Quantitative approach using multiple single parameters versus visual assessment in dobutamine stress echocardiography

ABSTRACT: BACKGROUND: A number of myocardial Doppler-derived velocity, strain myocardial imaging parameters (DMI) and speckle tracking imaging (STI) have been proposed for the quantification of myocardial ischemia during stress echocardiography. The purpose of the study was to identify the best single ultrasound quantitative parameter for prediction of significant coronary stenosis and compare it with visual assessment during dobutamine stress echocardiography (DSE). METHODS: Prospective analysis included data of 151 patients (age 61.8 +/- 9.2) who underwent dobutamine stress echocardiography for known (n=35) or suspected CAD (n=36) or symptomatic chest pain (n=80), excluding patients with previous myocardial infarction. Systolic, post-systolic and diastolic velocities, strain and strain rate parameters were obtained at rest and at peak dobutamine challenge. Derivative markers as E'/A' ratio, post-systolic index and changes from rest to stress were calculated (98 parameters overall, predominantly longitudinal). Coronary angiography was chosen as reference method considering at least one stenosis greater than or equal to 70% per patient as significant CAD. The predictive value of quantitative parameters and wall motion score index (WMSI) was obtained using logistic regression and ROC analysis. RESULTS: The value of single parameters discriminated as independent predictors of CAD appeared to be modest (area under the curve [AUC] ranged from 0.63 to 0.72 for 16 PW-DMI, 12 CC-DMI and 12 STI markers), comparing to AUC of WMSI 0.88. Sensitivity, specificity and accuracy of visual DSE evaluation was 82.4% (95%CI 77.4%; 85.2%), 92.6% (95%CI 83.4%; 97.5%) and 86.0% (95%CI 79.5%; 89.6%), respectively, Youden index 0.75. Sensitivity, specificity and accuracy of single predictors ranged from 40.0% to 93.3% (95% CI 22.7%; 99.2%), from 34.2% to 88.7% (95% CI 25.6%; 94.1%) and from 45.8% to 80.0% (95% CI 37.5%; 87.2%) respectively, Youden index ranged from 0.20 to 0.52. CONCLUSIONS: Multiple single quantitative parameters showed limited predictive ability to identify significant coronary artery stenosis. Visual assessment of DSE appears to be more accurate than single velocity and strain/strain rate markers in the diagnosis of CAD.     

Dobutamine stress magnetic resonance imaging suffices for the demonstration of myocardial ischaemia and viability

We report three patients in whom dobutamine stress magnetic imaging (DS-MRI) was essential in assessing myocardial ischaemia. Two patients were referred to the cardiologist because of chest pain. Patient A had typical exertional angina and a normal resting electrocardiogram (ECG). Patient B had typical exercise-induced angina and had recently experienced an attack of severe chest pain at rest for 15 minutes. The ECG showed a complete left bundle branch block (LBBB). Patient C was referred for heart failure of unknown origin. There were no symptoms of chest pain during rest or exercise. Echocardiography in this patient demonstrated global left ventricular (LV) dilatation, systolic dysfunction and a small dyskinetic segment in the inferior wall. In all these patients exercise stress testing had failed to demonstrate myocardial ischaemia. Patients A and C produced normal findings whereas in patient B the abnormal repolarisation due to pre-existent LBBB precluded a diagnosis of ischaemia.Breath-hold DS-MRI was performed to study LV wall motion and wall thickening at rest through increasing doses of dobutamine. A test was considered positive for myocardial ischaemia if wall motion abnormalities developed at high-dose levels of the drug (20 μg/kg/min or more with a maximum of 40 μg/kg/min) in previously normal vascular territories or worsened in a segment that was normal at baseline. Recovery of wall thickening in a previously hypokinetic or akinetic segment at a low dose of dobutamine (5-10 μg/kg/min) was taken as proof of viability.Patients A and B developed hypokinesia progressing into akinesia at high-dose dobutamine in the anteroseptal area of the LV indicative of ischaemia. These findings were corroborated by coronary angiography demonstrating severe coronary artery disease which led to coronary artery bypass grafting (CABG) in patient A and balloon angioplasty in patient B. In patient C global recovery of LV contractions during low-dose dobutamine was followed by hypokinesia in the inferoseptal area during high-dose dobutamine. This biphasic response indicates myocardial viability as well as ischaemia. CABG was carried out because of multiple stenoses in the left coronary artery. Post-operatively LV function normalised.DS-MRI is a valuable method for detecting myocardial ischaemia and viability in patients with suspected coronary artery, and can be applied in every hospital with MRI equipment at its disposal.     

