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Background: In patients with low-gradient aortic stenosis (AS) and low transvalvular flow, dobutamine stress echocardiography (DSE) is recommended to determine AS severity, whereas the degree of aortic valve calcification (AVC) supposedly correlates with AS severity according to current European and American guidelines., Objectives: The purpose of this study was to assess the relationship between AVC and AS severity as determined using echocardiography and DSE in patients with aortic valve area <1 cm 2 and peak aortic valve velocity <4.0 m/s., Methods: All patients underwent DSE to determine AS severity and multislice computed tomography to quantify AVC. Receiver-operating characteristics curve analysis was used to assess the diagnostic value of AVC for AS severity grading as determined using echocardiography and DSE in men and women., Results: A total of 214 patients were included. Median age was 78 years (25th-75th percentile: 71-84 years) and 25% were women. Left ventricular ejection fraction was reduced (<50%) in 197 (92.1%) patients. Severe AS was diagnosed in 106 patients (49.5%). Moderate AS was diagnosed in 108 patients (50.5%; in 77 based on resting transthoracic echocardiography, in 31 confirmed using DSE). AVC score was high (≥2,000 for men or ≥1,200 for women) in 47 (44.3%) patients with severe AS and in 47 (43.5%) patients with moderate AS. AVC sensitivity was 44.3%, specificity was 56.5%, and positive and negative predictive values for severe AS were 50.0% and 50.8%, respectively. Area under the receiver-operating characteristics curve was 0.508 for men and 0.524 for women., Conclusions: Multi-slice computed tomography-derived AVC scores showed poor discrimination between grades of AS severity using DSE and cannot replace DSE in the diagnostic work-up of low-gradient severe AS., Competing Interests: Funding Support and Author Disclosures Dr Van Mieghem has received grant support/research contracts from Abbott Vascular, Boston Scientific, Medtronic, Edwards Lifesciences, Daiichy Sankyo, AstraZeneca, and PulseCath BV; and has received consulting/speaker fees from Abbot Vascular, Boston Scientific Corporation, Medtronic, Daiichy Sankyo, PulseCath BV, JenaValve, and Amgen. Dr Mehran has received grant support/research contracts from Abbott, Abiomed, Alleviant Medical, Amgen, AM-Pharma, Arena Pharmaceuticals, AstraZeneca, Atricure Inc, Biosensors, Biotronik, Boston Scientific, Bristol-Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, Cytsorbents, Daiichy-Sankyo, Element Science, Faraday, Humacyte, Idorsia Pharmaceuticals, Janssen Pharmaceuticals, Magenta, MedAlliance, Mediasphere, Medtelligence, Medtronic, MJH Healthcare, Novartis, OrbusNeich, Penumbra, PhaseBio, Philips, Pi-Cardia, PLx Pharma, Protembis, RenalPro, RM Global, Shockwave Medical, Vivasure, and Zoll; has received consulting/speaker fees from AstraZeneca, E.R. Squibb and Sons LLC, Esperion Science/Innovativa Biopharma, Ionis Pharmaceuticals, IQVIA, J-Calc, McVeigh Global, Novartis, Novo Nordisk, Overcome, Primer Healthcare of New Jersey, Radcliffe, SL Solutions, TARSUS Cardiology, Vectura, and WebMD; and she has equity in Applied Therapeutics, Elixir, and STEL. Dr Mehran’s spouse has equity in ControlRad. Dr Kodali has received grant support/research contracts from Admedus, Dura Biotech, Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve; has received consulting/speaker fees from Admedus, Dura Biotech, TriCares, X-Dot, Tioga, Helix Valve Repair, and Moray Medical; and has equity in Dura Biotech, Microinterventional Devices, Thubrika Aortic Valve Inc, Supira, Admedus, Triflo, and Adona. Dr Hahn has received consulting/speaker fees from Abbott Structural, Medtronic, Edwards Lifesciences, Boston Scientific, Baylis Medical, Navigate, Philips Healthcare, Siemens Healthcare, and 3mensio; and has equity in Navigate. Dr Bax has received grant support/research contracts from Biotronic, Boston Scientific, Medtronic, Bayer AG, and Edwards Lifesciences; and has received consulting/speaker fees from Abbott Vascular and Edwards Lifesciences. Drs Veulemans and Zeus have received consulting fees, travel expenses, or study honoraria from Medtronic, Edwards Lifesciences, and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Exercise-based cardiac rehabilitation is recognized to improve quality of life in heart failure patients. However, the effects on the cardiac function are understudied. The main objective was to assess the impact of a 4-week cardiac rehabilitation program on cardiopulmonary exercise testing (CPET) combined with simultaneous echocardiography parameters in chronic heart failure (CHF) patients. The secondary aim was to investigate patients' responses to training., Methods: Forty-one CHF patients with reduced ejection fraction (29.3 ± 0.1%) underwent CPET and stress echocardiography before and after a 4-week of exercise-training program. Blood parameters, echocardiography and cardiopulmonary parameters were assessed before and after training. Potential echocardiography derived predictive parameters like left and right contractile reserves, left ventricle elastance, end systolic volume and right ventricle S wave response to exercise were also assessed., Results: The training program increased the peak oxygen consumption (VO 