Echo-Particle Image Velocimetry (echoPIV) tracks speckle patterns from ultrasound contrast agent(UCA), being less angle-sensitive than colour Doppler. High frame rate (HFR) echoPIV enables tracking of high velocity flow in the left ventricle (LV). We aimed to demonstrate the potential clinical use of HFR echoPIV and investigate the feasibility and accuracy in patients.Nineteen patients admitted for heart failure were included. HFR contrast images were acquired from an apical long axis view (ALAX), using a fully-programmable ultrasound system. A clinical UCA was continuously infused with a dedicated pump. Additionally, echocardiographic images were obtained using a clinical system, including LV contrast-enhanced images and pulsed-wave (PW) Doppler of the LV inflow and outflow in ALAX. 11 patients underwent CMR and 4 cardiac CT as clinically indicated. These CMR and CT images were used as reference. In 10 patients with good echoPIV tracking and reference imaging, the intracavitary flow was compared between echoPIV, conventional and UCA echocardiography.2 = 0.77 to PW peak; R2 = 0.80 PW mean velocity) and moderate for the outflow , with a tendency for echoPIV to underestimate PW velocities. In selected patients, echoPIV was able in a single acquisition to demonstrate flow patterns which required multiple interrogations with classical echocardiography. Those flow patterns could also be linked to anatomical abnormalities as seen in CMR or CT.EchoPIV tracking quality was good in 12/19 (63%), moderate in 2/19 (10%) and poor in 5/19 (26%) subjects. EchoPIV could determine inflow velocity in 17/19 (89%), and outflow in 14/19 (74%) patients. The correlation of echoPIV and PW Doppler was good for the inflow (RHFR echoPIV tracks multidirectional and complex flow patterns which are unapparent with conventional echocardiography, while having comparable feasibility. EchoPIV tends to underestimate flow velocities as compared to PW Doppler. It has the potential to provide in one acquisition all the functional information obtained by conventional imaging, overcoming the angle dependency of Doppler and low frame rate of classical contrast imaging.The online version contains supplementary material available at 10.1186/s12947-022-00283-4. Blood flow in the heart is classically imaged by using colour Doppler, which has some inherent disadvantages: angle-dependency, relatively low frame rate, low velocity range and semi-quantitative nature. Recent advances in ultrasound technology may offer new opportunities for imaging the dynamics of the blood flow in the heart and vessels.Echo-Particle Image Velocimetry (echoPIV), tracks the speckle of ultrasound contrast agent (UCA) microbubbles [New ultrasound techniques, generally referred to as vector flow imaging, can estimate the location, direction and magnitude of velocity vectors describing the flow in a specific region of interest. One such technique, obubbles –3. One oCurrent clinical ultrasound systems use a line-by-line approach in order to construct an echocardiographic image, and lines are generated through focused beams. In order to increase the frame rate and maintain a low acoustic pressure we used a diverging-wave acquisition scheme –8. WhileHigh frame rate echoPIV (HFR echoPIV), using diverging-wave transmit sequences, allows for frame rates in the kHz range and makes tracking of multi-directional fast flow in the left ventricle (LV) possible –7.In this study we demonstrate the potential clinical application of the new HFR approach to echoPIV, and test its feasibility and accuracy in patients with a broad range of pathologies.Nineteen consecutive subjects were prospectively included, selected from patients admitted for heart failure symptoms, regardless of the underlying cause. The purpose of this selection was to test the method in a real-life setting, with everyday regular patients.HFR contrast images were acquired, in apical long axis view , using a fully programmable ultrasound system . We used four repeated diverging-waves, with two alternating polarity transmits , at a depth of 12 cm , aiming for a steady-state relatively low-concentration of bubbles into the LV, allowing for the tracking of individual bubble motion between frames . In the The beamforming and detection of the vector field have already been described in previous works –8. The HAll patients underwent conventional echocardiographic contrast imaging, using the same clinical ultrasound system, during the same imaging session . Complementary imaging studies: (cardiac magnetic resonance (CMR) and cardiac computed tomography (CCT)) were performed during the hospital stay, if clinically indicated.In cases where reference images (CT or CMR) were available, the intracavitary flow direction and particular vortices or jets as seen with HFR echoPIV could be visually related to confirmed anatomical abnormalities.HFR image quality and echoPIV tracking were qualitatively assessed offline by two independent observers  and graded as good, moderate and poor. In case of disagreement, cases were reviewed by an experienced imaging cardiologist (MS). The highest velocity of the inflow and outflow were determined by the automated tracking algorithm of the HFR echoPIV, and also measured by the peak and mean modal velocity of the conventional PW Doppler. For the purpose of this comparison, the only diastolic inflow velocity we measured was the early diastolic (E wave), which is present in all patients regardless of the underlying rhythm.p values < 0.05.Data normality was assessed using a Shapiro–Wilk test. Continuous variables were represented by mean ± standard deviation (SD) or as median (interquartile range = IQR), and discrete variables as proportions (%). Differences between percentages were assessed by using the Chi square test. Correlations were investigated using linear regression. The bias and limits of agreement between methods were computed using Bland–Altman plots. Statistical significance was considered for As the patients were selected in the order of their admission to the hospital for symptoms of heart failure, they exhibited a large palette of pathologies. Their baseline characteristics are presented in Table In the 19 patients, the image quality was good in 10 (53%), moderate in 5 (26%) and poor in 4 subjects (21%). The quality of the echoPIV tracking was good in 12 (63%), moderate in 2 (10%) and poor in 5 (26%).Four patients underwent cardiac CT, 11 patients CMR, while 4 had no reference imaging test. In the 12 patients where the echoPIV tracking was good, the direction and the velocity of the intracavitary vortices during the cardiac cycle could be optimally visualized , and outflow in 14/19 (74%). EchoPIV tended to underestimate the maximal velocity as determined by PW.2 = 0.77 with PW Doppler peak velocity tracing, p < 0.001 and R2 = 0.80 with PW mean velocity tracing, p < 0.001) and moderate for the outflow . The lowest bias was also noted for the inflow as compared to the mean PW velocity tracing  was admitted for increasing dyspnea and thoracic pain. An acute coronary syndrome was excluded. 2D echocardiography demonstrated LV hypertrophy Fig. . She furA 65-year-old male patient, operated 9 years before for idiopathic constrictive pericarditis , with known right ventricular (RV) dysfunction and pulmonary hypertension, was admitted for right heart decompensation. Transthoracic echocardiography demonstrated a dilated and dysfunctional RV , with persistent fatigue and unexplained diarrhea. He had recently been diagnosed with hypereosinophilic syndrome in the referring hospital. On echocardiography LV was dilated with EF = 29%, with calcified moderate aortic stenosis and insufficiency (AI). The AI seemed only trivial at first analysis Fig. .Fig. 10PClinical contrast images were non-contributive  , 11–16. This feasibility study included only a limited number of patients, with various pathologies. This prevents from obtaining conclusions pertaining to the clinical use of HFR echoPIV in particular diseases. We however benefited from this diversity, which simulated the normal variability encountered in clinical practice.Although most of the patients had multimodality imaging studies as clinically indicated, this prospective protocol did not include a gold standard method for flow tracking, we only used regular clinical echocardiography, CMR and cardiac CT. We quantitatively compared PW Doppler in only two precise sites in the LV, which had to be situated in line with the Doppler interrogation line (inflow and outflow of the LV).The present implementation of the HFR echoPIV is limited to 2D HFR echocardiography. The representation of the real intraventricular flow is limited to the position of the slice plane, and cannot detect out-of-plane motion. However, most of the echoPIV studies until now have been performed in 2D, by using the apical long axis view, which intersects the main directions of intraventricular inflow and outflow , 16. We As presented in Methods, the boundary mask for the blood flow analysis was fixed, therefore allowing some myocardial signal into the detection region during systole. We are currently working on a semi-automatic endocardial tracking method, making the boundary detection dynamic and adapted to the real LV endocardial contour.The current version of the software (not optimized for speed) allows for a total duration of this offline postprocessing of approximately 10 min per each recording of 2.5 s. This implies that a clinical application may be developed, in the first step for offline postprocessing, and later for real-time analysis .We demonstrate here the clinical application of HFR echoPIV which succeeds in surpassing the shortcomings of Doppler imaging (angle dependency) and classical contrast echo (low frame rate), with clinical promise and good feasibility in flow tracking and quantification.Additional file 1. HFR echoPIV in a normal subject, in apical longitudinal view. The region of interest is traced along the end-diastolic contours of the LV and include the LVOT. Note the normal diastolic mid-ventricular clockwise vortex induced by the mitral inflow.  