Dobutamine enhances both contractile function and energy reserves in hypoperfused canine right ventricle

Although the beta(1)-adrenergic agent dobutamine is used clinically to provide inotropic support to the failing myocardium, it could jeopardize the myocardium by depleting energy reserves. This investigation delineated the contractile and energetic effects of low versus high dobutamine doses in the hypoperfused right ventricular (RV) myocardium. The right coronary artery (RCA) of anesthetized dogs was cannulated for controlled perfusion with arterial blood, and regional RV contractile function was measured. RCA perfusion pressure was lowered from 100 mmHg baseline to 40 mmHg, and flow fell by 54%. At 15-min hypoperfusion, dobutamine was infused into the RCA at either 0.01 (low-dose dobutamine) or 0.06 microgram. kg(-1). min(-1) (high-dose dobutamine) for 15 min. Regional power (systolic segment shortening x isometric developed force x heart rate) stabilized at 63% of baseline during hypoperfusion. Low-dose dobutamine restored power to baseline but did not increase RV myocardial O(2) consumption (MVO(2)) and thus increased myocardial O(2) utilization efficiency (O(2)UE:power/MVO(2)). At 5 min, high-dose dobutamine enhancement of power was similar to that of low-dose dobutamine, but by 15 min, power and O(2)UE fell to untreated levels. Remarkably, low-dose dobutamine tripled cytosolic phosphorylation potential; in contrast, high-dose dobutamine lowered phosphorylation potential to 45% of the untreated value. Analyses of glucose uptake and glycolytic intermediates revealed sustained enhancement of glycolysis by low-dose dobutamine, but glycolysis became limited at glyceraldehyde 3-phosphate dehydrogenase during high-dose dobutamine treatment. In summary, low-dose dobutamine improved mechanical performance and efficiency of the hypoperfused RV myocardium while increasing myocardial energy reserves, but high-dose dobutamine failed to sustain improved function and depleted energy reserves. Dobutamine is capable of improving both contractile function and cellular energetics in the hypoperfused RV myocardium, but dosage should be carefully selected.     

Mechanisms involved in symptomatic myocardial bridging

Background.In patients with extensive myocardial bridging, evaluation of its clinical significance remains a challenge. Hypothesis.Sequential invasive testing is feasible and gives more insight into the pathophysiological mechanism of bridging-related angina. Methods.Twelve patients with chest pain, proven ischaemia and extensive myocardial bridging were assessed. Myocardial bridging was evaluated at rest, during intracoronary acetylcholine infusion, through coronary flow velocity and flow reserve measurements, and during dobutamine stress. Results.The mean length of the bridging segment was 24.9 mm (QCA; range 8.4-48.0 mm). Acetylcholine infusion caused severe vasospasm in two patients. In these two patients anginal symptoms were related to vasospasm and sequential testing was discontinued. In the remaining ten patients sequential testing was continued. Coronary flow reserve was normal in all patients: 3.3±0.6. In six patients reliable quantitative measurements could be performed during dobutamine stress. The mean systolic diameter of the bridging segment was 1.6±0.4 at baseline and 1.3±0.3 during dobutamine stress (mean of differences 0.38 (95% CI 0.1-0.7)). The difference between the diastolic and systolic diameter in the bridging segment increased from 0.3±0.2 mm at baseline to 1.0±0.5 mm during dobutamine infusion (mean of differences 0.6 (95% CI 0.3 to 0.9)). Conclusion.Sequential testing for bridging is feasible and may disclose endothelial dysfunction or spasm as an underlying mechanism in a minority of patients. Coronary flow reserve was preserved. Dobutamine stress unmasked further lumen reduction and may give further insight into the clinical significance of myocardial bridging in individual patients. (Neth Heart J 2008;16:10-5.)     