2 ) (P < 0.001), the peak systolic blood pressure, the left ventricular outflow tract velocity time integral (P < 0.05) and the circulatory (P < 0.001) and ventilatory (P < 0.01) powers. It also decreased the VE/VCO 2 slope (P < 0.001). As the median value of peak VO 2 gain was 17%, patients above this value were considered as responders and patients below as non-responders to training. The responders presented a higher left ventricle contractile reserve compared to non-responder patients. The peak left ventricle elastance and peak right ventricle S wave response tended to be higher in responders., Conclusion: Combination of CPET and stress echocardiography may contribute to establish the disease severity stratification and to predict response to training in CHF patients with reduced ejection fraction., Competing Interests: Declaration of Competing Interest None to declare for all authors., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The reduction in exercise capacity after mitral valve repair (MVr) for severe degenerative mitral regurgitation is an unsolved issue. This study aimed to evaluate hemodynamics after MVr using a partial semirigid band during exercise stress echocardiography and to identify predictive factors for achieving better exercise capacity after MVr., Methods: We retrospectively analyzed 48 patients using exercise stress echocardiography within 5 years of having undergone MVr using a partial semirigid band between 2013 and 2019. Values of maximal workload were converted into numbers of metabolic equivalents (METs) achieved for each patient. Age and sex expected METs (eMETs) were obtained, and percent eMETs (%eMETs [achieved METs / eMETs × 100]) were calculated. Multivariable linear regression analysis was used to identify the determinants of %eMETs., Results: Only one third of patients achieved eMETs. Significant determinants of %eMETs were age at exercise stress echocardiography (β coefficient 0.64; 95% confidence interval, 0.31 to 0.96; P < .001), female sex (β coefficient 16.9; 95% confidence interval, 8.58 to 25.17; P < .001), and larger indexed device size (device size/body surface area; β coefficient 4.10; 95% confidence interval, 1.74 to 6.46; P = .001). Receiver-operating characteristic curve analysis revealed that a cutoff value of 19.5 mm/m 2 or greater indexed device size was optimal for achieving %eMETs greater than 100%, with a sensitivity and specificity of 87% and 79%, respectively., Conclusions: Patients with larger indexed device size achieved greater exercise capacity after MVr using a partial semirigid band. Preoperative evaluation to decide whether we can use an annuloplasty device larger than 19.5 mm/m 2 may be important for patients who intend to exercise with high intensity., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: We examined whether the early development of exercise-induced pulmonary hypertension (EIPH) and right ventricular dysfunction during exercise stress echocardiography (ESE) may predict clinical deterioration in so-called "asymptomatic" patients with primary, at least moderate mitral regurgitation (MR)., Methods: 79 consecutive patients underwent a symptom-limited, graded ESE protocol on semi-supine bicycle at the beginning of the study. During the test, we assessed symptom development, test duration, and the following echocardiographic parameters: MR severity, maximum velocity of the tricuspid regurgitation jet (TR Vmax), pulmonary artery systolic pressure (PASP), and tricuspid annulus systolic excursion (TAPSE). All patients were then followed-up for at least 12 months for clinical end-points (heart failure-related symptoms requiring pharmaceutical therapy, heart failure hospitalization, and/or mitral valve surgery in case of refractory symptoms)., Results: After 16 ± 4 months of follow-up, 75 patients completed the study; 26 of them achieved any clinical end-point and were classified as 'high-risk', while the rest (49 patients) were assigned to the 'low-risk' group. High-risk group showed significantly higher exercise-induced TR Vmax and PASP levels at maximum workload of ESE than low-risk counterparts (p<0.001). Based on receiver operating characteristic analysis, the early (within the first two stages of ESE or up to 50 W) steep rise of calculated PASP ≥51 mmHg (TR Vmax ≥3.4 m/s) had a 92.3% sensitivity and 100% specificity to predict clinical deterioration within the following year. That cut-off value seemed superior predictor than peak value of PASP at the end of ESE. TAPSE levels during ESE did not add prognostic value in our sample., Conclusion: This is the first study demonstrating that the early development of EIPH has prognostic value in asymptomatic patients with primary at least moderate MR and may become a new valid determinant of mitral valve surgery. Additional larger prospective studies are needed to validate our findings., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Dobutamine stress echocardiography (DSE) is required to determine whether low-gradient aortic stenosis (AS) with a small aortic valve area (AVA) is truly severe. The purpose of the present study was to evaluate the usefulness of ejection dynamics parameters at resting echocardiography for predicting the result of DSE performed in patients with low-gradient AS., Methods: The results of resting