Additional file 2. Color Doppler of the LV cavity including the LVOT. In this view the LVOT flow acceleration and narrowing are not visible neither by 2D nor by Color Doppler.  Additional file 3. Classical LV contrast-enhanced echocardiography in the apical long axis view, demonstrating LV hypertrophy and possible narrowing of the LVOT, but the attenuation in the far field precludes optimal visualization.Additional file 4. CMR long axis cine-sequence. LV hypertrophy, systolic narrowing of the LVOT and flow acceleration.Additional file 5. HFR ecoPIV. The systolic outflow (downwards flow through LVOT) presents a narrowing, as well as local acceleration.  Additional file 6. Classical LV contrast-enhanced echocardiography in the apical long axis view, demonstrating mid-LV cavity collapse and apical diastolic dilatation (“mushroom-shaped LV”). The apex has a hyperkinetic motion.Additional file 7. CMR long-axis cine-sequence. The “mushroom” shape is explained by the rigid inferolateral pericardium up to the apical third of the LV  and by the paradoxical septal motion induced by RV overload. The apex is hyperkinetic and dilated in diastole.Additional file 8. HFR echoPIV. There is systolic and diastolic flow acceleration at the junction between the mid and apical LV. Despite the hyperkinetic apex, there is swirling and low velocity counter-clockwise vortex in the dilated apical LV.Additional file 9. Color Doppler of the LV cavity in apical long axis view. The intracavitary flow seems to have a general clockwise rotation towards LVOT, with low velocity . MI is present.Additional file 10. Classical LV contrast-enhanced echocardiography in the apical long axis view. The same global rotational flow is seen as in Color Doppler, with swirling and low flow. MI is not detectable in the far field.  Additional file 11. HFR echoPIV. Two conflicting diastolic vortices rotate clockwise. There is global low flow, both in diastole and in systole. In systole, a part of the downward-going flow converges into the mitral insufficiency.  Additional file 12. Color Doppler of the LV cavity in apical long axis view. Dilated LV with altered systolic function. A mild mitral insufficiency is observed, as well as a seemingly very mild aortic insufficiency.  Additional file 13. Classical LV contrast-enhanced echocardiography in the apical long axis view. Despite a good visualization of the LV structures, no extra information on flow can be deduced.Additional file 14. HFR echoPIV. The mitral inflow is impinged by a high-velocity aortic insufficiency, leading to the formation of multiple vortices and recirculation of the intraventricular flow. Systolic flow velocity in the LVOT is relatively low, accelerating towards the calcified aortic valve.Additional file 15. CMR long-axis cine-sequence. The presence, magnitude and direction of the AI as observed on the echoPIV are confirmed.


All patients underwent a complete stress Doppler echocardiographic examination. Total isovolumic time (T-IVT) as a marker of cavity dyssynchrony and wall motion score index (WMSI) were also calculated. Results: At peak dobutamine stress, the compromised LV longitudinal excursion (MAPSE), systolic septal and lateral velocities (s’), and diastolic indices were more pronounced in the CAD patients compared with those without CAD, but LV dimension did not differ between groups (p > 0.05). The WMSI was higher and t-IVT more prolonged in patients with CAD (p < 0.01 for both). Similarly, the changes were more pronounced in patients with significant CAD compared with insignificant CAD. On multivariate model, Δ mean s’, OR 2.016 , Δ E velocity OR 2.502 , Δ t-IVT 2.206  and Δ WMSI OR 1.911  were the most powerful independent predictors of the presence of CAD, particularly when significant (>75%). Δ mean s’ < 5.0 was 85% sensitive, 89% specific with AUC 0.92. Respective values for Δ E velocity <6.0 cm/s were 82%, 90% and 0.91; for Δ t-IVT > 4.5, 78%, 77% and 0.81 and for Δ FT ≥ 150 ms, 76%, 78% and 0.84 in predicating significant CAD. WMSI ≥ 0.7 was 75% sensitive, 77% specific with AUC of 0.81 in predicting significant CAD. The accuracy of DSE was higher in significant CAD compared to insignificant CAD . Conclusions: Compromised LV longitudinal systolic function, lower delta E wave, prolonged t-IVT, and increased WMSI were the most powerful independent predictors of the presence and significance of CAD. These finding strengthen the role of comprehensive DSE analysis in diagnosing ischemic disturbances secondary to significant CAD.Background and Aim: Dobutamine stress echocardiography (DSE) is a well-established noninvasive investigation for significant coronary artery disease (CAD). The aim of this study was to evaluate the accuracy of cardiac Doppler parameters in predicting CAD. Methods: We prospectively studied 103 consecutive patients with suspected CAD based on typical symptoms; 59 proved to have CAD, and 44 patients proved to have no-CAD ( Exercise electrocardiogram (ECG) remains a widely used technique for managing patients with suspected or established coronary artery disease (CAD), with good prognostic value. However, it is well known for its modest accuracy because of dynamic ST-T wave changes, being impacted by factors other than myocardial ischemia ,2. Over Dobutamine stress echocardiography is unique for not only assessing CAD induced myocardial ischemic dysfunction but also myocardial hibernation in patients with ischemic cardiomyopathy ,7. In adWe prospectively studied 103 consecutive patients with suspected CAD who presented to the cardiology department of the (Bedfordshire) Luton and Dunstable Hospital, UK, complaining of exertional angina, with or without ST-T waves changes on exercise ECG. All patients underwent DSE using conventional protocol, having been identified as carrying intermediate risk for atherosclerosis. The intermediate risk was evaluated by traditional models for which the consideration of another noninvasive technique can help and, consequently, may influence clinical decision making ,15.n = 59) or no-CAD (n = 44). In addition, according to the presence of luminal stenosis, the 59 patients were subdivided into significant CAD  and nonsignificant CAD , congenital heart disease, heart failure, atrial fibrillation, hemodynamic instability or significant pulmonary disease. All echocardiographic measurements were analyzed by two independent investigators blinded to the coronary angiography results. The study was conducted in accordance with institutional policies, national legal requirements and the revised Helsinki Declaration and was approved by the Ethics Committee of Bedfordshire, UK (16/NW/0247). All patients gave verbal informed consent to participate in the study.Data collection: Details of the clinical evaluation of chest pain and cardiovascular risk assessment including dyslipidemia, diabetes mellitus (DM), arterial hypertension (AH), smoking and family history of CAD were evaluated in all patients. The cardiovascular risk was stratified based on presence and the number of risk factors into low (0–1), moderate (2–3) and high (>3) risk for cardiovascular disease.Echocardiographic examination: All patients underwent full echocardiographic examination at rest and at peak pharmacological stress using conventional dobutamine protocol. The echocardiograms were performed by a single cardiologist with over 25 years of experience in DSE using a Philips IE33 Echocardiograph equipped with phased array transducer. All echocardiographic examinations were performed according to the recommendations of the European Association of Echocardiography and the American Association of Echocardiography .Conventional