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Background Stress echocardiography (SE) is used for diagnosis and risk stratification of patients with known or suspected coronary artery disease (CAD). Contrast-enhanced ultrasound (CEUS) detects carotid intraplaque neovascularization (IPN). The aim of this study was to test the hypothesis that combining SE with carotid CEUS in patients with known or suspected CAD might provide incremental prognostic value beyond clinical risk factors and either test alone for the occurrence of cardiovascular events. Methods One hundred eighty-five patients (mean age, 69 ± 8 years; 79% men) with known or suspected CAD referred for SE and found to have carotid plaque on screening were recruited for carotid CEUS imaging. IPN was graded by presence and location within plaque. Patients were followed for cardiovascular events (CVEs) including cardiac death, myocardial infarction, unstable angina, and transient ischemic attack or stroke. A subset of patients (n = 27) underwent carotid magnetic resonance imaging within 1 month of CEUS; carotid plaque was assessed for lipid-rich necrotic core, loose matrix, and presence of intraplaque hemorrhage. Results Sixty-nine patients had abnormal findings on SE. IPN was identified in 112 patients; 52 patients had IPN localized to plaque shoulder (IPNS). Plaques with IPNS had larger lipid-rich necrotic cores and were more likely to have intraplaque hemorrhage. During follow-up (median, 31 months), 26 CVEs occurred. Multivariate Cox proportional-hazard analysis showed IPN and IPNS to be predictors of CVEs (hazard ratios, 3.34 [95% CI, 1.25–8.93; P = .02] and 4.88 [95% CI, 1.77–13.49; P = .002], respectively). The presence of IPNS increased the likelihood of CVEs beyond SE and history of CAD (χ 2 = 9.0, P = .02). Conclusions Carotid IPN detected by CEUS and localized to plaque shoulder was an independent predictor of CVEs in patients referred for SE.

Background Myocardial work index (MWI) and work efficiency are new parameters for assessing left ventricular function. We aim to characterize the normal response to exercise in a mixed population and determine whether MWI can identify patients with inducible ischemia. Methods Patients were retrospectively enrolled from an existing database of exercise stress echocardiography. Inclusion criteria were a clinical indication of possible ischemia and technical suitability to calculate MWI. Exclusion criteria were abnormal baseline left ventricular function or inadequate image quality. Echocardiograms positive for ischemia were defined by independent visual assessment and compared with angiographic findings where available. Myocardial work index was determined using a proprietary algorithm and efficiency calculated as constructive work divided by the sum of constructive and wasted work. Results A total of 177 patients met inclusion criteria; 117 were excluded, leaving 40 normal and 20 positive tests. During normal exercise, global MWI increased 54% (from 2,296 to 3,523 mm Hg%) and efficiency remained at 96%. However, in patients with inducible ischemia, MWI decreased in affected segments, global MWI did not increase (2,069-2,070 mm Hg%), and global efficiency fell from 93% to 87%. The receiver operating characteristic curve for MWI had an area under the curve of 0.94. Conclusions During normal exercise, MWI increases and efficiency remains unchanged. However, during exercise-induced ischemia, MWI paradoxically decreases in affected segments, while globally MWI fails to increase and efficiency decreases. We have demonstrated that MWI can be applied to stress echocardiography to identify ischemia, but its utility remains uncertain. Further research that makes comparisons with an objective measure of functional ischemia is needed.

The safety and diagnostic accuracy of stress testing in anemic patients have not been well studied. Despite a lack of data, significant anemia may be considered a relative contraindication to stress testing because of safety concerns related to insufficient myocardial oxygen supply.The authors reviewed 28,829 consecutive patients with blood hemoglobin drawn within 48 hours of stress echocardiography (15,624 exercise and 13,205 dobutamine). The associations of blood hemoglobin concentration with arrhythmia and other stress echocardiographic findings were examined. Additionally, the effect of anemia on the positive predictive value of stress echocardiography for the detection of significant coronary artery stenosis (≥50%) was assessed in patients who subsequently underwent coronary angiography.Anemia was present in 6,401 patients (22.2%) and was severe (hemoglobin8.0 g/dL) in 52. Stress testing with either exercise or dobutamine was safe, with no significant increase in serious arrhythmia events or need for hospitalization. In the exercise cohort, worsening anemia was associated with reduced treadmill exercise time, lower peak heart rate, peak rate-pressure product, and achieved workload. In the dobutamine stress cohort, worsening anemia was associated with higher resting heart rate, more use of atropine, and fewer patients attaining target heart rate. The positive predictive value of stress echocardiography was higher in patients with moderate anemia compared with those without anemia (71.8% vs 60.2%, P = .01).This study demonstrates that stress testing is safe in patients with mild and moderately anemia, albeit with a small increase in mild supraventricular arrhythmias with exercise. However, worsening anemia was associated with a significant reduction in exercise capacity. Additionally, worsening anemia was associated with an improvement in the positive predictive value of stress echocardiography. Extrapolation of these data to patients with severe anemia should be performed with caution given the limited number of patients with severe anemia in this study.

Background: Long-term sequelae such as right ventricular dysfunction and reduced hemodynamic reserve are the main determinants of cardiovascular outcomes after repair of tetralogy of Fallot (TOF). Echocardiographic parameters at rest offer only partial information on impaired hemodynamics in these patients, and data during stress testing are lacking. The leg-positive pressure (LPP) maneuver has recently been reported to be able to apply acute preload stress. The aim of this study was to test the hypothesis that preload reserve is impaired and ventricular interaction is exacerbated in patients with TOF. Methods: In this prospective cross-sectional study, we recruited 44 consecutive patients with TOF and 30 normal control subjects. Echocardiography was performed both at rest and during LPP stress, and preload reserve was defined as the change between baseline stroke volume (SV) and that obtained during LPP stress. The eccentricity index was calculated as the ratio of the left ventricular anteroposterior to septal-lateral dimensions to quantify ventricular interaction. Results: LPP stress significantly increased SV from 73 ± 14 to 83 ± 16 mL (P < .01) in control subjects, while the increase in SV was significantly blunted (from 75 ± 19 to 79 ± 18 mL; P < .01 for interaction) in patients with TOF. The eccentricity index significantly changed during LPP stress in patients with TOF only from 1.07 ± 0.13 to 1.13 ± 0.14 (P < .01 for interaction). Patients with TOF were subdivided into two subgroups on the basis of the median value of increased response in SV (22 with sufficient and 22 with insufficient preload reserve). Multivariate analysis identified significant pulmonary regurgitation as the only independent determinant factor for insufficient preload reserve (odds ratio, 4.57; 95% CI, 1.048–19.90; P = .04). Conclusions: In patients after repair of TOF, ventricular interaction was exacerbated and preload reserve was impaired, especially in patients with significant pulmonary regurgitation. LPP stress testing may direct tailored treatment approaches, risk stratification, and clinical decision-making, such as more aggressive pharmacologic therapy, meticulous outpatient follow-up, or earlier reintervention.

Coronary flow velocity reserve (CFVR) of the left anterior descending artery is useful for risk stratification during stress echocardiography (SE) as an add-on to regional wall motion abnormalities (RWMA). We sought to provide sex- and age-specific prognostic cutoff values for CFVR.A total of 5,577 patients (2,284 women; 110 age ≥ 85 years) who underwent dipyridamole SE with evaluation of RWMA and CFVR were enrolled in a multicenter prospective SE registry. Death and myocardial infarction were the clinical end points.During 20 months' median follow-up, 649 events (236 deaths, 413 infarctions) occurred: 288 in women and 38 in patients ≥85 years. At receiver operating characteristics analysis, the best prognostic cutoff value for CFVR was similar for men (2.03) and women (2.02) and consistent across all age strata (45 years: 2.03; 45-54 years: 2.04; 45-64 years: 2.03; 65-74 and 75-84 years: 2.0) except for patients85 years, who showed 1.90 as the optimal value. Independent predictors of mortality or myocardial infarction were RWMA (hazard ratio [HR] = 5.42), reduced CFVR (HR = 3.26), resting ejection fraction (HR = 0.98), smoking habit (HR = 1.41), age (HR = 1.02), and prior percutaneous coronary intervention (HR = 1.20) in patients age85 years; and RWMA (HR = 5.42), smoking habit (HR = 3.24), and resting ejection fraction (HR = 0.97) in those age ≥85 years. CFVR added a prognostic contribution over clinical parameters, resting ejection fraction, and stress-induced RWMA in all age and sex groups except men85 years.A sex-independent value of CFVR ≤2.0 provides the optimal prognostication across all age groups, except for those ≥85 years in whom a cutoff ≤1.90 is needed. Risk stratification is more effective for all age groups when CFVR is combined with RWMA.

