Dobutamine Stress Echocardiography: Beyond Traditional Uses

Anthracyclines are among the most widely used and effective antineoplastic agents. A growing number of patients treated with anthracyclines may have the potential for substantial morbidity and mortality owing to anthracycline cardiotoxicity. Patients younger than 75 years and without heart failure or pulmonary disease are more likely to receive chemotherapy. The main manifestations of acute cardiotoxicity are cardiac rhythm disturbances and the pericarditis/myocarditis syndrome, while early (several days to months following therapy) and late (years to decades after treatment) cardiotoxicity is mainly characterized by deterioration of myocardial function. Subclinical cardiomyopathy is quite more prevalent than symptomatic heart failure. Various predisposing factors have been proposed, such as total dose of anthracyclines > 550mg/m2, high rate of administration, previous chest irradiation, young or advanced age, female sex, and coexistent heart disease and/or arterial hypertension. The early detection of cardiotoxicity may lead to the modification of chemotherapeutic regimen, and to the timely administration of medications for the treatment of cardiomyopathy, such as beta-blockers and ACE inhibitors. Echocardiography during low dose dobutamine infusion (10 mg/kg/min) has the potential to reveal abnormalities of myocardial contractile reserve, while Doppler echocardiography of the mitral valve inflow during diastole has been used for the assessment of left ventricular (LV) diastolic function. This study examines whether the combination of repetitive dobutamine stress echocardiography (DSE) with evaluation of Doppler mitral inflow pattern can be used to predict the development of anthracycline cardiomyopathy

Quantification of regional left ventricular function in Q wave and non-Q wave dysfunctional regions by tissue Doppler imaging in patients with ischaemic cardiomyopathy

OBJECTIVE: To quantify regional left ventricular (LV) function and contractile reserve in Q wave and non-Q wave regions in patients with previous myocardial infarction. DESIGN: An observational study. SETTING: Tertiary care centre. PATIENTS: 81 patients with previous myocardial infarction and depressed LV function. INTERVENTIONS: All patients underwent surface ECG at rest and pulsed wave tissue Doppler imaging at rest and during low dose dobutamine infusion. The left ventricle was divided into four major regions (anterior, inferoposterior, septal, and lateral). Severely hypokinetic, akinetic, and dyskinetic regions on two dimensional echocardiography at rest were considered dysfunctional. MAIN OUTCOME MEASURES: Regional myocardial systolic velocity (Vs) at rest and the change in Vs during low dose dobutamine infusion (DeltaVs) in dysfunctional regions with and without Q waves on surface ECG. RESULTS: 220 (69%) regions were dysfunctional; 60 of these regions corresponded to Q waves and 160 were not related to Q waves. Vs and DeltaVs were lower in dysfunctional than in non-dysfunctional regions (mean (SD) Vs 6.2 (1.9) cm/s v 7.1 (1.7) cm/s (p < 0.001), and DeltaVs 1.9 (1.9) cm/s v 2.6 (2.5) cm/s (p = 0.009), respectively). There were no significant differences in Vs and DeltaVs among dysfunctional regions with and without Q waves (Q wave regions: Vs 6.2 (1.8) cm/s, DeltaVs 1.6 (2.2) cm/s; non-Q wave regions: Vs 6.3 (1.9) cm/s, DeltaVs 2.0 (2.0) cm/s). CONCLUSIONS: Quantitative pulsed wave tissue Doppler demonstrated that, among dysfunctional regions, Q waves on the ECG do not indicate more severe dysfunction, and myocardial contractile reserve is comparable in Q wave and non-Q wave dysfunctional myocardium

Pulsed wave tissue Doppler imaging for the quantification of contractile reserve in stunned, hibernating, and scarred myocardium

