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A 44-year-old German fell ill in Libya, where he had been living for 10 years, with high fever, rigor and a nonitching centrifugally spreading macular rash, which had spared the head, hands and soles. In addition, a systolic cardiac murmur was heard. The Weil-Felix reaction had a titre rising within 3 days from 1:160 to 1:640, confirming the diagnosis of rickettsial disease, the total clinical picture indicating typhus. On treatment with chloramphenicol (1 g three times daily i.v.) the fever subsided within 5 days. On the ninth day treatment was changed to oral doxycyclin, 200 mg daily for 3 weeks. Echocardiography surprisingly revealed a floating thrombus, about 4 x 8 cm, attached to the hypo- and even akinetic apex of the left ventricle. In addition there was single-vessel coronary disease. Since the segmental contraction abnormality persisted after the typhus had been cured, a causal connection with the rickettsial disease is unlikely. The thrombus was removed at the time of a aortocoronary bypass operation: his course has been unremarkable since then.

Cardiopulmonary exercise testing (CPX) allows a non-invasive control of the cardiopulmonary exercise capacity. In this study, we wanted to investigate if the CPX can be securely, practicably, and accurately performed in patients with invasively documented coronary heart disease (CHD). Furthermore, we wanted to find out the clinical value of CPX in CHD diagnosis. The CPX measurements (symptom-limited; ramp program with 20 Watts increase/min; semi-supine position; continuous registration of the cardio-circulatory parameters (HR, RR, ECG), of the gas exchange parameters (O2, CO2) and of the ventilation) in 101 patients have shown that CPX is secure, accurate, and practicable. The day-to-day reproducibility is high (r > 0.8). The respiratory anaerobic threshold can be manually evaluated by means of the PET O2 criterion in 95% of the cases. The CCS-classification of angina pectoris could not accurately describe the cardiopulmonary exercise capacity as compared to the Weber-classification. The disadvantage of the Weber-classification is that it does not respect the age-, sex- and weight-dependent differences of the normal values. Our own data and results from the literature demonstrate that the anaerobic threshold, the maximum VO2 and the maximum O2-pulse are the more reduced the more coronary arteries are involved, the more reduced the left ventricular function is. But, nevertheless, the range of values shows large overlaps so that an exact differentiation, based upon these parameters, is not possible. Patients with similar functional results or degree of reduced exercise capacity have different morphological alterations. Most patients demonstrated typical ischemic cascade with anaerobic threshold, ST-segment alterations, angina pectoris and, finally, reduced max. VO2. In conclusion, CPX does not replace the traditional methods of non-invasive and invasive ischemia detection, but enables secure, practicable, and accurate measurements of the individual cardiopulmonary exercise capacity and the interaction between muscles, heart, circulation, and lungs. Possibly, CPX can be used in the near future for identifying CHD patients with low, medium or high risk.

We analyzed 128 cardiopulmonary exercise tests (CPX), performed in normal subjects (n = 31), in patients with coronary artery disease (n = 41), with chronic heart failure before (n = 14) and after (n = 14) application of oral PDE-inhibitors and in patients with HIV-infection on a bicycle-ergometer in semi-supine position using a ramp-program (dependent on study-population with 15, 20 or 35 Watt/min increases) with respect to the ability to determine the respiratory anaerobic threshold non-invasively, using the main criteria described by Wasserman et al.: the V-slope-method according to Beaver, the increase of the ventilatory equivalent for O2 (VE/VO2), the increase of the end-tidal PO2 (PETO2) and the increase of the respiratory quotient (RQ) during exercise. In the different study-populations we calculated the detection rates of the AT for each criteria separately. The typical changes in the end-tidal PO2 (124/128 = 96.9%) and the V-slope-method (119/128 = 92.9%) were the most reliable parameters to detect the anaerobic threshold. The characteristic changes of the ventilatory equivalent for O2 (VE/VO2) and of the respiratory quotient (RQ) we found in 100/128 (= 78.1%) and in 107/128 (= 83.6%) of the tests respectively. 86/128 tests (67.2%) showed typical changes in all four mentioned criteria. In another 24/128 tests (19.8%) three of four criteria were fulfilled. Therefore, our investigations showed that in 110/128 cases (85.9%) the AT could be determined by typical changes by means of at least three of the four described parameters. In 15/128 (11.7%) tests only two of four criteria were fulfilled.(ABSTRACT TRUNCATED AT 250 WORDS)

