Effects of beta-blockade and atropine on ischemic responses in left ventricular regions subtending coronary stenosis during dobutamine stress echocardiography

OBJECTIVES: This study was designed to examine the effects of a beta-adrenergic blocking agent on the ischemic response to dobutamine stress and to determine the degree to which these effects can be abolished by the addition of atropine. BACKGROUND: Whether beta-blockade affects the sensitivity of dobutamine stress echocardiography for the diagnosis of coronary artery disease has been controversial. METHODS: In nine pigs, a left anterior descending coronary artery stenosis was created to reduce flow reserve (maximal/rest flow) to 1.1 to 1.9 without baseline regional wall motion abnormalities. This corresponded to a 50% to 90% diameter stenosis. Wall thickening was measured using epicardial echocardiography. Regional lactate production and coronary venous pH were monitored from an adjacent cardiac vein. A standard protocol of dobutamine stress echocardiography was first performed. After normalization of the ischemic abnormalities elicited with this infusion, esmolol was infused at 50 micrograms/kg body weight per min and the dobutamine test was repeated, with 1.0 mg of atropine added at the maximal dobutamine dose. RESULTS: Without esmolol, dobutamine stress induced myocardial ischemia with a reduction in regional wall thickening and lactate production in all nine pigs. Multiple regression analysis revealed that coronary flow per heartbeat (p < 0.01) and lactate production (p < 0.05) independently correlated with regional wall thickening during dobutamine stress. The beta-blocker significantly reduced heart rate and regional oxygen consumption and altered the relation between coronary flow per heartbeat and regional wall thickening (p < 0.05) during dobutamine stress. Esmolol prevented dobutamine-induced ischemia (lactate production and wall motion abnormalities) in seven of nine pigs. The addition of atropine induced lactate production and a reduction in wall thickening in five of seven pigs in which ischemia had been prevented by beta-blockade. However, lactate production was higher and regional venous pH was lower with the baseline dobutamine infusion than with that performed after esmolol with atropine added at the maximal dobutamine dose (p < 0.05). CONCLUSIONS: A correlation between regional wall thickening and coronary flow per heartbeat was demonstrated during baseline dobutamine stress. Beta-blockade shifted this relation so that dobutamine stress-induced myocardial ischemia was attenuated. The mechanisms by which beta-blockade prevents dobutamine-induced ischemia appeared to be mainly through decreases in heart rate and rate of rise in left ventricular pressure, improvement of regional coronary flow per heartbeat and attenuation of regional ischemic lactate production. Adding atropine in conventional doses enhanced the ability of dobutamine stress to induce myocardial ischemia but did not completely abolish the effects of beta-blockade on either the severity of dobutamine-induced wall thickening abnormalities or regional metabolic disturbances.     

Comparison of myocardial contrast echocardiography and low-dose dobutamine stress echocardiography in predicting recovery of left ventricular function after coronary revascularization in chronic ischemic heart disease

BACKGROUND: Dobutamine stress echocardiography (DSE) and myocardial contrast echocardiography (MCE) can predict recovery of left ventricular function after myocardial infarction. DSE also has been shown to predict left ventricular functional recovery after revascularization in chronic ischemic heart disease, whereas MCE has not been evaluated in such patients. This study was performed to compare DSE and MCE in the prediction of left ventricular functional recovery after revascularization in patients with chronic ischemic heart disease. METHODS AND RESULTS: MCE and DSE were performed in 35 patients with chronic coronary artery disease and significant wall motion abnormalities (mean ejection fraction, 0.36 +/- 0.09). Regional wall motion was scored by use of a 16-segment model wherein 1 = normal or hyperkinetic, 2 = hypokinetic, 3 = akinetic, and 4 = dyskinetic. Each segment was evaluated for contractile reserve by DSE and perfusion by MCE. Revascularization (coronary artery bypass graft [n = 13] and percutaneous transluminal coronary angioplasty [n = 10]) was successful in 23 patients. Follow-up echocardiograms were done to assess wall motion 30 to 60 days later. In 238 segments with resting wall motion abnormalities, perfusion was more likely to present than contractile reserve (97% versus 91%, P < .02). Revascularization resulted in functional recovery in 77 of 95 hypokinetic segments (81%) but only 18 of 57 akinetic segments (32%, P < .0001). DSE and MCE were not significantly different in predicting functional recovery of hypokinetic segments. In akinetic segments, DSE and MCE had similar sensitivities (89% versus 94%, respectively) and negative predictive values (93% and 97%, respectively) in predicting functional recovery. However, DSE had a higher specificity (92% versus 67%, P < .02) and positive predictive value (85% versus 55%, P < .02) than MCE in predicting functional recovery. CONCLUSIONS: Both contractile reserve by DSE and perfusion by MCE are predictive of functional recovery in hypokinetic segments after coronary revascularization in patients with chronic coronary revascularization in patients with chronic coronary artery disease. In akinetic segments, myocardial perfusion by MCE may exist in segments that do not recover contractile function after revascularization. Thus, contractile reserve during low-dose dobutamine infusion is a better predictor of functional recovery after revascularization in akinetic segments than perfusion.     

