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Two-dimensional strain echocardiography (2D-SE) is a reliable method for measuring deformation of the left ventricle.Aim of the study was to determine changes in 2D-SE parameters over time collected during dipyridamole stress echo-cardiography (dipy-stress) and prognosis of patients with non-diagnostic dipy-stress results.In the first phase of the study, assessment of a prospective enrolled population with a non-diagnostic dipy-stress test result was conducted, checking through coronary CT angiography (CCTA) the presence of coronary artery disease (CAD). In the follow-up phase, an echocardiographic re-evaluation and outcome analysis during a mean follow-up of 78 months was carried out.In the first phase, Global Circumferential Strain (GCS) values were similar in the CCTA positive and CCTA negative groups at rest and after stress. For Global Longitudinal Strain (GLS), there was a significant reduction (p.0001) in the CCTA positive group compared to the CCTA negative group. After 78 ± 9 months none of the enrolled patients experimented cardiac events. Values of GCS, both at rest and after stress, did not differ statistically comparing follow-up values with baseline ones. No statistically significant changes were seen in the same analysis for GLS rest and stress values, between baseline and follow-up in the two groups.Performing 2D-SE during dipy-stress can detect mild CAD that conventional stress-tests miss. Patients with mild coronary stenosis may have a favorable mid-term prognosis, but efforts should be made to investigate the decrease trend in GLS, at rest and after stress, reported in this patient group.

An abnormal left ventricular contractile reserve is often seen in patients undergoing stress echocardiogram and may indicate the presence of obstructive coronary artery disease. The techniques and indexes used to identify abnormal left ventricular contractile response and its prognostic value in the absence of known causes has not been well studied. To describe the characteristics and clinical outcomes associated with an abnormal left ventricular contractile response, we performed a systematic review that identified 27 eligible studies. A diverse range of indices were utilised to measure left ventricular contractile reserve, most commonly Δleft ventricular ejection fraction in 11 studies. Dobutamine stress echocardiogram was the most commonly performed modality (19 studies) followed by exercise stress echocardiogram (4 studies), dipyridamole stress echocardiogram (2 studies), invasive hemodynamic measurement (1 study) and dobutamine stress magnetic resonance imaging (1 study). All but one study demonstrated a significant association between the absence of left ventricular contractile reserve and increased rate of cardiovascular events, cardiac death and all-cause mortality.

Background: Concern exists regarding adequacy of visualization of stress echocardiograms performed without intravenous contrast in persons with Class III obesity (body mass index ≥ 40 kg/m2). Methods: Dobutamine stress echocardiography (DSE) was performed on 128 candidates for bariatric surgery with class III obesity without chest pain or pre-existent coronary artery disease (CAD). DSE without intravenous contrast was initially performed on 62 patients with class III obesity, then was subsequently was performed with intravenous contrast on 66 patients with class III obesity. Left ventricular (LV) regional wall motion was assessed at baseline and peak stress using the 16-segment model. Results: In the intravenous contrast group 1046 of 1056 LV segments studied (99.1%) were well-visualized and interpretable at baseline and 1044 of 1056 LV segments studied (98.9%) were well-visualized and interpretable at peak stress. In the non-contrast group 905 of 992 segments studied (91.2%) were well-visualized and interpretable at baseline and 886 of 992 segments studied (89.3%) were well-visualized and interpretable at peak stress. A significantly greater number of LV segments were well-visualized and interpretable in the intravenous contrast group than in the group compared to the non-contrast group, at baseline and at peak stress (p < 0.00001 for both). DSE was positive for ischemia in 1 patient. All patients underwent bariatric surgery without cardiovascular complications. Six months after surgery, all patients were alive; none developed cardiovascular events. Conclusion: The use of intravenous contrast during DSE significantly improves visualization and interpretability of LV segments in patients with class III obesity.

OBJECTIVE Dobutamine stress echocardiography (DSE) is not always feasible in patients with low-gradient severe aortic stenosis (LG-SAS), and there are limited data available on the resting echocardiographic predictors for true-severe aortic stenosis (TSAS). This study investigated resting echocardiographic predictors for TSAS. METHODS Clinical data of 106 LG-SAS patients who underwent DSE were retrospectively analyzed. LG-SAS was defined as an aortic valve area index (AVAi)

The systemic load on the right ventricle (RV) after Senning atrial switch leads to ventricular dysfunction. Quantitative assessment of RV contractile reserve is mandatory to anticipate the need for anti-fibrotic treatment. We aimed to quantitatively assess RV contractile reserve in Senning children by estimating speckle-based global longitudinal strain (GLS) during dobutamine stress echocardiography (DSE).This prospective study compared thirty-one post-Senning children (group I) and thirty controls (group II). In post-Senning children, echocardiographic RV systolic function using one-plane ejection fraction (RVEF), RV fractional area change (RVFAC), tricuspid annulus plane systolic excursion (TAPSE), its Z-score, and RVGLS were recorded at rest and peak DSE. Contractile reserve was defined as improvement5% in RVEF,2% in GLS, and/or to near normal TAPSE.RVEF, RVFAC, TAPSE, and TAPSE Z-score were significantly lower in patients than controls [RVEF:40.13 ± 2.93% vs 53.17 ± 3.17% (P .001*), RVFAC: 21.17 ± 2.37% vs 37.23 ± 2.13% (P .001*), TAPSE:13.81 ± 1.26 vs 17.45 ± 2.93 mm (P .001*), TAPSE Z-score: -3.47 ± 0.46 vs -2.09 ± 0.48 (P .001*)]. Also, RVGLS was significantly impaired in Senning children than controls[ (-11.89 ± 2.31% vs -22.35 ± 6.73% (P .001*)]. At peak DSE, contractile reserve was not evident as measured by RVEF which increased none significantly to 42.47 ± 2.80% (P = .063). However, RVGLS improved significantly to -15.78 ± 0.93% (P .001*) and discovered the masked contractile reserve in Senning children. The 19(61.29%) children who showed masked contractile reserve (improvement in RVGLS 2%) underwent continuation of anti-fibrotic medications.Despite systemic RV function in post-Senning children was impaired at rest and during DSE, RVGLS was useful in quantitative assessment of masked contractile thus promoted continuing anti-fibrotic treatment.

BACKGROUND Stress echocardiography (SE) is an established technique for assessment of coronary artery disease (CAD) which is difficult to perform and interpret. Left ventricular stroke volume (SV) is readily estimated with Doppler echocardiography. It can be affected by myocardial ischemia, with possible adjunctive value during SE. METHODS Patients underwent Bruce protocol SE with SV estimated before and after maximal treadmill exertion post routine regional wall analysis. Incremental change in SV (ΔSV) with exercise was measured. RESULTS A derivation cohort (n = 273) was established to test the hypothesis. An optimal cutoff for detection on inducible ischemia was ΔSV ≤ +10 mL. The validation cohort of consecutive patients (n = 1093, 376 [34%] female; age 59 ± 12 years) were followed clinically after SE for 20 460 patient-months. There were 1000 patients with nonischemic SE, and 93 patients with studies suggestive of myocardial ischemia. Secondary analysis yielded 831 patients with a normal exercise response (ΔSV > +10 mL) and 192 with an abnormal ΔSV ≤ +10 mL. Time to first combined adverse cardiac event (composite of angina, acute coronary syndrome, cardiac revascularization, worsening New York Heart Association (NYHA) class, a reduction in EF, and cardiovascular death) was analyzed and adjusted using Cox proportional hazards regression. The hazard ratio for an adverse event with an abnormal ΔSV response (≤10 mL) was 10.3 (95% confidence intervals 5.6-19.1, P