OBJECTIVES: To assess whether quantification of myocardial systolic velocities by pulsed wave tissue Doppler imaging can differentiate between stunned, hibernating, and scarred myocardium. DESIGN: Observational study. SETTING: Tertiary referral centre. PATIENTS: 70 patients with reduced left ventricular function caused by chronic coronary artery disease. METHODS: Pulsed wave tissue Doppler imaging was done close to the mitral annulus at rest and during low dose dobutamine; systolic ejection velocity (Vs) and the difference in Vs between low dose dobutamine and the resting value (DeltaVs) were assessed using a six segment model. Assessment of perfusion (with Tc-99m-tetrofosmin SPECT) and glucose utilisation (by 18F-fluorodeoxyglucose SPECT) was used to classify dysfunctional regions (by resting cross sectional echocardiography) as stunned, hibernating, or scarred. RESULTS: 253 of 420 regions (60%) were dysfunctional. Of these, 132 (52%) were classified as stunned, 25 (10%) as hibernating, and 96 (38%) as scarred. At rest, Vs in stunned, hibernating, and scar tissue was, respectively, 6.3 (1.8), 6.6 (2.2), and 5.5 (1.5) cm/s (p = 0.001 by ANOVA). There was a gradual decline in Vs during low dose dobutamine infusion between stunned, hibernating, and scar tissue (8.3 (2.6) v 7.8 (1.5) v 6.8 (1.9) cm/s, p < 0.001 by ANOVA). DeltaVs was higher in stunned (2.1 (1.9) cm/s) than in hibernating (1.2 (1.4) cm/s, p < 0.05) or scarred regions (1.3 (1.2) cm/s, p = 0.001). CONCLUSIONS: Quantitative tissue Doppler imaging showed a gradual reduction in regional velocities between stunned, hibernating, and scarred myocardium. Dobutamine induced contractile reserve was higher in stunned regions than in hibernating and scarred myocardium, reflecting different severities of myocardial damag

Relation between left ventricular contractile reserve during low dose dobutamine echocardiography and plasma concentrations of natriuretic peptides

BACKGROUND: In ischaemic cardiomyopathy, raised plasma concentrations of natriuretic peptides are associated with a poor long term prognosis, while the presence of contractile reserve is a favourable sign. OBJECTIVE: To assess the relation between plasma natriuretic peptides and contractile reserve. DESIGN: Prospective observational study. SETTING: Tertiary referral centre. PATIENTS: 66 consecutive patients undergoing low dose dobutamine stress echocardiography to evaluate contractile reserve in regions with contractile dysfunction at rest, divided into two groups: group 1, 31 patients with ischaemic cardiomyopathy (left ventricular ejection fraction < or = 40%) and heart failure symptoms; group 2, 35 patients with normal left ventricular function. MAIN OUTCOME MEASURES: Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), measured using immunoradiometric assays. Contractile reserve was defined as an improvement in segmental wall motion score during infusion of low dose dobutamine. RESULTS: Plasma ANP and BNP concentrations were higher in group 1 than in group 2 (mean (SD): ANP, 17.8 (32.8) v 7.2 (9.7), p < 0.005; BNP, 24.4 (69.0) v 5.0 (14.3) pmol/l, respectively; p < 0.001). In group 1, the presence of contractile reserve was inversely related to ANP and BNP levels; however, patients with contractile reserv

Cardiac dysfunction in cancer survivors unmasked during exercise

Introduction: The cardiac dysfunction associated with anthracycline-based chemotherapy cancer treatment can exist sub-clinically for decades before overt presentation. Stress echocardiography, the measurement of left ventricular (LV) deformation and arterial haemodynamic evaluation have separately been used to identify sub-clinical cardiovascular (CV) dysfunction in several patient groups including those with hypertension and diabetes. The purpose of the present cross-sectional study was to determine whether the combination of these techniques could be used to improve the characterisation of sub-clinical CV dysfunction in long-term cancer survivors previously treated with anthracyclines. Materials and methods: Thirteen long-term cancer survivors (36±10 years) with prior anthracycline exposure (11±8 years post-treatment) and 13 age-matched controls were recruited. Left ventricular structure, function and deformation were assessed using echocardiography. Augmentation index was used to quantify arterial haemodynamic load and was measured using applanation tonometry. Measurements were taken at rest and during two stages of low-intensity incremental cycling.Results: At rest, both groups had comparable global LV systolic, diastolic and arterial function (all P>0.05), however longitudinal deformation was significantly lower in cancer survivors (-18±2 v -20±2, P<0.05). During exercise this difference between groups persisted and further differences were uncovered with significantly lower apical circumferential deformation in the cancer survivors (-24±5 v -29±5, -29±5 v 35±8 for first and second stage of exercise respectively, both P<0.05). Conclusion: In contrast to resting echocardiography the measurement of LV deformation at rest and during exercise provides a more comprehensive characterisation of sub-clinical LV dysfunction. Larger studies are required to determine the clinical relevance of these preliminary findings

Long term outcome in patients with silent versus symptomatic ischaemia during dobutamine stress echocardiography

