Isolated noncompaction of the left ventricular myocardium in an elderly patient.

Noncompaction of the ventricular myocardium (NVM) is a rare disorder of endomyocardial morphogenesis characterized by numerous, prominent trabeculations and deep intertrabecular recesses. It is commonly associated with congenital heart disease, but the isolated form (INVM) is not associated with other structural heart diseases. Clinical reports of INVM have been limited to a few case reports and small series of pediatric patients. INVM is considered to be a form of congenital abnormal endomyocardial morphogenesis caused by abnormal cessation of the embryonic development of the ventricular myocardium; most reported cases have been pediatric patients, and autopsy cases of elderly patients have been quite rare. In the present case, an elderly female had INVM associated with severely disturbed left ventricular (LV) function and an enlarged left ventricle similar to dilated cardiomyopathy. The echocardiogram showed prominent trabeculations and deep intertrabecular recesses of the LV walls, especially in the posterior and apical areas. LV contrast echocardiography revealed markedly protruberant trabeculations, which were also observed with computed tomography. Five years later, the patient died of refractory heart failure and ventricular fibrillation. The autopsy revealed numerous excessively prominent trabeculations in the LV myocardium, with deep intertrabecular recesses containing thrombi.

[Primary malignant pericardial mesothelioma temporarily reduced by radiation therapy: a case report].

A 47-year-old woman was referred to our hospital because of cardiomegaly and pericardial effusion. She complained of a cough. Computed tomography, echocardiography, and magnetic resonance imaging showed a mass on the pericardium. Exploratory surgery revealed a solid tumor invading the pericardium over the aortic arch and main pulmonary artery. Histological examination indicated primary malignant pericardial mesothelioma. After 58 Gy radiation, the size of the tumor was temporarily reduced and the patient's symptoms disappeared. However, the tumor enlarged and her symptoms reappeared 7 months after temporary improvement. Eighteen months after the development of cough, the patient died suddenly.

Circulating matrix metalloproteinase-1 and -3 in patients with an acute coronary syndrome.

To elucidate the diagnostic value of serum matrix metalloproteinase (MMP) levels, we measured MMP-1 and MMP-3 by a 1-step sandwich enzyme immunoassay. The transcardiac gradients of both MMPs were greater in patients with unstable angina and acute myocardial infarction than in patients with stable effort angina or control patients. Serum MMP levels appear to be a marker of plaque instability in patients with acute coronary syndrome.

Prediction of short-term progression or regression of atherosclerotic coronary artery disease by lipoprotein (a): a quantitative coronary angiographic study.

This study assessed whether progression of coronary artery atherosclerotic lesions could be predicted in the short term using various lipid profiles. In 37 patients (61.9 +/- 9.5 years) undergoing coronary angioplasty and with 6-month follow-up angiography, quantitative coronary angiography of a new or changed lesion was performed in the follow-up examination, except for intervention vessels. The progression-regression score of the assessed lesion was calculated as the baseline minus the follow-up minimal lumen diameter. The serum lipoprotein (a) level was higher in the progression group (progression-regression score > 0.15 mm), than in the regression group (< or = -0.15 mm; p < 0.01) and the no change group (within +/- 0.15 mm; p < 0.05). Remnant-like lipoprotein particle-cholesterol and apolipoprotein-B levels were also higher in the progression group. However, multiple regression analysis of the progression showed that the progression-regression score was independently correlated with lipoprotein (a) alone (R = 0.50, p < 0.05). This shows that lipoprotein (a) is an independent predictor of coronary atherosclerotic lesion progression over the short term.

Fluvastatin attenuates nitrate tolerance in patients with ischemic heart disease complicating hypercholesterolemia.

