achieved in 11 patients, while in the remaining 6, PHP was obtained. No adverse events were reported. CONCLUSIONS: The above criteria enabled SHBP and PHP to be validated easily and clearly. A longer follow-up will be needed in order to ascertain whether the clinical outcome of these two approaches differs.


Subject(s)
Arrhythmias, Cardiac/prevention & control , Bundle of His , Cardiac Pacing, Artificial/methods , Electrocardiography/methods , Patient Selection , Aged , Electrocardiography/instrumentation , Female , Humans , Male , Pacemaker, Artificial , Treatment Outcome
3.
Neurobiol Aging ; 24(7): 927-31, 2003 Nov.
Article in English | MEDLINE | ID: mdl-12928052

ABSTRACT

Interleukin-1alpha (IL-1alpha) and IL-1beta are two pro-inflammatory cytokines involved in the pathogenesis of Alzheimer's disease (AD). The genes coding for IL-1alpha (IL-1A) and for IL-1beta (IL-1B) are clustered in chromosome 2q14-2q14.2. In a previous work, we investigated the role of IL-1A promoter polymorphism (-889 position) in AD pathogenesis: IL-1A -889 TT genotype was associated with sporadic early onset AD. We now report the study on polymorphism of exon 5 IL-1B in position +3953, the nearest polymorphism to -889 IL-1A. We found that the genotype distribution of IL-1B +3953 varied significantly between patients with early and late onset of AD (P<0.0001). Patients carrying IL-1B +3953 CT or TT genotypes had 4 or 5 years anticipation of AD onset (P=0.0034; odds ratio for early onset, 3.01) and 7 years anticipation if they also carried the IL-1A -889 TT genotype (P<0.0001; odds ratio for early onset, 7.4). These data further support a role for inflammation-related genes in AD or indicate linkage disequilibrium with an unknown chromosome 2 locus.


Subject(s)
Alzheimer Disease/genetics , Chromosomes, Human, Pair 2/genetics , Interleukin-1/genetics , Polymorphism, Genetic , Aged , Aged, 80 and over , Apolipoproteins E/genetics , Female , Genetic Predisposition to Disease , Humans , Italy , Linkage Disequilibrium , Male , Matched-Pair Analysis , Middle Aged , Reference Values
4.
Eur Heart J ; 24(5): 442-63, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12633546

ABSTRACT

BACKGROUND: The European Society of Cardiology (ESC) has published guidelines for the investigation of patients with suspected heart failure and, if the diagnosis is proven, their subsequent management. Hospitalisation provides a key point of care at which time diagnosis and treatment may be refined to improve outcome for a group of patients with a high morbidity and mortality. However, little international data exists to describe the features and management of such patients. Accordingly, the EuroHeart Failure survey was conducted to ascertain if appropriate tests were being performed with which to confirm or refute a diagnosis of heart failure and how this influenced subsequent management. METHODS: The survey screened consecutive deaths and discharges during 2000-2001 predominantly from medical wards over a 6-week period in 115 hospitals from 24 countries belonging to the ESC, to identify patients with known or suspected heart failure. RESULTS: A total of 46788 deaths and discharges were screened from which 11327 (24%) patients were enrolled with suspected or confirmed heart failure. Forty-seven percent of those enrolled were women. Fifty-one percent of women and 30% of men were aged >75 years. Eighty-three percent of patients had a diagnosis of heart failure made on or prior to the index admission. Heart failure was the principal reason for admission in 40%. The great majority of patients (>90%) had had an ECG, chest X-ray, haemoglobin and electrolytes measured as recommended in ESC guidelines, but only 66% had ever had an echocardiogram. Left ventricular ejection fraction had been measured in 57% of men and 41% of women, usually by echocardiography (84%) and was <40% in 51% of men but only in 28% of women. Forty-five percent of women and 22% of men were reported to have normal left ventricular systolic function by qualitative echocardiographic assessment. A substantial proportion of patients had alternative explanations for heart failure other than left ventricular systolic or diastolic dysfunction, including valve disease. Within 12 weeks of discharge, 24% of patients had been readmitted. A total of 1408 of 10434 (13.5%) patients died between admission and 12 weeks follow-up. CONCLUSIONS: Known or suspected heart failure comprises a large proportion of admissions to medical wards and such patients are at high risk of early readmission and death. Many of the basic investigations recommended by the ESC were usually carried out, although it is not clear whether this was by design or part of a general routine for all patients being admitted regardless of diagnosis. The investigation most specific for patients with suspected heart failure (echocardiography) was performed less frequently, suggesting that the diagnosis of heart failure is still relatively neglected. Most men but a minority of women who underwent investigation of cardiac function had evidence of moderate or severe left ventricular dysfunction, the main target of current advances in the treatment of heart failure. Considerable diagnostic uncertainty remains for many patients with suspected heart failure, even after echocardiography, which must be resolved in order to target existing and new therapies and services effectively.


