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We evaluated the efficacy of isosorbide dinitrate (ISDN) spray (E-1000) in exercise-induced anginal attacks in 20 patients with stable effort angina pectoris. E-1000 is a newly developed angina-relieving agent which contains 0.125 mg of ISDN in 1 spray and has a quick onset of action when applied to buccal mucosa by spraying. The patients were divided into two groups with different protocols. In protocol 1, the patientsunderwent treadmill exercise tests (Bruce protocol) and 1 or 2 sprays of E-1000 or a placebo were administered at moderate anginal pain, when the exercise was stopped after 1 min of cooling down, and pain-relieving time as well as 50% ST recovery time was measured in a single-blind cross-over manner. In protocol 2, the patients were administered 2 sprays of E-1000 or a placebo at the onset of chest pain and exercise was continued until it reached a moderate degree, and time from the onset of pain to the exercise end-point (onset-end point time), pain-relieving time, and ST recovery time were compared in a single-blind manner.In protocol 1, no significant differences in pain-relieving time nor in ST recovery time were observed. On the .other hand, in protocol 2, onset-end point time was longer (111.3±41.4 sec vs. 73.1±21.9 sec, P

Out of 330 patients with acute myocardial infarction (AMI) admitted to our institution, 256 patients entered our 3-week rehabilitation program and discharged from the hospital. Through the execution of the program, its feasibility and safety were examined, and guidelines for the progress of the program were re-evaluated. The state of outpatient community life and its determining factors were also investigated by a questionnaire. The following results were obtained: 1) Over 90% of patients with uncomplicated MI could complete the rehabilitation nearly on schedule, indicating the feasibility of the program. 2) Mortality after ambulation and serious complications related to rehabilitative activities were very few, indicating the safety of our rehabilitation program. 3) Among guidelines for the progression of the program generally accepted, the case for tan elevation of blood pressure as well as an ST depression was found to be especially important in order to prevent serious complications. 4) Age, discharge exercise capacity, left ventricular function and the severity of coronary disease were important factors influencing the patients' returning to work.

We attempted to differentiate between myocardial ischemia and left ventricular asynergy as the underlying mechanisms of exercise-induced ST-segment elevation in patients with previous myocardial infarction (MI). Sixty patients with previous anterior MI, who underwent stress myocardial scintigraphy (SMS) and coronary angiography (CAG), which revealed a single vessel disease of the left anterior descending artery, were entered in this study. SMS and CAG were performed within 3 months of MI onset, and SMS and ECG were quantitatively analyzed. T wave changes to a complete upright position with concomitant ST-segment elevation (T-dominant ST-elevation) was seen in 56% of the patients with post-MI angina pectoris (N = 16) and in 50% of those with significant redistribution in SMS (n = 20). On the other hand, ST-segment elevation without T wave reversion (ST-dominant ST-elevation) was seen in 43% of patients with severe LV asynergy (akinesis and dyskinesis, n = 39) and in 50% of those with severe scintigraphic defect in delayed images (relative thallium uptake less than or equal to 40%, n = 10). When these findings were combined, T-dominant ST-elevation had sensitivity and specificity of 54% and 78%, respectively, for the diagnosis of myocardial ischemia, while the corresponding values for ST-dominant ST-elevation were 44% and 100%, for the diagnosis of severe ventricular asynergy. We conclude that the two underlying mechanisms, ischemia and asynergy, may produce different changes in ST-T shape in patients with previous myocardial infarction.

心筋梗塞症患者の急性期管理におけるriskの判別を行ない,早期離床・早期退院の妥当性を検討した.対象は発症48時間以内に入院した急性心筋梗塞症患者222人である. riskとして心筋虚血,左室機能不全,心破裂を取り上げ,判別変数として病歴および発症4日以内の臨床所見など24変数を用いた.心筋虚血重症度の判別には4日以内の狭心発作,非貫壁性梗塞,梗塞既往,梗塞前狭心症が,左室機能不全重症度の判別には肺動脈楔入圧, 1回拍出量,房室ブロック, CPK最高値,梗塞既往が有意であり,判別は比較的良好であつたが,心破裂の予測は困難であつた.欧米の報告にみられる早過ぎる退院には問題点が示唆された.