Background Calcific aortic stenosis (AS) is a progressive disease, and once moderate AS is present, the likelihood of symptom onset within 5 years is significant. The aim of this study was to determine the incremental value of global longitudinal strain (GLS) and basal longitudinal strain (BLS) at rest and during exercise on outcomes among asymptomatic patients' with moderate and severe AS. Methods Seventy-five patients with isolated, asymptomatic AS and preserved left ventricular function were retrospectively enrolled and underwent symptom-limited exercise echocardiography. Clinical and echocardiographic data, including GLS and BLS at rest and during exercise, were assessed. Occurrence of AS-related cardiovascular events was recorded. Results The mean age was 71 ± 10 years, and 63% were men. The mean aortic valve gradient was 30 ± 11 mm Hg, and the mean aortic valve area was 0.98 ± 0.21 cm2. Resting GLS and BLS were −16.5 ± 4% and −16.9 ± 3.6%, respectively. Exercise stress test results were positive in 27 patients (36%). Mean exercise GLS was −17.8 ± 3.5%, and mean exercise BLS was −17.9 ± 4%. During mean follow-up of 34.5 ± 3.5 months, cardiovascular events were observed in 45 patients. In multivariate analysis, aortic valve mean gradient (HR, 1.073; 95% CI, 1.032–1.115; P Conclusions Reduced exercise BLS is associated with future cardiovascular events in patients' with asymptomatic AS, independently of clinical factors and conventional echocardiographic parameters. Detection of postexercise myocardial dysfunction in patients with asymptomatic AS with preserved left ventricular function can aid in risk assessment of these patients.

Background: Transcatheter aortic valve replacement (TAVR) is an alternative treatment in surgically intermediate- or high-risk patients with classical low-flow, low-gradient (LFLG) aortic stenosis (AS). The objective of this study was to investigate whether two-dimensional (2D) speckle-tracking echocardiography (STE) can predict left ventricular (LV) flow reserve during dobutamine stress echocardiography (DSE) and remodeling after TAVR in patients with LFLG AS.Methods: Seventy-five symptomatic patients with severe LFLG AS were recruited (mean age, 77.6 +/- 8.4 years). Patients underwent a complete clinical evaluation, standard echocardiography, 2D STE, and DSE. Echocardiographic analysis was performed before and 6 months after TAVR using global longitudinal strain (GLS) measured on 2D STE.Results: All patients received self-expanding transcatheter prosthetic valves. Six months after TAVR, LV GLS (12.8 +/- 3.2% vs 16.3 +/- 4.2%, P < .0001) significantly increased. In a multivariate analysis, LV GLS before TAVR (P < .0001) was an independent predictor of LV flow reserve during DSE. By receiver operating characteristic curve analysis, a cutoff value for LV GLS of

Background Vasodilator stress echocardiography (SE) allows combined evaluation of regional wall motion and Doppler coronary flow velocity reserve (CFVR) of both the left anterior descending coronary artery (LAD) and the right coronary artery (RCA). The aim of this study was to prospectively assess the prognostic correlates of LAD and RCA CFVR on SE. Methods A total of 1,365 patients with known or suspected coronary artery disease underwent dipyridamole SE with combined evaluation of CFVR in both the LAD and the RCA. Results Ischemia was present on SE in 263 patients (19%). CFVR was abnormal (≤2.0) in 545 patients (40%): 172 in the LAD only, 149 in the RCA only, and 224 in both the LAD and the RCA. During a median follow-up period of 20 months, 44 deaths and 98 myocardial infarctions occurred. In the overall population, LAD CFVR ≤ 2.0 (hazard ratio [HR], 3.93) and inducible ischemia (HR, 2.74) were multivariate prognostic predictors. In the subset with ischemia on SE, CFVR did not add to peak wall motion score index (HR, 2.23). In patients without ischemia on SE, age (HR, 1.04), anti-ischemic therapy at the time of testing (HR, 1.6) and LAD CFVR ≤ 2.0 (HR, 10.8) were independent prognostic indicators. In patients without ischemia on SE and LAD CFVR >2.0, the 4-year event rate was 4% in those with RCA CFVR > 2.0 and 18% in those with RCA CFVR ≤ 2.0 (P Conclusions Ischemia on SE with high peak wall motion score index identifies a high-risk subset regardless of the underlying CFVR response. Absence of ischemia on SE is associated with intermediate risk, and LAD CFVR is essential to identify a truly low-risk subset. RCA CFVR is less useful than LAD CFVR but may have a role for further risk stratification in patients without ischemia and normal LAD CFVR.

Background Anthracycline cardiotoxicity can cause significant long-term morbidity in childhood cancer survivors (CCS), but many CCS do not manifest clinical symptoms until adulthood. The aims of this study were to characterize the dynamic myocardial response to exercise of CCS at long-term follow-up by combining semisupine bicycle exercise stress echocardiography with myocardial imaging techniques and to establish whether semisupine bicycle exercise stress echocardiography could identify CCS with abnormal exercise response. Methods This was a single-center prospective cross-sectional study. One hundred CCS and 51 control subjects underwent semisupine bicycle exercise stress echocardiography. Color Doppler tissue imaging peak systolic (s′) and diastolic (e′) velocities, myocardial acceleration during isovolumic contraction, and longitudinal strain were measured at rest and at incremental heart rates in the left ventricular (LV) lateral wall, basal septum, and right ventricle. The relationship with increasing heart rate was evaluated for each parameter by plotting the values against heart rate at each stage of exercise. Kernel density estimate was used to establish the normality of the individual CCS exercise responses. Results At rest, no significant differences were found for LV lateral wall, right ventricular (RV), and basal septal systolic and diastolic velocities between CCS and control subjects. Only septal e′ was lower in CCS. LV longitudinal strain was similar between groups, while RV longitudinal strain was lower in CCS. At peak exercise, LV lateral wall, RV, and septal s′ were not different between groups, while e′ were significantly lower in CCS. LV lateral wall and septal isovolumic acceleration were also reduced in CCS. LV longitudinal strain was different between groups, while RV longitudinal strain was similar. The dynamic response of Doppler tissue imaging velocities, isovolumic acceleration, and strain was similar between CCS and control subjects. Kernel density estimate analysis confirmed that most CCS responses were within the normal range. Conclusions At 10-year follow-up, anthracycline-treated CCS with normal baseline ejection fractions have LV and RV systolic and diastolic myocardial exercise response comparable with that of control subjects. Minor differences were observed between CCS and control subjects at rest and at peak exercise, but the dynamic response is within the normal range.

Background The Valsalva maneuver is widely used to provoke left ventricular outflow tract obstruction in hypertrophic cardiomyopathy (HCM). Whereas early experiments used a standardized, goal-directed approach by maintaining an intraoral pressure >40 mm Hg for >10 sec, current practice depends on patients' understanding and effort. The aim of this study was to evaluate the clinical effectiveness of the goal-directed Valsalva maneuver (GDV) in HCM as a method to provoke left ventricular outflow tract obstruction. Methods In this prospective study, patients blew into a syringe barrel connected to a manometer with rubber tubing and maintained an intraoral pressure of >40 mm Hg for >10 sec (GDV). Using Doppler echocardiography, peak left ventricular outflow tract gradient (pLVOTG) was measured at rest and using the provocative maneuvers of the self-directed Valsalva maneuver (SDV), GDV, and exercise. Results A total of 52 patients were included. Mean pLVOTG with GDV was higher compared with SDV (48 vs 38 mm Hg, P = .001, n = 52) and was similar to exercise (GDV, 52 mm Hg; exercise, 58 mm Hg; P = .42; n = 43). Reclassification to obstructive HCM (pLVOTG ≥ 30 mm Hg) with GDV was significantly higher than with SDV (38% vs 16.6%, P = .016) and comparable with exercise (50%, P = .51). Reclassification to severe obstruction (pLVOTG ≥ 50 mm Hg) was higher with GDV compared with SDV (28.3% vs 13.5%, P = .045) and was similar to exercise (29.7%). Furthermore, GDV identified two patients with occult severe obstruction in isolation. Conclusions GDV is an objective, practical, and effective physiologic method of provoking left ventricular outflow tract obstruction. It can significantly alter patient management by reclassifying disease severity and should be incorporated in the routine clinical evaluation of patients with HCM.

