A hand-carried cardiac ultrasound device in the outpatient cardiology clinic reduces the need for standard echocardiography.

OBJECTIVE: To assess the potential value and cost-effectiveness of a hand-carried ultrasound (HCU) device in an outpatient cardiology clinic. METHODS: 222 consecutive patients were prospectively enrolled in the study. When standard echocardiography (SE) was specifically indicated on the basis of clinical history, electrocardiogram and physical examination, the same cardiologist (level-2 or level-3 trained) immediately performed an HCU examination. The cardiologist then reassessed the clinical situation to confirm or cancel the SE request according to the information provided by HCU. The SE examination was performed by a sonographer and examined in a blinded fashion by a cardiologist expert in echocardiography. Findings from the two examinations were compared. RESULTS: HCU was performed in 108/222 patients, and a definite diagnosis was established in 34 of them (31%), making SE examination potentially avoidable. In the 74 patients with inconclusive HCU results and for whom SE was still indicated, the decision was mainly dictated by the lack of spectral Doppler modality in the HCU system. The overall agreement between HCU and SE for diagnosis of normal/abnormal echocardiograms was 73% (kappa = 0.4). On the basis of the potentially avoided SE examinations and the obviated need for a second cardiac consultation, a total cost saving of euro2142 per 100 patients referred for echocardiography was estimated. CONCLUSIONS: The use of a simple HCU device in the outpatient cardiology clinic allowed reliable diagnosis in one third of the patients referred for echocardiography, which translates into cost and time saving benefits.

Comparative vascular effects of hormone replacement therapy and raloxifene in women at increased cardiovascular risk.

Hormone replacement therapy (HRT) improves endothelial function in postmenopausal women while the effects of raloxifene, a selective estrogen receptor modulator, are still under debate. The aim of this study was to evaluate endothelium-dependent flow-mediated vasodilatation in the brachial artery and plasma levels of nitrite, nitrate and endothelin-1 in 20 postmenopausal women with increased cardiovascular risk treated with either HRT or raloxifene for 4 weeks in a randomized double-blind single cross-over study. Patients had an endothelium-dependent flow-mediated dilatation of 4% prior to initiation of the study. Treatment with HRT resulted in a 67% increase in dilatation compared with baseline (from a 7.4% increase to a 12.4% increase, p < 0.01). Raloxifene treatment resulted in no change in vasodilatation from baseline. Endothelium-dependent dilatation was significantly improved by HRT compared with raloxifene treatment (12.4+/-0.6% vs. 6.1+/-2.0%; p < 0.01). Compared with baseline values, nitrate plus nitrite levels increased significantly (p < 0.05) with HRT but not with raloxifene. Similarly, endothelin-1 decreased from baseline with both treatments, but only the HRT-induced decrease was statistically significant (p < 0.05). In conclusion, HRT improved endothelial function and reduced plasma levels of endothelin-1 in postmenopausal women at risk of coronary artery disease. These beneficial effects were not shared by raloxifene.

Effect of estradiol valerate alone or in association with cyproterone acetate upon vascular function of postmenopausal women at increased risk for cardiovascular disease.

