tricuspid lateral annular TD velocities before dialysis were 13.05±2.49, 8.78±2.6,17.47±6.74cm/s, and after dialysis were 12.45±3.29,6.92±1.78,16.63±6.30cm/s.Myocardial early diastolic velocity decreased marginally by 1.86±2.14(p=0.044),but systolic and late diastolic velocities did not change significantly (p=0.313 and p=0.531, respectively).In our study population there was no statistically significant correlation between RV TDI velocities and LV systolic function.Conclusion: TDI assessment allows a quantitative evaluation of both systolic and diastolic RV function.Moreover, tricuspid annular velocities were not or only minimally affected by preload reduction in hemodialysis patients.

OBJECTIVES:We sought to identify the pattern of disturbed left ventricular physiology associated with symptom development in elderly patients with effort-induced breathlessness. BACKGROUND:Limitation of exercise tolerance by dyspnea is common in the elderly and has been ascribed to diastolic dysfunction when left ventricular cavity size and systolic function appear normal. METHODS:Dobutamine stress echocardiography was used in 30 patients (mean [+/-SD] age 70 +/- 12 years; 21 women, 9 men) with exertional dyspnea and negative exercise test results, and the values were compared with those in 15 control subjects. RESULTS:Before stress, left ventricular end-diastolic and end-systolic dimensions were reduced, fractional shortening was increased, and the basal septum was thickened (2.3 +/- 0.5 vs. 1.4 +/- 0.2 cm, p < 0.001, vs. control subjects) in the patients, but posterior wall thickness did not differ from that in control subjects. Left ventricular outflow tract diameter, measured as systolic mitral leaflet septal distance, was significantly reduced (13 +/- 4.5 vs. 18 +/- 2 mm, p < 0.001). Isovolumetric relaxation time was prolonged, and peak left ventricular minor axis lengthening rate was reduced (8.1 +/- 3.5 vs. 10.4 +/- 2.6 cm/s, p < 0.05), suggesting diastolic dysfunction. Transmitral velocities and the E/A ratio did not differ significantly. At peak stress, heart rate increased from 66 +/- 8 to 115 +/- 20 beats/min in the control subjects, but blood pressure did not change. Transmitral A wave velocity increased, but the E/A ratio did not change. Left ventricular outflow tract velocity increased from 0.8 +/- 0.1 to 2.0 +/- 0.2 m/s, and mitral leaflet septal distance decreased from 18 +/- 2 to 14 +/- 3 mm, p < 0.001. In the patients, heart rate rose from 80 +/- 12 to 132 +/- 26 beats/min and systolic blood pressure from 143 +/- 22 to 170 +/- 14 mm Hg (p < 0.001 for each), but left ventricular dimensions did not change. Peak left ventricular outflow tract velocity increased from 1.5 +/- 0.5 m/s (at rest) to 4.2 +/- 1.2 m/s; mitral leaflet septal distance fell from 13 +/- 4.5 to 2.2 +/- 1.9 mm (p < 0.001); and systolic anterior motion of mitral valve appeared in 24 patients (80%) but in none of the control subjects (p < 0.001). Measurements of diastolic function did not change. All patients developed dyspnea at peak stress, but none developed a new wall motion abnormality or mitral regurgitation. CONCLUSIONS:Although our patients fulfilled the criteria for "diastolic heart failure," diastolic dysfunction was not aggravated by pharmacologic stress. Instead, high velocities appeared in the left ventricular outflow tract and were associated with basal septal hypertrophy and systolic anterior motion of the mitral valve. Their appearance correlated closely with the development of symptoms, suggesting a potential causative link.