BACKGROUND: Long-term administration of nitrates results in the development of tolerance. Nitrate tolerance is considered to occur in association with oxidative stress, although its underlying mechanisms are multi-factorial. Fluvastatin, a newly developed statin, is considered to have not only a cholesterol-lowering effect but also anti-oxidative properties. METHODS: In this study, the effect of fluvastatin on nitrate tolerance was investigated in 12 dyslipidemic patients (nine men and three women, aged 63.5+/-6.7 years), who were complicated with ischemic heart disease and had received organic nitrates for a long period. RESULTS: Four months after fluvastatin therapy, symptoms of angina were significantly reduced. Consumption of sublingual nitrates over 2 weeks significantly decreased (14.4+/-11.2 to 2.3+/-2.5 tablets, P<0.01). In exercise stress testing, exercise duration was significantly prolonged (275+/-73 to 360+/-86 s, P<0.01) and the blood pressure-heart rate products significantly increased (16368+/-2246 to 18381+/-1772, P<0.01). Both the percent change in forearm blood flow with reactive hyperemia (232+/-83 to 282+/-104%, P<0.05) and that after sublingual nitroglycerine (2.5+/-4.7 to 5.8+/-4.7%, P<0.05) were increased. Although the levels of total cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol were unchanged, the serum anti-Ox-LDL titer (16.7+/-6.3 to 13.4+/-5.4 AcU/ml, P<0.05) and 8-OHdG level (1.11+/-0.34 to 0.73+/-0.34 ng/ml, P<0.05) decreased. CONCLUSIONS: Fluvastatin attenuated nitrate tolerance in dyslipidemic patients complicated with ischemic heart disease who had been receiving organic nitrates over long period. The anti-oxidative effect of fluvastatin may attenuate nitrate tolerance.

Stent-induced expression and activation of the leukocyte integrin Mac-1 is associated with neointimal thickening and restenosis.

BACKGROUND: Increased expression of the beta2 integrin Mac-1 (CD11b/CD18, alphaMbeta2), which is responsible for firm leukocyte adhesion to platelets and fibrinogen at injured vessels, is found in association with neointimal hyperplasia after coronary interventions. The role of Mac-1 in the pathophysiology of restenosis is incompletely defined. To clarify further the role of Mac-1, we determined whether coronary stenting induced activation of Mac-1, which is required for high-affinity receptor-ligand interactions. METHODS AND RESULTS: Expression of CD11b (alpha-subunit of Mac-1) and binding of 8B2 (monoclonal antibody against an activation-dependent neoepitope of Mac-1) on the surface of polymorphonuclear leukocytes were analyzed in 62 patients undergoing coronary stenting using flow cytometric analysis of whole blood obtained from the coronary sinus and femoral vein. Transcardiac CD11b expression increased significantly at 24 hours and maximally at 48 hours after stenting; 8B2 began to increase at 10 minutes and was maximally increased at 48 hours after stenting. These changes were more prominent in patients with subsequent restenosis. Multiple regression analysis showed that the late lumen loss by quantitative coronary angiographic analysis was independently correlated with the CD11b increase (R=0.42, P<0.01) and the 8B2 increase (R=0.55, P<0.001) 48 hours after the procedure. Mac-1 activation, as assessed by 8B2 binding, was the most powerful predictor of late lumen loss. CONCLUSIONS: Coronary stenting produced upregulation and early activation of the leukocyte integrin Mac-1, which is associated with late lumen loss and restenosis. These data support a role for inflammation in neointimal thickening and suggest the validity of targeting leukocyte recruitment for preventing clinical restenosis.

Accelerated plasminogen activator inhibitor may prevent late restenosis after coronary stenting in acute myocardial infarction.

BACKGROUND: Although acceleration of plasma plasminogen activator inhibitor-1 (PA-1) level after emergent coronary angioplasty in acute myocardial infarction (AMI) has been documented, its pathophysiologic role is still unknown. HYPOTHESIS: This study was designed to elucidate the role of PAI-1 in the development of restenosis after primary coronary stenting in AMI. METHODS: We selected for this study 66 patients with AMI, who underwent primary coronary stenting for infarct-related coronary artery lesions in an emergent situation. In all patients, plasma PAI-1 level was measured at admission, and at 3 h, 24 h, 48 h, and 1 month after coronary stenting. RESULTS: At admission, the PAI-1 level was equivalent in 24 patients who experienced restenosis and in 42 patients without restenosis (28 +/- 4 vs. 29 +/- 4 ng/ml). In patients with restenosis, the levels did not change during the course after coronary stenting. In patients without restenosis, however, the level significantly increased at 3 h (48 +/- 9 ng/ml, p < 0.001), 24 h (42 +/- 9, p < 0.01), and 48 h (38 +/- 7, p < 0.05) after coronary stenting, and was restored to the level equivalent to that at admission (27 +/- 2 ng/ml) I month aftercoronary stenting. The PA-1 level at 3 h after coronary stenting in patients without restenosis was significantly higher (p < 0.05) than the level (33 +/- 6 ng/ml) in patients with restenosis. Multiple logistic regression analysis indicated that the PAI-1 level 3 h after coronary stenting was an independent predictor of restenosis (Wald chi2 = 3.826, p = 0.019, odds ratio 0.921, 95% confidence interval 0.866-0.961). CONCLUSION: Accelerated PAI-1 after coronary stenting in patients with AMI may protect against the development of late restenosis.