Characterization of Regional Left Ventricular Function in Nonhuman Primates Using Magnetic Resonance Imaging Biomarkers: A Test-Retest Repeatability and Inter-Subject Variability Study

Pre-clinical animal models are important to study the fundamental biological and functional mechanisms involved in the longitudinal evolution of heart failure (HF). Particularly, large animal models, like nonhuman primates (NHPs), that possess greater physiological, biochemical, and phylogenetic similarity to humans are gaining interest. To assess the translatability of these models into human diseases, imaging biomarkers play a significant role in non-invasive phenotyping, prediction of downstream remodeling, and evaluation of novel experimental therapeutics. This paper sheds insight into NHP cardiac function through the quantification of magnetic resonance (MR) imaging biomarkers that comprehensively characterize the spatiotemporal dynamics of left ventricular (LV) systolic pumping and LV diastolic relaxation. MR tagging and phase contrast (PC) imaging were used to quantify NHP cardiac strain and flow. Temporal inter-relationships between rotational mechanics, myocardial strain and LV chamber flow are presented, and functional biomarkers are evaluated through test-retest repeatability and inter subject variability analyses. The temporal trends observed in strain and flow was similar to published data in humans. Our results indicate a dominant dimension based pumping during early systole, followed by a torsion dominant pumping action during late systole. Early diastole is characterized by close to 65% of untwist, the remainder of which likely contributes to efficient filling during atrial kick. Our data reveal that moderate to good intra-subject repeatability was observed for peak strain, strain-rates, E/circumferential strain-rate (CSR) ratio, E/longitudinal strain-rate (LSR) ratio, and deceleration time. The inter-subject variability was high for strain dyssynchrony, diastolic strain-rates, peak torsion and peak untwist rate. We have successfully characterized cardiac function in NHPs using MR imaging. Peak strain, average systolic strain-rate, diastolic E/CSR and E/LSR ratios, and deceleration time were identified as robust biomarkers that could potentially be applied to future pre-clinical drug studies.     

Two‐Dimensional Strain and Twist by Vector Velocity Imaging in Adolescents With Severe Obesity

The prevalence of severe obesity is increasing worldwide in adolescents. Whether it is associated with functional myocardial abnormalities remains largely unknown, potentially because of its frequent association with other cardiovascular risk factors and also use of insensitive techniques to detect subclinical changes in myocardial function. We used 2D vector velocity imaging (VVI) to investigate early changes in left ventricular (LV) myocardial function in youths with isolated severe obesity. Thirty‐seven asymptomatic severely obese adolescents free of diabetes and hypertension, and 24 lean controls were enrolled. LV longitudinal, basal, and apical circumferential strain, strain rate (SR), rotations, and LV twist were measured. Obese adolescents had greater LV mass and reduced systolic and early diastolic tissue Doppler imaging (TDI) velocities than lean counterparts. L strain (?24%) and systolic and early diastolic SR were also diminished in the obese, whereas no intergroup differences existed for the circumferential deformation indexes. LV twist was more pronounced in the obese (+1.7°, P < 0.01) on account of greater apical rotation only (4.1 ± 0.9 vs. 5.2 ± 1.2°, P < 0.01), potentially compensating for the loss in longitudinal function. Systolic—diastolic coupling, an important component of early filling and diastolic function, was maintained with severe obesity. No intergroup differences were reported regarding time to peak values for all VVI indexes highlighting that dynamics of strain and twist/untwist along the cardiac cycle was preserved with severe obesity. Isolated severe obesity in adolescents, at a preclinical stage, is associated with changes in myocardial deformation and torsional mechanics that could be in part related to alterations in relaxation and contractility properties of subendocardial fibers.     