Subject(s)
Cardiac Output, Low/therapy , Hospitalization/statistics & numerical data , Quality of Health Care , Aged , Cardiac Output, Low/complications , Cardiac Output, Low/mortality , Cardiovascular Diseases/complications , Cardiovascular Diseases/therapy , Europe/epidemiology , Female , Health Surveys , Hospital Mortality , Humans , Male , Middle Aged , Multivariate Analysis , Patient Readmission , Practice Guidelines as Topic , Risk Factors , Survival Analysis
5.
Eur Heart J ; 24(5): 464-74, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12633547

ABSTRACT

BACKGROUND: National surveys suggest that treatment of heart failure in daily practice differs from guidelines and is characterized by underuse of recommended medications. Accordingly, the Euro Heart Failure Survey was conducted to ascertain how patients hospitalized for heart failure are managed in Europe and if national variations occur in the treatment of this condition. METHODS: The survey screened discharge summaries of 11304 patients over a 6-week period in 115 hospitals from 24 countries belonging to the ESC to study their medical treatment. RESULTS: Diuretics (mainly loop diuretics) were prescribed in 86.9% followed by ACE inhibitors (61.8%), beta-blockers (36.9%), cardiac glycosides (35.7%), nitrates (32.1%), calcium channel blockers (21.2%) and spironolactone (20.5%). 44.6% of the population used four or more different drugs. Only 17.2% were under the combination of diuretic, ACE inhibitors and beta-blockers. Important local variations were found in the rate of prescription of ACE inhibitors and particularly beta-blockers. Daily dosage of ACE inhibitors and particularly of beta-blockers was on average below the recommended target dose. Modelling-analysis of the prescription of treatments indicated that the aetiology of heart failure, age, co-morbid factors and type of hospital ward influenced the rate of prescription. Age <70 years, male gender and ischaemic aetiology were associated with an increased odds ratio for receiving an ACE inhibitor. Prescription of ACE inhibitors was also greater in diabetic patients and in patients with low ejection fraction (<40%) and lower in patients with renal dysfunction. The odds ratio for receiving a beta-blocker was reduced in patients >70 years, in patients with respiratory disease and increased in cardiology wards, in ischaemic heart failure and in male subjects. Prescription of cardiac glycosides was significantly increased in patients with supraventricular tachycardia/atrial fibrillation. Finally, the rate of prescription of antithrombotic agents was increased in the presence of supraventricular arrhythmia, ischaemic heart disease, male subjects but was decreased in patients over 70. CONCLUSION: Our results suggest that the prescription of recommended medications including ACE inhibitors and beta-blockers remains limited and that the daily dosage remains low, particularly for beta-blockers. The survey also identifies several important factors including age, gender, type of hospital ward, co morbid factors which influence the prescription of heart failure medication at discharge.


Subject(s)
Cardiac Output, Low/drug therapy , Cardiovascular Agents/therapeutic use , Quality of Health Care , Adrenergic beta-Antagonists/therapeutic use , Age Factors , Aged , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Aspirin/therapeutic use , Calcium Channel Blockers/therapeutic use , Cardiac Glycosides/therapeutic use , Cardiac Output, Low/complications , Europe , Female , Fibrinolytic Agents/therapeutic use , Health Surveys , Hospitalization , Humans , Male , Multivariate Analysis , Platelet Aggregation Inhibitors/therapeutic use , Spironolactone/therapeutic use
6.
Lancet ; 360(9346): 1631-9, 2002 Nov 23.
Article in English | MEDLINE | ID: mdl-12457785

