Takashi Uegaito

Expression and distribution of atrial natriuretic peptide in human hypertrophic ventricle of hypertensive hearts and hearts with hypertrophic cardiomyopathy.

To investigate the ventricular expression of atrial natriuretic peptide (ANP) in human hypertrophic hearts, we conducted an immunohistochemical study of 130 endomyocardial biopsy specimens obtained from the right side of the ventricular septum (RVB), left ventricular free wall (LVB), or both from a total of 80 patients: 44 patients with hypertrophic cardiomyopathy (HCM), 14 with apical hypertrophic cardiomyopathy (APH), 13 with hypertensive hearts (HHD), and nine without hypertrophy (controls). No patients had apparent congestive heart failure. ANP was not seen in ventricular myocytes in controls but was identified in biopsy specimens of hypertrophic hearts, and its distribution was characteristic in each hypertrophic group: 15 RVB (37%) and two LVB (7%) of the HCM group, one RVB (7%) and two LVB (18%) of the APH group, and zero RVB (0%/) and five LVB (46%) of the HHD group. Clinical data (including echocardiographic, hemodynamic, and angiographic data) were not directly related to ventricular ANP expression in HCM, APH, or HHD with one exception. In HHD patients, LVB specimens with ANP showed greater ventricular wall thickness than LVB specimens without ANP. According to histological data, however, the ANP-present RVB specimens of HCM or ANP-present LVB specimens of HHD had greater myocyte size than did the ANP-absent specimens. In addition, in HCM patients, the ANP-present RVB specimens showed more severe fibrosis and myofiber disarray than did the ANP-absent specimens. We conclude that a failing state and hemodynamic overload are not likely to be indispensable for ANP expression in human hypertrophic ventricles and that ventricular ANP expression occurs as a response to disease-specific changes: hemodynamic overload in HHD and histological changes such as myocardial fiber disarray, hypertrophy of myocytes, and fibrosis in HCM, which may reflect the characteristic distribution of intraventricular ANP.

Long-term effects of early statin therapy for patients with acute myocardial infarction treated with stent implantation.

OBJECTIVES Statins are widely administered to patients with acute myocardial infarction (AMI), but knowledge of the effects of early statin therapy on the long-term mortality of AMI patients after stent implantation is still limited, especially for beyond low-density lipoprotein cholesterol (LDL-C) lowering effects. METHODS Our 378 consecutive AMI patients who were discharged alive from the hospital with successful stent implantation between 1997 and 2005 were included. We retrospectively evaluated the effects of statin therapy on major adverse cardiovascular events (MACE), including all-cause death, reinfarction, coronary artery bypass grafting, heart failure requiring rehospitalization, and target lesion revascularization. RESULTS Statins were given to 271 patients according to the physician to achieve a LDL-C level of less than 100mg/dL. The achieved LDL-C levels in the statin group were 100.7, 95.1, 96.7, and 102.8mg/dL at discharge, 6 months, 1 year, and 3 years, respectively, whereas those in the non-statin group were 103.2, 107.3, 102.8, and 103.0mg/dL. These levels were not significantly different between the groups during 3 years. Based on Kaplan-Meier estimates, statin therapy was associated with a reduction of long-term mortality (log-rank test P=0.007). Multivariate Cox regression analysis revealed that statin therapy (P=0.015, hazard ratio: 0.10; 95% confidence interval: 0.01-0.64) was a significant predictor of favorable prognosis. Multivariate analysis revealed that statin treatment had a beneficial effect against MACE over 3 years (P=0.008). CONCLUSIONS Early statin therapy was beneficial for long-term mortality of AMI patients treated with stenting.

Clinicopathological study of myocardial infarction with normal or nearly normal extracardiac coronary arteries. Quantitative analysis of contraction band necrosis, coagulation necrosis, hemorrhage, and infarct size

SummaryIn order to clarify the pathogenesis of acute myocardial infarction (MI) in hearts with normal coronary arteries, infarct size, and the extent of contraction band necrosis (CBN), coagulation necrosis, and hemorrhage were quantitatively examined using an image analyzer in 5 autopsy cases of MI with normal or nearly normal extracardiac coronary arteries. One patient died 40 h after acute MI. A second patient with acute MI due to severe spasm of segment 6, confirmed by cineangiography, died three days later. The third patient had already suffered a subarachnoid hemorrhage, and died 10 h after the onset of acute MI. The fourth patient had aortic stenosis and regurgitation. She developed acute MI due to total occlusion of segment 6, confirmed by cineangiography 4 h after the onset, and died 61 days later. Autopsy revealed old anteroseptal MI with normal coronary arteries and valvular thrombi. The fifth patient had a malignancy, and died one day after the onset of acute MI. Autopsy revealed multiple occlusive thrombi in the small intramural coronary arteries of the left ventricular wall supplied by segment 14, without any stenosis in the feeding vessel. Most infarcts were localized in the territory supplied by 1 or 2 of the 3 epicardial coronary arteries, and coincided with the clinically diagnosed infarct site. The infarct size ranged from 3%–26% of the left ventricular wall, and infarcts were generally localized to the inner third of the wall (67±20%). Histological examination of the four patients with acute MI revealed diffuse CBN (86±14% of the infarcted area) and/or hemorrhage. The findings suggested that MI associated with normal coronary arteries was caused by transient coronary arterial occlusion due to spasm and/or thromboembolism, with the CBN seen in these hearts representing reperfusion injury.

