Usefulness of cardiopulmonary exercise test combined with exercise stress echocardiography in mild chronic thromboembolic pulmonary disease.

PURPOSE: Chronic thromboembolic pulmonary disease (CTEPD) can lead to exercise limitations even without right ventricular (RV) dysfunction or pulmonary hypertension at rest. Combining exercise stress echocardiography with cardiopulmonary exercise testing (ESE-CPET) for RV function and pressure changes combined measuring overall function may be useful for CTEPD evaluation. This study aims to investigate CPET and ESE results to elucidate the mechanisms of exercise limitation in mild CTEPD cases. METHODS: Among our CTEPD registry, 50 patients who performed both right heart catheterization data of mild disease (less than 30 mm Hg of mean pulmonary arterial pressure (mPAP)) and ESE-CPET were enrolled. Echocardiography and CPET-derived parameters were compared with hemodynamic parameters measured through right heart catheterization. RESULTS: Peak VO2 (maximal oxygen consumption) was decreased in overall population (71.3 ± 16.3% of predictive value). Peak VO2 during exercise was negatively correlate with mPAP and pulmonary vascular resistance at rest. A substantial increase in RV systolic pressure (RVSP) was observed during exercise (RVSP: pre-exercise 37.2 ± 11.8 mm Hg, postexercise 64.3 ± 24.9 mm Hg, p-value < .001). Furthermore, RV function deteriorated during exercise when compared to the baseline (RV fractional area change: 31.5 ± 10.0% to 37.8 ± 7.0%, p-value < .001; RV global longitudinal strain: -17.1 ± 4.2% to -17.7 ± 3.3%, p-value < .001) even though basal RV function was normal. While an excessive increase in RVSP during exercise was noticed in both groups, dilated RV and RV dysfunction during exercise were demonstrated only in the impaired exercise capacity group. CONCLUSION: CTEPD patients with mild PH or without PH exhibited limited exercise capacity alongside an excessive increase in RVSP during exercise. Importantly, RV dysfunction during exercise was significantly associated with exercise capacity. ESE-CPET could aid in comprehending the primary cause of exercise limitation in these patients.

High Resting Coronary Flow Velocity by Echocardiography Is Associated With Worse Survival in Patients With Chronic Coronary Syndromes.

BACKGROUND: Resting coronary flow velocity (CFV) in the mid-distal left anterior descending coronary artery can be easily assessed with transthoracic echocardiography. In this observational study, the authors sought to assess the relationship between resting CFV, CFV reserve (CFVR), and outcome in patients with chronic coronary syndromes. METHODS AND RESULTS: In a prospective multicenter study design, the authors retrospectively analyzed 7576 patients (age, 66±11 years; 4312 men) with chronic coronary syndromes and left ventricular ejection fraction ≥50% referred for dipyridamole stress echocardiography. Recruitment (years 2003-2021) involved 7 accredited laboratories, with interobserver variability <10% for CFV measurement at study entry. Baseline peak diastolic CFV was obtained by pulsed-wave Doppler in the mid-distal left anterior descending coronary artery. CFVR (abnormal value ≤2.0) was assessed with dipyridamole. All-cause death was the only end point. The mean CFV of the left anterior descending coronary artery was 31±12 cm/s. The mean CFVR was 2.32±0.60. During a median follow-up of 5.9±4.3 years, 1121 (15%) patients died. At multivariable analysis, resting CFV ≥32 cm/s was identified by a receiver operating curve as the best cutoff and was independently associated with mortality (hazard ratio [HR], 1.24 [95% CI, 1.10-1.40]; P<0.0001) together with CFVR ≤2.0 (HR, 1.78 [95% CI, 1.57-2.02]; P<0.0001), age, diabetes, history of coronary surgery, and left ventricular ejection fraction. When both CFV and CFVR were considered, the mortality rate was highest in patients with resting CFV ≥32 cm/s and CFVR ≤2.0 and lowest in patients with resting CFV <32 cm/s and CFVR >2.0. CONCLUSIONS: High resting CFV is associated with worse survival in patients with chronic coronary syndromes and left ventricular ejection fraction ≥50%. The value is independent and additive to CFVR. The combination of high resting CFV and low CFVR is associated with the worst survival.