echocardiography and DSE performed on 51 AS patients with low mean-gradient (<40 mmHg) and small indexed AVA (<0.60 cm 2 /m 2 ) were retrospectively reviewed. Acceleration time (AT) and the ratio of AT to ejection time (ET) were measured on the recorded images. True-severe AS was defined as that with indexed projected AVA < 0.60 cm 2 /m 2 ., Results: Twenty-six (51%) patients had true-severe AS, while 22 (43%) patients had preserved left ventricular ejection fraction (≥50%). Baseline indexed AVA and AT/ET were independently associated with indexed projected AVA at DSE. AT/ET was the only independent determinant of valve compliance. Indexed AVA ≤ 0.493 cm 2 /m 2 and AT/ET > 0.334 at baseline had sensitivities of 69% and 65% and specificities of 84% and 84%, respectively, for predicting true-severe AS. The presence of either indexed AVA ≤ 0.493 cm 2 /m 2 or AT/ET > 0.334 had a higher sensitivity (88%), and their co-occurrence had a higher specificity (100%)., Conclusions: Indexed projected AVA at DSE was predicted by AT/ET, which represented valve compliance, along with indexed AVA. The true severity of low-gradient AS can be screened using a combination of resting indexed AVA and AT/ET without performing DSE., (Copyright © 2020. Published by Elsevier Ltd.)

Functional classification of children and adults with repaired and unrepaired congenital heart disease is a challenge for clinicians, due to the heterogeneity of congenital heart disease. Functional studies may be complemented with a stress echocardiogram, which analyzes the hemodynamic behavior of surgical repair zones, residuals, and sequelae. The integration of the anatomical and functional classification criteria developed for congenital heart disease and the results of a stress echocardiogram can establish a more precise functional classification. Stress echocardiograms also provide early diagnosis of functional complications of the congenital heart, allowing timely management decisions. This paper reviews the most important aspects of stress echocardiograms in pediatric and adult congenital heart disease, seeking to spark cardiologists' interest in extending its applications in congenital heart disease., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: This study sought to assess the relationship between E/e' and exercise capacity in patients with chronic kidney disease (CKD) and evaluate its prognostic role., Background: Patients with CKD have diastolic dysfunction, reduced physical fitness, and elevated risk of cardiovascular disease., Methods: Patients with stage 3 and 4 CKD without previous cardiac disease underwent resting and exercise stress echocardiograms with assessment of exercise E/e'. Patients were compared to age-, sex-, and risk factor-matched control individuals and were followed annually for 5 years for cardiovascular death and major adverse cardiovascular event(s) (MACE). Exercise capacity was assessed as metabolic equivalents (METs), with reduced exercise capacity defined as METs of ≤7. Raised exercise E/e' was defined as >13., Results: A total of 156 patients with CKD (age 62.8 ± 10.6 years; male: 62%) were compared to 156 matched control individuals. Patients with CKD were more likely to be anemic (p < 0.01) and had increased left ventricular mass (p < 0.01), larger left atrial volumes (p < 0.01), and higher resting (p < 0.01) and exercise E/e' (p < 0.01). Patients with CKD achieved lower exercise METs (p < 0.01), and more patients with CKD had METs of ≤7 (p < 0.01). Receiver-operating characteristic curves showed exercise E/e' (area under the curve [AUC]: 0.89; 95% CI: 0.84 to 0.95; p < 0.01) as the strongest predictor of reduced exercise capacity in patients with CKD. Over a follow-up period of 41.4 months, a raised exercise E/e' of >13 was an independent predictor of cardiovascular death and MACE on unadjusted and adjusted hazard models., Conclusion: E/e' is a strong predictor of exercise capacity and METs achieved by patients with CKD. Exercise capacity was reduced in patients with CKD, presumably consequent to diastolic dysfunction. Elevated exercise E/e' in patients with CKD is an independent predictor of cardiovascular death and MACE., Competing Interests: Author Disclosures Dr. Kadappu is supported by an National Health and Medical Research Council Scholarship (GNT1018215). Dr. Gan is supported by a University of New South Wales University Postgraduate Award (UNSW3080080). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Dobutamine stress echocardiography (DSE) and coronary computed tomography angiography (CTA) can provide perioperative prognostic information in risk stratification of patients undergoing noncardiac surgery. This study directly compared the prognostic value of DSE and CTA in patients undergoing noncardiac surgery., Methods: Between 2014 and 2016, 215 patients with more than one clinical risk factor for perioperative cardiovascular (CV) events were enrolled prospectively. They received both DSE and CTA before noncardiac surgery. Perioperative clinical risk was classified according to the revised cardiac risk index (RCRI), DSE results were categorized as abnormal (inducible ischemia and/or nonviable infarction) or not. CTA results were assessed using the severity of stenosis, with significant stenosis being ≥50% of the luminal diameter). After the