Tissue Doppler imaging during dipyridamole and dobutamine stress echocardiography in the diagnosis of coronary heart disease

The aim of the study was to determine the sensitivity and specificity of combined high-dose dipyridamole and dobutamine stress echocardiography (stress EchoCG) in the diagnosis of coronary artery stenotic lesions in coronary heart disease in a group of patients who were unable to perform physical exercise, by using different assessment criteria (local contractile impairments and systolic velocity changes during tissue Doppler imaging). The study enrolled 68 men who had undergone dipyridamole and dobutamine stress EchoCG, longitudinal tissue Doppler imaging, and coronary angiography. Stress EchoCG could bring up to diagnostic criteria in all the patients. Coronary angiography revealed no coronary artery lesion in 18 patients, but showed single and multiple vascular lesions in 31 and 19 patients, respectively. The sensitivity and specificity of combined stress EchoCG were significantly higher than those of stress EchoCG examination. The results of combined stress EchoCG allow one to judge to a greater validity (96% sensitivity and 100% specificity) local contractile impairments corresponding to the blood supply area in the atherosclerosis-afflicted coronary artery. Analysis of systolic velocity parameters during tissue Doppler imaging permits the diagnostic value of the technique to be insignificantly improved particularly when the test results are controversial.     

Myocardial Feature Tracking Reduces Observer-Dependence in Low-Dose Dobutamine Stress Cardiovascular Magnetic Resonance

Objectives

To determine whether quantitative wall motion assessment by CMR myocardial feature tracking (CMR-FT) would reduce the impact of observer experience as compared to visual analysis in patients with ischemic cardiomyopathy (ICM).

Methods

15 consecutive patients with ICM referred for assessment of hibernating myocardium were studied at 3 Tesla using SSFP cine images at rest and during low dose dobutamine stress (5 and 10 μg/kg/min of dobutamine). Conventional visual, qualitative analysis was performed independently and blinded by an experienced and an inexperienced reader, followed by post-processing of the same images by CMR-FT to quantify subendocardial and subepicardial circumferential (Ecc_endo and Ecc_epi) and radial (Err) strain. Receiver operator characteristics (ROC) were assessed for each strain parameter and operator to detect the presence of inotropic reserve as visually defined by the experienced observer.

Results

141 segments with wall motion abnormalities at rest were eligible for the analysis. Visual scoring of wall motion at rest and during dobutamine was significantly different between the experienced and the inexperienced observer (p<0.001). All strain values (Ecc_endo, Ecc_epi and Err) derived during dobutamine stress (5 and 10 μg/kg/min) showed similar diagnostic accuracy for the detection of contractile reserve for both operators with no differences in ROC (p>0.05). Eccendo was the most accurate (AUC of 0.76, 10 μg/kg/min of dobutamine) parameter. Diagnostic accuracy was worse for resting strain with differences between operators for Ecc_endo and Ecc_epi (p<0.05) but not Err (p>0.05).

Conclusion

Whilst visual analysis remains highly dependent on operator experience, quantitative CMR-FT analysis of myocardial wall mechanics during DS-CMR provides diagnostic accuracy for the detection of inotropic reserve regardless of operator experience and hence may improve diagnostic robustness of low-dose DS-CMR in clinical practice.     

Different contribution of extent of myocardial injury to left ventricular systolic and diastolic function in early reperfused acute myocardial infarction

Background

We sought to investigate the influence of the extent of myocardial injury on left ventricular (LV) systolic and diastolic function in patients after reperfused acute myocardial infarction (AMI).

Methods

Thirty-eight reperfused AMI patients underwent cardiac magnetic resonance (CMR) imaging after percutaneous coronary revascularization. The extent of myocardial edema and scarring were assessed by T2 weighted imaging and late gadolinium enhancement (LGE) imaging, respectively. Within a day of CMR, echocardiography was done. Using 2D speckle tracking analysis, LV longitudinal, circumferential strain, and twist were measured.

