Problems of idiopathic congestive cardiomyopathy

It is reported on the course of an idiopathic congestive cardiomyopathy in a younger man which could be observed during three years. After a longer period free of symptoms acutely appeared the signs of a myocardial failure, in which case disturbances of cardiac rhythm at length caused death. In detail the clinical fingings, pathologo-anatomical changes as well as the differential-diagnostic considerations are discussed, which are important for the demarcation of the other forms of the idiopathic and secondary cardiomyopathies.     

Disturbance of peripheral microvascular function in congestive heart failure secondary to idiopathic dilated cardiomyopathy

OBJECTIVES: Previous studies of peripheral microvascular function in human heart failure have concentrated on changes in flow, and there is little information concerning the impact of heart failure on the principal determinants of transcapillary fluid exchange. This study investigated whether alterations in capillary pressure and microvascular fluid permeability can be detected in subjects with idiopathic dilated cardiomyopathy. METHODS: Finger nailfold capillary pressure and calf capillary filtration coefficient (CFC) were measured in parallel studies of two overlapping groups of 12 non-oedematous subjects with idiopathic dilated cardiomyopathy and mild to moderate heart failure and in age- and sex-matched healthy controls. Capillary pressure was measured by direct cannulation using an electronic resistance feedback servonulling technique, and CFC by mercury-in-silastic strain gauge plethysmography using a modification of the technique which avoids assumptions concerning isovolumetric venous pressure. RESULTS: Following correction for differences in skin temperature, capillary pressure was lower in the subjects with heart failure (P = 0.02). Both CFC and isovolumetric venous pressure were greater in the subjects with heart failure than in controls (3.4 +/- 0.9 vs. 2.6 +/- 0.7 ml.min-1.mmHg-1.100 ml-1, P = 0.03; 27.1 +/- 8.4 vs. 17.2 +/- 7.2 mmHg, P = 0.01). CONCLUSIONS: These data suggest that factors other than changes in arterial inflow and venous outflow pressures are likely to play an important role in the disruption of microvascular homeostasis which occurs in heart failure. Changes in capillary hydraulic conductance may contribute to the pathogenesis of oedema.     

Oxygen transport to muscle during exercise in chronic congestive heart failure secondary to idiopathic dilated cardiomyopathy

In chronic heart failure, oxygen delivery during exercise is impaired mainly because of failure of cardiac output to increase normally. Compensatory mechanisms are hemoglobin concentration increase, right-ward shift in the oxyhemoglobin dissociation curve, and blood flow redistribution from the nonexercising organs to the exercising muscles.     

An analytical comparison of cobalt cardiomyopathy and idiopathic dilated cardiomyopathy

Toxic cardiomyopathy (TC) has a rapid clinical course and morphologically resembles idiopathic dilated cardiomyopathy (IDC). To further characterize TC, we used light microscopy to compare lesions caused by cobalt (Co) to those of IDC. Cobalt levels were also measured as a chemical marker to differentiate TC from IDC. We reviewed cases with TC and IDC and excluded all cases with chemotherapy-induced myopathy and catecholamine toxicity as well as cases with possible infectious, ischemic, or hypersensitivity-induced myopathies. We compared the light microscopic findings of 12 TC cases of 12 cases of IDC, and measured trace Co levels on digested heart tissue samples. The TC cases had prominent myofibrillar loss and atrophy; no cases had neutrophil infiltration or frank myocyte necrosis. In contrast, IDC had minimal myofibril loss and atrophy. Cobalt levels in the range of 0.6 to 5.45 micrograms/g of dry tissue were obtained for the TC cases, while IDC demonstrated Co levels of 0.01-0.2 micrograms/g. Distinction between TC and IDC is predominantly a function of myocyte change, with TC showing myofibrillar loss and atrophy in the absence of inflammatory infiltrates and fibrosis; IDC is predominantly associated with myocyte hypertrophy, atrophy, and fibrosis.     

