[Löffler fibroblastic endocarditis in the thrombotic stages in isolated right ventricular tissue eosinophilia]. / Endokarditis fibroplastica Löffler im thrombotischen Stadium bei isolierter rechtsventrikulärer Gewebe-Eosinophilie.

We report on a male, 31 year old, Turkish patient with an intracardiac mass in the right ventricle, reduction of performance and weight, as well as intermittent fever. No eosinophilia was documented in the peripheral blood; cardiac function was primarily normal. Besides the differential diagnosis of Löffer's endocarditis (endomyocardial fibrosis) an inflammatory disease and a malignant cardiac tumor were suggested. The diagnosis of Löffler's endocarditis could not be confirmed morphologically by echocardiography nor histologically by right ventricular biopsy. Operative removal of the mass lesion was necessary because of fast tumor progression, fulminant pulmonary embolism, and infiltration of the tricuspid valve. Only then, histologically Löffler's eosinophilic endocarditis of thrombotic stage was diagnosed. Antiphlogistic therapy with cortisone was initially performed. With a dose reduction after 6 months, a relapse of the thrombotic mass occurred. Therefore, continuous treatment with cortisone and azathioprine was induced followed by further tumor regression and further clinical stabilization since 8 months of treatment.

N-acetylcysteine attenuates nitroglycerin tolerance in patients with angina pectoris and normal left ventricular function.

The aim of this study was to assess whether N-acetylcysteine (NAC) is able to prevent tolerance to a 48-hour infusion of nitroglycerin (NTG) in the setting of normal left ventricular function. In 16 patients, the hemodynamic response to 0.8 mg sublingual (s.l.) NTG was assessed by measuring mean arterial, pulmonary artery, pulmonary capillary wedge and right atrial pressures, cardiac output, and calculation of the systemic and pulmonary vascular resistances. The parameters were obtained at baseline and 1 to 10 minutes after the s.l. NTG application (day 1). NTG was started at 1.5 microg/kg/min; concomitantly, a bolus of 2,000 mg of NAC was administered, followed by an infusion of 5 mg/kg/hour. Both infusions were continued for 48 hours, and the hemodynamic study was repeated (day 3). The same measurements were obtained in a matched control group of 15 patients with NTG infusion alone. Plasma renin activity, aldosterone, and norepinephrine were measured before and after the infusion period. The first s.l. NTG infusion (day 1) caused a significant decrease in mean arterial (p <0.01), pulmonary artery (p <0.001), and right atrial pressures (p <0.001), and in systemic (p <0.01) and pulmonary vascular resistances (p <0.001) in both groups. After the 48-hour infusion (day 3), there was a total loss of nitrate-mediated vasodilation (pressure values and vascular resistances day 3 > day 1) in 5 of 16 patients (NAC nonresponders), whereas in the other 11 of 16 patients (NAC responders), there was significant vasodilation throughout the infusion period. Tolerance had developed in 14 of 15 patients with NTG infusion alone. The same difference (responder vs nonresponder vs NTG alone) held true regarding the response to the second s.l. NTG infusion after 48 hours. The neurohormonal counter-regulation and intravascular volume expansion (increase in plasma renin activity, p <0.001, and norepinephrine, p <0.05; decrease in aldosterone, p <0.01) did not differ between responders and nonresponders. We conclude that NAC attenuates tolerance development to a continuous NTG infusion in a specific patient subgroup and that this occurs despite the same amount of neurohormonal counter-regulation and intravascular volume expansion compared with patients with tolerance development.

[Persistent dilatation of non-stenosed epicardial arteries in 24- and 48-hour nitroglycerin infusion]. / Persistierende Dilatation nichtstenosierter Epikardarterien unter 24- und 48stündiger Nitroglycerin-Infusion.