Safety and sensitivity of gradient-echo magnetic resonance imaging (MRI) for the identification of significant coronary artery stenoses using pharmacologic stress testing was assessed in 61 patients with > or = 70% stenosis of a major coronary artery and a normal left ventricle. After MRI at rest 28 patients underwent dobutamine-MRI during steady-state dobutamine infusion (5, 10, 15 and 20 micrograms/kg/min) and 33 patients had dipyridamole-MRI after high-dose dipyridamole infusion (0.75 mg/kg over 10 min). All patients additionally performed standard ECG exercise stress testing (EST). Segmental wall motion analysis was performed in basal and midventricular short axis tomograms by two observers. A segment was graded pathologic if transient dobutamine or dipyridamole induced wall motion abnormalities could be detected. For comparison to coronary angiography findings, each segment was assigned to one of the coronary artery perfusion territories. There were no serious side-effects during dobutamine and dipyridamole infusion leading to termination of the study protocol. Peak double product during dobutamine infusion was significantly higher (p < 0.001) than after dipyridamole infusion (18.493 +/- 4.311 versus 12.799 +/- 2.694 mm Hg/min). Overall sensitivity of dobutamine and dipyridamole-MRI for coronary artery disease (CAD) was 85% and 84%. Regional asynergy by dobutamine and dipyridamole-MRI was observed in 73% versus 79% patients with single- and 100% versus 92% with multi-vessel disease. Individual coronary artery stenoses were correctly identified by segmental wall motion abnormalities in 87% versus 81% for left anterior descending, 62% versus 86% for left circumflex and 78% versus 92% for right coronary artery stenoses. In conclusion, dobutamine and dipyridamole-MRI are well tolerated and safe non-exercise dependent tests for detection and localization of hemodynamically significant coronary artery stenoses with a similar diagnostic accuracy but with a better control of stress intensity and duration provided by dobutamine.

In a prospective and double-blind study, the long-term effects of low dose fish oil on serum lipids and lipoproteins was tested in patients with normal or moderately elevated serum lipids and compared to the effects of olive oil. The compliance to the study medication was evaluated by analysis of serum fatty acids and proved to be very good. Dietary supplementation with 9 g fish oil, respective 3.15 g n-3 fatty acids per day over one year resulted in a decrease of serum-triglycerides by 26% and increase of HDL-cholesterol by 26%. Treatment with 9 g olive oil resulted in an 18% increase of HDL-cholesterol. There was no effect on serum-triglyceride levels.

In a prospective pilot study, subjective and objective parameters of the health status were assessed in 148 male patients (mean age 56 +/- 8.4 years) before and 4 months after successful coronary angioplasty (PTCA). Restenosis was defined as residual diameter stenosis > 50%. Although 96 patients (65%) had not developed restenosis at 4 months' invasive follow-up, subjective assessment of general well-being was unchanged in 26% or worse in 71%; overall anginal status and exercise performance had however improved. Of 71 men younger than 60 years who had no restenosis at follow-up, 4 men retired and 13 remained on medical leave. The striking disparity between subjective and objective parameters was not related to significant differences of age, exercise capacity, and left ventricular ejection fraction, as well as to baseline characteristics (previous myocardial infarction, extent of coronary heart disease, comorbidity) compared with 52 patients with restenosis. Thus, despite documented sustained success after PTCA, the majority of patients failed to resume the status of subjective well-being.

