Effects of benazepril and metoprolol OROS alone and in combination on myocardial ischemia in patients with chronic stable angina.

The efficacy of benazepril, metoprolol OROS and their combination was evaluated in 29 patients (42 to 74 years of age) with chronic stable angina and documented coronary artery disease in a placebo-controlled, double-blind, crossover trial using serial quantitated exercise testing and ambulatory electrocardiographic (ECG) monitoring. The mean (+/- SEM) exercise time was 8.5 +/- 0.7 min with placebo, 8.3 +/- 0.6 min (95% confidence interval [CI]-1.06 to 0.54) with benazepril, 9.4 +/- 0.5 min (95% CI -0.32 to 2.14) with metoprolol OROS and 9.6 +/- 0.5 min (95% CI -0.25 to 2.47) with the combination of benazepril and metoprolol OROS. The mean exercise time to the development of 1 mm ST segment depression was prolonged from 6.0 +/- 0.6 min with placebo to 6.3 +/- 0.6 min (95% CI -0.93 to 1.45) with benazepril, 7.9 +/- 0.5 min (95% CI 0.83 to 3.0) with metoprolol OROS and 8.1 +/- 0.6 min (95% CI 0.88 to 3.29) with the combination of benazepril and metoprolol OROS. Benazepril did not alter the rest or maximal heart rate, whereas metoprolol OROS alone and in combination significantly lowered the heart rate at rest and during maximal exercise. Systolic blood pressure at rest was nonsignificantly reduced, whereas diastolic blood pressure was lowered significantly by all treatments in comparison with placebo. At maximal exercise, only metoprolol OROS, whether given alone or in combination with benazepril, was able to blunt significantly systolic blood pressure and rate-pressure product.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency of magnetic resonance signal abnormalities of the brain in patients aged less than 50 years with idiopathic dilated cardiomyopathy.

Twenty patients with idiopathic dilated cardiomyopathy (IDC) aged less than 50 years (mean 41) and an age-matched group of 20 healthy volunteers were studied. All subjects were free of cerebrovascular symptoms and risk factors for stroke. Magnetic resonance imaging of the brain, extracranial Doppler ultrasonography, heart catheterization and echocardiography were performed. In patients with IDC, a higher frequency of ventricular enlargement (p less than 0.02), cortical atrophy (p less than 0.01) and white matter lesions (p less than 0.05) was observed. Cerebral infarcts were found in 4 patients (p less than 0.05) who showed clinically severe limitation of functional capacity (New York Heart Association class III or IV). The extent of cortical atrophy, and the duration of clinical evidence of IDC showed a significant correlation (p less than 0.04). The data indicate a high incidence of parenchymal abnormalities of the brain in young, neurologically asymptomatic patients with IDC.

Sulfoconjugated and free plasma catecholamine levels at rest and during exercise in patients with idiopathic dilated cardiomyopathy.

Plasma levels of sulfoconjugated (sc) catecholamines (CA) have been shown to be increased with activation of the sympathoadrenal system in a number of clinical settings. We evaluated the relation between scCA and clinical or hemodynamic parameters of patients with idiopathic dilated cardiomyopathy (IDC) at rest and during incremental exercise testing. Eleven healthy subjects, nine patients in New York Heart Association (NYHA) functional class I (IDC-A group) and 11 in NYHA functional class II and III (IDC-B group) performed a symptom-limited, graded bicycle exercise test. Resting, peak and various postexercise levels of plasma free and scCA were determined by high-pressure liquid chromatography. Resting CA levels obtained in the supine position were remarkable for elevations of free norepinephrine (NE) in IDC-B patients (355 +/- 157 ng/l) as compared to IDC-A patients (177 +/- 54, p = 0.006) or healthy controls (193 +/- 74, p = 0.007). Similarly, scNE was highest in IDC-B patients with 1856 +/- 1089 ng/l, followed by IDC-A (1028 +/- 187, p = 0.025) and control subjects (1109 +/- 440, p = 0.025). There was a highly significant correlation between free and scNE (r = 0.76, p < 0.0005). Whereas resting free dopamine (DA) levels were comparable in all three groups, scDA was found to be elevated clearly in IDC-B patients (8772 +/- 2097 ng/l) and significantly different to IDC-A (5786 +/- 2481, p = 0.01) or control subjects (4892 +/- 1575, p = 0.0005). The NYHA functional class and maximum exercise performance correlated best with resting scDA (r = 0.68, p = 0.001 and r = 0.56, p = 0.005, respectively). At peak exercise, IDC-B patients exhibited a significant decrease in scNE and sc epinephrine (E) (from 1856 +/- 1089 to 1495 +/- 932 ng/l, p < 0.005 and from 491 +/- 173 to 282 +/- 143 ng/l, p < 0.01) compared to controls (from 1109 +/- 444 to 1094 +/- 548 ng/l and from 379 +/- 200 to 329 +/- 134 ng/l). In IDC-B patients this decrease in scNE and scE at peak exercise was related inversely to the rise in free NE and E (r = -0.81, p < 0.005 and r = -0.68, p < 0.05). Resting hemodynamic indices generally were reflected better by some free CA rather than by conjugated forms or by parameters of clinical performance. These findings suggest that in addition to free or scNE levels, resting scDA is elevated in symptomatic patients with IDC.(ABSTRACT TRUNCATED AT 400 WORDS)

