Usefulness of dobutamine radionuclide ventriculography for prediction of left ventricular function improvement after coronary artery bypass grafting for ischemic cardiomyopathy

Ventricular function may improve after coronary artery bypass grafting (CABG) in patients with ischemic cardiomyopathy depending on the amount of contractile myocardial reserve. Based on the studies using dobutamine echocardiography to predict regional wall improvement after revascularization, we investigated the benefit of low-dose dobutamine radionuclide ventriculography for assessing functional contractile reserve in this population. The study group included 56 patients with ischemic cardiomyopathy (mean left ventricular [LV] ejection fraction [EF] of 23 +/- 5%) and multivessel disease, who were referred for viability assessment. All underwent radionuclide ventriculography before and during infusion of 5 and 10 microg/kg/min of dobutamine. An increase in global LVEF from rest to dobutamine was calculated, and 10% was considered the cutoff value to predict ventricular improvement after CABG. Of the 35 patients who underwent CABG 1 month later, 29 were available for repeated radionuclide ventriculography after 12 +/- 5 months. Of these, 15 showed improvement (delta LVEF > or = 5%, mean 10 +/- 5%) and 14 did not (delta LVEF < 5%, mean -1 +/- 3%). The increase in EF with dobutamine had the highest univariate predictive value of all parameters evaluated. The sensitivity, specificity, and positive and negative predictive values of dobutamine radionuclide ventriculography were 67%, 93%, 91%, and 72%, respectively. We conclude that dobutamine radionuclide ventriculography is a useful method to assess contractile reserve and predict ventricular functional improvement after CABG in patients with ischemic cardiomyopathy.     

Usefulness of dobutamine-induced changes of the two-dimensional longitudinal deformation predict clinical and neurohumoral improvement in men after levosimendan treatment in acutely decompensated chronic heart failure

Levosimendan reduces symptoms and improves hemodynamics in patients with acutely decompensated chronic heart failure (ADCHF). The aim of this study was to investigate (1) the association of changes induced by low-dose dobutamine stress echocardiography in 2-dimensional strain parameters with the corresponding changes in the left ventricular (LV) ejection fraction (EF) and LV outflow tract velocity time integral (VTI) in patients with ADCHF and (2) whether LV contractile reserve assessed by conventional and speckle-tracking echocardiography is associated with clinical and neurohumoral improvement after levosimendan treatment. Twenty-eight consecutive patients with ADCHF (mean age 65 +/- 10 years, mean New York Heart Association class 3.6 +/- 0.3, mean EF 22 +/- 6%) were studied using dobutamine stress echocardiography before 24-hour infusion of levosimendan. The LV EF, VTI, and mean longitudinal, circumferential, and radial strain and strain rate using speckle-tracking imaging were measured. Twenty-one patients (75%) had evidence of contractile reserve (LV EF increase >10% and VTI increase >20% after peak dobutamine dose). Patients with versus without contractile reserve demonstrated greater improvements in New York Heart Association class (mean change -1.0 +/- 0.5 vs -0.5 +/- 0.3, p = 0.01) and reductions in B-type natriuretic peptide levels (-34 +/- 30% vs +4 +/- 31%, p <0.01) 48 hours after treatment. On multivariate analysis, mean longitudinal systolic strain rate reserve (peak longitudinal strain rate minus longitudinal strain rate at rest) was the best predictor of improvement in New York Heart Association class (p = 0.039) and B-type natriuretic peptide level (p = 0.042) after levosimendan among the reserve of LV fractional shortening, the EF, VTI, and longitudinal, circumferential, and radial strain and strain rate. In conclusion, dobutamine-induced changes in longitudinal systolic strain rate are associated with clinical and neurohumoral improvement after levosimendan treatment in patients with ADCHF.     

Low-level exercise echocardiography fails to elicit left ventricular contractile reserve in patients with aortic stenosis, reduced ejection fraction, and low transvalvular gradient

BACKGROUND: Low-level exercise echocardiography is useful to assess left ventricular (LV) contractile reserve after an acute myocardial infarction. Whether low-level exercise can elicit LV contractile reserve in patients with severe aortic stenosis, reduced LV systolic function and low transvalvular gradient are unknown. Accordingly, the value of low-level exercise to elicit contractile reserve was assessed in these patients using dobutamine administration as the gold standard method. METHODS AND RESULTS: Seventeen patients with severely decreased aortic valve area (0.75 +/- 0.03 cm(2)), reduced LV ejection fraction (35 +/- 2%) and low mean transvalvular gradient (23 +/- 3 mmHg) underwent low-level exercise and dobutamine echocardiography. Ejection fraction increased by 23% (P < 0.001) with dobutamine and decreased by 8% (P = 0.2) with low-level exercise. Left ventricular outflow tract velocity time integral increased from 13 +/- 1 to 16.7 +/- 1 cm (P < 0.001) with dobutamine but did not change with low-level exercise (13 +/- 1 vs. 13.5 +/- 1, P = 0.5). CONCLUSION: Low-level exercise fails to elicit LV contractile reserve in patients with severe aortic stenosis, reduced LV systolic function, and low transvalvular gradient.     