exclusion, a total of 206 patients remained. Perioperative CV events were defined as CV death, non-fatal myocardial infarction (MI), myocardial injury, pulmonary edema, non-fatal stroke, and systemic embolism within 30 days after surgery., Results: Twenty-four patients (12%) had perioperative cardiac events (1 cardiac death, 10 non-fatal MI, 8 myocardial injury, 11 pulmonary edema, 1 non-fatal stroke, and 1 pulmonary embolism). Following adjustment for baseline RCRI score, abnormal result on DSE (OR, 6.08, 95% CI, 2.41 to 15.31, P < 0.001), significant CAD on CTA (OR, 18.79; 95% CI, 5.24 to 67.42, P < 0.001), and high CACS (OR, 4.19; 95% CI, 1.39 to 12.60, P = 0.011) remained significant predictors of perioperative CV events., Conclusions: DSE and CTA are independent predictive factors of events in patients undergoing noncardiac surgery. Among them, assessment of significant CAD using CTA might show a higher prognostic value compared with DSE before noncardiac surgery., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02250963., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to assess the functional and prognostic correlates of B-lines during stress echocardiography (SE)., Background: B-profile detected by lung ultrasound (LUS) is a sign of pulmonary congestion during SE., Methods: The authors prospectively performed transthoracic echocardiography (TTE) and LUS in 2,145 patients referred for exercise (n = 1,012), vasodilator (n = 1,054), or dobutamine (n = 79) SE in 11 certified centers. B-lines were evaluated in a 4-site simplified scan (each site scored from 0: A-lines to 10: white lung for coalescing B-lines). During stress the following were also analyzed: stress-induced new regional wall motion abnormalities in 2 contiguous segments; reduced left ventricular contractile reserve (peak/rest based on force, ≤2.0 for exercise and dobutamine, ≤1.1 for vasodilators); and abnormal coronary flow velocity reserve ≤2.0, assessed by pulsed-wave Doppler sampling in left anterior descending coronary artery and abnormal heart rate reserve (peak/rest heart rate) ≤1.80 for exercise and dobutamine (≤1.22 for vasodilators). All patients completed follow-up., Results: According to B-lines at peak stress patients were divided into 4 different groups: group I, absence of stress B-lines (score: 0 to 1; n = 1,389; 64.7%); group II, mild B-lines (score: 2 to 4; n = 428; 20%); group III, moderate B-lines (score: 5 to 9; n = 209; 9.7%) and group IV, severe B-lines (score: ≥10; n = 119; 5.4%). During median follow-up of 15.2 months (interquartile range: 12 to 20 months) there were 38 deaths and 28 nonfatal myocardial infarctions in 64 patients. At multivariable analysis, severe stress B-lines (hazard ratio [HR]: 3.544; 95% confidence interval [CI]: 1.466 to 8.687; p = 0.006), abnormal heart rate reserve (HR: 2.276; 95% CI: 1.215 to 4.262; p = 0.010), abnormal coronary flow velocity reserve (HR: 2.178; 95% CI: 1.059 to 4.479; p = 0.034), and age (HR: 1.031; 95% CI: 1.002 to 1.062; p = 0.037) were independent predictors of death and nonfatal myocardial infarction., Conclusions: Severe stress B-lines predict death and nonfatal myocardial infarction. (Stress Echo 2020-The International Stress Echo Study [SE2020]; NCT03049995)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Myocardial bridge (MB) may cause angina in patients with no obstructive coronary artery disease (CAD). We previously reported a novel stress echocardiography (SE) pattern of focal septal buckling with apical sparing in the end-systolic to early-diastolic phase that is associated with the presence of an MB. We evaluated the diagnostic accuracy of this pattern, and prospectively validated our results., Methods: The retrospective cohort included 158 patients with angina who underwent both SE and coronary CT angiography (CCTA). The validation cohort included 37 patients who underwent CCTA in the emergency department for angina, and prospectively underwent SE. CCTA was used as a reference standard for the presence/absence of an MB, and also confirmed no obstructive CAD., Results: In the retrospective cohort, an MB was present in 107 (67.7%). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 91.6%, 70.6%, 86.7% and 80%, respectively. On logistic regression, focal septal buckling and Duke treadmill score were associated with an MB. In the validation cohort, an MB was present in 31 (84%). The sensitivity, specificity PPV and NPV were 90.3%, 83.3%, 96.5% and 62.5%, respectively. On logistic regression, focal septal buckling was associated with an MB., Conclusion: Presence of focal septal buckling with apical sparing on SE is an accurate predictor of an MB in patients with angina and no obstructive CAD. This pattern can reliably be used to screen patients who may benefit from advanced non-invasive/invasive testing for an MB as a cause of their angina., Competing Interests: Declaration of competing interest VSP: Research fellowship support; Gilead Sciences. JAT: Honoraria; Abbott Vascular, Boston Scientific, Medtronic, Terumo; Stocks/equity; Recor. Others nothing to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Pulmonary capillary stress failure is potentially involved in exercise-induced hypoxemia (ie, a significant fall in hemoglobin oxygen saturation [Spo 2 ]) during sea level exercise in endurance-trained