Prednimustine combined with mitoxantrone and 5-fluorouracil for first and second-line chemotherapy in advanced breast cancer.

A total of 60 patients with advanced breast cancer were treated with a combination of prednimustine (P: 110 mg/m2, days 1-5), mitoxantrone (M: 12 mg/m2, day 1) and 5-fluorouracil (F: 500 mg/m2, day 1) (PMF). Treatment was repeated every 3 weeks. In all 53 patients were evaluable for response. A total of 12 subjects had failed prior chemotherapy for metastatic disease. In response to PMF treatment we observed 21 partial remissions and 3 complete remissions, amounting to a total response rate of 45%. The median duration of response was 39 weeks, and median survival was 56 weeks. Dose-limiting side effects were leukopenia (40 cases) and thrombocytopenia (11 patients). Nausea and vomiting was experienced by 93% of subjects; in 56% of cases it reached WHO stage II-III. Alopecia occurred in 18% of our patients. Our results suggest that PMF represents an active regimen in the treatment of advanced breast cancer and yields a response rate of 45%. Considering that the majority of our patients had not received prior chemotherapy, the question remains open as to whether a 45% response rate outweighs the observed toxicity.

Combination therapy of 4'-O-tetrahydropyranyl-doxorubicin, 5-fluorouracil, and high-dose folinic acid in patients with advanced breast cancer: a phase I-II study (preliminary results).

Previous clinical studies have suggested that 4'-O-tetrahydropyranyl-doxorubicin (THP) as well as 5-fluorouracil/high-dose folinic acid (5-FU/HDFA) are active and well-tolerated drugs in breast cancer treatment. This phase I-II study was designed to determine the maximum tolerated dose (MTD) of THP in combination with 5-FU/HDFA as a weekly schedule and to examine the activity and safety of this drug regimen in patients with advanced breast cancer. 5-FU and HDFA were set at doses of 350 mg/qm i.v. and 500 mg/qm i.v., respectively, whereas the THP dose has been escalated in increments of 5 mg/qm i.v. beginning at a dose level of 10 mg/qm until reaching of MTD in at least four patients in one dose level. For determination of MTD the first six cycles of each patient have been taken into account. Up to July 1990, 21 patients previously not treated with chemotherapy for metastatic breast cancer were entered into the study; the latest patient entered at 35 mg/qm THP dose level. A total of 270 cycles have been administered so far. Anemia and leukopenia was limited to ECOG grades I and II. Other toxicities were mild or moderate. No acute or subacute cardiotoxicity has been observed. Up to July 1990, MTD had not been reached. In the second part of the study, at least another 14 patients have to be entered in a dose level one below the MTD to evaluate the activity and safety of this regimen in a phase II trial.

A "lipo-protective" effect of a fixed combination of captopril and hydrochlorothiazide in antihypertensive therapy.