Comparison of real-time contrast echocardiography and low-dose dobutamine stress echocardiography in predicting the left ventricular functional recovery in patients after acute myocardial infarction under different therapeutic intervention

BACKGROUND: Early prediction of left ventricular (LV) functional recovery after acute myocardial infarction (AMI) remains challenging. This prospective study aims to compare real-time myocardial contrast echocardiography (MCE) with low-dose dobutamine stress echocardiography (LDDSE) in predicting the LV functional recovery in patients after AMI who underwent different therapeutic interventions. METHODS: Ninety-two patients with AMI were divided into 3 groups: primary coronary intervention group (n=34), thrombolysis group (n=30) and conservative therapy group (n=28). MCE was performed 2.3+/-0.7 days after chest pain onset. LDDSE was done within 2 days of MCE study. Follow-up echocardiography was performed 4 months later. RESULTS: Patients treated by primary coronary intervention or thrombolysis had significantly lower regional perfusion score (0.65+/-0.53 vs. 1.01+/-0.49, p=0.008; 0.78+/-0.55 vs. 1.01+/-0.49, p=0.03), better contractile reserve (regional dobutamine Deltawall motion score -1.12+/-0.39 vs. -0.80+/-0.43, p=0.01; -0.99+/-0.50 vs. -0.80+/-0.43, p=0.08) and LV function recovery (regional Deltawall motion score -1.67+/-0.53 vs. -1.02+/-0.46, p=0.003; -1.42+/-0.58 vs. -1.02+/-0.46, p=0.03) than those of conservative therapy group. MCE and LDDSE showed good concordance for predicting LV functional recovery (kappa=0.63, p<0.001). Perfusion score index had a good correlation with LV functional recovery (r=-0.75, p<0.001). CONCLUSIONS: This study demonstrates that perfusion score index obtained from real-time MCE is comparable to LDDSE in predicting the LV functional recovery even under different therapeutic interventions. Revascularization results in better preservation of myocardial microvascular integrity, regional contractile reserve and LV functional recovery.     

Right vs. left ventricular contractile reserve in one-year prognosis of patients with idiopathic dilated cardiomyopathy: assessment by dobutamine stress echocardiography.

AIM: To determine prognostic implications of the assessment of right (RV) vs. left ventricular (LV) contractile reserve with dobutamine echocardiography in patients with idiopathic dilated cardiomyopathy. METHODS AND RESULTS: Forty-eight consecutive patients (41 male, NYHA class III/IV 13 patients, LV ejection fraction 19+/-8%) were subjected to dobutamine stress echocardiography in incremental stages lasting 5 min each. Contractile reserve was defined as the difference between the values of LV ejection fraction and RV fractional area change obtained at peak dobutamine dose and the baseline values. Patients were followed for one year after enrollment for combined end-point of cardiac death, partial left ventriculectomy and hospitalization for congestive heart failure. During the follow-up 15/48 patients reached combined end-point. Patients who reached end-point had lower RV and LV contractile reserves (14+/-5 vs. 8+/-6%, p=0.0014, and 9+/-5 vs. 3+/-2%, p<0.001, respectively). Kaplan-Meier curves demonstrated that both LV and RV contractile reserves can identify patients with dismal prognosis (log rank=17.02 and log rank=14.66, respectively, p<0.001 for both). Multivariate analysis identified dobutamine induced change in LV functional reserve as the only independent predictor of combined end-point (beta=-0.63, p=0.0035). CONCLUSION: Both RV and LV contractile reserves can be used for prognostic stratification in patients with idiopathic dilated cardiomyopathy. It appears that dobutamine induced change in LV functional reserve may better identify patients with dismal prognosis.     