ABSTRACT

BACKGROUND: Heart failure is a prevalent condition that is generally treated in primary care. The aim of this study was to assess how primary-care physicians think that heart failure should be managed, how they implement their knowledge, and whether differences exist in practice between countries. METHODS: The survey was undertaken in 15 countries that had membership of the European Society of Cardiology (ESC) between Sept 1, 1999, and May 31, 2000. Primary-care physicians' knowledge and perceptions about the management of heart failure were assessed with a perception survey and how a representative sample of patients was managed with an actual practice survey. FINDINGS: 1363 physicians provided data for 11062 patients, of whom 54% were older than 70 years and 45% were women. 82% of patients had had an echocardiogram but only 51% of these showed left ventricular systolic dysfunction. Ischaemic heart disease, hypertension, diabetes mellitus, atrial fibrillation, and major valve disease were all common. Physicians gave roughly equal priority to improvement of symptoms and prognosis. Most were aware of the benefits of ACE inhibitors and beta blockers. 60% of patients were prescribed ACE inhibitors, 34% beta blockers but only 20% received these drugs in combination. Doses given were about 50% of targets suggested in the ESC guidelines. If systolic dysfunction was documented, ACE inhibitors were more likely and beta blockers less likely to be prescribed than when there was no evidence of systolic dysfunction. INTERPRETATION: Results from this survey suggest that most patients with heart failure are appropriately investigated, although this finding might be as a result of high rates of hospital admissions. However, treatment seems to be less than optimum, and there are substantial variations in practice between countries. The inconsistencies between physicians' knowledge and the treatment that they deliver suggests that improved organisation of care for heart failure is required.


Subject(s)
Cardiotonic Agents/therapeutic use , Heart Failure/drug therapy , Practice Patterns, Physicians' , Primary Health Care/methods , Aged , Attitude of Health Personnel , Data Collection , Europe/epidemiology , Female , Heart Failure/epidemiology , Heart Failure/mortality , Humans , Male
7.
Echocardiography ; 18(6): 469-77, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11567591

ABSTRACT

BACKGROUND: Although flow velocities curves recorded with pulsed-wave Doppler in systemic vein are known to provide functional data on the right circulatory function, little information is available on the relationship between right heart filling dynamics and right ventricular function. METHODS: Consecutive patients with chronic heart failure due to severe systolic left ventricular dysfunction and in sinus rhythm underwent echocardiography and right heart catheterization. In the initial part of the study, the hemodynamic correlates of different flow velocity patterns recorded into the superior vena cava were evaluated in 120 patients. The accuracy of the prediction of different right heart hemodynamic profiles by means of the different venous flow patterns was then prospectively tested in a subsequent series of 86 patients. RESULTS: The venous flow pattern was closely related to right heart hemodynamics. A normal Doppler pattern identified patients with normal right heart hemodynamics (sensitivity 86%, specificity 78%); a "predominant systolic wave" pattern identified patients with a reduced thermodilution-derived right ventricular ejection fraction (< 30%) and normal or slightly elevated right atrial pressure (< or = 8 mmHg) (sensitivity 69%, specificity 81%); a "predominant diastolic wave" pattern identified patients with a reduced right ventricular ejection fraction (< 3 0%) and elevated right atrial pressure (> 8 mmHg) (sensitivity 52%, specificity 95%). The observed and the predicted hemodynamic profiles turned out to be concordant in 80% of patients. CONCLUSIONS: The analysis of the flow velocity pattern into the superior vena cava is a useful tool to estimate the extent of the right circulatory impairment in patients with congestive heart failure.


Subject(s)
Coronary Circulation/physiology , Echocardiography, Doppler , Heart Failure/diagnostic imaging , Heart Failure/physiopathology , Rheology , Vena Cava, Superior/diagnostic imaging , Adult , Blood Flow Velocity/physiology , Feasibility Studies , Female , Heart Atria/diagnostic imaging , Hemodynamics/physiology , Hepatic Veins/diagnostic imaging , Humans , Male , Middle Aged , Predictive Value of Tests , Reproducibility of Results , Sensitivity and Specificity , Ventricular Function, Left/physiology
9.
Eur J Heart Fail ; 3(2): 257-60, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11246065

ABSTRACT

In Italy, the National Health System is funded from the taxation system of the state. It is organized by general practitioners in the community and specialists in the hospitals. All Italian citizens are registered with one of the general practitioners. Patients with suspected heart failure are generally referred from the family practitioner to a higher level of medical care. Only a minority of patients with heart failure are cared for by cardiologists, either as in- or outpatients. Echocardiography is widely available; nevertheless, few patients admitted to internal medicine divisions receive an echocardiogram compared to cardiology units. The ACE inhibitor usage by Italian cardiologists in patients with heart failure is satisfied, and the use of beta blockers is increasing in Italy at this time. Since only a small proportion of patients with heart failure are followed by cardiologists in Italy, further efforts are necessary until internists and general practitioners could be involved in treatment trials in heart failure. The aim of this approach is to transfer the beneficial effects observed in the trials to clinical practice.