OBJECTIVES: To compare the long term prognosis of patients having silent versus symptomatic ischaemia during dobutamine stress echocardiography (DSE). DESIGN: Observational study. SETTING: Tertiary referral centre. PATIENTS: 931 patients who experienced stress induced myocardial ischaemia during DSE. RESULTS: Silent ischaemia was present in 643 of 931 patients (69%). The number of dysfunctional segments at rest (mean (SD) 9.6 (5.1) v 8.8 (5.0), p = 0.1) and of ischaemic segments (3.5 (2.2) v 3.8 (2.1), p = 0.2) was comparable in both groups. During a mean (SD) follow up of 5.5 (3.3) years, there were 169 (18%) cardiac deaths and 86 (9%) non-fatal infarctions. Multivariable Cox regression analysis showed age (hazard ratio (HR) 1.1, 95% confidence interval (CI) 1.02 to 1.05), previous myocardial infarction (HR 1.4, 95% CI 1.1 to 2.0), and number of ischaemic segments during the test (HR 2.0, 95% CI 1.0 to 3.7) as independent predictors of cardiac death and myocardial infarction. For every additional ischaemic segment there was a twofold increment in risk of late cardiac events. The annual cardiac death or myocardial infarction rate was 3.0% in patients with symptomatic ischaemia and 4.6% in patients with silent ischaemia (p < 0.01). Silent induced ischaemia was an independent predictor of cardiac death and myocardial infarction (HR 1.7, 95% CI 1.1 to 2.0). During follow up symptomatic patients were treated more often with cardioprotective therapy (p < 0.01) and coronary revascularisation (145 of 288 (50%) v 174 of 643 (27%), p < 0.001). CONCLUSIONS: Patients with silent ischaemia had a similar extent of myocardial ischaemia during DSE compared to patients with symptomatic ischaemia but received less cardioprotective treatment and coronary revascularisation and experienced a higher cardiac event rate

Caveolin contributes to the modulation of basal and β-adrenoceptor stimulated function of the adult rat ventricular myocyte by simvastatin: A novel pleiotropic effect

The number of people taking statins is increasing across the globe, highlighting the Importance of fully understanding statins effects on the cardiovascular system. The beneficial impact of statins extends well beyond regression of atherosclerosis to include direct effects on tissues of the cardiovascular system (pleiotropic effects). Pleiotropic effects on the cardiac myocyte are often overlooked. Here we consider the contribution of the caveolin protein, whose expression and cellular distribution is dependent on cholesterol, to statin effects on the cardiac myocyte. Caveolin is a structural and regulatory component of caveolae, and is a key regulator of cardiac contractile function and adrenergic responsiveness. We employed an experimental model in which inhibition of myocyte HMG CoA reductase could be studied in the absence of paracrine influences from non-myocyte cells. Adult rat ventricular myocytes were treated with 10 μM simvastatin for 2 days. Simvastatin treatment reduced myocyte cholesterol, caveolin 3 and caveolar density. Negative inotropic and positive lusitropic effects (with corresponding changes in [Ca2]¡) were seen in statin-treated cells. Simvastatin significantly potentiated the inotropic response to β2-, but not β1-, adrenoceptor stimulation. Under conditions of β2-adrenoceptor stimulation, phosphorylation of phospholamban at Ser16and troponin I at Ser23/24was enhanced with statin treatment. Simvastatin increased NO production without significant effects on eNOS expression or phosphorylation (Ser1177), consistent with the reduced expression of caveolin 3, its constitutive Inhibitor. In conclusion, statin treatment can reduce caveolin 3 expression, with functional consequences consistent with the known role of caveolae in the cardiac cell. These data are likely to be of significance, particularly during the early phases of statin treatment, and in patients with heart failure who have altered ß-adrenoceptor signalling. In addition, as caveolin is ubiquitously expressed and has myriad tissue-specific functions, the impact of statin-dependent changes in caveolin is likely to have many other functional sequelae

Shrimp Farming Practices in the Puttallam District of Sri Lanka: Implications for Disease Control, Industry Sustainability, and Rural Development

Shrimp farming has great potential to diversify and secure income in rural Sri Lanka, but production has significantly declined in recent years due to civil conflicts, some unsustainable practices and devastating outbreaks of disease. We examined management practices affecting disease prevention and control in the Puttalam district to identify extension services outputs that could support sustainable development of Sri Lankan shrimp farming. A survey on 621 shrimp farms (603 operational and 18 nonoperational) was conducted within the Puttalam district over 42 weeks comprising a series of three-day field visits from August 2008 to October 2009, covering two consecutive shrimp crops. Fundamental deficits in disease control, management, and biosecurity practices were found. Farmers had knowledge of biosecurity but the lack of financial resources was a major impediment to improved disease control. Smallholder farmers were disproportionately constrained in their ability to enact basic biosecurity practices due to their economic status. Basic breaches in biosecurity will keep disease as the rate limiting step in this industry. Plans to support this industry must recognize the socioeconomic reality of rural Sri Lankan aquaculture