Results

Extent of LGE were significantly correlated with LV systolic functional indices such as ejection fraction (r?=?-0.57, p?<?0.001), regional wall motion score index (r?=?0.52, p?=?0.001), and global longitudinal strain (r?=?0.56, p?<?0.001). The diastolic functional indices significantly correlated with age (r?=?-0.64, p?<?0.001), LV twist (r?=?-0.39, p?=?0.02), average non-infarcted myocardial circumferential strain (r?=?-0.52, p?=?0.001), and LV end-diastolic wall stress index (r?=?-0.47, p?=?0.003 with e’) but not or weakly with extent of LGE. In multivariate analysis, age and non-infarcted myocardial circumferential strain independently correlated with diastolic functional indices rather than extent of injury.

Conclusions

In patients with timely reperfused AMI, not only extent of myocardial injury but also age and non-infarcted myocardial function were more significantly related to LV chamber diastolic function.     

Cardiac performance in Turner's syndrome patients on growth hormone therapy.

OBJECTIVES: To investigate possible cardiac morphofunctional alterations observed in 26 Turner's syndrome (TS) patients on prolonged high-dose growth hormone (GH) therapy. STUDY DESIGN: We examined 26 TS subjects treated with rhGH (1 U/kg/week) for a mean period of 4.9 years (range 1-7.8) and 37 age-, weight- and height-matched healthy girls. Left ventricular volume, mass, systolic function, cardiac index, systemic vascular resistance and diastolic function were evaluated by two-dimensional and Doppler echocardiography. RESULTS: Heart rate and systolic blood pressure (BP) were higher in TS patients than in controls, while diastolic BP was lower. Left ventricular volumes, ejection fraction, mass index, M/V ratio and cardiac index did not differ significantly; systemic vascular resistance was slightly decreased. Left ventricular fractional shortening and mean velocity of circumferential shortening were slightly increased while end-systolic meridional stress was decreased in TS. Contractile state was normal in TS. Diastolic function assessment showed a shortening of isovolumetric relaxation and diastolic filling times with an increased atrial contribution and a normal pulmonary venous flow. CONCLUSION: Cardiac morphology in TS patients on GH therapy is similar to controls. The observed changes in left ventricular systolic and diastolic function should be interpreted as an adaptation to the higher heart rate and reduced peripheral vascular resistance induced by GH therapy.     

Right and left ventricular adaptation to hypoxia: a tissue Doppler imaging study

Hypoxia has been reported to alter left ventricular (LV) diastolic function, but associated changes in right ventricular (RV) systolic and diastolic function remain incompletely documented. We used echocardiography and tissue Doppler imaging to investigate the effects on RV and LV function of 90 min of hypoxic breathing (fraction of inspired O(2) of 0.12) compared with those of dobutamine to reproduce the same heart rate effects without change in pulmonary vascular tone in 25 healthy volunteers. Hypoxia and dobutamine increased cardiac output and tricuspid regurgitation velocity. Hypoxia and dobutamine increased LV ejection fraction, isovolumic contraction wave velocity (ICV), acceleration (ICA), and systolic ejection wave velocity (S) at the mitral annulus, indicating increased LV systolic function. Dobutamine had similar effects on RV indexes of systolic function. Hypoxia did not change RV area shortening fraction, tricuspid annular plane systolic excursion, ICV, ICA, and S at the tricuspid annulus. Regional longitudinal wall motion analysis revealed that S, systolic strain, and strain rate were not affected by hypoxia and increased by dobutamine on the RV free wall and interventricular septum but increased by both dobutamine and hypoxia on the LV lateral wall. Hypoxia increased the isovolumic relaxation time related to RR interval (IRT/RR) at both annuli, delayed the onset of the E wave at the tricuspid annulus, and decreased the mitral and tricuspid inflow and annuli E/A ratio. We conclude that hypoxia in normal subjects is associated with altered diastolic function of both ventricles, improved LV systolic function, and preserved RV systolic function.     