Subject(s)
Cardiovascular Agents/administration & dosage , Cross-Cultural Comparison , Heart Failure/drug therapy , Patient Care Team , Adrenergic beta-Antagonists/administration & dosage , Adult , Aged , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Chronic Disease , Echocardiography , Female , Heart Failure/diagnosis , Humans , Italy , Male , Middle Aged
10.
Ital Heart J ; 2(2): 130-8, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11256541

ABSTRACT

BACKGROUND: Beta-blockers improve survival and ventricular function in patients with heart failure. We evaluated the long-term persistence of metoprolol-induced improvement and its impact on prognosis in idiopathic dilated cardiomyopathy. METHODS: Two hundred and four of 586 patients enrolled in a registry on the natural history of idiopathic dilated cardiomyopathy survived 4 years without transplantation; 98 of them were on standard heart failure treatment, whereas 106 took metoprolol in addition. We analyzed the effects of treatment using beta-blockers in terms of changes in left ventricular ejection fraction (LVEF), NYHA functional class and left ventricular end-diastolic diameter index (LVEDDI) after 1, 2 and 4 follow-up years in order to elaborate an improvement score that was related to the subsequent outcome over 60 months after the 4-year follow-up visit. RESULTS: Greater LVEF increases and NYHA functional class and LVEDDI decreases were observed in patients submitted to metoprolol vs standard treatment at all stages of follow-up. Changes (delta vs baseline) for LVEF (p = 0.02), NYHA functional class (p = 0.0001) and LVEDDI (p = 0.004) were maximal during the first year (10 +/- 11 vs 6 +/- 12 units, -0.72 +/- 0.77 vs -0.23 +/- 0.81, -3.5 +/- 5 vs -1.6 +/- 3.5 mm), persisted at 2 (12 +/- 12 vs 8 +/- 12 units, -0.80 +/- 0.70 vs -0.37 +/- 0.87, -4.2 +/- 5 vs -2.3 +/- 4 mm) but showed a trend to decline at 4 years (11 +/- 12 vs 8 +/- 13 units, -0.54 +/- 0.90 vs -0.24 +/- 0.91, -4.3 +/- 5 vs -2.3 +/- 5 mm) of follow-up. Improvement at 4 years was associated with a better transplant-free survival (81 vs 52%, p = 0.0005, odds ratio 0.36, 95% confidence interval 0.18 to 0.74). CONCLUSIONS: In idiopathic dilated cardiomyopathy, the more significant improvement in symptoms and left ventricular function and size, that is observed following treatment using metoprolol, translates into a better outcome. These benefits peak within the first 2 years of start of treatment but may begin to fade thereafter.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Cardiomyopathy, Dilated/drug therapy , Metoprolol/therapeutic use , Ventricular Function, Left/drug effects , Cardiomyopathy, Dilated/mortality , Cardiomyopathy, Dilated/physiopathology , Female , Humans , Logistic Models , Male , Metoprolol/pharmacology , Prognosis , Survival Analysis , Treatment Outcome
11.
Eur Heart J ; 22(1): 73-81, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11133212

ABSTRACT

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.


Subject(s)
Cardiomyopathy, Dilated/epidemiology , Cardiomyopathy, Dilated/genetics , X Chromosome , Adult , Cardiomyopathy, Dilated/diagnosis , Case-Control Studies , Echocardiography , Electrocardiography/methods , Evidence-Based Medicine , Female , Genes, Dominant , Genetic Linkage , Humans , Male , Pedigree , Prevalence , Prospective Studies
12.
J Am Coll Cardiol ; 37(1): 183-8, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11153735

ABSTRACT

OBJECTIVES: We sought a better understanding of the coupling between right ventricular ejection fraction (RVEF) and pulmonary artery pressure (PAP), as it might improve the accuracy of the prognostic stratification of patients with heart failure. BACKGROUND: Despite the long-standing view that systolic function of the right ventricle (RV) is almost exclusively dependent on the afterload that this cardiac chamber must confront, recent studies claim that RV function is an independent prognostic factor in patients with chronic heart failure. METHODS: Right heart catheterization was performed in 377 consecutive patients with heart failure. RESULTS: During a median follow-up period of 17 +/- 9 months, 105 patients died and 35 underwent urgent heart transplantation. Pulmonary artery pressure and thermodilution-derived RVEF were inversely related (r = 0.66, p < 0.001). However, on Cox multivariate survival analysis, no interaction between such variables was found, and both turned out to be independent prognostic predictors (p < 0.001). It was found that RVEF was preserved in some patients with pulmonary hypertension, and that the prognosis of these patients was similar to that of the patients with normal PAP. In contrast, when PAP was normal, reduced RV function did not carry an additional risk. CONCLUSIONS: These observations emphasize the necessity of combining the right heart hemodynamic variables with a functional evaluation of the RV when trying to define the individual risk of patients with heart failure.


