In 18 patients with dilated cardiomyopathy (DCM), the effects of a new cardiotonic agent, TA-064, given in both consecutive and intermittent (3 days on, 11 days off) oral doses were studied for 3 months by echocardiography and endomyocardial biopsy. After 3 months of consecutive administration. 11 patients (61%) had improved symptomatically and the %US increased (p< 0.001) and LVDd decreased (p<0.05), but the other 7 patients had not improved. At the pretreatment state these 7 patients in whom Ta-064 was not effective had smaller %US (p<0.01) and larger LVDd (p<0.05) than the 11 patients in whom the drug was effective. The non-effective group also had more severe myocardial fibrosis (p<0.05) and cellular hypertrophy (p<0.01) than the effective group. After 3 months of intermittent administration in 10 patients in whom consecutive administration had been proved effective, 7 patients sustained symptomatic improvement and increased %US (p<0.01), but the other 3 patients did not sustain the improvement. The latter group had smaller %US, larger LVDd and more severe myocardial fibrosis than the former group at the pretreatment state. These results indicate that the effects of TA-064 are dependent on the severity of basal cardiac function and myocardial damage, and that in patients with milder DCM, the effects can be sustained by intermittent administration.

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Westudiedthemetabolicandcardiacresponsestoexercisebyexpiratorygasanalysisin40patientswitholdmyocardialinfarctionand33normalsedentarymales.Onthebasisofexerciseenergymetabolism, theelevationoftherespiratoryquotient(RQ;RQ=VCO2/VO2)duringexerciseiscausedbytheincreaseofbloodlactateduetotheaugmentedanaerobicmetabolism.Functionalaerobicimpairment(FAI)inourstudywassignificantlyadvancedinthecontrolgroupandtheNYHAfunctionalclassI, classIIandclassIIIgroups, thatis, 2.3±11.2%, +14.8±10.4%, +27.8±13.8%and+49.4±2.8%respectively.TheRQvaluesweresimilaramongallgroups;0.29±0.09respectively.Functionalchronotropicimpairment(FCI)forthesamegroupswas0.9±7.0%, +1.4±6.1%, +3.8±4.8%and+8.7±6.0%, andthatoftheclassIIIgroupwassignificantlylargerthanthatofthecontrolgroup.Thus, intheclassIIIcongestiveheartfailuregroup, thechronotropicresponsetothemetabolicrequirementwasimpairedincomparisontothecontrolgroup.ItwasconcludedthatthereducedchronotropicreservewaspresentinNYHAclassIIIpatientswitholdmyocardialinfarction, andthatthismechanismmightcontributetoadecreaseinthepumpreserveoftheheart, resultinginfurtherimpairmentofphysicalcapacityinthesepatients.

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In this study ECG changes were analyzed to assess the acute effects of ante-grade blood flow on the ECG in patients with AMI. The study population consisted of 22 patients with MI in whom the totally occluded left anterior descending artery (LAD) or right coronary artery (RCA) was recanalized by intracoronary urokinase infusion (recanalized group) and 14 patients in whom the occluded coronary artery was not successfully recanalized (control group). No significant difference was found in the sum of ST segment elevation(V2-V4 leads for the LAD-occluded group, II, III, and aVF leads for the RCA-occluded group) before urokinase infusion. In the recanalized group ΣST abruptly increased at 5 min after recanalization i 13 of 16 LAD-occluded patients from 1.49±0.89 mV to 2.44±1.67 mV (p<0.005), and in 4 of 6 RCA-occluded patients from 0.66±0.12 mV to 1.42±0.52 mV (p<0.01). However increased ΣST in the recanalized group was reduced to the control value existing before recanalization within 30 min after recanalization and continued to decline more rapidly than in the control group. These transient ST segment elevations were not correlated with long-term angiographic determinants of left ventricular function. We conclude that ST segment shows abrupt augmentation after successful thrombolysis and that continuous ST segment monitoring is useful for assessing thrombolysis in AMI.