Purpose Two-dimensional (2D) strain derived from speckle tracking proved to be feasible and accurate in the quantitative evaluation of myocardial ischemia during stress echocardiography. We compared the accuracy in detecting myocardial ischemia of the transmural segmental analysis with an endocardial specific evaluation in 20 patients undergoing dobutamine stress echocardiography (DSE) and coronary angiography. Methods Peak systolic global strain (G-e) and at the subendocardial level (Endo-e) were measured off-line at rest, a low dose, and peak stress; then, we compared the results with wall-motion analysis and significant coronary artery disease (CAD > 70% diameter stenosis). Endocardial strain variation from basal to low and peak dose was computed both for global or subendocardial analysis. The utilization of the ROC curve allowed us to derive optimal cutoffs, sensibility and specificity for ischemic segments. Results The subendocardial analysis at high dose showed to be able to increase significantly the accuracy of the test to detect the ischemic segments (sens 90.2% vs 85.4%; spec 93.1% vs 92.2%). Moreover, at the low dose, the subendocardial analysis showed to be able to increase significantly, mostly the specificity of the test (sens 69.6% vs 68.3%; spec 92.2% vs 86.2%). Notably, the strain subendocardial analysis at low dose showed to reach a high specificity, similar to the peak dose transmural analysis. Conclusions Measurement of subendocardial strain during DSE is feasible and can increase the accuracy of the test. Moreover, the subendocardial strain during DSE can reach a high specificity, even limiting the test at a low dose infusion.

Background Approximately 1% to 2% of patients with stable atypical chest pain (SACP) experienced a major coronary event, even after a negative functional or anatomical test. Methods Over the past 15 years, 1706 patients with SACP evaluated in our clinics underwent functional stress testing or coronary computed tomographic angiography (CTA). In these patients, we also assessed the presence of three major modifiable lifestyle‐related risk factors (cigarette smoking, low intake of fruit and vegetables, and physical inactivity). Patients were stratified according to the presence of at least one risky lifestyle factor or no risky lifestyle factors. Functional or anatomical tests were positive in 170 patients (10%). We followed the remaining 1536 patients with negative tests for 1 year to evaluate the incidence of major coronary events. Results The percentage of patients reporting major coronary events was 1.2% in the group with risky lifestyles and 0.2% in the non‐risky lifestyle group (P

BACKGROUND We compared the diagnostic accuracy of longitudinal strain (LS) imaging during stress echocardiography with visual assessment of wall motion (WM) for detecting significant coronary artery disease (CAD). METHODS Our systematic search included studies reporting diagnostic measures for LS imaging and visual assessment of WM for detecting significant CAD during stress echocardiography. Summary diagnostic accuracy measures including area under the curve (AUC), sensitivity, specificity, diagnostic odds ratio (DOR), and likelihood ratios (LRs) were estimated. RESULTS In thirteen studies with 978 patients, ten studies used invasive coronary angiography as the reference standard. Pooled AUC for diagnosing significant CAD was 0.92 (95% confidence interval [CI] 0.89-0.94) for LS imaging as compared to 0.83 (95% CI 0.80-0.86), P < 0.001 for visual assessment of WM. LS imaging had higher sensitivity (88% [95% CI 84-92] vs 74% [95% CI 68-80], P < 0.001) and comparable specificity to visual assessment of WM (80% [95% CI 72-87] vs 83% [95% CI 74-90], P = 0.592). The DOR for LS imaging and visual assessment of WM was 31 and 15, P = 0.254, respectively. The positive LR was 4.5 for both; negative LR was 0.14 and 0.31, P = 0.002 for LS imaging and visual assessment of WM, respectively. CONCLUSIONS Longitudinal strain imaging during stress echocardiography has better diagnostic accuracy for detecting significant CAD as compared to visual assessment of WM. Studies using larger sample size and standardized techniques of strain measurement are required to further ascertain the added advantage of strain measurement over visual assessment alone.

OBJECTIVES Right ventricular (RV) contractile reserve reflects the ability of RV to accommodate the increased afterload and may play an essential role in the evaluation of precapillary pulmonary hypertension (PH). This study aimed to assess RV contractile reserve based on exercise stress echocardiography (ESE) and to determine the echocardiographic determinants of exercise capacity in patients with precapillary PH. METHODS A total of 31 patients with precapillary PH and 15 age- and sex-matched healthy control subjects were prospectively recruited. All subjects underwent ESE to assess RV function at rest and under peak exercise. Changes in these parameters during exercise were calculated to quantify the RV contractile reserve. Patients with precapillary PH also underwent cardiopulmonary exercise test (CPET), and data pertaining to peak oxygen uptake (peak VO2 ) and minute ventilation/carbon dioxide production (VE/VCO2 ) were collected. RESULTS Right ventricular contractile reserve including change in tricuspid annular plane systolic excursion (∆TAPSE), change in RV fractional area change (∆RVFAC), and change in Doppler-derived tricuspid lateral annular peak systolic velocity (∆S') was significantly depressed in precapillary PH patients compared with control subjects (P

Background No data are available about whether Coronavirus disease 2019 (COVID‐19) pandemic have led to changes in clinical profiles or results of exercise testing once the usual activity was reassumed, as well as if wearing a facemask has any impact on the tests. The aim of this study is to evaluate differences in the patients referred to exercise stress testing in the context of COVID‐19 pandemic and analyse the feasibility and results of these tests wearing a facemask. Methods We included all patients referred for an exercise test from 1 June to 30 September 2020 and compared them with the patients attended within the same period in 2019 before and after propensity score matching. All patients referred in 2020 wore a facemask. Results A total of 854 patients were included: 398 in the 2020 group and 456 in 2019. No significant differences in baseline characteristics of the patients were observed, with the exception of dyspnoea, which was nearly twice as high in 2020 as compared with 2019. Regarding the results of the tests, no differences were observed, with almost 80% of maximal tests, similar functional capacity and over a 20% of positive exercise tests in both groups. These results remained after propensity score matching. Conclusion COVID‐19 pandemic has not changed the clinical profile of patients referred to exercise testing. In addition, performing exercise testing wearing a facemask is feasible, with no influence in functional capacity and clinical results.

Background Dipyridamole stress echocardiography (DSE) represents a fundamental test in patients with suspected coronary artery disease (CAD). The diagnosis of microvascular disease is still challenging. We aimed to determine the diagnostic value of left ventricular (LV) layer-specific longitudinal (LS) and circumferential strain (CS) by Speckle Tracking in detecting CAD during DSE and to study if they can help in discriminate between a negative echo and a suspected microvascular angina. Methods and results We enrolled 66 patients with known or suspected CAD. All underwent standard DSE. We identified 3 groups according to the result of DSE (36 negative DSE, 19 positive DSE, 11 indicatives for microvascular disease). Wall motion score index, global LV LS and CS (global longitudinal strain [GLS] and global circumferential strain [GCS]), and layer-specific LV LS and CS were measured at rest and peak stress. The Delta between rest and peak stress values was calculated. GLS increased after injection in negative DSE and microvascular disease while reducing in positive DSE. Endocardial GCS and transmural GCS values were stable in microvascular disease while increasing significantly in negative DSE, helping in the diagnosis. The specific analysis of endocardial LS showed the most powerful difference between healthy and macrovascular CAD patients, both for LS and CS. Conclusions Global circumferential strain can be a new valuable added tool in the echocardiographic diagnosis of microvascular disease. Endocardial GLS is the best indicator of an altered wall deformation in the presence of macrovascular ischemia.