Detection of myocardial contractile reserve by low-dose dobutamine quantitative gated single-photon emission computed tomography in patients with Kawasaki disease and severe coronary artery lesions

We studied 24 patients with severe coronary artery lesions to assess myocardial perfusion and left ventricular contractile reserve simultaneously using low-dose dobutamine quantitative electrocardiographically gated single-photon emission computed tomography in patients with Kawasaki disease. Low-dose dobutamine infusion was started after an injection of technetium-99m tetrofosmin at rest. Myocardial contractile reserve was evaluated using the post-stress and low-dose dobutamine images, and myocardial perfusion was evaluated using the stress and rest images. Quantitative electrocardiographically gated single-photon emission computed tomography during low-dose dobutamine infusion is a useful and safe method for the combined evaluation of myocardial contractile reserve and myocardial perfusion.     

Predictors of myocardial contractile reserve in patients with nonischemic dilated cardiomyopathy. An echo-stress dobutamine study

INTRODUCTION AND OBJECTIVES: Myocardial contractile reserve studies with low-dose dobutamine echocardiography have been shown to be useful to assess functional myocardial status. However, the variables associated with contractile reserve after inotropic stimulation are not well known. PATIENTS AND METHOD: We studied 50 patients (35 men, mean age 56.4 +/- 9.5 years) with nonischemic dilated cardiomyopathy (NIDC), LVEF 28.7% +/- 8.5% and wall motion score index (WMSI) 2.42 +/- 0.34 with low-dose dobutamine echocardiography. Left ventricular contractile reserve was assessed by a differential parameter defined as the difference between rest and stress WMSI (DeltaWMSI). RESULTS: After dobutamine infusion the WMSI was 1.95 +/- 0.58; from this value we calculated a DeltaWMSI of 0.45 +/- 0.39. None of the clinical variables showed a relationship with the presence of contractile reserve. In contrast, the following echocardiographic parameters correlated with DeltaWMSI: end-diastolic (p=0.05) and end-systolic (p=0.02) diameters, end-systolic volume index (p=0.01) and LVEF (p=0.002). In the multivariate analysis, only end-diastolic diameter was an independent predictor of contractile reserve (hazard ratio=0.852; 95% CI, 0.735-0.987; p=0.03). CONCLUSIONS: Ventricular diameters, end-systolic volume index and LVEF are related with improvements in myocardial contractility after dobutamine infusion, although only end-diastolic diameter was an independent predictor of contractile reserve. Thus, this parameter should receive particular attention in evaluations of the functional status of the myocardium in patients with NIDC.     

Prediction of global left ventricular function after bypass surgery in patients with severe left ventricular dysfunction. Impact of pre-operative myocardial function, perfusion, and metabolism.

AIMS: Previous studies have compared the accuracy of various tests of viability for the prediction of recovery of regional left ventricular function; global left ventricular recovery has been less well studied, although it has important prognostic and functional ramifications. We sought to identify the relative contribution of ischaemia, regional and global contractile reserve, perfusion and metabolic function to changes in left ventricular volumes and global function after coronary artery bypass surgery in patients with severe left ventricular dysfunction. METHODS AND RESULTS: Dipyridamole stress Rb-82, fluorodeoxyglucose positron emission tomography and low and high-dose dobutamine-atropine stress echocardiography were obtained in 66 patients with left ventricular impairment. Myocardial segments were considered viable if ischaemia or either metabolic or contractile reserve were present, on positron emission tomography or dobutamine echocardiography. Resting left ventricular function was reassessed after surgery (mean 10+/-3 weeks) in the 59 patients who had not suffered a major peri-operative event; functional improvement was defined by a 5% increment of ejection fraction. Myocardial viability was found in 37 (63%) patients using positron emission tomography and in 42 (71%) patients using dobutamine echocardiography; post-operative functional improvement was noted in 28 (47%) patients. In univariate analyses, predictors of global post-operative functional recovery included: the extent of viability according to positron emission tomography [OR (odds ratio): 2.08 for each additional viable segment, 95% CI (confidence interval): 1.33-3. 25, P=0.001] or dobutamine echocardiography (OR: 2.06 for each additional viable segment, 95% CI: 1.28-3.30, P=0.003) and the increase in ejection fraction with low-dose dobutamine (OR: 1.9 for each 1% increase in ejection fraction with low dose dobutamine, 95% CI 1.39-2.61, P<0.0001). In a multivariate model which included evidence of viability by either technique, and change in ejection fraction with low-dose dobutamine echocardiography, only change in ejection fraction with low-dose dobutamine echocardiography was predictive of post-operative left ventricular functional recovery (adjusted OR: 1.81, 95% CI: 1.30-2.52, P=0.0005). CONCLUSION: Among patients with severe left ventricular dysfunction who are referred for surgical revascularization, the overall accuracies of positron emission tomography and dobutamine echocardiography for the prediction of post-operative myocardial recovery are comparable. However, the strongest predictor of overall improvement of post-operative left ventricular function is an increase of ejection fraction with a low-dose dobutamine infusion.     