OBJECTIVE: To assess the effect of ACE-inhibition on left ventricular filling and wall motion in patients with a clinical diagnosis of heart failure. DESIGN: Prospective examination of left ventricular systolic and diastolic function using M mode echocardiography and pulsed and continuous wave Doppler before and three weeks after starting an ACE inhibitor. SETTING: A tertiary referral centre for cardiac disease equipped with non-invasive facilities. SUBJECTS: 30 outpatients with a clinical diagnosis of heart failure in whom treatment with an ACE inhibitor was started; age 61 (SD 11) years; 27 male; 3 female; 21 healthy controls of similar age. RESULTS: Left ventricular cavity was dilated both at end systole and end diastole, and fractional shortening reduced. Although mean isovolumetric relaxation time (IVRT) and transmitral E (early) to A (late) filling velocity (E/A) ratio were not different from normal, a value of 1.0 on the normal frequency plot of the E/A ratio divided the patients bimodally into two groups: 20 patients (group A) with E/A ratio > 1.0 and 10 patients (group B) < 1.0. In group A patients, IVRT was short as was transmitral E wave deceleration time compared to normal (P < 0.001), fulfilling the criteria of restrictive left ventricular physiology. Left ventricular wall motion during IVRT was coordinate and left ventricular end diastolic pressure was raised on the apex-cardiogram (P < 0.001). In group B, E wave deceleration time was longer, relaxation incoordinate, and apexcardiogram normal. With an ACE inhibitor: in group A, left ventricular dimensions fell at end diastole (P < 0.05) and end systole (P < 0.01) but fractional shortening did not change; long axis total excursion (P < 0.01) and peak rate of shortening (P < 0.05) both increased; IVRT increased (P < 0.001) with the appearance of markedly incoordinate wall motion, minor axis lengthening, and long axis shortening (P < 0.001 for both); A wave amplitude also consistently increased (P < 0.001); finally, transmitral E wave velocity fell and A wave velocity increased. ACE inhibition did not alter any of the left ventricular minor and long axis or transmitral Doppler variables in patients in group B. CONCLUSIONS: Patients with a clinical diagnosis of heart failure differ in their presentation and response to ACE inhibition according to baseline haemodynamics. In restrictive left ventricular physiology, ACE inhibition reduces cavity size and prolongs IVRT, compatible with a fall in left atrial pressure. At the same time, ventricular relaxation becomes very delayed and incoordinate, greatly reducing early diastolic left ventricular filling velocity. Thus ACE inhibition unmasks major diastolic abnormalities in patients with restrictive left ventricular disease.

OBJECTIVE: To assess the effect of acute alterations in afterload by aortoiliac clamping, during peripheral vascular surgery, on left ventricular function. DESIGN: Prospective examination of the left ventricular long axis and transmitral Doppler flow preoperatively and intraoperatively; before aortic clamping, during clamping and 5 min, 15 min, and 5 days after unclamping. SETTING: A tertiary referral centre for cardiac and vascular disease equipped with invasive and non-invasive facilities. PATIENTS: 20 patients (11 men; mean (SD) age 61 (8) years) with significant aortoiliac disease and documented coronary artery disease and 21 normal controls of similar age. RESULTS: Preoperatively: long axis function was abnormal compared with that in normal controls. In systole total long axis excursion and peak shortening rate were reduced, onset of shortening delayed, and there was pre-ejection lengthening (P < 0.001). In diastole there was abnormal shortening during isovolumic relaxation, delaying the onset of long axis lengthening (P < 0.001). Peak lengthening rate was also reduced and A wave excursion increased (P < 0.001). Transmitral Doppler showed increased A wave velocity and reduced peak E/A diastolic flow velocities ratio (P < 0.001). Intraoperatively: preclamping results did not differ from those before operation. With clamping the extent of systolic and diastolic abnormalities promptly increased as to a lesser extent did those of transmitral flow velocity, although heart rate and blood pressure did not change significantly. Total long axis excursion and A wave amplitude were more reduced by aortic than iliac clamping, whereas the onset of lengthening was more delayed and the lengthening velocity more reduced with iliac clamping. Some 5 min after unclamping systolic long axis function had already returned towards normal; total excursion increased, as did the peak shortening rate, and the onset of shortening became less delayed (P < 0.001). In diastole the delayed onset of lengthening regressed, its lengthening velocity increased, and A wave excursion fell (P < 0.001). Early diastolic transmitral flow velocity also increased. This improvement in systolic and diastolic long axis function had progressed 15 min after unclamping but showed no further change at 5 days. At 5 days after operation, however, systolic and diastolic measurements had improved compared with those preoperatively. CONCLUSION: Resting left ventricular long axis function is abnormal in patients with combined coronary artery disease and peripheral vascular disease. It is unaffected by anaesthesia but deteriorates with aortic or iliac clamping, although blood pressure remains unchanged. It promptly improves with unclamping after successful peripheral arterial reconstruction. Thus, even in apparently stable coronary artery disease, resting subendocardial function is labile, showing pronounced alterations with changing after-load, even when arterial pressure itself does not change.