Increases of triglycerides and total cholesterol have been reported during treatment with antihypertensive drugs, most notably with beta blockers and diuretics. ACE inhibitors, on the other hand, are not known for having a negative effect on lipid profile. To evaluate the effects of a fixed combination of captopril and hydrochlorothiazide on lipid metabolism, blood pressure, and quality of life, we performed an open prospective study. A total of 2,154 patients with or without hypercholesterolemia, but not receiving lipid lowering drugs, were enrolled. Of the 1891 evaluable patients at baseline, 34.1% had a moderate risk with total cholesterol between 5.2 and 6.5 mmol/l (mean 5.8 mmol/l) and 41.3% had a high coronary heart disease (CHD) risk with total cholesterol higher than 6.5 mmol/l (mean 7.3 mmol/l). After six months of treatment, the median cholesterol level in the moderate risk group decreased from 5.8 to 5.4 mmol/l (p less than 0.0003) and in the high risk group from 7.3 to 6.3 mmol/l (p less than 0.0001). Triglycerides also decreased, whereas high density lipoprotein (HDL) increased in both risk groups. Systolic and diastolic blood pressure fell as expected and quality of life improved. The fixed combination was well tolerated. We observed a significant improvement of lipid profile in patients with mild to moderate hypertension while undergoing treatment with the fixed combination of captopril and hydrochlorothiazide. We suggest that captopril may balance the negative effects of hydrochlorothiazide on lipid metabolism in patients with hypertension and concomitant hyperlipidemia.

Coronary revascularization: influence on ventricular arrhythmias.

Myocardial ischemia may cause severe cardiac arrhythmias. In the present study, the influence of revascularization on ventricular arrhythmias was investigated. A total of 68 patients (61 male, 7 female; mean age 53 years) with coronary artery disease was divided into three groups: Group A (21 patients) underwent percutaneous transluminal coronary angioplasty (PTCA); Group B (37 patients) had coronary artery bypass grafting (CABG); and Group C were 10 patients who served as controls, who had simple coronary angiography. All patients had a Holter ECG on the day before angiography. PTCA patients and controls were restudied on the day after the procedure, while in Group B, Holter ECG was repeated three weeks after surgery. Groups A and B were again studied 18 months after the first Holter ECG. The PTCA group showed a slight reduction in complex arrhythmias immediately following PTCA, which increased again after 18 months; the CABG group, however, revealed a significant increase in complex arrhythmias three weeks after bypass surgery, but a decrease after 18 months. There was no significant change in the control group before or after angiography. Thus, successful revascularization has no influence on ventricular arrhythmias after 18 months.

Perforated ventricular aneurysm in a male suffering from pneumonia.

In a 49-year-old male with fever, dyspnea, and chest pain, thoracic x-ray revealed pneumonia with enlarged heart silhouette. Antibiotics were successful, pneumonia healed and complaints disappeared. Yet, during the following 3 months, echocardiography showed mild persistent pericardial effusion while in ECG both sinus tachycardia and ST-T changes were found suggesting chronic pericarditis. Magnetic resonance imaging, however, revealed an extensive posterobasal aneurysm with pericardial effusion substantiated by ventriculography. Coronary angiography showed diffuse three-vessel disease. Surgery revealed aneurysm with distinct perforation of the left ventricle and pericardial thrombi, thus aneurysmectomy as well as bypass grafts were performed. One year postoperatively, magnetic resonance imaging confirmed the absence of aneurysm with only a small irreversible posterobasal perfusion defect remaining as shown by thallium scintigraphy.

Giant dissecting aortic aneurysm with concealed perforation in an 81-year-old female.

