Noninvasive prediction of coronary atherosclerosis by quantification of coronary artery calcification using electron beam computed tomography: comparison with electrocardiographic and thallium exercise stress test results.

OBJECTIVES: This study was designed to compare the usefulness of electron beam computed tomography for prediction of coronary stenosis with that of electrocardiographic (ECG) and thallium exercise tests. BACKGROUND: Electron beam computed tomography can quantify coronary calcifications; however, its clinical value has yet to be established. METHODS: Using the volume mode of electron beam computed tomography, we studied 251 consecutive patients who underwent elective coronary angiography because of suspected coronary artery disease and compared the results with those of ECG and thallium exercise tests. The total coronary calcification score was calculated by multiplying the area ( > or = 2 pixels) of calcification (peak density > or = 130 Hounsfield units) by an arbitrarily weighted density score (0 to 4) based on its peak density. The mean of two scans was log transformed. RESULTS: Calcification was first noted in women in the 4th decade of life, approximately 10 years later than its occurrence in men. Among patients with advanced atherosclerosis (two- and three-vessel disease), calcification scores were uniformly high in women but ranged widely in men. Nine percent of patients with significant stenoses ( > or = 75% by densitometry) had no calcification. The calcification scores of patients with significant stenosis in at least one vessel were significantly higher than those of patients without significant stenosis in the study group as a whole and in most patient subgroups classified according to age and gender. A cutoff calcification score for prediction of significant stenosis, determined by receiver operating characteristic curve analysis, showed high sensitivity (0.77) and specificity (0.86) in all study patients; sensitivity was similarly high even in older patients ( > or = 70 years) and was enhanced in middle-aged patients (40 to < or = 60 years). The difference in specificity between calcification scores and ECG exercise test results had borderline significance (p = 0.058) and that between calcification scores and thallium test results was significant (p = 0.001). The latter difference became small but remained significant (p = 0.01) even after the reevaluation of thallium test results in light of each subject's clinical data. CONCLUSIONS: Quantification of coronary artery calcification with electron beam computed tomography noninvasively predicted angiographically confirmed coronary stenosis. Results obtained with this method were at least as useful and potentially better in some patient groups than those obtained with thallium and ECG exercise testing.

Coronary calcification and coronary atherosclerosis: site by site comparative morphologic study of electron beam computed tomography and coronary angiography.

OBJECTIVES: We compared, on a site by site basis, the morphologic features of coronary calcifications determined by electron beam computed tomography (EBCT) and angiographically defined coronary atherosclerosis. BACKGROUND: Quantification of coronary calcification using EBCT is clinically useful for the prediction of coronary stenosis. However, the relation between calcification and angiographic findings has not been evaluated by site. METHODS: We studied 251 consecutive patients who underwent elective coronary angiography for suspected coronary artery disease by EBCT and analyzed findings by site. Coronary calcifications were classified according to their length and width versus the diameter of the coronary artery in which the calcification was observed as: none, spotty, long, wide and diffuse. RESULTS: Coronary calcifications were found in 666 (27%) of 2,470 segments. The positive predictive value (PPV) of coronary calcification for significant stenosis (> or = 75% densitometric narrowing) and for all angiographically detectable atherosclerotic lesions in a segment was 0.36 and 0.80, respectively. The PPV for significant stenosis and all atherosclerotic lesions was 0.04 and 0.17 in none, 0.18 and 0.59 in spotty, 0.32 and 0.87 in long, 0.40 and 0.84 in wide and 0.56 and 0.96 in diffuse calcifications, respectively. The PPV for both significant stenosis and all lesions differed significantly (p = 0.001) among the morphologic groups. Of the 105 eccentric significant stenoses, 54 (53%) were classified as long or diffuse calcifications. Of the 95 significant stenoses with multiple irregularities, 61 (64%) showed diffuse calcification. CONCLUSIONS: Morphologic evaluation of coronary calcifications using EBCT improved the prediction of coronary stenosis on a site by site basis and provided information related to angiographic morphology.

Estimation of mitral valve area in patients with mitral stenosis by the flow convergence region method: selection of aliasing velocity.