athletes. It is unknown whether there are specific properties of pulmonary vascular function in athletes exhibiting oxygen desaturation., Methods: Ten endurance-trained athletes with exercise-induced hypoxemia (EIH), nine endurance-trained athletes with no exercise-induced hypoxemia (NEIH), and 10 untrained control subjects underwent an incremental exercise stress echocardiography coupled with lung diffusion capacity for carbon monoxide (Dlco) and lung diffusion capacity for nitric oxide (Dlno) testing. Functional adaptation of the pulmonary circulation was evaluated with measurements of mean pulmonary arterial pressure (mPAP), pulmonary capillary pressure, pulmonary vascular resistance (PVR), cardiac output (Qc), and pulmonary vascular distensibility (alpha) mathematically determined from the curvilinearity of the multi-point mPAP/Qc relation., Results: EIH athletes exhibited a lower exercise-induced PVR decrease compared with the untrained and NEIH groups (P < .001). EIH athletes showed higher maximal mPAP compared with NEIH athletes (45.4 ± 0.9 mm Hg vs 41.6 ± 0.9 mm Hg, respectively; P = .003); there was no difference between the NEIH and untrained subjects. Alpha was lower in the EIH group compared with the NEIH group (P < .05). Maximal mPAP, Pcap, and alpha were correlated with the fall of Spo 2 during exercise (P < .01, P < .01, and P < .05). Dlno and Dlco increased with exercise in all groups, with no differences between groups. Dlno/Qc was correlated to the exercise-induced Spo 2 changes (P < .05)., Conclusions: EIH athletes exhibit higher maximal pulmonary vascular pressures, lower vascular distensibility, or exercise-induced changes in PVR compared with NEIH subjects, in keeping with pulmonary capillary stress failure or intrapulmonary shunting hypotheses., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Due to a marked temporal decline in inducible myocardial ischemia over recent decades, most diagnostic patients now referred for cardiac stress testing have nonischemic studies. Among nonischemic patients, however, long-term risk is heterogeneous and highly influenced by a variety of clinical parameters. Herein, we review 8 factors that can govern long-term clinical risk: coronary risk factor burden; patient symptoms; exercise capacity and exercise test responses; the need for pharmacologic stress testing; autonomic function; musculoskeletal status; subclinical atherosclerosis; and psychosocial risk. To capture the clinical benefit provided by both assessing myocardial ischemia and these additional parameters, the authors propose that a cardiac stress tests report have an additional component beyond statements as to the likelihood of obstructive coronary artery disease and/or magnitude of ischemia. This added component could be a comment section designed to make referring physicians aware of aspects of long-term risk that may influence clinical management and potentially lead to changes in the intensity of risk factor management, frequency of follow-up, need for further testing, or other management decisions. In this manner, the increasingly frequent normal stress test result might more commonly influence treatment recommendations and even patient behavior, thus leading to improvement in patient outcomes even in the setting of normal stress test results., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Alternative stress echocardiography protocols such as handgrip exercise are potentially more favorable towards large-scale screening scenarios than those currently adopted in clinical practice. However, these are still underexplored because the maximal exercise levels are not easily quantified and regulated, requiring the analysis of the complete data sequences (thousands of images), which represents a challenging task for the clinician. We propose a framework for the analysis of these complex datasets, and illustrate it on a handgrip exercise dataset including complete acquisitions of 10 healthy controls and 5 ANT1 mutation patients (1377 cardiac cycles). The framework is based on an unsupervised formulation of multiple kernel learning, which is used to integrate information coming from myocardial velocity traces and heart rate to obtain a lower-dimensional representation of the data. Such simplified representation is then explored to discriminate groups of response and understand the underlying pathophysiological mechanisms. The analysis pipeline involves the reconstruction of population-specific signatures using multiscale kernel regression, and the clustering of subjects based on the trajectories defined by their projected sequences. The results confirm that the proposed framework is able to detect distinctive clusters of response and to provide insight regarding the underlying pathophysiology., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: The aim of this study was to identify the pattern of exercise left atrial (LA) dynamics, its gas exchange correlates, and prognosis in mitral regurgitation (MR) of primary and secondary origin., Background: The adaptive response and clinical significance of LA function during exercise in MR is undefined., Methods: A total of 196 patients with MR (81 with primary MR, 115 with secondary MR) and 54 control subjects underwent exercise stress echocardiography and cardiopulmonary exercise testing