[Gallopamil and molsidomine in patients with coronary heart disease. A comparative study]. / Gallopamil und Molsidomin bei Patienten mit KHK. Vergleichende Untersuchung.

In a randomised, crossover trial, 20 patients with electrocardiographically proven coronary heart disease and exercise-inducible angina pectoris, the antiischemic effect of gallopamil (3 x 50 mg) and molsidomine (2 x 2 mg) were studied. Both therapies showed a clear anti-ischemic effect in bicycle exercise tests. The average ST-segment depression at maximal comparable workload was reduced from 0.16 mV (without medication) to 0.06 mV with gallopamil and 0.09 mV with molsidomine, the difference between the two therapies was significant (p less than or equal to 0.05). The increase in the heart rate, as well as systolic and diastolic blood pressure during exercise, were less marked with both therapies. The correlation between rate-pressure product and average ST-segment depression showed a better reduction in ST-segment depression at comparable myocardial O2-consumption for gallopamil in comparison with molsidomine. It is concluded that gallopamil improves myocardial perfusion and microcirculation in ischemic areas more than molsidomine.

Determinants of survival in patients with congestive cardiomyopathy: quantitative morphologic findings and left ventricular hemodynamics.

We analyzed data from 68 consecutive patients with congestive cardiomyopathy to evaluate the prognostic significance of quantitative morphologic findings in left ventricular myocardium as compared with the prognostic significance of left ventricular hemodynamics. Left ventricular endomyocardial biopsy specimens were obtained from all patients during diagnostic heart catheterization. Myocardial fiber diameter, volume fraction of interstitial fibrosis, and intracellular volume fraction of myofibrils were determined by light-microscopic morphometry. All patients had normal coronary arteriograms, but reduced left ventricular ejection fractions. There were 23 deaths during a mean follow-up period of 1124 days. Multivariate regression analysis (Cox model) revealed that left ventricular ejection fraction (p less than .00001) and left ventricular systolic pressure (p less than .01), but not morphometric findings in biopsy specimens, were independent predictors of cardiac death. Thus, morphologic findings in the left ventricular myocardium do not contribute significantly to the prognostic evaluation in patients with congestive cardiomyopathy studied by hemodynamic and angiographic methods.

[Significance of morphological findings in congestive cardiomyopathy]. / Die Bedeutung morphologischer Befunde bei der kongestiven Kardiomyopathie.

In 48 consecutive patients with myocardial disease, left ventricular biopsies were taken during diagnostic heart catheterization. Morphometric quantification of ultrastructural alterations of the heart muscle was performed. The patients were subdivided into 3 groups by means of clinical criteria: Group A: 18 surviving patients with pathological ECG, normal left ventricular ejection fraction, and normal coronary arteries. The mean follow-up in this group was 22 months. Group B: 23 surviving patients with congestive cardiomyopathy, i.e., normal coronary arteries and depressed left ventricular ejection fraction. The mean follow-up in this group was 23 months. Group C: 7 patients with congestive cardiomyopathy, who died during the study period from cardiac complications. The mean survival time of these patients after heart catheterization was 23 months. Myocardial fiber diameter, volume fraction of interstitial fibrosis, intracellular volume fraction of myofibrils, and the total myofibrillar mass per 100 g heart muscle were determined by light microscopic morphometry. In a pilot study comprising 26 patients the reproducibility of the morphological results were assessed by investigation of two different biopsy specimens taken from different areas of the left ventricular wall of each patient. The study revealed a coefficient of variation of 6% for myocardial fiber diameter, 28% for myocardial fibrosis, and 4% for myofibrillar volume fraction. Since there are only poor results from morphological investigations of the diseased myocardium, it was the purpose of the follow-up study presented in this paper: To quantify ultrastructural alterations of the heart in congestive cardiomyopathy by morphometric techniques. To correlate the quantitative morphometric data with the contractile state of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of coronary reserve: a mechanism for angina pectoris in patients with arterial hypertension and normal coronary arteries.

The pathogenesis of angina pectoris in patients with left ventricular hypertrophy secondary to arterial hypertension and with normal coronary arteries remains uncertain. We measured coronary blood flow (argon method) in 12 control subjects and in 16 patients with arterial hypertension at rest and after intravenous administration of dipyridamole (0.5 mg/kg). In the patients with arterial hypertension, coronary blood flow response to dipyridamole was markedly reduced (p less than .001 as compared with control values). During coronary vasodilation there was a linear correlation between coronary resistance and left ventricular end-diastolic pressure (r = .67, p less than .001). Left ventricular catheter biopsy specimens did not reveal alterations in myocardial microvasculature. These findings suggest that reduction of coronary reserve may be an important contributor to the pathogenesis of angina pectoris in these patients.

Quantitative morphologic findings of the myocardium in idiopathic dilated cardiomyopathy.

