Accuracy of cardiac output measured by continuous wave Doppler echocardiography during dynamic exercise testing in the supine position in patients with coronary artery disease.

To estimate the accuracy of cardiac output measured by continuous wave Doppler echocardiography from the suprasternal notch and the utility of this method for evaluating left ventricular function during dynamic exercise, simultaneous thermodilution and Doppler cardiac output were measured in 34 patients with coronary artery disease during multistage ergometer exercise in the supine position. Cardiac output was measured at rest and during each stage of exercise. Twenty-five of the 34 patients whose thermodilution curves were adequate for analysis were studied during exercise. The correlation coefficient for the two methods was 0.85 at rest and 0.84 during exercise. Differences between the two methods were not significant at rest but were significant during exercise, with the thermodilution method giving the higher values. Underestimation by the Doppler method is probably due to technical problems and changes in aortic diameter during exercise. The 25 patients were classified into two groups according to pulmonary artery wedge pressure at peak exercise. There were 11 patients in Group 1 pressure (greater than or equal to 20 mm Hg at peak exercise) and 14 in Group 2 pressure (less than 20 mm Hg at peak exercise). There were significant differences in the change in cardiac index and in peak aortic velocity from rest to peak exercise between the two groups. A significant linear correlation between the percent change in peak aortic velocity and in pulmonary artery wedge pressure from rest to peak exercise was observed (r = -0.66, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of a new second generation calcium channel blocker, nilvadipine (FR34235), on exercise-induced hemodynamic changes in stable angina pectoris.

The mechanism of the antianginal actions of nilvadipine was investigated in 11 patients with effort angina pectoris. Hemodynamic data were obtained by angina-limited supine multistage bicycle ergometer exercise testing before and after a single 6 mg dose of nilvadipine. Compared with chest pain during control exercise testing, pain at peak exercise disappeared or abated and the ST segment at peak exercise also showed less significant depression after administration of nilvadipine. At rest and at peak exercise, mean blood pressure, pulmonary artery wedge pressure and systemic vascular resistance decreased significantly, whereas heart rate and cardiac index increased significantly after nilvadipine. Rate-pressure product and stroke volume index did not change significantly. Coronary sinus flow at peak exercise increased significantly and total coronary vascular resistance at rest and at peak exercise decreased significantly after nilvadipine. The plasma concentrations of nilvadipine 1.5 hours after administration ranged from 1.15 to 8.23 ng/ml. These data suggest that the principal factors in the antianginal actions of nilvadipine are an increase in myocardial oxygen supply due to increased coronary blood flow and a reduction in myocardial oxygen demand mainly by a decrease in afterload and additionally by a decrease in preload.

Effects of diltiazem on left ventricular diastolic behavior in patients with hypertrophic cardiomyopathy: evaluation with exercise pulsed Doppler echocardiography.

To estimate the effects of diltiazem on the left ventricular diastolic abnormalities in patients with hypertrophic cardiomyopathy, transmitral flow velocity during diastole was studied before and immediately after dynamic leg exercise with the pulsed Doppler technique combined with two-dimensional echocardiography. Seventeen patients with hypertrophic cardiomyopathy and 24 apparently healthy men performed bicycle ergometer exercise in the supine position with the target heart rate set at 120 beats/min. The patients with cardiomyopathy were directed to perform the exercise at the same intensity after receiving 30 to 60 mg of diltiazem, three times daily, for 1 or 2 weeks. The pattern of transmitral flow velocity in diastole had two components, one corresponding to the rapid filling phase in early diastole and the other to the atrial contraction phase in late diastole. To assess left ventricular diastolic behavior, the following variables were analyzed: peak velocity in the rapid filling and atrial contraction phases, the ratio of peak velocity in the atrial contraction phase to that in the rapid filling phase, and pressure half-time. The changes in peak velocity in the atrial contraction phase, pressure half-time and the ratio of peak velocity in the atrial contraction phase to that in the rapid filling phase with exercise differed significantly between patients with hypertrophic cardiomyopathy with no medication and control subjects. After diltiazem, the response of these variables to exercise was almost identical in the two groups. These results suggest that diltiazem can lessen the left ventricular diastolic abnormality in patients with hypertrophic cardiomyopathy on dynamic exercise of mild intensity.

Effects of diltiazem hydrochloride on cardiovascular response, platelet aggregation and coagulating activity during exercise testing in systemic hypertension.