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From July 1978 to June 1984, 540 St. Jude Medical valve prostheses were implanted in 462 adult patients. Overall operative mortality was 4.8% (22/462): 5.7% after aortic valve replacement (AVR) (8/140); 3.3% after mitral valve replacement (MVR) (8/244); and 7.7% after aortic and mitral valve replacement (DVR) (6/78). There were 16 late deaths among 440 operative survivors: six (38%) were valve related. The actuarial survival rate at six years was 94.5% in AVR and 93.5% in MVR. At five years it was 91.6% in DVR. The freedom from valve-related death at six years after AVR, MVR and at five years after DVR was 97.8%, 98.6% and 95.8%, respectively. The incidence of valve-related complications (expressed as %/patient-year (number of events)) was as follows: thrombo-embolism (AVR 0.7 (2), MVR 2.0(13), DVR 2.8 (5)), valve thrombosis (AVR 0.3 (1), MVR 0.2 (1), DVR 0 (0)), prosthetic valve endocarditis (AVR 0.3 (1), MVR or DVR 0 (0)). There were no cases of primary structural failure, serious anticoagulant-related hemorrhage or clinical event of hemolysis. The incidence of all valve-related complications in AVR, MVR and DVR was 1.3, 2.2 and 2.8%/pt-yr, respectively. The freedom from thrombo-embolism at six years after AVR and MVR and at five years after DVR were 91.4%, 92.4% and 88.7% respectively. Re-operation was performed in only one patient with MAR because of valve thrombosis (0.2%/pt-yr after MAR, overall 0.1%/pt-yr). These results indicate that St. Jude Medical prosthesis has provided a satisfactory performance with acceptable risks of late complications in patients who were properly anticoagulated during six-year follow-up period.

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To investigate the electrocardiographic abnormalities of left ventricular hypertrophy (LVH), body surface potential maps were acquired from 42 patients with essential hypertension. We adopted the time integral technique for analyzing body surface mapping data and used echocardiographic left ventricular muscle mass (LV mass) as the index of advance of LVH. The QRS, STAT and QRST isointegral maps in normal volunteers all demonstrated smooth bipolar surface distribution patterns, with positive values located over the precordium and negative values over the right upper chest and back. In patients with essential hypertension, changes in the isointegral maps were observed as LVH advanced; A^^- QRS increased on the upper left lateral chest and decreased (became more negative) on the right chest, A^^- STAT decreased on the lower left lateral chest and increased on the right upper chest, and areas of significant difference in A^^- QRS and A^^- STAT were expanded as LVH advanced. A^^- QRST decreased on the lower left lateral chest and increased on the right upper chest only in patients with severe LVH. We conclude that the changes of QRS and STAT isointegral maps depend on the degree of advance of LVH and the severe grade of LVH causes the alterations in intrinsic repolarization properties.

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Graphical analysis of the effects of serotonin on cardiac function and pulmonary circulation was performed, using the dog heart-lung preparation. The equilibrium points, at which the cardiac output (CO)-curve and venous return (VR)-curve cross in the right atrial pressure (RAP) or left atrial pressure (LAP)-CO relations, were directly recorded on two X-Y recorders. CO- and VR-curves were directly depicted by changing the blood level in the reservoir, and by inducing ventricular fibrillation and simultaneously occluding pulmonary arterial trunk, respectively. Single injections of serotonin, 300μg, into the right or left atrium, induced a negative inotropic response. Low rate (<30μg/min) of infusion of serotonin had no effect on the CO-curve or on the slope-gradient of VR-curve in the LAP-CO relation. At a rate of 60 or 120 μg/min, however, the CO-curve was moved downwards to the right, indicating a negative inotropic effect. Pulmonary mean filling pressure increased and the slope-^gradient of pulmonary VR-curve decreased, indicating an increased resistance to venous return from the pulmonary circulation. Pulmonary arterial pressure was markedly elevated. In order to obtain the capacitance ratio between the extracorporeal circuit and the pulmonary circulation, a shift of blood volume to the pulmonary circulation was induced by elevating the aortic pressure, which also decreased the slope-gradient. The calculated capacitance ratio became greater during the infusion of serotonin, indicating that the capacitance in the pulmonary circulation was lowered. It is likely that serotonin has contractile effects on the pulmonary arterial and venous vascular beds, elevating the pulmonary filling pressure and resistance to venous return.

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In Japan, the age-adjusted death rate from ischemic heart disease has decreased for both male and female since 1970, although the rate appears to be slightly affected by mortality from senility without mention of psychosis, "cardiac insufficiency", and sudden death in elderly persons. On the other hand, consultation rate has shown an increase, suggesting an increase in the number of recovered patients and a lengthening in the duration of ischemic heart disease from onset to termination by CCU treatment. A 7.5-year prospective study of ischemic heart disease (myocardial) infarction +angina pectoris on effort + sudden death) among residents 40 years and older was conducted at a rural community, Akadani-Ijimino district in Niigata Prefecture. Statistically significant risk factors appeared to be age, hypertension, ECG abnormalities and fuduscopic changes. Even in 1977-1984 when Japanese dietary habits were westernized, neither hyperlipidemia nor obesity was related to the development of ischemic heart disease in this agricultural district. Statistically significant risk ratios were not observed for any nutrient or food, although the ratio for animal fat, calcium, salted vegetables and caloric percent of animal protein was more than one respectively.