Resting strain analysis to identify myocardial ischemia in patients with advanced chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is associated with higher incidence of cardiovascular death. Screening for coronary artery disease in asymptomatic or mildly symptomatic patients is challenging. OBJECTIVE: The aim of this study was to investigate the incremental value of resting deformation analysis in predicting positive results for myocardial ischemia during stress transthoracic echocardiography in patients with end-stage CKD. METHODS: Sixty-one patients (mean age: 62.3 ± 11.8, 65.7% men) with end-stage CKD were included in the study. Patients underwent a resting transthoracic echocardiogram and a dobutamine stress contrast echo (DSE) protocol. Positive results of DSE were defined as stress-induced left ventricular (LV) wall motion abnormalities. RESULTS: The study cohort had normal or mildly impaired systolic function: mean LV ejection fraction (EF) was 49.2% (±10.4) and mean LV global longitudinal strain (GLS) was 14.4% (±4.5). Half of our population had impaired left atrial (LA) strain: mean LA reservoir, conduit, and contractile reserve were 24.1% (±12.6), 10.6% (±5.9), and 13.6% (±9.2), respectively. DSE was positive for ischemia in 55.7%. A significant negative association with DSE results was found for LV EF, LV GLS and the conduit phase of LA strain. Both LV and LA dimensions showed positive correlation with presence of ischemia in DSE. Multivariate logistic regression analysis showed that LV GLS was independently associated with DSE (p = 0.007), after controlling for covariates, with high diagnostic accuracy. CONCLUSION: Resting LV deformation could predict positive results during DSE, thus may be useful to better identify renal patients who might benefit from coronary artery screening.

Practice guidance for stress echocardiography.

Stress echocardiography has been one of the most promising methods for the diagnosis of ischemic heart disease, hypertrophic cardiomyopathy, and pulmonary hypertension. The Japanese Society of Echocardiography produced practical guidance for the implementation of stress echocardiography in 2018. At that time, stress echocardiography was not yet widely disseminated in Japan; therefore, the 2018 practical guidance for the implementation of stress echocardiography included a report on stress echocardiography and a specific protocol to promote its use at many institutions in Japan in the future. And now, an era of renewed interest and enthusiasm surrounding the diagnosis and treatment of valvular heart disease and heart failure with preserved ejection fraction (HFpEF) has come, which are driven by emerging trans-catheter procedures and new recommended guideline-directed medical therapy. Based on the continued evidence of stress echocardiography, the new practical guideline that describes the safe and effective methodology of stress echocardiography is now created by the Guideline Development Committee of the Japanese Society of Echocardiography and is designed to expand the use of stress echocardiography for valvular heart disease and HFpEF, as well as ischemic heart disease, hypertrophic cardiomyopathy, and pulmonary hypertension. The readers are encouraged to perform stress echocardiography which will enhance the diagnosis and management of these patients.

mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis.

BACKGROUND: Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L-1·min-1. A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown. METHODS: In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm2 underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141). RESULTS: One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48; P=0.036), indexed left atrial volume (OR per SD, 2.15; P=0.001), E/e' at rest (OR per SD, 1.61; P=0.012), mPAP/CO slope (OR per SD, 2.01; P=0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59; P=0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28; P=0.219). Peak Vo2 (percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area (P<0.001). These results were confirmed in the validation cohort. CONCLUSIONS: In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak Vo2 were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak Vo2 and mPAP/CO slope cumulatively improved risk stratification.

Development of artificial intelligence-based slow-motion echocardiography and clinical usefulness for evaluating regional wall motion abnormalities.