The effects of diltiazem hydrochloride on exercise-induced changes in cardiovascular response, plasma renin activity, platelet function and blood coagulability were evaluated with multistage treadmill exercise in 20 patients who had systemic hypertension of stage 1 to 2 (World Health Organization classification). Heart rates, blood pressure, and pressure-rate product at rest, at peak exercise and in the recovery period were significantly reduced after 4 weeks of diltiazem administration, 180 mg/day. Plasma renin activity tended to increase after the medication. However, platelet adenosine diphosphate-induced aggregation sensitivity, prothrombin time, activated partial thromboplastin time, plasma fibrinogen concentration and antithrombin III activity did not change significantly. It is concluded that diltiazem could ameliorate the hyperresponsiveness of heart rate and BP to exercise in hypertensive patients without affecting blood coagulability.

A comparative study of thallium-201 single-photon emission computed tomography and electrocardiography in Duchenne and other types of muscular dystrophy.

Single-photon emission computed tomography (SPECT) using thallium-201 was compared with 12-lead electrocardiography (ECG) in patients with Duchenne (29), facioscapulohumeral (7), limb-girdle (6) and myotonic (5) dystrophies, by dividing the left ventricular (LV) wall into 5 segments. SPECT showed thallium defects (37 patients, mostly in the posteroapical wall), malrotation (23), apical aneurysm (5) and dilatation (7). ECG showed abnormal QRS (36 patients), particularly as a posterolateral pattern (13). Both methods of assessment were normal in only 7 patients. The Duchenne type frequently showed both a thallium defect (particularly in the posteroapical wall) and an abnormal QRS (predominantly in the posterolateral wall); the 3 other types showed abnormalities over the 5 LV wall segments in both tests. The percent of agreement between the 2 tests was 64, 66, 70, 72 and 72 for the lateral, apical, anteroseptal, posterior and inferior walls, respectively. The 2 tests were discordant in 31% of the LV wall, with SPECT (+) but ECG (-) in 21% (mostly in the apicoinferior wall) and SPECT (-) but ECG (+) in 10% (mostly in the lateral wall). Some patients showed large SPECT hypoperfusion despite minimal electrocardiographic changes. ECG thus appeared to underestimate LV fibrosis and to reflect posteroapical rather than posterolateral dystrophy in its posterolateral QRS pattern. In this disease, extensive SPECT hypoperfusion was also shown, irrespective of clinical subtype and skeletal involvement.

Localization of coronary artery narrowings by applying R-wave amplitude correction to exercise-induced ST depression in angina pectoris and single-vessel coronary artery narrowing.

This study investigated whether coronary artery narrowings can be localized by applying R-wave amplitude correction to exercise-induced ST depression in multiple unipolar precordial lead electrocardiography using 20 electrodes covering the left chest wall. Ten normal subjects and 29 patients with stable angina pectoris and single-vessel coronary artery narrowing (greater than or equal to 75% luminal diameter stenosis in only 1-vessel) participated. Of the 29 patients, 5 had left main coronary artery disease (CAD), 14 had left anterior descending CAD, 4 had right CAD and 6 had left circumflex CAD. The exercise-induced ST depression with R-wave amplitude correction was defined as the exercise-induced ST depression divided by the R-wave amplitude. The 20 points of the lead system were divided into 4 areas: the left main, left anterior descending, right and left circumflex coronary arteries. Coronary artery narrowing was supposed to be in an artery corresponding to the area where the maximal value of the exercise-induced ST depression with and without R-wave amplitude correction was situated. By applying R-wave amplitude correction, the diagnostic ability of localization of coronary artery narrowings was improved significantly from 52% to 86% (p less than 0.005). In particular, localization of the left main coronary artery narrowing was correctly diagnosed in 100% (5 of 5) of angina pectoris patients with left main CAD.

Evaluation by pulsed Doppler echocardiography of the atrial contribution to left ventricular filling in patients with DDD pacemakers.

