A long-term follow-up study of acute viral and idiopathic myocarditis

In order to clarify the prognosis of myocarditis and the relationship between myocarditis and idiopathic cardiomyopathy, 20 patients with myocarditis (one with Coxsackie B; one with rubella and 18 with idiopathic myocarditis) were followed up for a long period using echocardiography and Holter electrocardiographic monitoring. The follow-up period was 49.1 +/- 39.3 months (mean +/- SD). Subjects were classified into the following 4 groups according to their prognoses, left ventricular end-diastolic dimensions (LVDd) and the presence of absence of life-threatening ventricular arrhythmias: Group I with a fatal prognosis, Group II with LVDd greater than or equal to 55 mm, Group III with LVDd less than 55 mm but associated with life-threatening ventricular arrhythmias, and Group IV with LVDd less than 55 mm and with no life-threatening ventricular arrhythmias. Patients of Group I (2 cases) had a marked left ventricular dilatation and a poor left ventricular function just before death. Patients of Group II (5 cases) had left ventricular and left atrial dilatation, and 2 of them had serious ventricular arrhythmias. All 3 patients of Group III had ventricular arrhythmia (ventricular tachycardias, coupled premature ventricular contractions and multifocal premature ventricular contractions, respectively), and 2 of them had asymmetric septal hypertrophy. All 10 patients of Group IV had no residual cardiac abnormalities. In conclusion, 50% of 20 myocarditis patients had residual cardiac abnormalities; 6 patients (2 of Group I and 4 of Group II) were complicated by left ventricular dilatation, simulating dilated cardiomyopathy, and 3 (one of Group II and 2 of Group III) showed asymmetric septal hypertrophy, simulating hypertrophic cardiomyopathy.     

Clinical, hemodynamic and morphologic findings in dilated cardiomyopathy

45 patients (39 men, six women), mean 41 (19-63) years of age with clinical, angiographic and morphologic diagnosis of dilated cardiomyopathy were evaluated in respect of three morphologic classes. Two groups of patients without signs of previous myocarditis were formed, with one-to-two mitochondria per two sarcomeres (group Ia, n = 19), or with more than two mitochondria per two sarcomeres, respectively (group Ib, n = 14); and one group with signs of previous myocarditis (group II, n = 12). The mean relative mitochondrial volume fraction in relation to myofibril volume fraction was significantly lower in group Ia (33 +/- 4/67 +/- 4%) compared to group Ib (39 +/- 5/61 +/- 5%) (p less than 0.01). Mean values of group II (36 +/- 6/64 +/- 6%) were in between the two other groups. Left ventricular enddiastolic pressure (18 +/- 11, 18 +/- 8, 16 +/- 10 mm Hg), pulmonary vascular resistance (473 +/- 414, 406 +/- 205, 458 +/- 495 dyn x s x cm-5), ejection fraction (36 +/- 21, 32 +/- 16, 28 +/- 16%), endsystolic volume index (131 +/- 82, 127 +/- 66, 132 +/- 60 ml/m2), enddiastolic volume index (187 +/- 81, 176 +/- 62, 181 +/- 63 ml/m2), dp/dt max (1951 +/- 875, 1737 +/- 575, 1741 +/- 478 mmHg x s-1) and mean VCF (0.76 +/- 0.58, 0.44 +/- 0.32, 0.54 +/- 0.39 s-1) showed no significant differences between the three groups. Follow-up of the patients in the three groups to median 19, 22, 24 months, respectively, after biopsy, showed an improvement of the clinical findings, especially concerning the groups with one-to-two mitochondria only and with signs of previous myocarditis, but no difference in survival within the three groups. For the individual case our morphologic parameters seem to be without predictive value.     

Cardiac catheterization and long-term chromosomal damage in children with congenital heart disease.