with LA function assessment. Patients with MR were divided into 4 groups according to etiology and severity using a cutoff of 3+., Results: LA dynamics was studied using speckle-tracking echocardiography. Compared with control subjects, patients with MR had a lower LA strain and strain rate at rest. Exercise LA strain and LA strain rate progressively worsened from primary MR <3+ through secondary MR ≥3+. In primary MR, some reserve in exercise LA strain and LA strain rate was observed, but not in secondary MR. In secondary MR, LA strain at rest and during exercise (18.1 ± 5.7 s -1 , 18.3 ± 6.9 s -1 , 18.6 ± 5.5 s -1 , 13.9 ± 3.8 s -1 ) and peak oxygen consumption (11.7 ± 3 ml/min/kg) were decreased compared with the other groups. In secondary MR ≥3+, the slope of ventilation versus carbon dioxide was higher compared with the other groups: 35.1 (interquartile range [IQR]: 29.0 to 44.2) compared with control subjects: 26.5 (IQR: 24.4 to 29.0); patients with primary MR <3+ (26.9; IQR: 24.0 to 31.9); those with primary MR >3+ (25.5; IQR: 23.4 to 29.0); and those with secondary MR <3+ (29.5; IQR: 26.5 to 33.7) (p < 0.05 for all). A progressive impairment in exercise LA mechanics combined with limited cardiac output increase and right ventricular-to-pulmonary circulation uncoupling was observed from primary to secondary MR. LAS during exercise was predictive of all-cause mortality and hospitalization for heart failure., Conclusions: In MR of any origin, exercise LA reservoir and pump function are impaired. For similar MR extent, secondary MR exhibits worse atrial function, resulting in the lowest exercise performance, limited cardiac output increase, impaired right ventricular-to-pulmonary circulation coupling, and the highest event rate., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Diastolic dysfunction is a key factor in the pathogenesis of heart failure. Around 50% of cases of heart failure, the hemodynamic correlate of which is increased left ventricular filling pressure, are caused by diastolic dysfunction in the setting of apparently normal systolic function. Due to its high prevalence, diastolic dysfunction is often recognized as an incidental finding. Many patients have Doppler echocardiographic evidence of impaired diastolic function but do not have any symptoms of heart failure at rest. In many of these patients, symptoms of diastolic dysfunction occur only during exercise, as left ventricular filling pressure is normal at rest, but increases with exercise. This implies that filling pressures should also be measured during exercise. The diastolic stress test refers to the evaluation of diastolic function, either invasively or noninvasively, during exercise. This review focuses on the clinical need for diastolic stress testing, both invasively and noninvasively., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Coronary allograft vasculopathy (CAV) is the main factor limiting long-term survival after cardiac transplantation. Dual imaging stress echocardiography with wall motion and Doppler-derived coronary flow reserve (CRF) of the left anterior descending artery (LAD) is a state-of-the-art methodology during dipyridamole stress echocardiography (DiSE). This study involving 74 heart transplanted patients has the purpose to assess the diagnostic value of dipyridamole stress echocardiography with evaluation of wall motion (WM) and Doppler-derived coronary flow reserve for the diagnosis of coronary allograft vasculopathy., Methods and Results: All patients underwent DiSE and coronary angiography. Moderate-severe CAV was defined according to International Society of Heart and Lung Transplant (ISHLT) recommended nomenclature for CAV, and CFR < 2 was considered to be impaired. Moderate-severe CAV was present in 11 patients. WM analysis revealed four patients (5%) with rest WM abnormalities. CFR analysis revealed that 40 (54%) individuals had an abnormal result. The combined evaluation of WM analysis and CFR resulted in a sensitivity of 72.7% (95% CI: 39.3 to 92.6%), a specificity of 49.2% (95% CI: 36.5 to 61.9%), a positive predictive value of 20% (95% CI: 9.6 to 36.1%), and negative predictive value of 91.1% (95% CI: 75.1 to 97.6%) for the diagnosis of CAV., Conclusions: Our results support the inclusion of DiSE performance in Heart transplant follow up protocol. The addition of CFR evaluation offers valuable information to the angiography findings in the detection of CAV and could be helpful in selected patients to adjust the time and indications of coronary angiography., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Recent studies indicate that the pretest likelihood of significant coronary artery disease (CAD) (≥50% luminal stenosis) is over-estimated and that the frequency and severity of positive stress tests have been decreasing. This suggests an increased prevalence of false-positive (FP) stress tests. The aims of this retrospective study were to investigate the predictors of FP stress echocardiography (SE) and to compare the outcomes of patients with FP results to those with true-positive (TP) results., Methods: Patients who underwent SE between 2013 and 2017 in a tertiary-care center were reviewed. Included were patients aged ≥40years who had cardiac catheterization (CC) within 1year of the index stress test. SE was considered FP