Safety and utility of atropine addition during dobutamine stress echocardiography for the assessment of viable myocardium in patients with severe left ventricular dysfunction

OBJECTIVE: To assess the feasibility safety and side effects of the addition of atropine to dobutamine stress echocardiography for the detection of viable myocardium in patients with left ventricular dysfunction (ejection fraction < or = 35%) prior to coronary revascularization. BACKGROUND: The assessment of viable and/or ischaemic myocardium has high prognostic value as regards improvement of function and survival after coronary revascularization. The addition of atropine to dobutamine during echocardiographic testing for the presence of viable myocardium is not common practice. Consequently, no data exist on the safety and additional diagnostic value of this practice. METHODS: Two hundred patients with left ventricular ejection fraction < or = 35% were studied. RESULTS: Test end-points were: target heart rate in 164 (82%) of the patients, severe angina in 18 (9%), maximum dobutamine-atropine dose in six (3%), severe ST segment changes in five (2%), cardiac arrhythmias in four (2%), and hypotension in three (1%). Viability could be assessed echocardiogaphically in 105/200 (53%) from a biphasic response (improvement of wall motion with low dose dobutamine and worsening with high dose), in 93 from ischaemia and in 12 from sustained or late improvements. In 36/105 (34%) patients, ischaemic myocardium could only be assessed after the addition of atropine. Cardiac arrhythmias occurred in 11/200 (6%) and hypotension (decrease of systolic blood pressure >30 mmHg) in 21/200 (11%). Neither the use of atropine nor the induction of ischaemia were associated with an increased incidence of cardiac arrhythmias or hypotension. CONCLUSIONS: In a large group of patients with severe left ventricular dysfunction, dobutamine stress echocardiography is feasible and safe in 186/200 (93%); the addition of atropine was necessary in 34% to assess myocardial viability. Hypotension and cardiac arrhythmias were the most frequent side effects, but were not related to the induction of ischaemia or addition of atropine.     

Effect of gender and left ventricular dysfunction on the incidence of hypotension induced by dobutamine stress echocardiography

BACKGROUND: Of patients who undergo dobutamine stress echocardiography (DSE), 14% to 38% experience hypotension that sometimes requires termination of the test before an adequate cardiac work-load is reached. The mechanisms of hypotension reportedly are related to peripheral vasodilation, a decrease in cardiac output, and left ventricular (LV) cavity obliteration. DSE is performed increasingly in women and in patients with LV dysfunction. However, the impact of gender and LV dysfunction on DSE-induced hypotension has not been elucidated. METHODS AND RESULTS: Clinical, hemodynamic, and echocardiographic characteristics were studied in 412 patients undergoing DSE, 82 patients with an LV ejection fraction of 40% or less, and 147 women. Hypotension, defined as a decrease in systolic blood pressure of at least 20 mm Hg, occurred in 117 (28%) patients. Hypotension was more common in women than men (36% vs 24%, P = .01). Hypotension was also more common in older adults (P = .004), persons taking diuretics (P = .025) or angiotensin-converting enzyme inhibitors (P = .01), and persons with higher baseline blood pressures (P < .0001). Hypotension was not related to the use of beta blockers, calcium channel blockers, digoxin, nitrates, LV dimensions, or ejection fraction. CONCLUSIONS: The incidence of DSE-induced hypotension is related to gender but not to the level of LV systolic function. It also is associated significantly with higher age, and use of angiotensin-converting enzyme inhibitors or diuretics.     