Intracoronary stenting was designed to handle acute vessel closure after balloon angioplasty and to reduce the rate of restenosis. In three cardiology centers the implantation of 200 balloon-expandable Palmaz-Schatz stents was attempted in 179 patients. The implantation was successful in 170 patients (95%). During bail-out implantation for acute vessel closure or symptomatic dissections after balloon angioplasty, implantation succeeded in 60 (91%) of 66 attempted patients, who recovered immediately from ischemia. Three patients received emergency bypass surgery and three patients were kept on medical therapy. Restenosis after 4 to 6 months, defined as > 50% diameter reduction, was documented angiographically in 18 (15.3%) of 118 presently controlled patients. Patients with single stent implantation (n = 106) presented a late restenosis rate of 10.4% in contrast to patients with multiple stent implantation (n = 12), who presented a restenosis rate of 58.4%. Similar results on restenosis were found for patients with elective and bail-out stent implantation. Acute thrombotic stent occlusion occurred in three patients (1.8%) during the first 24 h after stenting. Three to 9 days after implantation subacute stent thrombosis occurred in 15 (8.8%) of 170 patients. Despite adequate therapy including thrombolysis, balloon angioplasty or emergency bypass surgery in 14 of 15 patients Q-wave myocardial infarction was documented in six patients and non Q-wave myocardial infarction in five patients. The following parameters were identified as risk factors for the development of subacute stent thrombosis: bail-out indication, unstable angina, type C lesion, stenosis length > 1.5 cm, plaque area > 3.5 mm2, symptomatic dissection after balloon angioplasty, incomplete wrapping of the dissection after stenting and residual distal vessel irregularities after stenting. Bleeding complications occurred in 12.4% of the patients and were related to the anticoagulation and antiaggregation therapy. In conclusion, the implantation of Palmaz-Schatz stents is an excellent bail-out device to treat acute vessel closure or symptomatic dissections after angioplasty. Elective and bail-out single stent implantation is associated with a reduced rate of restenosis when compared to conventional balloon angioplasty. At present, subacute stent thrombosis and bleeding complications are the major limitations with a combined rate of 15.9%.

In 20 patients with an angiographically documented coronary artery stenosis of > or = 70% and normal LV function at rest MRI was performed before and after dipyridamole infusion (0.75 mg/kg BW). In all patients MIBI-SPECT was obtained at rest and after dynamic symptom-limited exercise. In 18 patients MIBI-SPECT showed ischemia and in 18 patients dipyridamole MRI showed a wall motion impairment. In the segments representing the 29 stenosed vessels ischemia in MIBI-SPECT was diagnosed correctly in 24 instances (sensitivity 83%, specificity 90%) and a wall motion abnormality was present in MRI in 23 instances (sensitivity 79%, specificity 90%). Dipyridamole GE-MRI is not superior to MIBI-SPECT in the diagnosis of ischemia.

To assess the feasibility, safety and usefulness of gradient-echo magnetic resonance imaging (MRI) combined with pharmacologic stress testing for the detection of coronary artery disease, 23 patients without previous myocardial infarction but with significant stenosis (greater than 70% diameter stenosis) of greater than or equal to 1 major coronary artery were selected for dipyridamole-MRI stress testing. Each patient underwent MRI at rest, and high-dose dipyridamole-MRI (0.75 mg/kg over 10 minutes) of corresponding basal and midventricular short-axis tomograms. Additionally, these patients performed symptom-limited exercise stress tests. All short-axis tomograms were evaluated on a standardized segmental basis by grading each segment as normal, hypokinetic, akinetic or dyskinetic. Dipyridamole-MRI was considered pathologic if segmental wall motion deteriorated by greater than or equal to 1 grade after dipyridamole. For comparison with coronary angiography, segmental wall motion gradings were related to the respective coronary artery territories in the short-axis plane. Pathologic dipyridamole-MRI was obtained in 18 of 23 (78%) patients. For 1- and 2-vessel diseases, sensitivity was 69 and 90%, respectively. Exercise stress tests were pathologic in 14 of 23 (66%) patients. For 1- and 2-vessel diseases, sensitivity of exercise stress test was 58% (7 of 12 patients) and 77% (7 of 9), respectively. Sensitivity/specificity of dipyridamole-MRI for the localization of the stenosed coronary artery was 78/100% for left anterior descending, 73/100% for left circumflex, and 88/87% for right coronary artery stenoses. It is concluded that dipyridamole-MRI is a feasible nonexercise-dependent test for detection and localization of functionally significant coronary artery disease.

The evaluation of flow velocities in left ventricular inflow tract (LVIT) by Doppler echocardiography gives information about the diastolic ventricular function. In late diastole, shortly after the flow velocity of atrial contraction V(A), we notice in the left ventricular outflow tract (LVOT) a laminar flow velocity directed to the aortic valve. The purpose of this study was to compare this flow velocity V(A*) in the LVOT with the flow velocity of the atrial contraction V(A), and the flow velocity of early diastole V(E) in LVIT, to determine whether such comparison would provide information concerning diastolic function. We studied three groups: 39 patients with left ventricular hypertrophy (HY) (mean age 56 +/- 12 y, 77% male), 41 patients with coronary heart disease (KHK) (mean age 53 +/- 10 y, 85% male) and 41 healthy subjects (N) (mean age 50 +/- 16 y, 51% male); all three groups were studied by pulsed Doppler from apical 4 chamber view in LVOT for maximal velocity (Vmax-A*) and time velocity integral of A* (TVI-A*), and in LVIT for maximal velocity of early diastole (Vmax-E), maximal velocity of atrial contraction (Vmax-A), ratio Vmax-E/Vmax-A, and the time velocity integrals (TVI-E, TVI-A). A slight correlation between Vmax-A* and Vmax-A was found (r = .60), being nearly the same as for TVI-A* and TVI-A (r = .64).(ABSTRACT TRUNCATED AT 250 WORDS)