Aim: To improve the prognosis of patients with heart failure, risk stratification in their early stage is important. We assessed whether the change in transmitral flow (TMF) velocity pattern during preload augmentation can predict future hemodynamic worsening in early-stage heart failure patients with impaired relaxation TMF pattern. Methods: We designed a prospective cohort study that included 155 consecutive patients with impaired relaxation (IR) pattern at rest. Preload stress echocardiography was achieved using leg positive pressure (LPP), and changes of TMF pattern during the LPP was observed during baseline echocardiographic examination. The patients whose TMF pattern developed to pseudonormal (PN) pattern throughout the study period were classified into the change to PN group, and patients whose TMF pattern stayed in IR pattern were classified into the stay in IR group. Results: The median follow-up period was 17 months. The average age was 68 ± 11 years old, and 97 patients (63%) were male. Among 155 patients, 27 were classified into the change to PN group. A Cox proportional hazard analysis confirmed that the change in the peak atrial systolic TMF velocity during the LPP (ΔA, hazard ratio = 0.58 per 1SD; 95% CI = 0.39 - 0.88, P = 0.010) was the powerful independent predictor of change into PN pattern. Kaplan-Meier analysis revealed that the patients with ΔA ≤ -7 cm/s had more likely to develop into PN pattern than patients with ΔA > -7 cm/s (P = 0.001). Conclusions: Evaluation of a response in TMF during the LPP might provide an incremental diagnostic value to detect future overt heart failure in patients with early-stage heart failure.

BACKGROUND Exercise stress echocardiography (SE) is commonly used for diagnosing coronary artery disease (CAD). The use of quantitative echocardiographic measures such as strain imaging is expected to improve the sensitivity of conventional SE which relies on the visual diagnosis of wall-motion abnormalities (WMAs). This study is set to demonstrate the added value of resting and exercise strain analysis to detect underlying microangiopathy and inducible myocardial ischemia during a resting and SE in comparison with the results of coronary computed tomographic angiogram (CCTA). METHODS A total of 103 consecutive outpatients from the executive screening program were identified and underwent resting and SE. Global longitudinal strain (GLS) and wall-motion changes at rest and peak exercise were analyzed and compared. Baseline demographics, heart rate, and blood pressure measurements were retrospectively extracted for analysis. CCTA was chosen as an alternative test to match with wall motion and strain imaging. RESULTS Patients who had abnormal CCTA had lower resting GLS (14.85% ± 3.05 vs 17.99% ± 2.88, P-value = .001) when compared to patients with normal CCTA. All patients who had abnormal CCTA had higher wall-motion score index (1.35 ± 0.2 vs 1.00, P-value

Background Current guidelines support exercise stress echocardiography (ESE) for evaluation of suspected obstructive coronary artery disease (OCAD) in ambulant patients with left bundle branch block (LBBB). Data regarding the diagnostic utility of ESE in patients with LBBB are limited. Hypothesis We hypothesized that the diagnostic performance of ESE for the assessment of suspected OCAD is reduced in the context of LBBB. Methods We studied 191 consecutive patients with resting LBBB undergoing ESE for the investigation of suspected OCAD between 2008 and 2015 at our center. The studies were categorized as inconclusive, normal, or abnormal. Patients with an abnormal response were subcategorized as regional ischemic response or globally abnormal. Results Eighty-two patients (43%) demonstrated a normal left ventricular contractile response (LVCR) to exercise; 92 (48%) developed an abnormal LVCR to exercise, including 70 patients with globally abnormal and 22 patients with regional ischemic responses. Of the patients with abnormal responses, 62 patients had anatomic imaging, only 29 of whom had significant OCAD, conferring an overall specificity of ESE for significant OCAD of 21% and accuracy of 52%. Of patients who developed a regionally abnormal response, 89% had significant OCAD. Conclusions For patients with LBBB who develop a globally abnormal LVCR during ESE, the specificity of ESE for reliably excluding significant OCAD is significantly reduced. ESE appears to be a suboptimal test for the evaluation of OCAD in patients with resting LBBB, as about 50% of patients will have an abnormal response, the majority due to globally abnormal contraction where OCAD cannot be reliably diagnosed. Alternative testing should be considered for the investigation of suspected OCAD in patients with resting LBBB.

Introduction The restrictive mitral valve annuloplasty (RMA) is the treatment of choice for degenerative mitral regurgitation (MR), but postoperative functional mitral stenosis remains a matter of debate. In this study, we sought to determine the impact of mitral stenosis on the functional capacity of patients. Methods In a cross-sectional study, 32 patients with degenerative MR who underwent RMA using a complete ring were evaluated. All participants performed treadmill exercise test and underwent echocardiographic examinations before and after exercise. Results The patients’ mean age was 50.1 ± 12.5 years. After a mean follow-up of 14.1 ± 5.9 months (6–32 months), the number of patients with a mitral valve peak gradient >7.5 mm Hg, a mitral valve mean gradient >3 mm Hg, and a pulmonary arterial pressure (PAP) ≥25 mm Hg at rest were 50%, 40.6%, and 62.5%, respectively. 13 patients (40.6%) had incomplete treadmill exercise test. All hemodynamic parameters were higher at peak exercise compared with at rest levels (all P

BACKGROUND The present study was designed to assess the underlying mechanism of decline in effort capacity seen with aging. METHODS We analyzed 250 healthy senior patients (≥65 years) with an ejection fraction ≥60% who underwent a stress echocardiogram test. The seniors (aged 65-94) were divided into 3 equal age groups (groups 1, 2, and 3), and their echo characteristics at rest and peak exercise (measured and calculated) were compared. RESULTS Diastolic function at rest declined significantly (E lateral, E septal, E/E', A) with age, while other rest parameters were similar. There was a significant reduction in peak cardiac output (CO) associated with age (time × age group interaction; P

Background The aim of this prospective study was to assess the diagnosis value of four-dimensional echocardiography area strain (AS) combined with exercise stress echocardiography to evaluate left ventricular regional systolic function in patients with mild single vessel coronary artery stenosis. Methods Based on treadmill exercise load status, two-dimensional conventional echocardiography and four-dimensional echocardiography area strain were performed on patients suspected coronary artery disease before coronary angiogram. Thirty patients (case group) with mild left anterior descending coronary artery stenosis (stenosis

Background Left ventricular (LV) contractile reserve assessed using imaging and cardiopulmonary exercise testing (CPX) has been shown to predict outcome in patients with dilated cardiomyopathy (DCM). Few clinical studies have, however, analyzed the relationship between them. Methods A cohort of 75 ambulatory patients with DCM underwent stress treadmill echocardiography with CPX. LV contractile reserve was calculated as absolute change (ΔLVEF=LVEFpeak−LVEFrest) and percent change (%LVEF=[(LVEFpeak−LVEFrest)/LVEFpeak)]×100) in LVEF, circumferential and longitudinal strain (LS). Exercise capacity was measured as peak oxygen uptake (peak VO2) and ventilatory efficiency as the slope of minute ventilation to CO2 production (VE/VCO2 slope). Values of contractile reserve were compared to matched controls. We also explored which metric of ventricular response (absolute or percent change) was less dependent on baseline LV function. Results Patients with DCM had a mean age, rest and peak LVEF of 44±10 years, 42±10% and 50±12%, respectively. Among parameters of contractile reserve, peak cardiac output was the strongest parameter associated with peak VO2 (r=.63, P

Background The relationship between visual and strain assessment of left ventricular (LV) function during dobutamine stress echocardiography (DSE) remains poorly investigated. We assessed systolic longitudinal strain (SLS) and strain rate (SLSR) in segments visually graded as normokinetic, hypokinetic, or akinetic at baseline (0) and peak stage (1) of DSE and compared deformation changes between segments with and without induced contractility worsening. Methods From 250 patients examined by DSE, 238 patients with diagnostic test were included, mean age of 62±9 years (105 females). Regional LV contractility was assessed visually and measured using SLS and SLSR in 4284 segments. Results The LV segments during baseline and peak stage of DSE revealed gradual decrease in absolute values of SLS (from 17.7±6.4% in normokinetic to 11.7±8.4% in akinetic segments at rest, and from 17.2±8.5% to 14.4±7.8% at peak, P 2% from baseline showed 90% and 76% sensitivity for the detection of contractility impairment. Conclusion Strain analysis quantifies segmental LV contractility not only at rest and peak DSE but may be helpful in detection of stress-induced contractility worsening.