OBJECTIVES: a large body of evidence has been accumulated suggesting that impairment of vascular endothelial function is an initial step in the development of atherosclerosis. Recent studies have shown that estrogen replacement therapy in postmenopausal women (PMW) improves endothelium-dependent, flow-mediated dilatation (FMD) while the cyclical adjunct of a progestin may reverse this effect. METHODS: the purpose of this study was to evaluate endothelium-dependent, FMD in the brachial artery and the plasma levels of Endothelin-1 in menopausal females treated with estradiol valerate with and without cyclical cyproterone acetate in 20 PMW (mean age 64+/-6 years) with more than one risk factor for coronary artery disease. After a baseline evaluation, PMW entered a double-blinded, placebo controlled single cross-over study and were randomized to receive either estradiol valerate (2 mg) for 21 days or estradiol valerate (2 mg) for 11 days and estradiol valerate (2 mg) and cyproterone acetate (1 mg) for 10 days. Patients were crossed-over the complementary treatment 7 days after completing the first treatment phase. The study of forearm blood flow was repeated at the end of each treatment period. RESULTS: estradiol valerate significantly increased FMD as compared with baseline (12+/-3 vs. 7+/-4%, P<0.01) the adjunct of cyproterone acetate did not affect the effect of estradiol valerate upon FMD (12+/-3 vs. 11+/-4%, P=NS). Similarly reactive hyperemic flow increased after estradiol valerate alone (24%) or in association with cyproterone acetate (24%) compared with baseline. Plasma levels of Endothelin-1 were significantly reduced by estradiol valerate alone or in association with cyproterone acetate. CONCLUSIONS: in conclusion hormone replacement therapy with estradiol valerate and cyproterone acetate improves endothelial function and reduces plasma levels of Endothelin-1 in PMW at risk of coronary artery disease. These effects may be relevant for cardioprotection.

Anti-ischemic effect of chronic oestrogen replacement therapy alone or in combination with medroxyprogesterone acetate in different replacement schemes.

BACKGROUND: Oestrogen replacement therapy in postmenopausal women has a protective effect upon the cardiovascular system and improves exercise-induced myocardial ischemia. Although in hormone replacement schemes progestins are required to reduce the likelihood of uterine malignancies, little is known on the cardiovascular effect of progestins. The purpose of this study was to evaluate the effect of oestrogen replacement alone and two different estrogen-progestin replacement therapy schemes upon exercise induced myocardial ischemia. MATERIAL AND METHOD: The study population included 18 female menopausal patients with coronary artery disease. After a baseline exercise test patients received conjugated equine estrogens (CEE) 0.625 mg alone for 30 days when they underwent a second exercise test and were randomized to receive in a cross-over design medroxyprogesterone acetate (MPA) either in continuous combined therapy (2.5 mg/daily) for 28 days or in cyclical therapy (10 mg o.d. from day 16 to day 28). RESULTS: After CEE alone two patients with a previously positive exercise test showed a negative exercise test. CEE increased time to 1 mm ST compared to baseline (352+/-185 vs 265+/-133 s, P<0.01). In the 2 pts in whom the exercise test was negative after CEE the test remained negative during continuous combined MPA therapy while become positive during cyclical MPA. CEE+continuous combined MPA increased both time to 1 mm ST and exercise time compared to baseline (386+/-165 vs 265+/-133 s, P<0.01 and 545+/-198 vs 465+/-186 s, P<0.05, respectively). No difference was found between baseline and CEE+cyclical MPA in either time to 1 mm ST or exercise time (268+/-164 vs 265+/-133 s, P=NS and 455+/-223 vs 465+/-186 s, P=NS, respectively). CONCLUSION: Continuous combined therapy with CEE+MPA improves exercise-induced myocardial ischemia in female patients with coronary artery disease while the beneficial effect of CEE is reduced by cyclical therapy.

Effect of sildenafil citrate upon myocardial ischemia in patients with chronic stable angina in therapy with beta-blockers.

BACKGROUND: It has been suggested that phosphodiesterase 5 (PDE5) inhibition is potentially hazardous and that it increases the risk of cardiac events in patients with coronary artery disease. This study sought to evaluate whether PDE5 inhibition with sildenafil exerts any effect on exercise-induced myocardial ischemia in patients on beta-blockers. METHODS: Fourteen patients underwent a baseline exercise test off-therapy and were then started on atenolol (100 mg once daily). After a run-in phase of 1 week, patients underwent a second exercise test and were randomized to receive either sildenafil (50 mg) or placebo given in a random order on two different occasions, 2 days apart. Exercise test was repeated 2 hours after the administration of sildenafil or placebo. RESULTS: All patients had a > 1 mm ST-segment depression while off-therapy. Eight patients had a negative exercise test response after atenolol, which was unaltered by the adjunct of either sildenafil or placebo. In the remaining subjects, atenolol significantly prolonged the time to 1 mm ST-segment depression and the exercise time. Sildenafil and placebo did not reverse the beneficial effect of atenolol upon exercise-induced myocardial ischemia. CONCLUSIONS: PDE5 inhibition does not worsen exercise capacity and exercise-induced myocardial ischemia in patients with chronic stable angina whose symptoms and exercise test response are well controlled by beta-blocker therapy.