Diminished contractile reserve in patients with left ventricular hypertrophy and increased end-systolic stress during Dobutamine stress echocardiography

Left ventricular hypertrophy (LVH) is associated with decreased contractile response to inotropic stimulation in animal models, but this has not been documented in humans. To determine whether LVH is associated with decreased myocardial contractile reserve, we measured left ventricular mass, heart rate-corrected velocity of circumferential fiber shortening (Vcfc), end-systolic stress, and LV ejection fraction (LVEF) in patients with LVH and increased end-systolic stress (n = 6) and in patients without LVH (n = 7) who had a normal response to dobutamine stress echocardiography (increased LVEF and no wall motion abnormalities). The afterload-dependent indexes of left ventricular systolic performance were normal at baseline and showed significant increases at peak dobutamine dose (LVH group: Vcfc 0.91 +/- 0.11 to 1.76 +/- 0.59, p = 0.006; LVEF 49 +/- 5 to 65 +/- 6, p = 0.001; group without LVH: Vcfc 1.16 +/- 0.24 to 1.99 +/- 0.36, p = 0.001; LVEF 61 +/- 6 to 68 +/- 6, p = 0.05). The Vcfc/ end-systolic stress relation, a load-independent index of myocardial contractility, rose in a dose-dependent fashion in both groups, but the increment was significantly less for patients with LVH (p < 0.02), suggesting a blunted myocardial contractile reserve to inotropic stimulation. The change in heart rate-corrected velocity of circumferential fiber shortening per unit of change in end-systolic stress in each patient at each dobutamine dose showed a linear and inverse relationship. The increment in heart rate-corrected velocity of circumferential fiber shortening for a given reduction in end-systolic stress was larger in patients without LVH than in patients with LVH (p = 0.01). These results suggest that in patients with LVH and increased end-systolic stress, ventricular performance is maintained at the expense of limited myocardial contractile reserve, and that inotropic stimulation unmasks this abnormality, despite a normal response in LVEF and velocity of circumferential fiber shortening. This approach may identify patients with LVH at risk of developing systolic dysfunction and heart failure.     

Quantitation of global and regional left ventricular function by cine magnetic resonance imaging during dobutamine stress in normal human subjects

Magnetic resonance imaging (MRI) provides high-resolution images of the heart. However, physical exercise during MRI is difficult due to space restriction and motion artefacts. To evaluate the feasibility of MRI during stress conditions, dobutamine was used as an alternative to exercise. Haemodynamics, ventricular volumes and wall thickening were measured at rest and during peak dobutamine infusion (15 micrograms.kg-1 x min-1) in 23 normal human subjects. To calculate left ventricular volumes, eight short-axis views were obtained encompassing the left ventricle from base to apex. At six levels, percent systolic wall thickening (%WTh) was measured in 18 segments (20 degrees intervals). Heart rate, systolic and diastolic blood pressures, stroke index, cardiac output and left ventricular ejection fraction increased significantly during dobutamine infusion (all P values < 0.001). In addition, %WTh increased significantly (P < 0.001) during dobutamine compared to the control state at all levels except in the apical and low-left ventricular levels. Both in control conditions and during dobutamine, segmental wall motion analysis showed the highest %WTh at the posterolateral area and the lowest %WTh at the septal region (P < 0.05). MRI clearly identifies wall motion dynamics and provides calculations of segmental wall thickening and haemodynamic parameters. Dobutamine is a useful stress agent by virtue of its safety, operator control and its effects which resemble physical exercise.     