Possible relationship between insulin resistance and remnant-like lipoprotein particles in coronary endothelial dysfunction.

BACKGROUND: High insulin resistance and elevated remnant lipoprotein levels both correlate with impaired coronary vascular endothelial function. Hyperinsulinemia induces abnormalities of lipid metabolism. However, the correlation among insulin resistance, remnant lipoproteins, and endothelial function has not been clinically elucidated. HYPOTHESIS: This study was designed to elucidate the correlation among insulin resistance, remnant lipoproteins, and acetylcholine (ACh)-induced coronary artery response. METHODS: Forty-nine patients suspected of having ischemic heart disease, but without angiographically significant atherosclerotic coronary artery disease, underwent an ACh provocation test. Fasting venous blood was taken early in the morning on the day coronary angiography was performed. The insulin resistance index (IR) was determined from fasting plasma glucose and insulin concentrations, using the homeostasis model assessment (HOMA). Serum levels of remnant-like lipoprotein particle cholesterol (RLP-C) were measured. RESULTS: Homeostasis model assessment IR was significantly higher (3.65 +/- 1.38 vs. 0.75 +/- 0.14, p < 0.05) and log-transformed HOMA (Log HOMA) was even more significantly higher (0.20 +/- 0.12 vs. -0.29 +/- 0.08, p < 0.001) in the ACh-positive group (n = 23) than in the ACh-negative group (n = 26). The serum RLP-C level was also higher in the ACh-positive group than in the ACh-negative group (4.37 +/- 0.63 vs. 2.52 +/- 0.18 mg/dl, p < 0.01). Log HOMA and RLP-C levels correlated with each other (R = 0.54, p < 0.001). Multiple regression analysis indicated that only the RLP-C level was a dependent predictor of Log HOMA in various lipid profiles. CONCLUSIONS: Both high insulin resistance and elevated remnant lipoprotein levels correlated and might have a crucial role in the impairment of coronary vascular endothelial function, even in patients without angiographically significant coronary artery disease.

Clinical significance of the antibody against oxidized low-density lipoprotein in acute myocardial infarction.

To establish the clinical significance of the antibody against oxidized low-density lipoprotein (anti-Ox-LDL) titer in patients with acute myocardial infarction (AMI), we measured the anti-Ox-LDL titer in 39 patients with AMI and 25 controls. In all AMI patients, the anti-Ox-LDL titer on admission was higher (p < 0.05) than the value in the controls. One month after admission, the titer decreased significantly (p < 0.001) reaching control levels. In patients who underwent thrombolytic therapy, the anti-Ox-LDL titer on admission was identical in patients with occluded infarct-related arteries (IRA) and patients with patent IRA during emergency coronary angiography. In patients who did not undergo thrombolytic therapy, the anti-Ox-LDL titer on admission was higher in patients with occluded IRA than in patients with patent IRA. An increased anti-Ox-LDL titer may be a risk factor for the onset of AMI. Spontaneous recanalization of the IRA may be associated with increased anti-Ox-LDL titers, while thrombolysis-induced recanalization may be independent of it.

A new thrombolytic agent, monteplase, is independent of the plasminogen activator inhibitor in patients with acute myocardial infarction: initial results of the COmbining Monteplase with Angioplasty (COMA) trial.

