Angiotensin receptor blocker (ARB) and angiotensin-converting enzyme (ACE) inhibitor (ACEI) each act in a different manner to prevent myocardial fibrosis and left ventricular (LV) stiffness in animals with pathways in the heart for generating ANG II as well as ACE. A model of pacing-induced congestive heart failure (CHF) was used to test the central hypothesis that ARB + ACEI prevents myocardial fibrosis and decreases LV stiffness to a greater extent than ARB or ACEI alone. Thirty-five dogs were assigned to the following treatment protocols on the 8th day of a 4-wk pacing schedule: 1) rapid ventricular pacing, 2) ARB (candesartan cilexetil, 1.5 mg.kg(-1).day(-1)) with pacing, 3) ACEI (enalapril, 1.9 mg.kg(-1).day(-1)) with pacing, 4) ARB (candesartan cilexetil, 0.75 mg.kg(-1).day(-1)) + ACEI (enalapril, 0.95 mg.kg(-1).day(-1)) with pacing, and 5) sham operation. The LV stiffness coefficient was significantly increased after rapid pacing but was significantly lower with ARB + ACEI than with ARB or ACEI alone. The collagen volume fraction and mRNA levels of collagen I and III, which were increased by rapid pacing, were significantly lower with ARB + ACEI than with ARB or ACEI alone. Thus ARB + ACEI prevents myocardial fibrosis and decreases LV stiffness during the progression of CHF compared with ARB or ACEI alone.

Whether cardiovascular responses to bradykinin are augmented by additional treatment with angiotensin II receptor antagonism (ATRA) to angiotensin-converting enzyme inhibition (ACEI) in congestive heart failure (CHF) is unknown. To clarify the level and functional effects of endogenous bradykinin in CHF with combined ATRA and ACEI, 35 dogs were assigned to the following treatment protocols: 1). rapid ventricular pacing (240 bpm), 2). concomitant ATRA (TCV116, 1.5 mg x kg-1.day-1) and rapid pacing, 3). concomitant ACEI (enalapril 1.9 mg x kg-1.day-1) and rapid pacing, 4). concomitant combined ATRA (TCV116, 0.75 mg x kg-1.day-1) and ACEI (enalapril 0.95 mg x kg-1.day-1) and rapid pacing, and 5). sham-operated control. Plasma bradykinin levels were increased and B(2) receptors were synergistically upregulated in CHF groups treated with combined ATRA and ACEI compared with those treated with ATRA or ACEI alone. HOE-140 (0.3 mg/kg), a bradykinin B(2) receptor antagonist, produced an increase in total systemic resistance and a decrease in left ventricular contractility in CHF with combined therapy compared with either monotherapy. Thus, endogenous bradykinin partially contributes to the synergistic improvement of cardiovascular function in CHF with additional treatment with ATRA to ACEI.

rimary tumors of the heart are rare and are often classified histologically as 'benign'. One-sixth of these are papillary fibroelastomas, which usually originate in the heart valves. 1 A few previous reports have shown papillary fibroelastomas arising from the mural endocardium of the heart chambers, papillary fibroblastomas attached to the atrial septum are extremely rare. 2 Case ReportA 61-year-old woman was in good health until 2 months prior to admission to the Yamamoto General Hospital in June 1998. On admission she complained of progressive fatigue. The week before, she had had intermittent fever peaking at 39.5°C and 2 months prior she had had a tooth extraction.On physical examination, the patient was anxious, but did not appear to be ill. Her body temperature was 39.2°C, pulse rate was 84 beats/min, respiratory rate was 16 breaths/min and her blood pressure was 108/80 mmHg. The first and second heart sounds were normal with no gallop. A grade 2/6 mid-systolic murmur was heard at the apex. The lungs were clear on auscultation. The abdominal examination was unremarkable and the extremities showed no clubbing, edema, arthritis, Osler's nodes, or Janeway lesions. Neurological examination was unremarkable. Two-dimensional echocardiography showed a 5.0×1.5 cm heavy stick-like mass attached to the atrial septum, in the left atrium during ventricular systole and passing freely into the left ventricle in diastole. The head of the mass had a high-density echo that was thought to be vegetation (Fig 1) A 61-year-old woman had intermittent fever of 2 months' duration following a dental extraction. On admission, her body temperature was 39.2°C. A mid-systolic murmur was heard at the apex on ausculation. A 2-dimensional echocardiogram revealed a mobile, heavy stick-like mass with vegetation (5.0×1.5 cm) attached to the left atrial septum. Multiple blood cultures grew Streptococcus constellatus. On diagnosis of an infected left atrial myxoma, antibiotics were administered daily and 4 weeks later, the left atrial tumor was resected. The tumor was 5.3 cm long, 1.5 cm in diameter at the inter-atrial wall and had vegetation on the free edge. On microscopic examination, colonies of Gram-positive cocci were found in the thrombus, on the papillary fibroelastoma. After treatment with antibiotics for a further 4 weeks, the patient was discharged. This is the first report of infected papillary fibroelastoma.

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The present study demonstrates that in animals with a non-ACE pathway, candesartan suppressed myocardial fibrosis during the progression of CHF in comparison with enalapril. Furthermore, candesartan prevented an increase in LV stiffness. These findings imply potential clinical applications for candesartan in the management of CHF to prevent myocardial fibrosis. Further prospective evaluation and clinical study will be necessary before deciding on the net benefits of candesartan in comparison to enalapril.