The diagnostic accuracy of exercise stress echocardiography (ESE) for myocardial ischemia requires improvement, given that it currently depends on the physicians' experience and image quality. To address this issue, we aimed to develop artificial intelligence (AI)-based slow-motion echocardiography using inter-image interpolation. The clinical usefulness of this method was evaluated for detecting regional wall-motion abnormalities (RWMAs). In this study, an AI-based echocardiographic image-interpolation pipeline was developed using optical flow calculation and prediction for in-between images. The accuracy for detecting RWMAs and image readability among 25 patients with RWMA and 25 healthy volunteers was compared between four cardiologists using slow-motion and conventional ESE. Slow-motion echocardiography was successfully developed for arbitrary time-steps (e.g., 0.125×, and 0.5×) using 1,334 videos. The RWMA detection accuracy showed a numerical improvement, but it was not statistically significant (87.5% in slow-motion echocardiography vs. 81.0% in conventional ESE; odds ratio: 1.43 [95% CI: 0.78-2.62], p = 0.25). Interreader agreement analysis (Fleiss's Kappa) for detecting RWMAs among the four cardiologists were 0.66 (95%CI: 0.55-0.77) for slow-motion ESE and 0.53 (95%CI: 0.42-0.65) for conventional ESE. Additionally, subjective evaluations of image readability using a four-point scale showed a significant improvement for slow-motion echocardiography (2.11 ± 0.73 vs. 1.70 ± 0.78, p < 0.001).In conclusion, we successfully developed slow-motion echocardiography using in-between echocardiographic image interpolation. Although the accuracy for detecting RWMAs did not show a significant improvement with this method, we observed enhanced image readability and interreader agreement. This AI-based approach holds promise in supporting physicians' evaluations.

The clinical use of stress echocardiography in chronic coronary syndromes and beyond coronary artery disease: a clinical consensus statement from the European Association of Cardiovascular Imaging of the ESC.

Since the 2009 publication of the stress echocardiography expert consensus of the European Association of Echocardiography, and after the 2016 advice of the American Society of Echocardiography-European Association of Cardiovascular Imaging for applications beyond coronary artery disease, new information has become available regarding stress echo. Until recently, the assessment of regional wall motion abnormality was the only universally practiced step of stress echo. In the state-of-the-art ABCDE protocol, regional wall motion abnormality remains the main step A, but at the same time, regional perfusion using ultrasound-contrast agents may be assessed. Diastolic function and pulmonary B-lines are assessed in step B; left ventricular contractile and preload reserve with volumetric echocardiography in step C; Doppler-based coronary flow velocity reserve in the left anterior descending coronary artery in step D; and ECG-based heart rate reserve in non-imaging step E. These five biomarkers converge, conceptually and methodologically, in the ABCDE protocol allowing comprehensive risk stratification of the vulnerable patient with chronic coronary syndromes. The present document summarizes current practice guidelines recommendations and training requirements and harmonizes the clinical guidelines of the European Society of Cardiology in many diverse cardiac conditions, from chronic coronary syndromes to valvular heart disease. The continuous refinement of imaging technology and the diffusion of ultrasound-contrast agents improve image quality, feasibility, and reader accuracy in assessing wall motion and perfusion, left ventricular volumes, and coronary flow velocity. Carotid imaging detects pre-obstructive atherosclerosis and improves risk prediction similarly to coronary atherosclerosis. The revolutionary impact of artificial intelligence on echocardiographic image acquisition and analysis makes stress echo more operator-independent and objective. Stress echo has unique features of low cost, versatility, and universal availability. It does not need ionizing radiation exposure and has near-zero carbon dioxide emissions. Stress echo is a convenient and sustainable choice for functional testing within and beyond coronary artery disease.

Contrast Stress Echocardiography Findings in Myocardial Bridging Compared to Normal Coronary Course, With and Without Coronary Artery Disease.

