Mordechai Averbuch

The effects of hormone replacement therapy in normal postmenopausal women: Measurements of Doppler-derived parameters of aortic flow

In this study the effects of hormone replacement therapy on cardiac function in healthy postmenopausal women were evaluated by Doppler echocardiography that was performed before (T1) and 2.5 months after the initiation of hormone replacement therapy (T2) in the peak estrogenic phase. The following parameters of aortic flow were measured: peak flow velocity, acceleration time, and ejection time. Additional parameters were calculated: flow velocity integral and mean acceleration. The study group included 24 postmenopausal women aged 43 to 60 years (mean 51.6 years). The control group consisted of 19 postmenopausal women aged 46 to 60 years (mean 53.5 years) who were not receiving hormone replacement therapy and who underwent the same evaluation. There were no changes in all Doppler parameters between T1 and T2 in the control group. However, in the study group there were significant increases in peak flow velocity (108.3 +/- 16.7 cm/sec at T1 vs 123 +/- 20.7 cm/sec at T2; p = 0.002), flow velocity integral (17.7 +/- 3.9 vs 21.5 +/- 4.7 cm; p = 0.0003), mean acceleration (11.5 +/- 1.9 vs 13.1 +/- 2.6 m/sec/sec; p = 0.001), and ejection time (324 +/- 37.6 vs 348.8 +/- 40.7 msec; p = 0.002). There was no change in acceleration time (94.8 +/- 6.6 vs 95 +/- 10.9 msec). These results demonstrate that estrogens increase both stroke volume and flow acceleration. The latter probably reflects a combination of enhanced inotropism and vasodilatation. We assume that the cardioprotective effect of hormone replacement therapy in postmenopausal women may be due not only to changes in lipid profile but also to direct effects of estrogens on central and peripheral hemodynamic parameters.

Exercise echocardiography in postmenopausal hormone users with mild systemic hypertension

Rest and exercise echocardiography (at dynamic and isometric exercise) were performed in 30 postmenopausal women (aged 54 +/- 4 years) with borderline to mild hypertension. They were then divided into 2 groups: 17 women who started oral hormone replacement therapy (0.625 mg/day conjugated estrogens or 2 mg/day estradiol) and a control group of 13 nonusers. After 6 to 9 months, a second echocardiography was performed in 26 women (4 withdrew). There were only a few changes in values obtained in the 12 controls at the end of follow-up compared with baseline. Primarily, these changes included a slight decrease in systolic blood pressure at rest and on exercise. Several significant morphologic and hemodynamic alterations appeared in 14 hormone users. Left ventricular cavity dimensions and mass became smaller: mean end-diastolic diameter decreased from 45.9 +/- 3 mm at baseline to 44.4 +/- 3 mm at study termination (p = 0.007). The corresponding values for end-systolic diameter were 25.8 +/- 4 mm and 23.9 +/- 4 mm (p = 0.006); for left atrium diameter, it was 34.5 +/- 4 mm and 32.5 +/- 4 mm (p = 0.001); for left ventricular wall width, it was 19.9 +/- 2 mm and 19.3 +/- 2 mm (p = 0.02); for left ventricular mass, it was 197 +/- 28 g and 179 +/- 32 g (p = 0.006). The resting aortic blood flow velocity and acceleration increased: 119 +/- 18 cm/s before therapy versus 129 +/- 23 cm/s while on hormone substitution (p = 0.04), and 13.6 +/- 3 m/s2 versus 16.5 +/- 4 m/s2 (p = 0.008), respectively. Mean rest to peak exercise systolic blood pressure difference became smaller after hormones: 39 +/- 19 mm Hg versus 28 +/- 13 mm Hg (p = 0.03) during dynamic exercise, and 43 +/- 22 mm Hg versus 25 +/- 13 mm Hg (p = 0.004) during isometric exercise. The above data probably indicate that with hormone replacement therapy, there is an improvement in cardiac function both at rest and during exercise.

The effects of sublingual estradiol on left ventricular function at rest and exercise in postmenopausal women: an echocardiographic assessment.