AIMS: Medical radiological exposure is associated with an additional risk of cancer. Children with repaired congenital heart disease (CHD) are theoretically at a relatively greater cancer risk as the radiological exposure can be intensive in these patients. Chromosomal aberrations test (CA) and micronucleus assay (MN) in peripheral blood lymphocytes are biomarkers of chromosomal damage and intermediate endpoints in carcinogenesis. METHODS AND RESULTS: The frequency of CA and MN was assessed in three groups of patients: Group I, 32 exposed patients (17 males, age=15.5+/-8.3 years) who underwent cardiac procedures employing ionizing radiation (mostly cardiac catheterization) for CHD between 1965 and 2000; Group II, 32 healthy age- and sex-matched subjects (17 males, age=14.1+/-12.3 years), and Group III, 10 newborn non-exposed patients (7 males) with CHD. Exposed patients of Group I had a mean value of 2.9+/-1.4 cardiac catheterization (range 1-5) procedures per person. The mean frequency of CA was higher in the exposed patients (Group I=2.8+/-1.9% vs. Group II=0.7+/-0.7%; vs. Group III=0.8+/-0.8%; P<0.0001). Similarly, the mean values of MN were higher in the exposed patients (Group I =12.3+/-5.1 per thousand vs. Group II=6.0+/-3.8 per thousand; vs. Group III=4.4+/-1.4 per thousand; P<0.0001). CONCLUSION: Cardiac ionizing procedures are associated with a long-lasting mark in the chromosomal damage of exposed children with CHD.     

Heart mitochondrial respiratory chain complexes are functionally unaffected in heavy ethanol drinkers without cardiomyopathy

BACKGROUND: Harmful effects of chronic ethanol intake on liver mitochondria have been clearly demonstrated; however, mitochondria from skeletal muscle are preserved, and the effect of ethanol on heart mitochondria remains controversial. We assessed individual enzyme activity of mitochondrial respiratory chain (MRC) complexes and membrane oxidative damage of heart mitochondria in active ethanol drinkers before the development of dilated cardiomyopathy. PATIENTS AND METHODS: Heart samples were obtained from otherwise healthy organ donor individuals with a sudden death of traumatic or neurological cause in whom hearts could not be used because of absence of matched receptors or size inadequacy. Detailed history of alcohol intake was achieved from the relatives. Citrate synthase activity was spectrophotometrically assayed, as well as absolute (nmol x min(-1) x mg protein(-1)) and relative (corrected by citrate synthase) activities of complex I, II, III, and IV of the MRC. Oxidative damage of myocardium membranes was assessed measuring the degree of lipid peroxidation by fluorescence using cis-parinaric acid as probe. RESULTS: We included 10 ethanol drinkers (age 53 +/- 13 years, 100% males, mean lifetime intake of 15.6 +/- 7.9 kg ethanol kg body weight(-1)) and 12 controls (age 60 +/- 10 years, 75% males). Mitochondrial content did not differ between the two groups. Absolute enzyme activities for ethanol drinkers and controls were, respectively, 145 +/- 75 and 130 +/- 50 for complex I (p = NS); 399 +/- 193 and 376 +/- 100 for complex II (p = NS); 719 +/- 288 and 714 +/- 308 for complex III (p = NS); and 475 +/- 139 and 570 +/- 160 for complex IV (p = NS). After correcting such activities by citrate synthase activity, we failed again to demonstrate differences between ethanol drinkers and controls. Lipid peroxidation of myocardium membranes was similar in both groups. CONCLUSIONS: Chronic ethanol drinkers without cardiomyopathy exhibit normal MRC activity in the heart and do not show increased oxidative damage in myocardial membranes.     

Studies on cytosol thyroid hormone binding proteins in the rat liver: Part II. Alterations of thyroid hormone binding proteins in various thyroid function states

Alterations of binding characteristics of cytosolic thyroid hormone binding proteins (CTHBPs) were examined in livers of rats with different thyroid function. Seven days after thyroidectomy, rats were divided into three groups. Group I received no treatment. Group II was treated with 230 ng triiodothyronine (T3)/100 g body weight per day for three days, and Group III with 40 micrograms T3/100 g body weight per day for three days. On the fourth day, each rat was given 0.7 microCi of 125I-T3/100 g body weight intraperitoneally and exsanguinated two hours later. During three days' treatment, body weight in Group II increased significantly compared with that in Group I (P less than 0.05), and body weight in Group III actually decreased. The ratio of liver weight to body weight in Group II was significantly higher than that in Group I or Group III (P less than 0.01). Percent distributions of 125I-T3 in cytosol fraction per liver or concentrations of cytosolic protein did not differ significantly among these three groups. Serum T3 concentrations (mean +/- SD ng/ml: Group I; not detectable, Group II; 0.50 +/- 0.27, Group III; 7.10 +/- 2.31), cytosolic T3 concentrations (mean +/- SD ng/ml: Group I; not detectable, Group II; 0.59 +/- 0.26, Group III; 10.38 +/- 3.08) and mitochondrial alpha-glycerophosphate dehydrogenase activities (mean +/- SD delta OD500 millimicrons/min/mg: Group I; 28.0 +/- 1.5, Group II; 46.7 +/- 7.3, Group III; 267.7 +/- 9.1) suggested that Group I was in hypothyroid state, Group II in euthyroid state and Group III in thyrotoxic state. Binding characteristics of cytosolic T3 binding protein (CT3BP) were different among the three groups.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prognostic implications of tissue Doppler in patients with dilated cardiomyopathy.