To clarify the clinical and prognostic significance of silent myocardial ischemia (SMI) after acute myocardial infarction (MI), the clinical characteristics and long-term prognosis after discharge in 525 medically treated survivors after acute MI were investigated. According to the presence of post-infarction angina and results of all exercise tests during hospitalization, 309 patients without ischemic episodes were classified into control group, 59 patients with SMI into SMI group and 157 patients with post-infarction angina into AP group. Previous MI (29%, 24%, 11%, respectively), non-Q wave MI (34%, 34%, 15%) and multivessel disease (69%, 61%, 33%) were more frequent in the SMI and AP groups than in the control group. These indicated clinical characteristics in patients with SMI were similar to those in patients with angina pectoris. The incidence of angina prior to MI onset in patients with SMI was lower than in patients with post-infarction angina. This may suggest that there is some common mechanism keeping them silent in the pre- and post-MI period. During the mean follow-up period of 5.5 years, 93 patients died and 78 had a recurrent MI. Cumulative total and cardiac mortality, and incidence of recurrent MI by actuarial method were higher in the SMI as well as AP group than in the control group. There was no statistically significant difference in prognosis between SMI and AP group. We conclude total ischemic burden, not only symptomatic but SMI, should be treated using currently available therapeutic modalities for further improvement of long-term prognosis in survivors after acute MI.

We studied the clinical characteristics of 153 patients with angina pectoris associated with coronary artery spasm (CAS). The study was designed to investigate the relationship of CAS to ST segment deviation and to the site of fixed stenosis, and hemodynamic alteration during a spastic event. Analysis of coronary arteriograms and multilead electrocardiograms obtained simultaneously from 170 events of CAS by the use of radioluscent carbon-fiber electrodes resulted in 58 events with ST elevation which were related to total occlusion of major coronary arteries due to CAS; another 54 events with ST depression, in which the affected coronary arteries demonstrated severe but incomplete occlusion, or total occlusion but were visualized via collateral vessels; and remaining 58 events without ST deviation showing mild occlusion. The results indicate a close correlation between magnitude of CAS and ST segment deviation. CAS occurred at the site of pre-existing fixed stenosis including minor plaque defect in 133 patients and at apparently normal site in 20 patients. In the former group, only four patients had triple vessel disease, while 95 had nonsignificant fixed lesion. In the latter group, 10 patients had minor lesion distant from the site of CAS. Thus, CAS is closely related to fixed stenosis, which may have but a limited role as a cause of CAS. Hemodynamic measurements during spastic events were obtained from 49 patients including 41 events with spasm of the left anterior descending artery (LAD) and 21 events with spasm of the right coronary artery (RCA). The onset of an increase in left ventricular (LV) filling pressure and a reduction in LV dP/dt preceded ST segment deviation in all events. The first hemodynamic variable manifested in the spastic event was the reduction of LV contraction dP/dt in the majority of patients. The increase of LV filling pressure was greater in LAD spasm than RCA spasm (11 +/- 6 mmHg vs 7 +/- 4 mmHg, P less than 0.0125) and in events with ST elevation than with ST depression (11 +/- 5 mmHg vs 6 +/- 5 mmHg, p less than 0.001). Right ventricular functional impairment was mild in most patients during CAS. The study indicates that mechanical impairment precedes electrical impairment during CAS and that LAD spasm with ST elevation represents the most severe LV dysfunction.

The characteristics of 93 patients in whom electrocardiographic recordings were obtained within 12 hours of the onset of non-Q-wave myocardial infarction were studied. Patients were divided into the three groups according to what electrocardiographic changes were seen. Forty nine patients had ST segment depression, 35 had ST segment elevation, and nine had T wave changes. Patients with ST segment depression had a higher rate of pump failure and multivessel disease than the other two groups. There were no significant differences in peak serum creatine kinase activity among the three groups. Twelve of 13 patients who died of non-Q-wave myocardial infarction in hospital had ST segment depression. Furthermore nine of them had attacks of non-Q-wave myocardial infarction with severe ST segment depression in many leads. At necropsy five of six patients who had shown severe ST segment depressions in many leads at the onset of non-Q-wave myocardial infarction were found to have circumferential subendocardial lesions with triple vessel disease. This study suggests there are electrocardiographic subtypes of non-Q-wave myocardial infarction that are associated with specific patient characteristics.