Acute anti-ischemic effect of testosterone in men with coronary artery disease.

BACKGROUND: The role of testosterone on the development of coronary artery disease in men is controversial. The evidence that men have a greater incidence of coronary artery disease than women of a similar age suggests a possible causal role of testosterone. Conversely, recent studies have shown that the hormone improves endothelium-dependent relaxation of coronary arteries in men. Accordingly, the aim of the present study was to evaluate the effect of acute administration of testosterone on exercise-induced myocardial ischemia in men. METHODS AND RESULTS: After withdrawal of antianginal therapy, 14 men (mean age, 58+/-4 years) with coronary artery disease underwent 3 exercise tests according to the modified Bruce protocol on 3 different days (baseline and either testosterone or placebo given in a random order). The exercise tests were performed 30 minutes after administration of testosterone (2.5 mg IV in 5 minutes) or placebo. All patients showed at least 1-mm ST-segment depression during the baseline exercise test and after placebo, whereas only 10 patients had a positive exercise test after testosterone. Chest pain during exercise was reported by 12 patients during baseline and placebo exercise tests and by 8 patients after testosterone. Compared with placebo, testosterone increased time to 1-mm ST-segment depression (579+/-204 versus 471+/-210 seconds; P<0. 01) and total exercise time (631+/-180 versus 541+/-204 seconds; P<0. 01). Testosterone significantly increased heart rate at the onset of 1-mm ST-segment depression (135+/-12 versus 123+/-14 bpm; P<0.01) and at peak exercise (140+/-12 versus 132+/-12 bpm; P<0.01) and the rate-pressure product at the onset of 1-mm ST-segment depression (24 213+/-3750 versus 21 619+/-3542 mm Hgxbpm; P<0.05) and at peak exercise (26 746+/-3109 versus 22 527+/-5443 mm Hgxbpm; P<0.05). CONCLUSIONS: Short-term administration of testosterone induces a beneficial effect on exercise-induced myocardial ischemia in men with coronary artery disease. This effect may be related to a direct coronary-relaxing effect.

Impaired baroreflex sensitivity and sympathovagal balance in syndrome X.

Alterations of autonomic nervous control of cardiac function have been described in syndrome X. The characteristics, however, of the autonomic control of the cardiovascular system in patients with syndrome X have not been adequately studied; thus, the aim of the present study was to investigate the role of baroreceptor sensitivity and sympathovagal balance in syndrome X. The study group included 12 patients with syndrome X, 12 age- and sex-matched control patients with coronary artery disease, and 12 age- and sex-matched controls with no evidence of heart disease. Baroreceptor sensitivity was evaluated by calculating the regression line relating phenylephrine-induced increases in systolic blood pressure to the attendant changes in the RR interval. Sympathovagal balance was assessed by using heart rate variability in the time and frequency domain and measuring plasma norepinephrine at rest and during incremental bicycle exercise. Baroreceptor sensitivity was significantly reduced in syndrome X compared with that in control normal subjects (7.4 +/- 1.2 vs 16.8 +/- 2.3 ms/mm Hg; p < 0.02). This was associated with a significantly lower percentage of adjacent normal RR intervals that differ by >50 ms, lower root-mean-square of the difference of adjacent RR intervals, and lower logarithmic value of the high-frequency component in patients with syndrome X compared with normal subjects. A nonsignificant trend toward lower baroreceptor sensitivity was found in patients with syndrome X compared with control ischemic patients (7.4 +/- 2 vs 12.2 +/- 1.3 ms/mm Hg). A nonsignificant trend toward a higher value of the low- to high-frequency ratio was also observed in patients with syndrome X than in both control groups. No difference was detected in norepinephrine levels either at rest or during exercise or in the exercise-induced norepinephrine increase between the 3 groups. No difference was also observed between ischemic patients and normal subjects in either baroreceptor sensitivity or heart rate variability measurements. A significant correlation (r = 0.80, p < 0.01) was found between baroreceptor sensitivity and the high-frequency component in normal controls but not for other measurements of autonomic function in the 3 groups. In conclusion, patients with syndrome X have an altered autonomic control of the cardiovascular system characterized by impaired baroreceptor sensitivity and reduced heart rate variability. Abnormal autonomic regulation of the cardiovascular system may be of pathophysiologic importance in syndrome X.