To evaluate the significance of the left atrial (LA) contribution to left ventricular (LV) filling in cardiac pacing, LV inflow velocity was recorded with pulsed Doppler echocardiography in 20 patients with a DDD pacemaker. The pacemaker was programmed to atrioventricular (AV) sequential pacing with AV intervals of 50, 100, 150, 200 and 250 ms, and then to VVI pacing at a fixed rate of 70 beats/min. To evaluate the relative changes of LV filling volume in individual patients, the percent change in time-velocity integral of LV inflow velocity in each pacing mode was calculated as the ratio to that of AV sequential pacing with an AV interval of 150 ms. To estimate the degree of LA contribution to LV filling, the ratio of time-velocity integral during LA ejection phase to that during total LV filling phase was measured at the optimal AV interval. The percent LV inflow volume in AV sequential pacing was 74% for an AV interval of 50 ms, 87% for 100 ms, 98% for 200 ms and 90% for 250 ms. The percent LV inflow volume in VVI pacing was 72%. The percent LV inflow volume at AV intervals of 150 ms was significantly greater than that at an AV interval of 50, 100 and 250 ms, and in VVI pacing (p less than 0.05). The degree of LA contribution to LV filling showed a positive correlation with the percent increase of LV inflow volume with mode conversion from VVI to AV sequential pacing (p less than 0.005) and also with age (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of isosorbide-5-mononitrate on exercise-induced hemodynamic changes in angina pectoris.

Hemodynamic effects of isosorbide-5-mononitrate (ISMN) were studied in 14 patients with effort angina pectoris. Hemodynamic and echocardiographic data were obtained by angina-limited supine multistage bicycle ergometer exercise testing before and 120 minutes after single oral administration of 20 mg of ISMN. Compared with control exercise testing, the ST segment at peak exercise showed less depression after administration of ISMN (p less than 0.001). At rest, systolic and diastolic blood pressure decreased significantly after administration of ISMN (p less than 0.001 and p less than 0.01, respectively). At rest and at peak exercise, pulmonary artery wedge pressure (both p less than 0.001), left atrial volume (both p less than 0.001) and left ventricular end-diastolic volume (both p less than 0.05) decreased, whereas cardiac index, pressure-rate product and systemic vascular resistance did not change significantly after administration of ISMN. Average time to peak plasma ISMN concentration was 90 minutes and average peak plasma concentration was 460 ng/ml with an elimination half-life of 7 hours. These data suggest that the main mechanism of the antianginal action of ISMN is a reduction in left ventricular preload followed by diminution of myocardial oxygen requirements.

Effects of oral elastase on lipid metabolism, platelet function, and blood coagulability in patients with diabetes mellitus.

Lipid metabolism, platelet function, and blood coagulability were evaluated in 20 patients with diabetes mellitus and stable fasting blood sugar levels before, during, and after treatment with the pancreatic enzyme elastase for 16 weeks. Serum high-density lipoprotein cholesterol levels increased from 46.9 mg/dl before treatment to 53.2 mg/dl after treatment (P less than 0.001) and serum triglyceride levels decreased from 151.4 to 125.4 mg/dl (P less than 0.05); no significant changes in total cholesterol levels were noted. Platelet counts in whole blood and in platelet-rich plasma increased from 17.1 and 27.5 X 10(4)/mm3, respectively, to 19.8 and 31.3 X 10(4)/mm3 after treatment (P less than 0.01 and less than 0.05). Plasma beta-thromboglobulin levels decreased from 117.0 to 72.7 ng/ml after treatment (P less than 0.001). No significant changes in platelet sensitivity to adenosine diphosphate aggregation were noted. Plasma fibrinogen and antithrombin III levels increased from 421.0 and 25.8 mg/dl, respectively, to 470.6 and 32.0 mg/dl after treatment (P less than 0.05 and less than 0.001). It is concluded that, since it has been shown that elastase improved lipid metabolism, inhibited platelet release, and increased antithrombin III levels, it may play a useful role in the prevention of vascular complications in diabetic patients.

Prognostic implications of cardiac scintigraphic parameters obtained in the early phase of acute myocardial infarction.

A cohort of 76 patients with acute myocardial infarction was studied with infarct-avid scan, radionuclide ventriculography, and thallium-201 myocardial perfusion scintigraphy. Infarct area, left ventricular ejection fraction, and defect score were calculated as radionuclide indices of the extent of myocardial infarction. The correlation was studied between these indices and cardiac events (death, congestive heart failure, postinfarction angina, and recurrence of myocardial infarction) in the first postinfarction year. High-risk patients (nonsurvivors and patients who developed heart failure) had a larger infarct area, a lower left ventricular ejection fraction, and a larger defect score than the others. Univariate linear discriminant analysis was done to determine the optimal threshold of these parameters for distinguishing high-risk patients from others. Radionuclide parameters obtained in the early phase of acute myocardial infarction were useful for detecting both patients with grave complications and those with poor late prognosis during a mean follow-up period of 2.6 years.

Influence of risk factors on long-term survival following acute myocardial infarction: a follow-up study in central Japan.