To examine the alteration in control function of the heart, which may account for the pathophysiologic condition precipitating coronary arterial spasm, the dynamic property of heart rate response to exercise in vasospastic angina was evaluated by using our previously developed frequency analytic procedure. We studied 21 patients with vasospastic angina, divided into two groups (active angina and inactive angina) and 12 normal control subjects. When compared with the transfer function of the heart rate control system in normal control subjects, the transfer function in patients with active vasospastic angina showed moderately lower gain, especially in the middle frequency range, and significantly delayed phase angle over the whole frequency range, especially in the middle and high frequency ranges. These abnormalities were not observed in inactive vasospastic angina. The present exercise test to detect abnormal heart rate control can feasibly be used in the detection and management of vasospastic angina.

For an appraisal of effectiveness and limitation of the current coronary care unit (CCU) in treatment of patients with complications following acute myocardial infarction (MI), consecutive 557 patients hospitalized to our CCU during five years were studied. In order to assess the severity of complicating pump failure, patients were divided into four classes according to Killip's classification. Number of patients, total mortality (%) and mortality due to pump failure (%) were as follows; 333 (6%, 2%) in class I, 118 (17%, 8%) in class II, 42 (19%, 17%) in class III and 55 (84%, 80%) in class IV. Warning arrhythmias, cardiac rupture and interventricular septal perforation complicated in 184 patients, 11 and 10, respectively, and mortality due to these complications was 2%, 91% and 84% in the order. Right ventricular infarction complicated in 54 patients, but only one patient died from right heart failure. Post-MI angina manifested in 156 patients and six of them died postoperatively. Our data indicate that improvement in mortality due to pulmonary edema and arrhythmias and reduction in incidence of cardiac rupture are evident effectiveness of the CCU, and that there is no improvement in survival rate of patients with cardiogenic shock even under the use of newly introduced vasodilator and catecholamine therapy or intraaortic balloon pumping.

We studied 272 patients undergoing coronary artery bypass surgery (CABS) to clarify the long-term effects of CABS and to identify problems in long term management. Data on patients' pre and postoperative medical status were obtained from hospital files. A specially designed questionnaire was sent to all patients to assess residual angina, return to work, non-work physical activity and improvement in the quality of life after a mean follow-up of 29 months. Multivessel disease accounted for 89% of all patients and complete revascularization was achieved in 55%. A total of 131 events of complications associated with CABS occurred in 112 patients ; post-transfusion hepatitis was the most frequent complication (26%). Graft patency rate was 89% at the time of hospital discharge. Bypass grafts were patent in 95% of 243 grafts which were restudied at a mean period of 19 months after the first study. There was no significant difference in the patency rate between patients with well controlled, poorly controlled or discontinued anticoagulant therapy. Patients who were relieved from angina, returned to gainful work and had no limitation in non-work physical activity accounted for 74%, 79% and 73%, respectively. By subjective assessment, the quality of life improved in 76% of all patients. Objectively, contributing factors preventing improvement in the life quality were residual angina and post-transfusion hepatitis. There were 13 patients who were readmitted because of cardiac events. Three patients died from these events including two from sudden death during follow-up. We conclude that the beneficial effects of CABS are actually attainable. New approaches shoud be considered for increasing graft patency rate to an angina-producing artery and in preventing post-transfusion hepatitis. In this study, the benefits of the long-term use of anticoagulant therapy is questionable.