Background We compared the long-term outcome of subjects without prior cardiac disease who underwent either vasodilator single-photon emission computed tomography (SPECT) or contrast stress-echocardiography (cSE) for suspected coronary artery disease (CAD). Methods Subjects who underwent vasodilator SPECT or cSE between 2008 and 2012 for suspected CAD but no history of cardiac disease were included. We retrospectively compared the association of each method with combined all-cause death and nonfatal myocardial infarction and their positive predictive value (PPV) for angiographically obstructive CAD. Results A total of 1,387 subjects were selected: 497 who underwent SPECT and 890 who underwent cSE. During 4 years of mean follow-up there were 78 hard events in the cSE group and 51 in the SPECT group. Event-free survival in subjects testing positive for ischemia, either with SPECT or cSE, was significantly worse both in the overall population and after propensity matching patients. In multivariable analyses, vasodilator SPECT or cSE demonstrated significant stratification capability with an ischemic test doubling (SPECT) or more than doubling (cSE) the risk of future hard events independently from other variables. PPV of vasodilator SPECT for the diagnosis of obstructive CAD was inferior to vasodilator cSE (PPV = 63% vs 89%, respectively; P Conclusions Our study suggests that the associations of vasodilator SPECT or cSE with outcome are comparable, with cSE demonstrating better diagnostic PPV for CAD. The absence of ionizing radiation and anticipated lower costs from higher PPV suggest that vasodilator cSE is a valid alternative to vasodilator SPECT as a gatekeeper in subjects without a prior history of CAD.

Background Exercise intolerance is the most common symptom in hypertrophic cardiomyopathy (HCM). We examined whether inability to augment myocardial mechanics during exercise would influence functional performance and clinical outcomes in HCM. Methods Ninety-five HCM patients (32 nonobstructive, 32 labile-obstructive, 31 obstructive) and 26 controls of similar age and gender distribution were recruited prospectively. They underwent rest and treadmill stress strain echocardiography, and 61 of them underwent magnetic resonance imaging. Mechanical reserve (MRES) was defined as percent change in systolic strain rate (SR) immediately postexercise. Results Global strain and SR were significantly lower in HCM patients at rest (strain: nonobstructive, −15.6 ± 3.0; labile-obstructive, −15.9 ± 3.0; obstructive, −13.8 ± 2.9; control, −17.7% ± 2.1%, P −1 , P = .002); and immediately postexercise (strain: nonobstructive, −15.6 ± 3.0; labile-obstructive, −17.6 ± 3.6; obstructive, −15.6 ± 3.6; control, −19.2 ± 3.1%; P = .001; SR: nonobstructive, −1.41 ± 0.37; labile-obstructive, −1.64 ± 0.38; obstructive, −1.32 ± 0.29; control, −1.82 ± 0.29 s −1 , P P = .001, respectively). Postexercise SR and MRES were associated with exercise capacity ( r = 0.47 and 0.42, P r = 0.74, P = .003). Postexercise SR was correlated with extent of late gadolinium enhancement ( r = 0.34, P = .03). By Cox regression, exercise SR and MRES predicted ventricular tachycardia/ventricular fibrillation (VT/VF) even after adjustment for age, gender, family history of sudden cardiac death, septum ≥ 3 cm and abnormal blood pressure response ( P = .04 and P = .046, respectively). Conclusions Nonobstructive and obstructive patients have reduced MRES compared with labile-obstructive and controls. Postexercise SR correlates with LGE and exercise capacity. Exercise SR and MRES predict VT/VF.

In patients with asymptomatic aortic stenosis (AS), exercise stress echocardiography (ESE) provides additional prognostic information beyond baseline. The coronary flow velocity reserve (CFVR) is impaired in AS, but its link with exertion is unknown in this setting. The aim of this study was to test the hypothesis that CFVR could predict exercise capacity and abnormal exercise test results in AS.Noninvasive CFVR and symptom-limited semisupine ESE were prospectively performed the same day in 43 patients with asymptomatic isolated severe AS (mean age, 68.5 ± 11 years; 26% women; mean aortic valve area, 0.8 ± 0.16 cmResting, hyperemic left anterior descending coronary artery flow velocity and CFVR (2.45 ± 0.8 vs 2.4 ± 0.8) were similar between the group unable to perform ESE and the ESE group (P = NS for all). Compared with patients with normal results on ESE, those with abnormal results on ESE (n = 22) were older, had higher E/e' ratios, had higher resting left anterior descending coronary artery flow velocities (39 ± 12 vs 31 ± 8 cm/sec), and had lower CFVR (2.01 ± 0.3 vs 2.85 ± 0.7; P .01 for all). Furthermore, CFVR was significantly correlated with age, changes in transvalvular pressure gradient and left ventricular ejection fraction with exercise, workload (in watts), and exercise duration (P .05 for all). After adjusting for other variables, CFVR remained independently correlated with exercise duration, workload, and abnormal results on ESE (P .01 for all). On receiver operating characteristic curve analysis, CFVR 2.3 was the best cutoff to predict abnormal results on ESE (area under the curve = 0.88 ± 0.06, P .01).In patients with asymptomatic severe AS, noninvasive CFVR is correlated with exercise duration and workload, and low CFVR predicts abnormal results on ESE with good accuracy.

Background: In patients with aortic stenosis, subtle alterations in myocardial mechanics can be detected by speckle-tracking echocardiography before reduction of left ventricular ejection fraction (LVEF). Methods: In this prospective study, 162 patients with aortic stenosis with an average aortic valve area of 0.7 ± 0.2 cm2 and a mean LVEF of 60 ± 11% were included. Global longitudinal strain (GLS) and mechanical dispersion (SD of time from Q/R on the electrocardiogram to peak strain in 16 left ventricular segments) were assessed using echocardiography, and all-cause mortality (n = 37) was recorded during 37 ± 13 months of follow-up. Results: Overall, nonsurvivors had more pronounced mechanical dispersion and worse GLS compared with survivors (74 ± 24 vs 61 ± 18 msec [P < .01] and −14.5 ± 4.4% vs −16.7 ± 3.6% [P < .01], respectively). In the 42 conservatively treated patients without surgical aortic valve replacement, a similar pattern was observed in nonsurvivors versus survivors (mechanical dispersion, 80 ± 24 vs 57 ± 14 msec [P < .01]; GLS, −14.0 ± 4.9% vs −17.1 ± 3.8% [P = .04], respectively). Mechanical dispersion was significantly associated with mortality (hazard ratio per 10-msec increase, 1.23; 95% CI, 1.07–1.42; P < .01) in a Cox model adjusted for LVEF and with aortic valve replacement treatment as a time-dependent covariate. Continuous net reclassification improvement showed that mechanical dispersion was incremental to LVEF, GLS, and valvulo-arterial impedance when adjusting for aortic valve replacement treatment in the total population. Conclusion: Increased mechanical dispersion may be a risk marker providing novel prognostic information in patients with aortic stenosis.