1. After initial acute administration of 20 or 60 mg ISDN, 2 mg molsidomine and 20 mg nifedipine, a clear effect on the circulation and an increase in work tolerance is detectable. 2. Following 4 weeks' treatment with 3 X 20 mg ISDN, there is no essential loss of action in the venous branch or with respect to working capacity. 3. After 4 weeks' treatment with 3 X 60 mg ISDN, the improvement in working capacity is partially retained, but the action on the venous branch is significantly poorer. 4. During 4 weeks' treatment with 3 X 20 mg nifedipine, there is no essential loss of action in the arterial or venous branches, or with respect to working capacity. 5. Our results with continuous high doses of ISDN indicate that high doses should be used only in monitored exceptions.

Coronary angioscopy (CA) was performed in 30 patients (pts) during cardiac catheterization (Group 1) and in 11 pts during coronary bypass surgery (Group 2) using ultrathin fiberoptic angioscopes (phi 1.2-1.8 mm). For percutaneous CA (Group 1) the angioscope was introduced through a 9F guiding catheter from the femoral artery. The viewing field was cleared by flushing Ringer's solution and short-time occlusion of the coronary ostium by the guiding catheter. In Group 2 CA was performed retrogradely from the distal arteriotomy and through the bypass vein during flushing with cardioplegic solution. In Group 1 in 17/30 pts the coronary artery could be successfully examined by CA. In 13 pts the obstruction was eccentric and irregular shaped. In 2/5 pts, in whom CA was performed successfully pre and post balloon dilatation, CA after PTCA revealed an intimal rupture without clinical or angiographical signs of the intimal dissection. In Group 2 in 9/11 pts good visualization of stenoses could be achieved. At the obstruction site CA revealed thrombi in 3 pts and ulcer in 1 pts. In contrast to angiography, which estimates the lumen diameter of a segmental lesion, CA gives information about the luminal shape and the underlying substance of the obstruction (e.g. atheroma, thrombus, ulceration). The main problems in percutaneous CA are the insufficient intraluminal guidance, the insufficient depth of view of the angioscopes, and the limited examination time.

On the occasion of a routine medical check-up 256 out of 1100 individuals with an accumulation of coronary risk factors were screened for silent myocardial ischaemia by exercise testing and Holter monitoring. Of these individuals 5.5% had a pathological exercise test, 7.4% had ischaemia-like events on the Holter ECG, 11.3% had at least one pathological test, but only 1.6% had ischaemic signs in both ECG tests. The outcome of the ECG tests appears to be independent of the type and the total number of risk factors. To date, 13 of the 29 individuals with a positive test have undergone thallium myocardial imaging: only three individuals had signs of ischaemia. Holter monitoring and exercise ECG show comparable results in this population. The pathological ECG findings were only partly confirmed by the thallium test. The follow-up will show the prognostic significance of the ECG changes.

In a population of 40 patients with coronary artery disease the overall incidence of spontaneous ischemic episodes during 24-h Holter monitoring could be significantly reduced with ISDN 120 mg ret. and ISDN 120 mg plus Diltiazem 120 mg ret. However, the intraindividual day-to-day variability of ischemic episodes on three consecutive days of Holter monitoring is taken into consideration, an intraindividual reduction of ischemic episodes of at least 97% is required to separate a true therapeutic effect from the considerable spontaneous variability.

