No abstract

Transplant-free survival is better for patients with CS than for IGCM diagnosed by EMB. Presentation with heart failure predicted IGCM, and presentation with heart block or more than nine weeks of symptoms predicted CS.

The peroxisome proliferator-activated receptor ␣ (PPAR␣) is a member of the nuclear receptor superfamily and mediates the biological effects of peroxisome proliferators. To determine the physiological role of PPAR␣ in cardiac fatty acid metabolism, we examined the regulation of expression of cardiac fatty acid-metabolizing proteins using PPAR␣-null mice. The capacity for constitutive myocardial ␤-oxidation of the medium and long chain fatty acids, octanoic acid and palmitic acid, was markedly reduced in the PPAR␣-null mice as compared with the wild-type mice, indicating that mitochondrial fatty acid catabolism is impaired in the absence of PPAR␣. In contrast, constitutive ␤-oxidation of the very long chain fatty acid, lignoceric acid, did not differ between the mice, suggesting that the constitutive expression of enzymes involved in peroxisomal ␤-oxidation is independent of PPAR␣ . Indeed, PPAR␣-null mice had normal levels of the peroxisomal ␤-oxidation enzymes except the D-type bifunctional protein. At least seven mitochondrial fatty acid-metabolizing enzymes were expressed at much lower levels in the PPAR␣-null mice, whereas other fatty acid-metabolizing enzymes were present at similar or slightly lower levels in the PPAR␣-null, as compared with wild-type mice. Additionally, lower constitutive mRNA expression levels of fatty acid transporters were found in the PPAR␣-null mice, suggesting a role for PPAR␣ in fatty acid transport and catabolism. Indeed, in fatty acid metabolism experiments in vivo, myocardial uptake of iodophenyl 9-methylpentadecanoic acid and its conversion to 3-methylnonanoic acid were reduced in the PPAR␣-null mice. Interestingly, a decreased ATP concentration after exposure to stress, abnormal cristae of the mitochondria, abnormal caveolae, and fibrosis were observed only in the myocardium of the PPAR␣-null mice. These cardiac abnormalities appeared to proceed in an age-dependent manner. Taken together, the results presented here indicate that PPAR␣ controls constitutive fatty acid oxidation, thus establishing a role for the receptor in cardiac fatty acid homeostasis. Furthermore, altered expression of fatty acid-metabolizing proteins seems to lead to myocardial damage and fibrosis, as inflammation and abnormal cell growth control can cause these conditions.

eart failure (HF) is a major and growing public health problem in developed countries. 1 In the United States, approximately 5 million individuals have HF, and more than 550,000 new cases are diagnosed annually. 1 To our knowledge, only a few reports have focused on this issue in Japan. 2,3 The purpose of this study was to estimate the impact of population aging on the number of outpatients with left ventricular dysfunction (LVD) over the next 5 decades in Japan. All study participants provided informed consent and the study design was approved by the ethics review board of Niigata University Graduate School of Medical and Dental sciences.We applied estimated age-, gender-, and conditionspecific prevalences to the projected Japanese population in each age group and gender for the future until 2055, to provide a prospective estimate of the number of these patients. The primary data source was the Sado Heart Failure Study, a hospital-based research project primarily designed to count the number of patients with LVD by total enumeration in all hospitals on the island of Sado. The proportion of echocardiographically diagnosed systolic (SD) and isolated diastolic dysfunction (IDD) patients (together referred to as LVD) in the general population in 2003 4,5 was used as a substitute for the prevalence of LVD in the present study

One of the possible causes of dilated cardiomyopathy is considered to be a sequel to myocarditis. Two mechanisms have been proposed in the process of progression of myocarditis into dilated cardiomyopathy: one is a persistent viral infection, and the other is an autoimmune myocardial injury. To clarify the possible part played by the autoimmune mechanism in the process, using an animal model, we investigated whether autoimmune myocarditis, exclusively not related to viral infection, might develop into dilated cardiomyopathy. Experimental autoimmune myocarditis was elicited in Lewis rats by immunization with cardiac myosin fraction. Rats of the control group were immunized with ovalbumin. The clinical course was observed over 4 months. Six rats from the myosin-immunized group died during the acute phase and the healing phase, and all those rats had severe myocarditis. All rats that survived until the end of the study showed enlarged and discolored hearts. Aneurysmal changes were observed in the right ventricle during thoracotomy. The ratio of heart weight to body weight of the myosin-immunized group was significantly higher than that of the control group (3.36 +/- 0.49 versus 2.69 +/- 0.06 g/kg, respectively; P < .005). The lengths of the anterior interventricular fissure and the posterior interventricular fissure of the hearts of the myosin-immunized group were significantly longer than those of the control group. The external diameter of the left ventricle of the myosin-immunized group was also significantly larger than that of the control group. Diffuse myocardial muscle loss and replacement fibrosis were the prominent histological findings of the rats of the myosin-immunized group.(ABSTRACT TRUNCATED AT 250 WORDS)