Ventricular systolic reserve in asymptomatic children previously treated with low doses of anthracyclines: A longitudinal, prospective exercise echocardiography study

Background: The time course of mild cardiotoxicity induced by anthracycline remains unknown. The aim of this study was to evaluate the long-term evolution of decreased myocardial reserve in children previously treated with a cumulative dose of anthracycline up to 100mg/m 2. Patients and Methods: Twenty-seven asymptomatic cancer survival patients (25 with lymphoblastic leukemia), in continuous remission and off treatment for >12 months with no alterations in conventional echocardiograms were evaluated by exercise echocardiography at 37±15.4 months (T1) and 101±24 months (T2) after finishing treatment (ADRIA group). This group was compared with 25 healthy individuals (control group) similar to the ADRIA group with respect to age and body surface area (BSA). All individuals underwent treadmill exercise testing according to Bruce protocol. Echocardiograms were performed before and immediately after exercise. Results: The groups were similar regarding cardiac structure and left ventricular (LV) systolic function at rest at T1 and T2. The growth of LV posterior wall thickness related to BSA was lower in the ADRIA group at T2. Post exercise, smaller LV ejection indexes and attenuated changes in the afterload in ADRIA group were observed at T1 and T2. Conclusion: The decreased systolic reserve induced by a low dose of anthracycline in asymptomatic children and adolescents remains unaffected over a 5-year period, suggesting that positive outcomes in chronic cardiotoxicity would be expected in patients with mild impairment after anthracycline treatment. © 2011 Wiley Periodicals, Inc.

Incremental cost-effectiveness of exercise echocardiography vs. SPECT imaging for the evaluation of stable chest pain

Aims Technological advances in cardiac imaging have led to dramatic increases in test utilization and consumption of a growing proportion of cardiovascular healthcare costs. The opportunity costs of strategies favouring exercise echocardiography or SPECT imaging have been incompletely evaluated. Methods and results We examined prognosis and cost-effectiveness of exercise echocardiography (n=4884) vs. SPECT (n=4637) imaging in stable, intermediate risk, chest pain patients. Ischaemia extent was defined as the number of vascular territories with echocardiographic wall motion or SPECT perfusion abnormalities. Cox proportional hazard models were employed to assess time to cardiac death or myocardial infarction (MI). Total cardiovascular costs were summed (discounted and inflation-corrected) throughout follow-up. A cost-effectiveness ratio = 2% annual event risk), SPECT ischaemia was associated with earlier and greater utilization of coronary revascularization (P < 0.0001) resulting in an incremental cost-effectiveness ratio of $32 381/LYS. Conclusion Health care policies aimed at allocating limited resources can be effectively guided by applying clinical and economic outcomes evidence. A strategy aimed at cost-effective testing would support using echocardiography in low-risk patients with suspected coronary disease, whereas those higher risk patients benefit from referral to SPECT imaging.

Incremental benefit of myocardial contrast to combined dipyridamole-exercise stress echocardiography for the assessment of coronary artery disease

Background-Although assessment of myocardial perfusion by myocardial contrast echocardiography (MCE) is feasible, its incremental benefit to stress echocardiography is not well defined. We examined whether the addition of MCE to combined dipyridamole-exercise echocardiography (DExE) provides incremental benefit for evaluation of coronary artery disease (CAD). Methods and Results-MCE was combined with DExE in 85 patients, 70 of whom were undergoing quantitative coronary angiography and 15 patients with a low probability of CAD. MCE was acquired by low-mechanical-index imaging in 3 apical views after acquisition of standard resting and poststress images. Wall motion, left ventricular opacification, and MCE components of the study were interpreted sequentially, blinded to other data. Significant (>50%) stenoses were present in 43 patients and involved 69 coronary territories. The addition of qualitative MCE improved sensitivity for the detection of CAD (91% versus 74%, P=0.02) and accurate recognition of disease extent (87% versus 65% of territories, P=0.003), with a nonsignificant reduction in specificity. Conclusions-The addition of low-mechanical-index MCE to standard imaging during DExE improves detection of CAD and enables a more accurate determination of disease extent.