UNLABELLED: It is still a matter of dispute to what extent a direct loss of nitrate mediated vasodilatation (true tolerance) contributes to the development of nitrate tolerance. Aim of this study was to assess to what extent the dilatation of non-obstructed segments of epicardial arteries is attenuated during a continuous 24- and 48-h-infusion of nitroglycerin. In a prospective, randomized and blinded study we investigated 32 patients who underwent diagnostic coronary angiography. All cardiac medication was withdrawn at least for 24 h; patients were randomized to either a 24 h NTG-infusion (group A; 0-24 h saline infusion followed by a 24 h NTG-infusion; n = 16) or a 48 h NTG-infusion (group B; 0-48 h of NTG-infusion; n = 16) in a dosage of 1.5 micrograms/ kg/min. The patients were included if 5 proximal segments of the left coronary artery showed no visible atherosclerosis. A coronary angiography was performed after 24 and 48 h respectively. The lumen diameters were measured by quantitative coronary analysis at baseline and 1 and 3 min after application of 0.2 mg of NTG intracoronarially (i.c.). Blood samples were drawn before and after 24 and 48 h of infusions to measure hematocrit and neurohormones. In group A after 24 h of saline infusion there was a significant increase in lumen diameter from 3.14 +/- 0.17 mm at baseline to 3.51 +/- 0.11 mm (p < 0.001) and 3.60 +/- 0.21 mm (p < 0.001) after 1 and 3 min of NTG i.e. respectively. After 24 h of NTG-infusion there were no significant changes in baseline and values after further NTG i.e. In group B after 24 h of NTG-infusion no significant change in lumen diameter was detectable after NTG i.e. (3.57 +/- 0.23 mm to 3.63 +/- 0.13 mm) and the mean diameter remained unchanged after prolongation of NTG to 48 h (3.58 +/- 0.33 mm). There were no significant differences between the baseline values and the responses to i.e. NTG after 24 and 48 h of NTG infusion. Hematocrit and aldosterone levels decreased significantly after NTG-infusion but not following saline. Renin and norepinephrine remained unchanged throughout the NTG-infusion-periods. IN CONCLUSION: The vasodilatation of non-obstructed segments of epicardial arteries persists during a prolonged infusion period and there is no induction of vascular tolerance between the 24 and 48 h infusion period. These findings further support that there is a different susceptibility of arteries and veins to nitrate tolerance.

Influence of captopril on nitroglycerin-mediated vasodilation and development of nitrate tolerance in arterial and venous circulation.

We investigated whether captopril is able to potentiate vasodilation and prevent tolerance to a 48-hour infusion of nitroglycerin (NTG). Twenty-six patients were randomly assigned to a 7-day regimen of captopril (50 mg/day) or placebo. The hemodynamic response to a 0.8 mg sublingual NTG dose was assessed by measuring mean arterial pressure (MAP), mean pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), and cardiac output (CO), and calculating systemic (SVR) and pulmonary vascular resistances (PVR). The parameters were obtained serially at baseline and 1 to 10 minutes after the sublingual NTG application (day 1). Then intravenous NTG was started and maintained for 48 hours (1.5 micrograms/kg/min), and the hemodynamic study was repeated (day 3). There was no difference between the captopril and the placebo groups at day 1 (baseline values and response to sublingual NTG). After the 48-hour infusion, there was a complete loss of the NTG effects in the placebo group (day 1 vs day 3: PAP, 20 +/- 5 mm Hg vs 21 +/- 8 mm Hg; MAP, 86 +/- 11 mm Hg vs 90 +/- 9 mm Hg; SVR, 1295 +/- 330 mm Hg vs 1380 +/- 465 dyne.sec.cm-5) whereas there was still evidence of a persistent vasodilation in the captopril group (day 1 vs day 3: PAP, 19 +/- 4 mm Hg vs 13 +/- 4 mm Hg; MAP, 84 +/- 9 mm Hg vs 74 +/- 10 mm Hg; SVR, 1265 +/- 280 mm Hg vs 1140 +/- 425 dyne.sec.cm-5). The response to sublingual NTG on day 3 was markedly attenuated in the placebo group only. We conclude that captopril does not increase the vasodilatory response to nitroglycerin but is able to prevent developing nitrate tolerance in arterial and venous circulation.

Valvular aortic stenosis: risk of syncope.

BACKGROUND AND AIMS: Syncope is a serious complication of aortic stenosis. The aim of this study was to determine whether hemodynamic parameters are useful for estimating the risk of syncope in aortic stenosis. METHODS: In 43 patients with aortic stenosis, cardiac catheterization and echocardiography were performed to measure the pressure gradient across the aortic valve, the aortic valve area, left ventricular mass index, systolic left ventricular wall stress and peak systolic coronary artery flow velocities. Hemodynamic parameters were correlated with syncope and the accuracy of those parameters for determining the risk of syncope were assessed. RESULTS: Ten out of 43 patients experienced syncope. The highest correlation with syncope was found for systolic left ventricular wall stress (R = 0.74, p < 0.001). In descending order of correlation were peak systolic coronary artery flow velocity (R = 0.68, p = 0.002), the pressure gradient across the aortic valve (R = 0.62, p = 0.01) and the aortic valve area (R = 0.43, p = 0.03). Left ventricular mass index was not significantly correlated with syncope. Multivariate analysis revealed systolic left ventricular wall stress to be the only factor contributing to determining syncope (F-to-remove: 47.8). A discriminative value of > 225 dyn/cm-2 x 103 for left ventricular wall stress identified patients with a history of syncope with a specificity of 97% and a sensitivity of 90%. CONCLUSIONS: Syncope in aortic stenosis is closely correlated to increased left ventricular wall stress and attenuated, peak systolic coronary flow velocities. Cut off values may be used to identify patients with an increased risk of syncope.