Background The aims of this study were to investigate the evolution of the transprosthetic pressure gradient and effective orifice area (EOA) during dynamic bicycle exercise in bileaflet mechanical heart valves and to explore the relationship with exercise capacity. Methods Patients with bileaflet aortic valve replacement ( n = 23) and mitral valve replacement (MVR; n = 16) prospectively underwent symptom-limited supine bicycle exercise testing with Doppler echocardiography and respiratory gas analysis. Transprosthetic flow rate, peak and mean transprosthetic gradient, EOA, and systolic pulmonary artery pressure were assessed at different stages of exercise. Results EOA at rest, midexercise, and peak exercise was 1.66 ± 0.23, 1.56 ± 0.30, and 1.61 ± 0.28 cm 2 , respectively ( P = .004), in aortic valve replacement patients and 1.40 ± 0.21, 1.46 ± 0.27, and 1.48 ± 0.25 cm 2 , respectively ( P = .160), in MVR patients. During exercise, the mean transprosthetic gradient and the square of transprosthetic flow rate were strongly correlated ( r = 0.65 [ P r = 0.84 [ P P = .004). In the latter group, systolic pulmonary artery pressures during exercise were strongly correlated with the peak transmitral gradient (ρ = 0.72, P Conclusions In bileaflet mechanical valve prostheses, there is no clinically relevant increase in EOA during dynamic exercise. Transprosthetic gradients during exercise closely adhere to the fundamental pressure-flow relationship. Indexed EOA at rest is a strong predictor of exercise capacity in MVR patients. This should be taken into account in therapeutic decision making and prosthesis selection in young and dynamic patients.

Background The authors used semisupine cycle ergometry stress echocardiography to assess cardiac function and unmask baffle stenosis in patients with d-transposition of the great arteries after atrial redirection surgery. Methods This was a retrospective review of semisupine cycle ergometry stress echocardiography performed in 53 patients (64% male; mean age, 24.0 years; 90% Mustard procedure) and 56 healthy control subjects. Incremental exercise to volitional fatigue was performed. Hemodynamic data, echocardiographic cardiac dimensions, area change, tissue Doppler velocities, strain, ventricular synchronization, and superior vena cava flow velocities before and immediately after exercise are reported. Results Patients had lower exercise capacity (870 vs 1,854 J/kg, P P 2 , P = .400). Cardiac index increased in both groups with exercise (3.0 vs 6.1 and 2.9 vs 7.0 L/min/m 2 , P P = .006). Right ventricular diastolic and systolic areas decreased significantly with exercise in both the short-axis and four-chamber views. Right and left ventricular contraction time shortened with exercise (405 vs 247 and 338 vs 217 msec, P P = .020) and normalized after catheter intervention (1.49 vs 1.46 m/sec, P = .800). Conclusions Patients with d-transposition of the great arteries have lower exercise capacity and peak heart rates. The systemic right ventricle presents a lesser but qualitatively normal systolic response and decreased diastolic filling. Semisupine cycle ergometry stress echocardiography unmasked SVC obstruction.

Recommendations for testing in patients with low pretest probability of coronary artery disease differ in guidelines from no testing at all to different tests. The aim of this study was to assess the value of exercise echocardiography (ExE) to define outcome in this population.A retrospective analysis was conducted of 1,436 patients with low pretest probability of coronary artery disease (15%) who underwent initial ExE. Overall mortality, major adverse cardiac events (MACEs), defined as cardiac death or nonfatal myocardial infarction, and revascularization during follow-up, were assessed. Ischemia (development of new wall motion abnormalities with exercise) and fixed wall motion abnormalities were measured.The mean age was 50 ± 12 years. Resting wall motion abnormalities were seen in 13 patients (0.9%) and ischemia in 108 (7.5%). During follow-up, 38 patients died, 10 of cardiac death (annualized death rate, 0.39%); 20 patients had MACEs (annualized MACE rate, 0.21%); and 48 patients (29 with ischemia) underwent revascularization (annualized revascularization rate, 0.51%). The number and percentage of MACEs in the abnormal and normal ExE groups were similar (two [1.7%] vs 18 [1.4%], P = .70), as was the annualized MACE rate (0.31% vs 0.21%, P = .50). Peak left ventricular ejection fraction exhibited a nonsignificant trend for predicting MACEs (P = .11). The number of studies needed to detect an abnormal finding was 12.6 and to detect a patient with extensive ischemia was 26.1.ExE offers limited prognostic information in patients with low pretest probability of coronary artery disease. The small number of abnormal findings on ExE and low event rates and the large number of studies needed to detect an abnormal finding limit further the value of imaging in this population.

Exercise stress echocardiography (ESE) is a valuable diagnostic and prognostic tool in adults with hypertrophic cardiomyopathy (HCM). Inducible and resting left ventricular outflow tract gradients are important predictors of heart failure. However, there are minimal data on the utility of this modality in children.Retrospective review of all pediatric HCM patients who underwent ESE at Boston Children's Hospital (January 2007-June 2018) was carried out. Patients were assigned to one of three categories based on left ventricular outflow tract gradients: group 1:30 mm Hg at rest and exercise; group 2:30 mm Hg at rest and ≥30 mm Hg with exercise; and group 3: ≥ 30 mm Hg at rest and exercise. Records were reviewed for earliest occurrence of composite endpoint of any one of the following: cardiac syncope, chest pain, nonsustained and sustained ventricular tachycardia, aborted cardiac arrest, heart failure class ≥ II, or HCM-related death/transplantation.A total of 91 children (67% males) with median age 12 years (6-24 years) at first ESE and median left ventricle wall thickness of 20 mm formed the cohort. Median follow-up duration was 3 years. During ESE, only one child experienced an event and was resuscitated. Of the 91 children, 25 were classified as group 1, 40 as group 2, and 26 as group 3. Twenty-six patients met the composite endpoint, including two heart transplant, one aborted cardiac arrest, and one sudden cardiac death. Group 3 patients had a 5 times higher risk of developing symptoms and/or serious clinical outcome at any age (hazard ratio = 5.18; 95% CI, [1.39-19.2]; P = .014). During our short follow-up time, group 2 patients had a higher risk of outcome, but this did not achieve statistical significance (hazard ratio = 1.95; 95% CI, [0.5-7.6]; P = .33).In this large series of pediatric patients with HCM, ESE can be performed safely and served as an effective tool to identify the lowest risk patients for cardiac outcome.

Objective Combining stress echocardiography with strain analysis is a promising approach for early detection of subclinical cardiac dysfunction not apparent at rest. Data on normal myocardial strain and strain rate (SR) response to exercise in adolescents and young adults are contradictory and limited. The aim of this study was to propose a standardized protocol for semisupine bicycle stress echocardiography and to provide corresponding reference values of left ventricular (LV) two-dimensional speckle-tracking echocardiography (2D STE) strain and SR in adolescents and young adults. Methods Fifty healthy adolescents and young adults (mean age, 17.8 ± 3.2 years, 44% female) were prospectively assessed. Images were acquired at rest, low stress, submaximal stress, and during recovery. Optimal image quality for offline strain analysis was pursued, and image quality was rated. Global longitudinal strain and SR from apical four-/two-/three-chamber views and short-axis circumferential strain and SR were analyzed using vendor-independent software. Interobserver variability was assessed. Results Strain and SR increased during progressive exercise stress. Mean LV global longitudinal strain was −20.4% ± 1.3%, SR −1.1 ± 0.15/sec at rest (heart rate, 79.4 ± 12.0 beats/minute), increasing to −22.6% ± 1.6% and −1.5 ± 0.16/sec at low stress level (heart rate, 117.1 ± 8.7 beats/minute) and −23.7% ± 1.1% and −1.9 ± 0.29/sec at submaximal stress level (heart rate, 154.2 ± 7.0 beats/minute), respectively, returning to −20.6% ± 1.4% and −1.2 ± 0.16/sec postexercise (heart rate, 90.1 ± 9.4 beats/minute). Restriction on submaximal stress level ensured adequate image quality for 2D STE strain analysis. Interobserver variability for strain was acceptable even during submaximal stress. Conclusions This study provides a systematic, standardized protocol and corresponding reference data for 2D LV STE-derived strain and SR during semisupine bicycle exercise testing in adolescents and young adults. According to our results, global longitudinal strain and SR appear to be the most comprehensible parameters for cross-sectional studies.