Response of B-type natriuretic pepticle to exercise in hypertensive patients with suspected diastolic heart failure: Correlation with cardiac function, hemodynamics, and workload

Background Diastolic heart failure (DHF) is characterized by dyspnea due to increased left ventricular (LV) filling pressures during stress. We sought the relationship of exercise-induced increases in B-type natriuretic peptide (BNP) to LV filling pressures and parameters of cardiovascular performance in suspected DHF. Methods Twenty-six treated hypertensive patients with suspected DHF (exertional dyspnea, LV ejection fraction >50%, and diastolic dysfunction) underwent maximal exercise echocardiography using the Bruce protocol. BNP, transmitral Doppler, and tissue Doppler for systolic (So) and early (Ea) and late (Aa) diastolic mitral annular velocities were obtained at rest and peak stress. LV filling pressures were estimated with E/Ea ratios. Results Resting BNP correlated with resting pulse pressure (r=0.45, P=0.02). Maximal exercise performance (4.6 +/- 2.5min) was limited by dyspnea. Blood pressure increased with exercise (from 143 +/- 19/88 +/- 8 to 191 +/- 22/90 +/- 10 mm Hg); 13 patients (50%) had a hypertensive response. Peak exercise BNP correlated with peak transmitral E velocity (r = 0.41, P <.05) and peak heart rate (r = -0.40, P <.05). BNP increased with exercise (from 48 57 to 74 97 pg/mL, P =.007), and the increment of BNP with exercise was associated with maximal workload and peak exercise So, Ea, and Aa (P <.01 for all). Filling pressures, approximated by lateral E/Ea ratio, increased with exercise (7.7 +/- 2.0 to 10.0 +/- 4.8, P <.01). BNP was higher in patients with possibly elevated filling pressures at peak exercise (E/Ea >10) compared to those with normal pressures (123 +/- 124 vs 45 +/- 71 pg/mL, P =.027). Conclusions Augmentation of BNP with exercise in hypertensive patients with suspected DHF is associated with better exercise capacity, LV systolic and diastolic function, and left atrial function. Peak exercise BNP levels may identify exercise-induced elevation of filling pressures in DHF.

Relationship between myocardial perfusion and dysfunction in diabetic cardiomyopathy: A study of quantitative contrast echocardiography and strain rate imaging

Objective: To use quantitative myocardial contrast echocardiography (MCE) and strain rate imaging (SRI) to assess the role of microvascular disease in subclinical diabetic cardiomyopathy. Methods: Stress MCE and SRI were performed in 48 patients (22 with type II diabetes mellitus (DM) and 26 controls), all with normal left ventricular systolic function and no obstructive coronary disease by quantitative coronary angiography. Real-time MCE was acquired in three apical views at rest and after combined dipyridamole-exercise stress. Myocardial blood flow (MBF) was quantified in the 10 mid- and apical cardiac segments at rest and after stress. Resting peak systolic strain rate (SR) and peak systolic strain (epsilon) were calculated in the same 10 myocardial segments. Results: The DM and control groups were matched for age, sex and other risk factors, including hypertension. The DM group had higher body mass index and left ventricular mass index. Quantitative SRI analysis was possible in all patients and quantitative MCE in 46 (96%). The mean e, SR and MBF reserve were all significantly lower in the DM group than in controls, with diabetes the only independent predictor of each parameter. No correlation was seen between MBF and SR (r = -0.01, p = 0.54) or between MBF and epsilon ( r = -0.20, p = 0.20). Conclusions: Quantitative MCE shows that patients with diabetes but no evidence of obstructive coronary artery disease have impaired MBF reserve, but abnormal transmural flow and subclinical longitudinal myocardial dysfunction are not related.

Excessive blood pressure increase with exercise and risk of all-cause mortality and cardiac events

The association of an excessive blood pressure increase with exercise (EBPIE) on cardiovascular outcomes remains controversial. We sought to assess its impact on the risk of all-cause mortality and major cardiac events in patients with known or suspected coronary artery disease (CAD) referred for stress testing. Exercise echocardiography was performed in 10,047 patients with known or suspected CAD. An EBPIE was defined as an increase in systolic blood pressure with exercise ≥80 mmHg. The endpoints were all-cause mortality and major cardiac events (MACE), including cardiac death or nonfatal myocardial infarction (MI). Overall, 573 patients exhibited an EBPIE during the tests. Over a mean follow-up of 4.8 years, there were 1,950 deaths (including 725 cardiac deaths), 1,477 MI, and 1,900 MACE. The cumulative 10-year rates of all-cause mortality, cardiac death, nonfatal MI and MACE were 32.9%, 13.1%, 26,9% and 33% in patients who did not develop an EBPIE vs. 18.9%, 4.7%, 17.5% and 20.7% in those experiencing an EBPIE, respectively (p <0.001 for all comparisons). In Cox regression analyses, an EBPIE remained predictive of all-cause mortality (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.59-0.91, p = 0.004), cardiac death (HR 0.67, 95% CI 0.46-0.98, p = 0.04), MI (HR 0.67, 95% CI 0.52-0.86, p = 0.002), and MACE (HR 0.69, 95% CI 0.56-0.86, p = 0.001). An EBPIE was associated with a significantly lower risk of mortality and MACE in patients with known or suspected CAD referred for stress testing.