Mitochondrial DNA in idiopathic cardiomyopathy

143 women treated in 28 departments from 1980 to 1995 were retrospectively analysed to study the impact of prognostic factors in primary carcinoma of the fallopian tube. The mean age of the patients was 62.5 years. Sixty (42%) tumours were FIGO stage I, 28 (20%) stage II, 38 (27%) stage III, 17 (12%) stage IV. Complete radical resection was achieved in 102 (71%) patients. In 122 (85%) women, surgery involved removal of the uterus, the adnexa, and/or the omentum or lymph nodes. Postoperative therapy consisted of either irradiation (n = 40; 28%) or chemotherapy (n = 70; 49%); 33 women (23%) did not receive any treatment after surgery. The 5-year survival rate for all cases was 43%. The 5-year survival rate was 59% for stages I and II and 19% for stages III and IV (P < 0.00001). FIGO stage, histological grade and presence of residual tumour had an independent prognostic impact in multivariate analysis. In order to investigate the role of p53 in primary fallopian tube carcinomas, we analysed the immunohistochemical expression of p53 protein regarding survival and FIGO stage in 63 patients (44%). No statistical significance was observed.     

Dystrophin analysis in idiopathic dilated cardiomyopathy

Idiopathic dilated cardiomyopathy (DCM) is characterised by ventricular dilatation and impaired systolic function resulting in congestive heart failure and frequently death. A dilated cardiomyopathy is common in patients with symptomatic Duchenne/Becker muscular dystrophy, a disease caused by dystrophin gene defects. However, cardiomyopathy is rarely the predominant clinical feature of this form of muscular dystrophy. To determine whether dystrophin gene defects might account for a significant number of patients with apparently isolated idiopathic DCM, we performed dystrophin gene analysis in 27 DCM patients, who were ascertained as part of a prospective study on idiopathic DCM. No dystrophin gene defects were found in our patients, whose average age was 50 years. These data suggest that dystrophin defects are not a common cause of idiopathic DCM in this age group in the absence of skeletal muscle cramps or weakness.     

Complex atrial dysrhythmias in a patient with congestive cardiomyopathy

A patient with primary cardiomyopathy and long standing atrial fibrillation presented with atrial tachycardia and AV block. Atrial pacing sequentially converted the atrial tachycardia to atrial flutter (biatrial) and to the dissimilar atrial rhythms of right atrial fibrillation with left atrial flutter, right atrial flutter with left atrial electrical standstill and right atrial fibrillation with left atrial standstill. The clincial milieu and intracardiac recordings are presented.     

Left ventricular diastolic stiffness in dogs with congestive cardiomyopathy and volume overload

Mean functional diastolic stiffness, an estimate of the left ventricular resistance to filling during diastole, was measured in 10 normal dogs, 7 dogs with diseases causing volume overload (patent ductus arteriosus and primary mitral valve insufficiency), and 4 dogs with idiopathic congestive cardiomyopathy. It was measured as the increase in pressure during diastole (deltaP), divided by the corresponding increase in volume (deltaV). The pressure was measured at cardiac catheterization, and the volume was derived by a cineangiocardiographic method. There was no increase in diastolic stiffness of the hearts with volume overload compared with the normal hearts, but those with cardiomyopathy had a large increase, although the end-diastolic volumes in cardiomyopathy were generally less than in volume overload.     

Comparison of clinical and morphologic cardiac findings in patients having cardiac transplantation for ischemic cardiomyopathy, idiopathic dilated cardiomyopathy, and dilated hypertrophic cardiomyopathy

This article compares intergroup and intragroup clinical and morphologic findings in patients with ischemic cardiomyopathy (IC), idiopathic dilated cardiomyopathy (IDC), and dilated hypertrophic cardiomyopathy (HC) undergoing cardiac transplantation (CT). Few previous publications have described findings in native hearts explanted at the time of CT. The explanted heart in 92 patients having CT was examined in uniform manner with particular attention to the sizes of the ventricular cavities and the presence of and extent of ventricular scarring. Of the 92 hearts examined, 47 had IC, 35 had IDC, and 10 had dilated HC. Although considerable degrees of intragroup variation occurred, the mean degree of left ventricular dilatation was similar among the patients with IC, IDC, and dilated HC. All patients with IC had left ventricular free wall scarring more extensive than that involving the ventricular septum, but the intragroup variation in the amounts of scarring was considerable. Nine of the 10 patients with dilated HC also had ventricular wall scarring, but it was more extensive in the ventricular septum than in the left ventricular free wall and involvement of the right ventricular wall also was present. Eight (23%) of the 35 IDC patients also had grossly visible ventricular scars but they were small and only 1 of the 8 had coronary narrowing and that was not in the distribution of the scarring. Narrowing of 1 or more epicardial coronary arteries >75% in cross-sectional area by plaque was present in all 47 IC patients, in 8 of the 35 IDC patients (7 had no ventricular scars), and in none of the 10 dilated HC patients. Coronary angiography was the major clinical tool allowing separation of the IC, IDC, and HC patients. Coronary angiography did not detect narrowing in any of the 8 patients with IDC who were found to have coronary narrowing on anatomic study. Thus, among patients with IC, IDC, and dilated HC having CT, distinctive anatomic features allow separation of patients with IC, IDC, and dilated HC, but within each group considerable variation in left ventricular cavity size and extent of ventricular scarring occurs.     

