Apoproteins and lipids as discriminators of severity of coronary heart disease.

Serum apoprotein and lipid concentrations were measured in 63 patients undergoing coronary angiography. Thirty-eight patients had 50% or higher grade stenoses, 25 had chest pain, but no significant stenoses. Among the patients with higher grade stenoses 71% had hyperlipoproteinemias as opposed to 12% in patients without stenoses. As compared to suitable normal controls, patients with angiographically documented coronary heart disease showed significant changes in all lipid and apoprotein concentrations under study. However, differences between the two patients groups were also noted. Among these, apo A-I, A-II and B, total cholesterol and LDL cholesterol were statistically significant. These results indicate that apoprotein A and B levels, total cholesterol and LDL cholesterol are good discriminators of the severity of coronary heart disease, while HDL cholesterol is a more suitable parameter for epidemiological studies.

Left ventricular structure and determinants in normotensive offspring of essential hypertensive parents.

OBJECTIVE: To assess whether currently normotensive offspring of essential hypertensive parents may have alterations in left ventricular mass (LVM) and function, and how these relate to some potential determinants. DESIGN AND METHODS: Echocardiographical indices of LVM (assessed by two-dimensional guided M-mode echocardiogram), 'clinic' blood pressure and daytime ambulatory blood pressure profiles, blood pressure responses to dynamic and isometric exercise testing, haematocrit, plasma and 24-h urinary electrolytes and catecholamines, and plasma angiotensin II were assessed on a defined Na+ intake in 31 normotensive lean sons of essential hypertensive parents (OHYP group) and 30 body mass index- and age-matched sons of normotensive parents (ONORM group). RESULTS: Clinic supine systolic blood pressure was higher in the OHYP than the ONORM group, but clinic diastolic and daytime ambulatory mean blood pressures, blood pressure loads and blood pressure during dynamic or isometric exercise did not differ significantly. LVM index (LVMI), interventricular septum thickness (IVST), posterior wall thickness (PWT), the IVST:PWT ratio, ejection fraction, fractional shortening, cardiac index and measured biochemical variables also did not differ significantly between groups. In the whole study population the LVMI correlated positively with the body mass index and negatively with plasma noradrenaline. CONCLUSIONS: In young lean men with one essential hypertensive parent and blood pressure still in the normal range, left ventricular structure and systolic function, as assessed by echocardiography, seem to be often unaltered and appropriate relative to the existing body habitus and blood pressure. Moreover, an early tendency for increasing resting blood pressure in genetically hypertension-prone humans may be more apparent under clinic than usual ambulatory conditions, whereas the blood pressure reactivity to physical stress seems to be largely normal at this stage.

The effect of anticoagulant therapy in primary and anorectic drug-induced pulmonary hypertension.

In a retrospective study, we tested the hypothesis that anticoagulant therapy with warfarin sodium (Coumadin) has a beneficial influence on the long-term prognosis in patients with primary pulmonary hypertension (PPH) and aminorex-induced plexogenic pulmonary hypertension. The study included a total of 173 patients from two European cities. One hundred four of these patients took the anorectic drug aminorex (Menocil), which was available in some European countries almost 30 years ago; 69 patients had pulmonary hypertension of unexplained etiology, ie, PPH. Fifty-six of the 104 aminorex-treated patients and 24 patients in the PPH group received warfarin after diagnosis was established. For analysis, patients were divided into four groups according to their history of aminorex intake and anticoagulant therapy. Survival time, changes in hemodynamics (pulmonary arterial pressure), and improvement in quality of life (scored by the New York Heart Association [NYHA] classification) were compared and analyzed. We found that aminorex-treated patients had a better long-term prognosis than those with PPH (7.5 vs 3.9 years; p < or = 0.001). The best mean survival time of 8.3 years was found in anticoagulated aminorex-treated patients, compared to 6.1 years in nonanticoagulated aminorex-treated patients. Moreover, aminorex-treated patients who received anticoagulant therapy soon after the onset of symptoms showed significantly better prognosis (10.9 years) than those who commenced treatment 2 years thereafter (5.9 years) (p < or = 0.05). In patients with PPH, systolic pulmonary pressure was shown to influence survival time significantly (p < or = 0.0005); however, this correlation was not found in aminorex-treated patients. An improvement of symptoms like dyspnea on exertion was seen in 44.8% of the anticoagulated aminorex-treated patients, while deterioration was evident in 72.2% of the nonanticoagulated aminorex-treated patients. In conclusion, our study has shown that anticoagulant therapy had a positive influence on long-term survival and a significant improvement in quality of life in patients with PPH, in particular in patients with a history of anorectic drug intake.