Previous studies have shown that a ratio of early transmitral flow velocity to early diastolic velocity of the mitral annulus (E/E') of > 15, obtained by tissue Doppler imaging (TDI), correlates with left ventricular filling pressure. OBJECTIVE: The aim of our study was to assess whether E/E' provides prognostic information in patients with dilated cardiomyopathy. METHODS: We studied 33 patients with dilated cardiomyopathy and mean ejection fraction of 31%. All the patients underwent routine two-dimensional and Doppler echocardiographic examination and TDI to determine early peak velocity of the mitral annulus. Pro-B-type natriuretic peptide (pro-BNP) and peak oxygen consumption (VO2max) were also measured. Patients were divided into two groups according to the value of E/E': Group I (n = 15 patients) with E/E' > or = 15 and Group II (n = 18 patients) with E/E' < 15. Patients were followed for 12+/-4 months; new hospital admission due to heart failure, heart transplantation and death were considered as cardiac events. RESULTS: There were significant differences between the two groups in conventional two-dimensional echocardiographic measurements (dimensions and ejection fraction) and Doppler parameters (mitral inflow). With regard to mitral annular velocities obtained by TDI at two different points (septum and lateral wall), the E', A' and S' velocities differed significantly between the two groups, with lower velocities in Group I. Systolic velocity measured in the lateral portion of the mitral annulus showed the most significant difference: Group I - 4.46 cm/sec versus Group II - 7.19 cm/sec, p < 0.00001. Pro-BNP was 5622 pg/ml in Group I, and 1254 pg/ml in Group II, p = 0.004. VO2 max was significantly different between the two groups: Group I - 17.6 ml/kg/min versus Group II - 22.8 ml/kg/min, p = 0.004. During follow-up, events were more common in Group I, with 9 patients (60%) having events, while in Group II, the event rate was 11.1% (2 patients), p = 0.004. CONCLUSION: The ratio of early transmitral flow velocity to early diastolic velocity of the mitral annulus is a powerful predictor of clinical outcome. Lower velocities of mitral annulus on TDI are expected in patients with E/E' > or = 15. Systolic velocities of under 5 cm/sec measured in the lateral portion of the mitral annulus appeared to be strongly related to prognosis.     

Left ventricular filling in dilated cardiomyopathy: relation to functional class and hemodynamics

Left ventricular systolic function does not correlate well with functional class in patients with dilated cardiomyopathy. To determine whether the correlation is better with Doppler indexes of left ventricular diastolic function, 34 patients with dilated cardiomyopathy (M-mode echocardiographic end-diastolic dimension greater than 60 mm, fractional shortening less than 25%, increased E point-septal separation) were studied. Patients were classified into two groups according to functional class. Group 1 consisted of 16 patients in New York Heart Association functional class I or II; group 2 included 18 patients in functional class III or IV. Left ventricular dimensions, fractional shortening, left ventricular mass, meridional end-systolic wall stress, peak early and late transmitral filling velocities and their ratio, isovolumetric relaxation period and time to peak filling rate were computed from pulsed wave Doppler and M-mode echocardiograms and calibrated carotid pulse tracings. Right heart catheterization was performed in 20 of 34 patients. No differences were observed between groups with regard to age, gender distribution, heart rate, blood pressure and M-mode echocardiographic-derived indexes of systolic function. Peak early filling velocity (72 +/- 13 versus 40 +/- 10 cm/s, p less than 0.001) was higher and atrial filling fraction (27 +/- 4% versus 46 +/- 8%, p less than 0.001) was lower in group 2 than in group 1. The ratio of early to late transmitral filling velocities was higher in group 2 patients (2.3 +/- 0.5 versus 0.7 +/- 0.2, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiac asystole: a manifestation of neurally mediated hypotension-bradycardia