This paper describes the history of an 81-year-old female suffering from a giant dissecting aortic aneurysm with concealed perforation within the thorax. The patient had suffered from arterial hypertension for about 10 years and had been treated with thiazide. Nine months prior to admission the patient was in a state of collapse, and ultrasound examination revealed an intra-abdominal aortic aneurysm. At this time thoracic x-ray showed aortic sclerosis and elongation of the aorta but no signs of aneurysm formation. After this episode the patient was symptom-free for the next 9 months. Following a further syncopal attack with severe thoracic pain, the patient was hospitalized at the intensive care unit. Both in thoracic x-ray and computed tomography of the thorax, a pronounced dissecting aortic aneurysm with perforation of the thoracic aorta into the mediastinum could be established. Because of the patient's poor general condition and advanced age, as well as far-reaching pathological findings, surgery was not advised by either the heart and vascular surgeon or the anesthetist. Following 1 week's intensive therapy, the patient's general condition improved greatly, with stabilization of thoracic pain, blood pressure, and respiratory action. On the other hand, thoracic x-ray, computed tomography, and magnetic resonance imaging produced a distinct progression of the aneurysm with consequent mild displacement of mediastinum and left lung. Laboratory examinations for syphilis showed no evidence of that disease. After further improvement the patient was discharged 4 weeks after admission and has been symptom-free for 6 months in spite of the extensive pathological findings described herein.(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive and invasive diagnosis of a huge congenital aneurysm of the left atrium: a case report.

An intrapericardial aneurysm of the left atrium in a twenty-eight-year old asymptomatic woman is reported. The aneurysm was diagnosed by two-dimensional echocardiography and the specific intraaneurysmatic flow pattern was described by color blood flow imaging. To the authors' knowledge such a noninvasive diagnosis of a left atrial aneurysm has never been reported in the literature before. The diagnosis was confirmed by angiocardiography. The aneurysm was successfully resected. The patient was discharged without medication and continues to do well.

Circadian blood pressure pattern in patients with treated hypertension and left ventricular hypertrophy.

Left ventricular hypertrophy in hypertensives is an important determinant of prognosis. In the present study 45 patients with treated essential hypertension were divided into two groups: 23 patients had normal left ventricular dimension and 22 patients had echocardiographic signs of left ventricular hypertrophy (LVH). All patients were adequately treated during daytime, but ambulatory blood pressure monitoring showed a distinct abnormal pattern in the LVH group characterized by a lack of blood pressure reduction during the night; 16 of 22 patients with LVH had no blood pressure decline during the night, whereas 17 of 23 patients without hypertrophy showed this reduction (P less than 0.01). In conclusion, patients with hypertension and LVH often reveal a lack of blood pressure decline during the night, which may be the reason for the development of left ventricular hypertrophy (and thus should be managed by a different circadian blood pressure therapy) or which may be the consequence of progressive structural changes in the resistance vessels, along with the development of left ventricular hypertrophy. It is suggested that patients with hypertension and left ventricular hypertrophy should have ambulatory twenty-four hour blood pressure monitoring.

Long-term outcome and prognostic factors in dilated cardiomyopathy. Preliminary results.

UNLABELLED: To investigate long-term follow-up and identify prognostic factors in patients with dilated cardiomyopathy (DCM) the authors investigated 167 consecutive patients on an outpatient basis. All patients underwent left- and right-heart catheterization; follow-up comprised clinical and echocardiographic investigations. RESULTS: After a mean follow-up period of ninety-three +/- thirty-six months 82 patients (49%; 71 men, 11 women, mean age fifty-five +/- eleven years) were alive. 29 of them (27 men, 2 women, mean age fifty-two +/- nine) showed normal left ventricular ejection fraction (LVEF) after a mean follow-up period of one hundred four +/- forty months. The remaining 53 patients (44 men, 9 women, mean age fifty-six +/- eleven) revealed LVEF similar to that of the first examination. Eighty-five patients died (51%; 73 men, 12 women). Causes of death were the following: progressive heart failure, 24; sudden death, 23; stroke, 3; pulmonary embolism, 2; noncardiac death, 4; unknown causes, 29. The median period from the onset of first symptoms until definite diagnosis was two months in patients with stable conditions, three months in those with normalization of LVEF and twenty-four months in those who died, respectively (P < 0.01). At the time of diagnosis, patients with stable outcome had a mean LVEF (LVEF 1) of 37%, those who returned to normal had 40% (ns). Patients who died had a mean LVEF 1 of 32% and therefore differed significantly from both groups of survivors (P < 0.001). Left ventricular end-diastolic pressure (LVEDP) at the time of diagnosis was highest in patients who died (22 mmHg) and therefore differed significantly from both groups of survivors (normalization: 16 mmHg, stable patients: 18 mmHg, P < 0.001). CONCLUSIONS: According to their results, time until diagnosis, LVEF, and LVEDP are prognostic indicators. No difference was noted between the groups concerning etiology, medical treatment, or functional classification according to the New York Heart Association.