OBJECTIVES To determine the clinical features of a novel heart syndrome with transient left ventricular (LV) apical ballooning, but without coronary artery stenosis, that mimics acute myocardial infarction, we performed a multicenter retrospective enrollment study. BACKGROUND Only several case presentations have been reported with regard to this syndrome. METHODS We analyzed 88 patients (12 men and 76 women), aged 67 ± 13 years, who fulfilled the following criteria: 1) transient LV apical ballooning, 2) no significant angiographic stenosis, and 3) no known cardiomyopathies. RESULTS Thirty-eight (43%) patients had preceding aggravation of underlying disorders (cerebrovascular accident [n = 3], epilepsy [n = 3], exacerbated bronchial asthma [n = 3], acute abdomen [n = 7]) and noncardiac surgery or medical procedure (n = 11) at the onset. Twenty-four (27%) patients had emotional and physical problems (sudden accident [n = 2], death/funeral of a family member [n = 7], inexperience with exercise [n = 6], quarreling or excessive alcohol consumption [n = 5] and vigorous excitation [n = 4]). Chest symptoms (67%), electrocardiographic changes (ST elevation [90%], Q-wave formation [27%] and T-wave inversion [97%]) and elevated creatine kinase (56%) were found. After treatment of pulmonary edema (22%), cardiogenic shock (15%) and ventricular tachycardia/fibrillation (9%), 85 patients had class I New York Heart Association function on discharge. The LV ejection fraction improved from 41 ± 11% to 64 ± 10%. Transient intraventricular pressure gradient and provocative vasospasm were documented in 13/72 (18%) and 10/48 (21%) of the patients, respectively. During follow-up for 13 ± 14 months, two patients showed recurrence, and one died suddenly. CONCLUSIONS A novel cardiomyopathy with transient apical ballooning was reported. Emotional or physical stress might play a key role in this cardiomyopathy, but the precise etiologic basis still remains unclear.

SummaryBackgroundThe accuracy of two-dimensional transesophageal echocardiography (2D-TEE) for the measurement of aortic valve area (AVA) in patients with aortic stenosis (AS) depends upon the cross-section selected for imaging. Real-time three-dimensional transesophageal echocardiography (3D-TEE) may overcome this limitation of 2D-TEE. The goal of this study was to compare 3D-TEE with 2D-TEE for the measurement of AVA.Methods and resultsTwenty-five patients with AS underwent TEE. In 2D-TEE, the aortic valve image was obtained at the orifice level in the short-axis view, and AVA was measured by planimetry of the acquired images (2D-AVA). In 3D-TEE, 3D data containing the entire aortic valve were obtained. Then, a short-axis cross-section containing the smallest orifice in mid-systole was cut from the 3D data during image postprocessing, and the AVA was measured by planimetry (3D-AVA). The 3D-AVA was significantly smaller than the 2D-AVA (0.79±0.35cm2 vs. 0.93±0.40cm2, p

We examined the effects of administration of calcium antagonists on the heart rate response to treadmill exercise in 11 patients with vasospastic angina and 8 healthy young volunteers. The exercise test was performed by walking on a treadmill at a constant speed and grade according to a scheme of pseudo-randomized sequence for 19 min. The dynamic property of heart rate response to exercise was evaluated by using a frequency analytic procedure. The exercise test was also studied in 21 age-matched normal controls without drug administration. Administration of calcium antagonists revealed no significant effects on heart rate and blood pressure at rest in young healthy subjects or in patients with vasospastic angina. Young volunteers showed the same normal properties of heart rate response to exercise before and after calcium antagonists. Vasospastic angina showed abnormal heart rate response to exercise and revealed characteristically different transfer function from that in normal controls. These characteristics were not affected by treatment with calcium antagonists except for a slight, uniform decrease of gain of the system over the whole frequency range. Accordingly, the present exercise test can feasibly be used in the diagnosis and management of vasospastic angina even when calcium antagonists are administered to the patients.

We studied the effects of right ventricular ischemia on left ventricular three-dimensional geometry and the end-diastolic pressure-volume relationship in 16 open-chest dogs before and after pericardiectomy. Left ventricular volume was calculated from three internal dimensions measured with ultrasonic crystals. In one group of eight dogs, right coronary artery (RCA) occlusion for 2 min with the pericardium intact reduced aortic flow by 24 +/- 9% (p less than .001) and septal-lateral dimension by 8 +/- 5% (p less than .01), without changing anterior-posterior and apical-basal dimensions. However, parameters of left ventricular systolic function (aortic flow, left ventricular systolic pressure, peak dP/dt, and mean percent systolic shortening) were similar to those observed at a comparable level of left ventricular end-diastolic volume during inferior vena caval occlusion. In the other group of eight dogs, during RCA occlusion before pericardiectomy the left ventricular end-diastolic pressure-volume relationship determined during rapid blood transfusion shifted leftward and upward significantly from the preocclusion relationship. After pericardiectomy, RCA occlusion caused less significant changes in aortic flow and septal-lateral dimension as well as in the left ventricular end-diastolic pressure-volume relationship. We concluded that right ventricular ischemia causes a leftward shift of the interventricular septum in end-diastole and an alteration of the left ventricular end-diastolic pressure-volume relationship without changing left ventricular myocardial performance. These changes are enhanced by the intact pericardium.

