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Background: Severity of pulmonary hypertension (PH) in dogs is related to clinical signs and prognosis., Hypothesis/objectives: We hypothesized that Doppler echocardiographic (DE) indices of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) are influenced by independent factors that create clinically important variability of DE-based estimates of PH in dogs., Animals: Thirty-eight client owned dogs with naturally acquired degenerative atrioventricular valve disease and tricuspid regurgitation (TR)., Methods: Dogs were prospectively enrolled, and target variables were acquired during 4 echocardiographic study periods (lateral recumbency, standing, lateral recumbency after a 6-minute walk test [6MWT], and lateral recumbency after sedation with butorphanol 0.25 mg/kg IM). Statistical methods included repeated measures ANOVA, mixed model analysis, and Chi-squared test of association., Results: There was a significant increase in peak TR flow velocity (TRFV; P < 0.01) after sedation in 78% of dogs, with TRFV increasing by >0.4 m/s in 42% of dogs, independent of stroke volume. A significant effect of study period on DE-estimated PVR was not found (P = 0.15). There were negligible effects of sonographer, body position, and 6MWT on echocardiographic variables of PH. Clinically relevant cyclic variation of TRFV was found. There was an association between estimation of right atrial pressure based on subjective assessment and estimation based on cranial vena cava collapsibility (P = 0.03)., Conclusions and Clinical Importance: The increase in TRFV observed with sedation could change assessment of PH severity and impact prognostication and interpretation of treatment response. Further studies with invasive validation are needed., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: The role of thyrotropin (TSH) on the cardiovascular system has been poorly investigated. It is unknown whether the changes in the vasculature associated with thyroid diseases result from altered thyroid hormone action or whether they are a consequence of a direct effect of TSH on endothelial cells. The present study was designed to evaluate the endothelial response of coronary flow to TSH in patients with differentiated thyroid cancer (DTC) without cardiovascular risk factors., Methods: The study population consisted of three men and seven women (M age  = 32.6 ± 8 years) who underwent total thyroidectomy for DTC. All were receiving therapy with L-thyroxine to maintain TSH within the reference range. No patient was obese, or had hypertension, diabetes, or dyslipidemia. Patients underwent standard echo-Doppler examination with evaluation of the coronary flow reserve (CFR) of the distal left anterior descending artery obtained by cold pressure test (CPT) before and 24 h after the second recombinant human TSH (rhTSH) injection., Results: Left ventricular morphology and systolic and diastolic function were normal in all patients. Levels of thyroid hormones and thyroglobulin and antithyroglobulin antibodies did not differ significantly pre- versus post-rhTSH treatment, whereas TSH levels were higher after rhTSH administration. Blood pressure and heart rate were not affected by rhTSH. Coronary flow peak velocity at rest (22.3 ± 6 vs 23.2 ± 8.7; p = 0.66) did not differ between baseline and 24 h after rhTSH, while post-CPT velocity (29.3 ± 6.8 vs 34.4 ± 10.9; p < 0.05) and the CFR were higher after rhTSH administration (1.32 ± 0.2 vs. 1.53 ± 0.2; p < 0.01)., Conclusions: rhTSH administration may improve the CFR after the non-pharmacological stressor CPT in DTC patients. The increase of coronary blood flow after rhTSH suggests that TSH may exert a protective effect on the coronary endothelium.

Unlabelled: The interaction between the heart and the arterial system (ventricular-arterial coupling - VA) is an important determinant of cardiovascular performance. Vascular stiffness (Ea) and left ventricular (LV) endsystolic stiffness (Elv) augment with age and in heart failure (HF). Beta blockers (BB) are recommended therapy for patients with HF. However, data about the effects of BB on VA coupling are scarce., Aims of the Study: TO ASSESS: 1) changes in VA after BB therapy; 2) interactions between VA and LV functions, 3) predictive factors influencing VA change., Methods: Eight hundred seventy-seven elderly patients with HF (aged ≥ 65, NYHA ≥ II, LV ejection fraction (LVEF) ≤ 45%), treated with BB according to the CIBIS-ELD protocol of up-titration, underwent Doppler echocardiography with clinical and laboratory assessment before and after 12 weeks of BB. VA coupling was calculated as Ea/Elv ratio., Results: Ventriculo-arterial interaction improved after 12 weeks of BB in elderly patients with HF. Values of Ea significantly decreased from 2.73 ± 1.16 to 2.40 ± 1.01, p < 0.001, resulting in a VA level close to the optimal range i.e. from 1.70 ± 1.05 (1.46) to 1.50 ± 0.94 (1.29), p < 0.001. A similar degree of VA change was found in the patients with ischemic and non-ischemic HF after the treatment. Improvement in the clinical stage of HF closely correlated with VA coupling change after BB (p = 0.006). The strongest predictor of VA coupling alteration during BB was the improvement in global LVEF (p < 0.001) followed by the age of patients (p = 0.014)., Conclusions: The beneficial effect of BB in elderly patients with HF was achieved by optimizing VA coupling close to recommended range, associated with an improvement in LVEF and contractility.

Purpose: To evaluate the effects of anesthetic induction on bi-ventricular function in patients with known preoperative left ventricular (LV) diastolic dysfunction undergoing coronary artery bypass grafting surgery (CABG)., Methods: Fifty patients with diastolic dysfunction undergoing CABG were studied. Preoperative transthoracic echocardiographic (TTE) examination was performed on the day before surgery and transesophageal echocardiography (TEE) assessment was undertaken after induction of anesthesia with sufentanil, midazolam, isoflurane, and pancuronium. Mean arterial pressure (MAP) and heart rate (HR) were recorded. The diameters of the left atrium (LA) and right atrium (RA) and right ventricular (RV) end-diastolic area (EDA), end-systolic area (ESA) and fractional area change (FAC) were obtained from the apical 4-chamber view. The LV EDA, LV ESA and LV FAC were measured from a transgastric midpapillary view. Pulsed wave Doppler of the transmitral flow (TMF) and transtricuspid flow (TTF), pulmonary venous flow (PVF) and hepatic venous flow (HVF) were measured. Mitral (Em, Am) and tricuspid (Et, At) annulus velocities were assessed by tissue Doppler imaging (TDI). Assessment of diastolic dysfunction was graded from normal to severe using a validated score., Results: Following induction of anesthesia, HR decreased (66 +/- 12 vs 55 +/- 9 beats.min(-1), P < 0.0001) while MAP remained unchanged (86.1 +/- 9.0 vs 85.6 +/- 26.5 mmHg, P = 0.94). The diameters of the LA, RA and RV chambers increased, and these increases were associated with opposite changes in LV dimensions. The RV FAC decreased, but the LV FAC remained unchanged. While most Doppler velocities decreased (P < 0.05), a greater reduction in the atrial components of the TMF, TTF and TDI ratios was observed. The LV diastolic function score improved after induction of anesthesia (100% of patients with a score > or = = 3 pre-induction compared to 58% of patients with a score > or = 3 post-induction; P = 0.0004)., Conclusion: In patients with left ventricular diastolic dysfunction, cardiac dimensions and bi-ventricular filling patterns are significantly altered after induction of general anesthesia. These changes can be explained to some extent by a reduction in venous return with general anesthesia, reduced atrial contractility, and the effect of positive pressure ventilation. Although the LV diastolic function score improved after induction of anesthesia, it is difficult to dissociate this effect from that of altered loading conditions.

Optimal therapy for diastolic heart failure (DHF), the most common form of heart failure in older persons, is unclear. To determine the effect of aldosterone antagonism in DHF, the authors conducted an open-label preliminary trial of spironolactone 25 mg/d in 11 women with DHF. Cardiopulmonary exercise testing, Doppler echocardiography, and a quality-of-life survey were administered at baseline and after 4 months. Peak exercise VO(2) increased by 8.3% (P=.001), the ratio of Doppler diastolic early filling velocity to mitral annulus velocity decreased by 25% (P=.02), quality-of-life score improved by 21% (P=.16 for trend), and median New York Heart Association class improved from class III to class II (P=.004). Findings from this preliminary study confirm the role of aldosterone in the pathophysiology of DHF and suggest that aldosterone antagonism may benefit such patients. These hypotheses are currently being tested in two separated National Institutes of Health-funded, randomized trials, the Spironolactone for Failure in the Elderly (SPIFFIE) and the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trials.