M-mode and pulsed-wave myocardial Doppler velocities were recorded at rest and peak stress . Total amplitude of long axis motion was recorded from mitral annular peak systolic excursion (MAPSE) . Total aThe stress echocardiogram was performed using dobutamine infusion and an IVAC pump with a starting dose of 10 µg/kg/min and increasing by similar incremental dose every 3 min, to a maximum dose of 40 µg/kg/min. Stress endpoints in patients were development of symptoms , a drop in systolic blood pressure by 20 mmHg, ischemic ECG changes such as ST segment shift, T wave inversion or arrhythmia. When patients failed to reach the target heart rate with maximum dobutamine dose, they were given 300 mic of atropine iv. Blood pressure (systolic and diastolic) was measured automatically at rest and at the end of each stress stage using automated sphygmomanometer  . A 12-leCoronary angiography: All patients underwent conventional coronary angiographic examination based on the extent of risk factors, symptoms and stress echocardiographic findings. The Judkin’s technique was used with at least four views of the left coronary system and two views of the right coronary system. Coronary angiograms were processed off-line using raw DICOM format and were analyzed by two senior cardiologists independently.t test and discrete data with chi-square test. Variables were compared between the two groups using the unpaired Student t test or Fisher’s exact probability test. Clinical  and echocardiographic predictors  of the presence and significant CAD were identified using univariate analysis, and multivariate logistic regression method. The receiver operational characteristic (ROC) analyses were performed, and the best cut-off, sensitivity and specificity were determined. A significant difference was defined as p < 0.05 (2-tailed).Statistical analysis was performed using SPSS Software Package version 26.0 . Data are summarized using frequencies (percentages) for categorical variables and mean ± standard deviation (SD) for continuous variables or median interquartile (IQR) ranges. Continuous data were compared with two-tailed Student p = 0.01) and less frequently females  and had higher cardiovascular risk factors compared with those with no-CAD . Out of 103 patients, only 39 (37.8%) had typical exertional chest pain. Some 65 (63.1%) had hypertension, 24 (23.3%) diabetes and 69 (67.1%) dyslipidemia; 51 (49.5%) smoked and 52 (50.4%) had family history of CAD. Low risk factors for cardiovascular disease were present in 29 (28.1%), moderate risk in 66 (64.1%) and high risk in 15 (14.5%) patients. Patients with CAD were older . In patients with CAD, LV longitudinal systolic function was reduced: MAPSE-l, MAPSE-s and MAPSE-p  compared with no-CAD. Again, in patients with CAD, markers of global LV dyssynchrony including t-IVT  and Tei index  were worse compared with those with no CAD. Furthermore, WMSI was significantly higher in CAD compared with no-CAD patients , MAPSE-l , MAPSE-s  and MAPSE-p  compared with resting values . Similarly, LV lateral, septal and posterior systolic velocities (s’) were lower in the CAD compared with no-CAD . LV lateral and septal e’ and a’ velocities increased  equally in both groups (p > 0.05). In contrast, LV cavity E wave  and A wave velocities increased more  while E/e’ ratio decreased  in CAD compared with no-CAD patients. Likewise, markers of global LV dyssynchrony worsened in CAD patients; t-IVT prolonged  and Tei index increased  compared to no-CAD patients. WMSI was significantly higher (p = 0.001) in CAD patients . LV MAPSE-l, MAPSE-s and MAPSE-p were lower in significant CAD  compared with nonsignificant CAD. LV lateral, septal and posterior s’ tended to be lower in the significant CAD patients . LV septal and posterior e’ velocities (p > 0.05) as well as E/a and E/e’ ratio did not differ between groups (p > 0.05 for both). Similarly, there was no difference in LV global dyssynchrony, in the form of t-IVT or Tei index, between groups (p > 0.05 for both), while WMSI was higher in the significant CAD (p = 0.01) compared with nonsignificant CAD patients . LV EF increased in the two groups (p < 0.05) but to a lesser extent in the significant CAD patients , as did systolic longitudinal function . In the same way, LV left, septal and posterior s’ were more compromised in the significant than in the nonsignificant CAD patients . LV lateral e’ and a’ velocities increased similarly in both groups , and E/e’ ratio was higher  in patients with significant CAD. Global LV markers of dyssynchrony were worse in significant CAD patients with t-IVT: −24.1 vs. −37.1%, p = 0.01 and Tei index: −23.5 vs. −32.6, p = 0.001, compared with no significant CAD. WMSI was higher (p = 0.01) in significant CAD patients (At peak stress: The Δ LV dimensions was similar in both groups (patients .p = 0.002), female gender (p = 0.001), diabetes (p = 0.03), dyslipidemia (p = 0.001) and number of risk factors (p < 0.001) predicted the presence of CAD. In the multivariate model, only age , female gender  and number of cardiac risk factors  predicted the presence of CAD (p < 0.001) and female gender  predicted significant CAD , Δ WMSI (p = 0.001), Δ E/A ratio (p = 0.03), Δ A velocity (p = 0.01), Δ mean s’ (p < 0.001) Δ E wave velocity (p = 0.001), Δ A wave velocity (p-0.03), Δ t-IVT (p < 0.001) and Δ Tei index (p = 0.03) predicted the presence of CAD. Δ mean s’, OR 2.016 , Δ E velocity OR 2.502 , Δ t-IVT 2.206  and Δ mean WMSI OR 1.911  independently predicted the presence of CAD on multivariate analysis . However, in multivariate analysis, Δ mean s’, Δ E wave velocity, Δ t-IVT and Δ WMSI independently predicted significant CAD (p < 0.01) p = 0.03, In univariate analysis, Δ EF , and WMSI < 0.7 was 70% sensitive and 71% specific with AUC of 0.72, p < 0.001 in predicting CAD  At peak DSE, basal LV dimensions did not differ between groups; (b) the compromised LV longitudinal systolic function and systolic velocities indices (s’) were more pronounced in the CAD compared with no-CAD patients as well as between significant and nonsignificant CAD; (c) in the same group with significant CAD, the LV diastolic function and global markers of dyssynchrony were more distributed; and finally; (d) The most powerful echo predictors (in accuracy order) of presence of CAD were Δ E wave velocity , t-IVT , Δ mean s’ , Δ FT  and WMSI  and predictors of significant CAD were Δ mean s’ , Δ E wave velocity , t-IVT , Δ FT  and WMSI .Data interpretation: Stress echocardiography has been practiced to diagnose myocardial ischemic dysfunction based on segmental wall motion abnormalities in the form of hypo, akinesia or dyskinesia. The use of this 2D modality resulted in an average DSE accuracy of 63–73% in predicting significant coronary artery stenosis ,27. The It is of significant interest that our results confirm other findings in that diastolic dysfunction in the form of reduced delta E wave velocity was the most accurate predictor of the presence of CAD, irrespective of its severity ,32,33. TClinical implications: While LV wall motion analysis during DSE remains an important noninvasive and radiation-free method for the routine evaluation of patients with suspected coronary artery disease, additional function parameters can increase the accuracy of the investigation in predicting the presence and severity of coronary disease. Early diastolic LV cavity filling velocity attenuation highlights the development of cavity ischemic dysfunction enough to suggest the presence of CAD, irrespective of its severity. Attenuated longitudinal cavity systolic velocity and prolonged total isovolumic time are additional two simple measurements that are 91% accurate in predicting the presence of over >50% coronary branch stenosis. Such measurements, although not built in the routinely used commercial stress echo software, they are routinely acquired in all transthoracic echocardiographic examinations, hence should assist in raising the accuracy of the daily use of such patient-friendly investigation.Limitations: This study has some limitations. The relatively small number of participants did not allow us to stratify the patients into more subgroups according to the severity and distribution of the coronary disease, as well as prevalence of cardiac risk factors. Details about the myocardial deformation parameters including speckle tracking parameters to compare with were not available. None of our studied patients had conduction disease, so the application of the findings in this subset of patients remains to be tested.Compromised LV longitudinal systolic function, lower delta E wave, prolonged total isovolumic time and increased WMSI were the most powerful independent predictors of the presence and significance of CAD. These findings strengthen the role of comprehensive DSE analysis in diagnosing ischemic disturbances secondary to significant CAD.