Achievement Rates of Japan Atherosclerosis Society Guidelines 2007 LDL‐Cholesterol Goals with Rosuvastatin or Atorvastatin in Patients Who Had Not Achieved Their Goal with Atorvastatin

BACKGROUND The Japan Atherosclerosis Societys 2007 Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases (JAS2007GL) advocate reducing LDL cholesterol (LDL-C) to target levels in patients with dyslipidemia, but achievement rates are frequently unsatisfactory even in the presence of lipid-lowering therapy. This multicenter, open-label, randomized, parallel-group study compared the efficacy of rosuvastatin and atorvastatin on JAS2007GL LDL-C goals in Japanese patients not achieving their target goal with atorvastatin treatment. METHODS The study involved 20 clinical institutes in Japan (Kishiwada Atherosclerosis Prevention Study [KAPS] Group). Patients with category II or III risk of coronary artery disease (CAD), or those with a history of CAD (secondary prevention), who had not achieved their JAS2007GL LDL-C goals during treatment with atorvastatin for at least 4 weeks were switched either to rosuvastatin 5 mg/day (from atorvastatin 10 mg/day) or rosuvastatin 10 mg/day (from atorvastatin 20 mg/day) (n = 75) or continued to receive atorvastatin (n = 77). The primary endpoint was achievement of LDL-C goals at 3 months. The main secondary endpoint was achievement of LDL-C goal + high-sensitivity C-reactive protein level <1.0 mg/L at 3 months. RESULTS Achievement rates for the primary endpoint were 49.3% in the rosuvastatin group and 31.7% in the atorvastatin group (P = 0.022). Achievement rates for the main secondary endpoint were 40.0% in the rosuvastatin group and 20.8% in the atorvastatin group (P = 0.010). Rosuvastatin and atorvastatin were both well tolerated in this study. CONCLUSIONS Rosuvastatin is a useful treatment option for Japanese patients who are not achieving their JAS2007GL LDL-C goal with atorvastatin.

Hypertrophy of surviving myocytes overlying the infarct in human old myocardial infarctions with abnormal Q waves.

The time course of hypertrophy of surviving myocytes overlying the infarct after the onset was examined and the hypertrophy was analyzed in relation to the transmural extent of infarct in 34 autopsied hearts with Q wave infarction. The 34 hearts were divided into 4 groups according to the length of time between the onset of infarction and death. This was less than 5 days in group 1 (n = 10), 20-30 days in group 2 (n = 7), 40-60 days in group 3 (n = 7), and 12-24 months in group 4 (n = 10). To clarify the regional hypertrophy of myocytes overlying the infarct, the size of the surviving myocytes in the outer third of the left ventricular wall in the 1-cm wide central zone of the infarct was compared with that of the myocytes in the outer third of the left ventricular wall without infarction (control wall) in the same heart. To exclude factors which stimulate the hypertrophy of the whole left ventricle, the ratio of the monocyte diameter in the infarcted wall to that in the control wall was examined. It was 1.0 +/- 0.0 (mean +/- SD) in group 1, 1.0 +/- 0.1 in group 2, 1.2 +/- 0.1 in group 3, and 1.3 +/- 0.1 in group 4. The ratio was significantly higher in group 3 than in group 1 and 2, and was highest in group 4. In group 4, the corrected percentage transmural extent of infarct indicating the original transmural extent of infarct at the acute stage was 63 + 8%, and this transmural extent correlated positively with the ratio of myocyte diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Failure to reduce infarct size by intracoronary infusion of recombinant human superoxide dismutase at reperfusion in the porcine heart: Immunohistochemical and histological analysis

Failure to Reduce Infarct Size by Intracoronary Infusion of Recombinant Human Superoxide Dismutase at Reperfusion in the Porcine Heart: Immunohistochemical and Histological Analysis. Journal of Molecular and Cellular Cardiology (1991) 23, 1287-1296. We quantitatively determined the extent of infarction and contraction band necrosis in porcine hearts, and analyzed the distribution of administered recombinant human superoxide dismutase (h-SOD) in the myocardium using a polyclonal antibody to h-SOD. After 1 hour of occlusion, h-SOD was infused for the first 30 min of reperfusion in SOD group, while pigs received only arterial blood in control group. The extent of infarction or contraction band necrosis was not significantly different between SOD group and control group. Positive staining by polyclonal antibody to h-SOD was detected only in the infarcted area in SOD group. Thus, h-SOD only entered irreversibly damaged myocytes and neither diminished reperfusion injury nor reduced infarct size in pigs.