OBJECTIVES: We attempted to determine the most suitable aliasing velocity for applying the hemispheric flow convergence equation to calculate the mitral valve area in mitral stenosis using a continuity equation. BACKGROUND: The flow convergence region method has been used for calculating mitral valve area in patients with mitral stenosis. However, the effect of varying aliasing velocity on the accuracy of this method has not been investigated fully. METHODS: We studied 42 patients with mitral stenosis using imaging and Doppler echocardiography. Aliasing velocities of 17, 21, 28, 34, 40 and 45 cm/s were used. The transmitral maximal flow rate (Q [ml/s]) was calculated using the hemispheric flow convergence equation Q = 2 x pi x R2 x AV x alpha/180, where R (cm) is the maximal radius of the flow convergence region, AV is the aliasing velocity, and alpha/180 is a factor accounting for the inflow angle (alpha). Mitral valve area (A [cm2]) was calculated according to the continuity equation A = Q/V, where V (cm/s) is the peak transmitral velocity by the continuous wave Doppler method. RESULTS: Mitral valve area was progressively underestimated with increasing aliasing velocity. The actual and percent differences noted between the mitral valve area by the flow convergence region method and that by two-dimensional echocardiographic planimetry were -0.06 +/- 0.23 cm2 (mean +/- SD) and 0.09 +/- 15.7% at an aliasing velocity of 21 cm/s, increasing gradually with increasing aliasing velocity, and were -1.24 +/- 0.9 cm2 and -72.56 +/- 16.4% at an aliasing velocity of 45 cm/s. Mitral valve areas estimated by the flow convergence region method at an aliasing velocity of 21 cm/s in 11 patients with associated > 2+ mitral regurgitation (2.12 +/- 1.17 cm2) and 8 with associated > 2+ aortic regurgitation (1.28 +/- 0.71 cm2) were not significantly different using planimetry (2.24 +/- 1.39 cm2, p > 0.05 and 1.27 +/- 0.74 cm2, p > 0.05, respectively) but were significantly different by the pressure half-time method (1.59 +/- 1.12 cm2, p < 0.001 and 1.63 +/- 0.93 cm2, p < 0.01, respectively). CONCLUSIONS: This study indicated the most appropriate aliasing velocity for the accurate estimation of mitral valve area in patients with mitral stenosis.

Hemodynamic effects of dibutyryl cyclic AMP in congestive heart failure.

To evaluate the hemodynamic effects of dibutyryl cyclic AMP (DBcAMP) in congestive heart failure (CHF), right-sided cardiac catheterization was performed in 11 patients with CHF, and hemodynamic variables were investigated before and after infusion of various doses of DBcAMP at a rate of 0.025 to 0.2 mg/kg/min (mean 0.14 +/- 0.077 [standard deviation]). DBcAMP reduced total systemic vascular resistance index from 3,171 +/- 1,158 to 1,880 +/- 554 dynes s cm-5 X m2 (mean +/- standard deviation) and pulmonary arterial end-diastolic pressure from 23 +/- 13 to 20 +/- 11 mm Hg, and increased cardiac index from 2.24 +/- 0.60 to 3.41 +/- 1.02 liters/min/m2. Mean arterial blood pressure decreased from 91 +/- 14 to 84 +/- 13 mm Hg, and heart rate increased from 91 +/- 16 to 99 +/- 13 beats/min. The increase in cardiac index was accompanied by a proportional decrease in total systemic vascular resistance index in all patients except 1. In 8 patients the decrease in pulmonary arterial end-diastolic pressure was accompanied by an increase or no change in the left ventricular stroke work index. In 6 patients, DBcAMP was given in incremental doses of 0.05, 0.1, and 0.2 mg/kg/min every 20 minutes, and 5 of 6 patients tolerated the full dose and showed dose-related hemodynamic changes for the incremental doses of DBcAMP. These data suggest that DBcAMP has powerful vasodilating effects on resistance vessels in patients with CHF; hence, it can be a useful vasodilating agent for treatment of CHF.

Dilated cardiomyopathy defines serum autoantibodies against G-protein-coupled cardiovascular receptors.

In order further to identify the prevalence of anti-receptor autoantibodies in the sera of patients with dilated cardiomyopathy (DCM), we attempted to detect autoantibodies against a series of G-protein-coupled cardiovascular receptors in a well-defined population of DCM patients from Japan. Peptides corresponding to the sequences of the second extracellular loops of the human beta 1 and beta 2 adrenoceptors, alpha 1 adrenoceptors, M2 muscarinic acetylcholine receptors and angiotensin II-1 (AT1) receptors were used as antigens in an enzyme immunoassay to screen the sera from patients with DCM (n = 28). Nine sera from patients with DCM (32%) and 2 sera from healthy subjects (9%) recognized the beta 1 adrenoceptor peptide. Ten sera from patients (36%) and 3 sera from healthy subjects (13%) recognized the M2 receptor peptide. Thirty-six per cent of the patients with autoantibody against the beta 1 adrenoceptor peptide. Ten sera from patients (36%) and 3 sera from healthy subjects (13%) recognized the M2 receptor peptide. Thirty-six per cent of the patients with autoantibody against the beta 1 adrenoceptor had autoantibody against the M2 receptor. However, no significantly high frequencies of autoantibodies against the beta 2 adrenoceptor, alpha 1 adrenoceptor and AT1 receptor were found in DCM patients. Our results demonstrate that a subgroup of patients with DCM have a specific spectrum of autoantibodies which are specifically directed against the second extracellular loops of the beta 1 adrenoceptors and M2 muscarinic receptors rather than other cardiovascular receptors.