Background: Cardiac amyloidosis is an underdiagnosed condition and simple methods for accurate diagnosis are warranted. We aimed to validate a novel, dual-modality approach to identify transthyretin cardiac amyloidosis (ATTR-CA), employing echocardiographic relative wall thickness (RWT), and ECG S-wave from aVR (SaVR), and compare its accuracy with conventional echocardiographic approaches. Material and methods: We investigated 102 patients with ATTR-CA and 65 patients with left ventricular hypertrophy (LVH), all with septal thickness > 14 mm. We validated the accuracy of echocardiographic measures, including RWT, RWT/SaVR, posterior wall thickness (PWT), LV mass index (LVMI), left atrial volume index (LAVI), global longitudinal strain (GLS), and relative apical sparing (RELAPS) to identify ATTR-CA diagnosed using DPD-scintigraphy or abdominal fat biopsy. Results: PWT, RWT, RELAPS, troponin, and RWT/SaVR were significantly higher in ATTR-CA compared to LVH. RWT/SaVR > 0.7 was the most accurate parameter to identify ATTR-CA . RELAPS was found to have much less accuracy . Conclusion: We can confirm the very strong diagnostic accuracy of RWT/SaVR to identify ATTR-CA in patients with septal thickness > 14 mm. Given its high sensitivity and specificity, RWT/SaVR > 0.7 has the potential to implement as a non-invasive, simple, and widely available diagnostic tool when screening for ATTR-CA. Transthyretin cardiac amyloidosis (ATTR-CA) is a disease caused by misfolded transthyretin-protein (TTR). Misfolded TTR aggregates and accumulates in the heart muscle. This causes myocardial cell death and increasing thickening of the heart, which interferes with the myocardial function and can later cause heart failure (HF). ATTR is either inherited (ATTRv) or acquired (ATTRwt) and both types may have similar cardiac involvement . HF due Since ATTR-CA has a unique pathophysiological pattern, is it important to avoid common and conventional HF pharmaceuticals. ß-blockers, ACEI/ARB, and diuretics are commonly used to treat HF. ß-blockers inhibit the cardiovascular sympathetic activity and thereby block the full inotropic and chronotropic potential of the heart. Amyloid hearts require adequate heart rate in order to fulfill the peripheral blood need. ACEI/ARB are usually poorly tolerated in ATTR-CA due to the risk of vasodilatation, causing symptomatic hypotension with disease worsening. However, diuretic treatment is well tolerated and is also an important treatment option in ATTR-CA patients ,5.In addition, several specific ATTR-CA treatment options are now available or are being studied in late clinical phase trials. Available treatments either stabilize circulating TTR  or decreDifferentiating ATTR-CA from LVH is complex since they share common phenotype characteristics. The signature appearance of both conditions is abnormal myocardial thickness. There are, however, some clues to differentiate between the conditions. Myocardial hypertrophy is mostly pronounced in the interventricular septum. In comparison, TTR accumulation is more generally distributed, with concentric increased wall thickness, but with less influence in the apical section. This generates a certain heart dynamic that can be illustrated with an echocardiographic presentation called apical sparing pattern . CommonlDifferentiation between LVH and ATTR-CA can also be completed with ECG-parameters, especially in combination with echocardiography . HypertrDespite increasing awareness, ATTR-CA continues to be an underdiagnosed cause of HF . We and The aim of this study is to validate the accuracy of the RWT/SaVR formula in a large cohort of ATTR-CA and LVH patients.This was a retrospective case control study, comparing ATTR-CA with a heterogenous group of LVH patients. Diagnosis was set at the Umea University Hospital in Umea, Sweden. This study also included a validation cohort comprising patients with ATTR-CA from Karolinska University Hospital in Stockholm, Sweden.In total, 102 patients with ATTR-CA and interventricular septum > 14 mm were retrospectively identified from patients seen at Umea University Hospital. ATTR-CA diagnosis was set either non-invasively according to the algorithm proposed by Gillmore et al. using DPD scintigraphy  or by abThe exclusion of light chain amyloidosis (AL-amyloidosis) was performed using blood and urine samples, which were analyzed for serum free light chain (FLC) abnormalities  and the presence of monoclonal bands. Patients with abnormalities in these analyses were evaluated, and their clinical history and disease progression were reviewed to assess the probability of AL-amyloidosis.2). HCM diagnosis was based on exclusion criteria and an interventricular septum hypertrophy (IVST > 14 mm) not explained by increased afterload or infiltrative cardiac disease.A total of 65 patients were included in an LVH control group, all with septal thickness > 14 mm. This group included 14 patients with severe aortic stenosis, 24 with HCM, and 27 with mainly hypertensive heart failure. All had normal LV ejection fraction. Cardiac amyloidosis had been ruled out in the hypertensive heart failure cohort by using DPD scintigraphy and hematological blood workup. Aortic stenosis diagnosis was verified with echocardiographic measurement of the aortic valve area (AVA). Preoperative data was collected exclusively from patients with severe AS  validated the cut off values from deviation study testing RWT and RWT/SaVR.All clinical records were collected from a database at Umea University, within a catchment area of the northern hospital region in Sweden. The following information was collected from all patients included in this study: mortality, height, weight, NT-pro BNP, Troponin T, ECG, and echocardiography. TTR-gene sequencing results were collected from the ATTRv group. DPD-scintigraphy Perugini gradings were collected from the ATTRwt group.A standard 12-lead ECG examination  was recorded for all patients at the time, for diagnosis. In this study we used the S-wave amplitude in aVR (SaVR), more suited for international standards, in contrast to our previous study utilizing the inverted equivalent, R-wave amplitude in -aVR . ECG ampEchocardiographic examination was performed using a Vivid E9 system  equipped with an adult 1.5–4.3 MHz phased array transducer. All echoes were performed and analyzed by one investigator (co-author PL). Standard views were used from the parasternal long axis, short axis, and the apical four-chamber views. Chamber quantification and flow velocities were obtained using pulsed and continuous-wave Doppler techniques, as proposed by recent guidelines ,19.3 [LVDd]3)) + 0.6). LV wall thickness was measured as septal thickness + posterior wall thickness. Pulsed wave Doppler analysis was also undertaken, to assess the transmitral early diastolic E velocity and E deceleration time [Relative wall thickness (RWT) was calculated according to the American society of echocardiography (ASE) recommendations /Left ventricular diastolic diameter (LVDd)). LV mass was calculated through the Devereux formula (0.8(1.04([LVDd + PWT + IVSd]ion time .All Doppler recordings were obtained at a sweep speed of 50–100 mm/s with a superimposed ECG (lead II). Off-line analyses were completed using commercially available software , and the means of three consecutive cardiac cycles were calculated.Anatomical landmarks were used, and care was taken with echocardiographic image acquisition to ensure adequate LV tracking, and to avoid foreshortening of the LV cavity when measuring the global strain of the LV. Longitudinal myocardial deformation was assessed by two-dimensional echocardiography using speckle tracking and was analyzed offline. From the apical four-chamber, two-chamber, and apical parasternal long-axis views, the endocardial border of the septal, apical, and lateral wall of the LV were undertaken manually in order to analyze global LV strain measurements. Strain recordings from three cardiac cycles were averaged to assess the global longitudinal strain (GLS). GLS was measured at end systole with the reference point set at the onset of two consecutive QRS-complexes of the superimposed ECG. We also calculated relative apical sparing (RELAPS) as the average apical strain/. Strain analyses were measured using a dedicated workstation .All patients were investigated with an Infinia Hawkeye hybrid single-photon-emission computed-tomography gamma camera  with a low-energy, high-resolution collimator. An intravenous injection of ~750 MBq DPD was performed 3 h prior to the acquisition of a whole-body planar image, followed by a non-contrast, low-dose CT scan and a SPECT acquisition, which provided 60 projections, iteratively reconstructed into a 128 × 128 matrix  with scatter and CT-based attenuation correction. Reconstruction of SPECT images was performed on the Xeleris workstation . DPD scores were reported by two experienced clinicians using the Perugini grading system , with gr®, version 26 (IBM). Data were presented as either mean and standard deviation or median and interquartile range for continuous variables. Normal distribution was tested using Shapiro–Wilk analysis. Percentages were used to describe categorical variables. Categorical variables were compared using Chi-square tests, and continuous variables were compared using Student’s T-test or Mann–Whitney non-parametric test. ROC analysis was performed to determine the area under the