Observations on plasma ANP levels during short-term transient myocardial ischemia produced by PTCA in patients with LAD stenosis.

Ten patients with coronary artery disease and stable angina (mean age fifty-seven) were included in the study. Five of the patients had normal left ventricular function, 5 had local hypokinesia or akinesia; 8 had one-stem and 2 had two-stem disease, but all had left anterior descending (LAD) lesions ranging from 75% to 100%. Ejection fraction varied between 35% and 75% (mean 59%). Immunoreactive atrial natriuretic polypeptide (ANP) levels in the femoral vein (FV) and the coronary sinus (CS) were measured before, immediately after, and up to twenty-four hours after percutaneous transluminal coronary angioplasty (PTCA) of the LAD. ANP secretion increased by 83% (FV) and 11% (CS) within minutes after PTCA and reached control levels after thirty to sixty minutes. In patients with hypokinesia of the anterior wall, ANP secretion was significantly lower, 48% (FV) and 11% (CS) respectively. ANP secretion during PTCA was higher in patients with concomitant increase in pulmonary capillary pressure (PCP) but was also observed without an increase of PCP, suggesting ventricular ANP secretion. IN conclusion, transient myocardial ischemia leads to immediate ANP secretion even in the absence of significant pressure elevation in the left atrium. As a part of the continuous medical education program of the American College of Angiology the second part of the paper reviews the mechanisms that allow the ischemic heart to counteract the ischemic condition and thus to escape from myocardial infarction. A review of this subject is presently not available in the literature.

[Tl-201 myocardial SPECT in silent myocardial ischemia and angiographically proven coronary heart disease]. / Tl-201-Myokard-SPECT bei stummer Myokardischämie und angiographisch gesicherter koronarer Herzkrankheit.

Silent myocardial ischemia is defined as true myocardial ischemia without angina pectoris in patients with angiographically detected coronary artery disease. In this study 52 patients (46 male, 8 female: mean age 53 years) with a pathological exercise test but no symptoms were investigated. They showed stenosis of 75% or more of the diameter in at least one coronary segment on angiography. Prior to or after catheterization (within 14 days) Tl-201 SPECT was done and evaluated independently of angiography. A clear correlation between angiographically confirmed stenosis and reversible perfusion defects with Tl-201 SPECT was established (62 out of 76 lesions). Furthermore, there was a significant relation between angiographically detected subtotal or total occlusions of coronary vessels and irreversible perfusion defects using Tl-201 SPECT (35 in 44 lesions) (p less than 0.001). In patients with ST depression but without angina pectoris during the exercise test, the Tl-201 SPECT is highly suited to determine the hemodynamic effect of coronary stenoses.

[Redilatation with the trefoil balloon catheter in 2 patients with a high degree of aortic stenosis]. / Redilatation mit dem Trefoil-Ballonkatheter bei 2 Patienten mit hochgradiger Aortenstenose.

Percutaneous transluminal balloon valvuloplasty (PTBV) is successfully applied in the treatment of calcified aortic stenosis. However, results following redilatation have not yet been dealt with in the literature. This method was successfully used in two patients (62a m/70a f) suffering from severe sclerotic aortic stenoses. Redilatation was undertaken in the first case after one month and after four in the second. A second redilatation by balloon catheter was done upon request of the patients after a further nine months. Following this third dilatation both patients suffered from femoral thrombosis which was treated surgically in the second case, while in the first local thrombolysis was done. In the management of the first patient valve replacement had to be performed four months after the last dilatation due to renewed complaints, while the second patient showed no evidence of recurrence within three months after the last dilatation.

A physiological oral magnesium supplement does not influence total serum magnesium, left ventricular ejection fraction and prognosis in patients with dilated cardiomyopathy.