From among 899 consecutive patients who underwent their first coronary arteriography, we selected 147 pts with vasospastic angina (VA) and 356 pts with classic angina (CA) and divided them into three different age groups: −49 years old, 50 to 59, and 60−. In these 899 pts, incidences of VA showed no increase with aging. Prevalence of coronary risk factors in CA, such as diabetes, hypercholesterolemia, hypertension, and obesity, was higher than in VA, although prevalence of smoking in CA was lower than in VA. In VA, we found an age-related increase in the incidence of smoking only, in contrast to the other four risk factors. The VA showed no age-related increase in the incidence of complication of fixed coronary stenosis. These findings suggest that aging and atherosclerosis might not play a major role in pathogenesis of VA, although the mere presence of atherosclerosis irrespective of its severity could interact with local susceptibility to spasm, leading to coronary vasospasm.

Elaminらの提唱したST/HR slopeを標準多段階運動負荷試験に応用し,冠動脈疾患(CAD)の有無とその重症度診断における有用性を他の診断基準と比較検討した.さらにこれを改良した修正ST/HR score (MSHS)を考案し,その診断的価値を検討した.冠動脈造影施行79例で,運動負荷時のaVFとV5誘導のST indexとST/HR slopeを算出した. CAD患者の診断率は,通常のST判定基準とST indexでは57%と71%であり, ST/HR slopeでも72%であった. ST/HR slopeでのみCAD中の3枝病変の診断が可能であった. MSHSではCAD診断率は96%と良好で, CAD重症度判定も可能であった. ST/HR slopeは3枝病変の診断に,それを改良したMSHSはCADの有無と重症度診断に有用であると思われた.

The factors associated with the development of pump failure in patients with acute myocardial infarction (MI) were studied in 475 patients admitted to our coronary care unit (CCU) and a clinical and hemodynamic re-evaluation of vasodilator and catecholamine therapy was carried out in patients with pump failure. The severity of pump failure as represented by Killip's classification was closely related to left ventricular (LV) dysfunction as judged by LV ejection fraction, number of previous MIs and peak creatinine phosphokinase (CPK) value, and the severity of coronary atherosclerotic lesions as assessed by coronary arteriography. Retrospective hemodynamic analysis of vasodilator therapy (intravenous nitroglycerin, nitroprusside and phentolamine) in 94 patients with pump failure revealed that a significant decrease in pulmonary capillary wedge pressure (PCW) with no significant change in cardiac index (CI) resulted in a clinical improvement in pulmonary congestion in Forrester's hemodynamic subset 2. However, in patients in subsets 3 and 4, the slight increase in CI induced by vasodilator therapy was not enough to restore normal systemic perfusion in spite of a significant decrease in PCW and total systemic resistance; catecholamine was far more effective in increasing CI. Thus, the major indication for vasodilator therapy is in patients of subset 2, while combined use with catecholamine is preferable in those with low cardiac output.

Long-term prognosis of hospital survivors with myocardial infarction (MI) was investigated to assess the validity of previous reports on the low incidence of ischemic heart disease in Japan. Among 686 patients with acute MI, 115 (16.8%) died during hospitalization and eight were lost to follow-up. The cumulative mortality rate of the 563 hospital survivors was 6.2% in the first year, 12.0% in the third year, and 19.1% in the fifth year, with cardiac death accounting for 63% of the deaths. Cumulative rates for recurrent MI were 4.4% in the first year, 11.0% in the third year, and 13.2% in the fifth year. Parameters influencing long-term mortality rates obtained by stepwise discriminant analysis were arteriosclerosis-related factors, presence of congestive heart failure at admission, age, and presence of previous MI, while parameters influencing the recurrence of MI were congestive heart failure, arteriosclerosis-related factors, and ischemic findings at discharge. Our findings indicate that the prognosis for patients with MI is far better in Japan than in Western countries and support the previous reports on the low incidence of ischemic heart disease in Japan, while factors influencing the prognosis are similar to those previously reported.