It has been proposed that prolonged cardiac asystole mimicking an episode of sudden cardiac death may occur as a manifestation of neurally mediated hypotension-bradycardia syndrome. To assess this possibility, electrocardiographic and hemodynamic findings during upright tilt testing were evaluated in six survivors of suspected asystolic sudden cardiac arrest with normal conventional electrophysiologic evaluation (Group I). These observations were compared with findings in two control groups: six patients with syncope but without evident asystole and with normal conventional electrophysiologic evaluation but demonstrable neurally mediated hypotension-bradycardia (Group II), and six patients with syncope in whom conventional electrophysiologic evaluation provided a presumptive diagnosis (Group III). Patients in all three groups ranged in age from 16 to 59 years. During head-up tilt testing (either alone or with isoproterenol infusion), patients in both Groups I and II developed syncope in less than or equal to 5 min, whereas patients in Group III remained asymptomatic. Patients in Groups I and II exhibited a similar tilt-induced decrease in mean arterial pressure (-46 +/- 9 and -40 +/- 9 mm Hg, respectively, p = NS) and heart rate (-44 +/- 28 and -49 +/- 12 beats/min, respectively, p = NS). In contrast, patients in Group III manifested only a moderate decrease in mean arterial pressure (-14 +/- 5 mm Hg) and had an increase in heart rate (+14 +/- 8 beats/min). Both mean arterial pressure and heart rate changes in Group I and Group II patients differed significantly (p less than 0.001) from values in Group III patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of beta-blocker on metabolism and contraction of doxorubicin-induced cardiotoxicity in the isolated perfused rabbit heart

The effect of beta-blocker (propranolol) on the metabolism and contraction of doxorubicin-induced cardiomyopathy during pacing or ischemia was examined by the phosphorus 31-nuclear magnetic resonance (31 P-NMR) in Langendorff hearts of chronically treated rabbits after cumulative doses of 16 mg doxorubicin/kg. After 8 weeks of doxorubicin treatment, beta-blocker (propranolol) was given orally over a period of 2 weeks for a cumulative dose of 1.4 mg/kg. Isolated hearts were paced at higher heart rates, or hearts were perfused on low flow. Adenosine triphosphate (ATP), creatine phosphate (PCr), inorganic phosphate (Pi), pH, left ventricular systolic developed pressure (LVDev P), and coronary flow were measured. The hearts were divided into three experimental groups: Group I consisted of controls, Group II consisted of doxorubicin treatment, and Group III consisted of doxorubicin treatment with propranolol. Group II showed a significant decrease of ATP during pacing (48 +/- 2%) and during low flow (61 +/- 6%) compared with Group I (86 +/- 9% at pacing, 94 +/- 6% on low flow). But Group III showed a significantly marked improvement of ATP during pacing (95 +/- 10%) and during low flow (83 +/- 3%) compared with Group II. Furthermore, Group II showed a significant decrease of LVDev P during pacing (69 +/- 6 mm Hg) and during low flow (63 +/- 3 mm Hg) compared with Group I (101 +/- 5 mm Hg at pacing, 95 +/- 9 mm Hg on low flow). But Group III showed a significantly marked improvement of LVDev P during pacing (93 +/- 5 mm Hg) and during low flow (83 +/- 14 mm Hg) compared with Group II. In conclusion, propranolol had a significant beneficial effect on metabolism and contraction during high-energy demand and during low oxygen supply of doxorubicin cardiomyopathy.     

The septal arteries in the differential diagnosis of constrictive pericarditis

Angiographic study of the motion of the septal and left marginal arteries was performed in patients with restriction in ventricular diastolic filling in order to separate patients with constrictive pericarditis from those with restrictive cardiomyopathy. Twelve patients with constrictive pericarditis (group I) and 10 patients with restrictive cardiomyopathy (group II) were evaluated and compared with 21 patients with normal coronary angiograms (group III). The displacement of the septal arteries (23 +/- 2.04 mm) was abnormally exaggerated in group I and normal (9 +/- 0.81 mm) in groups II and III. The displacement of the left marginal arteries as seen by the "corrugating index" was similar in all groups. We conclude that study of the displacement of the septal arteries is a useful angiographic sign that helps to separate constrictive pericarditis from restrictive cardiomyopathy and normals.     

