In failing human hearts (FHH) (NYHA IV) the cardiac output is inadequate to meet the metabolic needs of the peripheral systems. By means of thermo-mechanical analysis we have shown that epicardial strips from FHH (37 °C) have a depressed tension independent heat (TIH) and tension independent heat rate (dTIH/dt) liberation that correlates with depression in peak isometric force and the rate of relaxation. Furthermore, in response to a change in frequency of stimulation, FHH shows a severe blunting of the force-frequency relationship resulting in a decrease in myocardial reserve and in the frequency at which optimum force is obtained. We used ventricular ANF as an index of the severity of myocardial disease and demonstrated an inverse relationship between ANF mRNA and the sarcoplasmic reticulum (SR) calcium cycling proteins (SERCA 2, Phospholamban, Ryanodine Receptor) while these latter proteins all had a positive correlation with each other. At the same time there was an increase in sarcolemmal sodium calcium exchange protein. The decrease in SR pump proteins correlates with the decrease in myocardial reserve and optimum frequency of contraction. The latter mechanical changes are explainable in terms of a frequency dependent decrease in calcium concentration (aequorin light) in FHH. (Jpn Heart J 2000; 41:103-116)

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Mechanical stress is a major cause of cardiac hypertrophy. Although the mechanisms by which mechanical load induces cardiomyocyte hypertrophy have long been a subject of great interest for cardiologists, the lack of a good in vitro system has hampered the understanding of the biochemical mechanisms. For these past several years, however, an in vitro neonatal cardiocyte culture system has made it possible to examine the biochemical basis for the signal transduction of mechanical stress. Passive stretch of cardiac myocytes cultured on silicone membranes activates phosphorylation cascades of many protein kinases including protein kinase C, Raf-1 kinase and extracellular signal regulated kinases, and induces the expression of specific genes as well as an increase in protein synthesis. During that process, the secretion and production of vasoactive peptides such as angiotensin II and endothelin, are increased and they play critical roles in the induction of these hypertrophic responses. Although the involvement of vasoactive peptides in the development of cardiac hypertrophy is clinically important, the “mechanoreceptor" which receives the mechanical stress and converts it into intracellular biochemical signals remained unknown. We have recently obtained evidence suggesting that ion channels and integrins may be the “mechanoreceptor”, the activation of which leads to cardiac hypertrophy. (Jpn Heart J 2000; 41: 117-129)

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Recently a novel biochemical method that uses an immunoassay to quantitate serum smooth muscle myosin heavy chain (SMMHC) levels was developed for diagnosis of aortic dissection.¹⁾ The purpose of this study was to determine whether SMMHC released from the coronary arterial wall can be used to predict restenosis after percutaneous transluminal coronary angioplasty (PTCA). Fifty-two consecutive patients undergoing successful PTCA for single vessel disease were examined (40 men, 12 women, 63±8 years). Intracoronary blood samples were obtained distal to the lesion, and from the femoral artery after PTCA. In 10 patients, blood samples were taken immediately after the final balloon inflation, and 10 and 20 minutes after PTCA. SMMHC levels were measured by ELISA using SMMHC-specific monoclonal antibodies. Follow-up coronary angiography was performed 3 months after PTCA. Intracoronary serum SMMHC levels were significantly higher than those obtained from the femoral artery (10.6±1.5 vs 2.1±0.1 ng/ ml, p≤0.001). Of 40 patients without apparent dissection, the 23 patients who did not develop restenosis in the follow-up study were found to have had higher levels of intracoronary SMMHC levels immediately after PTCA compared to the 17 patients with restenosis (15.2±2.9 vs 7.1±1.2 ng/ml, p≤0.05). We suggest that elevated intracoronary SMMHC levels after PTCA may reflect the extent of injury to the arterial wall. Intracoronary SMMHC may be a possible biochemical marker for the prediction of restenosis. (Jpn Heart J 2000; 41: 131-140)