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To elucidate recent trends in the mortality and morbidity of myocardial infarction (MI), we investigated death certificates and changes in the survival rate of MI patients at coronary care units (CCUs), which may affect the death rates. (1) for all cases of MI, acute heart failure (AH), heart failure (HF) as underlying cause, and hypertension as underlying cause with HO or AH (categorized as hypertensive heart disease) on death certificates in two rural and two urban populations between 1981 and 1984, medical records were reviewed and case histories obtained from interviews with patients' families to validate the diagnosis. The number of MI deaths on the death certificates was not underestimated bacause some MI deaths were misdiagnosed as AHF, HF and hypertensive heart disease and some MI death certificates wee misdiagnosed. (2) Survival of MI patients at CCUs improved in several major cities, Tokyo, Osaka, Wakayama and Asahikawa between 1978 and 1984; a total of 4318 MI deaths were estimated to be averted by CCUs in 1984 compared with the number of deaths in 1978. Therefore, improvement of MI cases at CCUs may be one of the factors attenuating the rise in death rates in all of Japan.

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Changes in the incidence of coronary heart disease (CHD) in the past 20 years have been observed in workers in the city and residents in rural areas and the risk factors of CHD studied. Findings show that the incidence of CHD in the residents in rural areas has hardly changed, and remains still low. However, the incidence of CHD in workers in the city has recently shown a tendency to increase. Furthermore, a study of CHD risk factors shows that in the rural areas residents hypertension has a strong influence on the incidence of CHD, while the role of serum total cholesterol is weak. In the city workers a high serum total cholesterol has become a risk factor. Therefore, it appears that the incidence of CHD caused by hypertension and by hypercholesterolemia are mixed in Japan. At present it appears that the influence of hypertension is becoming weaker, while the influence of hypercholesterolemia is becoming stronger. The resulting balance between them may be expressed as a rise and fall of CHD in Japan at present.

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Shiritus Asahikawa Hospital received a total of 922 patients with acute myocardial infarction (AMI) from 1961 through 1985. the numbers of AMI patients and deaths during 1981-1985 were 2.8 times and 2.3 times, respectively, those observed during 1971-1975. However, decreasing trends were noted in the overall and age-adjusted mortality due to ischemic heart disease (IHD) per population of 100, 000 Asahikawa residents between 1975 and 1984, suggesting a discrepancy between our CCU data and the city's records. We investigated the prehospital condition, out-of-hospital cardiac arrest, and the mechanism of early deaths in patients hospitalized with AMI. It was found that the increase of AMI patients admitted to our hospital was due to an increase in the hospitalization rate of AMI patients and the establishment of the coronary care unit (CCU) which allowed the admittance of patients who might have been declared dead out-of-hospital in the past. On the other hand, the declining trends in IHD mortality in the entire city of Asahikawa were attributable to reductions in the in-hospital and out-of-hospital fatality rates of patients with AMI, to improved hospital fatality rates of patients with AMI, and to improved survival rates in AMI patients who developed ventricular fibrillation (Vf) or who experienced out-of-hospital cardiac arrest episode. In order to further decrease the case-fatality rate of patients with AMI, it is essential to continuously educate residents on emergency treatment to be given at the onset of AMI.

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Three hundred and eighty-six patients with acute myocardial infarction in the past 11 years between 1975 and 1985 were investigated retrospectively to clarify fatality, cause of death and long-term prognosis in relation to their risk factors and age. The average number of patients admitted in each year was 24.4 for the first 5 years and 44.0 cases per year in the last 5 years. the fatality decreased from 20.3% in the first 5 years to 15.7% in the last 5 years. A major cause of hospital death was cardiogenic shock and congestive heart failure. One hundred and thirty-six patients had coronary arteriography within 2 months after admission. They were divided into three groups; the young (&les;40 years old)- middle (41-50 year old)-, and old (&ges;51-year old)-aged groups. Among the young-aged group, serum cholesterol levels at admission were significantly higher in patients with multi-vessel lesions than those in patients without multi-vessel lesions, while there were many heavy smokers who did not show a significant lesions of the coronary artery. These observations suggest that hypercholesterolemia may act as an important risk factor for coronary arteriosclerosis in young patients, and also that a heavy smoking may promote an initiation of myocardial infarction in young patients without severe coronary artery stenosis. The cumulative 5 and 10 year survival rate for all groups was 84% and 61% respectively. Fifty-seven patients had reinfarctions, and thirty patients died. The survivors were younger and had a good tolerance to treadmill exercise test at discharge.