Alterations of the mitochondrial respiratory chain in human dilated cardiomyopathy

The defects underlying the impairment of systolic pump function in human dilated cardiomyopathy (DCM) are not known. We isolated mitochondrial particles from 10 hearts of transplant recipients with DCM and from nine normal hearts not used for transplantation. Yield was similar in both groups (2.77 vs 2.81 mg mitochondrial protein per gram heart). Cytochrome content (difference spectrophotometry) was found reduced in DCM mitochondria, e.g. cytochrome c was 0.295 +/- 0.06 in the DCM group and 0.371 +/- 0.04 mumol g-1 in the control group (P less than 0.05). Enzymatic activity of the cytochrome-containing complexes III (3.77 +/- 0.82 vs 4.95 +/- 1.15 mumol min-1.mg-1) and IV (2.63 +/- 0.96 vs 3.65 +/- 0.6 mumol min-1.mg-1) of the respiratory chain was reduced in the DCM group (P less than 0.05). Complex IV, the cytochrome c oxidase, in the DCM group showed impaired activity also in whole heart homogenates (0.173 +/- 0.04 vs 0.258 +/- 0.8 mumol min-1.mg-1). Subunit composition of the cytochrome c oxidase on sodium dodecyl sulphate-gel electrophoresis did not differ between DCM and normal hearts. Activity of complexes II and V of the respiratory chain, not containing cytochromes, was unchanged in DCM mitochondria compared with the control group. The present data show a decrease in cytochrome content and in cytochrome-dependent enzyme activity in human dilated cardiomyopathy. Further studies are necessary to clarify whether these findings are specific for dilated cardiomyopathy or whether they are epiphenomena of failing hearts.     

Extracellular matrix structure after heart transplantation

Following heart transplantation remodeling of the donor heart causes changes in the extracellular myocardial matrix. We investigated 20 right ventricular endomyocardial biopsies taken 17+/-4 days (group I, n=9) and 63+/-13 days (group II, n=11) after heart transplantation from 16 patients transplanted for end-stage cardiomyopathy (15 dilated/1 ischemic). Immunohistochemical staining for collagen I, collagen III, collagen IV, and fibronectin was used. Evaluation was performed at a magnification of 400x using a computer-assisted image analyzing system measuring the relative area stained by the immunoperoxidase method, the number of cells in the given area, and the total area. Collagen I per cell was 13.9+/-5.9 microm2 in group I and increased significantly 66+/-13 days after heart transplantation in the perimysium around the myocardial cells as well as in the endocardium to 49.9+/-15.1 microm2 (P<0.05). No quantitative change in collagen III was noted (75.7+/-12.4 versus 75.5+/-16.0 microm2 n.s.). Collagen IV was found in the perimysial, in the capillary bed and in the vascular network. Significant quantitative change in the amount of collagen IV was not found (64.1+/-12.6 versus 61.0+/-8.9 microm2). Fibronectin was found in the entire perimysial extracellular matrix and in the endocardium in relationship with collagen I and III. An increased amount of fibronectin from 87.09+/-9.9 microm2 (group I) to 140.8+/-17.9 microm2 (group II, P<0.05) was found. The cell area and cell diameters were not significantly different (group I; cell area 772+/-227 microm2, diameter 31.3 microm; group II; cell area 776+/-224 microm2, diameter 31.4 microm). It is concluded that remodeling of the donor heart after transplantation is characterized by a specific increase in collagen I and fibronectin, whereas a change in other collagen subtypes was not observed.     