BACKGROUND: Myocardial bridging (MB) correlation with ischemia remains a diagnostic challenge. There is a lack of studies that have assessed MB using contrast stress echo and compared the findings with those in patients demonstrating a normal coronary course, with or without obstructive coronary artery disease (CAD). METHODS: We evaluated all consecutive patients who underwent contrast stress echocardiography and coronary computed tomography angiography (CCTA) due to suspected symptoms of CAD within 3 months in Parma Hospital. Coronary computed tomography angiography served as the reference standard for detecting MB and obstructive CAD. The patients were divided into 3 groups: (1) MB and no evidence of obstructive CAD (MB group, N = 64), (2) no evidence of obstructive CAD or MB (NoCAD group, N = 135), (3) obstructive CAD without MB (CAD group, N = 68). RESULTS: The coronary flow velocity reserve in the LAD (CFVR-LAD) was reduced in the MB and CAD groups, measuring 1.91 ± 0.21 and 1.82 ± 0.28, respectively, whereas it was 2.27 ± 0.34 in the NoCAD group (P < .001). The MB and CAD groups exhibited a higher prevalence of reversible myocardial perfusion defects (rMPDs) compared to the NoCAD group (57.8% vs 64.7% vs 3.7%, P < .001). Reversible wall motion abnormalities were frequently observed in the CAD group and rarely found in the MB and NoCAD groups (47.1% vs 18.8% vs 4.4%, P < .001). In multivariable analyses, the presence of MB was independently associated with reduced CFVR-LAD (odds ratio = 14.55; 95% CI, 6.84-30.93; P < .001) and the presence of rMPD (odds ratio = 37.96; 95% CI, 13.49-106.84; P < .001). Patients with deep MB (>2 mm depth) and very deep MB (≥5 mm depth) exhibited significantly greater CFVR-LAD reduction and rMPD than those with superficial MB. CONCLUSIONS: Myocardial bridging is capable of inducing rMPD and reducing CFVR-LAD similar to obstructive CAD. The depth of the MB correlates with the abnormalities found in the stress echo evaluation. Contrast stress echo may serve as a valuable noninvasive tool for evaluating patients with MB.

A knowledge graph-based analytical model for mining clinical value of drug stress echocardiography for diagnosis, risk stratification and prognostic evaluation of coronary artery disease.

The three major techniques for clinically diagnosing coronary heart disease, including angina associated with myocardial ischemia, are coronary angiography, myocardial perfusion imaging, and drug stress echocardiography. Compared to the first two methods, which are invasive or involve the use of radionuclides, drug stress echocardiography is increasingly used in clinical practice due to its non-invasive, low-risk, and controllable nature, and wide applicability. We developed a novel methodology to demonstrate knowledge graph-based efficacy analysis of drug stress echocardiography as a complement to traditional meta-analysis. By measuring coronary flow reserve (CFR), we discovered that regional ventricular wall abnormalities (RVWA) and drug-loaded cardiac ultrasound can be used to detect coronary artery disease. Additionally, drug-loaded cardiac ultrasound can be used to identify areas of cardiac ischemia, stratify risks, and determine prognosis. Furthermore, adenosine stress echocardiography(ASE) can determine atypical symptoms of coronary heart disease with associated cardiac events through CFR and related quantitative indices for risk stratification. Using a knowledge graph-based approach, we investigated the positive and negative effects of three drugs - Dipyridamole, Dobutamine, and Adenosine - for coronary artery disease analysis. Our findings show that Adenosine has the highest positive effect and the lowest negative effect among the three drugs. Due to its minimal and controlled side effects, and high sensitivity for diagnosing coronary microcirculation disorders and multiple lesions, adenosine is frequently used in clinical practice.

Exercise-induced B-lines for the diagnosis of heart failure with preserved ejection fraction: a two-centre study.