if a new or worsening wall motion abnormality was present in the absence of significant corresponding CAD., Results: Of the 5100 patients with SE, 1069 satisfied inclusion criteria. A total of 305 patients had positive SE results; of which 162 (53%) were FP. Logistic regression revealed that female gender (p=0.009), the absence of diabetes (p=0.03), the absence of a personal history of CAD (p=0.004), and lower stress WMSI (p=0.03) were independently associated with FP results. Patients with FP results on SE had similar all-cause mortality to those with TP results., Conclusions: Accounting for predictors of FP findings on SE could improve the interpretation of SE results and limit the use of unnecessary CC. Furthermore, patients with FP results on SE could benefit from aggressive risk factor control and careful clinical follow-up., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: This study determined the test performance of dobutamine stress echocardiography (DSE) in end-stage liver disease (ESLD)., Background: The reported sensitivity of DSE in ESLD has been variable., Methods: Data from 633 ESLD patients who had coronary angiography within 6 months after DSE was analyzed., Results: The prevalence of coronary arterial disease (CAD) (≥70% stenosis by quantitative angiography) was 12% (74 of 633 patients). DSE sensitivity was 24% (17 of 72 patients), and specificity was 90% (503 of 559 patients). The positive and negative predictive values were 23% (17 of 73 patients) and 90% (503 of 558 patients), respectively. Stratifying the cohort into low-, intermediate-, and high-risk CAD groups yielded sensitivities of 0%, 21%, and 32%, respectively. Independent predictors of an accurate ischemic DSE result included left ventricular internal dimension at end-diastole (LVIDd) >4.8 cm and assigning ischemia based on tardokinesis or lack of low-to-peak dose hyperkinesis (p < 0.05 for all). DSE sensitivity was 38% in LVIDd >4.8 cm versus 13% with LVIDd ≤4.8 cm (p = 0.013). The sensitivity was 67% when tardokinesis or lack of hyperkinesis was considered abnormal versus 15% (p < 0.001) for readings that did not consider tardokinesis or lack of hyperkinesis abnormal. There was a higher frequency of cardiac events in patients with significant CAD who had abnormal (45%) versus normal (18%) DSE (p = 0.01)., Conclusions: The sensitivity of DSE in ESLD was low. DSE sensitivity was higher for those with larger cavity dimension and when tardokinesis or lack of hyperkinesis was considered abnormal. An abnormal DSE in those with significant CAD was associated with worse outcome., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Obesity is a risk factor for coronary artery disease (CAD), but adiposity may mimic symptoms of CAD and reduce the accuracy of diagnostic testing., Methods: Patients from the PROMISE trial (n = 8889) were classified according to body mass index (BMI). We assessed relationships between BMI, physician's preference of functional test, test positivity, and results of invasive coronary angiography (Cath) using logistic regression models., Results: Nearly half (48%) of the patients had BMI ≥ 30 kg/m 2 , and 20% had BMI ≥ 35. Providers were more likely to prefer nuclear myocardial perfusion imaging (MPI) over other functional tests as BMI increased. The rate of test positivity with coronary computed tomographic angiography (CTA) was not different (10% vs. 12%) in patients with BMI ≥35 vs. < 35. The same was true for stress echocardiogram and stress electrocardiogram (positivity 8-13%, P > 0.8 for both). In contrast, MPI was significantly more likely to be positive in those with BMI ≥35 vs. <35 (18% vs. 13%; P = 0.001). The likelihood of obstructive CAD at Cath did not differ with BMI ≥35 vs. <35 in patients having CTA (52% vs. 59%, P = 0.22), but among MPI patients, Cath positivity was only 29% with BMI ≥35 vs. 48% with BMI <35 (P = 0.005). Radiation exposure increased with higher BMI in both MPI and CTA groups., Conclusions: Increasing levels of obesity adversely affect the diagnostic yield of MPI more than CTA. The degree of obesity should be considered when choosing evaluation strategies for patients with chest pain., Clinical Trial Registration: PROMISE ClinicalTrials.gov number, NCT01174550., (Copyright © 2019. Published by Elsevier Inc.)

Background: The underlying mechanisms causing myocardial ischemia in non-obstructive coronary artery disease (CAD) are still unclear. We explored whether left ventricular hypertrophy (LVH) was associated with myocardial ischemia in patients with stable angina and non-obstructive CAD., Methods: 132 patients (mean age 63 ± 8 years, 56% women) with stable angina and non-obstructive CAD diagnosed as <50% stenosis by coronary computed tomography angiography (CCTA) underwent myocardial contrast stress echocardiography. Left ventricular (LV) hypertrophy (LVH) was identified by LV mass index >46.7 g/m 2.7 in women and >49.2 g/m 2.7 in men. Patients were grouped according to presence or absence of myocardial ischemia by myocardial contrast stress echocardiography. The number of LV segments with ischemia at peak stress was taken as a measure of the extent of myocardial ischemia., Results: Myocardial ischemia was found in 52% of patients, with on average 5 ± 3 ischemic LV segments per patient. The group with myocardial ischemia