Background: Pimobendan (PIMO) is a novel inodilator that has shown promising results in the treatment of advanced mitral valve disease (MVD), but little is known about its hemodynamic effects, especially regarding the mitral regurgitant volume in naturally occurring MVD., Hypothesis: The addition of pimobendan to treatment decreases the regurgitant fraction (RF) in dogs with asymptomatic MVD., Animals: Twenty-four client-owned dogs affected by International Small Animal Cardiac Health Council class Ib MVD., Methods: Prospective, blinded, and controlled clinical trial. Dogs were assigned to a PIMO treatment group (n = 19) (0.2-0.3 mg/kg q12h) or a control group (n = 5). Echocardiographic evaluations were performed over a 6-month period., Results: The addition of PIMO to treatment did not decrease the RF of dogs affected by asymptomatic class 1b MVD over the study period (P= .85). There was a significant increase in the ejection fraction of the PIMO treated dogs at 30 days (80.8 +/- 1.42 versus 69.0 +/- 2.76, corrected P= .0064), and a decrease in systolic left ventricular diameter (corrected P= .011) within the PIMO group compared with baseline. However, this improvement in systolic function was not sustained over the 6-month trial period., Conclusion and Clinical Importance: This study did not identify beneficial long-term changes in the severity of mitral regurgitation after addition of PIMO to angiotensin converting enzyme inhibitor treatment of dogs with asymptomatic MVD.

Echocardiography is an essential diagnostic tool for accurate noninvasive assessment of cardiac structure and function in vivo. However, the use of anesthetic agents during echocardiographic studies is associated with alterations in cardiac anatomical and functional parameters. We sought to systematically compare the effects of three commonly used anesthetic agents on echocardiographic measurements of left ventricular (LV) systolic and diastolic function, LV dimensions, and LV mass in rats. Adult male Fischer 344 rats underwent echocardiographic studies under pentobarbital (PB, 25 mg/kg i.p.) (group I, n = 25), inhaled isoflurane (ISF, 1.5%) (group II, n = 25),or ketamine/xylazine (K/X, 37 mg/kg ketamine and 7 mg/kg xylazine i.p.) (group III, n = 25) anesthesia in a cross-over design. Echocardiography was also performed in an additional group of unanesthetized conscious rats (group IV, n = 5). Postmortem studies were performed to validate echocardiographic assessment of LV dimension and mass. Rats in group I exhibited significantly higher LV ejection fraction, fractional shortening, fractional area change, velocity of circumferential fiber shortening corrected for heart rate, and heart rate as compared with groups II and III. LV end-diastolic volume, end-diastolic diameter, and cross-sectional area in diastole were significantly smaller in group I compared with groups II and III. Cardiac output was significantly lower in group III compared with groups I and II. Postmortem LV mass measurements correlated well with echocardiographic estimation of LV mass for all anesthetic agents, and the correlation was best with PB anesthesia. Limited echocardiographic data obtained in conscious rats were similar to those obtained under PB anesthesia. We conclude that compared with ISF and K/X anesthesia, PB anesthesia at a lower dose yields echocardiographic LV structural and functional data similar to those obtained in conscious rats. In addition, PB anesthesia also facilitates more accurate estimation of LV mass.

The experimental calf model is used to assess mechanical circulatory support devices and prosthetic heart valves. Baseline indices of cardiac function have been established for the normal awake calf but not for the anesthetized calf. Therefore, we gathered hemodynamic and echocardiographic data from 16 healthy anesthetized calves (mean age, 189.0 +/- 87.0 days; mean body weight, 106.9 +/- 32.3 kg) by cardiac catheterization and noninvasive echocardiography, respectively. Baseline hemodynamic data included heart rate (65 +/- 12 beats per minute), mean aortic pressure (113.5 +/- 17.4 mm Hg), left ventricular end-diastolic pressure (16.3 +/- 38.9 mm Hg), and mean pulmonary artery pressure (21.7 +/- 8.3 mm Hg). Baseline two-dimensional echocardiographic data included left ventricular systolic dimension (3.5 +/- 0.7 cm), left ventricular diastolic dimension (5.6 +/- 0.8 cm), end-systolic intraventricular septal thickness (1.7 +/- 0.2 cm), end-diastolic intraventricular septal thickness (1.2 +/- 0.2 cm), ejection fraction (63 +/- 10%), and fractional shortening (37 +/- 10%). Doppler echocardiography revealed a maximum aortic valve velocity of 0.9 +/- 0.5 m/s and a cardiac index of 3.7 +/- 1.1 L/minute/m2. The collected baseline data will be useful in assessing prosthetic heart valves, cardiac assist pumps, new cannulation techniques, and robotics applications in the anesthetized calf model and in developing calf models of various cardiovascular diseases.

An infant with myocardial infarction due to congenital stenosis of the left coronary artery with consecutive left ventricular dysfunction and mitral regurgitation developed refractory pulmonary hypertension (PHT) and recurrent PHT crises. Catecholamines to support cardiac function, or pulmonary vasodilators like inhaled nitric oxide showed no effect. Treatment with Levosimendan (Simdax), a new inodilator, combining both inotropic and pulmonary vasodilating effects, improved left ventricular dysfunction, increased cardiac index, decreased pulmonary vascular resistance and reduced frequency and extent of the PHT crises. This case may suggest the use of Levosimendan as a long-term inotropic agent and pulmonary vasodilator in children with depressed cardiac function.

The effect of torasemide and furosemide therapy was compared in 50 patients who had chronic heart failure and symptoms [NYHA class II-III] despite long-term therapy with both low-dose furosemide and angiotensin-converting enzyme inhibitors. In this randomized 6-month, open-label trial, baseline and follow-up echocardiograms and neurohumoral assays were obtained in 25 group F patients (continued same dose of oral furosemide at 20-40 mg/day) and in 25 group T patients (received torasemide at 4-8 mg/day in place of furosemide). At 6 months, parameters were unchanged in group F whereas the group T patients had a lower left ventricular end-diastolic diameter (p<0.005) and left ventricular mass index (p<0.005) with improved Doppler filling parameters, decreased plasma B-type natriuretic concentration (p<0.001) and increased plasma concentrations of active renin (p<0.005) and aldosterone (p<0.001). The magnitude of these changes appeared dose dependent and it is suggested these favorable effects of switching from furosemide to torasemide may be related to aldosterone receptor blockade.

Background: Beta-adrenergic blocking agents are the cornerstone in the treatment of coronary artery disease (CAD). The exact pathophysiologic mechanism is not clear but depends largely on the oxygen-sparing effect of the drug. Thus, the effect of metoprolol on coronary flow reserve and coronary flow velocity reserve (CFVR) was determined in patients with CAD., Methods: Coronary blood flow velocity was measured with the Doppler flow wire in 23 patients (age: 56 +/- 10) undergoing percutaneous transluminal coronary angioplasty for therapeutic reasons. Measurements were carried out at rest, after 1-min vessel occlusion (postischemic CFVR) as well as after intracoronary adenosine (pharmacologic CFVR) before and after 5 mg intravenous metoprolol. In a subgroup (n = 15), absolute flow was measured from coronary flow velocity multiplied by coronary cross-sectional area., Results: Rate-pressure product decreased after metoprolol from 9.1 to 8.0 x 10(3) mm Hg/min (p < 0.001). Pharmacologic CFVR was 2.1 at rest and increased after metoprolol to 2.7 (p = 0.002). Likewise, postischemic CFVR increased from 2.6 to 3.3 (p < 0.001). Postischemic CFVR was significantly higher than pharmacologic CFVR before as well as after metoprolol. Coronary vascular resistance decreased after metoprolol from 3.4 +/- 2.0 to 2.3 +/- 0.7 mm Hg x s/cm (p < 0.02)., Conclusions: The following conclusions were drawn from this study. Metoprolol is associated with a significant increase in postischemic and pharmacologic CFVR. However, postischemic CFVR is significantly higher than pharmacologic CFVR. The increase in CFVR by metoprolol can be explained by a reduction in vascular resistance. The increase in CFVR (= increased supply) and the reduction in oxygen consumption (= decreased demand) after metoprolol explain the beneficial effect of this beta-blocker in patients with CAD.

Background: Small-sized mechanical aortic prostheses are commonly associated with generation of high transvalvular gradients, particularly in patients with large body surface area, and can result in patient-prosthesis mismatch. This study evaluates the hemodynamic performance of 21-mm Sorin Bicarbon bileaflet mechanical prostheses using dobutamine stress echocardiography., Methods: Fourteen patients (7 women; mean age, 63+/-8 years) who had undergone aortic valve replacement with a 21-mm Sorin Bicarbon bileaflet mechanical prosthesis 32.4+/-5.1 months previously were studied. After a resting Doppler echocardiogram, a dobutamine infusion was started at a rate of 5 microg x kg(-1) x min(-1) and increased to 30 microg x kg(-1) x min(-1) at 15-minute intervals. Pulsed- and continuous-wave Doppler echocardiographic studies were performed at rest and at the end of each increment of dobutamine. Both peak and mean velocity and pressure gradient across the prostheses were measured, and effective orifice area, discharge coefficient, and performance index were calculated., Results: Dobutamine stress increased heart rate and cardiac output by 83% and 81%, respectively (both p < 0.0001), and mean transvalvular gradient increased from 15.6+/-5.5 mm Hg at rest to 35.4+/-11.9 mm Hg at maximum stress (p < 0.0001). Although the indexed effective orifice area was significantly lower in patients with a larger body surface area, this was not associated with any significant pressure gradient. The performance index of this valve was unchanged throughout the study. Regression analyses demonstrated that the mean transvalvular gradient at maximum stress was independent of all variables except resting gradient (p = 0.05). Body surface area had no association with the changes in cardiac output, transvalvular gradient at maximum stress, and effective orifice area., Conclusions: These data show that the 21-mm Sorin Bicarbon bileaflet mechanical prosthesis offers an excellent hemodynamic performance with full utilization of its available orifice when implanted in the aortic position. The lack of significant transvalvular gradient in patients with a larger body surface area suggests that patient-prosthesis mismatch is highly unlikely when this prosthesis is used.