The long-term survival rate following acute myocardial infarction (AMI) was studied in 358 patients in central Japan who were monitored for 8 to 20 years after discharge from hospital for AMI. Fifteen-year cardiac survival rates were 65% in males and 72% in females. In both sexes, the survival rate decreased with increasing age at the time of AMI. The survival rate was significantly lower in recurrent MI than in first MI patients. Those who had smoked cigarettes before AMI or had hyperlipidemia during hospitalization did not show any significant decrease in cardiac survival rate, which may be due to cessation of smoking or control of hyperlipidemia after AMI. The 15-year survival rate was significantly lower in patients with a past history of angina pectoris or hypertension. Patients with a large infarct had a lower survival rate, as did those with a large cardiothoracic ratio on chest x-ray, and those who received digitalis during hospitalization. On the other hand, patients who were administered anticoagulants during hospitalization had a higher survival rate. Multiple regression analysis gave similar results. In conclusion, factors that reduced long-term survival rate after AMI were older age at time of the first attack, reduced cardiac function, and a history of angina pectoris or hypertension. Anticoagulant therapy appeared to improve the long-term survival rate.

Blood coagulability and fibrinolytic activity before and after physical training during the recovery phase of acute myocardial infarction.

The effects of physical training on hemostatic parameters were evaluated in 56 postmyocardial infarction (MI) patients before and after one month of systematic physical training and in 30 control post-MI patients, who did not undergo such training. There were no significant changes in prothrombin time (PT) and alpha 1-antitrypsin (alpha 1AT) at the beginning and end of the study in either group. Levels of fibrinogen, Factor VIII: C (VIII:C) and von Wildebrand antigen (vWf:Ag), and activities of ATIII and plasminogen (Plg) were significantly decreased in the group with physical training (p less than 0.05), while values were unchanged in the control group. Hematocrit, platelet counts, and alpha 2-plasmin inhibitor (alpha 2PI) activities also decreased in the physical training group (p less than 0.05). In contrast, these variables increased in the control group (p less than 0.05). Activated partial thromboplastin time (aPTT) tended to be prolonged in the group with physical training, while it was shortened in the control group. In a subset of 20 patients with physical training, resting levels of plasmin-alpha 2PI complex (PIC), thrombin-antithrombin III complex (TAT), protein-C (P-C:Ag), plasminogen activator inhibitor-1 (PAI-1), VII:C, and P-C activities had significantly decreased after one month of physical training (p less than 0.05), although tissue plasminogen activator activities remained unchanged. Physical training appeared to suppress coagulability as indicated by the decrease in fibrinogen, VIII:C, vWf:Ag, VII:C, and TAT, and prolongation of aPTT. The decrease in plasminogen, t-PA:Ag, alpha 2PI, PAI-1, and PIC after physical training may result from the decreased coagulability. In conclusion, physical training appears to induce a suppression of the coagulation system in patients in the recovery phase of MI.

Left ventricular performance at rest and during exercise in patients with dual-chamber pacemakers.

In 13 patients with an implanted dual-chamber atrioventricular (AV) demand pacemaker, left ventricular performance was elicited by pacing mode manipulation for study using gated cardiac pool scintigraphy at rest and during exercise. There was no significant difference between DDD and VVI at 70 and 90 beats/min with respect to cardiac output, peak ejection rate or peak filling rate. At 110 beats/min, the cardiac output was greater with DDD as compared to VVI. The peak filling rate was also significantly greater with DDD as compared to VVI (DDD: 3.6 vs VVI: 2.8 EDV/s, p less than 0.05). During exercise the cardiac output was greater with DDD as compared to VVI at the same rate. The peak filling rate during exercise was significantly greater with DDD as compared to VVI (DDD: 3.0 vs VVI: 2.5 EDV/s, p less than 0.01). We conclude that DDD is more beneficial than VVI in maintaining cardiac performance during exercise.

Long-term efficacy of acute thrombolytic therapy for myocardial infarction.

We conducted a retrospective study (1981-1990) to determine whether the efficacy of intracoronary thrombolysis (ICT) could be evaluated from data obtained solely after recanalization. We investigated 55 successful ICT patients (38 with anterior and 17 with inferior myocardial infarction (MI)), and 31 control infarct patients without recanalization. The total serum creatine phosphokinase release (sigma CPK), the extent of infarction measured by T1-201 single photon emission computed tomography (total DS) and the disturbance of regional wall motion (asyn.%) were investigated as parameters for distinguishing the successful ICT and control groups. Discriminatory ability for the two groups was highest with the total DS in all patients. Only the total DS differed significantly between the two groups in patients with inferior infarction. Misidentification of control patients as successful patients was least frequent (25.5%) when using the total DS. These findings suggest that the effectiveness of ICT for acute MI may be assessed on the basis of data obtained solely after recanalization, with the total DS being particularly useful.