A clinical and echocardiographic score for assigning risk of major events after dobutamine echocardiograms

OBJECTIVES We sought to develop and validate a risk score combining both clinical and dobutamine echocardiographic (DbE) features in 4,890 patients who underwent DbE at three expert laboratories and were followed for death or myocardial infarction for up to five years. BACKGROUND In contrast to exercise scores, no score exists to combine clinical, stress, and echocardiographic findings with DbE. METHODS Dobutamine echocardiography was performed for evaluation of known or suspected coronary artery disease in 3,156 patients at two sites in the U.S. After exclusion of patients with incomplete follow-up, 1,456 DbEs were randomly selected to develop a multivariate model for prediction of events. After simplification of each model for clinical use, the models were internally validated in the remaining DbE patients in the same series and externally validated in 1,733 patients in an independent series. RESULTS The following score was derived from regression models in the modeling group (160 events): DbE risk = (age (.) 0.02) + (heart failure + rate-pressure product <15,000) (.) 0.4 + (ischemia + scar) (.) 0.6. The presence of each variable was scored as 1 and its absence scored as 0, except for age (continuous variable). Using cutoff values of 1.2 and 2.6, patients were classified into groups with five-year event-free survivals >95%, 75% to 95%, and <75%. Application of the score in the internal validation group (265 events) gave equivalent results, as did its application in the external validation group (494 events, C index = 0.72). CONCLUSIONS A risk score based on clinical and echocardiographic data may be used to quantify the risk of events in patients undergoing DbE. (C) 2004 by the American College of Cardiology Foundation.

Functional and prognostic implications of left ventricular contractile reserve in patients with asymptomatic severe mitral regurgitation

Objective: To evaluate contractile reserve (CR) determined by exercise echocardiography in predicting clinical outcome and left ventricular (LV) function in asymptomatic severe mitral regurgitation (MR). Design: Cohort study. Setting: Regional cardiac centre. Patients and outcome measures: LV volumes and ejection fraction (EF) were measured at rest and after stress in 71 patients with isolated MR. During follow up (mean (SD) 3 (1) years), EF and functional capacity were serially assessed and cardiac events ( cardiac death, heart failure, and new atrial fibrillation) were documented. Results: CR was present in 45 patients (CR+) and absent in 26 patients (CR-). Age, resting LV dimensions, EF, and MR severity were similar in both groups. Mitral surgery was performed in 19 of 45 (42%) CR+ patients and 22 of 26 (85%) CR2 patients. In patients undergoing surgery, CR was an independent predictor of follow up EF (p = 0.006) and postoperative LV dysfunction (EF < 50%) persisted in five patients, all in the CR2 group. Event-free survival was lower in surgically treated patients without CR (p = 0.03). In medically treated patients, follow up EF was preserved in those with intact CR but progressively deteriorated in patients without CR, in whom functional capacity also deteriorated. Conclusions: Evaluation of CR by exercise echocardiography may be useful for risk stratification and may help to optimise the timing of surgery in asymptomatic severe MR.

Valor pronóstico del incremento de la tensión arterial sistólica con el ejercicio en pacientes hipertensos con enfermedad coronaria conocida o sospechada.

La asociación entre un incremento exagerado de la presión arterial sistólica con el ejercicio (IEPASE) y la probabilidad de eventos cardiovasculares es controvertida. Nuestro propósito fue determinar la posible asociación de un IEPASE con la supervivencia y con el riesgo de eventos cardíacos graves en pacientes hipertensos con enfermedad coronaria conocida o sospechada. Se trata de un estudio retrospectivo y observacional sobre una muestra de 5.226 pacientes con historia de hipertensión arterial y enfermedad coronaria conocida o sospechada referidos a ecocardiografía de ejercicio. El IEPASE se definió como un incremento de la presión arterial sistólica con el ejercicio igual o superior al percentil 95 de esta población (80 mmHg). Los objetivos fueron mortalidad total, mortalidad de origen cardíaco e infarto de miocardio (IM). En un seguimiento medio de 4,7 años, se registraron 978 muertes (371 de origen cardíaco) y 798 IM. Las tasas anuales de mortalidad, mortalidad de origen cardíaco e IM fueron del 2,73; 0,83 y 2,63% en pacientes con IEPASE y de 4,4; 1,58 y 3,98%, respectivamente en aquellos sin IEPASE (p < 0,001; p = 0,012 y p = 0,014, respectivamente). Tras un ajuste multivariado, el IEPASE resultó predictor de mortalidad por cualquier causa (HR: 0,70; IC 95%: 0,52-0,95; p = 0,023) e IM (HR: 0,69; IC 95%: 0,50-0,95; p = 0,022), pero la asociación con mortalidad cardiaca no alcanzó significación estadística (HR: 0,72; IC 95%: 0,43-1,20; p = 0,2). El IEPASE se asoció con mayor probabilidad de supervivencia y menor riesgo de IM en pacientes hipertensos con enfermedad coronaria conocida o sospechada.