STUDY OBJECTIVE:To assess possible effects of systemic sclerosis on ventricular function.DESIGN:Retrospective analysis of patients referred for echocardiographic examination to assess ventricular function.SETTING:Tertiary referral center for cardiac and chest diseases equipped with invasive and noninvasive facilities.PATIENTS:Thirty-four patients with clinical diagnosis of systemic sclerosis, aged 49 +/- 12 years; 24 had pulmonary fibrosis and 10 did not. There were 21 normal controls of similar age.MEASUREMENTS:Two-dimensional guided M-mode echocardiographic recordings of the left ventricular minor and long axis at the left and septal sites and right ventricle were obtained. Transmitral and transtricuspid Doppler flow velocities were also obtained with ECG and phonocardiogram.RESULTS:In 24 patients with pulmonary fibrosis, long-axis excursion was reduced 2.1 +/- 0.5 vs 2.7 +/- 0.4 cm/s as was peak rate of shortening and lengthening, 8.5 +/- 3.3 vs 10.8 +/- 2.4 cm/s and 7.5 +/- 2.5 vs 12 +/- 3.6 cm/s, respectively (p < 0.001), at the right side compared with 10 patients without. The onset of right long-axis shortening and lengthening was delayed with respect to the Q wave of the ECG and P2 of the phonocardiogram (p < 0.001 in both vs controls). The onset of tricuspid forward flow from the second heart sound was also delayed in the two groups, 110 +/- 15 ms and 100 +/- 20 ms vs 80 +/- 15 ms, respectively (p < 0.001). Right ventricular late diastolic filling velocities were increased 35 +/- 15 and 35 +/- 12 cm/s vs 20 +/- 10 cm/s in both groups (p < 0.01), and hence E:A ratio reduced 1.25 +/- 0.5 and 1.4 +/- 0.3 vs 1.9 +/- 0.4, respectively (p < 0.001). Pulmonary flow acceleration time was reduced only in patients with pulmonary fibrosis, 105 +/- 30 ms vs 125 +/- 30 ms (p < 0.001). At the left side, total long-axis excursion was reduced only in patients with pulmonary fibrosis (p < 0.01), while peak shortening and lengthening rates were reduced in both groups (p < 0.05). The onset of shortening from the Q wave and lengthening from the second heart sound were both delayed in the two groups with the latter greatly delayed in patients with pulmonary fibrosis (p < 0.05).CONCLUSIONS:Right and left ventricular long-axis function is frequently abnormal in patients with systemic sclerosis. Abnormalities are more profound in patients with CT evidence of pulmonary fibrosis than in those without. We suggest that these disturbances are due to myocardial fibrosis which, from the anatomic distribution of longitudinally directed fibers, is likely to have been subendocardial.

We studied 31 patients with dilated cardiomyopathy, correlating mitral valve cusp motion with the continuous wave Doppler signal of mitral regurgitation and the signal averaged electrocardiogram (ECG). Sixteen patients had a B point (early partial closure) on the mitral echogram and 15 did not. Fifteen normal cases were used as controls. The duration of ventricular early potentials (< 40 microV) was measured on the signal averaged ECG of the QRS complex. The PR interval was increased in patients with a B point (190 (33) ms vs. 145 (16) ms in normal, P < 0.01) and PR-AC interval was reduced (25 (71) ms vs. 65 (11) ms in normal, P < 0.05). The B point itself was effectively synchronous with the onset of low velocity early systolic mitral regurgitation, and followed the Q wave of the succeeding beat by 20 ms or less. Early low velocity on mitral regurgitation was not present in patients without a B point. The duration of early potentials was greatly increased in patients with a B point (43 (26) ms) compared both to those without (17 (20) ms, P < 0.01) and to normals (12 (7) ms, P < 0.01) and their duration correlated with B-C interval (r = 0.6, P < 0.02). We conclude that a B point on the mitral echogram in patients with left ventricular disease is due to early systolic low velocity mitral regurgitation which itself results from an abnormal pattern of left ventricular activation, probably bilateral bundle branch block. Once established, this low velocity jet delays complete mitral valve closure.