Effects of vasodilators on venous tone in vivo in dogs.

The authors investigated, in vivo, the effects of four vasodilators on venous tone in dogs. Baseline venous tone was determined from the pressure: diameter relationships in the inferior vena cava (VSIVC) and femoral vein (VSFV) as measured during several seconds of occlusion of the proximal inferior vena cava. All of the slopes were nearly linear. All vasodilators were administered in dosages sufficient to lower blood pressure by approximately 20%; these dosages also decreased systemic vascular resistance by 15% to 30%. Isosorbide dinitrate reduced VSIVC from 7.17 +/- 0.81 to 5.81 +/- 0.73 mmHg/mm and VSIVC from 59.4 +/- 13.5 to 37.2 +/- 6.6 mmHg/mm. Neither nifedipine nor nisoldipine altered VSIVC or VSFV. However, prazosin decreased VSIVC from 13.2 +/- 3.3 to 10.7 +/- 2.7 mmHg/mm and VSFV from 43.5 +/- 11.3 to 29.9 +/- 8.8 mmHg/mm. These results suggest that isosorbide dinitrate and prazosin decrease venous tone in vivo, whereas nifedipine and nisoldipine do not.

Distribution of abnormal Q waves on body surface in relation to left ventricular wall motion abnormalities in myocardial infarction.

This study was undertaken to determine the possible one-to-one relationship between each site of asynergy of the left ventricle and the body surface area to which ensuing abnormal electrical phenomena are reflected. In 140 post-myocardial infarction (MI) patients, distribution of abnormal Q waves on the body surface was correlated with the abnormal segments of LV wall motion identified by left ventriculography (LVG). Unipolar lead electrocardiograms (ECGs) were recorded from 87 lead points over the precordium and the back with Wilson's central terminal as the reference point. Data acquisition and mapping was accomplished through a mapping system HPM 5100 microcomputer. In all cases, coronary arteriography (CAG) and LVG were performed at least 2 months after the acute episode of MI. The LVG findings were evaluated separately in seven wall segments in accordance with the American Heart Association (AHA) reporting system. Sensitivity, specificity, diagnostic accuracy, positive predictive value, and negative predictive value of the abnormal Q wave in each lead point were obtained in cases with abnormal wall motion in segments 2, 3, and 6, respectively, and in infero-posterior segments 4 or 5. Statistical analysis was performed by comparing two groups of patients with or without asynergy of each wall segment concerned. Results of the study revealed some abnormal Q areas of high diagnostic accuracy that correlated highly with the site of abnormal contractility.

[Analysis of circulatory responses to orthostatic stress in the elderly].

An active orthostatic stress test was conducted on 32 elderly patients over 65 years (elderly group) and 17 normal adults, for a comparative evaluation of their blood pressure, heart rates, and plasma catecholamine responses. In addition, 8 patients in the elderly group underwent a study of orthostatic responses with or without sublingual administration of isosorbide dinitrate (ISDN). The results of the orthostatic responses were evaluated by Schellong's method. The elderly group produced a positive reaction in one (3.1%), and a weakly positive reaction in two (6.3%), while the remaining 29 (90.6%) and all of the normal adults showed negative responses. The systolic blood pressure pattern that developed in response to rising among the elderly group was significantly different (p less than 0.001) from that of the normal adult group, but the response pattern seen in the heart rates of the former approximated that of the latter. The plasma norepinephrine concentration 10 minutes after rising increased significantly (p less than 0.001) in both the elderly and normal adult groups. This increase amounted to 1.5-fold in the elderly group and 2-fold in normal subjects, with a less prominent increase shown by the elderly. The norepinephrine levels of the elderly group were significantly higher than those of the normal adults both before and 10 minutes after rising (p less than 0.001 and p less than 0.01, respectively). In the elderly, ISDN caused a significant drop in the systolic blood pressure immediately after rising and a significant increase in the heart rate. Sublingual ISDN administration resulted in a significant increase in the norepinephrine level (p less than 0.05) in association with rising. These findings indicated that the circulatory responses to orthostatic stimuli are inappropriate as clinical data among the elderly and the administration of ISDN exaggerates this shortcoming further.