curve, as well as to find optimal sensitivity, specificity, negative and positive predictive values, and accuracy. A p-value of less than 0.05 was considered as of statistical significance.Statistical analyses were performed using SPSSAll subjects gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Umea .Demographic and echocardiographic data from both ATTR-CA and LVH is presented in p = 0.001)). HR and height were higher in ATTR, whereas weight was higher in LVH. Troponin-T (p = 0.02) differed between groups, whereas NT-proBNP did not. Systolic and diastolic blood pressure were higher in LVH patients (p < 0.001) (ATTR-CA patients were older than LVH patients (mean = 76 years for ATTR-CA and mean = 68 years for LVH. (< 0.001) .p = 0.003), and relative wall thickness (RWT) (p < 0.001) were observed in the ATTR-CA group. LVEF/LV mass was significantly lower in ATTR-CA  ( ATTR-CA .p < 0.001).Furthermore, RWT/SaVR and PWT/SaVR were both significantly increased in the ATTR-CA group compared to the control group . In comparison, PWT/SaVR had AUC of 0.95, (p < 0.001). Remaining parameters produced the following AUC: RELAPS  and PWT .Four echocardiographic and ECG-derived parameters with a statistically significant difference between groups were further investigated with ROC (receiver operating characteristics) curves. RWT/SaVR generated the highest AUC among the studied selection , and PWT/SavR (p < 0.001) had a sensitivity of 94% and specificity of 82%. RWT > 0.5 had the highest combined sensitivity and specificity, which was 84% and 82% (p < 0.001). RELAPS > 1.2 showed the highest combined sensitivity and specificity of 74% and 76% (p < 0.001). PWT > 11.5 had sensitivity and specificity of 82% and 78%, respectively (RWT/SaVR > 0.7 presented the highest combined sensitivity (97%) and specificity (90%) to identify ATTR-CA . Most conditions causing increased cardiac wall thickness are characterized by myocardial hypertrophy and thus show electronically active myocardium causing higher QRS-amplitudes. Myocardial amyloid buildup in the heart, however, has the opposite effect, lowering QRS-amplitudes. The mechanism behind this is most probably amyloid infiltration, which suppresses the electrical signal.The sensitivity and specificity of RWT/SaVR in our study (97% and 90%) are surprisingly high. They are actually comparable to DPD-scintigraphy (98% and 92%) and higher when compared to both MRI (84% and 87%) and PET (78% and 95%) presented in a recent meta-analysis study . HoweverDespite the increasing availability of cardiac MRI, PET, and technetium bone tracer scintigraphy in some parts of the world, these investigations remain costly and not readily accessible for a vast number of patients. The availability of ECG and echocardiography makes the RWT/SaVR ratio a highly useful tool for selecting patients for further work up, and possibly for epidemiological studies where advanced imaging is not possible.Limitations: There are limitations in this study. We used a cut-off value of >14 mm investigating ATTR-CA whereas others recommended a cut of >12 mm. However, we consider >14 mm to be a more appropriate cut-off due to the numbers to investigate with DPD scintigraphy for final diagnosis. Patients with aortic stenosis and patients with HCM had not undergone work up to rule out CA (DPD scintigraphy). However, mean age in each group (62 and 65 years) reduces the suspicion of ATTRwt.Being a retrospective study, the analyses were not blinded and therefore at risk of bias. Furthermore, the study does not include patients with very mild disease nor patients with AL amyloidosis, so further evaluations including a more heterogenous CA population, and preferably more centers, are warranted.We confirm the very strong diagnostic accuracy of using RWT/SaVR to identify ATTR-CA in patients with moderate or advanced disease. RWT/SaVR > 0.7 demonstrated the highest combined sensitivity and specificity, with which to identify ATTR-CA, when compared with conventional echocardiographic variables. The proposed method is simple to measure and widely used in cardiology centers.


This study aimed to investigate the course of tricuspid annulus dilation in functional tricuspid regurgitation with varied severities by direct intraoperative assessment.A total of 317 patients who underwent left heart surgery and concomitant tricuspid repair were divided into three groups according to the severity of the functional tricuspid regurgitation . Demographic and echocardiographic data were collected. The length of each tricuspid annulus segment was measured intraoperatively. The risk factors for preoperative severe functional tricuspid regurgitation and its postoperative recurrence were identified, and the impact of each tricuspid annulus segment on postoperative recurrence was compared.p < 0.01), the anterior annulus dilated 13.4% , and the septal annulus dilated 11.4% . Tricuspid annulus circumference index (p < 0.01) independently correlated with preoperative severe tricuspid regurgitation and postoperative recurrence. When patients were grouped based on the length of each segment, the septal annulus demonstrated significantly higher sensitivity (p < 0.001) to postoperative recurrence than the anterior (p = 0.085) or posterior annulus (p = 0.262).In the course of tricuspid annulus dilation, the posterior annulus dilated 17% (group 1: 33.31 ± 6.94 mm vs. group 2: 35.56 ± 7.63 vs. group 3: 38.98 ± 8.70, This study revealed that each segment of tricuspid annulus could dilate in functional tricuspid regurgitation and highlighted the potential benefits of septal annulus plication in tricuspid annuloplasty, which may aid in the development of a methodology for prosthetic ring annuloplasty. Functional tricuspid regurgitation (FTR) is the most common pathology involving the tricuspid valve, which generally occurs secondary to left-sided heart disease, atrial fibrillation (AF), or pulmonary hypertension as a consequence of tricuspid annulus (TA) dilation. Recently, the research is focused on the treatment of FTR , as it mProsthetic ring annuloplasty plays an important role in tricuspid repair , which iFurthermore, when we selected the ring size during tricuspid annuloplasty based on the length of the septal annulus, we observed that Carpentier's technique of measurement was not applicable in some cases because the septal annulus could be larger than the largest size of the obturator . SeveralBased on these conflicting results, there is an urgent need for a better understanding of the changes in TA during its pathological course. Therefore, this study aimed to investigate the course of TA dilation in patients with FTR with varied severities using direct intraoperative assessment, which could contribute to developing a methodology for tricuspid annuloplasty.2), or mild tricuspid regurgitation with AF. Surgical procedures of the left heart included mitral and aortic valve repair, mitral and aortic valve replacement, combined mitral and aortic valve replacement. If necessary, Cox-Maze IV procedure and coronary artery bypass grafting (CABG) were simultaneously performed in patients with AF and coronary heart disease, respectively. Patients who previously underwent left heart surgery or had right coronary artery disease were excluded. All patients were followed up after discharge.A total of 317 patients with left-heart valvular disease and FTR who underwent left-heart surgery and TA repair between August 2017 and October 2020 in our hospital were enrolled. The surgical indications for TA repair included either moderate and severe tricuspid regurgitation, mild tricuspid regurgitation with annular dilation of ≥40 mm (or ≥21 mm/m2), mild (VC <3 mm), moderate (VC <7 mm), and severe (VC ≥7 mm). Left ventricular ejection fraction and heart chamber diameters were assessed according to the American College of Cardiology/American Heart Association (ACC/AHA) guidelines  width in the apical four-chamber plane view and was qualitatively graded as trivial , and Sorin Sovering flexible ring  according to the manufacturers' protocol.t-test, one-way analysis of variance, Mann–Whitney U test, and Kruskal–Wallis H test were used to compare continuous variables between groups. Factors correlated with preoperative severe FTR and postoperative recurrence of FTR were analyzed using binary logistic regression and Cox proportional hazards regression analysis. In univariate analysis, significant factors (p < 0.1) were included in the multivariate analysis, and forward conditional logistic regression was used to identify the risk factors. The validation of the prediction model was presented as receiver operating characteristic (ROC) curves. Kaplan–Meier (KM) survival analysis was performed to investigate the impact of the length of TA on postoperative FTR recurrence. All statistical analyses were performed using statistical package of social sciences  and Prism 8.2.1  software, and a p-value of < 0.05 was considered statistically significant.Categorical variables were expressed as the number and percentage of patients. Continuous data were presented as either means ± standard deviations if the variables were normally distributed or as medians with interquartile ranges (1st−3rd) if they were non-normally distributed. Fisher's exact test or chi-square test was used to compare categorical variables. The unpaired student's p < 0.01). Patients in groups 2 and 3 had higher proportion of