This study assesses the relation between quantitative morphologic findings and left ventricular contractile function in patients with idiopathic dilated cardiomyopathy. Left ventricular endomyocardial catheter biopsy specimens were obtained from 73 patients during diagnostic heart catheterization. All patients had normal coronary arteriograms but abnormal electrocardiograms. Twenty-six patients had normal left ventricular function (ejection fraction greater than or equal to 55%), whereas 47 patients had contractile dysfunction (ejection fraction less than or equal to 54%). Myocardial fiber diameter, volume fraction of interstitial fibrosis, and intracellular volume fraction of myofibrils were determined by light microscopic morphometry. Results of light microscopic morphometry were confirmed by electron microscopic morphometry in 12 patients. The coefficient of variation (analysis of several biopsies from the same patient) was 6% for determination of fiber diameter, 43% for interstitial fibrosis, and 3% for volume fraction of myofibrils. Fiber diameter (r = -0.32, p less than 0.01) and fibrosis (r = -0.47, p less than 0.001) showed a negative correlation, the volume fraction of myofibrils (r = 0.55, p less than 0.001) and calculated myofibrillar mass per 100 g of myocardium (r = 0.64, p less than 0.001) a positive correlation with the ejection fraction. Thus, (1) sampling error is low for determination of fiber diameter and myofibrils but high for evaluation of fibrosis, and (2) a reduction in the volume fraction of myofibrils and an increase in fibrosis are morphologic correlates of left ventricular dysfunction in patients with idiopathic dilated cardiomyopathy.

[Angina pectoris syndrome in patients with normal coronary arteriograms (X syndrome) (author's transl)]. / Das Syndrom pektanginöser Beschwerden bei Patienten mit normalem Koronarogramm (syndrom X).

In 37 patients with typical exercise-dependent angina pectoris but with normal coronary arteriograms and normal left ventricular function at rest (X syndrome), the dipyridamole-induced dilatory reserve of the coronary vascular system was reduced significantly to about 50% of control values (P less than 0.001). There were no changes in the small vessels causing the reduced dilatory reserve, but ultrastructural changes in the mitochondria were demonstrable. In the patients with X syndrome there was a significant reduction of lactate extraction (P less than 0.05) after electrical atrial stimulation (150/min) and in most cases lactate production was demonstrable. In the control group the myocardial lactate uptake was unchanged. Left ventricular function in patients with X syndrome was normal at rest whereas during exercise it was significantly reduced (P less than 0.001). These results show that X syndrome consists of a particular form of ischaemic heart disease with still normal left ventricular function at rest, but disordered pump activity during physical stress.

[Apico-aortic conduit for surgical treatment of supravalvular aortic stenosis with hypoplastic ascending aorta (author's transl)]. / Die chirurgische Behandlung supravalvulärer Aortenstenosen mit hypoplastischer aszendierender Aorta durch einen apiko-aortalen Conduit.

Surgical treatment of two patients with diffuse supravalvular aortic stenosis including hypoplastic aortic valve ring was undertaken. In both patients a left ventricular apical-thoracic aorta conduit containing a bioprosthesis was used. Intra- and postoperative pressure measurements demonstrated relief of the systolic pressure gradients present preoperatively between left ventricle and ascending aorta distal to the stenosis. Both patients are asymptomatic at four and eleven months after surgery, respectively.

Reduced coronary dilatory capacity and ultrastructural changes of the myocardium in patients with angina pectoris but normal coronary arteriograms.

Hemodynamic and metabolic studies were performed in 15 patients without heart disease (controls, group A), in 21 patients with typical stress-induced anginal pain but normal coronary and left ventricular angiograms (angina pectoris with normal arteriogram, group B), and in 10 patients with angiographically proved coronary artery disease (CAD, group C). Coronary dilatory capacity, determined by measuring total myocardial blood flow at rest and during maximal coronary vasodilatation (dipyridamole, 0.5 mg/kg i.v.), was markedly reduced in group B and C patients. In group B patients, left ventricular catheter biopsy specimens revealed no evidence of small-vessel disease, but did show histologic alterations of mitochondria. During atrial pacing, the control subjects showed no changes in myocardial lactate uptake, whereas in group B patients, myocardial lactate production occurred. In contrast to controls, patients in group B showed a significant decline in ejection fraction and circumferential fiber shortening during isometric exercise. These findings suggest that myocardial ischemia is the cause of angina pectoris in patients who have angina but normal coronary arteriograms.

Comparison between the effect of postextrasystolic potentiation and the effect of nitrates on left ventricular function for the differentiation between reversible and irreversible left ventricular asynergy.