Circumscribed areas of injured myocardium which lead to late ventricular depolarization represent the pathologic-anatomic substrate for reentry mechanisms potentially capable of propagating ventricular tachycardia at the ventricular level. If the myocardial area from which delayed ventricular depolarization and, consequently, late potentials eminate, exceeds a critical minimal size, documentation of such signals can not only be achieved with direct endocardial mapping or catheter mapping but also by means of special high-resolution ECG techniques from the body surface. Since high amplification of the conventional ECG results in registration of noise signals in amplitude of up to 50 microV, late potentials with their amplitudes at the body surface ranging from 5 to a maximum of 20 microV, can only be discriminated after substantial enhancement of the signal-to-noise ratio. The noise arises from no less than three sources: physiologic noise, for example, from muscle activity; electronic noise from amplifiers and background noise of 50 or 60 Hz, respectively. To improve the signal-to-noise ratio, currently three methods are employed: sequential or temporal signal averaging, spatial signal averaging and fast Fourier transformation analysis of the frequency spectrum of the highly-amplified ECG. Temporal signal averaging has the purpose of smoothing randomly-occurring background noise and, at a specified point in time of the ECG cycle, to sum the signal incurred. The effectivity of this technique, however, is subject to certain conditions: the signal to be registered and the background noise must be independent from each other, the noise must be stationary and show normal random distribution, the signal of interest must be periodic and/or coupled with a fixed interval to a point in the ECG cycle which can be used as a trigger. The quality of the averaged signal is dependent on trigger stability. There are three approaches to trigger processing: voltage threshold determination, slope detection and the pattern matching technique, the accuracy, reliability and time-consumption of which increases in the order listed. A trigger stability of +/- 0.5 ms is necessary to detect ventricular late potentials with sufficient sensitivity and without meaningful deformation or attenuation of their form and temporal extent. Intercurrently, a number of commercially-acquirable signal averaging computers have been made available which differ with respect to registration and analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

In order to test the clinically supposed development of tolerance during chronic high-dose nitrate therapy, we studied a total of 24 patients with angiographically proven coronary heart disease at rest and during ergometric exercise (supine position, 50 w for 3 min). Pulmonary arterial pressure (PAP, floating catheter), arterial blood pressure (cuff method), cardiac output (Fick principle), heart rate, and exercise capacity (w X min) were measured at rest and exercise before and during chronic (4 weeks) oral therapy with 5-isosorbide mononitrate (5-ISMN), 3 X 20 mg/day (n = 14) and 3 X 50 mg/day (n = 10). After acute administration, both doses of 5-ISMN decreased mean PAP at rest and during exercise (rest: by 25% with 20 mg and by 29% with 50 mg; exercise: by 30% with 20 mg and by 45% with 50 mg), whereas cardiac output and stroke volume were only reduced by 5-ISMN at rest. During chronic treatment with 60 mg and 150 mg 5-ISMN, and additional administration of 20 mg or 50 mg respectively lowered PAP at rest by 15% and 19%; during ergometric exercise PAP was 22% and 14% lower than during ergometry before any drug treatment. The exercise capacity slightly increased during treatment to 60 mg 5-ISMN, whereas it decreased by 25% on chronic treatment with 150 mg 5-ISMN per day. Our results show that acute administration of 5-ISMN in either dose (20 mg and 50 mg) exerts unloading effects on the heart and will increase the exercise tolerance. In contrast to the higher dose of 150 mg 5-ISMN per day, chronic treatment with the lower dose of 60 mg 5-ISMN daily will not result in drug tolerance.

Haemodynamic effects of 5-isosorbide mononitrate (5-ISMN) were studied at rest and on exercise in 31 patients with angiographically confirmed coronary heart disease. A decrease in arterial blood pressure and mean pulmonary artery pressure without significant change in heart rate, cardiac output and stroke volume occurred both at rest and on exercise after 20 mg of 5-ISMN to 12 patients. Administration of 50 mg 5-ISMN to 19 patients achieved greater decrease in mean pulmonary artery pressure; cardiac output and stroke volume were highly significantly reduced at rest, while on exercise both cardiac output and stroke volume remained unchanged. Ten patients, in whom after a single dose of 50 mg 5-ISMN the mean pulmonary artery pressure at rest and on exercise had decreased 28% and 45%, respectively, with a definite rise in exercise tolerance, repeat acute administration of a single dose of 50 kmg 5-ISMN produced a fall in mean pulmonary artery pressure at rest by 20% after 50 mg three times daily for four weeks. On exercise the fall was only 14% below the control levels before treatment. In addition, exercise tolerance was reduced. These results indicate that acute administration of 5-ISMN at rest and on exercise decreases cardiac work load. But on chronic administration of high doses, tolerance to the drug may develop.