Noninvasive, continuous evaluation of peripheral vascular resistance in humans.

We sought a noninvasive alternative method of monitoring peripheral vascular resistance continuously in humans, based on the analysis of arterial pressure waveforms. Radial arterial pressure waveforms were recorded noninvasively with a tonometer and analysed using a neural network method. To test the accuracy of this method, the peripheral vascular resistance was also determined by an invasive thermodilution method using a Swan-Ganz catheter in 20 subjects. To test the method in a clinical application, peripheral vascular resistance was determined by the noninvasive method before and after administration of nifedipine in 6 patients with essential hypertension. Neural network analysis of waveforms reliably yielded values between 0.00 and 1.00. Peripheral vascular resistance determined by neural network analysis and according to the invasive method showed a significant (p< 0.005) positive linear correlation. The peripheral vascular resistance measured by neural network analysis showed a significant (p< 0.05) decrease 30 min after administration of nifedipine, paralleling a decrease in blood pressure. Neural network analysis of tonometric radial artery waveforms provides an accurate, noninvasive, and continuous index of peripheral vascular resistance in human subjects. This simple method should permit more extensive homodynamic studies and larger epidemiological surveys in contrast to those undertaken using invasive techniques.

Nifedipine in hypertension and heart failure.

The use of nifedipine in patients with hypertension, heart failure, and acute myocardial infarction is discussed. Data from over a ten-year period are presented. Results indicate that nifedipine, although frequently prescribed as an antianginal agent, is also useful as an antihypertensive agent, especially when used concomitantly with other drugs. Its ability to cause fluctuations in blood pressure remains a shortcoming, however.

Efficacy of dibutyryl cyclic AMP in heart failure unresponsive to catecholamines.

The efficacy of dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) was evaluated in eight patients with heart failure unresponsive to catecholamine therapy. Seven patients who were hemodynamically at Forrester's hemodynamic subset stage H-IV and had a left ventricular stroke work index (LVSWI) of less than 20 g-m/m2 despite administration of unloading drugs and catecholamines were studied both hemodynamically and clinically. Another patient with dilated cardiomyopathy, in whom invasive hemodynamic monitoring could not be carried out, was studied clinically. The DBcAMP was administered intravenously at a mean (+/- SD) of 0.05 +/- 0.036 mg/kg/min, and hemodynamic measurements were made 63 +/- 37 min after administration. The cardiac index (CI) increased from 1.92 +/- 0.22 to 2.49 +/- 0.59 L/min/m2, and LVSWI from 14 +/- 4.0 to 18 +/- 5.1 g-m/m2, both significantly (CI, P less than 0.01; LVSWI, P less than 0.025). The total systemic vascular resistance index (TSVRI) decreased significantly from 2,746 +/- 427.2 to 2,218 +/- 582.6 dan.sec.cm-5.m2 ( P less than 0.01). The increase in CI was accompanied by a proportional decrease in TSVRI in all patients. Left ventricular function, which was estimated by the relation between pulmonary arterial end-diastolic pressure and LVSWI, was improved in five of seven patients after administration of DBcAMP. Two patients in whom DBcAMP was given intermittently improved clinically and survived. The authors conclude that DBcAMP has powerful vasodilating and mild positive inotropic effects and hence can be useful for treating heart failure unresponsive to catecholamines.

The potent role of increased sympathetic tone in pathogenesis of essential hypertension with neurovascular compression.