[Selective double-isotope coronary scintigraphy with 99mTc- and 111In-HSA-microspheres]. / Zur Technik der selektiven Doppelisotopen-Koronarszintigraphie mit 99mTc-und 111In-HSA-Mikrosphären.

A small fraction of a commercially available kit for the preparation of human serum albumin (HSA)-microspheres is labeled with 111In or 99mTc. The regional coronary blood flow is determined after selective injection of these labeled microspheres at rest and during rapid atrial pacing using a double-isotope coronary scintigraphy with a gamma camera.

Effects of pindolol therapy on the size of experimentally induced myocardial infarction in the pig.

The effect of pindolol on experimental myocardial infarction was studied in a pig model. Intravenous application of 0.05 mg pindolol per kg body weight was initiated one hour after coronary ligation and repeated at 12-hour intervals for five days. No significant difference in infarct size could be found between pindolol-treated animals (20.4 +/- 0.6% SEM of whole ventricular mass, n = 6) and untreated controls (20.5 +/- 1.2% SEM, n = 9). Hemodynamic data did not change significantly throughout the experiment. These results differ in part from those reported by other investigators: The disagreement may be due to the specific pharmacological properties of the applied drug, to variations in the dosages of beta blockers, as well as to differences in the study design.

Cardiogoniometry: a new noninvasive method for detection of ischemic heart disease.

Cardiogoniometry is a new vectorcardiographic method. The vector-loops are constructed from three orthogonal ECG leads and registered on-line by a microprocessor. The angle between the maximal QRS and T vectors, as well as the spatial orientation of these vectors are very constant in healthy individuals. Deviations of these vectors and angles are sensitive indicators for changes in repolarization occurring, for instance, during coronary insufficiency. The changes in these variables were evaluated in 50 patients with suspected coronary artery disease and correlated with angiographic findings. Cardiogoniometry showed a sensitivity of 79% and a specificity of 82%, which is comparable to exercise testing. In contrast to the latter cardiogoniometry can be performed at rest, is free of risk, and therefore also suitable for elderly patients.

Comparative diagnostic value of a new computerized vectorcardiographic method (cardiogoniometry) and other noninvasive tests in medically treated patients with chest pain.

The diagnostic value of cardiogoniometry (CGM), a new computerized vectorcardiographic method, for the identification of coronary artery disease was compared with other noninvasive tests in 48 medically treated patients with chest pain. Coronary angiography revealed one-vessel disease in 18, two- or three-vessel disease in 21, and normal coronary arteries in 9 patients. Cardiogoniometry was less sensitive (63%) than thallium-201 (201T1) scanning (82%), but slightly more sensitive than the exercise ECG (50%) or a recently proposed parameter of exercise performance (50%). On the other hand, specificity was comparable among these tests (exercise ECG 78%, thallium-201 scanning 72%, CGM 67%, new parameter of exercise performance 66%). Moreover, the false negative rate of noninvasive testing was reduced from 8 to 3% when CGM was added to thallium-201 scanning and exercise ECG. Our findings indicate that in view of the easier feasibility with computerized technology, the future role of vectorcardiographic methods such as CGM in the noninvasive diagnosis of coronary artery disease should be redefined.