Rifampicin, an antituberculosis agent, is known to be a potent inducer of microsomal drug-metabolizing enzymes in the liver. Elimination or clearance of many drugs has been reported to be enhanced, and their effectiveness reduced; however, no report in the literature has dealt with the interaction between rifampicin and dihydropiridine calcium entry-blocking drugs such as nifedipine. We present here evidence for the possible interaction between rifampicin and nifedipine in a patient with angina pectoris, which was exacerbated during coadministration or rechallenge with rifampicin. The peak plasma level and area under the curve were reduced and the apparent oral clearance of nifedipine was increased by rifampicin, suggesting that rifampicin enhanced the elimination of nifedipine via induction of a hepatic microsomal drug-metabolizing enzyme, as has been reported on other drugs widely metabolized in the liver.

Consecutive 200 patients with angina pectoris (AP) and 310 with acute myocardial infarction (AMI) were studied in order to elucidate the significance of symptoms and treatment of AP associated with AMI, and to evaluate the classification of unstable angina (UA) according to the American Heart Association (AHA). The AMI group consisted of 110 patients without preinfarction AP, 99 with UA and 101 with AP who did not meet the criteria of UA and were designated as non-UA (NUA) in this study, while the AP group consisted of 65 with UA and 135 with NUA. Among 19 patients who developed AMI during their hospitalization, 12 were UNA. Patients with NUA of both groups revealed various modes of anginal attacks. Eighteen patients of the AMI group and 29 of the AP group were considered to be clinically stable and the others were unstable. Treatment of the AP group resulted in an improvement of AP in 191 patients, while in the AMI group AP was not treated in 93 and improved in 23. The participation of fixed stenosis and/or spasm of coronary arteries was examined in the AP group. There was no difference in the participation of these factors as a causative mechanism for anginal attack between UA and NUA. In conclusion, it is not pertinent to dispute that UA of the AHA is the only high risk AP for developing AMI, but for the prevention of AMI it is important to treat AP by the precise evaluation of its symptoms and by the determination of the participation of fixed stenosis or spasm of coronary arteries in each case.

In order to discuss the mechanism of onset in myocardial infarction (MI), clinical cases were reviewed and various clinical findings were analyzed according to the premise that the onset of MI requires both a predisposition and a trigger. The majority of subjects did present conditions that constituted predispositions for MI, including a history of angina pectoris (especially unstable angina), poor therapeutic results for angina pectoris, organic stenosis of the coronary artery, life changes, and overwork. Patients with multiple factors tended to develop MI without a definite trigger, i.e., onset during sleep or rest whereas, in patients with fewer predisposing factors, it was obvious effort, excitation or stress that triggered MI. However, not a few of the patients presented with no organic stenosis of the coronary artery or no history of angina pectoris. There were patients without ST segment elevation at onset of MI, and patients in whom ST elevation was recorded after onset. These findings suggest the existence of mechanisms other than coronary occlusion in onset of MI. Occlusion of the coronary artery distributed to the infarct region occurred frequently among patients with delayed CPK efflux as well as prolonged chest pain and ST segment elevation. These lines of evidence suggest extension of infarction due to secondary coronary occlusion.

The clinical spectrum and outcome of 119 patients with acute non-Q wave myocardial infarction (NQMI) were studied, in comparison with those of 354 patients with acute Q wave myocardial infarction (QMI). The patients with NQMI had a significantly higher incidence of preinfarction angina (73% vs 63%), previous myocardial infarction (43% vs 22%), multivessel disease (73% vs 51%), postinfarction angina (55% vs 21%), and recurrent myocardial infarction during follow-up for an average of 25 months (17% vs 8%). NQMI patients also had a lower rate of complication of pump fallure and smaller infarct size estimated by peak creatine phosphokinase (CPK) levels (1361 ± 1243 vs 2711 ± 1684 IU/L) than those with QMI. There was no difference in in-hospital mortality between the two groups (17% vs 17%). However, death due to cardiac rupture was exclusively noted in the QMI group. The present study suggests that NQMI is more unstable than QMI in the clinical course.