Background: It has previously been shown that, in preterm babies, routine sodium supplementation from 24 hours after birth is associated with increased risk of oxygen dependency and persistent expansion of the extracellular compartment., Objective: To explore whether this is mediated by a delayed fall in pulmonary artery pressure (PAP). Postnatal changes in PAP, estimated as the ratio of time to peak velocity to right ventricular ejection time, corrected for heart rate (TPV:RVET(c)), were compared in preterm infants who received routine sodium supplements that were either early or delayed., Methods: Infants were randomised, stratified according to sex and gestation, to receive a sodium intake of 4 mmol/kg/day starting either from 24 hours after birth or when a weight loss of 6% of birth weight was achieved. Echocardiographic assessment was made on the day of delivery (day 0), and on days 1, 2, 7, and 14. Babies with congenital heart disease were excluded., Results: There was no difference between the two groups in TPV:RVET(c) measured sequentially after birth. On within group testing, when compared with values at birth, the ratio was higher by day 3 in the early supplemented group, suggesting a more rapid fall in PAP compared with the late supplemented group, in whom a significant fall did not occur until day 14., Conclusions: The timing of sodium supplementation after preterm birth does not appear to affect the rate of fall in PAP as measured by the TPV:RVET(c) ratio. The previous observation linking routine sodium supplementation from 24 hours after birth with increased risk of continuing oxygen requirement therefore does not appear to be mediated by a delayed fall in PAP. Instead, the increased risk of continuing oxygen requirement is likely to be a direct consequence of persistent expansion of the extracellular compartment and increased pulmonary interstitial fluid, resulting from a sodium intake that exceeded sodium excretory capacity. This adds further weight to the view that clinical management, in this case the timing of routine sodium supplementation, should be individually tailored and delayed until the onset of postnatal extracellular volume contraction, marked clinically by weight loss.

Objective: Our goal was to investigate the short-term and intermediate effects of low-dose hormone replacement therapy on echocardiographic parameters of cardiac function in healthy postmenopausal women., Study Design: In a prospective, controlled study 30 healthy postmenopausal women (mean age, 52 +/- 3 years) were randomly assigned to 2 groups. Women in the hormone replacement therapy group (n = 15) received 1 mg micronized 17 beta-estradiol daily sequentially combined with 5 or 10 mg dydrogesterone for 14 days of each 28-day cycle during 12 months and thereafter 2 mg 17 beta-estradiol combined with 10 mg dydrogesterone for a period of 3 months. The control group (n = 15) received no treatment. M-mode, quantitative 2-dimensional, and Doppler echocardiographic measurements were performed at baseline and within the 17 beta-estradiol phase at 3, 12, and 15 months., Results: After 12 months significant differences in change between the 2 groups were found for left ventricular end-diastolic and left ventricular end-systolic diameters, left ventricular mass index, and stroke volume index. These differences were caused by changes in the control group rather than in the hormone replacement therapy group, in which no significant within-group changes were found. All other parameters measured showed no effect., Conclusion: Within 15 months of 17 beta-estradiol and dydrogesterone treatment no clinically relevant differences were found in the M-mode, quantitative 2-dimensional, and Doppler echocardiographic parameters measured in this study. It is suggested that 15 months of treatment probably is too short a period for detection of direct effects on the heart itself.

The objective of this study was to determine the effect of oral losartan on the degree of mitral regurgitation (MR). The regurgitant volume and effective regurgitant orifice were quantified using 3 methods (flow convergence, quantitative Doppler, and quantitative 2-dimensional echocardiography) in 32 patients (26 men, mean age 67 +/- 14 years) with MR, both at baseline and 4 hours after losartan (50 mg orally). Twenty-eight patients were also reevaluated after 1 month of continued treatment with losartan (50 mg/day). With treatment, systolic blood pressure decreased from 143 +/- 16 to 130 +/- 18 mm Hg and left ventricular end-systolic wall stress from 173 +/- 46 to 156 +/- 44 g/cm2 (both p < 0.001). With treatment, regurgitant volume decreased (from 77 +/- 28 to 64 +/- 26 ml, - 18 +/- 10%; p < 0.001) in direct relation to the effective regurgitant orifice change (from 43 +/- 16 to 37 +/- 15 mm2, -17 +/- 10%; p < 0.001) but without significant change in regurgitant gradient or duration. Wide individual variability in response was observed unrelated to the magnitude of blood pressure changes. Larger reduction in regurgitant volume was observed in patients with a marked decrease in wall stress (r = 0.47, p = 0.01) and higher baseline end-diastolic volume index (r = -0.38, p = 0.03) and regurgitant volume (r = -0.45, p = 0.01). Acute improvements were sustained and unchanged at 1 month (all p > 0.15). Treatment of MR using the angiotensin receptor antagonist losartan produces a significant and sustained decrease in the degree of MR, with decreases in regurgitant volume and effective regurgitant orifice. However, the changes are of modest and variable magnitude.

Serial echocardiographic investigations were carried out on patients with idiopathic dilated cardiomyopathy, to evaluate treatment effects on left ventricular (LV) performance during therapy with either metoprolol or captopril. Thirty-two patients (23 males and 9 females) with mild to moderate symptoms of heart failure (NYHA II-III) and a mean age of 49 years were included in the investigation. The patients were investigated with Doppler echocardiography before treatment, after 3 and 6 months of treatment (either metoprolol or captopril) and 1 month after withdrawal of treatment. Intra- and inter-investigator reproducibility was acceptable, with a coefficient of variation of less than 5% for LV dimensions. A reduction in LV dimensions was seen in both treatment groups. In the metoprolol group there was also an increase in LV stroke volume and fractional shortening. The non-invasive data were in accordance with invasive measurements of stroke volume and LV filling pressure. In patients with idiopathic dilated cardiomyopathy and mild to moderate symptoms of heart failure, echocardiography seemed to be sufficiently reproducible to be used for determination of treatment effects in a longitudinal heart failure study. Both metoprolol and captopril were well tolerated and had favourable effects on LV performance.

Background: Trimetazidine has been shown to improve anginal symptoms without altering hemodynamic variables in patients with coronary artery disease. The aim of this study was to compare the effect of trimetazidine and atenolol upon symptoms, resting left ventricular filling dynamics and exercise tolerance., Methods: Sixteen patients (3 males, 13 females, mean age 62 +/- 7 years) were randomized to receive trimetazidine for 2 weeks (20 mg 3 times daily) or atenolol (100 mg daily), according to a double-blind, randomized, cross-over, placebo-controlled design. At the end of each treatment period patients underwent symptom-limited exercise testing, an echocardiogram and a Doppler assessment of transmitral flow pattern. Daily life anginal symptoms were annotated on a diary throughout the study. Two patients discontinued trimetazidine because of severe palpitations and only 14 patients completed the study., Results: Atenolol significantly reduced the number of anginal episodes as compared to placebo or trimetazidine (0.44 +/- 0.53, 4.8 +/- 4, 2.9 +/- 4.9, p < 0.01). On atenolol, the exercise test was negative in 8 patients, but none of the patients had a negative test while on trimetazidine. Atenolol increased both time to 1 mm ST segment depression (668 +/- 213 vs 838 +/- 81 s, p < 0.05) and Doppler-derived indices of ventricular filling (E/A ratio 0.87 +/- 0.20 vs 1.21 +/- 0.26, p < 0.05)., Conclusions: These results confirm the beneficial effects of atenolol in improving symptoms, exercise performance and diastolic function in syndrome X patients. Trimetazidine did not exert any significant effect on any of the analyzed variables. Since trimetazidine has been previously shown to improve myocardial ischemia in patients with overt coronary artery disease to a similar extent of beta-blockers, it is likely that other mechanisms are responsible for angina in patients with syndrome X.