Low-dose dobutamine induces left ventricular mechanical dyssynchrony in patients with dilated cardiomyopathy and a narrow QRS: A study using real-time three-dimensional echocardiography

AimsThe effects of inotropic agents on left ventricular (LV) synchrony in heart failure patients are still unknown. The purpose of this study was to investigate the effects of dobutamine on LV mechanical dyssynchrony and LV systolic performance in patients with dilated cardiomyopathy (DCM) and a narrow QRS using real-time three-dimensional echocardiography (RT3DE).Methods and resultsThirty-three patients with idiopathic DCM and a narrow QRS underwent low-dose dobutamine stress echocardiography (LDSE) with RT3DE. A time-global LV volume curve and time-regional LV volume curves were derived from RT3DE. Regional LV stroke volumes were summed in each stage, and the dobutamine-induced increase in the sum of regional LV stroke volumes was considered as the sum of regional contractile reserve. Systolic dyssynchrony index (SDI) was calculated as follows: (standard deviation of time to minimal volume for regional LV segments) × 100/RR duration. Among the 33 patients, low-dose dobutamine increased global LV stroke volume (SV) in 28 (85%), but decreased global LVSV in the remainder (15%). The sum of regional contractile reserve was modestly correlated with the dobutamine-induced increase in global LVSV (R = 0.57, p < 0.001). In contrast, low-dose dobutamine increased SDI in 14 (42%) patients without a significant change in QRS duration, and there was an inverse correlation between the increase in SDI and the increase in global LVSV induced by dobutamine (R = ?0.67, p < 0.001).ConclusionsDobutamine may induce LV mechanical dyssynchrony in a substantial proportion of patients with DCM and a narrow QRS. In such cases, regional LV contractile reserve does not fully contribute to an increase in global LVSV.     

Neuroadrenergic activation and response to dobutamine in congestive heart failure secondary to idiopathic dilated cardiomyopathy

Detection of contractile reserve is important in heart failure patients. To determine if detection of contractile reserve is influenced by neuroadrenergic activation, we examined the relation between dobutamine stress echocardiography (DSE) findings and plasma norepinephrine levels (NE) at rest in 35 patients with nonischemic left ventricular (LV) dysfunction (New York Heart Association class >III in all; LV ejection fraction 0.27 +/- 0.5). Changes in global wall motion score (WMS), and separately in WMS of hypokinetic segments and akinetic segments, were analyzed. A patient was considered to be responsive to dobutamine if the change in global WMS was >/=4. Twenty-three patients were responsive and 12 were not responsive to dobutamine. Plasma NE and baseline heart rate were significantly higher in nonresponsive patients (p <0.001). Changes in global WMS and in hypokinetic segment WMS were inversely related to either plasma NE (r -0.68 and -0.67, respectively) or baseline heart rate (r -0.60 and -0.66, respectively). The change in akinetic segment WMS was related to plasma NE only (r -0.50). Changes in WMS were not related to age, diastolic and systolic LV volume, baseline global WMS, or number of akinetic segments at baseline. Plasma NE >602 pg/ml predicted a blunted or absent contractile reserve at DSE (sensitivity 92%; specificity 87%). Neuroadrenergic activation may influence contractile reserve found at DSE in patients with heart failure due to nonischemic LV dysfunction.     

Prognostic value of low-dose dobutamine echocardiography in patients with idiopathic dilated cardiomyopathy