To test the clinically supposed development of tolerance during chronic molsidomine therapy we studied a total of 11 patients with angiographically-proven coronary heart disease at rest and during ergometric exercise (supine position; submaximal, i.e. 50 W for 3 min, and maximal exercise). Pulmonary arterial pressure (PAPmean, floating catheter), arterial blood pressure (RR, cuff method), work capacity (W x min) and duration of exercise loading (sec) were measured at rest and on exercise before and during chronic (4 weeks) oral therapy with 3 x 4 mg day-1 of molsidomine. Acute administration of 4 mg molsidomine reduced the mean arterial resting pressure by 12% and under submaximal exercise loading by 8%. After molsidomine, the PAPmean was reduced by 35% at rest; following a period of treatment of 4 weeks no significant decrease in efficacy could be discerned (PAPmean reduction by 31%). Under submaximal and maximal exercise the PAPmean dropped by 44% and 37%, respectively (35.5 +/- 6.7 cf. 19.9 +/- 4.5 mmHg; 39.2 +/- 6.5 cf. 24.8 +/- 7.0 mmHg), whilst simultaneously the work capacity increased by 93% (281 +/- 108 cf. 545 +/- 254 W x min). After 4 weeks treatment with 12 mg day-1 of molsidomine, the PAPmean of 22.4 +/- 6.6 mmHg and 30.1 +/- 9.9 mmHg under identical exercise loading conditions, remained significantly below the exercise load value prior to the onset of medication. The molsidomine-induced increase in the exercise tolerance was maintained throughout the long-term medication (537 +/- 268 W x min). With a four-week treatment with daily doses of molsidomine there was a persistent effect on the pulmonary arterial pressure and the work capacity. Thus development of tolerance during high dose, long-term molsidomine therapy is not to be expected.

After extensive animal experiments a new method of high-frequency current coronary angioplasty (HFCA) via a specially developed catheter system was used in ten patients with haemodynamically significant coronary artery stenoses. In eight patients the stenoses affected the anterior interventricular branch (AIVB), in one patient each the circumflex branch and the right coronary artery, respectively. In nine patients the stenosis cross-section was reduced by at least 20% (from a mean of 91.9% +/- 5.8% to 52.6 +/- 17.5%). In three patients HFCA was followed by balloon angioplasty. The total number of applications per patient ranged from 3 to 12 (mean total duration of current flow: 3.9 +/- 1.0 s). There was only one severe complication, in a patient with subtotal AIVB occlusion after initially successful HFCA: balloon angioplasty successfully restored the lumen to the post-HFCA state. The new technique of HFCA is worthy of further development. It promises to be a valuable addition or alternative to balloon coronary angioplasty.

In 45 patients with coronary artery disease, proven by coronary arteriography, and 15 patients without such disease 0.5 mg dipyridamole (Persantin) per kg body weight was injected i.v. over ten minutes. In 40 of the 45 patients with coronary artery disease anginal pain occurred during or immediately after dipyridamole injection and ceased immediately after intravenous administration of 0.24 g aminophylline (positive test), while in three it had stopped spontaneously without aminophylline (questionable positive test). Only in two of the 45 patients with confirmed coronary artery disease was there no anginal pain (false-negative result). None of the 15 patients without coronary artery disease had anginal pain during the test. It is concluded from these results that the "dipyridamole test", which is simple to perform and does not stress the patient significantly, is at least equivalent diagnostically to the exercise E.C.G. test.

To evaluate spontaneous variability of ST-segment changes within the Holter ECG, in 20 patients with documented coronary heart disease (CHD) long-term ambulatory ECG recordings were performed over 3 consecutive days, when the patients were only receiving short-acting nitrates. ST-segment alterations per day were measured as the area beneath the baseline (mV x min), and were compared day-to-day intraindividually. The intra-day variations of ST-segment area alterations were a factor of about 10, when compared with the baseline values. Following administrations of 120 mg ISDN ret. at the beginning of day 4, the number of anginal attacks was reduced, as was the acute medication with short-acting nitrates. There was also a trend to reduction of ischemic ST-segment changes, but these reductions could not be confirmed statistically. In studies on the course and therapeutic interventions of patients with CHD, the phenomenon of spontaneous variability of ST-segment alterations must be taken into account--as applies also to the arrhythmia analysis within the Holter ECG--and the recording period must probably be prolonged beyond the 24-h limit presently used.