Prolonged and fractionated right atrial electrograms during sinus rhythm in patients with paroxysmal atrial fibrillation and sick sinus node syndrome

Intraatrial catheter mapping of the right atrium was performed during sinus rhythm in 92 patients: Group I = 43 control patients without paroxysmal atrial fibrillation or sick sinus node syndrome; Group II = 31 patients with paroxysmal atrial fibrillation but without sick sinus node syndrome; and Group III = 18 patients with both paroxysmal atrial fibrillation and sick sinus node syndrome. Atrial electrograms were recorded at 12 sites in the right atrium. The duration and number of fragmented deflections of the atrial electrograms were quantitatively measured. The mean duration and number of fragmented deflections of the 516 atrial electrograms in Group I were 74 +/- 11 ms and 3.9 +/- 1.3, respectively. The criteria for an abnormal atrial electrogram were defined as a duration of greater than or equal to 100 ms or eight or more fragmented deflections, or both. Abnormal atrial electrograms were observed in 10 patients (23.3%) in Group I, 21 patients (67.7%) in Group II and 15 patients (83.3%) in Group III (Group II versus Group I, p less than 0.001; Group III versus Group I, p less than 0.001). The mean number of abnormal electrograms per patient with an abnormal electrogram was 1.3 +/- 0.7 in Group I, 2.5 +/- 1.9 in Group II and 3.5 +/- 2.5 in Group III (Group I versus Group II, p less than 0.01; Group II versus Group III, p less than 0.05). A prolonged and fractionated atrial electrogram characteristic of paroxysmal atrial fibrillation can be closely related to the vulnerability of the atrial muscle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy—echocardiographical follow-up

To evaluate the effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy (DCM), two groups (Group I: 18 patients, Group II: 17 patients) with DCM divided by the order at the entry were followed echocardiographically for 16.9 +/- 3.0 months in Group I and 21.4 +/- 3.9 months in Group II. Metoprolol (final dose: 60 mg/day) was administered in Group I, but not in Group II (the control), although the conventional treatment for heart failure was continued. The left ventricular end-systolic dimension and ejection fraction assessed by echocardiography improved significantly after 6 months in Group I, but not in Group II, even after 48 months, although there were no significant differences in baseline data between the two groups. The end-diastolic dimension decreased significantly after 12 months in Group I only. It was estimated, using the point count method on a left ventricular endomyocardial biopsy specimen taken at entry, that the improvement (delta EF) of the ejection fraction 12 months after metoprolol administration inversely correlated (r = -0.677, p less than 0.01) with percent fibrosis, indicating that the more myocardium remains, the more improvement is expected. These findings suggested a favorable effect of beta blockade in DCM, especially in cases with less fibrosis, showing that the endomyocardial biopsy could be of clinical use in selecting candidates for chronic beta-blocker therapy in DCM.     

Long-term (2 year) beneficial effects of beta-adrenergic blockade with bucindolol in patients with idiopathic dilated cardiomyopathy.

Beta-adrenergic blockade represents a promising therapeutic approach to idiopathic dilated cardiomyopathy. Bucindolol, a new beta-blocker, showed favorable effects in a short-term (3 month) trial in idiopathic dilated cardiomyopathy. To assess long-term response, 20 study patients (7 of 9 patients previously assigned to the placebo group and 13 of 14 patients previously assigned to bucindolol therapy) received long-term bucindolol therapy and were followed up for a mean of 23 +/- 4 months (range 17 to 30). The mean patient age was 49 years (range 29 to 66) and the median duration of disease was 11 months (range 1 to 190). Ten patients were in functional class II and 10 were in class III; 15 patients were men. At the end of the common follow-up time, all 20 patients were alive, 17 continued to receive bucindolol (mean dose 176 mg/day, range 25 to 200), and 2 underwent cardiac transplantation. Left ventricular ejection fraction increased from a baseline value of 25 +/- 8% to 35 +/- 13% (n = 19 pairs, p less than 0.001). Functional class improved in 12, was unchanged in 5 and deteriorated in 3 (p = 0.056). Exercise time was maintained (9.4 +/- 3.1 versus 9.1 +/- 3.5 min, n = 19, p = NS), as was maximal oxygen uptake (19.2 +/- 4.9 versus 18.8 +/- 5.7 ml/kg per min, n = 19, p = NS). Thus, long-term bucindolol therapy leads to substantial increases in ejection fraction and to improved functional class while stable exercise performance is maintained.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial fibrillation in mitral stenosis: histologic, hemodynamic and metabolic factors