Aims: To assess the effects of 6 months intervention with +ramipril on resting and post exercise left ventricular function in patients with stable ischaemic heart disease and preserved left ventricular systolic function., Methods and Results: Patients (n=98, age 65+/-9 years, 37% women) were randomized to double-blind treatment with ramipril 5 mg. day(-1)(n=32), ramipril 1.25 mg. day(-1)(n=34), or placebo (n=32). Resting and post maximum exercise echocardiography/Doppler examinations were performed at baseline and after 6 months. Changes over 6 months in resting transmitral E-wave deceleration time (Edt) and Edt adjusted for heart rate (Edt/RR) differed between the ramipril 5 mg, ramipril 1.25 mg, and placebo groups: Edt 24+/-82, -1+/-69, and -29+/-64 ms, respectively, P=0. 012; Edt/RR 30+/-105, 2+/-61, and -28+/-69 ms, respectively, P=0.015. Changes in the difference between resting and post exercise Edt/RR also varied between groups: -53+/-137, -28+/-118, and 35+/-101 ms, respectively, P=0.029. No differences in E/A indices were noted. Resting atrioventricular plane displacement improved in the combined ramipril groups vs the placebo group: 0.2+/-0.8 vs -0.2+/-1.3 mm, P<0.05.Conclusion Six months ramipril treatment in patients with stable ischaemic heart disease and preserved left ventricular systolic function improved resting left ventricular function and reduced the exercise induced diastolic filling abnormalities usually seen in these patients., (Copyright 1999 The European Society of Cardiology.)

Aim: limited information is available on estrogen influences on diastole. We aimed to investigate the acute effects of a single dose of sublingual 17beta-estradiol on left ventricular diastolic function in postmenopausal women., Methods: the study included 28 women aged 55.6 +/- 6 (15 normotensive and 13 hypertensive), who underwent Doppler echocardiography and estradiol plasma levels determination before and 60 min after sublingual administration of 4 mg of 17beta-estradiol., Results: there were no modifications in heart rate. Both systolic and diastolic blood pressure dropped significantly in the hypertensives and remained unchanged in normotensives. Estradiol levels were 1790 +/- 869 pg/ml in the normotensives and 2664 +/- 1490 in the hypertensives (P < 0.05). Peak early velocity, in the population as a whole, increased from 84 +/- 18 to 91 +/- 18 cm/s and the early-to-atrial velocity ratio from 1.1 +/- 0.4 to 1.4 +/- 0.6 (P < 0.0001 for both). Both acceleration and deceleration rates increased significantly (P < 0.0001). These changes were shared by all the patients. In addition, the hypertensive patients, who presented a baseline pattern characterized mainly by a grossly increased peak atrial velocity with reduction in the early-to-atrial velocity ratio, demonstrated a decrease in peak atrial velocity from 92 +/- 12 to 78 +/- 10 cm/s (P < 0.0001), associated with significant reductions in deceleration time (P < 0.0001) and pressure half time (P < 0.005). Therefore, the typical picture of impaired ventricular relaxation was favorably changed after estradiol administration., Conclusions: the sublingual administration of estradiol induces acute modifications in left ventricular diastolic function in postmenopausal women, with improvement in the age-related left ventricular relaxation pattern, and that these beneficial changes are more pronounced in hypertensive that in normotensive women.

Objectives: We sought to develop and validate a definition of coronary microvascular dysfunction in women with chest pain and no significant epicardial obstruction based on adenosine-induced changes in coronary flow velocity (i.e., coronary velocity reserve)., Background: Chest pain is frequently not caused by fixed obstructive coronary artery disease (CAD) of large vessels in women. Coronary microvascular dysfunction is an alternative mechanism of chest pain that is more prevalent in women and is associated with attenuated coronary volumetric flow augmentation in response to hyperemic stimuli (i.e., abnormal coronary flow reserve). However, traditional assessment of coronary volumetric flow reserve is time-consuming and not uniformly available., Methods: As part of the Women's Ischemia Syndrome Evaluation (WISE) study, 48 women with chest pain and normal coronary arteries or minimal coronary luminal irregularities (mean stenosis = 7%) underwent assessment of coronary blood flow reserve and coronary flow velocity reserve. Blood flow responses to intracoronary adenosine were measured using intracoronary Doppler ultrasonography and quantitative angiography., Results: Coronary volumetric flow reserve correlated with coronary velocity reserve (Pearson correlation = 0.87, p < 0.001). In 29 (60%) women with abnormal coronary microcirculation (mean coronary flow reserve = 1.84), adenosine increased coronary velocity by 89% (p < 0.001) but did not change coronary cross-sectional area. In 19 (40%) women with normal microcirculation (mean flow reserve = 3.24), adenosine increased coronary velocity and area by 179% (p < 0.001) and 17% (p < 0.001), respectively. A coronary velocity reserve threshold of 2.24 provided the best balance between sensitivity and specificity (90% and 89%, respectively) for the diagnosis of microvascular dysfunction. In addition, failure of the epicardial coronary to dilate at least 9% was found to be a sensitive (79%) and specific (79%) surrogate marker of microvascular dysfunction., Conclusions: Coronary flow velocity response to intracoronary adenosine characterizes coronary microvascular function in women with chest pain in the absence of obstructive CAD. Attenuated epicardial coronary dilation response to adenosine may be a surrogate marker of microvascular dysfunction in women with chest pain and no obstructive CAD.

Left ventricular heart function and its response to long-term estrogen replacement therapy was assessed in 30 postmenopausal women, 20 of whom had modest to severe hot flushes and 10 of whom had never had them. Continuous transdermal estradiol was given to women who had surgically induced menopause, and a combination of transdermal estradiol and sequential medroxyprogesterone acetate was given to those who had spontaneous menopause. Left ventricular systolic and diastolic function was evaluated by complete two-dimensional M-mode and pulsed Doppler echocardiography before and after 6 and 12 months of therapy. The parameters assessed were: systolic and diastolic blood pressure, heart rate, cardiac septal and posterior wall dimensions, left ventricular end-systolic and end-diastolic dimensions and volumes, ejection fraction (EF), ejection time, peak left ventricular outflow velocity (PFV), flow velocity integral (FVI), acceleration time (AT), mean acceleration of systolic flow (MA), duration of early and late filling phase, peak velocity of the early (E) and late (A) mitral flow, and A/E velocity ratio. Although no difference in chamber and wall dimensions between flushers and non-flushers was found, women with hot flushes had lower (not significantly) EF, PFV, FVI, MA, blood pressure and heart rate before therapy. Twelve-month estrogen replacement therapy significantly reduced cardiac wall dimensions and improved systolic function in both flushers and non-flushers. However, stroke volume, EF and MA were increased whereas systolic blood pressure and heart rate were decreased more in flushers. Also, the increase in E mitral flow and decrease in A/E were more pronounced in flushers. Thus, although estrogen replacement therapy significantly improves heart function in healthy postmenopausal women, there appears to be some minor differences in response between flushers and non-flushers.

Successful cardioversion of atrial fibrillation may result in prolonged recovery of normal atrial mechanical function. This prolonged recovery of atrial contraction (so-called atrial stunning) might depend on: the amount of energy delivered during direct current cardioversion; the time course between the onset of atrial fibrillation and the conversion to sinus rhythm; the size of the left atrium; the underlying cardiac disease. The aim of this study was to evaluate, in subjects with normal atrial size and without heart disease, the phenomenon of atrial stunning soon after pharmacological cardioversion of an episode of atrial fibrillation of recent onset. Twenty-five patients with an acute episode of atrial fibrillation, without evidence of heart disease and M-mode left atrial dimension (< or = 40 mm received i.v. propafenone or flecainide 2 mg/kg/10 min in order to restore sinus rhythm. Atrial fibrillation lasted < 48 hours in all patients. Doppler echocardiography was used to assess atrial function, by recording the peak velocity of atrial contraction (A wave). An echocardiographic study was performed within 12 hours of successful cardioversion and was repeated on day 3, 12 and 30. The size of the left atrium (37 +/- 3.9; 37.57 +/- 2.9; 37.4 +/- 4; 37.82 +/- 3.7 mm) and peak E velocity (57.97 +/- 18.3; 59.4 +/- 18.3; 59.0 +/- 16; 59.07 +/- 16.7 cm/s) did not show any significant differences over the time, as demonstrated by the serial echocardiographic evaluations. In contrast, both peak A velocity (cm/s) and E/A ratio evaluated within 12 hours of cardioversion (60.29 +/- 12.3 and 1.0 +/- 0.37) and on day 3 (73.71 +/- 10.7 and 0.82 +/- 0.27) were statistically different (p < 0.000001 and p < 0.00001). No further statistically significant increase was found in subsequent examinations (respectively 76.31 +/- 12 and 0.78 +/- 0.24 on day 12, and 76.91 +/- 14.8 and 0.78 +/- 0.21 on day 30). In conclusion, this study suggests that patients with alone atrial fibrillation of recent onset have a delayed recovery of normal atrial systolic function even after pharmacological cardioversion.

