[Left cerebral ischemia in mitral valve aneurysm]. / Linkszerebrale Ischämie bei Mitralklappenaneurysma.

An anterior mitral leaflet aneurysm was detected by two-dimensional echocardiography using the transesophageal approach in a 53-year-old patient with cerebral ischemic event. The transesophageal examination allowed a clear description of the aneurysm which was confirmed during surgery. This case demonstrates that transesophageal echocardiography is the method of choice in evaluation of distinct valvular lesions. The importance of TEE examination in patients with a neurological history is evident.

Myocardial echinococcosis with perforation into the pericardium.

Though rare, cardiac echinococcosis should be included in the differential diagnosis of cardiac tumors, particularly in patients originating from endemic areas or with manifestation of hydatid disease in other organs. Diagnosis and localisation of the cysts is best accomplished with non-invasive methods such as 2-D transthoracic and transesophageal echocardiography, computed tomography and NMR. Excision of the cardiac cyst from the interventricular septum in a 21 year old patient with polyvisceral echinococcosis was performed with cardiopulmonary bypass. Adjunctive medical therapy with mebendazol is being continued for 24 months postoperatively. Twelve months after surgery the patient is asymptomatic without echocardiographic signs of recurrence.

[Papillary fibroelastoma of the aortic valve: primary echocardiography diagnosis in an asymptomatic patient]. / Papilläres Fibroelastom der Aortenklappe: Primär echokardiographische Diagnose bei asymptomatischer Patientin.

A rare case of a cardiac tumor located between the right coronary ostium and cusp of the aortic valve is reported. Diagnosis was confirmed by two-dimensional echocardiography. Histologic evaluation revealed a papillary fibroelastoma.

Effectiveness of converting enzyme inhibition (enalapril) for mild congestive heart failure.

The present study investigates the effectiveness of converting enzyme inhibition (CEI) on cardiac performance of patients with congestive heart failure (New York Heart Association functional class II). Outpatients (n = 12) were treated with enalapril, 5 to 10 mg twice daily, in addition to stable doses of digitalis and diuretic drugs. Before and after 4 and 12 weeks of treatment a treadmill exercise test and echocardiography were performed. Maximal oxygen uptake and exercise tolerance increased significantly and mean arterial pressure at rest and on exertion decreased significantly. Heart rate did not change. Left ventricular end-diastolic diameter decreased significantly. Serum angiotensin converting enzyme activity was reduced to nearly 0; plasma renin concentration, which was already elevated, increased further. Plasma norepinephrine levels did not change significantly. Treatment was tolerated well by all patients. CEI decreased preload and afterload, suggesting that they might have had an inappropriately elevated arteriolar and venous tone owing to a moderately stimulated renin angiotensin system and sympathetic nervous system. These conditions may lead to further deterioration of cardiac performance. By means of CEI one may be able to interrupt these pathogenetic mechanisms, relieving the already damaged heart from inappropriate elevations of preload and afterload and delaying or even preventing further deterioration of cardiac performance.

[Therapy of dilated cardiomyopathy with digitalis, diuretics and vasodilators]. / Therapie der dilatativen Kardiomyopathie mit Digitalis, Diuretika und Vasodilatatoren.