BACKGROUND: Diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging despite the use of scores/algorithms. This study intended to assess the diagnostic value of exercise lung ultrasound (LUS) for HFpEF diagnosis. METHODS: We studied two independent case-control studies of HFpEF patients and control subjects undergoing different exercise protocols: (i) submaximal exercise stress echocardiography (ESE) with LUS performed by expert cardiologists (N = 116, HFpEF = 65.5%), and (ii) maximal cycle ergometer test (CET) (N = 54, HFpEF = 50%) with LUS performed by unexperienced physicians shortly trained for the study. B-line kinetics (i.e. peak values and their changes from rest) were assessed. RESULTS: In the ESE cohort, the C-index (95% CI) of peak B-lines for HFpEF diagnosis was 0.985 (0.968-1.000), whereas the C-index of rest and exercise HFA-PEFF scores (i.e. including stress echo findings) were < 0.90 (CI 0.823-0.949), and that of H2FPEF score was < 0.70 (CI 0.558-0.764). The C-index increase of peak B-lines on top of the above-mentioned scores was significant (C-index increase > 0.090 and P-value < 0.001 for all). Similar results were observed for change B-lines. Peak B-lines > 5 (sensitivity = 93.4%, specificity = 97.5%) and change B-lines > 3 (sensitivity = 94.7%, specificity = 87.5%) were the best cutoffs for HFpEF diagnosis. Adding peak or change B-lines on top of HFpEF scores and BNP significantly improved diagnostic accuracy. Peak B-lines showed a good diagnostic accuracy in the LUS beginner-led CET cohort (C-index = 0.713, 0.588-0.838). CONCLUSIONS: Exercise LUS showed excellent diagnostic value for HFpEF diagnosis regardless of different exercise protocols/level of expertise, with additive diagnostic accuracy on top of available scores and natriuretic peptides.

Assessment of Postsystolic Shortening and Global Longitudinal Strain Improves the Sensitivity of Dobutamine Stress Echocardiography in End-Stage Liver Disease.

BACKGROUND: Dobutamine stress echocardiography (DSE) remains a widely used method for detection of coronary artery disease (CAD) in patients with end-stage liver disease (ESLD) despite low sensitivity. Speckle-tracking assessment of strain may enhance the sensitivity of DSE in the general population, but the value of strain analysis in ESLD is unknown. METHODS: Dobutamine stress echocardiography with two-dimensional speckle-tracking and quantitative coronary angiography were performed in 146 patients with ESLD. Thirty-six patients (25%) had CAD (≥50% diameter stenosis of a major vessel). Global longitudinal strain at rest (GLSr) and at peak stress (GLSp) and an index of postsystolic (PSSi) shortening ([maximal extent of shortening - extent of shortening in systole]/[extent of shortening in systole]) were determined. A PSSi of ≥ 0.25 was considered evidence for CAD. Receiver operating characteristic analysis was used to determine the optimal thresholds of GLSr and GLSp for CAD and to assess the diagnostic performance of visual assessment of wall motion (WMA) and strain parameters. The sensitivity and specificity of WMA, GLSr, GLSp, and PSSi were compared. RESULTS: Thirty-six patients (25%) had significant CAD. The areas under the curve for WMA, GLSr, GLSp, and PSSi were 0.60, 0.72, 0.68, and 0.78, respectively. Visual assessment of wall motion had a sensitivity of 28%. The sensitivity of each of the strain parameters, GLSr (53%, P = .016), GLSp (69%, P = .004), and PSSi (78%, P < .001), exceeded the sensitivity for WMA. Visual assessment of wall motion specificity was 92%, which exceeded the specificity for each of the strain parameters (GLSr = 82%, P = .037; GLSp = 63%, P < .001; and PSSi =78%, P = .009). Of the strain parameters, PSSi had the best balance between sensitivity and specificity (both 78%). CONCLUSION: Assessment of GLS and PSSi with DSE yields better sensitivity than WMA in ELSD patients. Index of postsystolic shortening had the best diagnostic performance of all parameters in this population with a low prevalence of CAD.

Impact of diabetes on cardiopulmonary function: the added value of a combined cardiopulmonary and echocardiography stress test.

Type 2 diabetes mellitus (T2DM) represents a major health issue worldwide, as patients with T2DM show an excess risk of death for cardiovascular causes, twice as high as the general population. Among the many complications of T2DM, heart failure (HF) deserves special consideration as one of the leading causes of morbidity and reduced life expectancy. T2DM has been associated with different phenotypes of HF, including HF with reduced and preserved ejection fraction. Cardiopulmonary exercise testing (CPET) can evaluate the metabolic and ventilatory alterations related to myocardial dysfunction and/or peripheral impairment, representing a unique tool for the clinician to study the whole HF spectrum. While CPET allows for a thorough evaluation of functional capacity, it cannot directly differentiate central and peripheral determinants of effort intolerance. Combining CPET with imaging techniques could provide even higher accuracy and further insights into the progression of the disease since signs of left ventricular systolic and diastolic dysfunction can be detected during exercise, even in asymptomatic diabetic individuals. This review aims to dissect the alterations in cardiopulmonary function characterising patients with T2DM and HF to improve patient risk stratification.