To evaluate the acute hemodynamic effects of 4 mg estradiol given sublingually. Design Rest and exercise echocardiographies were performed prior to estradiol administration. Then, another set of tests was done post-dose: rest examination at 1 h post-dose, isometric exercise at 65 min post-dose, and dynamic exercise at 100 min post-dose. Results The administration of 4 mg sublingual estradiol to 24 postmenopausal women (aged 48–58 years) was followed 60 min post-dose by a surge in mean estradiol serum levels (1759 ± 704 pg/ml). At rest a slight drop in systolic and diastolic blood pressure was measured after estrogen ingestion: 132 ± 24 mm Hg versus 127 ± 21 mm Hg, p < 0.05; 83 ± 11 mm Hg versus 78 ± 10 mm Hg, p < 0.02. There were no changes in resting heart rate, double product, or vascular resistance. The left heart cavities became smaller: the left atrium diameter decreased from 33.7 ± 4 mm to 32.3 ± 4 mm, p < 0.01; the end-systolic diameter decreased from 24.9 ± 3 mm to 23.6 ± 4 mm, p < 0.01; the end-diastolic diameter decreased from 44.5 ± 4 mm to 42.7 ± 4 mm, p < 0.01. The peak aortic blood flow velocity fell from 120 ± 19 cm/s to 116 ± 22 cm/s (p < 0.05), and the flow velocity integral fell from 26.3 ± 4 cm to 24.9 ± 5 cm (p < 0.01); the cardiac output underwent a small change, with borderline significance: 7 ± 2 L/min versus 6.7 ± 2 L/min, p = 0.06. Only minor changes in the hemodynamic and echocardiographic parameters were recorded after estrogen for both isometric and dynamic exercises. Analyses were also made for two subgroups: 13 normotensive women were compared with 11 hypertensive women. The post-estrogen decreases in resting blood pressure and in peak blood velocity were observed only in the hypertensive subjects, whereas the changes in heart dimensions and in flow velocity integral were the same in both subgroups. Conclusions Sublingual estradiol was associated with acute hemodynamic alterations mainly at rest but also after exercise. (Menopause 1998;5:79–85. ± 1998, The North American Menopause Society.)

The acute effects of sublingual 17β-estradiol on the cardiovascular system

The beneficial effects of estrogen in postmenopausal women have been well documented. Cardioprotection by estrogen, which is probably the result of several metabolic alterations, appears after 2 or more years of constant use. However, acute administration of estrogen (intravenous or intracoronary) was found to improve cardiac hemodynamics and function through various non-genomic mechanisms. This article reviews data on the consequences of sublingual administration of estrogen, a non-invasive and simple dosing route which is associated with rapid absorption and prompt cardiovascular reactions. It appears that sublingual estradiol at 1 or 2 mg may improve ischemia and exercise performance in women with coronary artery disease, and augment the aortic and brachial blood flow as a result of vasodilation, whereas larger doses (4 mg) may lead to a decrease in myocardial contractility and aortic blood flow, and a slight drop in blood pressure. More data are needed to evaluate the actual clinical significance of sublingual estradiol in healthy women, in situations when endothelial dysfunction is anticipated (diabetes, hypertension) and in women with diagnosed coronary artery disease.

AORTIC DISSECTION MANIFESTED AS FEVER OF UNKNOWN ORIGIN

Aortic dissection is accompanied by fever in about one third of the patients. However, fever of unknown origin as the predominant manifestation of aortic dissection seems to be extremely rare. A review of the English literature revealed only 3 patients characterized by fever as the principal sign of aortic dissection. Herein an additional patient is reported. All 4 patients presented with pain or discomfort in the chest, back or abdomen, followed by persistent fever, lasting 5-11 weeks and associated with anemia and a high sedimentation rate. The outcome was favorable in all cases regardless of the location of the dissection or the type of treatment.

Combined Effect of Captopril and Aspirin in Renal Hemodynamics in Elderly Patients with Congestive Heart Failure

Captopril and aspirin have been claimed to adversely affect renal function. This study was designed to evaluate the safety of concomitant administration of both drugs in patients with moderate to severe congestive heart failure (CHF). The study group consisted of 10 patients with a mean age of 77.6 +/- 4.4 years and a mean New York Heart Association functional class of 2.6 +/- 0.5. Captopril was administered in a rapidly escalating dose regimen over a 4-day period to a maximum dose of 75 mg/day. Aspirin 0.25 g/day was added from day 5 on. Renal plasma flow (RPF) was measured by iodohippurate scan and the creatinine clearance test (Ccr) was used as an index of glomerular filtration rate (GFR). Both Ccr and RPF remained unchanged throughout the study period; 48.9 +/- 16; 48.2 +/- 16.5; 49.4 +/- 16, and 222 +/- 67, 241 +/- 97, 237 +/- 88 ml/min, for days 0, 4, 9, respectively. Only 1 patient developed a significant decrease in Ccr following the administration of captopril. This patient had a further decrease when aspirin was added. The decrease in Ccr was accompanied by a marked reduction in filtration fraction and in mean arterial pressure. Our data suggest that the administration of aspirin to elderly patients with moderate CHF treated with captopril is relatively safe and is not associated with further deterioration in renal function.

Budd-Chiari syndrome in Israel: predisposing factors, prognosis, and early identification of high-risk patients.

In twenty-seven patients with venography-documented Budd-Chiari syndrome (BCS), underlying diseases included polycythemia vera (nine patients), membranous occlusion of the inferior vena cava (three), and cirrhosis (two). In only nine patients did the syndrome occur in the absence of any predisposing factor. All patients with a membranous web were relatively young (mean age 29 years) and were born in Morocco. With regard to prognosis, three groups could be delineated. Eight patients formed a rapidly progressive group, with mean survival from first symptom of only 4.3 weeks, and were characterized mainly by their relatively advanced age and minimal enlargement of the spleen.