The treatment of dilated cardiomyopathy is primarily concerned with that of congestive heart failure. Digitalis is widely use in dilated cardiomyopathy but an improvement in the prognosis has not yet been demonstrated. Furthermore, the effects of digitalis in patients with sinus rhythm are debatable. If dilated cardiomyopathy induces atrial fibrillation and tachyarrhythmia, digitalis should be used. Diuretics are helpful in the treatment of congestive heart failure associated with dilated cardiomyopathy. By reducing hypervolemia and by venous dilatation, diuretics lower preload and afterload. This leads to relief of congestion and termination of the vicious cycle of congestive heart failure. Accordingly, the prognosis of dilated cardiomyopathy might be improved by diuretics. There are numerous diuretics acting differently on the renal tubules, the choice of which depends on the renal function and serum electrolyte concentrations. Reduction of preload and afterload improves congestive heart failure as has been demonstrated repeatedly. Many substances have therefore been used for arterial and venous dilation with differing results. At least for short-term periods, congestion is reduced and cardiac output increases. Especially inhibitors of angiotensin II converting enzyme are very effective since they act both in the arterial and venous systems. Additionally, inhibition of the action of angiotensin may be regarded as causal therapy since the renin-angiotensin system is the trigger for vasoconstriction and fluid retention in congestive heart failure. Unlike other substances, ACE inhibitors have been demonstrated to improve prognosis of patients with congestive heart failure. At present, combined diuretic therapy and angiotensin conversion enzyme inhibition would seem the most reasonable treatment for patients with dilated cardiomyopathy and sinus rhythm. If atrial fibrillation and tachyarrhythmia develop, additional digitalis therapy is effective.

Vasopressin and renin in high output heart failure of rats: hemodynamic effects of elevated plasma hormone levels.

We studied the hemodynamic effects of vasopressin and the renin-angiotensin system in an animal model of high output heart failure in conscious rats (aorto-caval fistula). We found significantly elevated levels of plasma renin concentration (p less than 0.025), norepinephrine (p less than 0.02), and up to 4 to 5 times higher values of vasopressin (p less than 0.002) in the rats with heart failure as compared with control animals. In contrast to the control rats that had a normally functioning osmoreceptor system, we found an inverse relationship between plasma osmolality and arginine vasopressin in the rats with heart failure in association with edema. Using a specific antagonist of the pressor activity of vasopressin, we found no significant effect on heart rate, mean arterial pressure, cardiac output (thermodilution), and peripheral vascular resistance in the control animals and in the rats with aorto-caval fistula. Captopril resulted in a significant fall of mean arterial pressure in the rats with shunt (p less than 0.001). The coincidence of high values of vasopressin and, in a number of animals, low plasma osmolalities and edema suggests a role of vasopressin in the formation of edema and in the development of "dilutional hypo-osmolality."

Coronary hemodynamic and metabolic effects of nifedipine in patients with coronary artery disease treated with beta-blocking drugs.

In humans, reflex sympathetic nerve activation modulates the direct cardiac action of nifedipine after systemic administration and results in a positive chronotropic and inotropic response. The coronary hemodynamic and metabolic effects of nifedipine were evaluated after propranolol-induced acute beta-receptor blockade in 12 patients with angiographically documented coronary artery disease. The intravenous injection of propranolol led to a decrease in heart rate, coronary blood flow and myocardial oxygen consumption and an increase in coronary vascular resistance and the coronary arteriovenous oxygen difference. Mean aortic pressure did not change. The subsequent intravenous administration of nifedipine resulted in a transient increase in coronary blood flow and a reduction in coronary vascular resistance and the coronary arteriovenous oxygen difference and a sustained decrease in mean aortic pressure and myocardial oxygen consumption without significant changes in heart rate. Thus, in the presence of beta-receptor blockade, the positive chronotropic response to nifedipine is attenuated and nifedipine reduces myocardial oxygen consumption significantly. The vasodilatory effect of nifedipine is maintained and a potential propranolol-related inappropriate vasoconstriction may be reversed. The combination of nifedipine and beta-receptor blocking agents may be useful in the treatment of patients with both effort-induced angina and angina related to changes in coronary vasomotor tone.

Four years of experience in endomyocardial biopsy--an immunohistologic approach.