Despite previous studies demonstrating suboptimal appropriate use of stress echocardiography (SE), few interventions have been demonstrated to improve its appropriate use. The aim of this study was to develop a novel mechanism to improve the appropriateness of SE by implementing a point-of-care decision support tool and ordering requisition coupled with an educational strategy.A prospective pre- and postintervention analysis was conducted. The intervention included education and the development and implementation of novel ordering requisition coupled with a decision support tool that integrated appropriate use criteria (AUC) for SE.In the baseline period, 256 consecutive stress echocardiographic studies were evaluated, and 97% were classifiable by the 2011 AUC. During the intervention period, 159 studies were evaluated (98% classifiable). The intervention resulted in an increase in the appropriate proportion from 65% to 76% and a reduction in the rarely appropriate proportion from 31% to 19% (P = .017). After adjustment for physician specialty, the postintervention period had lower odds of rarely appropriate testing (0.54; 95% CI, 0.3-0.95; P = .04). Cardiology had significant lower odds of rarely appropriate testing (0.23; 95% CI, 0.11-0.50; P.001) compared with family practice (the reference standard). Vascular surgery had the highest odds (5.76; 95% CI, 2.18-21.52; P = .002) of rarely appropriate testing.AUC have not previously been applied to SE in a single-payer, publicly funded health system. The development of an educational intervention involving a new requisition and decision support tool that integrated AUC resulted in a significantly reduced proportion of rarely appropriate SE. Cardiologists ordered the highest proportion of appropriate SE. Further study is needed to determine the generalizability of the results.

The aim of this study was to compare the efficacy of myocardial perfusion (MP) and wall motion (WM) analysis obtained with real-time myocardial contrast echocardiography (RTMCE) and two widely used contrast agents in detecting coronary artery disease after injection of the vasodilator regadenoson.One hundred fifty patients were studied at two academic centers using regadenoson (400-μg intravenous bolus) vasodilator stress RTMCE (7.5% Optison infusion [n = 50] or 1.5% Definity infusion [n = 100]). Both MP and WM with RTMCE were analyzed at rest and after regadenoson bolus. Comparisons of WM and MP sensitivity, specificity, and accuracy were made. Quantitative angiography was performed in all patients within 1 month of the regadenoson stress study (50% and70% diameter stenosis was considered significant). Reviewers were blinded to all clinical and quantitative angiographic data.Rate-pressure product after regadenoson was higher in Optison than Definity patients (P = .004). Using a 50% diameter stenosis on quantitative angiography as a reference standard, overall sensitivity, specificity, and accuracy for combined WM and MP analysis were not different for both agents (Optison, 77%, 64%, and 73%; Definity, 80%, 74%, and 78%; P = NS). The sensitivity, specificity, and accuracy of WM analysis alone for Optison were 68%, 71%, and 69% compared with 60%, 72%, and 66% for Definity (P = NS). Adding MP analysis improved the sensitivity and accuracy of Definity for detecting both50% and70% stenoses (P.001 vs WM), while MP analysis did not improve the sensitivity of Optison for detecting either50 or70% stenoses.RTMCE during regadenoson stress using either Optison or Definity is a rapid and effective method for the detection of coronary artery disease. The ability of MP imaging to improve WM accuracy may depend on the rate-pressure product achieved.

Background The aim of this study was to investigate the incremental value of global longitudinal strain (GLS) by automated function imaging in respect to wall motion (WM) for the detection of coronary artery disease (CAD) during dipyridamole stress echocardiography. Methods Fifty-two patients (mean age, 65.3 ± 8.7 years; 22 men) underwent dipyridamole stress echocardiography followed by coronary angiography within 1 week. Diagnostic accuracy for the identification of single-vessel CAD was evaluated for WM and GLS. The study population was divided into two groups according to coronary angiographic findings: those with CAD ( n = 38; mean age, 67.2 ± 5.9 years; 19 men) and those without CAD ( n = 14; mean age, 63.3 ± 6.4 years; three men). Results A trend toward lower resting GLS values was found in patients with CAD than in those without (−18.7 ± 2.2% vs −20 ± 2.8%, P = .061). In patients without CAD, GLS progressively increased up to peak dose (from −20 ± 2.8% at rest to −20.7 ± 1.9% at low dose, P = .045; from −20.7 ± 1.9% at low dose to −21.5 ± 3.1% at peak dose, P = .032), whereas in patients with CAD, an increase of GLS from rest to low dose (from −18.7 ± 2.2% to −19.2 ± 3.9%, P = .046) followed by a decrease from low to peak dose (from −19.2 ± 3.9% to −17.5 ± 2.4%, P = .007) was observed. In addition, with regard to diagnostic accuracy in detecting CAD, WM yielded sensitivity of 44%, specificity of 55%, positive predictive value of 73%, and negative predictive value of 26%, whereas GLS, alternatively evaluated as the difference between peak dose and resting values or between peak and low-dose values, provided sensitivity of 61%, specificity of 90%, positive predictive value of 94%, and negative predictive value of 47% (respectively, P = .020, P = .001, P = .023, and P = .031, all vs WM) and sensitivity of 84%, specificity of 92%, positive predictive value of 96%, and negative predictive value of 68% (respectively, P P P = .001, P Conclusions GLS analysis, particularly performed by comparing peak-dose with low-dose values, improves the accuracy of dipyridamole stress echocardiography in the detection of single-vessel CAD compared with the sole assessment of WM changes.

Both resting echocardiography and exercise echocardiography produce variables predictive of outcomes in patients with hypertrophic cardiomyopathy (HCM). The aim of the present study was to compare the respective value of resting and exercise echocardiographic parameters as indicators of clinical outcomes in patients with HCM.Resting and exercise echocardiography was performed prospectively in patients with HCM evaluated at the HCM Competence Center of Bordeaux and followed up every 6 months. A composite cardiac event was defined.One hundred fifteen patients (mean age, 51.9 ± 15.2 years; 66% men) were evaluated by echocardiography and followed for a mean period of 19 ± 11 months. Eighteen patients (16%) reached the composite end point, including 10 progressions to New York Heart Association functional class III or IV. On rest echocardiography, in patients with cardiac events during follow-up, left atrial volume index was significantly more increased, as were lateral E/E' ratio and left ventricular outflow tract (LVOT) gradient, whereas mean global longitudinal strain (GLS) expressed in magnitude (14.0 ± 2.6% vs 17.0 ± 3.6%, P.001) and peak velocities at the lateral annulus by Doppler tissue imaging were significantly reduced compared with patients without events. At peak exercise, patients who developed cardiac events were characterized by lower ejection fractions and greater LVOT gradients (76 ± 55 mm Hg vs 40 ± 40 mm Hg, P.002). A Cox backward-entry selection model revealed that GLS ≤ 15% at rest and LVOT gradient ≥ 50 mm Hg at peak exercise were independently associated with an increased risk for poor outcomes in patients with HCM (hazard ratios, 3.8 [P = .017] and 3.3 [P = .028], respectively). On Kaplan-Meier survival analyses, peak exercise LVOT gradient evaluation showed additive value to predict outcomes, particularly in patients with rest GLS15% (log-rank P = .001) and despite a resting LVOT gradient ≥ 30 mm Hg (log-rank P = .001).This study supports the value of resting GLS and of peak LVOT gradient, measured during exercise echocardiography, in identifying patients with HCM at increased risk for adverse events during follow-up.

Background The prognostic value of Doppler-derived coronary flow velocity reserve (CFVR) of the left anterior descending coronary artery in patients with type 2 diabetes with preserved left ventricular systolic function and without flow-limiting stenoses on angiography remains undetermined. Methods The study sample consisted of 144 patients with type 2 diabetes (82 men; mean age 62 ± 10 years) with chest pain or angina-equivalent symptoms, no histories of coronary artery disease, and echocardiographic ejection fractions ≥ 50%. All patients underwent dipyridamole stress echocardiography with CFVR assessment of the left anterior descending coronary artery by transthoracic Doppler echocardiography and coronary angiography showing normal coronary arteries or nonobstructive coronary artery disease. Results Mean CFVR was 2.44 ± 0.57. On individual patient analysis, 109 patients (76%) had CFVR > 2, and 35 (24%) had CFVR ≤ 2. During a median follow-up period of 29 months (interquartile range, 14–44 months), 17 hard events (five deaths, 12 nonfatal myocardial infarctions) occurred. The annual hard-event rate was 13.9% in subjects with CFVR ≤ 2 and 2.0% in those with CFVR > 2. The annual event rate associated with CFVR ≤ 2 was significantly higher both in patients with left ventricular hypertrophy ( P P = .048). On Cox analysis, CFVR ≤ 2 (hazard ratio, 11.20; 95% confidence interval, 3.07–40.92), and male sex (hazard ratio, 7.80; 95% confidence interval, 1.74–34.97) were independent prognostic indicators, whereas nonobstructive coronary artery disease was not an independent predictor of outcomes. Conclusions Microvascular dysfunction before the occurrence of coronary artery involvement is a strong and independent predictor of outcomes in patients with type 2 diabetes. Vasodilator stress CFVR is a suitable tool to assess microvascular dysfunction in routine clinical practice.