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To clarify the current status of prehospital care of patients with acute myocardial infarction (AMI) in the Tokyo metropolitan area, the availability of the coronary care unit (CCU) network during the past 3 years (January 1982 through December 1984) was analyzed, examining: 1) final diagnosis, 2) circumstances at the onset of AMI<3) course of transportation to CCU, 4) time elapsed before admission, 5) severity of AMI, and 6) prognosis of patients. Of 6, 939 patients admitted to CCU by means of the CCU network, 2, 408 patients (34.7%) had AMI. The patient's decision time was, on the average, 12 hr 3 min, longer when the course of transportation to CCU was more complicated. The fatality for AMI was 17.2%. Causes of death were pump failure in 52.8%, arrhythmias in 62.8% and mechanical failure such as cardiac repture in 8.5%. Patients with complicated AMI were admitted earlier and had a higher fatality than those without complications. Thus, 1) Community oriented programs are required to more fully inform the population at risk of AMI to shorten the patient's decision time, and 2) more effective means to treat patients with pump failure and to prevent the development of pump failure nead to be established.

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In order to investigate the immediate and long-term prognoses of acute myocardial infarction, we followed up 790 consecutive patients who were admitted to the Sakurabashi Watanabe Hospital within 24 hours after the onset of infarction from January 1975 to December 1984 and evaluated early mortality, cumulative survival rate after discharge, cause of death and occurrence of recurrent myocardial infarction during follow-up. Early mortality (within 30 days after the onset) in all patients was 17.6% and declined serially in the most recent five years. Pump failure was the most common cause of death, followed by cardiac rupture and arrhythmias. Age, gender (female), presence of a previous infarct and anterior infarction were important contributing factors to the immediate prognosis. One hundred and thirty-five of the 651 patients who survived one month after the onset of infarct died during the follow-up period (mean follow-up interval: 41.0±29.9 (SD) months). cumulative survival rates calculated by the life-table method at one and 5 years after the onset were 91.0% and 76.0%, respectively, and the average annual mortality in the first 5 years was 4.8%. Age and reinfarction were the important determining factors of long-term prognosis. Recurrent myocardial infarction, pump failure and sudden caridac death were common causes of late death. One hundred and two reinfarctions in 93 patients occurred during the follow-up period. Thirty-two of 93 patients (34.4%) died due to fatal reinfarction. These results indicate that the immediate prognosis of acute myocardial infarction has improved serially, but the long-term prognosis is still poor. Thus, it is necessary to follow up a patient with acute myocardial infarction cerefully and to prevent recurrent myocardial infarction during the post-hospital period.

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To clarify the patho-etiologic factors of Japanese myocardial infarction, a comparative pathological study of myocardial infarction in the Osaka, Akita, Wakayama, and Hokkaido districts, and an extensive histopathological study of 94 autopsy cases with acute myocardial infarct (AMI) in less than 4 weeks at Osaka were carried out. Although AMI in Akita was highly complicated by hypertension. AMI in Osaka was associated with a history of diabetes mellitus and hypercholesterolemia, especially in the young generation (under 59 years of age); hypercholesterolemia was related to the occurrence of AMI. Moreover, in spite of increases in transmural myocardial infarct (TMI) in Osaka, Hokkaido and Wakayama, Akita showed an equal ratio of TMI and subendcardial myocardial infarct. In AMI in Osaka, significant stenosis (more than 75% stenosis) of the coronary artery was of the same grade between the proximal and distal portions in the epicardial coronary artery. AMI in Akita, however, showed more severe stenosis in the proximal than the distal portion. A high incidence (88.3%) of thrombosis formation corresponding to the site of infarction was observed in AMI in Osaka. Moreover, ruptured atheromatous plaques were identified as being responsible for 62.6% of the coronary thrombosis cases, and a high incidence (70.9%) of foamy cell infiltration was disclosed. Thus, it can be concluded that ruptured atheromatous plaque is a ;major factor in the progression of coronary atherosclerosis and/or thrombosis, which might be due to the process of plaque softening.

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