STUDY OBJECTIVES: Dobutamine echocardiography is widely used for the evaluation of myocardial contractile reserve. The purpose of the study was to determine the prognostic value of low-dose dobutamine echocardiography in patients with idiopathic dilated cardiomyopathy (IDCM). PATIENTS: The study group consisted of 77 consecutive patients with recently diagnosed IDCM (mean [+/- SD] age, 49 +/- 9 years; men, 82%) and left ventricular (LV) ejection fractions of < 40%. INTERVENTIONS: Two-dimensional and Doppler echocardiographic variables were measured before and after the infusion of dobutamine at the rate of 10 microg/kg/min for 5 min. MEASUREMENTS AND RESULTS: During a mean follow-up period of 63 +/- 7 months (range, 49 to 75 months) 30 patients (39%) died and five patients (6%) underwent successful heart transplantations. Using multivariate regression analysis, the only significant factors related to fatal outcome or the need for cardiac transplantation were the following: (1) LV end-systolic volume of > 150 mL after low-dose dobutamine infusion (odds ratio [OR], 2.2; confidence interval [CI], 1.2 to 4.1; p = 0.011); (2) no decrease of LV end-diastolic volume after dobutamine infusion (OR, 1.9; CI, 1.1 to 3.4; p = 0.031); (3) atrial fibrillation (OR, 2.7; CI, 1.4 to 5.3; p = 0.003); and (4) male gender (OR, 2.6; CI, 1.2 to 5.5; p = 0.017). A scoring system was proposed with one point assigned for each of the above-mentioned factors. The mortality rates for total scores of 0, 1, 2, 3, and 4 were 0%, 19%, 48%, 83%, and 100%, respectively. CONCLUSION: The response of the LV to low-dose dobutamine infusion adds clinically valuable prognostic information to the evaluation of the patient with IDCM.     

Attenuation of cardiac remodelling by endocardial injection of erythropoietin: ultrasonic strain-rate imaging in a model of hibernating myocardium.

AIMS: The aim of this study was to investigate whether erythropoietin (EPO) has cardioprotective effects in a chronic myocardial ischaemia model regarding strain-rate imaging parameters during dobutamine stress echocardiography (DSE). METHODS AND RESULTS: An ameroid constrictor was placed around the circumflex artery in 13 pigs to induce hibernating myocardium by a chronic vessel occlusion. The pigs were randomized 14 days later: seven pigs receiving 10,000 U EPO and six pigs receiving placebo injected into the ischaemic region using a NOGAtrade mark-guided transendocardial catheter. At weeks 2 and 6, animals were examined by DSE, electromechanical mapping, and coronary angiography. During incremental dobutamine infusion, regional radial function was monitored by measuring peak systolic strain-rates (SRsys), systolic strains (epsilonsys), and post-systolic strains (epsilonps). At week 6, the animals were pathohistologically investigated. Echocardiography revealed 2.2+/-0.8 hypokinetic segments in the EPO-treated animals in comparison with 3.3+/-0.9 akinetic segments per animal in the controls. The mean ejection fraction was reduced in the control group (55+/-3 vs. 66+/-4%, P=0.057). Strain-rate imaging revealed ischaemic myocardium in EPO-treated animals and non-viable myocardium in the controls (P=0.0001). Histological analysis of the ischaemic region revealed a reduction of myocardial fibrosis (8+/-1 vs. 27+/-5%) in the EPO-treated group. The transmural extension of fibrosis and the echocardiographic deformation data correlated in the posterior walls (EPO group): epsilonsys at rest r=0.83; peak SRsys during dobutamine stimulation r=0.92, P=0.01. CONCLUSION: Endocardial EPO injection may induce cardioprotective effects in chronic ischaemic myocardium and helps to obtain the myocardial contractile reserve, objectified by ultrasonic strain-rate imaging.     

Reduced Left Ventricular Contractile Reserve Identified by Low Dose Dobutamine Echocardiography as an Early Marker of Cardiac Involvement in Asymptomatic Patients with Thalassemia Major

