Cardiomyopathies: diagnosis of types and stages.

Primary cardiomyopathies have as dominant feature the involvement of heart muscle itself. They are not the result of other diseases and should be defined as diseases of heart muscle not consequent to disorders of other parts of the cardiovascular apparatus. Most of them are consequent to genetic defects and can be subdivided into three major groups: isolated, associated with skeletal muscle diseases, associated with neurological disorders. Primary cardiomyopathies show an evolution from mild to more severe stages. Four types of cardiomyopathies are classically described: dilated, hypertrophic, restrictive and arrhythmogenic. However, from a clinical point of view, it is possible to distinguish seven stages: pre-clinical, prevalently arrhythmogenic, prevalently pseudo-hypertrophic, spotty fibrotic, restrictive, dilated and refractory heart failure. In the course of their evolution, cardiomyopathies can shift from a clinical picture to another, consequently requiring frequent examinations of patients in order to adjust their treatment.

ST-segment displacement in Duchenne muscular dystrophy: myocardial necrosis or apoptosis?

An electrocardiographic pattern resembling myocardial infarction is a rare condition in Duchenne muscular dystrophy. We report the case of a Duchenne boy, aged 12 years and 7 month, who, during a programmed examination, showed electrocardiographic signs of ST segment elevation, without symptoms usually accompanying myocardial infarction (chest pain, dyspnoea, sweating). The biological markers of myocardial damage became positive on the 2nd day and recovered on the 5th day. Clinical features of this uncommon pattern are described, with the retrospective evaluation of similar cases from personal records. The differential diagnosis between myocardial necrosis and apoptosis is discussed.

Autonomic nervous system imbalance and left ventricular systolic dysfunction as potential candidates for arrhythmogenesis in Becker muscular dystrophy.

We evaluated the arrhythmic profile in a population of 20 Becker muscular dystrophy (BMD) patients searching for possible correlations between the severity of the arrhythmic events, the cardiac autonomic balance (assessed by heart rate variability analysis in the time domain) and the degree of left ventricular systolic impairment. A population of 14 male healthy individuals served as the control group. BMD subjects exhibited lower values of SDNN (P=0.013), SDANN index (P=0.008) and 24-h mean heart rate (P=0.002). The total number of premature ventricular beats (totPVB) and the number of PVB out of 1000 heartbeats (PVB/1000) appeared also higher in BMD subjects (P=0.05 and P=0.046, respectively). No difference was found in terms of 24-h mean QTc and 24-h longest QT among the two groups. TotPVB and PVB/1000 were inversely related to both the ejection fraction (r= -0.620, P=0.004 and r= -0.517, P=0.019) and to the shortening fraction (r= -0.568, P=0.009 and r= -0.469, P=0.037). Twenty-four-h mean QTc was also inversely related to both the ejection fraction (r= -0.520, P=0.019) and the fractional shortening (r= -0.491, P=0.028). These data suggest that in BMD there is cardiac autonomic imbalance characterized by sympathetic predominance and an increased susceptibility to ventricular arrhythmias, even in the absence of overt cardiomyopathy. Furthermore, the severity of the arrhythmic profile in BMD appears closely related to the degree of left ventricular systolic dysfunction.

Left ventricular function and perfusion in Becker's muscular dystrophy.

UNLABELLED: The aim of this study was to evaluate left ventricular (LV) perfusion and function in patients with Becker muscular dystrophy (BMD). METHODS: Fourteen male patients (age range 14-40 yr) with BMD were evaluated by 201Tl SPECT and radionuclide angiography both at rest and after dipyridamole stress test. RESULTS: All patients showed uptake defect demonstrated by 201Tl SPECT (mean 4.1 +/- 2.2 uptake defect/patient). Significant relationships (p < 0.05) were found between the number of uptake defects and rest LV ejection fraction (LVEF) (r = -0.54); peak filling rate (PFR) (r = -0.57) and dipyridamole LVEF (r = -0.65). Dipyridamole induced reversible uptake defects were found in 7/14 (50%) patients with BMD. The 14 patients were divided into two groups on the basis of the presence (Group A, n = 6) or the absence (Group B, n = 8) of severe irreversible uptake defect (i.e., < 50% 201Tl uptake). Group A showed lower values of PFR and LVEF when compared to patients of Group B. CONCLUSIONS: In patients with BMD there is a relatively high incidence of uptake defects and LV function (both at rest and after dipyridamole) appears to be related to the number of uptake defects. Moreover, the presence of severe irreversible uptake defects identifies a subgroup of patients with BMD characterized by a severely depressed LV function.

