[Hemodynamic effect of molsidomine in coronary patients with heart failure with clinically manifest nitrate tolerance]. / Hämodynamische Wirkung von Molsidomin bei herzinsuffizienten Koronarkranken mit klinisch manifester Nitrattoleranz.

Objective of the present study was to investigate the hemodynamic response to molsidomine in nitrate tolerance state. In 13 out of 16 patients (5 women, 11 men, 62 [53/71] years [median, 25%/75%-percentiles]) with chronic heart failure (NYHA stage II-III; median angiographic ejection fraction (EF) 55%) and coronary artery disease (stenosis of at least 75%) the development of tolerance under the continuous infusion of high doses of nitroglycerin (10 mg/h) was observed. Tolerance was defined as a benefit loss of at least 50% of the initial nitroglycerin effect with respect to the pulmonary capillary wedge pressure. Compared to the state of tolerance to nitroglycerin the infusion of 10 mg molsidomine over 15 minutes resulted in significant changes of the median values (25%/75%-percentiles) of mean right atrial pressure from 16 (12/21) to 9 (5/12) mmHg (p < 0.01), mean pulmonary artery pressure from 37 (30/40) to 24 (20/30) mmHg (p < 0.001), mean pulmonary capillary wedge pressure from 22 (18/25) to 15 (10/22) mmHg (p < 0.01) and cardiac output from 4.1 (3.5/4.7) to 5.2 (4.2/5.6) l/min (p < 0.01). This action of molsidomine corresponded to a complete overcoming (> 100%) of the benefit loss observed during the development of nitrate tolerance with respect to all above-mentioned hemodynamic parameters. Under parallel maintainance of nitroglycerin infusion (10 mg/h) these hemodynamic effects of molsidomine, i.e. at least 90% of the peak effect, lasted for 147 (130/182) minutes (median, 25%/75%-percentiles). Baseline values, i.e. a loss of at least 75% of the molsidomine effect, were only reached after 363 (319/412) minutes (median, 25%/75%-percentiles).(ABSTRACT TRUNCATED AT 250 WORDS)

[The effect of verapamil on left ventricular diastolic function in coronary heart disease]. / Einfluss von Verapamil auf die diastolische Funktion des linken Ventrikels bei koronarer Herzkrankheit.

Echocardiography was performed on 21 patients (6 women, 15 men; mean age 52 [40-68] years) with coronary heart disease (at least 75% stenosis), before and after taking 80 or 120 mg verapamil, to test the drug's acute effect on left-ventricular (LV) relaxation and filling. After taking 80 mg verapamil the only significant (P less than 0.05) decrease was in the proportion of isovolumetric relaxation time to cardiac cycle. The echocardiographic changes were significantly (P less than 0.01) greater after 120 mg than 80 mg: Isovolumetric relaxation time decreased by 13 and 4%, respectively, flow integral of early diastolic LV filling (E wave) increased by 17 and 2%, and atrial filling fraction (atrial component of LV filling) fell by 14 and 2%. Apparently verapamil has a positive effect on the energetically important early diastolic relaxation of the left ventricle. Thus diastolic abnormalities of LV function in patients with coronary heart disease are not fixed but can be at least partially improved with verapamil.

Noninvasive determination of pulmonary artery wedge pressure: comparative analysis of pulsed Doppler echocardiography and right heart catheterization.

To compare left ventricular filling variables as derived by transmitral pulsed Doppler echocardiography (tpDE) and hemodynamic variables as assessed at right heart catheterization (RHC), 104 ICU patients (64 male, 40 female) aged 26 to 73 yr (mean 54.6 +/- 10.3) without valvular heart disease were examined. Simultaneously with RHC, transmitral flow velocity profiles were obtained by tpDE, and the ratio of the velocity-time integrals of late diastolic active (A wave) and early diastolic passive inflow into the left ventricle (E wave) was calculated (A/E ratio). Invasively determined pulmonary capillary wedge pressure (WP) ranged from 3 to 36 mm Hg (median 13.35, 5%/95% 6/31 mm Hg). Linear regression analysis showed a highly significant correlation between the A/E ratio and WP (r = .98, p less than .001, standard error of the estimate [SEE] = 0.10). The A/E ratio also correlated with other hemodynamic variables such as cardiac output (r = -.68, p less than .001, SEE = 0.33), cardiac index (r = -.74, p less than .001, SEE = 0.31), and stroke volume index (r = -.68, p less than .001, SEE = 0.34). The interobserver agreement (derived by intraclass correlation analysis between two examiners) on the A/E ratio was high (r = .95, p less than .001, n = 26). We conclude that WP can be accurately determined noninvasively by tpDE. For the assessment of systolic ventricular function, tpDE is of limited diagnostic value.