Background Dobutamine stress echocardiogram (DSE) is a feasible and safe exercise-independent stress modality for diagnoses of coronary artery disease (CAD), but it is subjective, and operator dependant. Two-dimensional strain at peak stress could overcome these limitations and thus increase the accuracy of DSE. Methods and Results This was a prospective observational study in which 80 patients underwent DSE, two-dimensional strain at peak stress, and coronary angiography. Global longitudinal strains (GLS) cutoff point of −16.75 had 77.42% sensitivity and 83.33% specificity to detect significant CAD. Global circumferential strain (GCS) cutoff point of −20.75 had 93.55% sensitivity and 66.67% specificity to detect significant CAD (P=.003, areas under the curve [AUC]=0.73). The average territorial strain cutoff point for significant left anterior descending (LAD) lesion was −15.4 with 77.78% sensitivity and 82.86% specificity (P=.0001, AUC=0.78) and for non-LAD lesion was −16.9 with 82.93% sensitivity and 53.85% specificity (P=.0009, AUC=0.69). Two-dimensional strain at peak stress showed better agreement than DSE as regard number of vessels affected (K=0.579 vs 0.107), LAD lesion detection (K=0.783 vs 0.438), and non-LAD lesion detection (K=0.699 vs 0.233). Global longitudinal strain (GLS) at peak stress reduced DSE false positivity by 83%; the number of false-positive patients was reduced from 18 patients to only three patients. Conclusion Two-dimensional strain at peak stress had an incremental value over DSE visual assessment/ wall-motion score index (WMSI) in reducing false-positive results of DSE. Two-dimensional strain at peak stress had greater accuracy than DSE alone not only in detection of significant CAD but also in detection of number of vessels with significant lesion as well as CAD localization.

OBJECTIVES: We determined whether stroke and/or TIA subjects have exercise-induced blood flow through intrapulmonary arteriovenous anastomoses (QIPAVA ) and/or patent foramen ovale (QPFO ) and a genetic predisposition for ischemic stroke. METHODS: Twenty-eight stroke and/or TIA subjects (33-63 years old) underwent transthoracic saline contrast echocardiography concomitant with transcranial Doppler to detect QIPAVA and QPFO at rest and during supine exercise with and without breathing 100% O2 . We also examined genetic polymorphisms in FV Leiden (G1691A ; rs6025), factor II (FII) prothrombin (G20210A ; rs1799963), methylene tetrahydfropholate reductase (C677T, rs1801133), and plasminogen- activator inhibitor-1 (PAI-1) (4G/5G ; rs1799889) and angiotensin-converting enzyme (ACE ; I/D, rs4646994) in 24/28 subjects. RESULTS: No subject without PFO had QIPAVA at rest (n=17), but 12/17 did with exercise. All PFO subjects had QPFO at rest (n=11) and 7/11 had either QIPAVA or QPFO with exercise. Breathing 100% O2 during exercise reduced or eliminated left heart contrast in all subjects. Gene analyses revealed that 15/24 patients were either heterozygous or homozygous for methylenetetrahydrofolate reductase gene polymorphism ; 4G/4G and 4G/5G genotypes of plasminogen-activator inhibitor-1 were present in 7/24 and 13/24 patients, respectively ; polymorphisms of ACE D/D genotype were present in 6/24 and I/D in 14/24 patients. Having both I/D and 4G/4G genotypes was more prevalent in PFO+ subjects (P=.03), and there was a trend (P=.06) for PFO- subjects to have a greater D/D genotype prevalence. CONCLUSIONS: Novel genetic predispositions reported here in PFO subjects should be investigated further in larger stroke and/or TIA patient datasets.

AIMS Atrial fibrillation (AF) uncommonly occurs during dobutamine stress echocardiography (DSE). We aimed to characterize the predictors and long-term prognostic significance of AF during DSE. METHODS The clinical, echocardiographic, and outcome data of patients in sinus rhythm who developed AF during DSE were reviewed and compared to a propensity score-matched group of controls. RESULTS Atrial fibrillation developed in 73 (1% of 7026) patients (age 70±10 years, 58% men). Compared to 144 propensity score-matched controls without AF during DSE, those with AF were more likely to have had history of prior AF (23% vs 8%, P=.002), known coronary artery disease (CAD; 22% vs 10%, P=.037), enlarged left ventricle (LV; 27% vs 9%, P=.002), LV wall-motion abnormality (33% vs 12%, P

Background Nearly half of patients with heart failure have normal left ventricular ejection fraction (LVEF), but their prognosis is no better than those with reduced LVEF. Although peak oxygen consumption (VO2) is an independent predictor of mortality in heart failure, it is unclear how cardiac function during exercise contributes to peak VO2. Therefore, we explored the useful parameters measured by exercise stress echocardiography to predict peak VO2 in patients with heart failure with preserved LVEF (HFpEF). Methods and Results We assessed 80 patients being investigated for effort intolerance or dyspnea and finally analyzed 50 patients who satisfied the HFpEF criteria. Mean peak VO2 was 16.4±2.8 mL/kg/min. Twenty-three patients (46.0%) achieved a peak VO2

Background Dobutamine stress echocardiography (DSE) is a well-established imaging modality used to screen patients with mild-to-moderate risk for coronary artery disease. In heart transplantation recipients, cardiac allograft vasculopathy (CAV) is a common and lethal complication. The use of DSE to detect CAV showed promising results initially, but later studies showed limitation in its use to detect CAV. It is unclear if this cohort of patients derives benefit from DSE. Methods We searched PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Scopus from inception through March 2018 for studies examining the accuracy of DSE in correlation to coronary angiography (CA) or intravascular ultrasound (IVUS) to detect CAV. Original studies comparing the ability of DSE to detect CAV in comparison with CA or IVUS were included. Relevant data were extracted and hierarchical summary receiver operating characteristic analysis was conducted to test the overall diagnostic accuracy of DSE for patients with CAV. Results Eleven studies (749 participants) met the inclusion criteria. The sensitivity of DSE varied from 1.7% to 93.8%, and specificity, from 54.8% to 98.8%. Pooled sensitivity was 60.2% (95% confidence interval (CI), 33.0%-82.3%) and specificity 85.7% (95% CI, 73.8%-92.7%). DSE had an overall diagnostic odds ratio (OR) of 9.1 (95% CI, 4.6-17.8), positive likelihood ratio (LR+) of 4.1 (95% CI, 2.8-6.1), negative likelihood ratio (LR-) of 0.47 (95% CI: 0.23-0.73), and area under curve (AUC) of 0.73 (95% CI, 0.72-0.75). Heterogeneity among studies was not statistically significant (τ2 = 0.32, Cochran's Q = 9.5, P = 0.483). Conclusion Dobutamine stress echocardiography has a limited sensitivity to detect early CAV but its specificity is much higher. There remains a need for an alternative noninvasive modality which will have both high sensitivity and high specificity for detecting CAV.