Left ventricular function by echocardiography in children with fixed aortic stenosis

Left ventricular function was evaluated echocardiographically within 24 hours of cardiac catheterization in 45 children with fixed aortic stenosis. Left ventricular systolic time intervals, mean velocity of circumferential fiber shortening, left ventricular end-diastolic volume and shortening fraction were evaluated. Some patients with severe aortic stenosis had a shortened preejection period, prolonged ejection time and increased mean velocity of circumferential fiber shortening in comparison with normal subjects, but these findings were not consistent within the group with severe aortic stenosis or apparent in patients with mild or moderate aortic stenosis. Left ventricular end-diastolic volume was smaller in children with severe obstruction than in normal children. Evaluation of the shortening fraction provided good separation of patients with significant obstruction from those with mild disease. Further, there was a linear correlation between the shortening fraction and the left ventricular-aortic gradient demonstrated at cardiac catheterization. This correlation was also of use in evaluating the response of patients to surgical relief of obstruction. Pre- and postoperative echocardiographic evaluation of the shortening fraction appears to provide a readily available noninvasive method of assessing the course and severity of obstruction in fixed aortic stenosis in children.     

The classification and analysis of the blood pathway in left ventricular cavity observed by left ventricular contrast echocardiography

We can observe and analyse the blood pathway in left ventricular cavity by contrast echocardiography using sonicated albumin, because it can be through the pulmonary capillaries. I. The observational classification of the blood pathway in left ventricular cavity. Group I: The contrast medium comes to the apex directly from the mitral orifice. Group II: The contrast medium comes to the apex along the posterior wall forming the spiral flow and turns back to the outflow tract. Group III: The contrast medium is found like a fireworks only at the apex. II. The factors associated with the blood pathway in left ventricular cavity. 1. Abnormality of left ventricular wall motion, 2. The form of left ventricular cavity, 3. Early diastolic peak velocity of the transmitral flow, 4. A/E, 5. Left ventricular function.     

Changes of endothelin-1 and atrial natriuretic peptide during dobutamine stress echocardiography

The aim of this study was to test the hypothesis that plasma endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) concentrations in patients with ischemic heart disease are related either to myocardial ischemia or left ventricular (LV) dysfunction during dobutamine stress echocardiography. Plasma concentrations of ET-1 and ANP were measured in three patient groups. Group I (n = 21) patients had normal stress echocardiography and a resting LV ejection fraction (LVEF) of 40% or more. Group II (n = 32) had positive stress echocardiography and a resting LVEF of more than 40%. Group III (n = 18) had positive stress echocardiography with a resting LVEF of less than 40%. All three groups were subjected to thallium 201 scintigraphy and coronary angiography studies. The resting LV end-diastolic pressure was significantly higher in groups II and III than in Group I. The LVEF decreased significantly in group III compared to groups I and II. In the resting state, groups II and III had higher ET-1 concentrations than Group I (p = 0.021 and p = 0.039, respectively). The plasma ANP concentration was higher in group III than in groups I and II (p = 0.005 and p = 0.054, respectively). During peak dobutamine infusion, the ET-1 concentration dropped 8.7% from the baseline in group I, 10.2% in group II, and 10.5% in group III. The ANP concentrations were increased in all three groups but only the increase in Group II reached statistical significance. In conclusion, in patients with suspected ischemic heart disease, the concentrations of ET-1 and ANP may predict significant anatomic and functional coronary artery disease. However, ET-1 does not play a pathophysiologic role during an ischemic attack.     

Effects of critical coronary stenosis on global systolic left ventricular function quantified by pressure-volume relations during dobutamine stress in the canine heart