[Clinical application and limitations of bicycle stress echocardiography (echo-bike)]. / Campi di applicazione e limiti dell'ecocardiografia da sforzo (echo-bike).

Stress echocardiography is an imaging methodology that is widely used in cardiopathic patients for the optimization of diagnosis and prognosis of patients with valvular heart diseases, in defining the response to physical stress in patients with ischemic heart disease, hypertrophic cardiomyopathy, congenital heart disease, or heart failure. However, this method is not yet sufficiently used in clinical practice. Therefore, the aim of this literature review is to describe the main fields of application of stress echocardiography with echo-bike, describing its main advantages and limitations.

Ultrafast Myocardial Principal Strain Ultrasound Elastography During Stress Tests: In Vitro Validation and In Vivo Feasibility.

Objective myocardial contractility assessment during stress tests aims to improve the diagnosis of myocardial ischemia. Tissue Doppler imaging (TDI) or optical flow (OF) speckle tracking echocardiography (STE) has been used to quantify myocardial contractility at rest. However, this is more challenging during stress tests due to image decorrelation at high heart rates. Moreover, stress tests imply a high frame rate which leads to a limited lateral field of view. Therefore, a large lateral field-of-view robust ultrafast myocardial regularized OF-TDI principal strain estimator has been developed for high-frame-rate echocardiography of coherently compounded transmitted diverging waves. The feasibility and accuracy of the proposed estimator were validated in vitro (using sonomicrometry as the gold standard) and in vivo stress experiments. Compared with OF strain imaging, the proposed estimator improved the accuracy of principal major and minor strains during stress tests, with an average contrast-to-noise ratio improvement of 4.4 ± 2.7 dB ( p -value < 0.01). Moreover, there was a significant correlation and a very close agreement between the proposed estimator and sonomicrometry for tested heart rates between 60 and 180 beats per minute (bpm). The averages ± standard deviations (STD) of R2 and biases ± STD between them were 0.96 ± 0.04 ( p -value < 0.01) and 0.01 ± 0.03% in the axial direction, respectively; and 0.94 ± 0.02 ( p -value < 0.01) and 0.04 ± 0.06% in the lateral direction, respectively. These results suggest that the proposed estimator could be useful clinically to provide an accurate and quantitative 2-D large lateral field-of-view myocardial strain assessment at high heart rates during stress echocardiography.

Tissue tracking of segmental strain as a predictor of provoked dynamic left ventricular outflow tract obstruction.

BACKGROUND: Left ventricular outflow tract obstruction (LVOTO) is commonly observed in patients with hypertrophic cardiomyopathy (HCM) or left ventricular hypertrophy (LVH). Some patients develop LVOTO provoked by physical exertion, and hence termed dynamic LVOTO (DLVOTO). However, its precise prevalence and mechanism are still unclear. AIM: Two-dimensional speckle tracking echocardiography (2D STE) seems to be helpful for the detection of early LV structural abnormalities. This study aimed to examine the possible role of segmental as well as global longitudinal strain in identifying DLVOTO non-HCM patients as detected by dobutamine stress echocardiography (DSE). METHODS AND RESULTS: Two hundred and fifty patients without structural heart disease had undergone conventional transthoracic echocardiography, 2D STE, and DSE. All patients with non-ischemic evidence were divided into two groups according to the DSE results; DLVOTO (+) and DLVOTO (-). Among 250 patients, 50 patients (36%) had shown DLVOTO after DSE (15 males, 35 females; mean age 55±7years). They were compared with 90 non -LVOTO obstruction patients (43 males, 47 females; mean age 57±6years). Based on multivariate logistic regression analysis, the independent predictors of provoked DLVOTO during DSE were resting basal septal longitudinal strain BS-LS average (p < 0.001), resting LA reservoir strain (p < 0.001), and systolic LVOT diameter (p = 0.03). Resting BS-LS average with cut-off - 17.5% was recognized as a critical indicator of DLVOTO, with sensitivity 78%, and specificity 95% (better than systolic LVOT diameter of sensitivity 76%, and specificity 15% and resting LA reservoir strain which showed poor AUC at ROC curve 0.007). CONCLUSION: We demonstrate that provoked LVOTO during DSE in non HCM symptomatic patients is directly correlated to resting regional LS, where the increased BS-LS of ≥ -17.5% was a key determinant of LVOT gradient provocation. Assessment of baseline BS-LS average might be a bedside simple tool for detection of patients with DLVOTO not able to do DSE.