Pulmonary hypertension, "plexogenic pulmonary arteriopathy" and the appetite depressant drug aminorex: post or propter?

An epidemic of chronic pulmonary hypertension of vascular origin (CPHVO) has occurred in Austria, the Federal Republic of Germany, and Switzerland. The epidemic started in 1967 and reached its peak in 1968 and 1969. Since 1972, the prevalence of patients with CPHVO among individuals investigated by cardiac catheterization is again as low as in the pre-epidemic years. In Bern the prevalence of CPHVO during the peak of the epidemic was 20 times higher than during the 12-year period preceding the epidemic. The clinical, physical, electrocardiographic, radiologic, haemodynamic and respiratory findings of the patients observed in Bern (n = 102) are summarized. There has been a mortality between 12 and 20% at the time of the epidemic. Most patients observed for the first time during the epidemic have remained severely disabled over the years. A minute fraction seems to have recovered. There is a close geographic as well as temporal relation of the epidemic to the marketing and intake of the appetite depressing drug aminorex fumarate (Menocil). Acute administration of aminorex leads to a transient rise of the pulmonary artery pressure and vascular resistance in a number of animal species. It has not been possible to produce sustained precapillary pulmonary hypertension and chronic cor pulmonale vasculare under the conditions of chronic administration of the drug in the species tested. Morphologic examination of lung biopsy and autopsy material of patients who have died from CPHVO after the intake of aminorex reveals the presence of "plexogenic pulmonary arteriopathy". The vascular lesions are identical with those observed in pulmonary hypertension due to large congenital left-to-right shunts. In balancing the pros and cons, it appears that the arguments in favour of a cause-effect relationship between aminorex and pulmonary hypertension, which are derived from epidemiological evidence, outweigh the results of "negative" animal experiments. A "propter" in the title of this paper, therefore, seems to be more appropriate than a post".

[Problems of aortocoronary bypass. Indications for coronary angiography and ventriculography; results of direct bypassing coronary surgery]. / Probleme um den aorto-koronaren Bypass. Indikationen der selektiven Koronarangiographie und Ventrikulographie; Ergebnisse der überbrückenden direkten Koronarchirurgie

The introduction of selective coronary arteriography and aorto-to-coronary saphenous vein bypass surgery (a.-c bypass) has fundamentally altered our understanding of ischemic heart disease (IHD). The indications for the effective diagnostic procedure and the results of the new and increasingly important surgical technique are summarized. Selective coronary arteriography should be performed (a) in patients with known IHD in order to furnish the anatomical and functional information necessary to assess the indication for surgery, i.e. in patients below 60 years with intractable stable or unstable (impending infarction) angina. It is rarely indicated in patients with an old myocardial infarction who are free from symptoms. It is debatable in patients during the acute stage of infarction; (b) in patients with questionable IHD, with the aim of ruling out or confirming the condition, i.e. mainly in patients with atypical chest pain or with equivocal ecg findings. The risks of the procedure, if carried out by experienced personnel, are small. Selective arteriography will always be supplemented by a selective left ventricular angiography yielding important information concerning the functional behaviour of the myocardium. In judging the therapeutic value of a.-c. bypass surgery it should be noted that postoperatively 60 to 70 percent of the patients present without symptoms and 80 to 95 percent feel markedly better, and that physical performance is enhanced in about the same proportions. An improvement in left ventricular function under exercise conditions seems to be rare. Hospital mortality of a.-c. bypass operation is small and below 5 percent if patients with stable angina and without myocardial failure, previous infarctions or mitral regurgitation are considered. In the presence of an ischemic cardiomyopathy, on the other hand, the mere surgical risk soon reaches prohibitive limits. The incidence of early complicating myocardial infarctions ranges around 10 percent. Bypass occlusion occurs in some 5 to 15 percent during the early postoperative phase, while in the following months and years the patency rate diminishes but little. If the survival rates of operated and non-operated patients with IHD are compared it becomes evident that a prolongation of life is possible whenever surgery aims at a correction of two- and three-vessel disease (including the prognostically unfavourable isolated stenosis of the left anterior descending branch and stenosis of left main artery) whereas the natural course of isolated lesions of the right coronary artery and the left circumflex branch seems to balance the effect of corresponding surgical interventions. It should be borne in mind, however, that the follow-up periods on which these statements are based do not exceed 3-4 years.