OBJECTIVES: In this study we quantified the effects of a critical coronary stenosis on global systolic function using pressure-volume relations at baseline and during incremental dobutamine stress. BACKGROUND: The effects of coronary stenosis have previously been analyzed mainly in terms of regional (dys)function. Global hemodynamics are generally considered normal until coronary flow is substantially reduced. However, pressure-volume analysis might reveal mechanisms not fully exposed by potentially load-dependent single-beat parameters. Moreover, no systematic analysis by pressure-volume relations of the effects of dobutamine over a wide dose range has previously been presented. METHODS: In 14 dogs left ventricular volume and pressure were measured by conductance and micromanometer catheters, and left circumflex coronary flow by Doppler probes. Measurements in control and with left circumflex stenosis were performed at baseline and at five levels of dobutamine (2.5 to 20 microg/kg/min). The end-systolic pressure-volume relation (ESPVR) dP/dtMAX vs. end-diastolic volume (dP/dtMAX - V(ED)) and the relation between stroke work and end-diastolic volume (preload recruitable stroke work [PRSW]) were derived from data obtained during gradual caval occlusion. RESULTS: In control, dobutamine gradually increased heart rate up to 20 microg/kg/min, the inotropic effect blunted at 15 microg/kg/min. With stenosis, the chronotropic effect was similar, however, contractile state was optimal at approximately 10 microg/kg/min and tended to go down at higher levels. At baseline, the positions of ESPVR and PRSW, but not of dP/dtMAX - V(ED), showed a significant decrease in function with stenosis. No differences between control and stenosis were present at 2.5 microg/kg/min; the differences were largest at 15 microg/kg/min. CONCLUSIONS: Pressure-volume relations and incremental dobutamine may be used to quantify the effects of critical coronary stenosis. The positions of these relations are more consistent and more useful indices than the slopes. The positions of the ESPVR and PRSW show a reduced systolic function at baseline, normalization at 2.5 microg/kg/min and a consistent significant difference between control and stenosis at dobutamine levels of 5 microg/kg/min and higher.     

Dobutamine-atropine stress echocardiography for risk stratification in patients with chronic left ventricular dysfunction

OBJECTIVE: To assess the prognostic value of sustained improvement, scar and inducible ischemia with or without viability in patients with chronic left ventricular dysfunction (LVD). BACKGROUND: Dobutamine-atropine stress echocardiography (DASE) accurately detects scar, reversible dysfunction and the extent of coronary artery disease in LVD. METHODS: Three hundred fifty consecutive patients (age 62+/-13 years, mean+/-SD, 215 men/135 women) with moderate to severe LVD (LVEF < 40%, mean 30+/-8%) underwent DASE and were followed for > or =18 months. Dobutamine-atropine stress echocardiographic findings were classified according to sustained improvement in all vascular territories, scar, inducible ischemia (worsening wall motion at peak dose only or biphasic responses) and their extent. RESULTS: Sustained improvement occurred in 83 patients (24%), scar alone in 99 (28%) and inducible ischemia in 168 (48%, with biphasic responses in 104). Ischemia was induced in all vascular territories in 26 patients. Patients with sustained improvement or scar alone were treated medically, whereas 46% (78/168) with inducible ischemia were revascularized (coronary bypass surgery, n = 67 or angioplasty, n = 11). There were 76 hard events including cardiac death in 59, nonfatal myocardial infarction in 11, and resuscitated sudden death in 6. Hard events were rare in sustained improvement (5%, 4/83), uncommon in scar (13%, 13/99) and common (p < 0.01) in medically treated patients with inducible ischemia (59%, 53/90). Cardiac deaths were especially common (p < 0.01) in patients with biphasic responses (55%, 28/51). Inducible ischemia independently predicted hard events (chi2 = 75.35, p < 0.001) along with reduced LVEF at peak dose (chi2 = 8.38, p = 0.004). Hard cardiac events were uncommon (8%, 6/78, p < 0.001) in patients with inducible ischemia who underwent early revascularization. CONCLUSIONS: Inducible ischemia during DASE was the major determinant of outcome in LVD and independent of clinical data and left ventricular function. Improved wall thickening alone and scar alone predicted good outcome. Survival of patients with inducible ischemia was better after revascularization.     