Clinical course and decision-making in heart failure by preload stress echocardiography: a preliminary study.

AIMS: Abnormal left ventricular diastolic response to preload stress can be an early marker of heart failure (HF). The aim of this study was to assess clinical course in patients with HF with preserved ejection fraction (HFpEF) who underwent preload stress echocardiography. In the subgroup analysis, we assessed the prognosis of patients with unstable signs during preload stress classified by treatment strategies. METHODS AND RESULTS: We prospectively conducted preload stress echocardiographic studies between January 2006 and December 2013 in 211 patients with HFpEF. Fifty-eight patients had abnormal diastolic reserve during preload stress (unstable impaired relaxation: unstable IR). Of 58 patients with unstable IR, 19 patients were assigned to additional therapy by increased or additional therapy and 39 patients were assigned to standard therapy. Composite outcomes were prespecified as the primary endpoint of death and hospitalization for deteriorating HF. During a median period of 6.9 years, 19 patients (33%) reached the composite outcome. Unstable group with standard therapy had significantly shorter event-free survival than stable group. Patients with uptitration of therapy had longer event-free survival than those with standard therapy group after adjustment of laboratory data (hazard ratio, 0.20, 95% confidence interval, 0.05-0.90; P = 0.036); the 10 year event-free survival in patients with and without uptitration of therapy was 93% and 51%, respectively (P = 0.023). CONCLUSIONS: Patients with unstable sign had significantly shorter event-free survival than patients with stable sign. After additional therapy, the prognosis of patients with unstable signs improved. This technique may impact decision-making for improving their prognosis.

Prognostic Value of Exercise Stress Echocardiography in Pediatric Cardiac Transplant Recipients.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a leading cause of long-term morbidity and mortality in pediatric heart transplant (HTx) recipients. Exercise stress echocardiography (ESE) has been shown to be useful in the detection of angiographically confirmed coronary artery disease in children. However, the prognostic utility of ESE for prediction of cardiac events in HTx survivors is unknown. OBJECTIVES: We aim to assess whether an abnormal (positive) ESE is be associated with a higher risk of future cardiovascular (CV) outcomes in pediatric HTx recipients. METHODS: We conducted a retrospective review of CV outcomes in a cohort of 95 pediatric HTx recipients who underwent 188 ESEs over a 10-year period. A composite endpoint for CV events including myocardial infarction, hospitalization for nonrejection heart failure, coronary revascularization, need for repeat transplantation, and death was used. Based on the interpretation of the ESE results, each ESE study was classified for this study as either positive (abnormal) or negative (normal) for ischemia. Results of the coronary angiograms performed near the time of ESE were also assessed and classified for this study as positive (abnormal) or negative (normal) for CAV according to standard HTx criteria for CAV. RESULTS: Fifty-one (27%) ESEs were positive for ischemia. There was a total of 35 CV events in 23 patients. A positive ESE was associated with increased risk of any CV event (hazard ratio = 3.55; 95% CI, 1.52, 8.28), as well as an increased risk of CV death (hazard ratio = 3.19; 95% CI, 1.23, 8.28). Freedom from composite CV outcome at 1, 2, and 3 years following a positive ESE was 89.9% (95% CI = 77.3%, 95.7%), 81.5% (95% CI = 65.9%, 90.5%), and 63.2% (95% CI = 41.9%, 78.5%), respectively. Freedom from composite CV outcome at 1, 2, and 3 years following a negative ESE was 99.3% (94.8, 99.9), 98.4% (93.6, 99.6), and 97.0% (90.6, 99.1), respectively. No patient died within 1 year of a negative ESE. CONCLUSIONS: In this largest study of ESE in pediatric HTx recipients, a positive or abnormal ESE is associated with increased future CV morbidity and mortality. Conversely, a negative ESE can help predict CV event-free survival. Even in the setting of a normal coronary angiogram, our pilot data show that an abnormal ESE may still be clinically important. Use of ESE in follow-up may improve risk stratification and management of pediatric HTx recipients.