The importance of serial cardiac troponin measurement for evaluating the response to immunosuppressive therapy for myocarditis

A 71-year-old woman was admitted to our department because of acute myocarditis. She was ameliorated with conventional heart failure treatment, however she developed left ventricular dilatation and cardiac troponin T (cTnT) was elevated again to >1.0 ng/ml 6 month after the first admission. She was re-admitted because of recurrent decompensated heart failure in spite of conventional treatment. Right ventricular endomyocardial biopsy revealed active myocarditis. Immunosuppressive therapy with prednisolone and azathioprine improved her symptoms and left ventricular function accompanied by a striking decrease of cTnT levels. The decreased cTnT level indicated an effective response to immunosuppression early after the beginning of treatment. These findings suggested that it is possible to evaluate the response to immunosuppressive therapy by serial measurement of cardiac troponin.

Comparative effects of diltiazem, nifedipine, and verapamil on large and small coronary artery constriction induced by intracoronary acetylcholine in pigs.

Summary: The in vivo protective effects of diltiazem, nifedipine, and verapamil on large and small coronary artery constriction induced by intracoronary injection of acetylcholine were compared by coronary arteriography in pigs. The percent narrowing of the epicardial major right coronary artery was used as an indicator of large coronary artery constriction, and the time required for contrast medium to reach the posterior descending coronary artery from the ostium of the right coronary artery was used as an indicator of small coronary artery constriction. Doses of 12.5, 25, 50, 100, and 200 μg of acetylcholine were administered into the right coronary artery under left ventricular pacing to keep the systemic hemodynamics constant. Marked prolongation of the flow time of contrast medium to ≥8.1 s (control of ≤1.8 s) with mild narrowing of the epicardial major right coronary artery (≤35%) was observed at doses of 12.5–50 μg of acetylcholine and was accompanied by myocardial ischemia. Over 50% narrowing of the epicardial major coronary artery plus markedly slow flow of contrast medium were induced in 12 of the 15 pigs by 100–200 μg of acetylcholine. Narrowing of the epicardial major coronary artery and the delay time of contrast medium flow induced by acetylcholine were both significantly reduced to 12–33% (control: 36–81%) and to 4.3–16.8 s (control: 16.2–37.7 s) after intracoronary injection of 100 μg of diltiazem. The changes were 15–28% vs. 40–79% and 2.7–11.3 s vs. 18.1–36.1 s after nifedipine injection (10 μg), as well as 19–48% vs. 44–82% and 1.5–9.3 s vs. 15.4–41.6 s after verapamil injection (100 μg). The percent of the control constriction (100%) of large and small coronary arteries was reduced to 36 ∼ 7 and 38 ∼ 9% with diltiazem, respectively, 37 ∼ 6 and 27 ∼ 11% with nifedipine, respectively, and 47 ∼ 9 and 13 ∼ 5% with verapamil, respectively. These data indicate that although diltiazem, nifedipine, and verapamil all protected large and small porcine coronary arteries from constriction induced by acetylcholine, the potency and selectivity of their vasodilatory effects showed some differences.

A case of right atrial angiosarcoma: The utility of PET and CT fusion imaging in detecting a malignant cardiac tumor

A 49-year-old woman was admitted to the hospital because of cardiac tamponade. The hemorrhagic pericardial effusion was cytologically negative for malignant cells. Cardiac magnetic resonance imaging showed two masses in the anterior and lateral right atrium; however, positron emission tomography (PET) image using 18F-fluorodeoxyglucose revealed strong uptake in the anterior right atrium, without other tumors or metastasis. Intraoperatively, the lateral mass was confirmed as a thrombus, whereas the anterior mass was removed surgically and was diagnosed as an angiosarcoma with histopathological examination. However, she was re-admitted to the hospital 1 month after the operation because of cerebral hemorrhage, suspicious of distant metastasis. PET is useful for the detection of cardiac angiosarcoma.

A case of marked ST depression and myocardial injury as a result of disulfiram–ethanol reaction

We report a case of a 50-year-old man with intractable hypotension, which led to ischemic electrocardiogram (ECG) changes and myocardial injury due to relative myocardial ischemia as a result of a disulfiram-ethanol reaction. This is the first report that assessed cardiac function during hypotension and ischemic ECG changes by emergency coronary angiography, left ventriculography, and right heart catheterization. This case indicates that disulfiram potentially has fatal side effects due to a disulfiram-ethanol reaction.