Postresuscitation left ventricular systolic and diastolic dysfunction. Treatment with dobutamine

BACKGROUND: Global left ventricular dysfunction after successful resuscitation is well documented and appears to be a major contributing factor in limiting long-term survival after initial recovery from out-of-hospital sudden cardiac death. Treatment of such postresuscitation myocardial dysfunction has not been examined previously. METHODS AND RESULTS: Systolic and diastolic parameters of left ventricular function were measured in 27 swine before and after successful resuscitation from prolonged ventricular fibrillation cardiac arrest. Dobutamine infusions (10 micrograms.kg-1.min-1 in 14 animals or 5 micrograms.kg-1.min-1 in 5 animals) begun 15 minutes after resuscitation were compared with controls receiving no treatment (8 animals). The marked deterioration in systolic and diastolic left ventricular function seen in the control group after resuscitation was ameliorated in the dobutamine-treated animals. Left ventricular ejection fraction fell from a prearrest 58 +/- 3% to 25 +/- 3% at 5 hours after resuscitation in the control group but remained unchanged in the dobutamine (10 micrograms.kg-1.min-1) group (52 +/- 1% prearrest and 55 +/- 3% at 5 hours after resuscitation). Measurement of the constant of isovolumic relaxation of the left ventricle (tau) demonstrated a similar benefit of the dobutamine infusion for overcoming postresuscitation diastolic dysfunction. The tau rose in the controls from 28 +/- 1 milliseconds (ms) prearrest to 41 +/- 3 ms at 5 hours after resuscitation whereas it remained constant in the dobutamine-treated animals (31 +/- 1 ms prearrest and 31 +/- 5 ms at 5 hours after resuscitation). CONCLUSIONS: Dobutamine begun within 15 minutes of successful resuscitation can successfully overcome the global systolic and diastolic left ventricular dysfunction resulting from prolonged cardiac arrest and cardiopulmonary resuscitation.     

Left ventricular function in asthmatic children chronically treated with theophylline evaluated by exercise Doppler echocardiography

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.     

Left ventricular contractile performance, ventriculoarterial coupling, and left ventricular efficiency in hypertensive patients with left ventricular hypertrophy

Contractile performance of hypertrophied left ventricle may be depressed in arterial hypertension. Ventriculoarterial coupling is impaired when myocardial contractile performance is reduced and when afterload is increased. The left ventricular contractile performance and the ventriculoarterial coupling were evaluated in 30 hypertensive patients with moderate left ventricular hypertrophy and 20 control subjects. Left ventricular angiography coupled with the simultaneous recording of pressures with a micromanometer were used to determine end-systolic stress/volume index, the slope of end-systolic pressure-volume relationship, ie, end-systolic elastance, effective arterial elastance, external work, and pressure-volume area. In hypertensive patients, left ventricular contractile performance, as assessed by end-systolic elastance/ 100 g myocardial mass, was depressed (4.35 +/- 1.13 v 5.21 +/- 1.89 mm Hg/mL/100 g in control subjects P < .02), when end-systolic stress-to-volume ratio was comparable in the two groups (3.85 +/- 0.99 g/cm2/mL in hypertensive patients versus 3.51 +/- 0.77 g/cm2/mL in control subjects). Ventriculoarterial coupling, evaluated through effective arterial elastance/end-systolic elastance ratio, was slightly higher in hypertensive patients (0.53 +/- 0.08 v 0.48 +/- 0.09 mm Hg/mL in control subjects, P < .05), and work efficiency (external work/pressure-volume area) was similar in the two groups (0.78 +/- 0.04 mm Hg/mL in hypertensive patients versus 0.80 +/- 0.03 mm Hg/mL in control subjects). This study shows that despite a slight depression of left ventricular contractile performance, work efficiency is preserved and ventriculoarterial coupling is almost normal in hypertensive patients with left ventricular hypertrophy. Thus, it appears that left ventricular hypertrophy might be a useful means of preserving the match between left ventricle and arterial receptor with minimal energy cost.     

Left ventricular function during exercise in athletes and in sedentary men

Galactose-1-phosphate uridyltransferase (GALT) is a key enzyme in the metabolism of galactose. GALT activates the galactose-glucose interconversion and enables the synthesis of glucose-1-phosphate and UDP-galactose (UDP-Gal). UDP-Gal is the galactosyl donor for the incorporation of galactose into complex oligosaccharides, glycoproteins and glycolipids. The expression of GALT was characterized both in vivo and in vitro during late embryonic and postnatal development of the brain and peripheral nerve of the rat. Assays of GALT mRNA and protein showed that it is weakly expressed during late embryonic development with a second peak of expression concomitant with myelinogenesis. GALT was prominently expressed in myelinating Schwann cells in a rat dorsal root ganglia culture system. GALT deficiency in humans results in galactosemia, a disease characterized by long-term intellectual impairment, and probably dysmyelination. The developmentally regulated pattern of GALT expression during maturation of the nervous system may provide a molecular basis for these neurological complications which seriously compromise the outcome of many galactosemic patients.     