Left ventricular biopsies from 376 patients (including 78 patients undergoing bypass surgery) were analyzed by light microscopy (necrosis, infiltration with or without fibrosis) and by immunohistology (bound antibodies). Circulating antisarcolemmal antibodies (ASA) were determined at the time of biopsy using a double-sandwich technique. Circulating antimyolemmal antibodies were assessed in intact rat and human cardiocytes. Histologic findings, heart catheterization, and echocardiography together with the patient's history established the diagnosis of perimyocarditis, myocarditis, postmyocarditic dilated cardiomyopathy, healed myocarditis, and healed perimyocarditis. Both bound and circulating ASA were found in up to 100% of cases in acute inflammatory heart disease and postmyocarditic cardiomyopathy, indicating a secondary immunopathogenesis of the myocardial disease. Analysis of immunoglobulin subclasses revealed: IgG-binding does not discriminate between acute/healing/healed carditis and postmyocarditic dilated heart disease (61.1%-91.7% positive); IgM binding is diagnostic for acute or healing perimyocarditis but has a relatively low incidence (33.3%); IgA binding occurs in acute or healing myocarditis (45.5%), perimyocarditis (33.3%), and in postmyocarditic heart disease (39.4%), but not in controls; complement fixation was never seen in controls, but was seen in acute myocarditis (45.4%), perimyocarditis (25%), and postmyocarditic heart disease (46%). Pretreatment of cryostat sections with collagenase to avoid "nonspecific" binding of antibodies to collagen considerably reduced the sensitivity but increased the specificity. Thus, endomyocardial biopsy proved a safe and valuable method for the further analysis of patients with carditis and myocardial disease of unknown origin.

Muzolimine therapy in patients with congestive heart failure in comparison with furosemide pretreatment. Effect on digoxin plasma concentration.

Eight patients suffering from congestive heart failure (NYHA III-IV) and pretreated with digoxin received muzolimine over 14 days in an open clinical study. The muzolimine dose was adjusted to 3/4 of the daily furosemide dose necessary to keep the body weight constant at least three days prior to the onset of muzolimine treatment. Plasma concentrations of epinephrine, norepinephrine, aldosterone, renin and digoxin were determined on the last day of the furosemide treatment period and on the last day of the muzolimine period. No significant changes were observed in plasma concentrations of epinephrine, aldosterone, renin, creatinine, and potassium. After muzolimine treatment, however, body weight and sonographically determined liver size decreased further and plasma norepinephrine concentrations were significantly lower. The digoxin concentrations did not change after muzolimine treatment. The results demonstrate the beneficial effect of muzolimine in heart failure patients. Since plasma concentration of digoxin does not change despite marked diuretic effects of muzolimine no relevant interaction between both substances has to be expected.

[Effect of nifedipine and nitroglycerin on epicardial vessels in coronary heart disease]. / Wirkung von Nifedipin und Nitroglycerin auf die epikardialen Leitungsgefässe bei koronarer Herzkrankheit.

The effect of nifedipine and nitroglycerin on the diameter of epicardial coronary arteries, the stenosis diameter, as well as arterial blood pressure and heart rate were recorded in 20 patients with coronary-heart disease. Nifedipine (20 mg sublingually) caused a significant fall in arterial pressure and a significant rise in heart rate. Additional administration of nitroglycerin (0.8 mg sublingually) caused a further fall in arterial pressure while heart rate remained constant. A definite relaxation (vasodilatation) of the epicardial vessels was demonstrated after nifedipine and a further increase after nitroglycerin. While nifedipine on average led to a significant increase in the diameter at the site of stenosis, response of individual stenoses was highly variable. In one patient with subtotal stenosis of the anterior interventricular branch a complete, transitory occlusion at the site of the stenosis occurred during nifedipine medication. This paradoxical reaction was not noted after nitroglycerin. Relaxation of the epicardial coronary arteries by nifedipine with suppression of phasic tone thus seems to be the major part of its anti-anginal effect. This effect is potentiated by nitroglycerin so that the combination of nitrate and calcium-antagonist appears to be therapeutically reasonable. In individual patients, however, there may be a paradoxical reaction to nifedipine.

[Acute hemodynamic effects of alifedrine in patients with heart failure]. / Hämodynamische Akutwirkung von Alifedrin bei Patienten mit Herzinsuffizienz.