Prediction of renal impairment in elderly patients with congestive heart failure treated with captopril

SummaryThis study assessed the usefulness of the oral captopril test in the prediction of renal impairment among elderly patients with congestive heart failure (CHF). Fortyseven patients aged ≥65 years with CHF (EF <40%) participated in a prospective nonrandomized series. Blood samples for plasma renin activity (PRA) were drawn before and 60 minutes after 50 mg of oral captopril. Twenty-four hours later, captopril was administered (up to 75 mg/day over a 4 day period), and renal laboratory and clinical assessment were performed at baseline and for a 9 day period. In 7 of 47 patients (14.9%), deterioration of renal function was observed. During the captopril test, the PRA increased significantly after 1 hour in almost all patients and the mean blood pressure decreased from 99.2±14.6 mmHg to 92.2±13.7 mmHg (p<0.001). All patients whose baseline PRA level was <1.9 ng/ml/hr and whose stimulated PRA was <3.2 ng/ml/ hr maintained a stable renal function throughout the study period. Significant statistical correlation (p<0.05) was found between the initial PRA, the changes in PRA or mean blood pressure during the captopril test, and the change in plasma creatinine and creatinine clearance in the entire group, and was even more evident in a subgroup of patients with an ejection fraction ≥30%. All these correlations were not statistically significant in the patients with an ejection fraction <30%. It is thus concluded that measurement of pretreatment PRA levels might be a useful laboratory tool for predicting the renal safety of captopril use in patients with CHF whose EF ≥30%.

Influence of Ocular Tropicamide on Exercise Testing

This study was aimed to evaluate the effects of tropicamide 0.5% eye drops on cardiovascular parameters during exercise testing. The study group included 154 healthy subjects (mean age: 44.7 +/- 8 years). The subjects were divided into three groups according to the size of the pupils at the onset of exercise: A: pupils not dilated (n = 27), B: pupils partially dilated (n = 90) and C: pupils widely dilated (n = 37). They were compared to 66 healthy controls (age 43.8 +/- 8) who did not receive the drops. Rest and exercise parameters were affected in groups A and B, while the results of group C resembled those of the controls: (a) resting heart rate -66.7, 66.6, 70.9 and 69.3, respectively (p = 0.03); (b) heart rate at 50 and 100 W - 104, 107, 110 and 111 (p = 0.01) and 131, 131, 137, 139, respectively (p = 0.01); and (c) peak systolic blood pressure - 192, 186, 183, 175; respectively (p = 0.004). Reanalyzing the data by scoring of visual impairment gave identical results. As a whole, the study group achieved higher work loads than the controls (126 vs. 119 W; p = 0.03). We conclude that the instillation of ocular tropicamide has definite effects on cardiovascular parameters, both at rest and during exercise. Mainly, patients showed a lower heart rate at the initial levels of exercise. However, at symptom-limited level, tropicamide does not influence a patients ability to achieve the target heart rate, and stress testing results are not altered by the drug.

The New Editorial Board: 1991-1996

The New Editorial Board: 1991-1996 Cardiology was first published in 1937; the original editors were Drs. Bruno Kirsch of Cologne and W. Löffler of Zurich. The journal was originally named Cardiologia International Archives of Cardiology. In 1970, the name of the journal was changed to Cardiology. The Editorial Board at the time the journal was founded consisted of 24 distinguished cardiologists from Europe, North and South America, and Asia. The United States had 5 members including Paul D. White and Frank N. Wilson; Switzerland had 3 members, the UK and Czechoslovakia 2. The remaining 14 members came from the Netherlands, Portugal, Rumania, France, Germany, Sweden, Denmark, Austria, Mexico, and Japan. The 3 eastern European members are of even greater interest given current political changes in that region. More than half the articles in the first two volumes were in German, a quarter were in French, 15% were in Italian, and only 5% were in English. By 1960, the majority of the articles were in English, although French and German manuscripts were still being published. In 1970, when the journal took its present name, English became the sole language of the publication. Contributions in those first two volumes (1937-1938) came from the Netherlands, Italy, Germany, Denmark, France, Switzerland, and the USA. Each article ended with summaries in French, German, English, and Italian. There were no editorials and only occasional book reviews. Slightly more than one-third of the articles dealt with laboratory investigations in animals. Most studies were observational rather than experimental. It is interesting to review the topics covered in the first two volumes of Cardiologia. A number of animal studies were published including one of particular merit on the circulatory effects of intravenous epinephrine and adrenal cortical hormones. Clinical studies of note included work dealing with ventricular premature beats recorded by electrocardiography, congenital heart block, pathological observations on the etiology of atherosclerosis, and the application of cardiac output determinations to clinical problems. Thus, many of the topics which interest us today were already being considered in 1937 and 1938. Modern cardiology was already prefigured at that time. The new Editor and Editorial Board are honored to be part of a scholarly enterprise that is more than 50 years old. On behalf of the publisher and the members of the new Board, I would like to take a few minutes of 2 The New Editorial Board: 1991-1996