had higher prevalence of LVH (23 vs. 10%, p = 0.035), while age, sex and prevalence of hypertension did not differ between groups (all p > 0.05). In multivariable regression analyses, LVH was associated with presence of myocardial ischemia (odds ratio 3.27, 95% confidence interval [1.11-9.60], p = 0.031), and larger extent of myocardial ischemia (β = 0.22, p = 0.012), independent of confounders including age, hypertension, obesity, hypercholesterolemia, calcium score and segment involvement score by CCTA., Conclusions: LVH was independently associated with both presence and extent of myocardial ischemia in patients with stable angina and non-obstructive CAD by CCTA. These results suggest LVH as an independent contributor to myocardial ischemia in non-obstructive CAD., Clinical Trial Registration Number: ClinicalTrials.gov, identifier NCT018535271., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: This study sought to investigate the association of left ventricular (LV) untwisting rate (UT) and E/e' ratio with the response of exercise capacity to spironolactone in heart failure with preserved ejection fraction (HFpEF)., Background: In most patients with HFpEF, LV filling abnormalities represent a central component in the development of dyspnea. LV diastolic filling is determined by the interplay of passive (LV stiffness and myocardial collagen content, reflected by E/e' ratio) and active myocardial properties (UT, a precursor to isovolumic pressure decay and contributor to diastolic suction)., Methods: In 194 patients with HFpEF (64 ± 8 years), a complete echocardiogram (including assessment of myocardial deformation and rotational mechanics) was performed. Echocardiography following maximal exercise was undertaken to assess LV systolic and diastolic responses to stress. A subset of 105 patients with an exercise-induced increase in estimated LV filling pressure were randomly assigned to spironolactone 25 mg (n = 51) or placebo (n = 54) for 6 months., Results: Baseline peak Vo 2 was associated with UT (β = 0.19; p = 0.01) and E/e' (β = -0.16; p = 0.03), independent of clinical data and exercise reserve in longitudinal deformation and ventricular-arterial coupling. An increase in peak Vo 2  with treatment was independently associated with changes in UT (β = 0.28; p = 0.003) and exertional increase in E/e' (β = -0.23; p = 0.01) from baseline to follow-up. A significant interaction with the use of spironolactone on peak Vo 2 was found for E/e' (p = 0.02) but not for UT (p = 0.62)., Conclusions: Both active and passive determinants of LV filling, as reflected by UT and E/e', contribute to reduced exercise capacity in HFpEF. Improvement in functional capacity with a 6-month therapy with spironolactone is associated with improvements in both indices. However, the possible mediating effect of this medication is observed only on E/e'., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to establish the diagnostic and prognostic value of a strategy for prediction of abnormal diastolic response to exercise (AbnDR) using clinical, biochemical, and resting echocardiographic markers in dyspneic patients with mild diastolic dysfunction., Background: An AbnDR (increase in left ventricular filling pressure) may indicate heart failure with preserved ejection fraction as the cause of symptoms in dyspneic patients, despite a nonelevated noncardiac at rest. However, exercise testing may be inconclusive in patients with noncardiac limitations to physical activity., Methods: In 171 dyspneic patients (64 ± 8 years) with suspected heart failure with preserved ejection fraction but resting peak early diastolic mitral inflow velocity/peak early diastolic mitral annular velocity ratio (E/e') <14, a complete echocardiogram (including assessment of myocardial deformation and rotational mechanics) and blood assays for biomarkers were performed. Echocardiography following maximal exercise was undertaken to assess AbnDR (exertional E/e' >14). Patients were followed over 26.2 ± 4.6 months for endpoints of cardiovascular hospitalization and death., Results: AbnDR was present in 103 subjects (60%). Independent correlates of AbnDR were resting E/e' (odds ratio [OR]: 8.23; 95% confidence interval [CI]: 3.54 to 9.16; p < 0.001), left ventricular untwisting rate (OR: 0.60; 95% CI: 0.42 to 0.86; p = 0.006), and galectin-3-a marker of fibrosis (OR: 1.80; 95% CI: 1.21 to 2.67; p = 0.004). The use of resting E/e' >11.3 and galectin-3 <1.17 ng/ml to select patients for further diagnostic processing would have allowed exercise testing to be avoided in 65% of subjects, at the cost of misclassification of 13%. The composite outcome of cardiovascular hospitalization or death occurred in 47 patients (27.5%). The predictive value of an AbnDR response and the combined strategy (resting echocardiography and galectin-3 or exercise testing in case of an inconclusive first step) showed similar event prediction (36 vs. 34; p = 0.95)., Conclusions: The implementation of a 2-step algorithm (echocardiographic evaluation of resting E/e' followed by the assessment of galectin-3) may improve the diagnosis and prognostic assessment of individuals with suspected heart failure with preserved ejection fraction who are unable to perform a diagnostic exercise test., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)