BACKGROUND: Both thrombolytic therapy and coronary angioplasty have been inconsistent together for primary acute myocardial infarction (AMI) therapy, because conventional thrombolytic agents accelerate plasminogen activator inhibitor-1 (PAI-1) activity. However, combining newly developed mutant tissue-type plasminogen activators with coronary angioplasty should be reconsidered. METHODS: This study was designed to investigate clinical usefulness of such an agent, monteplase, for treatment of AMI in light of PAI-1 kinetics. One hundred fifty-four consecutive patients with AMI were randomly assigned to receive direct coronary angioplasty (Group I) or coronary angioplasty after pretreatment with intravenous monteplase (Group II). In 90 of these patients, total PAI-1 antigen levels were serially measured. RESULTS: Baseline PAI-1 levels at admission were higher in patients with occluded infarct-related arteries than in patients with patent arteries in Group I (39 +/- 4 vs 20 +/- 2 ng/mL, P <.01) and in Group II (36 +/- 3 vs 27 +/- 2 ng/mL, P <.05). In the high PAI-1 level subgroup (> or =27 ng/mL, n = 53), Group II showed a higher patency rate than Group I (56 vs 18%, P <.01). Multiple logistic regression analysis indicated that patency could be predicted by the PAI-1 level in Group I (Wald chi2= 3.94, P =.02, odds ratio 0.924, 95% CI 0.855-0.999), but not in Group II. Serial change patterns in the PAI-1 level were identical in Group I and Group II. CONCLUSION: Because monteplase can be used independently of PAI-1 kinetics, a combination of monteplase administration at a community hospital with prompt transfer to a tertiary center for coronary intervention may be a powerful strategy for AMI.

Randomized comparison of cilostazol versus ticlopidine hydrochloride for antiplatelet therapy after coronary stent implantation for prevention of late restenosis.

BACKGROUND: Cilostazol is a newly developed antiplatelet drug that has been widely applied for clinical use. Its antiplatelet action appears to be mainly related to inhibition of intracellular phosphodiesterase activity. Recently, cilostazol has been used for antiplatelet therapy after coronary stent implantation. However, its evaluation has not been established yet. METHODS: This prospective randomized trial was designed to investigate the efficacy of cilostazol for the prevention of late restenosis and acute or subacute stent thrombosis in comparison with ticlopidine hydrochloride. One hundred thirty consecutive patients, scheduled for elective coronary stenting, were randomly assigned to receive oral aspirin (81 mg/day) plus ticlopidine hydrochloride therapy (200 mg/day; group I) or aspirin plus cilostazol therapy (200 mg/day; group II). These medications were started at least 2 days before coronary intervention and continued until follow-up coronary angiography was performed 6 months later. RESULTS: Subacute stent thrombosis was observed in 2 patients of group I but in no patients of group II. Major cardiac events were similarly present in both groups. Elevated transaminase levels were observed more frequently in group I than in group II (P <.05). Each of the quantitative coronary angiography variables before and immediately after coronary stenting were similar in both groups. At follow-up angiography, however, late lumen loss (0.69 +/- 0.79 mm vs 0.28 +/- 0.40 mm; P <.01) and loss index (0.42 +/- 0.56 vs 0.16 +/- 0.27; P <.01) were smaller in group II than in group I. Restenosis rate (13% vs 31%; P <.05) and target lesion revascularization rate (7% vs 21%; P <.05) were both lower in group II than in group I. CONCLUSION: Aspirin plus cilostazol therapy may be an effective regimen for prevention of not only stent thrombosis but also restenosis.

The influence of diabetes mellitus on late clinical outcomes following coronary stent implantation.

Diabetic patients have a higher restenosis rate and late morbidity following balloon angioplasty. However, the increased risk of restenosis after coronary stent implantation in diabetic patients is controversial. We compared the quantitative coronary angiographic (QCA) variables between 42 diabetic patients and 71 non-diabetic patients undergoing coronary stent implantation and for 6 months follow-up. Pre-procedural variables were identical in the diabetic and non-diabetic patients. The stent-artery ratio was lower (1.07+/-0.13 vs. 1.13+/-0.13, P=0.020), and acute gain after coronary stenting was lower (1.58+/-0.53 vs. 1.77+/-0.48, P=0.049) in the diabetic patients than in the non-diabetic patients. However, the late lumen loss (0.42+/-0.64 vs. 0.49+/-0.69), loss index (0.28+/-0.49 vs. 0.28+/-0.45), restenosis rate (19 vs. 23%) and target lesion revascularization rate (17 vs. 18%) after 6 months were identical in the diabetic and non-diabetic patients. These results suggest that diabetes itself does not increase stent restenosis.