We examined the histologic, hemodynamic and metabolic factors associated with rheumatic mitral stenosis. Eighteen patients comprised three groups: Group I - 7 patients in sinus rhythm; Group II - 5 patients in intermittent atrial fibrillation; Group III - 6 patients in chronic atrial fibrillation. The left atrial dimension was determined by echocardiography. Left atrial pressure, mitral valve gradient, mitral valve area and the presence or absence of calcium in the mitral valve were determined at catheterization. The left atrial appendage was removed during open heart surgery and the tissue was analyzed for cell size, percent fibrosis and content of cyclic AMP and GMP. There was no difference between the groups in pulmonary capillary wedge pressure, mitral valve gradient, mitral valve area or the presence of calcium. The Group I left atrial dimension (51 +/- 2 mm, means +/- SE) was significantly smaller than that of Group III (56 +/- 2 mm, P less than 0.05). Group II was not different from Groups I or III. Although the concentration of cyclic AMP did not differ among the groups, the cyclic GMP was significantly depressed in Group III (0.15 +/- 0.02 fmol/microgram protein) when compared to Group I (0.24 +/- 0.05 fmol/microgram protein, P less than 0.01). Group II had intermediate values which did not differ from Groups I or III. The percent fibrosis was greatest in Group III (34.8 +/- 1.8%) and least in Group I (27.2 +/- 2.8%, P less than 0.05). There was no difference in cell size among the groups. Although atrial fibrillation may lead to some of these irregularities, a depressed cyclic GMP, increased fibrosis and increased left atrial dimension may play a role in the pathogenesis of irreversible atrial fibrillation.     

Beta blocking agents in the treatment of dilated cardiomyopathy: review of the literature and clinical experience with 67 patients]

BACKGROUND. Several reports suggest that chronic beta blockade, most often with the beta 1 selective agent metoprolol, may improve hemodynamic and clinical function in patients with idiopathic dilated cardiomyopathy. However, controlled trials are limited and some studies have not shown beneficial effects in short term trials. Mechanisms of effectiveness are still debated and probably concern the capacity to avoid toxic myocardial damage by catecholamines, to induce receptor up-regulation, to contribute to the control of arrhythmias, to improve diastolic relaxation and other mechanisms. METHODS. After a revision of the literature, a preliminary clinical experience with metoprolol in dilated cardiomyopathy diagnosed according to the WHO definition is reported. Sixty-seven patients symptomatic for congestive heart failure or with complex ventricular arrhythmias associated with severe left ventricular dysfunction were submitted to test dose with metoprolol 5 mg bid for 2-7 days. All patients were completely studied, including coronary angiography and endomyocardial biopsy to exclude ischemic heart disease and active myocarditis. Four pts (6%) did not tolerate the first test dosage of metoprolol and twenty-two patients were excluded from analysis because of inadequate follow-up or because they were enrolled in an international trial. Forty-one patients underwent long-term treatment with metoprolol at a final mean dosage of 150 mg a day (range 50-200 mg) and are presently analyzed. The dosage was gradually increased during the first seven weeks. RESULTS. After 6 +/- 2 months and 12 +/- 2 months, 34 patients were stable or ameliorated (Group 1) and experienced an overall significant improvement of functional class (all pts in class I-II NYHA), of left and right ventricular ejection fraction (from 28 +/- 8.8% to 35.8 +/- 13.7% to 33.2 +/- 12.3% and from 38.6 +/- 11.8% to 42.4 +/- 5.8% to 45.2 +/- 12.2% respectively), of clinical signs of congestive heart failure, of cardiothoracic index, of left ventricular diameters and of arrhythmic pattern. Furthermore, the rate of ventricular couplets > 20/24h and of non-sustained ventricular tachycardia changed respectively from 46% and 54% to 4% and 21% at 12 +/- 2 months. None in Group 1 died nor is any waiting for heart transplantation. Eleven patients (Group 2) did not tolerate the drug acutely (4 pts) or deteriorated during the first 6 +/- 2 months (7 pts) of the treatment. In this group a worsening or an insignificant variation of all clinical and instrumental parameters was observed. During follow-up four patients of this group underwent heart transplantation (one died shortly after the operation because of infective complications), one died while waiting, two are currently waiting for heart transplantation, and three are still in heart failure (class III NYHA). No cases of sudden death occurred in any group of patients (15 pts with follow-up > 12 mo). CONCLUSIONS. Our uncontrolled study seems to confirm the beneficial effect of betablockers in a subgroup of patients with idiopathic dilated cardiomyopathy. The characterization of responders to this therapy is still undefined and will constitute the aim of future analyses.     