Subject(s)
Heart Failure/diagnosis , Pulmonary Wedge Pressure/physiology , Systole/physiology , Ventricular Function, Right/physiology , Adult , Chronic Disease , Female , Heart Failure/physiopathology , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/physiopathology , Male , Middle Aged , Prognosis , Stroke Volume/physiology
15.
Eur Heart J ; 21(22): 1872-6, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11052860

ABSTRACT

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%.


Subject(s)
Actins/genetics , Actins/metabolism , Cardiomyopathy, Dilated/genetics , Desmin/genetics , Mutation , Myocardium/metabolism , Base Sequence/genetics , Cardiomyopathy, Dilated/metabolism , Europe , Gene Frequency , Genetic Testing , Humans , Polymorphism, Single-Stranded Conformational
16.
Herz ; 25(3): 156-60, 2000 May.
Article in English | MEDLINE | ID: mdl-10904833

ABSTRACT

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.


Subject(s)
Cardiomyopathy, Dilated/genetics , Adult , Cardiomyopathy, Dilated/diagnosis , Child , Female , Genetic Carrier Screening , Genetic Predisposition to Disease/genetics , Genetic Testing , Genotype , Humans , Male
17.
Eur J Heart Fail ; 2(2): 123-32, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10856724

ABSTRACT

BACKGROUND: The EUROHEART programme is a rolling programme of cardiovascular surveys among the member nations of the European Society of Cardiology (ESC). These surveys will provide information on the nature of cardiovascular disease and its management. This manuscript describes a survey into the nature and management of heart failure. AIMS: The EuroHeart Failure survey aims to describe the quality of hospital care, diagnostic and therapeutic, for patients with suspected or confirmed heart failure in ESC member countries. Patients will be interviewed subsequent to hospital discharge to assess their understanding of their condition, side effects from and their compliance with therapy and their satisfaction with the management for heart failure. The quality of management will be judged against the recommendations contained in the ESC guidelines on diagnosis and treatment of heart failure. Outcome will be further assessed by repeat interviews in 6-12 months time. A further survey of heart failure in 2001/2002 is also planned. METHODS: A prospective survey of all deaths and discharges from medical (cardiology, internal medicine and geriatric medicine) and cardiac surgical wards to identify patients with heart failure, suspected or confirmed. Approximately 70 hospital clusters, comprising two to six hospitals in each cluster, in 24 member countries of the ESC are conducting the study. At the time of writing, approximately 30000 deaths and discharges have been screened and approximately 4000 patients have been enrolled. CONCLUSIONS: The EuroHeart Survey will allow actual practice to be compared to ESC guidelines on the diagnosis and treatment of heart failure. The surveys and guidelines should prove mutually informative. The main EuroHeart Failure project will be completed by late 2000. However, new centres volunteering to participate in the study (contact corresponding author) may be accepted providing they have the necessary research personnel and provided funding can be agreed for statistical support and administration.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Health Surveys , Heart Failure/therapy , Quality of Health Care , Europe , Heart Failure/complications , Heart Failure/diagnosis , Humans , Practice Guidelines as Topic , Prospective Studies , Ventricular Dysfunction, Left/complications , Ventricular Dysfunction, Left/drug therapy
18.
J Am Coll Cardiol ; 35(7): 1760-8, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10841222

ABSTRACT

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.