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False positive inferior wall perfusion defects restrict the accuracy of SPECT in diagnosis of coronary artery disease (CAD). Pulse-Wave Tissue Doppler (PWTD) has been recently proposed to assess regional wall motion velocities. The objectives of this study were to evaluate the presence of CAD by using PWTD during dobutamine stress echocardiography (DSE) in patients with an inferior perfusion defect detected by SPECT and compare PWTD parameters of normal cases with patients who had inferior perfusion defect and CAD. Sixty-five patients (mean age 58±8 years, 30 men) with a normal LV systolic function at rest according to echocardiographic evaluation with an inferior ischemia determined by SPECT and a control group (CG) of 34 normal cases (mean age 56±7 years, 16 men) were included in this study. All patients underwent a standard DSE (up to 40 mg/kg/min with additional atropine during sub-maximum heart rate responses). Pulse-wave Doppler tissue sampling of inferior wall was performed in the apical 2-chamber view at rest and stress. The coronary angiography was performed within 24 hours. The results were evaluated for the prediction of significant right coronary artery (RCA) and/or left circumflex coronary artery (CX) with narrowing (≥50% diameter stenosis, assessed by quantitative coronary angiography). It was observed that the peak stress mean E/A ratio was lower in patients with CAD when compared to patients without CAD (0.78±0.2 versus 1.29± 0.11 p<0.0001). Also the peak stress E/A ratio of normal cases was significantly higher than patients who had CAD (1.19±0.3 versus 0.78±0.2 p 0.0001). When the cut off point for the E/A ratio was determined as 1, the sensitivity and specificity of dobutamine stress PWTD E/A were 89% and 86 %, respectively. The peak stress E/A ratio was higher than 1 in all patients with a false positive perfusion defect. Systolic S velocity increase during DSE was significantly lower in patients with CAD (54 %±17 versus 99 %±24 p= 0.01). The analysis of S velocity increase yielded 81% sensitivity and 76% specificity for prediction of CAD when a 70 % increase was accepted as a cut-off value. Pulse-wave Doppler tissue sampling during DSE may help to identify false positive inferior wall defects detected by SPECT. (Jpn Heart J 2000; 41: 141-152)

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Only a few reports evaluating coronary arterial blood flow velocity patterns using magnetic resonance (MR) coronary angiography have appeared to date. This study reports an evaluation of coronary arterial blood flow velocity patterns in patients with ischemic heart disease and in healthy subjects using MR coronary angiography. The subjects consisted of 20 patients with ische mic heart disease (IHD group) and 20 normal healthy subjects (N group). Using the fCARD PC method, ECG-gated MR coronary angiography was performed using an anteroposterior opposing phased array coil. Regions of interest were placed on bilateral coronary arteries to measure coronary arterial blood flow velocity patterns. The IHD group was divided into two subgroups, based on the presence (MI group) or absence (AP group) of infarcted myo cardium using ^99mTc-methoxyisobutylisonitrile (MIBI) myocardial scinti graphy. Average diastolic peak velocity (ADPV) was lower in the IHD group than in the N group. In addition, the diastolic/systolic velocity ratio (DSVR) was significantly lower in the MI group. Moreover, in the AP group, both the ADPV and DSVR values were significantly increased in those who had undergone percutaneous transluminal coronary angioplasty postoperatively. Different from the Doppler guidewire method, MR coronary angiography facilitates noninvasive evaluation of coronary arterial blood flow velocity. Therefore, these results indicate that MR coronary angiography represents a potentially useful technique for diagnosing lesions of coronary arteries and evaluating their functions. This noninvasive method can be expected to replace the invasive Doppler guidewire method in the near future with development of MR coronary angiography technology. (Jpn Heart J 2000; 41: 153-164)

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The association between chlamydia pneumonia and coronary artery disease is well documented, however less is known about the correlation between chlamydia pneumonia infection and blood inflammatory markers or lipid levels.In 100 patients with proven coronary artery disease (25 females, 61.0±4.0 years old), and 60 healthy volunteer control cases (15 females, 60.6±3.4 years old), anti chlamydia pneumonia IgG, blood lipid, C-reactive protein and fibrinogen levels were detected. In cases with coronary artery disease seropositivity for IgG antibodies to chlamydia pneumonia (74% versus 34%, p<0.0001), C-reactive protein (mg/l) (2.8±0.6 versus 1.4±0.6, p<0.0001), fibrinogen (mg/dl) (317.4±38.2 versus 256.2±34.5, p<0.0001), triglyceride (mg/dl) (217.5±39.0 versus 191.0±25.9, p<0.0001), LDL-cholesterol (mg/dl) (126.9±19.2 versus 110.6±19.5, p<0.0001) levels and total cholesterol/ HDL-cholesterol ratio (7.7±1.8 versus 4.4±1.2, p<0.0001) were higher but the level of HDL-cholesterol (mg/dl) (26.4±6.7 versus 47.0±11.2, p<0.0001) was lower. The levels of total cholesterol did not differ between the two groups (p=0.9). Levels of triglyceride (r=0.60, p<0.00001), LDL-cholesterol (r=0.27, p=0.0004), C-reactive protein (r=0.69, p<0.00001), fibrinogen (r=0.60, p<0.00001) and total cholesterol /HDL-cholesterol ratio (r=0.74, p<0.00001) had a direct relation, but the level of HDL-cholesterol had a negative (r=-0.80, p<0.00001) relation with the seropositivity for chlamydia pneumonia.As a result, seropositivity for IgG antibodies to chlamydia pneumonia is considered as a risk factor for coronary artery disease by its association with the atherogenic lipid profile and procoagulant activity. (Jpn Heart J 2000; 41: 165-172)