Ventricular-arterial stiffening is a part of the aging process that is amplified by various comorbidities. It affects normal cardiovascular reserve and limits exercise capacity. The aim of this study was to explore the association of physiologic determinants of ventricular-arterial interaction with exercise capacity in patients referred for exercise echocardiography with exertional dyspnea.A total of 93 patients with exertional dyspnea without chest pain were evaluated using the Bruce protocol. Patients with left ventricular ejection fractions50% and those with exercise-induced myocardial ischemia were excluded. Poor exercise tolerance was defined as inability to achieve 8 metabolic equivalents.Thirty-seven patients (40%) had poor exercise tolerance. These patients were older (mean age, 60 vs 54 years, P = .01), more likely to carry the diagnosis of hypertension (84% vs 41%, P.01), and more likely to be treated with antihypertensive medications. In multivariate logistic regression analysis, left atrial volume index (P = .04) and arterial elastance (P.01) were significant predictor of poor exercise capacity, while left ventricular ejection fraction, tissue Doppler indices, and global longitudinal strain were not significant.Effective arterial elastance determined noninvasively before stress echocardiography appears to be an independent predictor of exercise tolerance in patients with exertional dyspnea.

The submitral apparatus maintains annular-papillary continuity and myocardial geometry. In mitral valve prolapse (MVP), elongated chords and redundant leaflets can interact at the region of myocardial attachment, leading to apparent discordant motion of the basal inferolateral wall. The aim of this study was to test the hypothesis that basal inferolateral wall inward motion would occur later in MVP and that this delay is associated with MVP severity.Thirty consecutive patients with MVP and matched controls underwent stress echocardiography. Time to peak transverse displacement (TPD) of the inferolateral wall compared with the anteroseptal wall was measured using speckle-tracking echocardiography. The time difference was analyzed as raw data, normalized to the RR interval, and as a percentage of the time to maximal displacement of the anteroseptal segment(s).Compared with controls, TPD was delayed in patients with MVP both at rest and at peak stress, when evaluating basal segments or basal-mid segments as a unit, both in real time and, more importantly, when correcting for anteroseptal TPD. In patients compared with controls, observed delay at rest and at peak stress was 50 ± 90 versus -30 ± 90 msec (P = .006) and 70 ± 80 versus -30 ± 60 msec (P.0001), respectively; relative to TPD of the anteroseptal segment, the observed delay at rest and at peak stress was 117 ± 24% versus 97 ± 22% (P = .007) and 144 ± 68% versus 95 ± 21% (P = .003), respectively. Similar significant findings were observed in basal-mid segments. TPD results were not statistically significant when stratified by prolapse severity. Intraclass correlation coefficients were 0.88 and 0.93, and two-tailed t tests indicated good interobserver and intraobserver variability.Inferolateral wall TPD is delayed in MVP. TPD is a novel method to characterize chordal-leaflet-myocardial interactions in patients with MVP. Prolapse severity does not predict TPD, likely because of the timing of prolapse and dynamic loading conditions. Implications of this observation include attribution of a perceived wall motion abnormality in MVP during stress echocardiography to a physiologic state and new mechanistic insights into mitral valve physiology.

Background Patients with anorexia nervosa (AN) have altered physiologic responses to exercise. The aim of this study was to investigate exercise capacity and ventricular function during exercise in adolescent patients with AN. Methods Sixty-six adolescent female patients with AN and 21 adolescent female control subjects who exercised to volitional fatigue on a semisupine ergometer, using an incremental step protocol of 20 W every 3 min, were retrospectively studied. Heart rate, blood pressure, and echocardiographic Doppler indices were measured at rest and during each stage of exercise. Fractional shortening, rate-corrected mean velocity of circumferential fiber shortening, stress at peak systole, cardiac output, and cardiac index were calculated. Minute ventilation, oxygen consumption, carbon dioxide production, and respiratory exchange ratio were measured using open-circuit spirometry. Results Patients with AN had significantly lower body mass index (16.7 vs 19.7 kg/m2, P Conclusions Adolescent patients with AN have reduced exercise capacity and peak cardiovascular indices compared with control subjects but normal patterns of cardiovascular response during progressive exercise. Systolic ventricular function is maintained during exercise in adolescents with AN.

Quantification of myocardial blood flow reserve in patients with coronary artery disease using real-time myocardial perfusion echocardiography (RTMPE) has been demonstrated to further improve accuracy over the analysis of wall motion and qualitative analysis of myocardial perfusion. The aim of this study was to determine the prognostic value of qualitative and quantitative analyses obtained by RTMPE in patients with known or suspected coronary artery disease.From March 2003 to December 2008, 227 consecutive patients with normal left ventricular function who underwent RTMPE were prospectively studied. Replenishment velocity reserve (β) and myocardial blood flow reserve were derived from RTMPE. Primary outcomes were cardiac death, myocardial infarction and unstable angina with need for urgent coronary revascularization, and secondary outcomes were coronary bypass graft surgery or angioplasty.During a median follow-up period of 32 months (range, 5 days to 6.9 years), 19 major events (two deaths, six myocardial infarctions, and 11 episodes of unstable angina) and 46 total events occurred. Wall motion (hazard ratio [HR], 2.8; 95% confidence interval [CI], 1.4-5.6; P = .003) and qualitative myocardial perfusion analysis (HR, 4.3; 95% CI, 2.1-8.5; P.001) were predictors of total events but not primary events. Abnormal myocardial blood flow reserve and abnormal β reserve were predictors of total events (HR, 8.1; 95% CI, 3-21; P.001; and HR, 16.5; 95% CI, 5.5-49; P.001) and primary events (HR, 3.8; 95% CI, 1-15; P = .048; and HR, 8.7; 95% CI, 1.8-40; P = .005). On multivariate analysis, only abnormal β reserve was an independent predictor of total (HR, 10.6; 95% CI, 2.5-43; P = .001) and primary (HR, 10.5; 95% CI, 1.5-6; P = .015) events. Abnormal β reserve added incremental value in predicting primary events (χ(2) = 2.0-13.2; P = .014).Quantitative adenosine stress RTMPE added independent and additional prognostic information over wall motion and qualitative myocardial perfusion analysis in patients with known or suspected coronary artery disease and normal left ventricular function.

The aim of this study was to compare appropriateness designations as determined by the updated 2011 appropriate use criteria (AUC) for echocardiography with prior versions of the AUC for transthoracic echocardiographic (TTE) imaging, transesophageal echocardiographic (TEE) imaging, and stress echocardiographic (SE) imaging. An additional goal was to define relationships between appropriateness determinations and echocardiographic findings for each modality.Previously published data sets of TTE, TEE, and SE studies were reclassified according to the 2011 AUC, and indication representation, appropriateness designations, and echocardiographic findings were compared with prior classifications according to the 2007 AUC for TTE and TEE imaging and the 2008 AUC for SE imaging.Overall, 2,247 echocardiographic studies were analyzed. The 2011 AUC addressed the vast majority of studies (98%), a marked increase compared with prior versions of the AUC (89%) (P.001). An increase in addressed studies was present in each echocardiographic modality (TTE imaging: n = 1,525, 98% vs 89%, P .001; TEE imaging: n = 405, 99.7% vs 91%, P.01; SE imaging: n = 289, 97% vs 88%, P.01). Among all echocardiographic procedures, the 2011 AUC found a lower frequency of appropriate studies compared with prior AUC (82% vs 88%, P.01), primarily because of new uncertain indications for TTE imaging. The frequency of inappropriate echocardiographic studies was unchanged (11%). Among all echocardiographic procedures, the 2011 AUC found appropriate studies to have more new abnormal echocardiographic findings compared with inappropriate studies (45% vs 13%, P.001). Interestingly, 2011 AUC inappropriate TTE studies had fewer major new echocardiographic abnormalities than 2007 AUC inappropriate TTE studies (9% vs 17%, P = .04).The updated 2011 AUC for echocardiography encompass the vast majority of echocardiographic procedures in a university hospital practice, filling virtually all of the gaps identified in prior versions of the AUC for TTE, TEE, and SE imaging. The 2011 AUC also reasonably stratify the likelihood of finding an echocardiographic abnormality, demonstrating improvement compared with the prior AUC.