Left ventricular function during dynamic exercise in untrained and moderately trained subjects

The influence of exercise training on left ventricular function at rest (R), at anaerobic threshold (AT), and during peak exercise (PE) was evaluated in 12 healthy untrained and 13 trained (T) subjects who underwent Doppler echocardiography at R and radionuclide ventriculography at R and during exercise. The end-diastolic volume and stroke volume were significantly higher in the T group than in the untrained group at R. The ejection fraction rose significantly from R to AT and from AT to PE (80.0 +/- 0.84 vs. 83.6 +/- 0.91%), but no significant difference was observed between groups. The peak diastolic filling rate rose significantly during exercise, with a further significant increase observed in the T group (AT, 6.38 +/- 0.40 vs. 5.01 +/- 0.16 end-diastolic counts/s; PE, 8.24 +/- 0.42 vs. 7.15 +/- 0.35 end-diastolic counts/s). The percent variation of minimal systolic counts fell significantly at AT and PE in relation to R. Our data demonstrate that exercise training produces a significant increase in peak diastolic filling rate but no change in systolic function during exercise and that metabolic acidosis caused by exercise does not limit systolic function.     

Left ventricular geometry and severe left ventricular hypertrophy in children and adolescents with essential hypertension

BACKGROUND: Left ventricular (LV) hypertrophy has been established as an independent risk factor for cardiovascular disease in adults. Recent research has refined this relationship by determining a cutpoint of 51 g/m(2.7) for LV mass index indicative of increased risk and defining LV geometric patterns that are associated with increased risk. The purpose of this study was to evaluate severe LV hypertrophy and LV geometry in children and adolescents with essential hypertension. METHODS AND RESULTS: A cross-sectional study of young patients (n=130) with persistent blood pressure elevation above the 90th percentile was conducted. Nineteen patients (14%) had LV mass greater than the 99th percentile; 11 of these were also above the adult cutpoint of 51 g/m(2.7). Males, subjects with greater body mass index, and those who had lower heart rate at maximum exercise were at significantly (P<.05) higher risk of severe LV hypertrophy. In addition, 22 patients (17%) had concentric LV hypertrophy, a geometric pattern that is associated with increased risk of cardiovascular disease in adults. Seven patients had LV mass index above the cutpoint and concentric hypertrophy. No consistent significant determinants of LV geometry were identified in these children and adolescents with hypertension. CONCLUSIONS: Severe LV hypertrophy and abnormal LV geometry are relatively prevalent in young patients with essential hypertension. These findings suggest that these patients may be at risk for future cardiovascular disease and underscore the importance of recognition and treatment of blood pressure elevation in children and adolescents. Weight loss is an important component of therapy in young patients with essential hypertension who are overweight.     

Exercise capacity in patients with beta-thalassemia major: relation to left ventricular and atrial size and function