Metabolic abnormalities following heart transplantation in patients with idiopathic cardiomyopathy

The purpose of this study was to evaluate the risk factors for coronary artery disease associated with initiation of immunosuppressive therapy in patients with a pre-heart transplant diagnosis of idiopathic cardiomyopathy. This study was performed in 15 consecutive patients, mean +/- SEM age of 39 +/- 2 years, with a pre-operative diagnosis of idiopathic cardiomyopathy, who underwent cardiac transplantation at the Tri-Services General Hospital, Taipei, Taiwan, from July 1992 to June 1993. All patients were treated with cyclosporine, azathioprine and prednisolone, and the following measurements were performed prior to hospital discharge (mean +/- SEM) 36 +/- 3 days after successful transplantation: 1) fasting plasma lipid and lipoprotein concentrations; 2) plasma glucose and insulin concentrations in response to a 75 g oral glucose challenge; and 3) steady-state plasma insulin (SSPI) and glucose (SSPG) concentrations in response to a continuous infusion of somatostatin, insulin, and glucose. Since the SSPI concentrations are similar in all individuals, the SSPG concentrations provide an estimate of the ability of insulin to stimulate glucose disposal. Only six of the patients had a normal oral glucose tolerance test and the following diagnoses were found in the remaining nine patients: not diagnised (n = 3), impaired glucose tolerance (n = 4), and non-insulin-dependent diabetes (n = 2). Plasma lipid and lipoprotein concentrations were also frequently abnormal in the heart transplant patients; eight of the 15 patients had a plasma cholesterol > 5 mmol/l, nine had a high density lipoprotein (HDL)-cholesterol concentration < 1 mmol/l, and nine had a ratio of total to HDL-cholesterol > 5.0. Finally, the SSPG concentration was greater than 11.0 mmol/l in eight of the 15 patients, a value rarely exceeded in healthy volunteers. In conclusion, significant metabolic abnormalities were present at discharge in patients who had undergone successful cardiac transplantation for idiopathic cardiomyopathy. These metabolic abnormalities were probably caused by the use of immunosuppressive drugs. Given the magnitude of these changes, it would seem prudent to initiate therapeutic programs in patients with cardiac transplants that are not simply aimed at preventing rejection, but also address the metabolic abnormalities associated with the immunosuppressive agents used to prolong allograft survival.     

Effects of maximally tolerated oral therapy on the six-minute walking test in patients with chronic congestive heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy

In patients with heart failure, therapy with "maximally tolerated" oral doses of diuretics, vasodilators, and digitalis results in a significant increase in the distance walked during the 6-minute walking test, compared with conventional therapy at "standard" doses, indicating an improvement in exercise tolerance. The 6-minute walk test is a simple, inexpensive, and well-tolerated test to measure changes in exercise tolerance induced by pharmacologic interventions, even on a short-term basis.     

Comparison of clinical features and prognosis of cardiac sarcoidosis and idiopathic dilated cardiomyopathy

In the present study, clinical findings of 15 patients with cardiac sarcoidosis presenting as dilated cardiomyopathy were compared with those of 30 consecutive patients with idiopathic dilated cardiomyopathy. The sarcoidosis patients had different clinical features, including female predominance, a high incidence of grave conduction disturbance and abnormal wall thickness, uneven wall motion abnormalities, and perfusion defects preferentially affecting the anteroseptal and apical regions, and poor prognosis compared with those with idiopathic dilated cardiomyopathy.     