Aims Left ventricular assist device (LVAD) therapy is a promising option for patients with advanced heart failure (HF), refractory to guideline‐mandated medical treatment either as a bridge to heart transplantation or as lifelong therapy. Functional capacity improves after LVAD implantation but remains reduced in patients with long‐term LVAD therapy. Exercise training (ET) improves functional capacity and quality of life (QoL) in HF and may provide incremental benefits in patients supported with LVAD therapy. Methods The primary objective of Ex‐VAD is to investigate whether a 12‐week supervised ET can improve peak oxygen uptake (peakVO2) measured by cardiopulmonary exercise testing (CPET) on an ergometer. The study is powered to demonstrate a group difference of 3 mL/min/kg in peakVO2 at week 12, with a power of 0.9 and a standard deviation of 5 mL/min/kg. After baseline assessments to determine whether ET is safe, 66 patients at six trial sites with advanced HF and LVAD therapy will be randomized 2:1 to supervised ET or to the control arm of usual care alone. Patients randomized to ET will perform supervised aerobic endurance and resistance ET (three times/week) for 12 weeks. At baseline and during follow‐up, anthropometry, CPET, echocardiography (at rest and exercise), and QoL evaluation will be performed. Blood samples will be collected to examine cardiac‐specific relevant biomarkers. Overall physical activity, training sessions, and adherence will be monitored and documented throughout the study using accelerometers and patient diaries. Conclusions The Ex‐VAD trial will assess the effects of a supervised ET programme on peakVO2 and QoL in patients with LVAD. As LVAD therapy moves from crisis support to ambulatory functional enhancement, this trial will provide a rationale to improve functional capacity and, in perspective, cardiovascular outcomes in LVAD‐supported patients with advanced HF., European Journal of Heart Failure, 21 (9), ISSN:1388-9842, ISSN:1879-0844

Background Exercise stress echocardiography (ESEcho) is sufficiently sensitive and has high enough specificity for the clinical detection of coronary artery disease (CAD) in women. However, there was little data about the ability of ESEcho to detect CAD and predict clinical outcomes in female patients with chest pain and low global cardiovascular (CV) risks. The purposes of this study were (1) to determine the diagnostic accuracy of ESEcho, (2) to evaluate the clinical outcomes of major cardiovascular outcome (MACE), and (3) to assess the incremental prognostic value of ESEcho for the prediction of MACE in Korean female patients with low CV risks. Methods Over a period of 15 years, 3396 patients (57±10 years) female patients with chest pain but no previous history of CAD undergoing ESEcho and exercise stress electrocardiography (ESECG) were assessed. Results During a median follow-up period of 4.8 years (2.8-6.2 years), there were 19 (0.61%) MACE. Positive results for ESEcho were seen in 134 patients (3.9%). The sensitivity and specificity of ESEcho were 66.7% and 84.8%, respectively. Positive ESEcho was an independent predictor of MACE (multivariate hazard ratio: 0.019, 95% CI: 0.004-0.081). ESEcho was incremental to clinical and ESECG parameters to predict the MACE in low CV risk women. Conclusions ESEcho is effective for the diagnosis of CAD in Korean female patients with chest pain, a population characterized by low cardiovascular risk profiles. Positive ESEcho was an independent predictor of MACE, and negative results were associated with favorable clinical outcomes. ESEcho was incremental to clinical and ESECG parameters to predict the MACE in low CV risk women.

Background Pharmacologic stress testing is utilized in preference to exercise stress echocardiography (ESE) for cardiac risk evaluation in potential renal transplant recipients due to the perceived lower feasibility of ESE for achieving adequate workload and target heart rate (THR) in this population. Methods Consecutive patients referred for cardiac risk evaluation prior to potential kidney transplantation were evaluated. All patients attempted ESE before pharmacologic testing was considered. Treadmill ESE utilized BRUCE protocol to maximum capacity. THR was defined as >85% of the maximum predicted heart rate (220-age). Functional capacity was assessed by metabolic equivalents (METs) and the rate pressure product (RPP). Results Of 535 patients (349 male, age 56±11), 372(70%) reached THR. Mean METs were 10±3 with 531(99%) achieving ≥4 METs and 87% ≥7 METs. Mean RPP was 25 821±5820 bpm×mm Hg (83% achieving >20 000 bpm×mm Hg). On multivariate analysis, independent predictors of failure to reach THR were rate-control medication and diabetes; failure to reach 7 METs: females, diabetics, age≥65, and previous cardiac disease; failure to reach RPP>20 000: rate-control medication. There were 97% of ESE completed to physiologic endpoints. Conclusion In unselected potential renal transplant candidates, cardiac assessment by ESE is well tolerated, with 9-in-10 exercising to satisfactory functional capacity. ESE should be considered a feasible alternative to pharmacologic testing in this population.

BACKGROUND: Preinvasive risk stratification is recommended in patients suspected of coronary artery disease (CAD). Stress echocardiography (SE), myocardial perfusion scintigraphy (MPS), and exercise test are the dominant methods of choice. Vasodilator SE is fast and induces only minor increase in heart rate. The diagnostic value of the absolute stress-rest difference in endocardial global longitudinal strain (ΔeGLS) and wall motion (ΔWMI) from adenosine SE was compared to summed stress score (SSS) from MPS and Duke treadmill score (DTS) from exercise test, using quantitative invasive coronary angiography (ICA) as the reference.METHODS AND RESULTS: A total of 128 patients (69% male, 62.7 (8.8) years) underwent adenosine SE, MPS, exercise test, and ICA. Forty-five patients (35%) had CAD. All stress outcomes differed significantly (PCONCLUSION: Alterations in eGLS and wall motion during adenosine SE were closely associated with the presence of CAD and the combined sensitivity similar to that of MPS. If nuclear medical facilities are unavailable or radiation issues important, vasodilator ΔeGLS could be an acceptable alternative for patients unable to exercise.

Background Diastolic dysfunction (DD) is associated with exercise intolerance. To evaluate mechanisms of exercise intolerance in patients with DD, we performed bicycle stress echocardiography. Method and Results Doppler measurements were performed at baseline, during exercise and recovery in 26 patients (58 ± 11 years) with DD and normal left ventricular ejection fraction and 6 normal controls (53 ± 5 years). Compared to controls, patients achieved similar target heart rates but lower METs (5.5 ± 2 vs. 9.8 ± 3, P < 0.01) and a higher peak pulmonary artery pressure (PAP) at peak exercise (50 ± 13 vs. 32 ± 7 mmHg, P < 0.01) despite similar PAP at rest and similar mean blood pressure at peak exercise (110.4 ± 18.0 vs. 106.9 ± 11.4 mmHg, P = NS). In patients versus controls, mitral E/E' was similar at baseline (10 ± 3 vs. 8 ± 1.3, P = NS) but higher at recovery (11 ± 2 vs. 7 ± 2, P < 0.05), % mitral filling time was shorter at baseline, onset, and peak exercise, whereas % LV and RV ejection time was similar to controls throughout exercise. Compared to controls, lateral mitral annular S' (11.8 ± 2.5 cm/sec vs. 14.9 ± 1.9 cm/sec, P < 0.02) and tricuspid annular S' (14.8 ± 4.1 cm/sec vs. 19.4 ± 4.0 cm/sec, P < 0.05) were lower at peak exercise in patients. Conclusion Diastolic filling time is reduced at rest and stress while LV ejection time increases normally during exercise in DD. There is a reduced systolic reserve in LV and RV during exercise in DD. These mechanisms contribute to exercise intolerance and elevation of left atrial and PAP in patients with DD.

Aim Left ventricular (LV) transient ischemic dilatation (TID) is not clear how it relates to inducible myocardial ischemia during stress echocardiography (SE). Methods and Results Eighty-eight SEs were examined from the site certification phase of the ISCHEMIA Trial. LV end-diastolic volume (EDV) and end-systolic volume (ESV) were measured at rest and peak stages and the percent change calculated. Moderate or greater ischemia was defined as ≥3 segments with stress-induced severe hypokinesis or akinesis. Optimum cut points in stress-induced percent EDV and ESV change that identified moderate or greater myocardial ischemia were analyzed. Analysis from percentage distribution identified a > 13% LV volume increase in EDV or a > 9% LV volume increase in ESV as the optimum cutoff points for moderate or greater ischemia. Using these definitions for TID, there were 27 (31%) with TIDESV and 12 (14%) with TIDEDV. By logistic regression analysis and receiver operating characteristic curves, the percent change in ESV had a stronger association with moderate or greater myocardial ischemia than that of EDV change. Compared to those without TIDESV, cases with TIDESV had larger extent of inducible wall-motion abnormalities, lower peak stress LVEF, and higher likelihood of moderate or grater ischemia. For moderate or greater myocardial ischemia detection, TIDESV had a sensitivity of 46%, specificity of 83%, positive predictive value of 70%, and negative predictive value of 64%. Conclusion Transient ischemic dilatation by SE is a marker of extensive myocardial ischemia and can be used as an additional marker of higher risk.