Different patho-anatomical and functional factors are considered to be involved in patients with unstable angina pectoris. Among these are a pre-existing plaque based on coronary atherosclerosis, the development of fissures or dissections of the plaque (often combined with thrombus formation at the site of the plaque) coronary vascular tone, and theoretically primary aggregation of platelets at a site of apparently normal vascular endothelium. Several comprehensive studies on patients who died from acute myocardial infarction or unstable angina, have convincingly shown that complications of an atherosclerotic plaque like fissures, dissections and thrombus formation may be present in 60 to 90% of cases. In addition, two groups of investigators, who have applied coronary angioscopy for direct visualization of offending coronary arteries, have confirmed these results, since in about 60-80% of patients with unstable angina complicated atheromata, i.e. rupture, ulceration, thrombus formation, could be documented, whereas in all patients with stable angina an uncomplicated atheroma was seen angioscopically. On the basis of these results a hypothetical sequence of events in patients with stable angina, unstable angina and acute myocardial infarction has been proposed. Stable angina pectoris may be seen in patients with uncomplicated atheroma in one of the major coronary artery branches. When dissections, ulcerations and thrombus formation occur as a complication of a formerly smooth plaque, patients show the clinical syndrome of unstable angina. If an occlusive thrombus develops, the patient will run into a fresh myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

The haemodynamic and antianginous efficacy of percutaneous nitroglycerin was evaluated in 24 patients with coronary heart disease. Groups of 8 patients each received one, two or four patches (nitroglycerin liberation 5 mg per patch within 24 hours). Prior to application and after 1 and 2 hours cardiac frequency, arterial and pulmonary arterial pressures and exercise tolerance were assessed. Cardiac frequency and arterial pressure showed no relevant changes after application of patches. The mean pulmonary arterial pressure decreased after application of one or two plasters by 18.5 and 22.2% at rest and by 12.7 and 21.1%, respectively, during exercise. The working capacity showed a trend towards improvement only. With four nitroglycerin patches the mean pulmonary arterial pressure at rest was lower by 26.2% and during exercise by 39.1%. The working capacity rose significantly by 48.7%. Comparison of these effects with oral single dosage of 20 mg 5-isosorbide mononitrate (ISMN) showed that two simultaneously administered plasters did not achieve efficacy of 20 mg 5-ISMN, four plasters, however, were more effective.

In 500 patients suffering from angina pectoris (454 males, 46 females) in whom coronary angiography had been performed a dipyridamole test was carried out. The test was positive in 319 of 396 patients with stenosing coronary heart disease (sensitivity 80%); ECG changes typical of ischaemia were demonstrated in 51%. The exercise ECG test was positive in only 68% of 229 patients with coronary heart disease. Among 104 patients without stenosing coronary heart disease the dipyridamole test was false-positive in 47, giving a specificity of 55%, while in 17 (16%) there were false-positive ECG-changes. The exercise test was falsely positive in 20 of 38 patients without stenosing coronary heart disease (specificity of 47%). Coronary blood flow was measured with the argon technique in 19 of 47 with a false-positive dipyridamole test and three with a false-positive exercise ECG. Maximal pharmacologically induced coronary blood flow was significantly reduced in all so that the diagnosis of "atypical coronary heart disease" or "small vessel disease" was made. The dipyridamole test or the exercise ECG test were falsely positive in these patients only with regard to the coronary arteriogram, correctly positive, however, in relation to angiographically non-demonstrable coronary blood flow abnormalities. The dipyridamole test is complementary to the exercise ECG test and has comparable accuracy. The same precautions must be observed for both tests.

Seventy-nine patients with angiographically documented coronary artery disease were studied with exercise ECG and Holter ECG for ischaemic ST segment changes. Fifty-four patients (68.3%) had ischaemia on exercise, 48 patients (62.0%) had ischaemic ST segment depression during Holter monitoring. Twenty-four (30%) of the patients with a positive exercise test and 30 (61%) with a positive Holter ECG were asymptomatic during the test, 83.7% of the total count of 456 episodes of spontaneous ischemia during Holter monitoring were silent. Forty-four patients (55.7%) had ischaemic ECG changes during exercise and Holter ECG, 20 patients (25.3%) were negative on both tests. Ten (12.7%) had only a positive exercise test and five (6.3%) only a positive Holter ECG. The sensitivity of Holter monitoring for the detection of ischaemia in patients with coronary artery disease is comparable to the sensitivity of the exercise ECG.