[Effects of nicotine on left ventricular diastolic function in patients with coronary disease. An echocardiographic study]. / Wirkung von Nicotin auf die linksventrikuläre diastolische Funktion bei koronarkranken Patienten.Eine echokardiographische Studie.

Echocardiography was performed before and after inhalation of 0.9 mg nicotine in 21 patients (6 women and 15 men with a mean age of 51.8 [38-73] years). All of them had angiographically confirmed coronary heart disease (stenosis greater than 50%) and smoked 20-50 cigarettes daily for at least 5 years. In addition, left ventricular filling parameters were determined by transmitral pulsed Doppler ultrasonography. In this technique the flow profile across the mitral valve is divided into the passive, early diastolic inflow (E wave) phase and the active, late diastolic inflow phase caused by atrial contraction (A wave). Isovolumetric relaxation time was measured by simultaneous M-mode recordings over the aortic and mitral valves. The following significant changes were noted after the dose of nicotine (medians; one-sided Wilcoxon test; P less than 0.05): peak velocity of the E wave decreased from 43 to 34.4 cm/s; the ratio between A and E wave peak velocities increased from 1.02 to 1.37; the velocity/time integral of the E wave decreased from 4.77 to 3.57 cm; the ratio between the velocity/time integrals of the A and E waves rose from 0.66 to 1.15; isovolumetric relaxation time increased from 90 to 121 ms. - In cigarette smokers with coronary heart disease, acute administration of nicotine hence caused a decrease in early diastolic transmitral blood flow and an increase in isovolumetric relaxation time. These changes point to significant impairment of left ventricular diastolic function.

Noninvasive measurement of left ventricular filling pressures by means of transmitral pulsed Doppler ultrasound.

In 54 consecutive patients, ages 59 +/- 11 years, the transmitral diastolic flow velocity profile was derived by means of pulsed Doppler echocardiography simultaneously with right-sided heart catheterization. In 30 of them, ages 57 +/- 10 years, left-sided heart catheterization was performed at the same time. The sample volume was positioned exactly in the mitral anulus plane, bisecting the anulus. The ratio of the time-velocity integrals of the A wave (atrial contraction) and E wave (early filling) was calculated (A/E ratio of integrals). Linear regression analysis showed a highly significant linear correlation of the A/E ratio of integrals with regard to left ventricular (LV) end-diastolic pressure (r = 0.98, p less than 0.001) and pulmonary capillary wedge pressure (r = 0.98, p less than 0.001). The A/E ratio of integrals also correlated with other hemodynamic parameters, such as cardiac output (r = -0.73, p less than 0.001), cardiac index (r = -0.74, p less than 0.001) and stroke volume index (r = -0.65, p less than 0.001). For 19 additional patients, ages 55 +/- 8 years, the values of LV end-diastolic pressure and pulmonary capillary wedge pressure were calculated by means of the corresponding formulas from the first data set. The correlation between the calculated and invasively measured LV filling pressures expressed in terms of intraclass correlation coefficients shows highly significant correlations for both LV end-diastolic pressure (intraclass correlation coefficient = 0.99, p less than 0.001) and pulmonary capillary wedge pressure (intraclass correlation coefficient = 0.99, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Non-invasive Doppler sonographic measurement of left ventricular end-diastolic pressure]. / Nichtinvasive dopplersonographische Messung des linksventrikulären enddiastolischen Druckes (LVEDP).

The purpose of this study was to measure left-ventricular end-diastolic pressure (LVEDP) noninvasively by pulsed Doppler ultrasound. In 30 consecutive patients of mean age 57.4 +/- 10.2 years (range 32 to 72 years) undergoing left-heart catheterization for exclusively diagnostic reasons LVEDP (range 5 to 33 mm Hg, mean 14.8 +/- 0.61 mm Hg) was measured invasively. Immediately before cardiac catheterization the flow profile along the mitral valve was derived by pulsed Doppler ultrasound. The typical flow profiles characterizing the early diastolic passive (e-wave) and late diastolic active by atrial contraction caused inflow (l-wave) into the left ventricle and represented the indexes of left ventricular diastolic function. The ratio of the velocity-time-integrals in early (e) and late diastole (l) corresponds to the ratio of blood flow along the mitral valve in early and late diastole. It could be shown that there is a highly significant linear correlation (r = 0.98, p less than 0.001) between the ratio of the velocity-time-integrals of late to early diastole (l/e-ratio) and LVEDP. LVEDP can be calculated by means of the l/e-ratio according to the formula: LVEDP (in mm Hg) = 15.15 X l/e-ratio + 1.06 With increasing LVEDP the proportional share of the active mitral blood flow in the diastole increased; the share of the early diastolic passive blood flow decreased proportionally. In patients with a l/e-ratio greater than 1.2 LVEDP, was always greater than 18.5 mm Hg; in patients with l/e-ratio greater than 0.9, LVEDP did not exceed 15 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)