Patients with beta thalassemia major present with severe anemia and need continuous transfusion therapy. The consequent iron overload leads to hemochromatosis. Initial cardiac involvement can be present in thalassemic patients without clinical manifestations of heart failure. The purpose of this study was to assess the contractile reserve of the left ventricle in patients with normal baseline two-dimensional (2-D) echocardiographic findings using low dose dobutamine echocardiography. The underlying hypothesis was that, at an early stage, structural impairment of the myocardial wall due to myocardial iron deposits and/or secondary fibrotic changes could be so subtle so as not to impair resting systolic function, but is severe enough to blunt or even exhaust the contractile response to inotropic stimulation. Twenty-four consecutive patients (13 men and 11 women; ages 18 +/- 3.8 years) with beta thalassemia major undergoing evaluation for bone marrow transplantation entered the study. By selection, all were asymptomatic, without clinical signs of cardiac failure, and had normal regional and global systolic function at baseline echocardiographic study. A control group of 16 age and sex matched subjects was also studied. All underwent baseline, 2-D, and Doppler study, as well as dobutamine stress (up to 5 &mgr;g/kg per min) 2-D echocardiographic study. Patients and controls showed comparable values of indexes of global (ejection fraction: 0.64 +/- 0.06 vs 0.65 +/- 0.05, P = NS) and regional (systolic thickening of posterior wall: 90 +/- 34 vs 91 +/- 34%, P = NS) function at baseline. Left ventricular diastolic filling was evaluated with Doppler echocardiography. Peak flow velocity in early diastole was increased in thalassemic patients compared to controls (114 +/- 16 vs 96 +/- 18 cm/sec, P < 0.01), and flow velocity deceleration time was reduced (139 +/- 17 vs 157 +/- 20 msec, P < 0.01). At peak dobutamine, thalassemic patients showed a blunted contractile response compared to controls for indexes of both global (ejection fraction: 0.62 +/- 0.06 vs 0.69 +/- 0.05, P < 0.01) and regional (% systolic thickening of posterior wall: 91 +/- 36 vs 130 +/- 39%, P < 0.01) function. When individual patient analysis was performed, echocardiographic parameters were beyond the 95% confidence limits obtained from normal controls in 5 (21%) of the 24 study patients by one or more Doppler diastolic indexes, in 6 (25%) by indexes of contractile reserve, and in 11 (46%) by one of either diastolic function or contractile reserve indexes. These data demonstrate that the "iron heart" of asymptomatic thalassemic patients is a weak heart. Even if the regional and global systolic functions are similar to normals under resting conditions, the application of an inotropic challenge unmasks the weakness of these hearts, which can be identified at an earlier stage of their natural history through the blunted contractile response following the infusion of low dose dobutamine. The information on contractile reserve is not redundant, but rather incremental and in addition to that provided by Doppler echocardiographic indexes, which may be abnormal in these patients. (ECHOCARDIOGRAPHY, Volume 13, September 1996)     

Changes in the response of hibernated myocardium to inotropic stimulation after angioplasty: a Doppler myocardial imaging study

BACKGROUND: Angioplasty of an infarct related artery (IRA) performed several weeks or months after myocardial infarction (MI) may improve myocardial function. HYPOTHESIS: We hypothesized that, as Doppler myocardial imaging (DMI) allows for the quantitative assessment of the systolic movement of myocardial segments, it may be a sensitive method for assessing changes in regional myocardial contraction and contractile reserve pre and post angioplasty of the IRA. METHODS: In all, 39 patients (30 men, mean age 53.4 +/- 8.3 years), 1 to 6 months after MI, who qualified for IRA angioplasty on the basis of myocardial viability in the infarcted zone as demonstrated by dobutamine stress echocardiography, were included in the study. Peak regional myocardial systolic velocities (S wave) of the infarcted segments were measured at rest and during low-dose dobutamine infusion (15 microg/kg/min) 1 day before angioplasty (Exam 1), 2 to 5 days (Exam 2), and 30 days (Exam 3) after successful angioplasty. The long-axis movement of the mitral annulus and of the basal and medial segments of the posterior (20 patients), anterior (17 patients), and lateral walls (2 patients) was evaluated. RESULTS: At rest, S-wave velocity of the infarcted segments increased between Exams 1 and 2, without further improvement between Exams 2 and 3 (4.9 +/- 1.2 vs. 5.6 +/- 1.3 cm/s, p < 0.05 and 5.6 +/- 1.3 vs. 5.5 +/- 1.3 cm/s, NS, respectively). However, S-wave velocities measured during low-dose dobutamine infusion differed significantly both between Exams 1 and 2, and 2 and 3 (7.0 +/- 1.5 vs. 7.8 +/- 1.8 cm/s; p < 0.01; 7.8 +/- 1.8 vs. 8.5 +/- 1.6 cm/s; p < 0.05). CONCLUSIONS: Resting contractility at an infarct zone demonstrated rapid initial improvement after angioplasty of the IRA with no further change, whereas contractile reserve improved not only immediately after angioplasty but also during the next month.     

Importance of contractile reserve for CRT.

AIMS: To assess whether response to cardiac resynchronization therapy (CRT) is related to myocardial viability in the paced left ventricular (LV) region, evaluated by contractile reserve (CR). Non-response to CRT may partly be due to inefficient pacing by the LV lead located in a fibrotic area. METHODS AND RESULTS: Nineteen patients (64 +/- 13 years, 14 men, 9 ischaemic) with severe heart failure (EF = 27 +/- 8%, QRS = 154 +/- 25 ms) were included in the week after device implantation. Stroke volume (SV) and LV dyssynchrony (by Tissue Doppler Imaging) were successively assessed with CRT on and CRT off. Afterwards, CRT device was maintained off during dobutamine infusion to assess CR in the LV-pacing region. LV end-systolic volume (ESV) was assessed after 6 months to quantify reverse remodelling. CR in the paced LV region (n = 10, 5/9 ischaemic and 5/10 non-ischaemic) was correlated to a reduction in LV dyssynchrony under CRT (120 +/- 76 vs. 78 +/- 64 ms, P = 0.02). Conversely, LV dyssynchrony was unchanged (161 +/- 100 vs. 163 +/- 80 ms) without CR. In desynchronized patients (>65 ms, n = 15), increase in SV under CRT and changes in ESV at 6 months were +22 and -18%, respectively, when CR was present and 0% and +9%, respectively, when absent. CONCLUSION: Acute haemodynamic response and reverse remodelling under CRT require viability in the target region of LV lead.     

Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up

OBJECTIVES: We report on the procedural and six-month results of the first percutaneous and stand-alone study on myocardial repair with autologous skeletal myoblasts. BACKGROUND: Preclinical studies have shown that skeletal myoblast transplantation to injured myocardium can partially restore left ventricular (LV) function. METHODS: In a pilot safety and feasibility study of five patients with symptomatic heart failure (HF) after an anterior wall infarction, autologous skeletal myoblasts were obtained from the quadriceps muscle and cultured in vitro for cell expansion. After a culturing process, 296 +/- 199 million cells were harvested (positive desmin staining 55 +/- 30%). With a NOGA-guided catheter system (Biosense-Webster, Waterloo, Belgium), 196 +/- 105 million cells were transendocardially injected into the infarcted area. Electrocardiographic and LV function assessment was done by Holter monitoring, LV angiography, nuclear radiography, dobutamine stress echocardiography, and magnetic resonance imaging (MRI). RESULTS: All cell transplantation procedures were uneventful, and no serious adverse events occurred during follow-up. One patient received an implantable cardioverter-defibrillator after transplantation because of asymptomatic runs of nonsustained ventricular tachycardia. Compared with baseline, the LV ejection fraction increased from 36 +/- 11% to 41 +/- 9% (3 months, p = 0.009) and 45 +/- 8% (6 months, p = 0.23). Regional wall analysis by MRI showed significantly increased wall thickening at the target areas and less wall thickening in remote areas (wall thickening at target areas vs. 3 months follow-up: 0.9 +/- 2.3 mm vs. 1.8 +/- 2.4 mm, p = 0.008). CONCLUSIONS: This pilot study is the first to demonstrate the potential and feasibility of percutaneous skeletal myoblast delivery as a stand-alone procedure for myocardial repair in patients with post-infarction HF. More data are needed to confirm its safety.     

Pronounced improvement in systolic and diastolic ventricular long axis function after treatment with metoprolol

BACKGROUND: Although it is well known that left ventricular (LV) function improves after treatment with beta-blockers in heart failure, little attention has been paid to the effects on LV long axis (LAX) function. AIMS: To evaluate LV LAX function after treatment with metoprolol, and to assess whether LV LAX contractile reserve could predict future long-term improvement. METHODS: Twenty-four heart failure patients were randomised to metoprolol or placebo for 6 months, followed by 6 months of open treatment with metoprolol. Rest and dobutamine stress echocardiography (DSE) was performed before and after each treatment period. RESULTS: After treatment with metoprolol, LV LAX function improved significantly, systolic velocity from 29+/-8 to 32+/-15 mm/s, p<0.01 (metoprolol) vs. 28+/-7 to 28+/-11 mm/s, ns (placebo); atrioventricular plane fractional shortening (AVP-FS) from 5.4+/-2.1 to 7.4+/-2.7%, p<0.001 (metoprolol) vs. 5.9+/-2.1 to 5.8+/-2.9%, ns (placebo). The improvement in function was maintained during DSE. LV LAX contractile reserve could not predict treatment response; the treatment effect on LV LAX function was significantly greater than the contractile reserve at baseline. The relative improvement in LV LAX function after metoprolol was 38%, compared with a 20% improvement in LV ejection fraction (EF). CONCLUSION: A significant improvement in LV LAX function was observed after treatment with metoprolol. AVP-FS and systolic velocities increased significantly, and to a greater extent than LVEF.     

Myocardial contractile reserve on dobutamine echocardiography predicts late spontaneous improvement in cardiac function in patients with recent onset idiopathic dilated cardiomyopathy.