Aim: Analysis of the effects of pharmacological stress echocardiography using dobutamine on left ventricular function in patients with and without evidence of coronary heart disease., Method: During dobutamine stress echocardiography, aortic flow and transmitral velocities, left ventricular end-diastolic and end-systolic diameters, wall thickness and fractional shortening were determined in 124 patients., Results: 36% of the patients showed a pathological wall motion response during echo, which indicates relevant coronary artery disease (group II). After dobutamine stress these patients had significantly lower peak (1.71 m/s) and mean (1.29 m/s) aortic outflow tract velocities compared to patients with normal stress echo (group I; 64%; 2.24 res. 1.67 m/s). Peak transmitral diastolic filling velocity increased significantly less among patients with abnormal stress echo compared to those with normal stress echo. E/A-relation remained unchanged. In addition there was a significantly decrease of the left ventricular end-diastolic and end-systolic diameter and of the fractional shortening in group I compared to group II., Conclusion: Dobutamine stress testing leads to different haemodynamic and left ventricular changes in patients with and without coronary heart disease. The frequency of false negative and false positive stress echocardiographies may be reduced especially by evaluating aortic Doppler parameters, left ventricular diameters and fractional shortening.

Aims: This study sought to determine predictors of left ventricular thrombus formation and resolution after acute anterior wall myocardial infarction., Methods and Results: We have analysed clinical, echocardiographic and angiographic data in 53 consecutive patients with anterior myocardial infarction. Two-dimensional and Doppler echocardiographic examinations were performed on days 1, 2, 3 and 7, after 3 and 6 weeks, and 3, 6, and 12 months following infarction. Coronary angiography was performed in 44 patients before hospital discharge. Left ventricular thrombus was detected in 30/53 patients (29/30 in the first week after infarction). Univariate analysis showed that left ventricular thrombus formation was associated with a higher initial end-systolic volume index (beta = 0.04, P = 0.001), and end-diastolic volume index (beta = 0.03, P = 0.03), a larger infarct perimeter (beta = 0.02, P = 0.01), a lower initial ejection fraction (beta = 0.06, P =0.001), a higher initial wall motion score index (beta = 1.75, P = 0.023), a higher peak creatine kinase level (beta = 3.90, P = 0.01), Killip class >1 (beta = 1.11, P = 0.003), infarct expansion (beta = 0.78, P = 0.04), occluded infarct-related artery (beta = -0.87, P = 0.04) and non-thrombolytic therapy (beta = -0.76, P = 0.047). According to the Cox proportional regression model, independent predictors of thrombus formation after anterior myocardial infarction were high end-systolic volume index (beta = 0.06, P = 0.001) and high peak creatine kinase level (beta = 5.17, P = 0.046). Thrombus disappeared in 11/30 (36.7%) patients during one-year echocardiographic follow-up. The only independent predictor of thrombus disappearance after acute myocardial infarction was the absence of apical dyskinesis 6 weeks after infarction (beta = -1.53, P = 0.045)., Conclusions: Our data demonstrate that the best predictor of left ventricular thrombus formation after acute anterior myocardial infarction is a high initial end-systolic volume. Thrombus resolution is more likely to occur in patients without apical dyskinesis at the end of the healing phase of infarction.

Unlabelled: Dobutamine stress echocardiography (DSE) leads to strong hypercontraction, tachycardia, and peripheral vasodilatation. In previous studies systolic obstruction of the left ventricular outflow tract (LVOT) was observed as a result of these factors. To evaluate left ventricular function and morphology in patients (pts) with induced systolic LVOT obstruction, we used continuous wave (CW) doppler registrations in combination with quantitative 2-D-echocardiography in 100 pts during routinely performed DSE (5-40 micrograms/kg/min). In addition left ventricular wall thickness was measured. Symptoms were registered using a standardised questionnaire and cardiac arrhythmias were counted over a two minute interval at rest and during the maximal heart rate of each patient. During DSE dynamic flow acceleration with late systolic peak velocity above 2 m/second (s) was considered to represent LVOT obstruction in pts with normal flow profiles in the LVOT before infusion of dobutamine. For invasive studies pts were investigated with femoral catheterisation by the method of Judkins. A greater than 50% stenosis was judged to be significant., Results: Examinations in 73 pts provided data of sufficient quality for echocardiographic and Doppler sonographic evaluations. 39 pts, 26 men, 13 women, mean age 64 +/- 8 years, developed late systolic flow velocities above 2 m/s and therefore formed the obstructive group (grp A). Grp B consisted of 34 pts, 26 men and 8 women, mean age 66 +/- 10 years, who showed normal time velocity integrals during DSE. In 41 pts invasive data provided information concerning the existence and severity of coronary artery disease. There were no significant differences in the increase of heart rate, the product of maximal systolic blood pressure and maximal heart rate or the percentage of pts, who reached their age corrected submaximal heart rate during DSE. Obstructive pts (group A) showed late systolic dynamic acceleration of systolic flow with a mean maximal speed of 315.4 +/- 139.8 cm/s, which peaked 0.12 +/- 0.04 s after the R-wave. From the velocities we calculated a mean pressure gradient of 47.5 +/- 39.7 mm Hg using the modified Bernoulli equation. Group B patients showed lower and earlier maximal speeds with a mean value of 158.2 +/- 37.6 cm/s, 0.09 +/- 0.04 s after the R-wave, corresponding to a pressure gradient of 10.6 +/- 4.9 mm Hg (p < 0.001). Ejection fractions were higher (p < 0.001) before the test in grp A: 68.2 +/- 8% compared to 55.7 +/- 10.4% in B. This difference increased during peak stress: 74.1 +/- 7.7% compared to 59.5 +/- 12.8%. End diastolic (EDVI) and end systolic volume indexes (ESVI) were lower in grp A (p < 0.001). During DSE, the decrease in ESVI was somewhat stronger for pts in grp A. Left ventricular hypertrophy was more often seen with obstruction. Septal thickness was increased in A: 1.45 +/- 0.34 cm compared to 1.13 +/- 0.27 cm in B (p < 0.001). Left ventricular posterior wall measured 1.03 +/- 0.28 cm in A and 0.83 +/- 0.23 cm in B (p < 0.01). 27 pts in grp B and only 9 in grp A had a history of previous myocardial infarction. Showing no difference at rest, wall motion score indexes raised under DSE in both groups and developed significantly higher scores in grp B at peak stress: 1.30 (1.0-1.90) compared to 1.18 (1.0-1.75) in A. We observed typical chest pain more often in grp B. Unspecific symptoms and arrhythmogenic complications were not statistically different, with the exception of ventricular bigeminy which was more often observed in grp B. A decline in the diastolic blood pressure was observed in pts with very severe obstruction (> 3.5 m/s, p < 0.05). Sensitivity of DSE was 84%, specificity 79%. No significant differences between pts with and without obstruction were observed., Summary: Intraventricular obstructions during DSE are often observed in pts with normal systolic function at rest and during peak stress, especially in the case of left ventricular hypertrophy. (ABSTRACT TRU

Background: Atrioventricular-synchronous pacing is beneficial in patients with hypertrophic obstructive cardiomyopathy. The effects of pacing in patients without significant left ventricular outflow tract obstruction at rest are, however, less well explored. This study compares the long-term outcome of pacing patients with and without significant left ventricular outflow tract obstruction at rest., Methods: Forty-one patients with hypertrophic obstructive cardiomyopathy were studied, 19 with a left ventricular outflow tract gradient < 40 mmHg at rest, but exceeding 50 mmHg during provocation with isoproterenol (group A), and 22 with a left ventricular outflow tract obstruction > 40 mmHg at rest (group B). Before the implantation of a permanent pacemaker, the patients were studied according to a temporary pacing protocol. This included graded isoproterenol provocation of the left ventricular outflow tract obstruction, which was assessed by echo Doppler. Following permanent pacemaker implantation, the patients were regularly followed up with echo Doppler, exercise testing and monitoring of the clinical condition., Results: Isoproterenol provocation was reproducible and the technique did not cause any clinically important side effects. Left ventricular outflow tract gradient reduction after chronic pacing did not differ between the two groups. In group A, it decreased from 98 +/- 30 mmHg in sinus rhythm to 42 +/- 26 mmHg during pacing. The corresponding values in group B were 87 +/- 40 mmHg to 36 +/- 24 mmHg. The clinical condition improved similarly in the two groups. Exercise capacity increased significantly and perceived dyspnoea and angina pectoris were significantly lower at submaximal levels of exercise after 6 months of pacing., Conclusion: Hypertrophic obstructive cardiomyopathy patients who only exhibit significant left ventricular outflow tract obstruction during provocation benefit as much from pacemaker treatment as do patients who already have significant obstruction at rest. Isoproterenol is a safe and reproducible method for pre-pacing evaluation of hypertrophic obstructive cardiomyopathy patients.