The newly synthesized cardiotonic agent alifedrine (1-cyclohexyl-3-[(1S, 2R)-2-hydroxy-methyl-2-phenylethylamino]-propan-1-one) was shown to have vasodilating and positive inotropic effects in experimental animals. The effectiveness was tested in 8 patients with congestive heart failure already receiving digitalis and diuretics. After the intravenous administration of 40 mg alifedrine, cardiac output and stroke volume index increased and systemic vascular resistance and left ventricular filling pressure decreased. Left ventricular ejection fraction improved and there were no significant changes in heart rate and mean aortic pressure. Alifedrine, therefore, improves left ventricular performance in patients with congestive heart failure treated with digitalis and diuretic agents.

Role of the renin-angiotensin system in the development of congestive heart failure in the dog as assessed by chronic converting-enzyme blockade.

Hormonal factors may be important in the regulation of peripheral vascular resistance (PVR) in congestive heart failure (CHF). The role of the renin-angiotensin system in the development of CHF was studied in 16 unanesthetized dogs. CHF was induced by rapid right ventricular pacing, with and without chronic converting-enzyme inhibition (CEI) by captopril. The hemodynamic changes and the activity of renin, aldosterone, norepinephrine and vasopressin were studied. The control dogs showed a greater decrease in cardiac output and a greater increase of mean pulmonary artery pressure than the captopril-treated group. In the group with CEI, only a small, transient increase in PVR was observed during the development of CHF; in the control group, there was an increase of 94% of basal values. The control group showed a continual increase of renin, aldosterone and norepinephrine. Four control dogs showed an inappropriately high secretion of arginine vasopressin. The increase of sympathetic nervous activity was only insignificantly attenuated by angiotensin II inhibition and was without a considerable influence on PVR except for an early transient increase in vascular tone. In our animal model, the renin-angiotensin system plays an important role in the regulation of PVR in CHF. In this kind of CHF the sympathetic nervous system appears to be of minor importance for the long-term regulation of PVR. Plasma arginine vasopressin levels were increased in control dogs; this increase may contribute to the increased vascular tone.

Diagnostic relevance of humoral and cytotoxic immune reactions in primary and secondary dilated cardiomyopathy.

Circulating muscle-specific antimyolemmal antibodies (AMLAs) were found in 18 of 61 patients with secondary dilated cardiomyopathy (DC). All 18 patients had clinical or histologic evidence of previous perimyocarditis. AMLAs were found both in patients' serum samples and bound to the sarcolemmal sheath of the autologous myocardial biopsy specimen. Only AMLAs in postmyocardiac DC induced cytolysis of vital cardiocytes in the presence of complement, whereas hepatocytes remained unaffected. Titers of AMLAs correlated with the degree of cardiocytolysis. In contrast, antiinterfibrillary antibodies were found in 49% patients with primary DC (n = 79) and in 61% of patients (n = 30) with alcoholic DC. The incidence of antifibrillary antibodies of the antimyosin type was 23 and 24%, respectively. Incidence of both antibodies increased according to the severity assessed by New York Heart Association functional classes. Circulating immune complexes assayed by a new Clq-solid phase fluorometric assay were present in 30% of patients with postmyocarditic DC only. Lymphocyte-mediated cytotoxicity against heterologous cardiac target cells (K-cell activity) was measured in 33% of patients each with primary and secondary alcoholic DC but not postmyocarditic DC. There were no blocking factors in primary but were some in alcoholic heart disease.

Effect of intravenous and intracoronary nifedipine on coronary blood flow and myocardial oxygen consumption.