Electrocardiographic and electrophysiologic studies in patients with torsades de pointe--role of monophasic action potentials

The study group consisted of 26 patients with a history of documented Torsade de Pointes (TdP) who were divides into 3 groups according to the causes of TdP. Group I consisted of 5 patients with congenital long QT syndrome. Group II consisted of 15 patients with TdP caused by antiarrhythmic drugs. Group III consisted of 6 patients with TdP caused by bradycardia resulting from third degree atrioventricular block. The QT interval was determined from a 12-lead electrocardiogram. Monophasic Action Potential (MAP) was recorded by a 6 F USCI electrode catheter. Isoproterenol infusion resulted in TU abnormality in all patients in Group I and induced a hump at phase 3 slope of MAP in all 3 patients tested. The QT interval change before and after IA administration was significantly larger in Group II patients compared to those without TdP (0.132 +/- 0.062 vs 0.029 +/- 0.31 sec, less than 0.005). Injection of 100 mg. of disopyramide in 2 patients in Group II resulted a hump at phase 3 slope of the MAP in both of them. The QT prolongation associated with decreasing the pacing rate from 70 to 50/min was significantly larger in patients with Group III compared to patients with bradycardia but without TdP (0.02 +/- 0.04 vs 0.07 +/- 0.05 sec, p less than 0.005). The results suggests: 1) different approaches are necessary for evaluation of TU abnormalities in patients with TdP according to the causes of TdP, 2) MAP might be a useful method for evaluating TU abnormality in patients with TdP.     

Uses and limitations of exercise Doppler echocardiography in the diagnosis of ischemic heart disease

This study tested the hypothesis that coronary artery disease might be identified by a decrease in Doppler measurements of flow velocity and acceleration. The response of aortic blood flow velocity and acceleration to exercise was determined in 102 subjects (28 young control subjects and 74 older patients) who underwent continuous wave Doppler echocardiographic examination before, during and immediately after near maximal treadmill exercise. Patients were grouped according to the results of thallium perfusion imaging: Group I = normal, Group II = ischemia with or without prior infarction and Group III = prior infarction only. A significant decrease in the level of velocity and acceleration achieved with exercise was observed both in patients in Group I (normal thallium study) (1.2 +/- 0.3 m/s and 36.8 +/- 14 m/s per s, p less than or equal to 0.005) and in patients in Group II (ischemia) (1.1 +/- 0.3 m/s and 27.7 +/- 11 m/s per s, p less than or equal to 0.0005) compared with values in young control subjects (1.4 +/- 0.2 m/s and 52.7 +/- 16 m/s per s). When groups of patients of similar age who differed in the presence (Group II) or absence (Group I) of ischemia on thallium scintigraphy were compared, no difference was found for maximal velocity (1.1 +/- 0.3 versus 1.2 +/- 0.3 m/s, p = NS), but acceleration was significantly lower in Group II (27.7 +/- 11 versus 36.8 +/- 14 m/s per s, p less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise capacity correlating to exercise hemodynamics in coronary artery disease

Forty-seven patients with coronary artery disease characterized by angina pectoris and/or old myocardial infarction underwent two maximal exercise tests, the supine ergometer test and the upright treadmill test, to study the relationship between exercise capacity and exercise hemodynamics. Subjects were divided into 3 groups: Group I (n = 19) achieved 25 or 50 watts, Group II (n = 15) achieved 75 watts and Group III (n = 13) achieved 100 or 125 watts. During ergometer exercise, the mean pulmonary capillary pressure elevated by 25.3 +/- 8.3 mmHg in Group I, 20.8 +/- 8.8 mmHg in Group II and 12.0 +/- 8.4 mmHg in Group III; the Group III value was significantly smaller than the other groups. The stroke volume index decreased by 3.6 +/- 8.8 ml/m2 in Group I, and increased by 10.9 +/- 8.7 ml/m2 in Group II and 10.7 +/- 14.7 ml/m2 in Group III. Thus, the impaired exercise capacity correlated with the abnormal exercise hemodynamics and its severity. In addition, the exercise capacity in the treadmill test was comparable to that in the ergometer test. It was concluded that the impaired exercise capacity in the both supine and upright exercise tests was well related to the development of abnormal exercise hemodynamics in patients with coronary artery disease.