Impact of gender on risk stratification by exercise and dobutamine stress echocardiography: long-term mortality in 4234 women and 6898 men

Aims Prior research is limited with regard to the diagnostic and prognostic accuracy of commonplace cardiac imaging modalities in women. The aim of this study was to examine 5-year mortality in 4234 women and 6898 men undergoing exercise or dobutamine stress echocardiography at three hospitals. Methods and results Univariable and multivariable Cox proportional hazards models were used to estimate time to cardiac death in this multi-centre, observational registry. Of the 11 132 patients, women had a greater frequency of cardiac risk factors (P < 0.0001). However, men more often had a history of coronary disease including a greater frequency of echocardiographic wall motion abnormalities (P < 0.0001). During 5 years of follow-up, 103 women and 226 men died from ischaernic heart disease (P < 0.0001). Echocardiographic estimates of left ventricular function (P < 0.0001) and the extent of ischaernic watt motion abnormalities (P < 0.0001) were highly predictive of cardiac death. Risk-adjusted 5-year survival was 99.4, 97.6, and 95% for exercising women with no, single, and multi-vessel ischaemia (P < 0.0001). For women undergoing dobutamine stress, 5-year survival was 95, 89, and 86.6% for those with 0, 1, and 2-3 vessel ischaemia (P < 0.0001). Exercising men had a 2.0-fold higher risk at every level of worsening ischaemia (P < 0.0001). Significantly worsening cardiac survival was noted for the 1568 men undergoing dobutamine stress echocardiography (P < 0.0001); no ischaemia was associated with 92% 5-year survival as compared with death rates of &GE; 16% for men with ischaemia on dobutamine stress echocardiography (P < 0.0001). Conclusion Echocardiographic measures of inducible wall motion abnormalities and global and regional left ventricutar function are highly predictive of long-term outcome for women and men alike.

Myocardial blood volume and perfusion reserve responses to combined dipyridamole and exercise stress: A quantitative approach to contrast stress echocardiography

Background: Qualitative interpretation of myocardial contrast echocardiography (MCE) improves the accuracy of wall-motion analysis for assessment of coronary artery disease (CAD). We examined the feasibility and accuracy of quantitative MCE for diagnosis of CAD. Methods: Dipyridamole/exercise stress MCE (destruction-replenishment protocol with real-time imaging) was performed in 90 patients undergoing quantitative coronary angiography, 48 of whom had significant (> 50%) stenoses. MCE was repeated with exercise alone in 18 patients. Myocardial blood flow (A*beta) was obtained from blood volume (A) and time to refill (beta). Results: Quantification of flow reserve was feasible in 88%. The mean A*beta reserve in the anterior wall was significantly impaired for patients with left anterior descending coronary artery disease (n = 28) compared with those with no disease (1.6 +/- 1.2 vs; 4.0 +/- 2.5, P <=.001). This reflected impaired beta reserve, with no difference in the A reserve. Applying a receiver operating characteristic curve derived cutoff of 2.0 for A*beta reserve, quantitative MCE was 76% sensitive and 71% specific for the diagnosis of significant left anterior descending coronary artery stenosis. Posterior circulation results were similar, with 78% sensitivity and 59% specificity for detection of posterior CAD. Overall, quantitative MCE was similarly sensitive to qualitative approach for diagnosis of CAD (88% vs 93%), but with lower specificity (52% vs 65%, P =.07). In 18 patients restudied with pure exercise stress, the mean myocardial blood flow reserve was less than after combined stress (2.1 +/- 1.6 vs 3.7 +/- 1.9, P =.01). Conclusion: Quantitative MCE is feasible for the diagnosis of CAD with dipyridamole/exercise stress. Dipyridamole prolongs postexercise hyperemia, augmenting the degree of hyperemia at the time of imaging.