The effect of intravenous and intracoronary nifedipine on coronary sinus blood flow, coronary vascular resistance, and myocardial oxygen consumption was studied in 20 patients with coronary artery disease. An intravenous infusion of 1.0 mg nifedipine resulted in a decrease in mean aortic pressure, an increase in heart rate and coronary blood flow, and no significant change in myocardial, oxygen consumption. In contrast, the intracoronary injection of 0.1 mg nifedipine led to a moderate reduction in mean aortic pressure, no change in heart rate, an increase in coronary blood flow, and a significant reduction in myocardial oxygen consumption. During rapid atrial pacing before and approximately 6 minutes after the intracoronary nifedipine injection, coronary blood flow and myocardial oxygen consumption reached identical levels. Thus, only intracoronary injection of nifedipine increases coronary flow in the presence of reduced myocardial oxygen consumption. After intravenous administration, reflex tachycardia counteracts the direct myocardial effect of nifedipine and the potential oxygen-saving effect of afterload reduction. There is no evidence of a prolonged oxygen-sparing effect after cessation of the immediate effects.

[Effect of intracoronary nifedipine on coronary sinus blood flow and myocardial oxygen consumption in patients with coronary artery disease]. / Koronarsinusfluss und myokardialer Sauerstoffverbrauch nach intrakoronarer Nifedipininjektion bei Patienten mit koronarer Herzerkrankung.

UNLABELLED: Reflex sympathetic nerve activation obscures the direct myocardial effect of Nifedipine after intravenous administration. Consequently, in 10 patients with coronary artery disease 0.1 mg of Nifedipine were injected into the left coronary artery to evaluate its specific effect on coronary sinus blood flow (CSF), coronary vascular resistance (CVR), and myocardial oxygen consumption (MVO2). One minute after Nifedipine, CSF increased from 115 +/- 15 to 193 +/- 47 ml/min (p less than 0.001), and CVR decreased from 0.92 +/- 0.16 to 0,54 +/- 0.12 mm Hg X min X ml-1 (p less than 0.001). Mean aortic pressure dropped from 107 +/- 5 to 99 +/- 3 mm Hg (p less than 0.01). MVO2 was reduced from 14.6 +/- 2.6 to 11.7 +/- 2.8 ml O2 X min-1 (p less than 0.05). After five minutes CSF (113 +/- 18) and MVO2 (14.9 +/- 3.1) had returned to their preinjection level. Additionally, CSF and MVO2 were measured during rapid atrial pacing (mean rate 118 +/- 6 min-1). Average CSF and MVO2 values were 172 +/- 63 and 19.8 +/- 5.0 before and 177 +/- 69 and 20.6 +/- 7.3 approximately 6 minutes after Nifedipine injection. CONCLUSIONS: Intracoronary Nifedipine results in coronary vasodilation and subsequently in an increase in coronary flow. The concomitant reduction in MVO2 provides evidence for an oxygen sparing, negative inotropic effect of Nifedipine, which, however, is of very limited duration. A sustained oxygen-saving effect during periods with increased oxygen demand could not be shown.

The renin-angiotensin-aldosterone system, antidiuretic hormone and sympathetic nerve activity in an experimental model of congestive heart failure in the dog.

1. Congestive heart failure was induced in dogs by rapid pacemaker stimulation of the heart (240-280/min) for 14 days. This represents a model of low output heart failure which permits the study of the development and reversal of congestive heart failure in an anatomically intact circulation in the unanaesthetized animal. 2. Cardiac output was reduced by 54%. Pulmonary artery pressure gradually increased by a factor of 2.4 and pulmonary capillary pressure rose to 4.6 times basal values. The animals retained a mean of 1.1 litres of fluid. 3. At the same time there was a gradual increase of plasma levels of renin, angiotension II, aldosterone, noradrenaline and adrenaline. After the pacemaker stimulation was discontinued all hormone levels returned to normal, the retained fluid was excreted, and intracardiac pressures and cardiac output returned to baseline values. 4. When heart failure was established at the end of the pacemaker stimulation period an inappropriately high secretion of antidiuretic hormone in relation to plasma osmolality was observed in five of six dogs. 5. It is concluded that beside the well-known non-hormonal renal factors, these hormone systems may be involved in the formation of oedema in congestive heart failure. The inappropriately high levels of antidiuretic hormone may cause hyponatraemia by water retention, representing a state of 'dilutional hypo-osmolality'.