OBJECTIVES: The objective of this study was to examine the association between exercise capacity and echocardiographic indexes of atrial and ventricular function and size in patients with beta-thalassemia major. BACKGROUND: In patients with beta-thalassemia major, the assessment of cardiac function with echocardiography alone does not always correspond to their functional status. Peak oxygen uptake and anaerobic threshold, on the other hand, constitute 2 objective and reproducible determinants of exercise capacity in patients with heart failure. METHODS AND RESULTS: Forty consecutive patients (22 women and 18 men, 18 to 30 years old) who were in stable condition while receiving regular transfusions and 30 age- and sex-matched control subjects were studied. At 2 to 3 days after the last transfusion, each subject underwent complete echocardiographic study followed by cardiopulmonary exercise testing. Left atrial volumes (maximal [Vmax], at onset of atrial systolic [Vp], and minimal [Vmin]) and left ventricular volumes were measured with the biplane area-length method, and left atrial active emptying fraction (ACTEF) and left ventricular ejection (LVEF) fraction were calculated. Peak oxygen uptake (Vo 2 max) and anaerobic threshold (AT) were also estimated. After transfusion, patients with beta-thalassemia major had reduced Vo 2 max and AT and greater left atrial volume in comparison with control subjects. Also, ACTEF and LVEF were significantly lower in the patient group. Moreover, Vo2 max and AT were inversely related to Vmax (r = -0.74 and r = -0.80, respectively) and directly related to ACTEF (r = 0.85 and r = 0.82, respectively) in beta-thalassemia major, whereas they were poorly related to LVEF (r = 0.50 and r = 0. 53, respectively). In the control group, Vo 2 max and AT parameters were related to Vmax and ACTEF in a similar way to that in the beta-thalassemia group. CONCLUSIONS: In patients with beta-thalassemia major, exercise capacity does not correlate with left ventricular dimensions and function. On the contrary, left atrial size and systolic dysfunction are probably predictors of decreased exercise capacity.     

Preclinical cardiac dysfunction in transfusion-dependent children and young adults detected with low-dose dobutamine stress echocardiography

Transfusion-dependent (TD) patients develop cardiac iron overload that will eventually lead to cardiac pump failure. Low-dose dobutamine stress echocardiography may complement resting echocardiography and identify preclinical myocardial dysfunction caused by early cardiac hemosiderosis. Twenty-six iron-overloaded TD patients had stress echocardiography with 5 microg/kg per minute of dobutamine. Indexed left ventricular (LV) mass, LV dimensions, meridional wall stress, and cardiac index were significantly increased. TD patients had similar LV shortening fraction by M-mode (40.5% +/- 5.6% vs 39.4% +/- 4.5%) but had a lower mean LV ejection fraction (53.3% +/- 3.9% vs 46.8% +/- 6.9%, P < .002) and a subnormal increase in cardiac index during dobutamine stress (35% +/- 20% vs 11% +/- 16%, P < .0001). Impairment in LV relaxation was demonstrated by a prolonged isovolumetric relaxation time (0.060 +/- 0.005 vs 0.088 +/- 0.019 seconds, P < .0001), increased peak mitral E wave, and abnormal E/A ratio. Asymptomatic TD patients demonstrate decreased systolic functional reserve and abnormal left ventricular relaxation that may be caused by cardiac hemosiderosis. Low-dose dobutamine stress echocardiography may be useful for detecting and following cardiac dysfunction in patients at risk for cardiac hemosiderosis.     

Left ventricular performance in mitral regurgitation assessed with systolic time intervals and echocardiography

Among 22 patients with isolated mitral regurgitation of various origins, systolic time intervals (preejection period [PEP] index, left ventricular ejection time [LVET] index and PEP/LVET) and echocardiographic measures of left ventricular performance (end-diastolic diameter [Dd], end-systolic diameter [Ds], and the percent change in minor axis diameter [% delta D]) were calculated. The patients were classified into two groups, those with a normal or supernormal % delta D (group I, 15 patients) and those with a decreased % delta D (group II, 7 patients). On group analysis, prolongation of the preejection period, shortening of the left ventricular ejection time and an increase in PEP/LVET was generally characteristic of patients with mitral regurgitation. These changes were accentuated when mitral regurgitation was complicated by echocardiographic evidence of diminished left ventricular contractile performance (% delta D less than 30 percent). An increase in PEP/LVET to greater than 0.05 was consistently associated with abnormal left ventricular performance, whereas a normal PEP/LVET ratio reflected normal or supernormal left ventricular performance. An inverse linear relation was found between PEP/LVET and % delta D. When compared with previous data on the relation of these variables among patients without valve insufficiency, PEP/LVET proved to be increased for any level of % delta D in mitral regurgitation. The state of digitalization did not appear to influence the relation between PEP/LVET and % delta D. The use of echocardiographic measurements augments the determination of systolic time intervals in the analysis of left ventricular performance in patients with mitral regurgitation.