Objectives: The aim of this study was to evaluate the hemodynamic performance of a sutureless bioprosthesis under high workload at mid‐term follow‐up. Methods: Thirty‐two patients who underwent isolated aortic valve replacement with a Perceval sutureless bioprosthesis with a minimum follow‐up of 1 year were enrolled in this study. S size prosthesis was deployed in 10 patients (31.3%), M size in 9 (28.1%), L size in 8 (25%) and XL size in 5 (15.6%). Effective orifice area (EOA), EOA index (EOAi), and transvalvular gradients were assessed at rest and during dobutamine stress echocardiography (DSE) a median of 19.5 months after surgery. Results: Dobutamine stress echocardiography (DSE) significantly increased heart rate, stroke volume, ejection fraction, and transvalvular gradients (peak gradient, 24.0 ± 7.6 vs 38.7 ± 13.6 mm Hg, P < .001; mean gradient, 12.6 ± 4.2 vs 19.8 ± 8.3, P < .001). When compared to baseline, estimated valve areas significantly increased at follow‐up (EOA, 1.48 ± 0.46 vs 2.06 ± 0.67, P < .001; EOAi, 0.84 ± 0.26 vs 1.17 ± 0.37, P < .001). Mean percentage increase in EOAi was 40.3% ± 28.0%. S size prostheses had the highest increase in EOA1, but the difference was not significant (S 46.0% ± 27.5% vs M 45.4% ± 34.5% vs L 32.7% ± 26.4% vs XL 32.1% ± 20.5%, P = .66). Severe patient‐prosthesis mismatch (EOAi ≤ 0.65 cm²/m²) was present at rest in 8 patients (25%), but only in one patient (3.1%) during DSE. Conclusions: The Perceval sutureless bioprosthesis demonstrated good hemodynamics at rest and under high workload. The significant increase in EOAi during DSE suggests the potential advantages of Perceval sutureless bioprostheses in case of small aortic annulus or when patient‐prosthesis mismatch is anticipated.

Background We evaluated the diagnostic value of resting echocardiographic findings including total heart calcification (THC) score in combination with dobutamine stress echocardiography (DSE) for detection of myocardial ischemia. Methods Altogether, 110 patients with suspected angina pectoris underwent resting echocardiography and DSE. On the basis of resting echocardiography, we determined the THC score, left anterior descending artery diastole-to-systole velocity ratio (LAD-DSVR), and positive myocardial velocity during isovolumic relaxation phase (VIVR) detected by color-coded tissue Doppler imaging. Myocardial ischemia was diagnosed by a 25% or greater reduction in the internal diameter of major coronary vessels with impaired fractional flow reserve (FFR ≤0.80). Results DSE had excellent specificity (89%) but modest sensitivity (52%) for wall-motion abnormality (WMA) analysis. Multivariate analysis showed that THC score ≥2 (odds ratio and 95% confidence interval: 4.49 [2.29–10.6]; P = 0.018), LAD-DSVR ≤1.5 (6.43 [1.39–20.3], P = 0.019), and duration of positive VIVR ≥71 msec (7.93 [3.72–12.1]; P

Summary Cardiac surgery patients are urged to resume light physical activity on the first postoperative day, even if cardiac function may not have recovered fully after the operation. To elucidate the postoperative recovery process, we examined cardiac surgery patients with exercise echocardiography before and on the first day after the operation. Patients undergoing on-pump coronary artery bypass grafting were examined with echocardiography during semirecumbent cycle exercise. Patients exercised for five minutes at 10 W intensity and five minutes at 30 W intensity in bed with the upper body supported to approximately 30°. Fourteen patients were studied. Mitral annulus excursion and pulsed wave Doppler from the left ventricular outflow tract indicated postoperatively reduced cardiac stroke volume. Early diastolic tissue velocities of the mitral annulus were reduced, and early trans-mitral flow velocity was increased. The ratio between early mitral flow velocity and early diastolic mitral tissue velocity was increased postoperatively, indicating impaired left ventricular relaxation and increased left atrial pressure. Postoperative systolic mitral annulus tissue velocities were similar to preoperative velocities, indicating maintained systolic function. Postoperative exercise was associated with improvements in myocardial function indices and cardiac stroke volume similar to preoperative improvements. There were no signs of further deterioration in myocardial function during 30 W exercise. In summary, reduced left ventricular diastolic function after surgery resulted in reduced cardiac stroke volume, increased left atrial pressure and a higher rate of perceived exertion on the first postoperative day.

Background Three-dimensional (3D) stress echocardiography is a relatively new technique offering the potential to acquire images of the entire left ventricle from 1 or 2 transducer positions in a time-efficient manner. Relative to two-dimensional (2D) imaging, the ability to quickly acquire full volume images during peak stress with 3D echocardiography can eliminate left ventricular (LV) foreshortening while reducing inter-operator variability. Our objectives were to (1) determine the practicality of a novel integrated 2D/3D stress protocol in incorporating 3D imaging into a standard 2D stress echocardiogram and (2) to determine whether the quality of imaging using the novel 2D/3D protocol was sufficient for interpretation. Methods Twenty-five patients referred for stress echocardiography underwent an integrated 2D/3D image acquisition protocol. LV segments were scored from 0 (absent or no clear endocardial visualization) to 3 (excellent/full visualization of endocardial border) with each modality. 2D segment quality scoring was compared with 3D. An integrated score was compared with either 2D or 3D imaging alone. Results Two-dimensional and 3D imaging were optimal for differing segments and the integrated protocol was superior to either modality alone. 3D imaging was superior in visualizing the anterior and anterolateral region of the base segments, compared to 2D imaging. 3D imaging was less useful for the base, the mid-inferior, and the inferoseptal segments, thus emphasizing the need to retain 2D imaging in stress echocardiography at this time. Conclusion The integrated 2D/3D protocol approach to stress echocardiography is technically feasible and maximizes image quality of dobutamine stress echocardiography, improving patient assessment.

Background Dobutamine stress echocardiography (DSE) is commonly used to risk stratify patients in the cardiac evaluation prior to orthotopic liver transplantation (OLT). Data remain limited regarding the accuracy to predict obstructive coronary artery disease (CAD) using this approach. Hypothesis We hypothesize that DSE may have limitations in the investigation of underlying CAD in patients with end-stage liver disease. Methods A retrospective chart review of all patients who underwent OLT at Mayo Clinic in Florida between 1998 and 2010 was performed. Sixty-six underwent invasive coronary angiography (ICA) within 1 year of DSE and were included in our study. Based on DSE results, patients were stratified into 1 of 3 groups: nonischemic, ischemic, and indeterminate. The relationship between DSE, ICA, and death from all cause and cardiac-related cause with a minimum 3-year follow-up period were analyzed. Results A total of 66 patients were included in our cohort. There was no difference in age, gender, severity of liver disease, and echocardiographic findings among the groups. Forty-three percent of patients (n = 12) with an abnormal result on DSE were found to have moderate or severe obstructive CAD on cardiac catheterization, whereas 49% of patients (n = 17) with a normal finding on DSE had moderate or severe CAD. Of 5 patients who died from a documented cardiac etiology, 3 had normal stress test results, 1 had abnormal findings, and 1 had an indeterminate DSE result. When compared with ICA, our study demonstrated that DSE has a sensitivity of 41.4% (95% confidence interval [CI]: 0.24-0.61), specificity of 47.1% (95% CI: 0.30-0.65), positive predictive value of 40.0% (95% CI: 0.23-0.59), and negative predictive value of 48.0% (95% CI: 0.31-0.66) in identification of underlying CAD. Conclusions Although widely used, DSE may not always accurately reflect the severity of obstructive CAD in patients undergoing OLT.