Background: In order to ascertain whether human adenosine-induced dilatation of epicardial arteries is direct or flow-mediated, we compared the effects of intracoronary adenosine infusion on epicardial coronary arteries with those produced by dipiridamole, a selective arteriolar vasodilator., Methods and Results: In 24 patients with angiographically normal coronary arteries, coronary blood flow velocity was measured by a Doppler wire during intracoronary infusion of adenosine or dipyridamole, which is known to increase intramyocardial adenosine concentration. Coronary angiograms were obtained at baseline and immediately after the end of each infusion period; coronary diameters 5 mm distal to the wire tip were measured by computer-assisted quantitative coronary angiography. Peak coronary blood flow velocities during adenosine or dipyridamole infusions were similar (52.0 +/- 15.5 and 47.9 +/- 24.2 cm.s-1, P = ns). Coronary diameters immediately after adenosine and dipyridamole infusions were similar and both higher than that at baseline (2.80 +/- 0.63 and 2.86 +/- 0.64 vs 2.44 +/- 0.69 mm, P < 0.05). The absolute and percentage increases of coronary artery diameters in response to adenosine were highly correlated to coronary blood flow velocity (R = 0.622, intercept -0.10 +/- 0.14, P = 0.002 and R = 0.617, intercept -15.2 +/- 9.9, P = 0.001, respectively); similar correlations were found in response to dipyridamole (R = 0.708, intercept -0.44 +/- 0.19, P < 0.001 and R = 0.649, intercept -13.5 +/- 8.7, P < 0.001, respectively). Finally the absolute and percentage changes of coronary artery diameters caused by adenosine were highly correlated to those caused by dipyridamole (R = 0.840 P < 0.001 and R = 0.836, P < 0.001 respectively)., Conclusions: A significant correlation exists between epicardial coronary vasodilation and coronary blood flow velocity during intracoronary adenosine infusion, thus suggesting that epicardial coronary vasodilation induced by adenosine is predominantly flow-mediated rather than direct. This conclusion is supported by the observation that similar findings were obtained using dipyridamole, which can only dilate epicardial coronary arteries indirectly, through the increase in coronary blood flow velocity caused by the inhibition of intramyocardial adenosine re-uptake.

Qualitatively, dobutamine stress echocardiography has become an established procedure. Quantitative results are in great demand but this is still difficult due to limited endo- and epicardial border definition. Transmitral Doppler variables are strictly quantitative and less subjective. Furthermore, ischemic alterations precede systolic ones (ischemic cascade). There are preliminary reports of the utility of dobutamine stress Doppler echocardiography, but proof of reproducibility and left ventricular filling patterns are still lacking. Fourteen healthy volunteers (10 men, 4 women, median age 25.9 years, range 21-32 years) were investigated according to the usual dobutamine stress echocardiographic protocol (5, 10, 15, 20, 30, 40 and 40 micrograms/kg/min + 0.5 mg atropine). At each titration step a standardized transmitral PW-Doppler recording with the sample volume positioned at the opened mitral leaflet tips was analyzed three times by two independent, experienced investigators. Of the early, late, and mean velocities (VmaxE, VmaxA, Vmean), time integrals (VTI-E, VTI-A, VTI), their ratios (E/A, E/A VTI), and various time intervals (Tacc, Tdec, E- and A-duration, FillT), VmaxE (0.82 to 1.09 m/s; P < 0.0001), VTI-E (16.17 to 17.19 cm; P < 0.0001) and Vmean (0.29 to 0.82 m/s; P < 0.0001) were found to have the greatest discriminatory power, commencing already at a dose of 10-15 micrograms/kg/min dobutamine. VmaxE and VTI-E demonstrated the smallest intra- and interobserver variation without any increase in variability during incremental dose titration. Assessment of the early diastolic filling pattern by Doppler echocardiography is a valuable quantitative and reproducible adjunct to conventional dobutamine stress echocardiography. Further controlled studies in coronary artery disease patients have to confirm, whether lower dobutamine doses could be used in the test and sensitivity increased due to better data acquisition in cases of limited echogenicity, less subjectivity, and earlier onset of ischemic alterations.

The negative inotropic effect of nearly all antiarrhythmic drugs, especially important in patients with impaired left ventricular function, represents a major drawback of medical therapy. The aim of this study is to evaluate the atrial and ventricular function and the exercise capacity in patients with mild heart failure treated with d,l-sotalol after electrical conversion of atrial fibrillation. The study included patients with persistent atrial fibrillation (for more than 2 weeks but less than 1 year) and mild heart failure (< or = class II NYHA). All patients had comparable basal echocardiographic findings, and received captopril. After successful cardioversion the patients were randomized in two groups: group 1 treated with sotalol (mean dose 240 mg q.d., max. 320 mg) and group 2--without sotalol. The drop-out criterion was the failure to maintain sinus rhythm. Finally, in the study remained 17 patients (10 men, 7 women, aged 41-60 years); group 1 included 10 patients and group 2-7 patients. They were assessed by quantitative echocardiography + Doppler and by standard ecg exercise test at less than 1 month but more than 2 weeks, and at 1, 3, and 6 months. When first evaluated (2 weeks-1 month), peak A wave velocity and atrial filling ratio were higher in group 2 than in group 1 (37 +/- 10 cm/s vs 20 +/- 5 cm/s and 23% +/- 7 vs 13% +/- 5, respectively) and group 1 had also a lower exercise tolerance (80 +/- 25 W vs 110 +/- 10 W). There were no significant differences between groups 1 and 2 in left atrial and left ventricular dimensions, ejection fraction and E wave deceleration time. After 1 month there were no significant differences in Doppler characteristics, echocardiographic parameters and exercise tolerance between the two groups. Group 1 remained at a lower heart rate and had a lower maximal double product (17250 mmHg/min vs 22100 mmHg/min) corresponding to a lower cardiac work. At 3 and 6 months there were no significant changes in all characteristics between the two groups. In conclusion, sotalol seems to be a well tolerated antiarrhythmic agent in patients with mild heart failure, after conversion of persistent atrial fibrillation. In this setting: 1. Sotalol could reversibly amplify the effect of atrial stunning after electrical cardioversion of atrial fibrillation, but this effect is brief. 2. Sotalol has no relevant negative inotropic effect, at least not in association with captopril. 3. Sotalol improves the effort capacity.

Long-term intermittent urokinase therapy has been developed for patients with severe coronary artery disease and refractory angina pectoris. This therapeutic approach is predominantly effective at the microcirculatory level based on a combination of rheologic and fibrinolytic effects; furthermore, plaque regression seems to be a possible mechanism. Patients with refractory angina pectoris are characterized by severe coronary artery disease without a therapeutic option for conventional revascularization procedures, only slight impairment of left ventricular systolic function and hyperfibrinogenemia, which results in further enhancement of myocardial ischemia due to microcirculatory impairment of blood flow. In this article data on the anti-ischemic effectiveness as well as first results on the impact of this therapeutic approach on hemodynamics are described. A dose-response study, which compared 3 x 50,000 IU with 3 x 500,000 IU urokinase three times a week over a treatment period of 12 weeks demonstrated subjective as well as objective antiischemic effectiveness. Only patients who were treated with 500,000 IU per injection achieved marked increases in exercise capacity, while some patients in the low-dose group presented even with a deterioration of exercise performance. First hemodynamic studies could not show marked changes of systolic parameters, either at rest or during exercise. But a decrease of pulmonary capillary wedge pressure at rest after treatment with 500,000 IU per injection indicates an improvement of diastolic function as a result of enhanced myocardial perfusion. Echocardiographic measurements of transmitral Doppler flow in 21 patients with end-stage coronary artery disease demonstrated normalization of early and late diastolic filling rates in most cases. These changes were accompanied by a reduction of clinical signs of heart failure. Long-term intermittent urokinase therapy is a valuable approach as it not only improves quality of life during the actual treatment period but by the persistence of therapeutic effects following the cessation of therapy.

Aims: A multicentre, double-blind, placebo-controlled trial was conducted in 542 patients, randomized 7-10 days after myocardial infarction, to study the effect of nisoldipine coat-core (nisoldipine-CC) on exercise after 6 months. Secondary endpoints included exercise-induced ischaemia, left ventricular function measured by Doppler echocardiography, adverse cardiac events and clinical outcome., Methods and Results: Patients had reduced left ventricular ejection fraction between 25 and 50%, but no heart failure. Exercise time was not different in the two groups. Nisoldipine-CC prolonged time to 1 mm ST deviation (P = 0.03). There was an effect of nisoldipine-CC of +3.6 cm.s-1 on early peak velocity (P = 0.01) and of -6.2 ms on isovolumic relaxation time (P = 0.005), but no effects on left ventricular volumes or ejection fraction. There was a trend towards reduced mortality (one death in the nisoldipine-CC group vs seven in the placebo group. P < 0.07) and the combined end-point of mortality and cardiac events (P = 0.09). Peripheral oedema occurred in 49 patients assigned to nisoldipine-CC and two assigned to placebo (P < 0.001). There were no differences in non-cardiac events., Conclusions: Nisoldipine-CC did not improve exercise time but increased time to 1 mm ST deviation, and improved diastolic left ventricular function. It is safe and well tolerated in post-infarction patients with impaired left ventricular function.