It has been postulated that patients with congestive heart failure (CHF) benefit from physiological oral magnesium supplements. In order to study the effect of such supplements upon patients with idiopathic dilated cardiomyopathy (IDC) we studied a group of 23 patients with the salient characteristics of IDC (18 male, 5 female; mean age 51 +/- 13 years [range: 23-72]; Mg group), who received oral magnesium supplements (15 mmol/day). All patients received oral ACE inhibitors and 22 were receiving digitalis and diuretics. A control group of 27 patients, matched for age, sex, symptoms, and additional treatment (22 male, 5 female; mean age 52 +/- 13 years [range 22-71]) were not given oral magnesium supplements. All these patients also received oral ACE inhibitors, 25 were receiving digitalis, and 23 were receiving diuretics. Mean serum magnesium concentration (total serum Mg) in the Mg group was 0.83 +/- 0.06 mmol/litre [mean +/- SD, range 0.69-0.99], while in the control group it was 0.83 +/- 0.07 mmol/litre [range 0.70-0.96], P = NS. Left ventricular ejection fraction (LV-EF) improved from 32 +/- 11 per cent [range 13-51] to 42 +/- 14 per cent [range 15-66] in the Mg group and from 30 +/- 13 per cent [range 10-52] to 42 +/- 11 per cent [range: 25-64] in the control group. We found that physiological oral Mg supplements did not influence serum magnesium, LV-EF, or prognosis. Furthermore, we found that 56 per cent of all patients improved when subjected to strict guidance and therapy with ACE inhibitors, digitalis, and diuretics.

[Early therapeutic intervention in heart failure]. / Frühe therapeutische Intervention bei der Herzinsuffizienz.

During the past years, several large trials (Consensus, VHEFT I and II, SOLVD) have shown a significant reduction of mortality in patients with moderate and severe heart failure. However, despite effective treatment with vasodilators, digitalis and diuretics mortality in these patients remains unacceptable high. It seems logic, to state treatment at an earlier stage of the disease to achieve more benefit. The main early pathophysiological disturbance is left ventricular hypertrophy, resulting from hypertension, coronary artery disease, increasing age and obesity. On the long run, LVH may lead to diastolic and systolic heart failure, myocardial ischemia, arrhythmias and sudden death. With ACE-inhibitors LVH can be reduced within 1 month of treatment. The large SAVE- and SOLVD-prevention trials will show, whether this early intervention will improve proposis in patients with asymptomatic heart failure.

New concepts in ischemia prevention.

Transient myocardial ischemia may result from obstruction to flow in the large epicardial coronary arteries or diminished flow reserve due to small vessel disease or left ventricular hypertrophy. In patients with coronary heart disease, calcium blockers have proven to reduce stress induced ischemia in patients with normal left ventricular function and in those with ischemic cardiomyopathy. However, recent studies indicate a need for caution when giving calcium antagonists to patients with postinfarction left ventricular systolic dysfunction. Moreover, calcium antagonists that reduce heart rate (diltiazem) are able as a monotherapy to reduce total ischemic burden. Calcium antagonists that may increase rate (dihydropiridines) have to be combined with beta-blockers to achieve this goal. For 24-h control of ischemia the ischemic threshold should be determined for a differentiated therapy in the individual patient. Is the ischemic threshold of the majority of episodes lower than the exercise threshold, a calcium blocker should work. Angiotensin-converting enzyme (ACE) inhibitors are not effective in stress-induced ischemia, but may reduce total ischemic burden, although this effect is not significant. In patients with left ventricular hypertrophy and/or small vessel disease, calcium blockers and ACE inhibitors are probably effective in regression of left ventricular hypertrophy and vascular hypertrophy. However, it remains to be shown that ischemia is reduced by these drugs.

[The patient following PTCA]. / Der Patient nach PTCA.

Diagnostic measures after PTCA consist of history, clinical findings, after 3 months and thereafter in 6 months intervals as well as ergometry in case of recurrency of complaints of after 3 months and then in 6 months intervals. A thallium-scintigraphy is done eventually. A repetition of a coronarography is indicated only in cases of typical symptoms or registration of ischemia. Therapy consists of lifelong ASS and calcium channel blockers for 3 months and treatment of risk-factors. Repetition of a PTCA, atherectomy, stent-implantation, laser-angioplasty or bypass-surgery varies from case to case; the decision has to be made individually.