Background Although retrospective studies have suggested that myocardial perfusion and wall motion analysis with real-time myocardial contrast echocardiography (RTMCE) improves the detection of coronary artery disease (CAD) during dobutamine or exercise stress echocardiography, a prospective randomized comparison with conventional stress echocardiography that did not use RTMCE has not been performed. Methods A total of 1,776 patients with preserved resting left ventricular wall motion undergoing dobutamine or exercise stress echocardiography for suspicion of CAD were randomized to either non-RTMCE, for which contrast was used only for the approved indication of enhancing left ventricular opacification, or RTMCE, for which contrast infusion was used in all cases to examine both wall motion and myocardial perfusion. Comparisons in test positivity, and positive predictive value in those subsequently referred for quantitative coronary angiography, were performed. Results Patients randomized to RTMCE had significantly higher test positivity (22% for RTMCE vs 15% with non-RTMCE, P = .0002). The increased test positivity occurred without a difference in positive predictive value in predicting >50% diameter stenoses by quantitative coronary angiography (67% for non-RTMCE, 73% for RTMCE). The mechanism for increased detection of CAD with RTMCE was mostly due to the detection of subendocardial wall thickening abnormalities that would have gone undetected when examining transmural wall thickening. Conclusions RTMCE improves the detection of CAD during dobutamine and exercise stress echocardiography, mainly by the detection of subendocardial ischemia.

Background Because of the shortage of donor hearts, the criteria for acceptance have been considerably expanded. Abnormal results on pharmacologic stress echocardiography are associated with significant coronary artery disease and/or occult cardiomyopathy on verification by cardiac autopsy. The aim of this study was to establish the feasibility of an approach based on pharmacologic stress echocardiography as a gatekeeper for extended heart donor criteria. Methods From April 2005 to April 2010, 39 "marginal" candidate donors (mean age, 56 ± 6 years; 21 men) were initially enrolled. After legal declaration of brain death, marginal donors underwent rest echocardiography, and if the results were normal, dipyridamole (0.84 mg/kg over 6 min, n = 25) or dobutamine (up to 40 μg/kg/min, n = 3) stress echocardiography. Results A total of 19 eligible hearts were found with normal findings. Of these, three were not transplanted because of the lack of a matching recipient, and verification by cardiac autopsy showed absence of significant coronary artery disease or cardiomyopathy abnormalities. The remaining 16 eligible hearts were uneventfully transplanted in marginal emergency recipients. All showed normal ( n = 14) or nearly normal (minor single-vessel disease in two) angiographic, intravascular ultrasound, hemodynamic and ventriculographic findings at 1 month. At follow-up (median, 14 months; interquartile range, 4–31 months), 14 patients survived and two had died, one at 2 months from general sepsis and one at 32 months from allograft vasculopathy in recurrent multiple myeloma. Conclusions Pharmacologic stress echocardiography can safely be performed in candidate heart donors with brain death and shows potential for extending donor criteria in heart transplantation.

Similar to power-to-weight ratio and weight-to-power ratio, which are measurements of the actual performance of any engine, the ratios of peak power output to left ventricular (LV) mass (peak power/mass) and of peak LV mass to power output (peak mass/power) are indices of LV performance potentially useful in heart failure (HF). This Doppler echocardiographic study was designed to evaluate peak power/mass and peak mass/power in patients with advanced HF compared with healthy subjects and to assess their prognostic value.Power output was measured at rest and at peak exercise in 75 subjects, 60 patients with advanced HF (LV ejection fraction ≤ 35%) and 15 controls. Peak LV power output (W) was calculated as the maximal product of (133 × 10⁻⁶) × stroke volume (mL) × mean arterial pressure (mm Hg) × heart rate (beats/min). LV mass was assessed using a standard M-mode echocardiographic method.Peak power/mass was 1.84 ± 0.46 W/100 g and 0.76 ± 0.31 W/100 g, and peak mass/power was 32 ± 10 g/m²/W and 84 ± 38 g/m²/W in controls and in patients with HF, respectively (both P values.0001). Peak power/mass was a powerful predictor of outcome on multivariate logistic regression analysis (hazard ratio, 0.907; P = .009). On receiver operating characteristic curve analysis, the areas under the curve for HF-related events were greater for peak power/mass (P = .002) and peak mass/power (P = .011) with respect to resting ejection fraction. Comparisons of Cox models showed that peak power/mass added prognostic value to a model that included age, New York Heart Association class, etiology, ejection fraction, and diastolic dysfunction (P.0001).Peak power/mass is useful to discriminate and risk stratify patients with advanced HF with additional power with respect to ejection fraction.

Background The aim of this study was to evaluate the clinical application of the American College of Cardiology Foundation and American Society of Echocardiography appropriateness criteria for stress echocardiography (SE) in a single-center university hospital. Methods Indications were determined for consecutive studies by two reviewers and categorized as appropriate, uncertain, or inappropriate. Results Of 477 studies for which primary indications could be determined, 188 specifically related to university transplantation programs were excluded. Of the remaining 289 studies, 88% were addressed in the appropriateness criteria for SE. Of these, 71% were appropriate, 9% were uncertain, and 20% were inappropriate. Inappropriate studies were more likely to be ordered on younger patients and women and were less likely to be ordered by cardiologists. Abnormal results on SE were more frequent among appropriate than inappropriate studies. Conclusions The appropriateness criteria for SE encompass and effectively characterize the majority of studies ordered in a single-center university hospital and appear to reasonably stratify the likelihood of abnormal results on SE. However, revisions will be required to fully capture and stratify appropriate clinical practice of SE.

It has been previously demonstrated that a new index of aortic stenosis (AS) severity derived from dobutamine stress echocardiography (DSE), the projected aortic valve area (AVA) at a normal transvalvular flow rate (AVA(proj)), is superior to traditional Doppler echocardiographic indices to discriminate true severe from pseudosevere low-gradient AS. The objectives of this study were to prospectively validate the diagnostic and prognostic value of AVA(proj) in a large series of patients and to propose a new clinically applicable simplified method to estimate AVA(proj).AVA(proj) was calculated in 142 patients with low-flow AS using 2 methods. In the conventional method, AVA was plotted against mean transvalvular flow (Q) at each stage of DSE, and AVA at a standardized flow rate of 250 ml/s was projected from the slope of the regression line fitting the plot of AVA versus Q: AVA(proj) = AVA(rest) + slope x (250 - Q(rest)). In the simplified method, using this equation, the slope of the regression line was estimated by dividing the DSE-induced change in AVA from baseline to the peak stage of DSE by the change in Q.There was a strong correlation between AVA(proj) calculated by the two methods (r = 0.95, P.0001). Among the 142 patients, 52 underwent aortic valve replacement and had underlying AS severity assessed by the surgeon. Conventional and simplified AVA(proj) demonstrated similar performance in discriminating true severe from pseudosevere AS (percentage of correct classification of AVA(proj)or = 1 cm(2), 94% and 92%, respectively) and were superior to traditional dobutamine stress echocardiographic indices (percentage of correct classification, 60%-77%). Both conventional and simplified AVA(proj) correlated well with valve weight (r = 0.52 and r = 0.58, respectively), whereas traditional dobutamine stress echocardiographic indices did not. In the 84 patients who were treated medically, conventional AVA(proj)or = 1.2 cm(2) (hazard ratio, 1.65; P = .02) and simplified AVA(proj)or = 1.2 cm(2) (hazard ratio, 2.70; P.0001) were independent predictors of mortality. Traditional dobutamine stress echocardiographic indices were not predictive.In patients with low-flow AS, AVA(proj) better predicts underlying AS severity and patient outcomes than traditional dobutamine stress echocardiographic indices. Simplified AVA(proj) is easier to calculate than conventional AVA(proj), facilitating the use of AVA(proj) in clinical practice.