class III–IV of New York heart association (NYHA) classification; a greater proportion of AF; and higher levels of N-terminal pro-brain natriuretic peptide (NT-BNP), total bilirubin, and creatinine than those in group 1. In the analysis of echocardiographic parameters (n = 107), mitral valve replacement (n = 167), mitral valve repair (n = 45), aortic valve replacement (n = 9), CABG (n = 4), and Cox-Maze IV (n = 5). The methods of TA repair included the Kay procedure and tricuspid annuloplasty using Sorin Sovering flexible ring and Edwards MC3 rigid ring. One patient each in group 2 and group 3 expired due to refractory heart failure on postoperative day 4 and cerebral hernia on postoperative day 1, respectively. The remaining patients were followed up until November 1, 2021, and the median follow-up time was 18.90 (11.39–26.03) months. FTR recurrence was observed in 27 patients (8.5%).A total of 317  patients with an average age of 57.67 ± 11.42 years were included in the study. They were divided into three groups according to the FTR severity . Preoperative and operative data are summarized in rameters , patientIntraoperative TA data are summarized in p < 0.01)], NYHA classification , preoperative AF , and preoperative mitral stenosis  were independent predictors of severe preoperative FTR . Moreover, when the TACI was combined with NYHA classification, preoperative mitral stenosis, and preoperative AF, the sensitivity and specificity for predicting preoperative FTR increased to 78.0 and 84.5%, respectively   and TA geometry, PASP, left atrium (LA) dimension, and etiology of mitral valve disease were found to be highly associated with severe FTR on univariate analysis . Multivative FTR . Using R < 0.01) .p < 0.05) and the TACI  independently correlated with FTR recurrence in Cox regression analysis. Patients were grouped into tertiles (T) based on the length of each annulus segment . KM survival analysis demonstrated no significant difference between T1 and T3 when the patients were grouped based on the length of the anterior or posterior annulus , which was significantly lower than the one reported previously  . Second,Cardiovascular surgeons often refer to Carpentier's technique of tricuspid repair, especially tricuspid annuloplasty using prosthetic rings . This teRecently, echocardiographic studies have reported that different mechanisms of FTR would lead to different geometric changes in TA . CompareBased on the echocardiographic study, TA demonstrated increased annular area, planarity, and circularity with the development of FTR. According to our measurements, each TA segment dilated with an increase in the FTR severity. Compared with group 1, group 2 demonstrated increased dilation of the anterior, posterior, and septal annuli of ≈4.1, 6.8, and 4.1%, respectively. Similarly, compared with group 2, the anterior, posterior, and septal annuli in group 3 were significantly more dilated by ≈9.0, 9.6, and 6.8%, respectively. We observed that from mild to severe FTR, each TA segment dilated significantly ranging from 10 to 20%. Specifically, the posterior annulus was dilated with the largest ratio of ≈17.0%, followed by the anterior (13.4%) and septal annuli (11.4%). Such tricuspid annulus dilation is considered almost proportionate. Based on our data, we confirmed Deloche's findings that the posterior annulus dilated with the largest ratio in FTR. However, there was no significant difference in the dilation ratio between each TA segment, as reported previously  .The reason for the above findings, especially septal annulus dilation, which are contrary to Deloche's theory, remains unknown. The possible reasons are as follows: first, Deloche's study had a small sample size with unknown inter-individual variations. Moreover, this study was executed with heart immersion in formalin fixation, which was known to cause morphometric changes in the preserved tissue, including the TA , 21.Second, Kawada et al. stated that the posteroseptal commissural point was located on the free wall of the RV rather than on the interventricular septum . In addiThird, in addition to the muscular part of the septal annulus , the fibrous part of the septal annulus (the part attached to the interventricular septum) might have also been affected by the dilation of the RV with pulmonary hypertension caused by any reason . SimilarFourth, differences among the races and disease spectra should be considered. To the best of our knowledge, the studies which proposed notions contrary to Deloche's theory and Carpentier's technique were predominantly from Japan . Kondoh 2 is considered an indication for tricuspid repair in patients undergoing left heart surgery  or RV, heart function, permanent pacemaker implantation, pulmonary hypertension, leaflet tethering, and rheumatic etiology of left heart disease , 29. ThiThe concept of tricuspid dilation is as follows: dilation of the tricuspid annulus chiefly occurs in the posterior and anterior annuli. Currently available tricuspid rings have markers indicating the suturing position of the anteroposterior and septoposterior commissures. Such rings are designed especially for posterior annulus plication; however, based on our data, which is in accordance with other studies, we observed that each TA segment could dilate in FTR. These findings have significant clinical implications, as the current tricuspid ring might not entirely support the septal annulus, resulting in FTR recurrence. Thus, we highlight the potential benefits of septal annulus plication. We previously reported our 3-J technique for tricuspid annuloplasty to improve the FTR outcome . The earFirst, this was not a randomized controlled study; whether a concomitant tricuspid repair should be performed in patients with trivial or mild FTR while undergoing left heart surgery was decided by surgeons, which would cause selection bias. Second, not all patients were entirely followed up due to poor medical conditions of some patients who cannot return for a follow-up and no available international medical data-sharing platform. Finally, echocardiographic evaluation of the right heart and TV function was not comprehensive, as some parameters such as RA area, RA volume, and TV tenting height and area, were not routinely measured in our center.Each TA segment could dilate with FTR severity  ranging from 10 to 20%, which varies from the previously reported results. The TACI is independently associated with severe preoperative FTR and postoperative FTR recurrence. The length of the septal annulus displays higher sensitivity to postoperative FTR recurrence than the anterior or posterior annulus. Based on our findings, septal plication should be performed during tricuspid annuloplasty to obtain favorable long-term results.The original contributions presented in the study are included in the article/The retrospective use of the database and this study were approved by the Institutional Review Board and Ethics Committee of the First Affiliated Hospital, College of Medicine, Zhejiang University.Study conception and design was performed by PT, LM, and YN. The echocardiographic data was collected by SY and YC. The clinical data was collected by XD. PT drafted the manuscript and was revised by YZ. All authors confirmed the final version of the paper, read, and approval the final manuscript.This study was funded by Key Research and Development Program, Zhejiang Province, Project Number: 2019C03008 and funded by Public Welfare Technology Application Research Project, Zhejiang Province, Project Number: LGF19H020012.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Chronic kidney disease patients have increased risk of cardiovascular abnormalities. This study investigated the relationship between cardiovascular abnormalities and the severity of chronic kidney disease using cardiac magnetic resonance imaging.n = 23; group II: stages 4–5, n = 20; group III: hemodialysis patients, n = 41) and 32 healthy subjects. The demographics and biochemical parameters of the study subjects were evaluated. All subjects underwent non-contrast cardiac magnetic resonance scans. Myocardial strain, native T1, and T2 values were calculated from the scanning results. Analysis of covariance was used to compare the imaging parameters between group I-III and the controls.We enrolled 84 participants with various stages of chronic kidney disease , global radial strain  and global circumferential strain  were significantly worse in group III patients compared with the controls. Furthermore, the global longitudinal strain had a significant decline in group II and III patients compared with the controls . Compared with the controls, the native T1 values were significantly higher in group II and III patients , and T2 values were obviously higher in group I-III patients . The advanced chronic kidney disease stage showed significant positive correlation with global radial strain , global circumferential strain , native T1  and T2  values. In comparison with the group II patients, hemodialysis patients showed significantly lower T2 values , but no significant difference in T1 values .The left ventricular ejection fraction .ChiCTR2100053561 ( Chronic kidney disease (CKD) is a major health problem worldwide with the rates of morbidity and mortality increasing by 29.3 and 41.5%, respectively, between 1990 and 2017 .Non-contrast cardiac magnetic resonance (CMR) imaging can be used to