Development of cardiomyopathy in female carriers of Duchenne and Becker muscular dystrophies.

OBJECTIVE: To characterize the presence and behavior of the dystrophinopathic myocardial damage in female carriers of a gene defect at the Xp21 locus of the X chromosome that causes Duchenne and Becker muscular dystrophies (DMD and BMD). DESIGN: Cohort study from April 1, 1985, to April 30, 1995, with cardiologic follow-up performed yearly for a minimum of 3 to a maximum of 10 years. SETTING: Counseling center for genetic muscular disorders. PATIENTS: A total of 197 women and girls aged 5 to 60 years ascertained to be carriers of the DMD (n = 152) or BMD (n = 45) gene. MAIN OUTCOME MEASURES: Cardiac status at yearly examinations as determined by 12-lead electrocardiogram (ECG), 24-hour ambulatory ECG, M-mode and 2-dimensional echocardiography, and carotid pulse tracing. Myocardial scintigram was performed on each individual at least twice during the study. Immunohistochemical analysis of dystrophin from myocardium and/or skeletal muscle biopsy was performed in 12 carriers. RESULTS: Preclinical or clinically evident myocardial involvement was found in 166 cases (84.3%), without significant differences in percentage and behavior between DMD and BMD carriers. Its occurrence increased significantly with age, from 54.5% (18 cases) in carriers aged between 5 and 16 years to 90.2% (148 cases) in carriers older than 16 years. Dystrophin anomalies were detected at the membrane level of the myocardial fibers in all endomyocardial biopsy specimens. CONCLUSIONS: Genetic anomalies can be considered the primary cause of myocardial damage in carriers of dystrophinopathic myopathies; myocardial damage shows the same behavior already described in DMD and BMD patients and progresses from preclinical to dilated cardiomyopathy, passing through stages of myocardial hypertrophy or dysrhythmias.

Evaluation of the cardiomyopathy in Becker muscular dystrophy.

To evaluate the features and the course of cardiomyopathy in Becker muscular dystrophy, 68 patients--identified by clinical assessment and by reduced dystrophin labeling and/or DNA analysis--were followed in the years 1976-1993, for periods ranging from 3 to 18 years (mean 8). Patients periodically underwent clinical, electrocardiographic, echocardiographic, nuclear, and radiological assessments. Preclinical cardiac involvement was found in 67.4% of patients under 16 years of age, decreasing to 30% in patients older than 40. Clinically evident cardiomyopathy was found in 15% of patients under 16 years of age, increasing to 73% in patients older than 40. A real, dilated cardiomyopathy is the most frequent type of myocardial involvement after the age of 20. Results show that the severity of cardiac involvement can be unrelated to the severity of skeletal muscle damage and confirm that cardiac dysfunction is a primary feature of Becker muscular dystrophy.

Mutation of dystrophin gene and cardiomyopathy.

The correlations between the type of gene mutation and the cardiac clinical picture were examined in 284 patients with dystrophinopathy (200 Duchenne and 84 Becker). The subjects with normal heart showed deletions including exons 48-49 in 21.4% DMD and in 25% BMD, and other deletions in 35.7% DMD and 25% BMD; vice versa the cases with severe cardiac involvement showed deletions including 48-49 in 38.8% DMD and 37.5% BMD and other deletions in 32.9% DMD and 20% BMD. The age of death was 18 years in DMD patients with deletions including 48-49 whereas the age was about 22 in the cases with other deletions. The differences were statistically significant.

The cardiomyopathy of Duchenne/Becker consultands.

Clinical, electrocardiographic, echocardiographic and other instrumental examinations were performed on 233 persons primarily seeking genetic advice about the Duchenne/Becker gene in order to reveal the incidence of dystrophic cardiomyopathy in a population of females with a close relationship with patients suffering from Duchenne or Becker muscular dystrophy. Among these consultands, 210 were Duchenne and 23 Becker. Eight five (40.4%) Duchenne and 8 (34.8%) Becker consultands showed a normal cardiac status; 35 (16.6%) Duchenne and 6 (26.1%) Becker had clinically evident cardiomyopathy; 90 (43%) Duchenne and 9 (39.1%) Becker showed minor signs of myocardial involvement. The link between myocardial involvement and the Duchenne/Becker carrier condition was demonstrated through the observation that the percentage of cases showing pre-clinical or clinically evident cardiomyopathy was higher in the consultands with pathological values of serum creatine kinase activity (obligatory carriers) and/or an estimated genetic risk higher than 70% than in the consultands showing a normal value of serum creatine kinase activity (less than 80 U/l) and/or a genetic risk lower than 70%.