Sensitivity Analysis of Left Ventricle with Dilated Cardiomyopathy in Fluid Structure Simulation

Dilated cardiomyopathy (DCM) is the most common myocardial disease. It not only leads to systolic dysfunction but also diastolic deficiency. We sought to investigate the effect of idiopathic and ischemic DCM on the intraventricular fluid dynamics and myocardial wall mechanics using a 2D axisymmetrical fluid structure interaction model. In addition, we also studied the individual effect of parameters related to DCM, i.e. peak E-wave velocity, end systolic volume, wall compliance and sphericity index on several important fluid dynamics and myocardial wall mechanics variables during ventricular filling. Intraventricular fluid dynamics and myocardial wall deformation are significantly impaired under DCM conditions, being demonstrated by low vortex intensity, low flow propagation velocity, low intraventricular pressure difference (IVPD) and strain rates, and high-end diastolic pressure and wall stress. Our sensitivity analysis results showed that flow propagation velocity substantially decreases with an increase in wall stiffness, and is relatively independent of preload at low-peak E-wave velocity. Early IVPD is mainly affected by the rate of change of the early filling velocity and end systolic volume which changes the ventriculo:annular ratio. Regional strain rate, on the other hand, is significantly correlated with regional stiffness, and therefore forms a useful indicator for myocardial regional ischemia. The sensitivity analysis results enhance our understanding of the mechanisms leading to clinically observable changes in patients with DCM.     

Distribution of myocardial stress and its influence on coronary blood flow

The myocardial stress was analyzed by biomechanical modeling in correlation with experimental findings. The pressure-volume relationship follows the stress-strain relationship of muscle fibers. From the knowledge of fiber orientation and the distribution of sarcomere length, the myocardial stress components including fiber, longitudinal, circumferential and radial stresses were expressed as a function of fraction of wall thickness. The coronary blood flow is influenced by the myocardial radial stress. With the use of vascular waterfall theory, it is possible to correlate the theoretically defined stress distribution with experimentally obtained stress distribution. An elevation of radial stress in myocardium causes a reduction of vessel patency. During both systole and diastole, vessel patency remains constant at epicardium. At endocardium, however, vessel patency undergoes rhythmic changes following the systolic and diastolic influences of the radial stress. The physiological implication is that during systole, the endocardium suffers low blood flow and this transient ischemic state requires compensatory replenishment from diastolic perfusion. Such phenomena become less apparent toward the epicardium.     

Heart size-independent analysis of myocardial function in murine pressure overload hypertrophy

Pressure overload cardiac hypertrophy may be a compensatory mechanism to normalize systolic wall stress and preserve left ventricular (LV) function. To test this concept, we developed a novel in vivo method to measure myocardial stress (sigma)-strain (epsilon) relations in normal and hypertrophied mice. LV volume was measured using two pairs of miniature omnidirectional piezoelectric crystals implanted orthogonally in the endocardium and one crystal placed on the anterior free wall to measure instantaneous wall thickness. Highly linear sigma-epsilon relations were obtained in control (n = 7) and hypertrophied mice produced by 7 days of transverse aortic constriction (TAC; n = 13). Administration of dobutamine in control mice significantly increased the load-independent measure of LV contractility, systolic myocardial stiffness. In TAC mice, systolic myocardial stiffness was significantly greater than in control mice (3,156 +/- 1,433 vs. 1,435 +/- 467 g/cm(2), P < 0.01), indicating enhanced myocardial contractility with pressure overload. However, despite the increased systolic performance, both active (time constant of LV pressure decay) and passive (diastolic myocardial stiffness constant) diastolic properties were markedly abnormal in TAC mice compared with control mice. These data suggest that the development of cardiac hypertrophy is associated with a heightened contractile state, perhaps as an early compensatory response to pressure overload.     

Insulin resistance in Chinese patients with type 2 diabetes is associated with C-reactive protein independent of abdominal obesity

Background

Patients with diabetes mellitus (DM) have high risk of heart failure. Whether some of the risk is directly linked to metabolic derangements in the myocardium or whether the risk is primarily caused by coronary artery disease (CAD) and hypertension is incompletely understood. Echocardiographic tissue Doppler imaging was therefore performed in DM patients without significant CAD to examine whether DM per se influenced cardiac function.

Methods

Patients with a left ventricular (LV) ejection fraction (EF) > 35% and without significant CAD, prior myocardial infarction, cardiac pacemaker, atrial fibrillation, or significant valve disease were identified from a tertiary invasive center register. DM patients were matched with controls on age, gender and presence of hypertension.