monitor changes in myocardial mass and biventricular volumes in CKD patients undergoing long-term hemodialysis (HD) . CMR is Previous CMR studies , 11 repoIn this prospective longitudinal observational study, 84 participants with different stages of CKD were enrolled from the Department of Nephrology, Wuhan Union Hospital, between March 2021 to October 2021. We also enrolled 32 healthy subjects of similar age, gender, and body mass index (BMI) from the Wuhan community between March 2021 to October 2021. This study was approved by the Ethics committee of the Tongji Medical College of Huazhong University of Science and Technology. It was first registered on 24/11/2021 with the registration number ChiCTR2100053561, and was conducted in accordance with the Helsinki Declaration. The written informed consent was obtained from all the study subjects.The inclusion criteria for participants with CKD were as follows: (1) clinically confirmed CKD at different stages; (2) age between 30 and 80 years; (3) absence of chest pain, dyspnea, and palpitations; (4) absence of history for cardiovascular diseases such as congenital heart disease, coronary artery disease, valvular heart disease, or cardiomyopathy; and (5) normal electrocardiographic manifestations. All dialysis patients had maintained hemodialysis for 4 hours, 3 times a week for at least 3 months. The inclusion criteria for the healthy controls were as follows: (1) age between 30 and 80 years; (2) absence of history for cardiovascular diseases, hypertension, hyperlipidemia, and diabetes; (3) normal physical examination; and (4) normal electrocardiographic manifestations. The exclusion criteria for the participants with CKD were as follows: (1) history of known specific cardiomyopathies, valvular heart disease or myocarditis; and (2) standard contraindications to CMR .2; n = 23), group II , and group III . The estimated GFR was calculated using the four-variable Modification of Diet in Renal Disease (MDRD) formula . Additionally, group II (CKD 4–5 non-HD patients) had very advanced CKD as evident by creatinine >500, hemoglobin 79 and calcium 1.9.Participants with CKD were divided into the following three groups: group I  of all the study subjects. We also extracted the values of systolic blood pressure (SBP), diastolic blood pressure (DBP), and serum biochemical parameters such as creatinine, hemoglobin, albumin, alkaline phosphatase (AKP), parathyroid hormone (PTH), urea nitrogen, uric acid, erythrocyte sedimentation rate (ESR), thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free tetraiodothyronine (FT4), triglycerides (TG), total cholesterol (TC), lactate dehydrogenase (LDH), calcium, and phosphorus for all patients from the electronic records before CMR scanning . Study sThe CMR scans were performed in a 1.5 T MAGNETOM Aera MRI scanner  equipped with 18-channel phased-array surface coils using the vector electrocardiogram gating. Participants with CKD were all scanned on the next day after confirmation of CKD by nephrologists. Dialysis patients were all scanned on non-dialysis days but not after a long break; thus, all scans were performed within 18 to 24 h after the most recent dialysis session . Cine imNative T1 mapping at the base, mid, and apical levels of the LV short axis were performed using the modified look-locker inversion recovery (MOLLI) sequence. The T1 mapping parameters were as follows: repetition time, 3.89 ms; echo time, 1.12 ms; slice thickness, 8 mm; flip angle, 35°; field of view, 360 × 270 mm; and matrix, 256 × 192. T2 values of the LV myocardium were estimated from the T2 map that was generated using the T2-prepared single-shot SSFP sequence. T2 mapping parameters were as follows: repetition time, 3.244 ms; echo time, 1.35 ms; slice thickness, 8 mm; flip angle, 70°; field of view, 360 × 75 mm; and matrix, 192 × 83.2) = √ ((weight (kg) × height (cm)/3600)).CMR image analysis was performed using the commercially available CVI42 software , and the analyst were blinded to the CKD group of study populations. The volumetric and functional parameters of the left ventricle were measured using the continuous short-axis slice cine images by manually tracing the endocardial and epicardial borders. The papillary muscles and trabeculations were excluded as part of the ventricular mass. CMR parameters such as LV end-diastolic volumes index (EDVI), end-systolic volume index (ESVI), stroke volume index (SVI), ejection fraction (EF), LV mass index (LVMI) and cardiac index (CI) were measured by the commercial CVI42 software  automatically. The left atrial volume index (LAVI) was calculated manually by tracing the endocardial left atrial (LA) borders in the two long-axis cine images (2 and 4-chamber views). The values were adjusted for the body surface area using the Mosteller formula (The regions of interest (ROIs) were manually delineated in the mid-layer of the myocardium among the basal, middle, and apical LV segments to measure native T1 and T2 values. Sixteen ROIs were drawn for each participant based on the American Heart Association 16-segment model –F. The iThe peak systolic LV strain parameters were calculated using the CVI42 software . Multiple long-axis cine images  and short-axis cine images were imported into the software. Then, the endocardial and epicardial borders of the LV were delineated in the end-diastolic frame (including papillary muscles and trabeculations) and automatically propagated throughout the cardiac cycle. The global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) of the LV were obtained manually from the cine images –I.t-test. Differences between the categorical variables were analyzed using the chi-square test. Differences in the clinical and CMR parameters between the three CKD patient groups and healthy subjects were compared by analysis of variance (ANOVA). Differences in the CMR variables after adjusting for age, BMI, and HR were assessed by analysis of covariance (ANCOVA). The relationships between CMR parameters and CKD stages of CKD patients without hemodialysis were examined using Spearman's correlation tests. P-value < 0.05 (two-tailed) was considered statistically significant.Statistical analysis was performed using the SPSS version 26.0 software . Kolmogorov–Smirnov test was used to analyze the normal distribution of continuous data. The normally and non-normally distributed data were summarized as means ± standard deviation and median , respectively. Differences between the normally distributed variables were analyzed using the independent-sample Student's p = 0.336), sex (p = 0.220), BMI (p = 0.064) and HR (p = 0.205) were similar between the group of participants with CKD and healthy subjects. However, significant differences in age (p < 0.001), BMI (p = 0.023), and HR (p = 0.001) were observed among the healthy subjects and the three groups of participants with CKD, namely, CKD 1–3, CKD 4–5, and HD . Furthermore, the CMR-derived parameters LVESVI, LVEF and maximum LAVI values never had significant change in patients without HD.p = 0.024) (= 0.024) .p = 0.003) (p < 0.001) (= 0.003) . Further< 0.001) . The sep< 0.001) .r = −0.246, p = 0.008) and positive correlation with HR . After adjusting for BMI and HR, CKD stages of patients without HD showed positive correlation with the LVEDVI , LVESVI , LVMI , CI , GLS , and GCS   and GRS   and T2 values  (As shown in < 0.001) ,B. Furth= 0.001) . Further< 0.001) ,E.p > 0.05). In contrast, T2 values in the HD patients were significantly lower compared with those non-HD patients with CKD stages 4-5  (= 0.002) ,B. The sThis study shows that CMR parameters reflecting LV myocardial structure and function get worsen with advancing CKD stages. Participants with CKD stages 4–5 were more likely to occur significantly increased T1 values, which may reflect myocardial fibrosis. The increased native T1 values and decreased T2 values of HD patients might be due to increasing myocardial fibrosis in the HD group but with reduction in oedema following effective fluid management on dialysis.In this prospective study, changes in the myocardial strain parameters like GLS, GCS, and GRS were associated with advanced CKD stage. This suggested significant alterations in the myocardial wall remodeling among patients with advanced or severe CKD. Furthermore, this study showed that GLS of participants with CKD decreased significantly from stages 4–5 onwards when compared with the healthy subjects, whereas LVEF values were reduced in the CKD patients undergoing hemodialysis. These results were in agreement with previous reports demonstrating GLS as a more sensitive parameter than LVEF in detecting subclinical LV dysfunction because GLS directly measures the movement of myocardial fibers , 17. TheA previous report  suggesteCKD progression facilitates the onset of myocardial fibrosis . HoweverIn our study, participants with CKD undergoing HD showed significantly reduced T2 values compared with non-HD patients with CKD stages 4–5. Previous studies reported that T2 values were related to myocardial fluid content –30. Our Our study has a few limitations. Firstly, the sample size of our single-center study was small. It was difficult to stratify patients into CKD 1-5 stage and directly state which stage of 1-5 shows the significant reduction in myocardial function. Therefore, large cohort, multi-center studies are necessary to confirm our findings and explore potential relationships