Background: Although real-time three-dimensional echocardiography (RT3DE) is useful for delineating the extent and severity of stress-induced wall motion abnormalities during dobutamine stress echocardiography (DSE), it also provides simultaneous multiple two-dimensional cut planes, which may potentially improve the detection of stress-induced wall motion abnormalities. The aim of this study was to determine the comparative diagnostic accuracy of RT3DE in multiplane and multislice modes for the diagnosis of coronary artery disease (CAD) during DSE against coronary angiography reference. Methods: Multiplane and multislice cut planes (3 V, GE Healthcare, Milwaukee, WI) at rest and peak dose of dobutamine were acquired in 71 patients with known or suspected CAD. In multiplane mode, matrix array transducer allowed the simultaneous visualization of parasternal long and short-axis views or apical 4-, 2-, and 3-chamber views. From full-volume datasets, 9 equidistant 2-dimensional short-axis images from LV base to apex were extracted and simultaneously displayed (multislice mode). Visual assessment of regional wall motion was performed. Coronary angiography was performed within 48 hours and used as a reference. Results: Abnormal findings (new or worsened wall motion abnormalities or fixed wall motion abnormalities) were noted in 36 patients by multiplane mode and 28 patients by multislice mode. Coronary angiography showed significant stenosis in 32 of 71 patients in 49 of 213 coronary arteries. On a patient basis, sensitivity was not different, but specificity was significantly higher in multislice mode (95%) compared with multiplane mode (77%, P < .05). Diagnostic accuracy for detecting right CAD was also significantly higher in multislice mode (93% vs 80%, P < .05). Conclusion: Assessment of LV wall motion from multiple short-axis slices extracted from full-volume RT3DE datasets improves the diagnosis of CAD and is thus a useful addition to DSE tools. (J Am Soc Echocardiogr 2009;22:437-442.)

Background: Clinical characteristics of patients, angiographic referral bias, and several technical factors may all affect the reported diagnostic accuracy of tests. The aim of this study was to assess their influence on the diagnostic accuracy of dobutamine stress echocardiography (DSE). Methods: The medical literature from 1991 to 2006 was searched for diagnostic studies using DSE and meta-analysis was applied to the 62 studies thus retrieved, including 6881 patients. These studies were analyzed for patient characteristics, angiographic referral bias, and several technical factors. Results: The sensitivity of DSE was significantly related to the inclusion of patients with prior myocardial infarctions (0.834 vs 0.740, P < .01) and defining the results of DSE as already positive in case of resting wall motion abnormalities rather than obligatory myocardial ischemia (0.786 vs 0.864, P < .01). Specificity tended to be lower when patients with resting wall motion abnormalities were included in a study (0.812 vs 0.877, P < .10). The presence of referral bias adversely affected the specificity of DSE (0.771 vs 0.842, P < .01). Conclusion: This analysis suggests that the reported sensitivity of DSE is likely higher and the specificity lower than expected in routine clinical practice because of the inappropriate inclusion of patients with prior myocardial infarctions, the definition of positive results on DSE, and the negative influence of referral bias. However, in the patient subset that will be sent to coronary angiography, the opposite results can be expected. (J Am Soc Echocardiogr 2009;22:1199-208.)

The helical arrangement of myocardial fibers leads to left ventricular (LV) torsion, a vital contributor to systolic and diastolic function. Rotation and torsion can now be measured; we sought to determine the utility of torsion as a marker of LV function at rest and after stress in patients with myocardial infarctions (MIs) and ischemia.Dobutamine echocardiography was performed in 125 patients. After the exclusion of 40 patients with suboptimal images, LV systolic rotation and torsion were measured offline using speckle-tracking echocardiography in 44 patients with and 41 without prior MIs. Hemodynamic findings and the extent of infarction and ischemia were correlated with length-corrected torsion measurements at baseline and at peak-dose dobutamine.Resting global and regional LV systolic torsion were significantly reduced in patients with compared with those without previous MIs (1.16 +/- 1.15 degrees /cm vs 3.16 +/- 1.3 degrees /cm, P.001), and global systolic torsion was an independent correlate of LV ejection fraction (LVEF) (P = .04). There was no difference in global LV systolic torsion in patients with anteroapical or inferoposterior infarcts (1.81 +/- 1.13 degrees /cm vs 2.27 +/- 1.18 degrees /cm, P = NS) and no differences in regional torsion. Torsion was most impaired in patients with multiple areas of infarction (1.03 +/- 0.89 degrees /cm, P.001). However, dobutamine-induced ischemia (2.59 +/- 1.14 ischemic segments) had no effect on global and regional systolic torsion at peak dose or change in torsion from rest to peak dose.The influence of MI on LV systolic torsion appears to be related to infarct size rather than site, and torsion was an independent determinant of resting function. LV torsion was not significantly influenced by stress-induced myocardial ischemia.

Stress echocardiography was initially developed in 1979 and has seen substantial success in the evaluation of patients with known or suspected coronary artery disease. It has proven applicable to clinical questions of diagnosis, prognosis and follow-up. It has been heavily dependent on technologic advancements, initially digital capturing for side-by-side visualization and, more recently, developments in detailed methods of evaluating myocardial mechanics and contrast echocardiography for perfusion.

This study sought to document the safety of a new accelerated dobutamine-atropine stress echocardiography protocol and to analyze its complications.Dobutamine-atropine stress echocardiography studies were performed using an incremental dobutamine infusion protocol from 20 to 40 microg/kg/min in 3-minute stages and followed by atropine.A total of 962 patients were included. Mean age was 64 +/- 11 years and 584 were male (61%). Mean ejection fraction was 62 +/- 10%. Complications included hypertensive responses in 66 patients (7%), arrhythmias in 26 (2.7%), and symptomatic hypotension in 16 (1.7%). No patient developed heart failure, acute myocardial infarction, ventricular fibrillation, or died. The independent predictors of hypertensive responses were age, baseline systolic blood pressure, and treatment with nitrates. The independent predictors of arrhythmias were history of hypertension, previous coronary artery disease, and baseline heart rate.This accelerated dobutamine-atropine stress echocardiography protocol is safe in a low-risk population and has a rate of complications similar to that reported for the standard protocol.

The development of dynamic left ventricular outflow tract (LVOT) obstruction (DLVOTO) during effort in patients without hypertrophic cardiomyopathy has been described only a few times and its clinical significance has not been established. This study was undertaken to determine DLVOTO during exercise in patients with angina and normal coronary arteries, and to analyze the potential mechanism involved. The study included 23 patients (60.7 +/- 7.2 years), with effort angina and normal coronary arteries who underwent exercise echocardiography. DLVOTO during exercise appeared in 7 patients (30.4%), with gradients ranging from 31.1 to 67.2 mm Hg (mean 41.3 +/- 12.6). These patients showed more symptoms (effort angina) during testing than the remaining patients (100% vs 47.3%; P = .014). LVOT size was the only predictive factor of DLVOTO (9.1 +/- 0.5 vs 10.3 +/- 1.2 mm/m(2); P = .017). In patients with angina and no epicardical coronary artery disease DLVOTO is associated with a lower LVOT size.

Aim This study aimed to assess the short-term predictive value of a pharmacologic stress echocardiography test performed with accelerated high-dose dipyridamole (0.84 mg/kg over 6 minutes). Methods In all, 301 patients (161 men, mean age 61.41 ± 11.62 years) were scheduled for accelerated high-dose dipyridamole stress test. A total of 22 tests were interrupted prematurely because of side effects (overall feasibility 92.7%). The patients were followed up for nonfatal myocardial infarction, unstable angina, myocardial revascularization, and sudden death at first and third months and each 6 months (maximum 18 months). Results A positive echocardiographic response was found in 25 patients. Six patients with negative stress test experienced events. Eight patients with positive stress test went to coronary revascularization procedure. Negative predictive value was 97.8%, positive predictive value was 32%, sensitivity was 57%, and specificity was 94%. Conclusions Risk stratification with accelerated high-dose dipyridamole stress echocardiography is effective. A negative test predicts favorable short-term cardiovascular prognosis.