Neurohormonal activation is present and neurohormonal responses to dynamic exercise are altered in patients with congestive heart failure (CHF). The aim of this study was to determine if the responses of atrial natriuretic peptide (ANP) normalized for peak oxygen consumption (peak VO₂) to exercise are augmented in patients with CHF. Ventilatory and ANP responses were assessed in 28 patients with CHF (NYHA classes II: 16, III: 12), 17 patients in NYHA class I, and 14 normal subjects during symptom-limited cardiopulmonary exercise testing. Plasma ANP was measured at rest and immediately after peak exercise. The increase in ANP was divided by peak VO₂ and this ratio [ANP-Exercise Ratio: (peak ANP-rest ANP)/peak VO₂] was compared among the 3 groups. Peak VO₂ (Normal, NYHA I, CHF: 29.9±1.7, 24.0±1.3, 17.4 ±0.8 ml/min per kg), anaerobic threshold and peak work rate were lower in patients with CHF. The resting ANP level was significantly higher in patients with CHF (Normal, NYHA I, CHF: 35.4±4.6, 42.9±5.8, 80.8±12.9 pg/ml). The ANP level increased during exercise in all 3 groups, and patients with CHF had a significantly higher ANP level than normal subjects and NYHA class I patients (Normal, NYHA I, CHF: 65.3±10.7, 75.9±14.4, 141.6±20.1 pg/ml). The ANP-Exercise Ratio in patients with CHF was significantly higher than those in normal subjects and NYHA class I patients (Normal, NYHA I, CHF: 0.96±0.26, 1.32±0.38, 3.59 ±0.72). These data suggest that patients with CHF but not those in NYHA class I have an augmented ANP response, as reflected by both absolute ANP levels and by the exercis, ratio, which was normalized by the peak exercise level. (Jpn Circ J 1996; 60: 909 - 916)

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In patients with hypertrophic cardiomyopathy (HCM), we conducted cine magnetic resonance imaging (MRI) studies in which our objectives were to quantify the regional early diastolic function of the left ventricle and to evaluate the relationship between regional diastolic function and hypertrophy. Short-axis images of the left ventricle were recorded by cine MRI in 8 control patients and 24 patients with HCM. The images were then divided into 10 blocks to evaluate regional early diastolic function. The regional wall-thickness-time curve, the radius-time curve, and their first-derivative curves were computed for each of the 10 blocks. There was no difference between the time-to-peak-radius-increasing ratio and the time-to-peak-wall-thickness-thinning ratio in the 10 blocks in the control patients. These 2 parameters in the patients with HCM were significantly longer than those in the control patients. There was also a significant linear correlation between the time-to-peak-wall-thickness-thinning ratio and regional wall thickness. Cine MRI was useful for evaluating regional early diastolic function, which is apparently related to regional hypertrophy, in patients with HCM. (Jpn Circ J 1996; 60: 917 - 924)

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We investigated the characteristics of decreased heart rate variability (HRV) in diabetic patients with ischemic heart disease (IHD). Twenty-one healthy control subjects, 17 diabetic patients without IHD, and 33 diabetic patients with IHD were studied. The diabetic patients with IHD were subdivided into 2 groups according to the severity of their IHD: severe or mild. HRV was evaluated in all subjects using the spectral variables of the all-frequency, Iow-requency, high-frequency (AF, LF, HF) components and the LF/HF ratio were determined from Holter recordings. The AF and LF components in patients with diabetes only or diabetes and severe IHD were significantly lower than in control group, but the HF component was significantly lower only in the group of patients with diabetes and severe IHD. The LF/HF ratio did not differ significantly among the 4 groups, but was the lowest in diabetic patients without IHD. Patients with diabetes and mild IHD showed a slight decrease in HRV, but this was not significant. With regard to the circadian rhythm of HRV, the AF and LF components in patients with diabetes-only or diabetes and severe IHD were significantly decreased and showed the same pattern throughout the day. However, the HF component was decreased during more time zones in patients with diabetes and severe IHD, whereas the LF/HF ratio was lower during more time zones in the diabetes-only group. All spectral variables showed a tendency to be inversely related to the duration of diabetes in all diabetic patients. In particular, the LF/HF ratio showed a significant negative correlation. The HRV of diabetic patients was characterized by a decreased LF/HF ratio. It was concluded that, although HRV in diabetic patients with severe IHD was reduced mainly as a result of diabetic neuropathy, this was also partly due to a decline in parasympathetic tone as a result of myocardial injury. (Jpn Circ J 1996; 60: 925 - 932)