Heart rhythms, ventricular arrhythmias, and death in chronic heart failure.

BACKGROUND: The aim of this study was to evaluate whether abnormalities in heart rate variability (HRV) could act as markers of ventricular tachycardia and prognosis in patients with advanced, chronic heart failure. Fifty patients with chronic heart failure (45 men; mean age, 59 +/- 9 years; New York Heart Association [NYHA] class II-III; left ventricular ejection fraction [LVEF], 19 +/- 9% and peak oxygen consumption, 16.6 +/- 5.4 mL/kg/min) caused by idiopathic dilated cardiomyopathy (n = 12) and ischemic heart disease (n = 38) were included in the study. Heart rate variability measures derived from 24-hour electrocardiographic (ECG) monitoring (Marquette 8500 recorder, Marquette Electronics, Milwaukee, WI) were calculated in the time domain and frequency domain. METHODS AND RESULTS: Twenty-five patients (50%) revealed episodes of ventricular tachycardia on 24-hour ECG monitoring (1-143 episodes). The presence of ventricular tachycardia was associated with lower LVEF but there was no difference in NYHA class and peak oxygen consumption between patients with and without ventricular tachycardia (LVEF, 16 vs 22%, P = .01; NYHA class, 2.6 vs 2.4; peak oxygen consumption, 16.5 vs 16.8 mL/kg/min, not significant). Patients with ventricular tachycardia exhibited markedly lower HRV measures. Multiple regression analysis was used to test HRV parameters as potential predictors of ventricular tachycardia. Among them, high-frequency power was the only independent predictor of the presence of ventricular tachycardia, and this predictive correlation was independent of LVEF and mean R-R interval duration. During a follow-up period of 24 +/- 18 months, 12 patients (24%) died. No difference was found in age, etiology, NYHA class, peak oxygen consumption, or occurrence of ventricular tachycardia, but a lower LVEF (15 +/- 6 vs 21 +/- 9%, P = .046) was observed in those who died compared with those who survived. Certain estimates of HRV were in contrast, lower in those who subsequently died: standard deviation of all normal R-R intervals (61 +/- 30 vs 101 +/- 33 ms), standard deviation of 5-minute mean R-R intervals (55 +/- 27 vs 92 +/- 31 ms), mean of all 5-minute standard deviations of R-R intervals (22 +/- 12 vs 37 +/- 11 ms), and the low-frequency (3.2 +/- 1.8 vs 4.8 +/- 0.9 ln ms2) and high-frequency (3.0 +/- 1.1 vs 3.8 +/- 0.8 ln ms2) components of the HRV spectrum (all differences, P < .01). In univariate Cox analysis, all of these HRV measures were independent predictors of death. Kaplan-Meier survival analysis revealed that the standard deviations of all normal R-R intervals and of 5-minute mean R-R intervals dichotomized at median values (99 and 90.5 ms, respectively) were the best predictors of mortality. CONCLUSIONS: In patients with moderate to severe chronic heart failure, depressed indices of HRV on 24-hour ambulatory ECG monitoring could be related to higher risk of ventricular tachycardia and death, suggesting that analysis of HRV could be usefully applied to risk stratification in chronic heart failure patients.