Left and right ventricular diastolic function was investigated at doppler echocardiography in patients with myocardiodystrophy exposed to organic aromatic solvents (30 female house painters). The control group consisted of healthy females and females with autonomic-dyshormonal myocardiodystrophy. The study group exhibited diastolic dysfunction characterized by disturbed active relaxation assessed by duration of isometric left and right ventricular relaxation.

Prostacyclin and its stable analog iloprost (ILO) are able to induce vasomotor effects in smooth muscle cells. These vasodilator effects have been demonstrated in several types of vessels, even in coronary arteries. Bugiardini et al. have previously claimed to have evidence for a coronary steal phenomenon in patients with coronary artery disease receiving ILO. They conclude the steal phenomenon from the appearance of angina and ST-segment changes. The aim of our trial was to study the coronary circulation by measuring coronary vessel diameter, coronary blood flow velocity (CBFV), heart rate and blood pressure in patients with high degree LAD stenosis following i.v. and i.c. infusion of ILO and papaverine (PAPA i.c.). Infusion of ILO i.v. (2 ng kg-1 min-1) induced no significant change in vessel diameter measured in the stenotic and in normal vessel segments. Following ILO i.c. (0.5 ng kg-1 min-1) and PAPA coronary vessel diameter increased proximal to the stenosis by 25.8 +/- 5.6% and 24.8 +/- 4.6% and within the stenosis by 50.1 +/- 10% and 56.2 +/- 11%, respectively (p < 0.01). At the end of the i.c. ILO infusion CBFV increased by 103.7 +/- 24.9% and was further elevated by PAPA (217 +/- 57.2%, p < 0.01). The elevated flow velocity with increased vessel diameter following ILO i.c. (0.5 ng kg-1 min-1) implicated an increased flow in the stenotic vessel and thus there was no evidence for a decreased perfusion or coronary steal phenomenon.

The influence of intracoronary enoximone at a dose of 0.075 mg/ kg/10 min on global and regional wall motion and myocardial perfusion (Group I, n = 10) as well as on diastolic LV function (Group II, n = 8) during pacing-induced ischemia was investigated in 18 patients with significant LAD stenoses. The hemodynamic parameters were determined by left heart catheterization, the systolic and diastolic left ventricular function by echocardiography including Doppler technique, and myocardial perfusion analysis was done after intracoronary application of contrast medium. Enoximone did not change either heart rate (79 +/- 9 vs 80 +/- 9 min-1) or blood pressure (LVSP: 159 +/- 7 vs 162 +/- 5 mm Hg) at rest. In the postpacing ischemic period after enoximone, LVEDP fell from a mean of 28.9 to 18.4 mm Hg (p < 0.001), dp/dtmax increased from 1050 to 1369 mm Hg/s (p < 0.001) and regional EF from 47% to 58% (p < 0.01), while global EF remained unchanged (45% vs 47%). ST-segment depression was reduced significantly from 2.3 to 1.5 mm (p < 0.01). Enoximone induced an increase in myocardial perfusion by 129% (p < 0.001) in the stenosis-dependent myocardial areas with shortening of the wash-out half-life time of the echo contrast medium from a mean of 14 s to 5 s (p < 0.001). The isovolumetric relaxation was shortened by 13% (p < 0.05), the E wave by 5%, and dp/dtmin increased by 17% (p < 0.01). In summary, intracoronary application of enoximone led to an improvement in both systolic and diastolic LV function without concomitant peripheral effect due to regression of myocardial ischemia.

We measured Doppler echocardiographic diastolic parameter during infusion of low-dose dobutamine in 14 untreated hypertensive subjects and in 14 normal controls. Low-dose dobutamine accelerated left ventricular relaxation in normal controls but not in hypertensive subjects.

In congestive heart failure captopril modifies the left ventricular filling pattern mainly by unloading the heart. We investigated whether the structural characteristics of the left ventricle may influence the acute effects of captopril on this pattern in patients with untreated hypertensive (H group, 6 patients) or idiopathic (I group, 14 patients) cardiomyopathy. We evaluated changes of pulsed Doppler mitral flow, of systemic arterial and wedge pulmonary pressures 40 min after 25 mg captopril administered sublingually, and correlated these changes with the M-mode echocardiographic relative wall thickness index (h/r). Baseline mean arterial pressure (H = 137 +/- 20 mm Hg, mean +/- SD, I = 95 +/- 19 mm Hg; p < 0.001), and h/r (H = 0.38 +/- 0.03, I = 0.28 +/- 0.09; p < 0.05) were greater in the high blood pressure group; wedge pressure, echocardiographic biplane ejection fraction, and Doppler indexes of the left ventricular filling were similar in the two populations. After captopril, ejection fraction did not change significantly, mean arterial pressure decreased significantly in hypertensive patients (H group, baseline = 137 +/- 20, captopril = 119 +/- 10, p = 0.02; I group, baseline = 95 +/- 19, captopril = 90 +/- 24, p = nonsignificant), and the wedge pressure was reduced by the same extent in both groups (H group, baseline = 27.7 +/- 3, captopril = 21 +/- 7, p < 0.05; I group, baseline = 20 +/- 12, captopril = 15 +/- 8, p < 0.05). In the H group early mitral flow increased [(E wave integral) x (mitral annulus area)] by 38 +/- 15%, and was almost steady in the I group (-1.3 +/- 30%; group H vs. I = p < 0.01); late mitral flow [(A wave integral) x (mitral annulus area)] showed a pattern exactly opposite to this (H = +0.4 +/- 40%, I = +38 +/- 19; p < 0.01). In the whole population there was a significant correlation between the early/late flow ratio variations and baseline h/r (r = 0.6, p < 0.05). In chronic congestive heart failure, changes in left ventricular filling with captopril are related to h/r: a higher index, as recorded in the H group, is associated with "true normalization' of the filling pattern after captopril; a lower index, as recorded in the I group, is associated with "pseudonormalization' despite a similar decrease of left ventricular filling pressure.

Data are submitted on the condition of haemodynamics of greater and lesser circulation in patients with ischemic heart disease (IHD) presenting with the bundle-branch block. On the basis of the results from a combined clinical-instrumental investigation involving electro- and echocardiography the authors present the early objective quantitative criteria for the diagnosis of those haemodynamic shifts occurring in formation of the bundle-branch block. The blockade of the left bundle of His has a more pronounced effect on the greater circulation haemodynamics while that of the right one--on the lesser circulation. The authors give a comparative assessment of haemodynamic effects of a single dose of isosorbide dindtrate and nifedinin in the patients. Nitrosorbide and corinfar improve contractility of the left ventricle, decrease pulmonary hypertension and overloading of the right side of the heart.

Background: Calcium channel blockers have been wide and successfully used in the treatment of coronary heart disease. Gallopamil, a metoxylic derivative of verapamil, has many of its properties and so, caution is recommended when given to patients with depressed left ventricular function. Clinical studies about this effect are scarce, and we have assessed it in patients with coronary heart disease and diminished left ventricular function., Methods: We studied 20 patients in a cross-over, randomized, double-blind study during three weeks active periods with two intercalating washout placebo periods of one week. Patients had history of previous myocardial infarction, positive exercise stress test and ejection fraction ranging from 30% to 50% by echocardiography., Results: There were no significant differences between each drug and corresponding placebo on either systolic or diastolic function. When we compared both drugs, patients showed a milder increase in area under E after propranolol than after gallopamil (p < 0.008). Clinical episodes of cardiac failure were not reported, and ejection fraction did not change., Conclusions: Both gallopamil and propranolol can be used in patients with coronary heart disease and moderately depressed left ventricular ejection fraction.