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Low heart rate variability and increased QT dispersion are risk factors for cardiac mortality in various patient populations. We studied dispersion of QT interval, i.e. an index of inhomogeneity of repolarization, and heart rate variability (HRV) i.e., a measure of cardiac autonomic modulation in 76 essential hypertension cases (45 women, 53.0± 11.1 years, body mass index: 25.1±1.4 kg/m²) and 70 healthy cases (42 women, 54.0±10.2 years, body mass index: 25.5±1.6 kg/m², p>0.05). QT-corrected QT intervals and their dispersions were significantly higher in the hypertensive group (p<0.0001), all showing a direct relation with the level of systolic and diastolic blood pressures, ventricular mass index and high Lown grade ventricular rhythm problems. Time domain measures like standard deviation of RR intervals, standard deviation of the means of all corrected RR intervals calculated at 5 min intervals (p<0.0001), proportion of adjacent RR intervals differing by>50 msec (p=0.005), HRV triangular index (p =0.007), the square root of the mean squared differences of successive RR intervals (p= 0.011), and the high frequency (HF, 0.16-0.40 Hz, p<0.0001) part of the frequency domain measure of HRV were all decreased, whereas the low frequency (LF, 0.04-0.15 Hz, p=0.013) part of the frequency domain measures and LF/HF ratio (p<0.0001) were increased in hypertensive cases. Time domain and the HF part of frequency domain measures of heart rate variability showed an inverse relation with the increased levels of both systolic and diastolic blood pressures and Lown grading system of ventricular rhythm problems, whereas LF and LF/HF showed direct relations with high levels of systolic and diastolic blood pressures and high Lown grade ventricular rhythm problems. The measures of heart rate variability apart from LF and LF/HF were inversely related with the QT intervals and dispersions, whereas LF/HF was directly related with them.Therefore, we conclude that the levels of both systolic and diastolic blood pressures are related to the generation of ventricular rhythm problems either via increasing left ventricular mass which results in an increase in QT parameter measurements, or by altering heart rate variability measures indicating a disturbance in cardiac autonomic balance in essential hypertension. (Jpn Heart J 2000; 41: 173-182)

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Various cytokines play important roles in the pathogenesis of congestive heart failure. TNF-α is one of the pro-inflammatory cytokines, and IL-10 has anti-inflammatory actions. The -308 (G/A) polymorphism of the TNF-α gene (TNFA1 and A2) and the single base -1082 (G/A) polymorphism of the IL-10 gene (IL-10 1^*G and 1^*A) have been identified as causing alterations to the in vivo production of TNF-α and IL-10, respectively. We examined TNF-α and IL-10 gene polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism technique in 48 Japanese patients with idiopathic dilated cardiomyopathy. The frequency of these polymorphisms was compared with 50 healthy Japanese. The clinical courses, such as disease onset, left ventricular function, progression during the follow up period and hospitalization from congestive heart failure, were also analyzed. Serum TNF-α levels were measured using an enzyme-linked immunosorbent assay (ELISA) technique in the patients with idiopathic dilated cardiomyopathy to reveal the correlation with genotypes. Patients with ischemic cardiomyopathy or other secondary cardiomyopathies were excluded from this study. The allele frequency of TNFA2 in idiopathic dilated cardiomyopathy was significantly higher than that of the healthy group (13.5% and 3.0%, respectively, p=0.0084). There was no difference in the allele frequency of the IL-10 gene between the two groups. Polymorphism of the TNFA2 gene was not associated with the clinical course. Serum TNF-α levels were elevated in the patient group compared with the healthy group. There were no differences in serum TNF-α levels between the patients with TNFA1 and those with TNFA2. In conclusion, the TNFA2 allele may be linked to the pathogenesis of idiopathic dilated cardiomyopathy in Japanese patients. (Jpn Heart J 2000; 41: 183-191)

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Previous studies report a significant prophylactic effect on the occurrence of atrial fibrillation by simultaneous multi-site atrial pacing. We investigated the effects of multi-site sequential ventricular pacing (MSVP), which may be preferable to simultaneous multi-site pacing in terms of the prophylaxis of the occurrence of ventricular fibrillation (VF). Needle electrodes were inserted at ten different epicardial sites on both ventricles for MSVP in 12 adult beagle dogs. Four premature ventricular extrastimuli (PVE) were introduced to provoke VF reproducibly from a separate electrode in the left ventricle. The 4 PVE were applied to try to provoke VF during MSVP in a comparable fashion to the activation sequence during sinus rhythm. We compared the prophylactic effects of MSVP on the inducibility of VF by changing the number of stimulation sites to either 1, 3, 5, or 10 epicardial sites. We performed a total of 363 trials of induction and suppression of VF. The occurrence rates of VF by the 4 PVE for the various number of epicardial stimulation sites of MSVP, i.e., at 1, 3, 5, and 10 sites, were 0.8263, 0.4286, 0.4450, and 0.2857, respectively (p0.05). There was a significant prophylactic effect of MSVP on the inducibility of VF, and this effect became stronger as the number of MSVP sites was increased from 3 to 10. The hemodynamic state was relatively stable during MSVP. MSVP seems to be a promising method with which to reduce the occurrence of VF, and a larger number of stimulation sites would be more effective in terms of the prophylaxis of VF. (Jpn Heart J 2000; 41: 193-204)