OBJECTIVE: To study the role of increased sympathetic tone in pathogenesis of hypertension in patients with essential hypertension with neurovascular compression. METHODS: Twenty-three patients with essential hypertension, 13 patients with secondary hypertension, and 46 normotensive subjects were investigated. Neurovascular compression was evaluated by MRT. The power spectral components of heart rate variability as indices of autonomic nerve tone were determined to investigate the possibility that sympathetic tone mediates the neurovascular compression-induced increase in blood pressure. RESULTS: Neurovascular compression of the rostral ventrolateral medulla (RVLM) was observed in 70% of essential hypertension group, none of secondary hyperension group and 16% of normotensive group (P < 0.001). The age-adjusted low-frequency power spectral density (A-PSD) (0.04 to 0.15 Hz), which is an index of sympathetic tone, was significantly higher in patients with essential hypertension (139.5 +/- 6.7%) with neurovascular compression than in essential hypertension patients without neurovascular compression (92.2 +/- 6.8%), normotensive subjects with (102.8 +/- 13.0%) and without neurovascular compression (100.1 +/- 4.1%), and patients with secondary hypertension (95.7 +/- 10.2%) (P < 0.001). There was no significant difference in the high-frequency A-PSD (0.15 to 0.40 Hz), which is an index of vagal tone, among groups. CONCLUSIONS: Neurovascular compression was not always associated with an increase in sympathetic nerve tone. Hypertension was present in subjects with neurovascular compression, who had increased sympathetic tone but not in those with normal sympathetic tone. An increase in sympathetic tone may mediate the neurovascular compression-induced increase in blood pressure. Journal of Human Hypertension (2000) 14, 807-811

Quantification of coronary artery calcification using ultrafast computed tomography: reproducibility of measurements.

BACKGROUND: Ultrafast computed tomography (CT) is a non-invasive method of visualizing and quantifying coronary artery calcification; its reproducibility, however, has not been fully elucidated. METHODS: To assess intra-observer, inter-observer, and inter-study reproducibility, 75 consecutive patients (51 men and 24 women) were studied. CT images were obtained using the volume mode of ultrafast CT (Imatron C-100). A total coronary calcification score (TCS) was calculated from the lesion area (> or = 2 pixels) and its peak CT density (> or = 130 HU). RESULTS: There was no intra-observer variability in two experienced observers. The TCS provided by these observers disagreed in 18 out of 75 (24%) cases, and the differences were -5.1 +/- 53 (mean +/- SD) for TCS and 0.014 +/- 0.13 for In(1 + TCS). They resulted from either 10 incorrect identifications of small coronary branches, or eight variations in determination of the ostial margin. The former was much smaller than the latter in TCS (0.66 +/- 3.0 and -48 +/- 165, respectively), but both were quite similar in In(1 + TCS) (0.082 +/- 0.31, 0.017 +/- 0.22, respectively). Between two scans, 50 out of 75 patients (67%) had different TCS values. The mean differences (95% confidence interval) were 1.8 +/- 106 (-210 to 214) in TCS, and -0.015 +/- 0.46 (-0.94 to 0.91) in In(1 + TCS). Because the differences increased with the mean values, the determination of TCS assumed a constant variance with increasing mean level. A comparison of scan images indicated that partial volume effects were responsible for this constant variance. CONCLUSION: Partial volume effects play a key role in producing the variability of TCS determination, and log transformation should be used to interpret TCS values. Thus, for clinical purposes, we recommend that two scans be performed in rapid succession, and that the average of these two scans be used to determine TCS.

Urinary carnitine excretion in patients with heart failure.

To evaluate the fatty acid metabolism in heart failure, the semiquantitative analysis of urinary free carnitine and acylcarnitine was made by fast atom bombardment mass spectrometry (FABMS) in 22 patients (mean age 67.3 years) with heart failure and 19 age-matched healthy controls (average age 60.4 years). Urinary excretion of free carnitine was 0.20 +/- 0.118 ratio/mg creatinine in the healthy controls and 1.32 +/- 1.170 ratio/mg creatinine in the patients with heart failure. The latter value was significantly higher (p < 0.01). Patients with heart failure were classified into two groups according to the urinary free carnitine concentration. One was the high excretion group (2.19 +/- 0.102 ratio/mg creatinine, 12 cases) and the other was the low excretion group (0.37 +/- 0.212 ratio/mg creatinine, 10 cases). In the high excretion group, urinary acetylcarnitine was also increased, but no significant abnormalities were observed in the urinary organic acid profile. In the high group, 1 patient was classified as NYHA class III and 11 as NYHA class IV. Four patients died in the hospital. In the low excretion group, five patients were classified as NYHA class III and five as NYHA class IV. Only one patient died in the hospital. In the high group, patients with severe and prolonged heart failure tended to maintain higher values of urinary free carnitine. We could not find any abnormalities in fatty acid metabolism in patients with heart failure, but it is suspected that the patients who excrete large amounts of free carnitine into the urine, namely the patients with severe heart failure, have some possibility of carnitine deficiency.

A comparison of the results of A-C bypass grafting in collateral and non-collateral groups.