Mechanisms underlying spontaneous and induced ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy

BACKGROUND: To define the electrophysiological mechanism(s) of inducible and spontaneously occurring ventricular arrhythmias associated with nonischemic cardiomyopathy, 3-dimensional intraoperative mapping from 156 intramural sites was performed in 6 patients with idiopathic dilated cardiomyopathy undergoing cardiac transplantation. METHODS AND RESULTS: Electrode density was sufficient to determine the mechanism for 52 of 74 beats of nonsustained ventricular tachycardia (VT) induced by programmed stimulation and 9 of 11 beats of spontaneous ventricular arrhythmias. The first, second, and third extrastimuli (S2 through S4) conducted with progressively greater degrees of conduction delay (total activation times [TAs] of 144+/-5, 166+/-5, and 194+/-5 ms, respectively) owing to slow conduction and on occasion intramural block. The first beats of induced VT arose from subendocardial or subepicardial sites distant from areas of marked conduction delay by a focal mechanism on the basis of the absence of intervening electrical activity between the termination of the last extrastimulus and the initiation of VT (123+/-31 ms). Subsequent beats arose by a focal mechanism and conducted with a TA of 127+/-6 ms (P=NS versus initiating beats of VT [118+/-9 ms]). Spontaneous ventricular arrhythmias initiated in the subendocardium by a focal mechanism and conducted with a TA of 138+/-5 ms. Tissue analysis demonstrated a variable degree of interstitial fibrosis at sites of focal activation. Sites of conduction delay or block typically exhibited marked interstitial and/or replacement fibrosis but were spatially distant from sites initiating VT. CONCLUSIONS: Spontaneous and induced ventricular arrhythmias in patients with end-stage idiopathic cardiomyopathy can arise in the subendocardium or subepicardium by a focal mechanism.     

Partial left ventriculectomy for idiopathic dilated cardiomyopathy: early results and six-month follow-up

BACKGROUND: Recent reports show that partial left ventriculectomy improves hemodynamic and functional status in patients with dilated cardiomyopathy. This study sought to determine the effects of partial left ventriculectomy on clinical outcome and left ventricular function during 6-month follow-up. METHODS: Twenty-two patients underwent partial left ventriculectomy. Mitral valve repair was performed whenever possible, otherwise the valve was replaced. Hemodynamic and functional data were obtained at baseline, as well as 2 weeks and 6 months postoperatively. RESULTS: Overall, 7 of 22 patients died; there were three early and four late deaths. One-year survival was 68%+/-10%. Ejection fraction increased from 23.9%+/-6.8% before the operation to 40.7%+/-12.5% at 2 weeks and to 36.8%+/-7.7% at 6 months (p<0.001, for both). The cardiac index before the operation, at 2 weeks, and at 6 months was 2.3+/-0.8, 2.9+/-0.6, and 3.4+/-1.0 L/m2 per minute, respectively (p = 0.035, and p = 0.009, compared with baseline). The increase in ejection fraction 2 weeks postoperatively was less in patients with left circumflex artery dominance (10.9%+/-3.2% compared with 19.9%+/-10.7%, respectively, p = 0.017). At 6-month follow up, all surviving patients except one improved New York Heart Association functional class when compared with preoperative status (from 3.8+/-0.4 to 1.4+/-0.6, p = 0.0002). CONCLUSIONS: Early hemodynamic improvement after partial left ventriculectomy was maintained during midterm follow-up.     

