I myocardial matrix metalloproteinase (MMP) activity has been reported to occur in clinical and experimental forms of dilated cardiomyopathy.1–3 Proinflammatory cytokines, such as tumor necrosis factor(TNF), are important regulators of MMP gene expression. Previous experimental studies have shown that TNFstimulates myocardial MMP activity and can lead to degradation of the extracellular matrix in the myocardium.4 However, few clinical studies of the relation between circulating MMP and TNFlevels in idiopathic dilated cardiomyopathy (IDC) have been conducted. Recently, we reported the presence of increased circulating TNFin patients with IDC, and that blockers could reduce the increased circulating TNFlevels in IDC.5,6 The present study further clarifies the relation between circulating levels of MMPs and TNFin patients with IDC. • • • We studied 34 consecutive patients with IDC between January 1999 and December 2001. The diagnosis of IDC was based on patient history, physical examination, electrocardiogram, echocardiogram, and cardiac catheterization. All patients underwent coronary angiography during the study period, and patients with epicardial coronary artery disease were excluded. Patients who had clinical or laboratory evidence of infections, neoplasms, autoimmune disease, or liver or renal dysfunction were also excluded from this study. Ten age-matched subjects who had no evidence of organic cardiac disease and no cardiac dysfunction were retrospectively selected as the control group. All subjects participated in this study after giving informed consent, and the protocol was approved by the Human Investigations Committee of our institution. In 20 patients who were poor responders to treatment with angiotensin-converting enzyme inhibitors or angiotensin II type-1 receptor blockers for 6 months, carvedilol, a nonselective blocker, was administered orally in addition to combination therapy after their hospital admission. In 18 patients with New York Heart Association functional class II or III congestive heart failure, the initial dosage was 2.5 mg twice daily; the doses were increased at weekly intervals for 8 weeks. In 2 patients in New York Heart Association functional class IV, the initial dosage was 1.0 mg twice daily; the doses were increased at weekly intervals for 12 weeks. The target dose was 25 mg/day, considering the weight of patients in this study of 75 kg. If a decrease in systolic blood pressure to 90 mm Hg or a decrease in heart rate at rest to 60 beats/min occurred, increments in dose were discontinued. As a result, the mean final dose of carvedilol was 19.2 mg. Maintenance of final doses was continued for an additional 6 months. Blood samples from patients were collected for measurement before and 6 months after initiation of carvedilol therapy. After bed rest for 30 minutes, peripheral venous blood samples were collected into chilled tubes and immediately centrifuged at 4°C. The serum samples were stored at 80°C until assay. Serum levels of TNFwere measured by enzyme-linked immunosorFrom The Second Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Onsen-gun, Ehime, Japan. Dr. Ohtsuka’s address is: The Second Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Onsen-gun, Ehime 7910295, Japan. E-mail: tohtsuka@m.ehime-u.ac.jp. Manuscript received October 24, 2002; revised manuscript received and accepted December 30, 2002. FIGURE 1. Serum levels of TNF, MMP-1, MMP-3, and MMP-9 in 10 age-matched normal control subjects (NC) and in 34 patients with IDC. *p <0.05; **p <0.001 versus control subjects.