Aminorex and pulmonary hypertension. A review.

There was an epidemic of chronic pulmonary hypertension in Austria, the Federal Republic of Germany and Switzerland, starting in 1967, peaking in 1968/69, and disappearing after 1972. The mechanism leading to pulmonary hypertension was chronic precapillary vascular obstruction due to plexogenic pulmonary arteriopathy. There was a close geographic as well as temporal relation of the epidemic to the marketing and intake of the appetite depressing drug aminorex fumarate (Menocil). 10 years after the epidemic, half of the patients have died, usually of right heart failure. Of those surviving, half present a definite regression of the pulmonary vascular obstruction. Average survival after the initial diagnosis was 3.5 years in those patients who died. Their PA pressure (+22%) and pulmonary arteriolar resistance (+40%) was higher at the onset of the observation period if compared with the corresponding values of the survivors; also the incidence of right heart failure was significantly higher (84 vs. 58%). Among the surviving patients, the only difference between those with an improved and those with a worsened haemodynamic situation was the age at the beginning of the weight-reducing treatment, those with a progression being 10 years older. The probability of survival after 10 years is considerably higher in chronic pulmonary hypertension of vascular origin (CPHVO) after aminorex than in "classical" primary pulmonary hypertension (CPHVO of unknown cause) and in CPHVO due to recurrent silent pulmonary thromboembolism. This difference in prognosis is an argument in favour of the identity of chronic pulmonary hypertension developing after the intake of the appetite depressing drug aminorex.

[Chronic pulmonary hypertension of vascular origin, plexogenic pulmonary arteriopathy and the appetite depressant aminorex: addenda to an epidemic]. / Chronische pulmonale Hypertonie vaskulären Ursprungs, plexogene pulmonale Arteriopathie und der Appetitzügler Aminorex: Nachlese zu einer Epidemie.

An epidemic of chronic pulmonary hypertension occurred in Austria, the Federal Republic of Germany, and Switzerland, starting in 1967, peaking in 1968/69, and disappearing after 1972. The mechanism leading to pulmonary hypertension was precapillary vascular obstruction due to plexogenic pulmonary arteriopathy. There was a close geographic and temporal relationship between the epidemic and the marketing and intake of the appetite-depressing drug aminorex fumarate (Menocil). The epidemic was limited to the three above countries where aminorex had been on sale. In the individual patient the symptoms, usually dyspnea, angina pectoris and syncope on exertion, used to follow the beginning of the drug in-take after one year. A similar phase shift could be observed between marketing of the anoretic and the incidence of patients with chronic pulmonary hypertension of vascular origin. The new disease is compared with known forms of pulmonary vascular obstruction. It cannot be distinguished from classical primary pulmonary hypertension or from recurrent silent pulmonary thromboembolism on either clinical or functional grounds; it has plexogenic pulmonary arteriography in common with the former. The prognosis, however, is different: survival is considerably longer in patients with aminorex-associated pulmonary hypertension, and a marked decrease in the pulmonary vascular obstruction after 10 years is no exception. Considering the closeness of the various associations between the event (i.e. the epidemic) and its suspected cause (the anoretic aminorex) from the viewpoint of epidemiological, pharmacological, morphological and prognostic findings and considerations, there is little doubt that aminorex, besides other partly known and partly unknown factors, can in fact favour or cause the development of plexogenic pulmonary arteriography and pulmonary hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)