Background: Previous studies suggest that microvascular abnormalities may contribute to the pathogenesis of Chagas’ heart disease. Coronary flow reserve (CFR) expressed by the maximum achievable flow relative to baseline flow in the coronary microcirculation, may be useful in identifying patients who may be developing cardiac manifestations of the disease. This study aims to assess the CFR in patients with indeterminate form of Chagas’ disease, and also to identify the determinants of CFR. Methods: Sixty-four asymptomatic patients (37% male; age 49.9 11.5 years) with normal cardiovascular exams classified as in indeterminate form of Chagas’ disease underwent transthoracic dipyridamole (0.84 mg/kg in 6 min) stress echocardiography, and were compared with a control group of healthy patients. Coronary flow reserve was assessed on left anterior descending artery using pulsed Doppler as the ratio of maximal peak vasodilation (dipyridamole) to rest diastolic flow velocity. A treadmill exercise test was performed to rule out ischemia. Results: All patients had good functional capacity assessed by exercise testing with peak oxygen consumption (VO2 )o f 28 11 mL/kg per minute, similar to the controls. There were no differences in the echocardiographic parameters of diastolic and systolic left ventricular function and right ventricular function between the patients and controls. Coronary flow reserve was significantly lower in Chagas’ disease patients than those in healthy individuals (1.9 0.4 vs. 2.6 0.5; P < 0.001). Several factors were correlated with the CFR, including age, ejection fraction, left ventricular diastolic function, heart rate recovery, and the presence of Chagas’ disease. In a multivariate analysis, age and positive serology for Chagas’ disease were independent factors associated with the CFR. Conclusions: Coronary flow reserve was impaired in Chagas’ disease patients in the indeterminate form compared with healthy individuals with similar clinical features. Among all variables tested, age and positive serology for Chagas’ disease were independent factors associated with the CFR. (Echocardiography 2013;00:1–7)

Background: We and others have shown previously that left ventricular (LV) contractile reserve assessed quantitatively by high-dose dobutamine stress-echocardiography (DSE) has prognostic implications in patients with dilated cardiomyopathy. Purpose: To assess the feasibility of semi-quantitative assessment of LV contractile reserve by differently skilled operators in patients with dilated cardiomyopathy. Methods: High-dose DSE was performed in 63 consecutive patients, mean age 50 ± 10 years and ejection fraction (EF) 19 ± 8%. LVEF was calculated 1) using Simpson's biplane formula, and 2) semi-quantitatively (5% increments) by novice and experienced echocardiographers, and by a DSE expert. Patients were considered to have preserved LV contractile reserve if LVEF dobutamine-induced change was ≥5%. Results: Twenty-seven (45.8%) patients died during the 5-year follow-up. The feasibility of the assessment was 89%, 94%, and 98% for novice and experienced readers and DSE expert, respectively. Kaplan-Meier analysis showed that LV contractile reserve assessed semi-quantitatively by DSE expert and experienced reader achieved the best prognostic separation (log rank 19.63 and 18.99, respectively, p < 0.001 for both), followed by quantitative assessment (log rank 9.76, p = 0.0018) and assessment by novice reader (log rank 8.76, p = 0.012). Areas under the curves were similar for quantitative and semi-quantitative assessment of LV contractile reserve. Conclusions: Our data indicate that semi-quantitative assessment of LV contractile reserve is feasible by differently skilled operators. © 2012 Wiley Periodicals, Inc. J Clin Ultrasound 40:405–409, 2012

Objectives. To evaluate and compare the diagnostic accuracy of semi-quantitative and quantitative real-time myocardial contrast echocardiography (RT-MCE) with low-dose dobutamine stress echocardiography (LD-DSE) in detecting viable myocardium. Methods. Thirty in-patients with coronary artery disease and regional wall motion abnormalities underwent RT-MCE without and with LD-DSE. Percutaneous coronary intervention was performed within 1 week after RT-MCE in all patients. Myocardial perfusion was evaluated from A, β, and A × β indices from microbubble replenishment curves. The motion of each myocardium segment was observed by routine echocardiography 1, 3, and 6 months after percutaneous coronary intervention and its improvement over time was the criterion of viable myocardium. Results. RT-MCE sensitivity and specificity for the assessment of viable myocardium were 71.7% and 69.8%, rising to 81.3% and 76.7% (p < 0.05) when combined with LD-DSE. Using quantitative RT-MCE with cutoff values of A, β, and A × β, the sensitivity and specificity were 75.6%, 78.8%, 82.1%, and 82.4%, 77.9%, 78.6%, respectively. When combined with LD-DSE, the sensitivity and specificity were 86.0%, 83.2%; 88.9% and 84.1%; 89.6%, 79.9%, respectively. Conclusions. Quantitative RT-MCE analysis yielded higher sensitivity and specificity than semi-quantitative RT-MCE with or without LD-DSE for the detection of viable myocardium. © 2012 Wiley Periodicals, Inc. J Clin Ultrasound, 2012

Aim The identification of responders remains challenging in cardiac resynchronization therapy (CRT). In this study we assessed the role of myocardial contractile reserve (CR) during dobutamine stress echocardiography (DSE) and resting severe diastolic dysfunction for identifying responders to CRT. Methods and results Sixty-nine patients (59% with ischaemic aetiology, ejection fraction: 26 ± 5%) referred for CRT underwent high-dose DSE. Contractile reserve was evaluated using a pressure–volume relationship, defined as systolic cuff pressure/end-systolic volume index difference between rest and peak DSE. We defined severe diastolic dysfunction as the presence of restrictive patterns and/or E/E′ > 15. We divided the patients into four groups as follows: presence (CR+) or absence (CR−) of myocardial CR and presence (Diast+) or absence (Diast−) of severe diastolic dysfunction. Patients with CR+ Diast− showed higher percentage of clinical responders (91 vs. 46%, P= 0.002) and echocardiographic responders (90 vs. 25%, P= 0.001) to CRT, compared with patients with CR− Diast+. By log-rank analysis, event-free survival was significantly poorer in patients with CR− Diast+ (log rank = 18.36, P= 0.0004). Conclusion Heart failure patients with severe diastolic dysfunction and absence of myocardial CR during DSE had a poorer clinical and echocardiographic response to CRT. The associated evaluations of diastolic function and CR had an additive value in the identification of responders to CRT.

Purpose. To determine the coronary hemodynamic characteristics of acute hibernating myocardium (AHM), evaluate the changes in coronary hemodynamics during dobutamine infusion, and investigate the mechanisms by which dobutamine stress echocardiography (DSE) detects AHM. Methods. The porcine model of acute hibernating myocardium was created in 10 animals, all of which underwent DSE with doses of 0–40 μg/kg/min. Myocardial segments abnormality was used as a DSE criterion for evaluating AHM. An intracoronary Doppler guidewire was used to measure the coronary hemodynamics; electrocardiography and systemic hemodynamics were recorded simultaneously. The ischemic regions of myocardium were reperfused, and all variables were recorded. Finally, the animals were euthanized and pathologic changes in the heart tissue were documented. Results. There was no myocardium necrosis. There were 55 myocardial segments with abnormal DSE responses after stenosis, among which 41 segments were judged as AHM because of a biphasic response. Average peak velocity (APV) and coronary flow velocity reserve were improved during DSE. Coronary and systemic hemodynamics were increased during dobutamine infusion. There were significant differences for APV at all evaluated doses and for heart rate blood pressure product at higher doses. The difference between APV resting values and the values for peak dosage (ΔAPV) correlated with the amount of AHM during DSE. Coronary volume blood flow and coronary flow velocity reserve decreased after stenosis. Conclusions. ΔAPV may reflect the number of hibernating segments. The relative imbalance between blood supply and oxygen consumption in regional myocardium may be one of the mechanisms by which DSE detects AHM. © 2011 Wiley Periodicals, Inc. J Clin Ultrasound, 2011