Circadian pattern of heart rate variability in chronic heart failure patients. Effects of physical training.

The effect of physical training on the circadian pattern of heart rate variability (recorded over 24 h in relation to both time and frequency) was assessed in 12 chronic heart failure patients randomized, in a cross-over design, to 8 weeks training or detraining, and compared with 12 age-matched normals. Training improved heart rate variability indices: all R-R interval 5 min standard deviations increased by 17.6%, the root mean square of the differences of successive R-R intervals by 34.9%, the percentage difference between adjacent normal R-R intervals > 50 ms by 112.5%, total power by 58.3%, high frequency by 128.5% and low frequency by 65.0%. Compared with controls, circadian variations in autonomic parameters were maintained in chronic heart failure. Training-induced changes were observed at different time intervals throughout the day: the highest values were at 0100 h-0700 h (detraining: low frequency 361 +/- 83 ms2, high frequency 126 +/- 47 ms2; training: low frequency 535 +/- 202 ms2, high frequency 227 +/- 115 ms2, P < 0.01) and the lowest at 1300 h-1900 h (detraining: low frequency 91 +/- 23 ms2, high frequency 39 +/- 14 ms2; training: low frequency 154 +/- 42 ms2, high frequency 133 +/- 67 ms2, P < 0.05). In chronic heart failure, training maintains and improves circadian variations in heart rate variability measures.

Relationship between arterial potassium and ventilation during exercise in patients with chronic heart failure.

The mechanisms underlying the increased ventilatory response to exercise seen in patients with chronic heart failure are not clearly understood. Arterial potassium has been suggested as an important ventilatory stimulant. The authors have investigated the arterial potassium response in patients with heart failure. Although arterial potassium rises during exercise, no evidence was found to suggest a greater potassium response in patients with heart failure compared to normal subjects. There was no direct correlation between the rise in ventilation and the rise in arterial potassium. It remains possible that there is an increased sensitivity to arterial potassium in patients with heart failure, but it would need to be three times greater than in normal subjects.

Immunodetection of human atherosclerotic plaque with 125I-labeled monoclonal antifibrin antibodies.

To test the affinity of a new F(ab')2 monoclonal antibody (TRF1) against human fragment D dimer of cross-linked fibrin for atherosclerotic plaques free of detectable thrombi, 6 atherosclerotic segments of carotid and femoral artery, and as a control 5 segments of atherosclerosis-free internal mammary artery, were drawn from 11 male patients undergoing bypass surgery. All segments were carefully washed in order to remove possible endoluminal thrombi, and cut to obtain pairs of intimal fragments of similar weight, containing either plaques (n = 16), or fatty streaks (n = 12), or normal endothelium (n = 20). Each fragment underwent a direct binding test to TRF1, or to a non-specific antibody, both labeled with 125I. The activity in each fragment was measured after 3 h of incubation at 37 degrees C, and after washing the fragments every hour for 3 h. TRF1 binding (as percentage of initial activity) was significantly higher (P < 0.001) in atherosclerotic than in normal fragments (26% +/- 11.5%, vs. 9.2% +/- 3.9% in fatty streaks, and 1.9% +/- 0.6% in normal endothelium), and indirect immunofluorescence confirmed TRF1 uptake within the plaque wall. By contrast, the non-specific antibody did not show any significant binding. These preliminary results demonstrate the high specific affinity of TRF1 for atherosclerotic plaques, probably due to the hemorheologic phenomena that activate platelets and provoke the formation of fragment D dimers of cross-linked fibrin on the plaque surface.

Exponential fit of QT interval-heart rate relation during exercise used to diagnose stress-induced myocardial ischemia.