In twelve patients with coronary heart disease and hemodynamically significant coronary artery stenoses (LAD: 11, LAD plus RCA: 1) the effect of intracoronary nifedipine, 0.2 mg, on PTCA-related myocardial ischemia was evaluated. The severity of angina pectoris during balloon inflation was not significantly reduced by nifedipine, whereas the sum of ST segment alterations in Einthoven and Goldberger leads on inflation was significantly decreased by the drug. Before inflation intracoronary nifedipine lowered the systolic arterial blood pressure significantly, whereas diastolic and mean aortic pressure and heart rate remained unchanged. At the end of the inflation period heart rates were significantly faster after nifedipine, and the heart rate-blood pressure product higher with nifedipine. No significant correlations could be calculated between the extent of ST segment alterations and any of the hemodynamic parameters. From our results we conclude that, besides the possibility of ventricular afterload reduction, the beneficial cardioprotective effect of intracoronary nifedipine may mainly be attained by the local "cardioplegic" action of this substance.

In ten patients with coronary heart disease molsidomine achieved a clear-cut decrease in pre- and after-load of the heart at rest. Due to decreased venous return at rest there was a fall in stroke volume resulting in a fall of systolic and diastolic aortic pressure. But at the same level of standardised exercise, systolic and diastolic arterial pressure and cardiac output were similar with or without molsidomine. Without changing after-load, there was a fall in pulmonary artery mean pressure (P less than 0.005), probably due to an increase in left-ventricular compliance and (or) a fall in pulmonary vascular resistance. A rise in venous capacity or a decrease in venous return during exercise was excluded as a possible mechanism of molsidomine action.

Coronary- and LV-angiography in coronary heart disease are indicated I) to clarify whether or not surgery is required (e.g. aorto-coronary-bypass operation, aneurysmectomy) in 1) drug resistent angina pectoris, 2) myocardial aneurysms (or the suspicion of), 3) VSD following myocardial infarction and/or 4) as preoperative investigations in mitral regurgitation or 5) other valve lesions. II) These investigations are furthermore indicated in the under-50-yr.-old considering their prognosis and diagnosis 1) following myocardial infarction 2) to clarify a pathological exercise test with or without angina pectoris 3) in the differential diagnosis of myocardial diseases and 4) occasionally in patients with a number of risk factors or exposed to particular occupational hazards or from families with a high incidence of early deaths from heart disease. Coronary- and LV-angiography are contraindicated in 1) generalized stenosing atherosclerosis, 2) acute myocardial infarction, 3) failure from other organ-systems (e.g. kidney), 4) drug resistent endogenous risk factors and/or relevant obesity, 5) biological age over 60-65.6) continued nicotine dependence. In many cases the specific diagnostic investigations will include the assessment of coronary flow at rest and during maximal drug induced coronary dilatation. This enables us to estimate the coronary reserve and to diagnose coronary insufficiency in patients with normal coronary angiograms.- Instructive morphological and/or functional results illustrate this presentation.

The following effects in treatment of coronary artery disease are desired: 1. Elimination or improvement of angina. 2. Improvement of physical capacity. 3. Prevention of imminent complications (myocardial infarct, cardiac arrhythmias, heart failure, embolism). 4. Elimination or diminuation of risk factors. 5. Prolongation of life. - In a critical survey concerning long-term studies of patients with aorto-coronary bypass or medical treatment in the literature subtile lists of indications for surgical and conservative treatment are put up (Table II and III), illustrated by case reports. - Useful criteria for diagnosis, follow-up, and prognosis are selective coronary angiography, ventriculography as well as determination of the coronary reserve (Argon Method). Indication for aorto-coronary bypass and resection of myocardial aneurysms are presented. Principles of medical treatment are: 1. Diminuation of myocardial oxygen requirement (release of pressure, economisation of work load, recompensation, regulation of arrhythmias) and 2. improvement of myocardial oxygen supply (Diminuation of coronary perfusion resistance including prevention and treatment of atherosclerosis). Indication for various medications are discussed (nitrites, beta-adrenergic blocking agents and antihypertensive drugs, glycosides, medication for arrhythmias, coronary dilatators, anticoagulants, and lipotropic substances). Their mode of action is debated and documented by own results. Present possibilities and limits in treatment of coronary artery disease are presented.