Growth hormone (GH) hypersecretion is associated with an increased incidence of cardiac hypertrophy and subclinical abnormalities of left ventricular (LV) function. The unlimited availability of biosynthetic GH has led to progressively increased dosage when treating GH-deficient children, raising the question of its cardiovascular effects during long-term therapy. We compared 22 children (8 girls, 14 boys), mean age 12.1 years (range 3-17 years) with GH deficiency who were receiving chronic GH treatment (GH group) with 22 normal controls matched for sex and body size in order to evaluate: (1) LV volume, mass, and systolic function by two-dimensional guided M-mode echocardiography; (2) LV diastolic function by pulsed-wave Doppler sampling of the transmitral flow; and (3) cardiac output and systemic vascular resistance by Doppler echocardiography. All patients had been on chronic GH therapy for 13.8 +/- 7.6 months (range 5-30 months) with an average dose of 0.95 +/- 0.12 IU/kg per week (range 0.69-1.17 IU/kg per week). Blood pressure did not differ between the two groups. LV volume, mass, ejection fraction, and mean velocity of circumferential shortening did not differ significantly between the GH group and controls; nor did the peak- and end-systolic meridional stress. All patients had a normal contractile state as estimated by the relation between mean velocity of circumferential shortening and end-systolic meridional stress. The LV filling parameters did not differ between the two groups, and there was no difference in cardiac index and systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to assess the long term effects of antihypertensive treatment on left ventricular diastolic function, 26 hypertensive patients were followed up for a mean of 4.25 years with two-dimensional and Doppler echocardiography. A significant reduction in left ventricular mass index was first apparent after 9 months of therapy (mean (S.D.) 124 (22) vs. 114 (18) g/m2, P < 0.01), and this was maintained over the 4.25 year period (124 (22) vs. 117 (17) g/m2, p < 0.05). At 9 months there was no change in either isovolumic relaxation time (108 (26) vs. 108 (17) ms, P = N.S.) or left ventricular filling as assessed by peak flow velocity E/A ratio (0.94 (0.22) vs. 0.95 (0.27), P = N.S.). However, after 4.25 years there was a significant improvement in IVRT (108 (26) vs. 83 (11) ms, P < 0.01) with a trend towards an improved peak flow velocity E/A ratio, although this did not reach statistical significance (0.95 (0.27) vs. 1.02 (0.26), P = N.S.). Of the 14 patients who had an abnormal isovolumic relaxation time at baseline, 12 normalised and 2 improved. These findings suggest that left ventricular diastolic dysfunction in hypertension may be reversed by prolonged antihypertensive treatment.

Objectives: This study was designed to evaluate the right ventricular function by means of the determination of right ventricular systolic time intervals measured in pulmonary artery flow detected by Doppler., Background: Left ventricular systolic time intervals have been used to evaluate left ventricular performance. There is, however, no information as to whether right ventricular systolic time intervals may be useful in the evaluation of right ventricular function., Methods: Simultaneous measurements of right ventricular ejection fraction and Doppler determination of right systolic time intervals were made in four pigs in 47 different hemodynamic conditions that permit the modification of the right ventricular ejection fraction from 15% to 68%. The preejection time, the ratio of right preejection time to right ventricular ejection time, with and without correction by the heart rate, were correlated simultaneously to invasively determined right ventricular ejection fraction and other hemodynamic parameters, measured with a modified pulmonary artery catheter with a rapidly responding thermistor., Results: There was a significant linear correlation between Doppler determination of right systolic time intervals and right ventricular ejection fraction. A similar correlation was found for preejection time (r = .80, p < .0001) and the ratio of right preejection time to right ventricular ejection time with correction by the heart rate (r = .83, p < .0001). When we used a preejection time > 70 msec as a criterion to detect a ejection fraction < 40% we found a sensitivity of 89% and specificity of 88%. A preejection time > 80 msec, as criterion of more severe ventricular disfunction (ejection fraction < 30%), displayed a sensitivity of 76% and specificity of 100%., Conclusion: These results show that right ventricular systolic time intervals determined by Doppler study correlate significantly with the right ventricular ejection fraction. In view of its simplicity and its accuracy in the prediction of right ventricular ejection fraction, this method may provide useful non-invasive alternative in the prediction of right ventricular ejection fraction.

To evaluate the chronic effects of theophylline on cardiac function, M-mode and pulsed Doppler derived variables were measured at rest and the suprasternal continuous wave Doppler measurement of ascending aortic flow was used during treadmill exercise testing. Subjects consisted of 13 children with stable asthma (mean 11.7 +/- 2.2 years) who were treated with theophylline for at least one year and 16 age-matched, untreated normal volunteers. In the resting state, the chronic administration of theophylline seemed to produce a slight increase in percent fractional shortening, outflow peak velocity and atrial contribution to ventricular filling in the asthmatic children as compared to normals, but these changes were not statistically significant. The asthmatic children showed significantly lower values than the controls in exercise induced changes in the peak velocity, stroke index and cardiac index, but not in the heart rate. Therefore, chronic administration of theophylline appears to have a minimal effect on resting cardiac function, but a possibly deleterious effect on the cardiac response to exercise testing.

Estrogen replacement therapy has been found to reduce the incidence of cardio- and cerebrovascular diseases in postmenopausal women. The mechanisms of this vasoprotection are controversial. In recent years, direct vascular actions of estrogens have been proposed in addition to beneficial effects on cardiac risk factors such as hypercholesterolemia. In an attempt to determine the role of direct hormonal influences on human arteries we analyzed the acute vascular responses to 17 beta-estradiol in a series of in vitro and in vivo studies. A dose-dependent estrogen-induced vasorelaxation was found in human coronary arteries in vitro which was more pronounced in women and associated with a significant increase in cyclic AMP and cyclic GMP content. This vascular response could be confirmed in healthy postmenopausal women during a clinical double-blind cross-over study using a quantitative duplex-sonographic approach. Estradiol induced a significant vasodilation and increase of blood flow in femoral arteries, whereas placebo had no effect. As measured by quantitative coronary angiography, high-dose estradiol application was also followed by a significant dilation of epicardial coronary arteries. These direct vascular actions such as vasodilation and increase of blood flow may contribute to the preventive estrogen effects on cardiovascular diseases in postmenopausal women.

Objectives: In order to study the efficiency of oral dose of propafenone in preventing childhood supraventricular tachycardias, we have treated 38 children without left ventricular dysfunction., Methods: The mean age has been 8 +/- 4.7 years old. All of them had suffered at least two episodes of supraventricular tachycardia, and eleven had undergone a previous antiarrhythmic treatment. The initial dose of propafenone has been 6.5 +/- 2.1 mg/kg/24 h (in 3 doses), which has been increased in case of inefficacy., Results: We have not advised neither side-effects, nor proarrhythmic effects, during a follow-up of 13 +/- 6 months. Propafenone has been efficient in preventing supraventricular tachycardias in all patients. The initial dose has been efficient in 17 patients, and we have increased the initial dose up to 11.1 +/- 3.7 mg/kg/24 h in 21 patients. The mean effective dose has been 8.9 +/- 3.6 mg/kg/24 h. We stopped treatment in 14 patients after been 6 months without supraventricular tachycardias., Conclusion: From our study, we conclude that propafenone has been efficient in preventing supraventricular tachycardias in childhood with a dose of 8.9 mg/kg/24 h. We have not found side-effects.

To investigate the short-term effects of cilazapril on left ventricular diastolic functions in patients with essential hypertension, 20 patients with mild-to-moderate essential hypertension were evaluated. Following 2 weeks of placebo washout, all patients underwent blood pressure determination and echo-Doppler ultrasonography recordings. Cilazapril, 2.5 mg, was given to all patients, and blood pressure was determined. Echo Doppler ultrasonography recordings were repeated 3 h after drug therapy. The investigated diastolic function parameters were peak and mean velocities of mitral E and A waves, ratio of peak E to peak A, and acceleration and deceleration rates of E and A waves. Both systolic and diastolic blood pressure changes were insignificant. The E wave peak and mean velocities were significantly increased (p = 0.006 and 0.02, respectively), and the A wave peak and mean velocities were significantly reduced (p = 0.006 and 0.02, respectively) after cilazapril therapy. The ratio of peak E to peak A velocity was also found to be increased following cilazapril therapy (p = 0.006). It is to be concluded that the immediate improvement of left ventricular diastolic functions after cilazapril therapy despite the lack of blood pressure decrease is probably a result of the inhibition of tissue angiotensin-converting enzyme and/or other local humoral factors, but this needs to be further investigated.

The incidence of ventricular arrhythmias following the intracoronary injection of papaverine was assessed. A 3F coronary Doppler catheter was placed in the proximal left anterior descending artery and 6-12 mg of papaverine was injected into the left coronary artery in 42 patients. After intracoronary papaverine, the corrected QT interval on the electrocardiogram was prolonged from 0.43 +/- 0.03 to 0.49 +/- 0.07 s (p < 0.001). Occasional premature beats were observed in 2 patients (4.5%) with dilated cardiomyopathy. In 1 patient (2.3%) with 99% stenosis of the left anterior descending artery, polymorphous ventricular tachycardia with marked QT prolongation occurred. This patient also had hypokalemia (2.5 mEq/l) due to primary aldosteronism. In conclusion, careful use of intracoronary papaverine is necessary because of the risk of occasional serious ventricular arrhythmias.