Combined study with FDG PET and Tl SPECT in patients with idiopathic dilated cardiomyopathy

This study aimed to determine whether combined examinations of myocardial 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) and stress-redistribution 201Tl single-photon emission computed tomography (Tl SPECT) were useful in clarifying myocardial ischaemia and evaluating the prognosis in patients with idiopathic dilated cardiomyopathy (IDCM). Twenty-two patients with IDCM underwent echocardiography, cardiac catheterization, FDG PET, and Tl SPECT. In scintigraphic analysis, the total defect score (TDS) was semiquantitatively determined as the sum of scores of the 17 left ventricular (LV) segments with a 5-point scale (0 as normal to 4 as absent). Patients were classified according to the scintigraphic findings as follows: eight patients with small defects on Tl and FDG (TDS < or = 20) (group I), eight patients with small defects on FDG (TDS < or = 20) with FDG uptake increased relative to Tl or 'mismatch' (group II), and six patients with large defects on FDG and Tl (TDS >20) (group III). Eleven patients (50%) showed reversible defects on Tl and all showed preserved FDG uptake. The patients in group III had significantly lower LV ejection fraction (LVEF) (P<0.05, respectively) and a poorer prognosis as shown by the Kaplan-Meier event-free curve compared with those in groups I and II (P<0.01, respectively). Although patients in group II had significantly greater TDS on Tl compared with those in group I (P<0.01), no significant differences in LVEF and prognosis were found between patients in groups I and II. In multivariate analysis, a TDS on FDG revealed an independent predictor of subsequent cardiac events. In conclusion, such mismatched areas can be assumed to consist of impaired but viable myocardium, and may be associated with ischaemia of the microvasculature. Impaired myocardial glucose metabolism is a more powerful predictor of future cardiac events than perfusion abnormality in patients with IDCM.     

Randomised investigation of effects of pentoxifylline on left-ventricular performance in idiopathic dilated cardiomyopathy

BACKGROUND: There is accumulating evidence that inflammatory cytokines have an important role in the pathogenesis of heart failure. Plasma concentrations of tumour necrosis factor alpha (TNF-alpha) are high in heart failure and have been correlated with the severity of symptoms. Pentoxifylline suppresses the production of TNF-alpha. This study aimed to assess the effects of pentoxifylline on left-ventricular function and functional class in patients with idiopathic dilated cardiomyopathy. METHODS: We undertook a single-centre, prospective, double-blind, randomised, placebo-controlled trial, in which 28 patients with idiopathic dilated cardiomyopathy were assigned pentoxifylline 400 mg three times daily or matching placebo. Clinical, echocardiographic, and radionuclide assessments were done at baseline and after 6 months of treatment. Primary endpoints were New York Heart Association (NYHA) functional class and left-ventricular function. FINDINGS: Baseline characteristics were similar in the two groups. Four patients died during the study period, all in the placebo group. After 6 months of treatment, the proportion of patients in NYHA functional class I or II was higher in the pentoxifylline group than in the placebo group (14/14 vs 10/14; p=0.01), and ejection fraction was higher in the pentoxifylline group than in the placebo group (mean 38.7% [SD 15.0] vs 26.8% [11.0], p=0.04). At 6 months, TNF-alpha plasma concentrations were significantly lower in the pentoxifylline-treated group than in the placebo group (2.1 [1.0] vs 6.5 [5.0] pg/mL, p=0.001). INTERPRETATION: Our results suggest that pentoxifylline improves symptoms and left-ventricular systolic function in patients with idiopathic dilated cardiomyopathy. These results must be confirmed in larger-scale trials.     

Effects of isometric handgrip exercise on coronary sinus blood flow in idiopathic cardiomyopathy

Rabbit proximal straight tubules from superficial nephrons were perfused in vitro in order to elucidate the mechanism of fluid and bicarbonate absorption. Both processes were greatly inhibited when sodium was replaced in the perfusate and bath by other cations, when ouabain was added to the bath, or when potassium was removed from the bath. We infer that these experimental manipulations inhibit active sodium tranport, and that active sodium transport is a primary process leading to fluid and bicarbonate absorption. Fluid absorption also decreased (but only by 22 to 36%) when bicarbonate was replaced by chloride in the perfusate and bath or when acetazolamide (10(-3)M) was added, suggesting that fluid and sodium transport depend in part on bicarbonate. We infer that the links between fluid, sodiu, and bicarbonate transport are complex and involve at least two mechanisms: 1) a sodium for hydrogen ion exchange mechanism located in the brush border membrane and 2) the transepithelial concentration difference for bicarbonate, which results from its absorption and which acts as an additional driving force for fluid and sodium absorption. Finally, bicarbonate absorption was unaltered when chloride was replaced by nitrate in the perfusate and bath, suggesting that chloride is not necessary for acidification in this nephron segment.