In patients with coronary heart disease (CHD) it is important to differentiate between reversible and irreversible left ventricular (LV) asynergy. Therefore global and regional LV function was investigated in the postextrasystolic beat (PES) and after isosorbide dinitrate (ISDN). In 24 patients LV angiograms were performed before and after ISDN. The ejection fraction (EF) was determined in a sinus beat and in PES. Regional LV performance was measured by the shortening of the length axis and six short hemiaxes. In 12 patients with normal LV function at rest EF increased from .72 +/- .04 (+/- 1 SD) to .77 +/- .04 (P less than 0.05) after ISDN and rose further to .81 +/- .02 in the PES (P less than 0.05). In 12 patients with CHD and LV asynergy EF increased from .43 +/- .12 to .47 +/- .13 after ISDN (P less than 0.05) and rose further to .57 +/- .13 in the PES (P less than 0.02). After ISDN 23/39 asynergic axes improved, 15/39 axes did not change, 1/39 axis decreased its shortening by 12%. In the PES 26/39 axes improved, 6/39 axes did not change; 7/39 axes showed less shortening, presumably due to a systolic shift of blood into dyskinetic regions with LV scar. It is concluded: The PES affects viable myocardium more than does ISDN; the PES is easier to perform and permits a more precise distinction between reversible and irreversible LV dyskinesis.

[Coronary reserve, left ventricular function, and coronary risk factors in patients with myocardial infarction, but normal coronary arteries (author's transl)]. / Koronarreserve, linksventrikuläre Funktion und Konstellation von "Risikofaktoren" bei Patienten mit transmuralem Myokardinfarkt und angiographisch normalen Koronararterien.

In 5 patients with angiographically normal coronary arteries and previous myocardial infarction (left ventricular a- or dyscinesia), measurement of coronary reserve revealed normal values. On average, patients with myocardial infarction and normal coronary arteries were younger than patients with angiographically proven obstructive coronary lesions (p less than 0,001), and did not exhibit a rise in coronary risk factors. These results suggest that in some cases myocardial infarction is due to acute, completely reversible occlusion or severe stenosis of larger coronary arteries without morphological or functional defects of coronary arteries detectable later on.

Nitrates and ectopic ventricular activity in mitral valve prolapse: clinical and experimental data.

Three patients with mitral valve prolapse, high grade ventricular arrhythmias and a strong family history of sudden death were studied utilizing continuous Ecg monitoring and intracardiac stimulation and recording techniques. Analysis of 6-hour ambulatory Ecgs revealed frequent premature ventricular beats (PVBs) including repetitive and multiform PVBs in each patient. The electrophysiological studies demonstrated normal parameters of intracardiac conduction and refractoriness providing no evidence for reentrant mechanisms. Acute drug testing with 0.4 mg sublingual nitroglycerin completely suppressed all ventricular arrhythmias. During maintenance therapy antiarrhythmic nitrate efficacy was only partly confirmed monitoring the effects of 4 x20 mg isosorbide dinitrate on 6-hour ambulatory Ecgs. The electrophysiological parameters of intracardiac conduction and refractoriness were not significantly altered by 0.4 mg sublingual nitroglycerin. Experimental data obtained from isolated rabbit atria and canine ventricles revealed no significant action of nitroglycerin in the parameters of cardiac automaticity and conduction including transmembrane electrical activity of normal and hypoxically damaged SA nodal, atrial and ventricular fibers. It is concluded that a) PVBs in patients with mitral prolapse appear related to ectopic automaticity; b)nitrates may suppress ventricular ectopy in these patients; c) antiarrhythmic nitrate efficacy is not related to direct membrane effects.

[Coronary heart disease in patients with primary type V hyperlipoproteinemia (author's transl)]. / Koronare Herzkrankheit bei Patienten mit Hyperlipoproteinämie Typ V.

In two patients with primary Type V hyperlipoproteinemia with typical clinical features including recurrent bouts of abdominal pain a myocardial infarction was diagnosed. In both cases coronary angiography revealed a severe three vessel disease. The case reports demonstrate that the incidence of ischemic heart disease in patients with Type V hyperlipoproteinemia is higher than reported in the literature. In each case of severe abdominal pain, even in younger Type V patients, a myocardial infarction has to be excluded, In both patients a selective depression in the activity of lipoprotein lipase was found. The possible pathogenetic implication of this finding will be discussed.

[Functional assessment of coronary-artery stenosis (author's transl)]. / Funktionelle Beurteilung von Koronararterienstenosen. Ermittlung linksventrikulärer lokaler Kontraktilitätsstörungne während der Belastung

Left-ventricular angiography was performed in 28 patients after measuring ascending aortic and left ventricular pressures and during isometric exercise (hand grip, 0.3-0.4 kg/cm2 for 3 min). In 13 patients coronary blood flow was measured at rest and during hand-grip exercise by means of the argon method. Eight patients without heart disease served as controls. In 14 patients with coronary heart disease abnormal left-ventricular kinetics, demonstrated already at rest, got worse during hand-grip exercise. In five patients with normal left-ventricular angiograms at rest hypokinesia and dyskinesia occurred during isometric exercise. The coronary artery supplying the abnormal ventricular wall had a 50-75% decrease in diameter. One patients with isolated 25% stenosis had normal left-ventricular kinetics both at rest and on hand-grip exercise. In all patients coronary blood flow rose by 60-90% during isometric exercise. It iducing a significant rise in myocardial oxygen demand and increased coronary blood flow.