Ninety patients who had aorto-coronary bypass grafting were divided into two groups: a collateral group, which had coronary arterial stenosis or occlusion with collateral circulation, and a non-collateral group, which had coronary arterial stenosis or occlusion without collateral circulation. The number of coronary arteries visualized through collateral circulation in coronary angiograms (CAG) was 32, left anterior descending arteries (LAD) 17, right coronary arteries (RCA) 11, and left circumflex arteries (LCX) 4. The results of A-C bypass grafting in the collateral and non-collateral groups were compared. Surgical mortality was 0% in the collateral group, and 5.4% in the non-collateral group. The differences in graft patency and graft flow between the two groups were not statistically significant. However, left ventricular ejection fraction and myocardial perfusion, which was estimated by thallium-201 myocardial perfusion scintigram, were significantly improved after A-C bypass in the collateral group. Although the coronary arteries visualized through collateral vessels seemed too narrow to undergo graft anastomosis, they were, in fact, large enough. A-C bypass grafting was achieved with more satisfactory results in the collateral group than in the non-collateral group.

Upregulation of cardiac ghrelin mRNA in leptin-deficient and leptin receptor-deficient mice with viral myocarditis.

Expression of cardiac and gastric ghrelin messenger (m) RNA, together with heart and body weights, were measured in leptin-deficient (ob) and leptin receptor-deficient (db) mice with heart failure induced by viral myocarditis. Significant elevations in cardiac ghrelin mRNA levels and heart weight were observed in ob and db mice 10 days after viral inoculation compared with baseline values. Expression of gastric ghrelin mRNA was not upregulated in ob and db mice on day 10. The elevated expression of cardiac ghrelin mRNA seems to compensate for the lack of upregulation in gastric ghrelin mRNA.

[Two cases of rupture of intraaortic balloon].

We reported two cases of rupture of intraaortic balloon (IAB). The most likely cause appears to be the rupture of IAB membrane against a calcific atherosclerotic aortic plaque. When the IAB ruptures by contact of calcific lesions in aorta, the leak detection of device of intraaortic balloon pumping is useless to diagnose this rupture. Therefore, the rupture of IAB through a pin hole is diagnosed by the transient presence of blood in the tube connecting the balloon. It is recommended that the balloon immediately should be removed at the transient presence of blood in the connecting tube.

Endocardial Invasion of Lung Cancer Undiagnosable before Autopsy.

A 59-year-old male patient presented with left chest discomfort on admission. His medical history included encephalitis in childhood and his smoking history was 20 cigarettes per day for 40 years. A physical examination showed an anemic and edematous face with weak respiratory sounds in the left lung. The patient had elevated calcium levels and decreased hemoglobin and potassium. His parathyroid hormone-related protein level was elevated. Thoracic radiography showed cardiomegaly and computed tomography revealed a left lung mass with invasion of the heart and pleural effusion. Magnetic resonance imaging showed endocardial invasion of the tumor mass. Gallium-68 imaging revealed positive accumulation in the region surrounding the heart. No diagnoses were possible upon frequent cytology of his sputum and pleural effusion. The patient died from congestive heart failure with anoxia 38 days after admission. An autopsy revealed tumoral mass occlusion in the left main bronchus and tumoral invasion of the left atrium, left ventricle, and aorta.

Spontaneous remission of epstein-barr virus-positive diffuse large B-cell lymphoma of the elderly.

A 94-year-old female patient presented with anorexia and left axillar lymphadenopathy on admission. Her past history was angina pectoris at 83 years of age and total gastrectomy due to gastric cancer at 87 years. The family history revealed that her son had had a malignant lymphoma, the histopathological diagnosis of which was diffuse large B-cell lymphoma. A physical examination showed both cervical, axillar, and inguinal lymphadenopathy without tenderness. She had elevated lactate dehydrogenase, ferritin, and soluble interleukin-2 receptor (sIL-2R). Whole-body computed tomography confirmed the cervical, axillary, and inguinal lymphadenopathy. Gallium-68 imaging revealed positive accumulation in these superficial lymph nodes. A right inguinal lymph node biopsy showed features of Epstein-Barr virus-associated lymphoproliferative disorder. Immunohistological studies on this lymph node biopsy showed CD20-positive large cells, CD3-positive small cells, and CD30-partly-positive large cells. In situ hybridization showed Epstein-Barr virus-positive, LMP-partly-positive, and EBNA2-negative cells. She refused chemotherapy as her son had died from hematemesis during chemotherapy. She received intravenous hyperalimentation for 1 month after admission. No palpable lymph nodes were identified by physical examination or computed tomography 3 months after admission, and regression of lactate dehydrogenase, ferritin, and sIL-2R was observed. She recovered from anorexia and was discharged. She died from pneumonia 10 months later after initial symptoms of anorexia. The autopsy showed no superficial lymphadenopathy.