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To determine whether a relationship exists between bronchial hyperreactivity and cardiac asthma, which is commonly observed in patients with left heart failure, a methacholine inhalation test was performed in 15 patients with stable left ventricular failure (LVF) and 10 normal subjects. The subjects were divided into 3 groups based on symptoms of nocturnal coughing and/or wheezing in acute exacerbation of LVF. Group A consisted of 8 patients with nocturnal coughing and/or wheezing, Group B consisted of 7 patients without such symptoms, and Group C consisted of the 10 age-matched normal controls. Eleven of the 15 patients with LVF showed a significant increase in respiratory resistance in the methacholine inhalation test, as opposed to none of the normal subjects. The median cumulative dose which produced a 35% decrease in respiratory conductance (PD₃₅Grs) was significantly lower in Group A than in Group B (1.45 log units and 1.90 log units, respectively, p<0 05). The results of pulmonary function tests were not significantly different between Groups A and B. The minimum cumulative dose required to initiate a decrease in respiratory conductance from the baseline, as an index of bronchial sensitivity to methacho-line, was significantly correlated with DLCO/VA (r=0.710, p<0.01). We conclude that bronchial hyperreactivity is responsible for cardiac asthma and that it might be related to pulmonary interstitial changes in stable patients with non-valvular LVF. (Jpn Circ J 1996; 60: 933 - 939)

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We studied the short- and long-term outcomes of 97 patients treated with percutaneous transluminal coronary angioplasty (PTCA) and 72 patients treated with coronary artery bypass graft surgery (CABG) for multivessel coronary artery disease in a single hospital in 1989. Patients treated with CABG had a higher angina class, a higher incidence of diabetes mellitus and a greater extent of the disease. Complete revascularization was achieved in 61 patients (85%) with CABG and in 45 patients (46%) with PTCA (p<0.001). Initial success of PTCA and CABG was obtained in 95% and 94% of the patients with PTCA and CABG, respectively. Actuarial survival rates at 5 years were similar (96% in the PTCA group; 94% in the CABG group). Fewer patients suffered from cardiac death or myocardial infarction in the CABG group than in the PTCA group, but this difference was not significant. The rate of survival free from death, myocardial infarction, CABG and repeat PTCA, was significantly higher in the CABG group than in the PTCA group (85% vs 48%; p<0.001). These results suggest that CABG provides a favorable long-term outcome in patients with multivessel coronary artery disease and that PTCA provides a similar out-come in these patients when applied to suitable lesions, although more patients who undergo PTCA require repeat procedures. (Jpn Circ J 1996; 60: 940 - 946)

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To investigate triggers for the occurrence of acute myocardial infarction (AMI) and sudden cardiac death (SCD), we examined the activities immediately before the time of onset in 149 cases of non-fatal AMI and 110 cases of SCD. All of the cases in which death occurred within 24 h from the onset of the underlying cause were considered SCD as long as the cause of death was of cardiac origin or unknown. We calculated the average time which is spent on each activity in the life cycle of Japanese people and estimated the number of incidence of each activity assuming a uniform distribution. Estimated values and actual values were compared. The results were as follows: 1) The incidence of non-fatal AMI and SCD was low while sleeping or resting or doing light work, and was high while using the toilet or doing sport or heavy work. 2) The incidence of SCD was also high even during moderate exertion, such as taking a bath or, walking or cycling, and it was significantly higher than that in the group of non-fatal AMI. 3) The incidence of non-fatal AMI was high while eating or drinking. 4) Many of the patients with SCD had past histories of circulatory diseases, compared to those with non-fatal AMI. This difference in past histories may account for the high incidence of SCD during moderate exertion. (Jpn Circ J 1996; 60: 947-953)