Modified Haller index is inversely correlated with true positive exercise stress echocardiographic results.

AIMS: The influence of chest wall shape on exercise stress echocardiography (ESE) results has been poorly investigated. We aimed at evaluating the main predictors of true positive (TP)-ESE in a population of subjects with suspected coronary artery disease (CAD), categorized according to chest wall conformation, assessed by modified Haller index (MHI, chest transverse diameter over the distance between sternum and spine). METHODS: All consecutive patients with suspected CAD referred to our EchoLab for performing ESE between September 2011 and October 2021 were retrospectively enrolled. Preliminary assessment of both pretest probability (PTP) and MHI was performed. All patients with positive ESE underwent coronary angiography. Obstructive CAD was diagnosed by ≥70% stenosis in any epicardial coronary artery. Outcome was TP ESE result. RESULTS: One thousand two hundred and seventy-five consecutive patients (64.9 ±â€Š13.0 years) entered the study. Subjects with concave-shaped chest wall (MHI > 2.5) (10.7%) and those with normal chest shape (MHI ≤ 2.5) (89.3%) were separately analyzed. PTP was similar in both groups (21.8 ±â€Š13.2 vs. 23.5 ±â€Š13.3%, P  = 0.15). One hundred and seventy patients were diagnosed with positive ESE: 129 (75.9%) had obstructive CAD (TP), whereas the remaining 41 (24.1%) had no CAD. Only 2.3% of TP ESE was detected in subjects with MHI >2.5. PTP [odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01-1.04], dyslipidemia (OR 4.37, 95% CI 2.81-6.80), dyssynergy in the left anterior descending territory (OR 8.21, 95% CI 5.07-13.3) were linearly correlated with TP ESE, whereas MHI >2.5 (OR 0.25, 95% CI 0.14-0.67) was inversely associated with outcome. CONCLUSIONS: Subjects with MHI >2.5 have low prevalence of TP ESE, regardless of PTP. Preliminary MHI assessment may reduce overestimation of PTP of CAD.

The feasibility and safety of stepwise protocol in cardiopulmonary exercise testing-exercise stress echocardiography for subjects with heart failure.

BACKGROUND: Exercise stress testing using a ramp protocol has been favored for cardiopulmonary exercise testing (CPX) in patients with heart failure (HF). However, the stepwise protocol for CPX was preferred for its possible combination with exercise stress echocardiography (ESE). We, therefore, investigated the feasibility and safety of using a stepwise protocol for CPX-ESE in patients with HF. METHODS: Ambulatory outpatients with chronic HF were enrolled for a symptom-limited stepwise bicycle exercise test in the semi-supine position on a cycle ergometer. The test was started at a workload of 30 W and increased by 15 W every 3 minutes until maximal exertion. The echocardiographic and respiratory variables and any complications during the exercise were recorded. RESULTS: Among a total of 36 participants (age 61.2 ± 12.4 years; 69.4% men), all subjects achieved anerobic threshold during CPX-ESE and reached 72.3% of the age-predicted peak heart rate. The peak oxygen consumption was 14.7 mL/kg/min, and the peak RER was 1.25. There were no severe adverse complications, and only two minor rhythmic events were reported: nonsustained supraventricular tachycardia and isolated ventricular premature beats. The echocardiographic images acquired at each stage were of good quality in 92.6% of all acquisitions, and the intra-observer and interobserver repeatability was >80%. CONCLUSION: The stepwise protocol, with an initial workload of 30 W, followed by 15 W increments every 3 minutes, was feasible and provided an adequate stress load for patients with HF. This exercise stress modality was safe and well-tolerated.