Subject(s)
Cardiomyopathy, Dilated/genetics , Dystrophin/metabolism , Adolescent , Adult , Cardiomyopathy, Dilated/pathology , Genotype , Humans , Male , Middle Aged , Pedigree , Phenotype , Prevalence
19.
Am Heart J ; 139(6): 1088-95, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10827392

ABSTRACT

BACKGROUND: In advanced chronic heart failure (CHF), correlation between heart rate variability (HRV) and parameters of disease severity is still unclear. A reduced HRV has been related to left but not to right ventricular function parameters. Moreover, the prognostic role of spectral measures is not fully defined. We sought to assess HRV by using a short electrocardiographic recording in ambulatory patients with severe CHF to investigate the relation of HRV with clinical neurohormonal and hemodynamic parameters and to determine its predictive prognostic power. METHODS AND RESULTS: HRV was obtained from 5-minute electrocardiographic recordings in 75 ambulatory patients with CHF referred for heart transplantation screening. Standard frequency-domain parameters (total power, low-frequency power, and high-frequency power) were calculated. Prognostic value of these autonomic markers and their correlation with clinical and instrumental parameters were also assessed. A low low-frequency/high-frequency ratio was an independent predictor of cardiac events (P =.015). No correlation was found between New York Heart Association class and HRV, whereas significant correlations were identified between norepinephrine plasma levels, several hemodynamic parameters, and spectral measures (P < or =.03). A reduced HRV, particularly a low-frequency power reduction (P =.000), was highly related to indexes of right ventricular dysfunction. CONCLUSIONS: The current data indicate that spectral analysis of HRV, calculated from short electrocardiographic recordings, may represent a simple but effective means contributing to risk stratification of patients with severe CHF. Autonomic information obtained from this analysis suggests that right ventricular dysfunction may be a critical element determining autonomic imbalance in patients with severe CHF.


Subject(s)
Circadian Rhythm , Electrocardiography, Ambulatory , Heart Failure/physiopathology , Heart Rate/physiology , Ventricular Dysfunction, Right/physiopathology , Biomarkers/blood , Cardiac Catheterization , Echocardiography, Doppler , Female , Heart Failure/mortality , Heart Failure/surgery , Heart Transplantation , Humans , Male , Middle Aged , Norepinephrine/blood , Prognosis , Pulmonary Wedge Pressure , Retrospective Studies , Severity of Illness Index , Survival Rate , Time Factors , Ventricular Dysfunction, Right/blood , Ventricular Dysfunction, Right/diagnostic imaging
20.
Am J Cardiol ; 85(7): 837-42, 2000 Apr 01.
Article in English | MEDLINE | ID: mdl-10758923

ABSTRACT

The prognostic value of ultrasound evaluation of right ventricular (RV) performance in patients with congestive heart failure (CHF) is still a matter of investigation. We studied 140 consecutive patients with chronic CHF and a left ventricular ejection fraction <35%. All patients underwent a complete echocardiographic evaluation that systematically included the measurement of the tricuspid annular plane systolic excursion (TAPSE). During a follow-up period of 24 +/- 14 months, 45 patients died and 7 underwent emergency heart transplantation. At the multivariate survival analysis (Cox regression model) backward stepwise selection identified a prognostic model with 2 parameters: New York Heart Association (NYHA) class III or IV and TAPSE < or =14 mm (p <000). In a subgroup of 97 patients in sinus rhythm in whom mitral inflow Doppler variables could be measured, survival was further analyzed according to a model in which the significant parameters were included in the same order as usually used in routine clinical practice: clinical variables first, left ventricular function data second, mitral Doppler variables third, and indexes of right ventricular (RV) function last. TAPSE < or =14 mm added significant (p <0.03) prognostic information to NYHA class III or IV, left ventricular ejection fraction of <20%, and mitral deceleration time of < 125 ms. In conclusion, in patients with CHF, TAPSE adds significant prognostic information to the NYHA clinical classification, to the echocardiographic evaluation of left ventricular function, and to mitral Doppler variables. Furthermore, the measurement of TAPSE is easy to obtain in all patients, irrespective of heart rate and rhythm.


Subject(s)
Cardiomyopathy, Dilated/complications , Echocardiography, Doppler , Heart Failure/diagnostic imaging , Heart Ventricles/diagnostic imaging , Myocardial Ischemia/complications , Tricuspid Valve/diagnostic imaging , Ventricular Function, Right/physiology , Cardiac Catheterization , Cardiomyopathy, Dilated/diagnostic imaging , Cardiomyopathy, Dilated/physiopathology , Female , Heart Failure/etiology , Heart Failure/mortality , Heart Failure/physiopathology , Heart Ventricles/physiopathology , Humans , Male , Middle Aged , Myocardial Ischemia/diagnostic imaging , Myocardial Ischemia/physiopathology , Prognosis , Reproducibility of Results , Retrospective Studies , Stroke Volume , Survival Rate , Tricuspid Valve/physiopathology
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