Objective-To assess possible mechanical influences underlying the reduced heart rate variability in patients with dilated cardiomyopathy.Design-Comparison of standard nonspectral indices of heart rate variability with echocardiographic Doppler measures of left ventricular function in patients and normal controls.Patients-20 patients with dilated cardiomyopathy and 15 normal subjects of similar ages were studied.Methods-Standard non-spectral indices of heart rate variability were measured over 24 hours. These were correlated with left ventricular cavity size, shortening fraction, and isovolumic relaxation time measured by M mode echocardiography, and the duration of functional mitral regurgitation and left ventricular filling time assessed by continuous wave Doppler.Results-Mean RR interval and estimates of short term variability (root mean square difference of successive RR intervals, proportion of adjacent RR intervals > 50 ms different, and SD indices) were not different from normal. The overall mean (SD) of the RR interval (65 (35)), and SD of five minute mean RR intervals (55 (30)), however, were reduced compared with normal values (115 (40) and 105 (45); p < 0.01 for both). Neither correlated with left ventricular cavity size or shortening fraction, but both were strongly related to left ventricular filling time (coefficient of variation, r = 0-82 and r = 0.81 respectively). Correlation persisted when the SD was corrected for RR interval (r = 0-69) although this correlation was not found in the controls. In individual patients, the difference between RR interval at the time of echo and minimum value during the 24 hours, a measure of ability to increase heart rate, also correlated closely with filling time (r = 0.92).Conclusion-As the duration of functional mitral regurgitation is effectively fixed, its presence can limit the time available for left ventricular filling in dilated cardiomyopathy when heart rate is high. This may become the mechanism by which maximum heart rate is set, becoming fixed to optimise cardiac output. This manifestation of dilated cardiomyopathy may be an important factor in reduction of heart rate variability in these patients.

By means of a cytokine release assay we have shown that in cell populations derived from primary breast carcinoma, epidermal growth factor (EGF) is secreted by cells with the characteristic morphological and immunophenotypic profile of activated macrophages (positive for CD68, CD16, CD25). EGF secretion was observed in 11 (31%) of 35 primary tumours. Secretion of EGF by normal or malignant epithelial cells was not observed. We found no association between EGF secretion by the primary tumour and recognised clinical indices of prognosis.

To establish the contribution of combination therapy in stable angina, the short- and long-term effects of diltiazem (120 mg and 360 mg/day, respectively), and the additive effects of sublingual isosorbide dinitrate, 10 mg, and atenolol, 100 mg, were studied in 11 patients with chronic stable angina using an open-label sequential design. All patients underwent exercise testing without therapy, and with each drug and their combinations. Exercise time and heart rate-blood pressure product were measured at 1-mm ST-segment depression, or at peak exercise if the test result was negative. Exercise time increased from a control value of 8.0 ± 2.3 minutes (mean ± standard deviation) to 11.4 ± 2.4 minutes (p < 0.0001) after the administration of isosorbide dinitrate, to 11.3 ± 1.8 minutes (p < 0.001) after short-term diltiazem and to 12.4 ±1.5 minutes (p < 0.001) after long-term diltiazem. The rate-pressure product increased from a control value of 19,070 ± 3,564 to 24,431 ± 4,795 beats/ min X mm Hg (p < 0.0001) after isosorbide dinitrate, to 22,287 ± 4,753 beats/min X mm Hg (p < 0.01) after short-term diltiazem and to 21,812 ±3, 976 beats/min × mm Hg (p < 0.007) after longterm dittiazem. The addition of atenolol to longterm diltiazem significantly reduced the rate-pressure product compared with long-term diltiazem alone (21,812 ± 3,976 vs 13,926 ± 2,880 beats/ min × mm Hg, p < 0.002), although there was no further significant increase in exercise time (12.4 ±1.5 vs 13.3 ± 1.6 minutes). There was no significant change in exercise response after the additional administration of isosorbide dinitrate to long-term diltiazem with atenolol. The weekly angina frequency was reduced from a mean of 30 ± 17 episodes/wk without therapy to 6 ± 5 with long-term diltiazem (p < 0.001) and to 5 ± 4 with longterm diltiazem combined with atenolol (difference not significant vs long-term diltiazem therapy). It was concluded that (1) short-term diltiazem therapy increases the ischemic threshold by an extent similar to that of short-term nitrate administration; (2) long-term diltiazem therapy improves exercise time by a combination of increased myocardial oxygen supply and reduced demand; and (3) the addition of atenolol does not additionally improve exercise time.