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We compared the effectiveness and practicability of dobutamine stress echocardiography (DSE) and treadmill exercise electrocardiographic testing (TMT) for detecting coronary artery disease. Ninety-six patients (mean age 58.8±9.0 years) who presented for coronary angiography underwent both DSE and symptom-limited TMT. Two-dimensional echocardiography was performed to detect ischemia-induced wall motion abnormalities during incremental dobutamine infusion (5-40 μg/kg per min administered in 5 min steps). The sensitivity of detecting ischemia was 63% for TMT and 79% for DSE (p<0.05); the specificity was 61% for TMT and 88% for DSE (p<0.05). The accuracy of TMT was 63% and of DSE 82% (p<0.01). In patients in whom both tests gave true-positive results, the maximum ST depression was evaluated during DSE and TMT (n=31). The ST segment depressions detected by DSE were significantly smaller than those detected by TMT (0.04±0.04 mV vs 0.17±0.07 mV, p<0.01), and 10 patients had no evidence of ST segment depression despite the presence of new wall motion abnormalities. DSE took significantly longer to perform than TMT (26.0±5.0 min vs 5.5±2.0 min, p<0.01). Thus, DSE is more sensitive, specific and accurate than TMT in detecting coronary artery disease and can detect ischemia at an earlier stage. However, it takes longer to perform than TMT and thus may be less suitable for routine clinical use. (Jpn Circ J 1996; 60: 954 - 960)

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The effect of acetylsaiicylic acid (ASA) on high-energy phosphates (adenosine triphosphate: ATP, creatine phosphate: CrP, inorganic phosphate: Pi) and intracellular pH during myocardial ischemia and reperfusion was studied using phosphorus 31-nuclear magnetic resonance (³¹P-NMR) in the isolated rabbit hearts. Coronary flow, left ventricular systolic developed pressure (LV Dev.P) and left ventricular end-diastolic pressure (LVEDP) were also measured. Langendorff hearts perfused at 37 °C with the perfluorochemical emulsion Fluosol-43 were subjected to 15 min and 30 min of zero-flow ischemia and to 15 min of low-flow ischemia (coronary perfusion pressure=20 mmHg) followed by 65 min of reperfusion (control, Group I). ASA (0.28 mmol/L) was infused either for the entire experimental period from beginning 45 min prior to ischemia (Group II) and infused immediately after reperfusion (Group III). During ischemia, Group II showed a significant suppression of the decrease in the ATP level and pH with both zero-flow and low-flow ischemia compared to those in the other groups, and moreover the increase in Pi and the decrease in CrP in low-flow ischemia were also suppressed. In Group III, the ATP level during reperfusion was significantly higher than that in Group I, but was not significantly different from that in 30 min zero-flow ischemia. In 30 min zero-flow ischemia, Pi, CrP and coronary flow after reperfusion in Group II tended to recover to preischemic values. There were no differences in LV Dev. P among the 3 groups. In conclusion, ASA has a protective effect on myocardial high-energy phosphates during ischemia and reperfusion in rabbit hearts. (Jpn Circ J 1996; 60: 961 - 971)