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Early diagnosis and treatment of heart failure lead to improved survival; pre-clinical detection would thus be beneficial. A non-invasive biochemical testing method would indeed be ideal to screen for the condition. In the present study, we sought to determine whether circulating levels of B-type natriuretic peptide (BNP) correlate with cardiac function in asymptomatic subjects. 294 consenting asymptomatic subjects were examined. BNP levels in elevated patients (>>18.4 pg/ml) showed significant correlation with echocardiographic parameters of the systolic and diastolic functions (EF r=-0.51, FS r=-0.50, E/A r=0.42, p<0.01). Moderate correlation with the CTR on chest X-ray was also seen (r=0.23, p<0.01). Multiple regression analysis showed numerous echocardiographic and hemodynamic parameters including those of systolic and diastolic function in addition to left ventricular wall thickness, blood pressure and serum creatinine levels to be significantly associated with raised BNP levels. Elevated BNP levels reflect cardiac function (both systolic and diastolic) in the asymptomatic population. Detection of cardiac dysfunction by the non-invasive biochemical test may prove useful in early pre-clinical diagnosis of heart failure. (Jpn Heart J 2000; 41: 205-214)

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Ventricular tachycardia (VT) in coronary artery disease arises mostly from endocardial sites. However, little is known about the site of origin in other diseases. We report two patients who had VT originating from an anterior aspect of the left ventricle just below the mitral annulus, adjacent to the left ventricular outflow tract. The QRS configuration of VT showed an inferior axis and monophasic R waves in all the precordial leads. Radiofrequency current delivered to this site from the endocardial site successfully ablated the tachycardia in both. (Jpn Heart J 2000; 41: 215-225)

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We describe a patient with supraventricular tachycardia with triple atrioventricular (AV) node pathway physiology. A discontinuous curve was present in the antegrade AV nodal function curves. During right ventricular pacing, the earliest retrograde atrial activation was recorded at the left-sided coronary sinus electrode. The retrograde ventricular-atrial interval was long and had decremental conduction. We induced a slow-slow AV node reentrant tachycardia (AVNRT) with eccentric retrograde left-sided activation. After slow pathway ablation, dual AV nodal pathway physiology was present. AVNRT with eccentric retrograde left-sided activation is relatively rare, and our findings suggest that eccentric retrograde left-sided atrial inputs consist partially of a slow pathway and disappear with slow pathway ablation. (Jpn Heart J 2000; 41: 227-234)

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A 2-year-10-month-old boy was diagnosed with a complex congenital heart disease: right atrial isomerism, left superior vena cava (LSVC), complete atrioventricular septal defect, secundum type atrial septal defect, transposition of the great arteries with pulmonary atresia, patent ductus arteriosus, absence of a right superior vena cava (RSVC), and dextrocardia. He had received a left Blalock-Taussig (BT) shunt at the age of 3 months and a left bidirectional Glenn shunt one year after BT shunt. Progressive cyanosis was noted after the second operation and cardiac catheterization showed a functional Glenn shunt with an engorged azygos vein, which was inadvertently skipped for ligation. Because of the absence of RSVC, transcatheter occlusion of the azygos vein was performed successfully via direct puncture of the innominate vein. (Jpn Heart J 2000; 41: 235-238)

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Cardiac fibromas are rare lesions which occur more often in infants and children than in adults. These tumors are benign proliferations of connective tissue most often found in the left ventricular myocardium or septum. In an 8-month-old infant with cyanosis and progressive exertional dyspnea, a huge cardiac tumor obstructing the right ventricular outflow tract (RVOT) was diagnosed by means of 2-dimensional echocardiography and cardiac catheterization. At surgery, a whitish gray solitary tumor measuring 5.0×4.5 cm could be well visualized. It was nearly totally resected, and the RVOT was reconstructed with an Equine pericardial patch. Histologic examination classified the tumor as a fibroma. Although surgical mortality in cardiac fibroma with RVOT obstruction is extremely high, early diagnosis and prompt excision of the tumor is mandatory in relieving its dangerous symptoms. (Jpn Heart J 2000; 41: 239-243)

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