Results

In total 31 patients with diabetes and 31 controls were included. Mean age was 58 ± 12 years, mean LVEF was 51 ± 7%, and 48% were women. No significant differences were found in LVEF, left atrial end systolic volume, or left ventricular dimensions. The global longitudinal strain was significantly reduced in patients with DM (15.9 ± 2.9 vs. 17.7 ± 2.9, p = 0.03), as were peak longitudinal systolic (S') and early diastolic (E') velocities (5.7 ± 1.1 vs. 6.4 ± 1.1 cm/s, p = 0.02 and 6.1 ± 1.7 vs. 7.7 ± 2.0 cm/s, p = 0.002). In multivariable regression analyses, DM remained significantly associated with impairments of S' and E', respectively.

Conclusion

In patients without significant CAD, DM is associated with an impaired systolic longitudinal LV function and global diastolic dysfunction. These abnormalities are likely to be markers of adverse prognosis.     

Visualization of elusive structures using intracardiac echocardiography: Insights from electrophysiology

Echocardiography has the ability to noninvasively explore hemodynamic variables during pharmacologic or exercise stress test in patients with heart failure. In this review, we detail some important potential applications of stress echocardiography in patients with heart failure. In patients with coronary artery disease and chronic LV dysfunction, dobutamine stress echocardiography is able to distinguish between viable and fibrotic tissue to make adequate clinical decisions. Exercise testing, in combination with echocardiographic monitoring, is a method of obtaining accurate information in the assessment of functional capacity and prognosis. Functional mitral regurgitation is a common finding in patients with dilated and ischaemic cardiomyopathy and stress echocardiography in the form of exercise or pharmacologic protocols can be useful to evaluate the behaviour of mitral regurgitation. It is clinical useful to search the presence of contractile reserve in non ischemic dilated cardiomyopathy such as to screen or monitor the presence of latent myocardial dysfunction in patients who had exposure to cardiotoxic agents. Moreover, in patients with suspected diastolic heart failure and normal systolic function, exercise echocardiography could be able to demonstrate the existence of such dysfunction and determine that it is sufficient to limit exercise tolerance. Finally, in the aortic stenosis dobutamine echocardiography can distinguish severe from non-severe stenosis in patients with low transvalvular gradients and depressed left ventricular function.     

Medium-term cardiovascular effects of high-dose growth hormone treatment in growth hormone-deficient children

AIM: To investigate the possible cardiac morphofunctional alterations inducd by prolonged and high-dose GH therapy in a group of 14 children with isolated GH deficiency. PATIENTS AND METHODS: Patients were evaluated at phase 1, after 1.1 +/- 0.6 years of treatment with GH 0.93 +/- 0.13 U/kg/week, and at phase 2, after 5.5 +/- 2.1 years of therapy 0.89 +/- 0.11 U/kg/week. At each phase left ventricular volume, mass and systolic function were evaluated by two-dimensional guided M-mode echocardiography; left ventricular diastolic function was assessed by PW-Doppler sampling of transmitral flow. RESULTS: Phase 1: diastolic blood pressure was lower (p < 0.05) and fractional shortening was not adequate for the level of afterload (stress shortening index p < 0.05) in patients compared to controls. Phase 2: diastolic blood pressure was lower (p < 0.01) and mass and mass/volume ratio were increased (mass index p < 0.05, mass/ volume ratio p < 0.05) in patients compared to controls. The increased mass/volume ratio, together with the normal systolic blood pressure, explains the reduction in peak systolic stress (p < 0.005). Among the parameters of left ventricular diastolic function, the peak E velocity/total area under mitral valve tracing and the area under E velocity/total area under mitral value tracing ratios were significantly decreased (p < 0.05). CONCLUSION: After a mean period of 5 years on high-dose GH treatment in GH-deficient children, subclinical morphofunctional alterations in the left ventricle were found.     