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To ascertain the pathophysiological roles of the renin-angiotensin system and endothelin in heart failure and cardiac hypertrophy, we assessed changes in cardiac angiotensin converting enzyme (ACE) and endothelin-1 (ET-1) receptor using rats in which myocardial infarction was induced by left coronary ligation. The animals were decapitated 1 or 8 months after the operation. Cardiac ACE and ET-1 receptor were quantified by computerized in vitro autoradiography using ¹²⁵I-MK351A (a lisinopril derivative) and ¹²⁵I-ET-1. One month after myocardial infarction, cardiac weight and plasma atrial natriuretic peptide had increased in rats with infarction, compared to sham-operated controls, indicating the presence of chronic left ventricular dysfunction, although exchangeable body sodium and plasma renin activity were unchanged. Cardiac ACE increased markedly in the infarcted area and moderately in hypertrophied myocardium without any change in affinity compared to sham-operated rats. On the other hand, there was no change in cardiac ET-1 receptors in infarcted rats. The same results were found even at 8 months after myocardial infarction. The present study indicates that cardiac ACE may participate in tissue repair at the site of myocardial infarction and may also play a role in the pathophysiology of cardiac hypertrophy in rats with chronic heart failure. However, the present results do not reveal whether ET-1 receptor participates in the pathophysiology of cardiac hypertrophy in this model. (Jpn Circ J 1996; 60: 972 - 980)

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We investigated the ability of various antithrombotic drugs, delivered locally, to prevent restenosis after angioplasty in hypercholesterolemic rabbits. After dilating atherosclerotic iliac stenoses by balloon angioplasty, a low dose of heparin or a new antithrombotic drug, such as low molecular weight heparin (fragmin), argatroban, or batroxobin, was delivered locally using the balloon double-occlusion technique. In 1 group, high-dose heparin was administered intravenously. Animals that received no drugs served as a control group. After angioplasty, the stenotic segment was dilated and the mean percentage luminal stenosis fell from 89% to 9% in the group that received locally delivered heparin, from 88% to 7% in the group that received locally delivered argatroban, from 87% to 11% in the group that received locally delivered fragmin, from 88% to 15% in the group that received locally delivered batroxobin, from 82% to 18% in the group that received iv heparin (p<0.0001 compared with before angioplasty in each case), and from 84% to 17% in the control group (p<0.005 compared with before angioplasty). Twenty-eight days after angioplasty, the percentage luminal stenosis remained at 14% in the group that received locally delivered argatroban, 15% in the group that received locally delivered fragmin, and 28% in the group that received locally delivered batroxobin, whereas it increased to 45% in the group that received iv heparin, 30% in the group that received locally delivered heparin and 72% in the control group (p<0.05 compared with after angioplasty in each case). Thus, Iocal delivery low doses of new antithrombotic drugs prevents restenosis after angioplasty without affecting systemic coagulability; heparin, whether administered locally or intravenously, was less effective than the new drugs in preventing restenosis. (Jpn Circ J 1996; 60: 981 - 992)

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We report an interesting case of aortic regurgitation. Phonocardiographically, the shape of the diastolic musical murmur in this case changed in each cardiac cycle despite being in sinus rhythm, in the same posture and in the same breathing phase. Experimentally, we were able to obtain a similar noise pattern using an artificial respirator and a hemispherical silicone membrane. We concluded that the irregular and chaotic change in the shape of the diastolic musical murmur in the present case occurred due to irregular swaying of the non-coronary cusp under the influence of the Venturi effect owing to a regurgitant jet stream. (Jpn Circ J 1996; 60: 993 - 997)

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We describe 3 cases of severe congestive heart failure. The patients exhibited a marked decrease in transmitral flow velocity during atrial contraction and an abnormal diastolic plateau wave of pulmonary artery pressure (PAP). The first patient was a 60-year-old man with acute myocardial infarction and acute renal failure in whom pulmonary capillary wedge pressure (PCWP) was raised to 20 mmHg. Pulsed Doppler echocardiography revealed a marked decrease in transmitral flow velocity during atrial contraction, and the PAP waveform showed a mid to late diastolic plateau wave. Treatment for congestive heart failure reduced PCWP to 10 mmHg and the PAP waveform returned to normal. Doppler examination revealed the normal transmitral flow velocity pattern. The second patient was a 37-year-old woman with subarachnoid hemorrhage and the third patient a 74-year-old man with acute myocardial infarction. In these patients, the PAP waveform also showed a diastolic plateau wave, which was abolished by treatment. We believe that the diastolic plateau wave of PAP indicates left ventricular diastolic dysfunction and marked elevation of left ventricular filling pressure. (Jpn Circ J 1996; 60: 998 - 1003)

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