Early recanalization and plasma brain natriuretic peptide as an indicator of left ventricular function after acute myocardial infarction.

BACKGROUND: Although plasma brain natriuretic peptide (BNP) levels have been widely measured in patients with acute myocardial infarction (AMI), it is still uncertain whether the early recanalization modulates the levels and whether the levels can predict chronic stage left ventricular function. This study was designed to elucidate these issues. METHODS: In 80 consecutive patients with AMI, plasma BNP levels were measured at admission and at 4 hours, 24 hours, 48 hours, and 1 month after admission. RESULTS: In 35 of the 80 patients, the infarct-related artery was patent within 6 hours from the onset of MI (6-hour patency group), and in 27 patients, the artery was still occluded after 6 hours (6-hour occlusion group). The remaining 18 patients in whom it was unclear whether recanalization of the infarct-related artery had occurred within 6 hours or not were excluded from the analyses. In the 6-hour patency group, the BNP level gradually increased and reached a maximum value at 24 hours after admission. In the 6-hour occlusion group, the level increased more, with the values at 4 hours, 24 hours, and 48 hours significantly higher than those in the 6-hour patency group (86 +/- 18 pmol/L versus 35 +/- 8 pmol/L; P <.01; 112 +/- 13 pmol/L versus 74 +/- 9 pmol/L; P <.05; 102 +/- 15 pmol/L versus 53 +/- 11 pmol/L; P <.01). Chronic stage left ventricular function was correlated with not only the BNP level at same stage but also that at 24 hours and that at 48 hours after admission. Multiple regression analysis indicated that the BNP level at 24 hours was the most powerful predictor of chronic stage left ventricular function. CONCLUSION: Plasma BNP levels can predict subsequent cardiac function. In addition, the importance of early recanalization may also be supported with BNP kinetics.

Lipid-lowering therapy with fluvastatin inhibits oxidative modification of low density lipoprotein and improves vascular endothelial function in hypercholesterolemic patients.

This prospective randomized trial was designed to elucidate clinically the effect of fluvastatin on inhibiting oxidation of the low density lipoprotein (LDL) and improving the vascular endothelial function as well as its lipid-lowering effects, in comparison with pravastatin. Of 64 consecutive dyslipidemic patients, 40 patients, whose level of total cholesterol or LDL-cholesterol maintained the criteria of the hypercholesterolemia in spite of 12-week dietary therapy, were randomly assigned to receive either fluvastatin (n=20) or pravastatin (n=20). We assessed the titer of antibody against oxidized LDL (anti-Ox-LDL) as a biomarker for LDL-oxidation, and the forearm blood flow response during reactive hyperemia by venous occlusion plethysmography, which indicates the endothelium-dependent vasodilator capacity. After the 16-week lipid-lowering therapy, the anti-Ox-LDL titer significantly decreased in the fluvastatin group (P<0.01) but did not change in the pravastatin group. The percent increase in the forearm blood flow at the peak reactive hyperemia from the baseline value (%RH) significantly increased in the fluvastatin group (P<0.001) but did not change in the pravastatin group. The ratio of the %RH after the therapy over the baseline value negatively correlated with that of the anti-Ox-LDL titer (R=0.73, P<0.001) in all patients. Fluvastatin may serve as an ideal drug for reducing the risk of atherosclerosis, not only by its cholesterol-lowering effect but also by its unique effects of inhibiting LDL oxidation and improving the vascular endothelial function.

A case of double-chambered right ventricle associated with an interventricular septal aneurysm in an elderly patient.

Double-chambered right ventricle is a congential malformation caused by an anomalous muscle band obstructing the right ventricular outflow tract. Most reported cases of this condition have been diagnosed in infants, or adolescents. We encountered a 61-year-old woman with a double-chambered right ventricle, associated with a large interventricular septal aneurysm, which is a rare complication. The right ventricular obstruction was corrected with surgery.