Dobutamine-tagged MRI for inotropic reserve assessment in severe CAD: relationship with PET findings

The impact of blood flow reductions on the intramyocardial inotropic reserve has not yet been established in coronary artery disease (CAD). We therefore evaluated in severe CAD the relationship between positron emission tomography (PET) patterns of perfusion and glucose uptake and the corresponding tagged magnetic resonance imaging (tagged MRI) values of midmyocardial strains under low-dose dobutamine. Eighteen patients underwent tagged MRI (at rest, with dobutamine) and H2(15)O/18F-fluorodeoxyglucose PET. Regional midmyocardial circumferential shortening (Ecc) and PET patterns (normal, match viable, mismatch viable, and infarcted) were assessed in three tagged MRI/PET short-axis slices. Regional Ecc at rest correlated with both perfusion (r = 0.49) and glucose uptake (r = 0.58). The presence of the inotropic reserve was similar in normal, match viable, and infarcted (approximately 40% of regions vs. 52% in mismatch viable, P < 0.05), but the extent of the increase after dobutamine was lower in infarcted regions (P = 0.06). Within each PET pattern, regions were grouped according to their Ecc values at rest into three categories (high, intermediate, and low contractile performance). In mismatch viable (hibernation), the inotropic reserve was similar among the three categories, but in the other PET patterns the presence and extent of the inotropic reserve was higher in those regions with lowest Ecc (without significant differences in perfusion). In severe CAD, the presence of the inotropic reserve assessed by midmyocardial changes under dobutamine does not relate to resting perfusion. At a similar level of perfusion, the presence of the inotropic reserve is inversely related to contractile performance at rest, but our results suggest that it may not be true for hibernating myocardium.     

Effect of repeated episodes of reversible myocardial ischemia on myocardial blood flow and function in humans

Nine patients with coronary artery disease and normal left ventricular (LV) function underwent two episodes of dobutamine-induced ischemia to determine whether repeated episodes of ischemia lead to cumulative stunning. Positron emission tomography (PET) and oxygen 15-labeled H(2)O was used to assess myocardial blood flow (MBF) at baseline, peak stress, and after stress for each ischemic episode. Quantitative echocardiographic assessment of global ejection fraction (EF) and regional systolic function (SF) was performed at rest and regular intervals after dobutamine. SF was assessed for regions subtended by a coronary artery with a >70% diameter stenosis. Both EF and SF were more severely impaired 45 min after the second episode of stress compared with 45 min after the first (both P < 0.01), despite no difference in duration of the two dobutamine infusions or MBF at peak stress (1.72 vs. 1.69). After both episodes of ischemia, when LV function was impaired but subsequently recovered, MBF (1.15 +/- 0.39 and 1.20 +/- 0.43, respectively) was no different to baseline MBF (1.02 +/- 0.35), confirming that repeated episodes of dobutamine-induced ischemia lead to cumulative myocardial stunning.     

Comparison of multislice spiral computed tomography and stress echocardiography in the evaluation of myocardial viability in patients with acute myocardial infarction

The purpose of the investigation was to analyze the data of 64-multislice spiral computed tomography (MSCT-64) versus those of low-dose dobutamine echocardiography (stress EchoCG) used to diagnose the viable myocardium in patients with acute myocardial infarction (AMI). The investigation enrolled 49 patients with AIM. Contrast-enhanced MSCT-64 and low-dose dubutamine stress EchoCG were performed in patients in the early periods of AMI. The viable myocardium was examined in 780 segments of the left ventricle (LV). The data of delayed MSCT and stress EchoCG agreed in 759 (97.3%) segments, did not in 21 (2.7%) segments; Cohen's kappa coefficient was 0.88. The affected segment index (As index) was introduced into the investigation, which is an integral indicator of the number of segments with perfusion defect and nonviable segments detected by MSCT. There was a statistically significant correlation of the As index with the asynergy index (r = 0.91; p = 0.000) and LV ejection fraction (r = -0.75; p = 0.000). Our previous study has demonstrated that MSCT-64 is an informative method to evaluate myocardial viability; the signs of myocardial perfusion and structural derangements can serve as predictors of diminished LV contractility.