The aim of this study was to analyze the dynamic changes of QT interval--heart rate relation during exercise, fitting their reciprocal variations to an exponential formula (QT = A - B.exp(-k.RR], in order to see whether diagnostic contributions might so be derived. The authors studied 139 patients who underwent a simultaneous assessment of regional myocardial perfusion and ventricular function by means of two injections of 99mTc-methoxy-isobutyl-isonitrile at rest and at peak of a submaximal exercise test, using first pass radionuclide angiography with multielement gamma-camera and single photon emission computerized tomography, in order to detect and localize the presence of stress-induced myocardial ischemia. According to radionuclide results, patients were divided into three groups: group A, 7 individuals with no sign of stress-induced myocardial ischemia; group B, 79 patients with evidence of ischemia in 1 (16.5%), 2 (65.5%), or 3 (17.7%) main coronary territories; and group C, 53 patients with previous infarction and evidence of ischemia in other territories. Conventional analysis of the exercise test (greater than or equal to 0.1 mV ST depression) showed a pathological response in no individual of group A, in 34 patients of group B (43%), and in 27 patients of group C (50.9%); overall sensitivity was 46.2%, specificity 100%, and diagnostic accuracy 48.9%. Exponential coefficients A, B, and k showed wide overlap of values among the three groups, although a significant difference was present in mean k values between groups A and B (p less than 0.001), and group C (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Variations in QT interval and ventricular volume during exercise-induced myocardial ischemia]. / Variazioni sotto sforzo dell'intervallo QT e dei volumi ventricolari indotte dall'ischemia miocardica.

Aim of this study was to evaluate the possible relationship among myocardial ischemia, left ventricular volume changes and QT interval changes during exercise in patients with coronary artery disease. QT interval, expressed as absolute value, corrected according to Bazett (QTc = aT/RR0.5) and Fridericia (QTf = QT/RR0.33) and calculated by adapting reciprocal changes in QT and heart rate during exercise to the exponential fit proposed by Sarma (QTs = A-B*exp (-K*RR], was compared to the scintigraphic finding of myocardial ischemia and to the changes in left ventricular volumes during exercise. We studied 151 patients (130 men and 21 women, mean age 56 +/- 11 years) with suspected or already ascertained coronary artery disease, who underwent a simultaneous evaluation of regional ventricular function and myocardial perfusion by means of first pass radionuclide angiography (multielement gamma-camera) and computerized tomography, with 2 injections of 99mTc-MIBI at rest and at peak of a computerized bicycle stress test. QT and RR intervals were measured on an averaged ECG complex through a magnifying lens, and the absolute values of left ventricular volumes were computed by radionuclide angiography. According to scintigraphic findings, patients were divided into normal subjects (n = 7) and ischemic patients with (n = 63) and without (n = 81) evidence of a previous myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

[Changes in R wave voltage during exercise: are they a sign of changes in ventricular volume or of myocardial ischemia?]. / Modificazioni di voltaggio dell'onda R sotto sforzo: indice di variazione dei volumi ventricolari o di ischemia miocardica?

In an attempt to assess the significance of R wave amplitude changes during exercise in patients with coronary artery disease, we retrospectively analysed radionuclide as well as exercise test results of 147 patients with either suspected or already ascertained coronary artery disease, 126 men and 21 women, whose mean age was 56.0 +/- 9.3 years, 56 of which with previous myocardial infarction (16 on the anterior, 33 on the inferior and 7 on the lateral wall), who underwent a simultaneous evaluation of regional ventricular function by means of first pass angiography with multielement gamma-camera and of myocardial perfusion by means of single photon emission computerized tomography. All patients received 2 iv injections of 99mTc-methoxy-isobutyl-isonitrile at rest and at peak of a computerized bicycle stress test, whose end-points were ST segment depression greater than or equal to 1 mm or the attainment of a heart rate greater than 85% of maximal age-predicted one. R wave amplitude was measured by means of a magnifying lens on an averaged ECG complex, selecting for each patient the precordial lead showing the largest R wave amplitude. Absolute values of left ventricular volumes were computed by means of a standardized method from first pass angiography data. Patients were divided in subgroups according to the presence and to the number of coronary territories with evidence of stress-induced myocardial ischemia at radionuclide study.(ABSTRACT TRUNCATED AT 250 WORDS)