Aims Previous small open label studies have shown that the advanced glycation end-product (AGE) breaker alagebrium may improve cardiac function in patients with chronic heart failure (HF). We report the design, methods and baseline characteristics of a double-blind, placebo-controlled, randomized trial evaluating the efficacy and safety of alagebrium (BENEFICIAL) in patients with HF and a left ventricular ejection fraction (LVEF) ≤ 0.45. Methods and results Patients with NYHA II–IV stable HF for at least 3 months were eligible for this study. One hundred and two patients were included in the study and randomized to either 200 mg alagebrium twice daily or placebo for a period of 36 weeks. The mean age of patients was 60 ± 11 years, 78% were male, and 17% were diabetic. Mean peak VO2 was 21.7 ± 5.9 mL/min/kg, mean LVEF was 0.32 ± 0.09. Diastolic function was worse (mean early tissue diastolic velocity (E′) 4.6 ± 1.7 vs. 6.1 ± 2.0 cm/s; P < 0.001) in patients with LVEF ≤ 0.35 compared to patients with LVEF between 0.35 and 0.45. Conclusion The BENEFICIAL study is a proof-of-concept study that will provide new data on the efficacy and safety of the AGE crosslink breaker alagebrium in systolic HF patients. EudraCT number of this trial is NCT00516646.

Aims To evaluate right-ventricular (RV) function during stress echocardiography (SE) and to assess its relationship with exercise capacity in heart failure (HF) patients. Methods and results We included 88 patients aged 60.9 ± 11.2 years with a mean LVEF of 27.2 ± 9.5%. The following RV parameters were measured at baseline and peak exercise during semi-supine SE: velocity (IVV) and acceleration during isovolumic contraction (IVA), S′, E′, A′, and ratio of early diastolic tricuspid velocity to E′ (E/E′) and longitudinal strain and strain rate. Patients were stratified into two groups according to their VO2peak values: group 1 (n = 35) with VO2peak

Aims Cardiac death remains the principal cause of mortality in β-thalassemia major (β-TM). Echocardiography may provide additional information, incremental to haematological profile, both for guiding chelation therapy and to assess prognosis. Methods and results Between 1993 and 1995, 36 patients with β-TM and normal cardiac function and 25 normal volunteers underwent evaluation using resting and dobutamine stress echocardiography (DSE). Dobutamine stress echocardiography was performed at baseline and repeated after 2 years. The primary endpoint was cardiac mortality. During a 12-year observation period, seven patients (19%) died from heart failure. All seven deaths occurred among the cohort of 12 patients with median ferritin concentrations ≥2800 ng/mg. In addition, a resting left ventricular ejection fraction (LVEF), 60% was also associated with increased late mortality. In multivariate analysis, increased serum ferritin levels and reduced LVEF but not DSE or other haematological variables were independent survival determinants. Conclusion Resting LVEF provides prognostic information that is additional to ferritin levels among patients with β-TM.

Timing of surgery in aortic regurgitation (AR) is important. Exercise testing is recommended upon uncertainty about functional limitations but reports on cardiopulmonary exercise testing (CPET) in populations with pure chronic AR are scarce.Twenty-eight patients referred for surgery because of chronic AR (13 in NYHA I, 10 in NYHA II and five in NYHA III) were tested by CPET pre- and 6 months postoperatively. Echocardiography, with measurement of left ventricular ejection fraction (LVEF), diameters (LVED, LVES) and volumes (LVEDV, LVESV) was also performed.The patients had normal LVEF pre- and postoperatively. LV diameters and volumes diminished significantly postoperatively (LVED from 67 to 57, LVES from 49 to 41 mm; P0.001). The majority of the patients had a 'low' physical work capacity, none of them performed better than 'average' according to Astrand's classification preoperatively and there was no significant postoperative improvement. The mean peak oxygen uptake (VO(2peak)) was 25 ml kg(-1) min(-1) both pre- and postoperatively, and six of the 28 patients had a VO(2peak) of less than 20 ml kg(-1) min(-1). VO(2peak) was not significantly related to NYHA class.LVEF, diameters and volumes at rest did not fulfil the criteria for surgery in most of our AR patients, of whom 46% were asymptomatic. However, many had a remarkably low work capacity, which was neither improved 6 months postoperatively nor correlated to echocardiographic LV dimensions. CPET predicted the postoperative work capacity and may, therefore, be a useful complement for timing of surgery in patients with chronic AR.

The purpose of this study was to characterize the functional consequences of the 393T>C polymorphism of the GNAS1 gene in vivo. PCR-RFLP assays were used to identify GNAS1 and beta 1-adrenoceptor genotypes. The heart rate (HR), blood pressure, left ventricular fractional shortening (LVFS), and left ventricular ejection fraction (LVEF) were determined in different genotypes through a modified dobutamine stress echocardiography protocol. Our results showed that individuals with homozygous or heterozygous C393 had an increased cardiovascular agonistic response to dobutamine, and the increases from baseline in LVFS at the 3 dosage levels of dobutamine were 19.3% +/- 1.0% versus 32.0% +/- 2.9%, 36.7% +/- 3.1% versus 41.3% +/- 4.1%, and 51.7% +/- 3.3% versus 58.7% +/- 2.6% in T393 homozygotes and C393 homozygotes or heterozygotes, respectively (P = .026). Significant differences were also found between these 2 groups with the increases from baseline in LVEF (P = .007) and SBP (P = .048). In addition, there were significant differences in the increases from atopine in LVFS (P = .011), LVEF (P = .004), and SBP (P = .046) between the T393 homozygotes and C393 homozygotes or heterozygotes. The change of LVEF in C393 homozygous was higher than that in T393 homozygous at the dose of 40 microg/kg/min (28.9% +/- 4.0% vs 36.4% +/- 2.1%; 95% CI, 18.8%-38.9%; P = .046). These data suggested that the 393T>C polymorphism of GNAS1 was functionally relevant in vivo.

Background B-type natriuretic peptide (BNP) is predictive of inducible ischemia in patients with coronary heart disease (CHD). Whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) has a comparable strength of association with ischemia is uncertain. Hypothesis Resting NT-proBNP levels are associated with inducible ischemia in patients with stable CHD. Methods We performed a cross-sectional study of 901 outpatients with stable CHD. NT-proBNP was measured in all patients prior to exercise treadmill testing and stress echocardiography. In addition, plasma BNP was measured in a subset of 355 participants. Logistic regression was used to examine the association of NT-proBNP and BNP quartiles with inducible ischemia. Results Inducible ischemia was found in 216 (24%) patients. The proportion with inducible ischemia ranged from 42% (95/225) in the highest quartile of NT-proBNP levels (>410 pg/ml) to 9% (21/226) in the lowest quartile (0–72 pg/ml). The highest quartile had a 7-fold greater odds of inducible ischemia than the lowest quartile (odds ratio [OR]: 7.1, 95% confidence interval [CI]: 4.2–12; P < 0.0001). This association remained robust after adjustment for traditional cardiovascular risk factors, left ventricular ejection fraction, and diastolic dysfunction (OR: 3.6, 95% CI: 1.4–9.1; P = 0.009). In the subgroup with measurements of both NT-proBNP and BNP, both natriuretic peptides were predictive of ischemia. The multivariable-adjusted c-statistics for inducible ischemia were 0.71 for NT-proBNP and 0.62 for BNP (entered as continuous variables). Conclusions Resting NT-proBNP levels are independently associated with inducible ischemia in outpatients with stable CHD. Baseline elevations of natriuretic peptide may indicate subclinical inducible ischemia in high risk patients with CHD. Copyright © 2009 Wiley Periodicals, Inc.