OBJECTIVES: The purpose of this study was to determine whether identification of contractile reserve with dobutamine would predict recovery of myocardial function during follow-up in patients with recent onset idiopathic dilated cardiomyopathy (IDC). BACKGROUND: The prognosis of patients presenting with new onset IDC is variable and difficult to predict. METHODS: Twenty-two patients (17 men, 5 women, 46 +/- 14 years) with recently diagnosed IDC (4 +/- 3 months) underwent dobutamine echocardiography. Left ventricular ejection fraction (LVEF) and LV sphericity before and at peak dobutamine infusion (30 +/- 11 microg/kg/min) were determined. A follow-up echocardiographic assessment was done at 6 +/- 4 months. RESULTS: The LVEF on dobutamine was directly related to baseline LV mass expressed as g/ml (Pearson r = 0.65, p = 0.0003). Baseline variables that were significantly predictive of follow-up LVEF were deceleration time (r = 0.69, p = 0.0006), wall motion score index (WMSI) (r = -0.63, p = 0.002), LV mass (r = 0.56, p = 0.008) and LVEF on dobutamine (r = 0.84, p = 0.0001). When either deceleration time or WMSI or LV mass was entered into a regression equation to predict follow-up LVEF, the LVEF on dobutamine added significantly to predictive power. However, if LVEF on dobutamine was entered first, none of the other three variables added significantly to prediction. Baseline LV sphericity at end diastole (ED) (r = 0.13, p = 0.6) did not correlate with follow-up LV sphericity in ED, whereas LV sphericity in ED on dobutamine (ED [r = 0.70, p = 0.0004]) correlated with LV sphericity in ED on follow up. CONCLUSIONS: This study demonstrates that dobutamine-induced improvement in baseline LVEF and LV sphericity identifies patients with IDC who exhibit substantial improvement in LV function and geometry over time.     

Effect of repeated intracoronary injection of bone marrow cells in patients with ischaemic heart failure the Danish stem cell study--congestive heart failure trial (DanCell-CHF)

BACKGROUND: It has been suggested that myocardial regeneration may be achieved by a single intracoronary bone marrow derived stem cell infusion in selected patients with ischaemic heart disease. The effect is uncertain in patients with chronic ischaemic heart failure and it is not known whether repeated infusions would have additional positive effects. AIMS: To assess whether two treatments of intracoronary infusion of bone marrow stem cells, administered 4 months apart, could improve left ventricular (LV) systolic function in patients with chronic ischaemic heart failure. METHODS: The study was prospective and non-randomised, comprising an observational baseline period of 4 months followed by an interventional period of 12 months. Intracoronary bone marrow cell infusion was performed at the end of the baseline period and repeated 4 months later. RESULTS: 32 patients were included. LV ejection fraction remained unchanged (33+/-9% vs. 34+/-10% after 8 months, p=0.30). Likewise, there was no significant change in LV end-systolic volume, wall motion score index (WMSI) or contractile reserve. At 12 months, a decrease in target vessel WMSI was seen (2.17+/-0.34 vs. 2.06+/-0.46, p=0.02). Furthermore, NYHA class improved (p<0.0001). No deaths were observed. CONCLUSION: In this non-randomised study, no change in LV ejection fraction could be demonstrated after repeated intracoronary bone marrow stem cell treatment in patients with chronic ischaemic heart failure.     

Levosimendan allows detection of contractile reserve in patients with chronic ischaemic left ventricular dysfunction and non-diagnostic dobutamine echocardiography

BACKGROUND: Dobutamine echocardiography is commonly used to detect contractile reserve in ischaemic left ventricular (LV) systolic dysfunction, although its sensitivity and specificity are not optimal. We tested the hypothesis that echocardiography with levosimendan could identify contractile reserve in patients with a non-diagnostic dobutamine test. METHODS: Twenty-two patients with LV ejection fraction <40% and non-diagnostic dobutamine echocardiography underwent levosimendan challenge (24 microg/kg in 10 min) prior to coronary angioplasty or surgery. RESULTS: Contractile reserve was identified by levosimendan in 10 patients (Gr. A) but was not seen in 12 patients (Gr. B). With levosimendan, LV ejection fraction increased and wall motion score index decreased significantly in Gr. A, but only slightly in Gr. B. Similarly, mean mitral annular plane excursion and peak systolic mitral annular motion velocity increased significantly in Gr. A only. Six months after revascularisation, contractile reserve was seen in 8/10 Gr. A patients but in only 2/12 Gr. B patients (80% vs 17%, p=0.011). LV ejection fraction, wall motion score index, mean mitral annular plane excursion and peak systolic mitral annular motion velocity were significantly higher in Gr. A than in Gr. B. CONCLUSION: Levosimendan echocardiography can identify contractile reserve in a sizeable proportion of patients with chronic ischaemic LV dysfunction and a non-diagnostic dobutamine test.