between myocardial abnormalities and CKD stages. Secondly, the cross-sectional nature of this study may have affected the results because of individual differences among the study subjects. We did not compare parameters of participants with CKD before and after dialysis. Therefore, in the future, a longitudinal study needs to be performed to confirm our results. Thirdly, although the CKD groups were matched with the healthy subjects based on age, BMI, and HR, significant inter-group differences existed among the four groups. Therefore, we used ANCOVA to exclude the influence of these confounding factors. Forthly, there was a lack of assessment of myocardial fibrosis and fluid status, either clinically or bioimpedance. Finally, because of the small sample size, we did not investigate the effects of important factors such as hypertension and diabetes that can influence cardiac functions.In conclusion, myocardial strain, native T1, and T2 values progressively got worse as the severity of CKD increased. Myocardial fibrosis and edema were observed more frequently in participants with advanced CKD or severe CKD requiring HD. The increased native T1 values and decreased T2 values of CKD patients undergoing HD might be due to increasing myocardial fibrosis in the HD group but with reduction in oedema following effective fluid management on dialysis. Further large cohort multi-center studies are needed to confirm our findings.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of the Tongji Medical College of Huazhong University of Science and Technology. The patients/participants provided their written informed consent to participate in this study.XJ, XH, and YC conceived and designed the study. YC and HS provided the administrative support. YW, FH, and CZ provided study materials and patients. XJ, XH, and YZ collected and assembled data of the study. XJ and XH analyzed and interpreted the study data. All authors read and approved the final version of the manuscript.Author XZ was employed by MR Collaborations, Siemens Healthineers Digital Technology (Shanghai) Co., Ltd., Shanghai, China. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


However, the binary logistic regression analysis revealed that only LV GLS, GCS, and LASr were independently associated with the presence of MF . None of the echocardiographic parameters correlated with fibrosis localization. Conclusions: In NIDCM patients, MF is correlated with reduced mechanical parameters in both ventricles and atria. LV GLS, LASr, and LV GCS are the most accurate 2D echocardiography predictive factors for the presence of MF.Background: In patients with non-ischemic dilated cardiomyopathy (NIDCM), myocardial fibrosis (MF) is related to adverse cardiovascular outcomes. The purpose of this study was to evaluate the potential relationship between the myocardial mechanics of different chambers of the heart and the presence of MF and to determine the accuracy of the whole-heart myocardial strain parameters to predict MF in patients with NIDCM. Methods: We studied 101 patients  with a first-time diagnosis of NIDCM who were referred for a clinical cardiovascular magnetic resonance (CMR) and speckle tracking 2D echocardiography examination. We analyzed MF by late gadolinium enhancement (LGE), and the whole-heart myocardial mechanics were assessed by speckle tracking. The presence of MF was related to worse strain parameters in both ventricles and atria. The strongest correlations were found between MF and left ventricle (LV) global longitudinal strain (GLS) (r = −0.586,  Heart failure (HF) is a major cause of morbidity and mortality worldwide and is expected to increase due to the aging population. Cardiomyopathies are a group of structural and functional disorders that often lead to HF . NIDCM iischemic coronary disease (ICD). All patients underwent invasive coronary angiography. ICD was defined as a history of myocardial infarction, revascularization, and the presence of epicardial coronary artery diameter stenosis > 50%;primary valvular heart disease;2);chronic kidney disease .This study population consisted of 101 patients with NIDCM treated at the Hospital of Lithuanian University of Health Sciences Kaunas Clinics between January 2019 and January 2022. The NIDCM diagnosis was defined according to the World Health Organization criteria and the latest European Society of Cardiology (ESC) proposal [All patients underwent a comprehensive clinical evaluation, laboratory test assessment, electrocardiogram (ECG), Holter monitoring , 2D transthoracic echocardiography, and CMR with LGE. Ethical approval was obtained for this study by the Kaunas Regional Biomedical Research Ethics Committee, and all participants gave written informed consent prior to enrollment.2D echocardiography was performed using commercial ultrasound systems (Philips EPIQ 7) according to a prespecified protocol with recommendations by the European Association of Cardiovascular Imaging . All imaFor 2D cardiac morphometric measurements, end-diastole was defined as the cardiac cycle frame when the LV or right ventricle (RV) internal diameter was the largest and end-systole as the frame when the LV or RV cavity was the smallest. Left atrial volume (LAV) and right atrial volume (RAV) were calculated using the apical biplane area-length method and were indexed to body surface area. LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LVEF were measured from the apical four- and two-chamber views and calculated by Simpson’s biplane method, following manual delineation of the endocardial border in the largest (end-diastolic) and smallest (end-systolic) boundaries. LVEF (%) was estimated by the following formula: (LVEDV−LVESV)/LVEDV × 100% .The EACVI/ASE/Industry Task Force consensus document was used to standardize left atrial (LA), right ventricular, and right atrial (RA) myocardial deformation parameters . RV longitudinal strain (RVLS) values were assessed from the modified RV-focused apical 4-chamber view. Global RV longitudinal strain was evaluated by averaging peak strain values from six segments: three from the RV free wall and three from the interventricular septum. RV free wall longitudinal strain was averaged from the free wall segments only  Figure .The single apical four-chamber view was used to automatically assess the values for LA strain during the reservoir (LASr), conduit (LAScd), and contraction (LASct) phases. To obtain the LA strain values from an optimized  apical four-chamber view, we used the Task Force recommendations . The zerFor the assessment of GLS, apical four-chamber, two-chamber, and long-axis views were acquired. LV circumferential and radial strains were measured by endocardial tracing in the basal, middle, and apical levels of LV short-axis views. The GLS, GCS, and global radial strain (GRS) were defined as the average peak strain values automatically generated from the 16 segmental strain curves by the software  Figure .Twenty patients were randomly selected, and a Bland-Altman analysis was performed to evaluate the intraobserver and interobserver variability, which shows a good agreement with a small bias of 0.5 ± 2.7% and 0.7 ± 3.9%, respectively.The CMR scans were performed on a 3T magnetic resonance imaging scanner with an 18-channel cardiac coil . Images were acquired during an expiratory breath hold with ECG gating. CINE images were acquired using standard balanced steady-state free precession sequences in three long axes  and an appropriate amount of short axis images (8 mm slices with a 2 mm inter-slice gap). LGE images were acquired in identical positions following an intravenous injection of gadobutrol (0.1 mmol/kg). LGE images were visually analyzed by an experienced reader for the presence and type (ischemic vs. non-ischemic) of enhancement . Subjectp-value of <0.05 to be statistically significant. Continuous variables were expressed as means ± standard deviations (SD). Categorical variables were presented as absolute numbers and percentages and were compared using the Chi-square test. The Kolmogorov–Smirnov test was used to assess the normal distribution of the data. The student’s t-test was used to compare normally distributed variables, and the Mann–Whitney U-test was used for abnormally distributed variables among groups. We divided our study population into two groups according to the presence of MF (fibrosis positive and fibrosis negative). If one variable was categorical and one was continuous, the point-biserial coefficient of correlation R2 was calculated. A binary logistic regression analysis was used to determine the predictors of MF. The receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of echocardiographic strains to detect MF. The cut-off value of the predictive model was defined as the point that yielded the maximum value of the sum of sensitivity and specificity.The data were analyzed using SPSS version 22 . We considered a p = 0.832). Patients with MF had higher rates of ventricular arrhythmias (ventricular tachycardia or fibrillation) compared to those without  or with severe HF . The baseline demographic and clinical characteristics of the patients and the data from cardiac 2D echocardiography are shown in p < 0.001). Moreover, the presence of MF was associated with a lower LVEF (p < 0.001) and more reduced LV strain values (p < 0.001). RV fractional area change was better in patients without LGE . RV-free wall longitudinal strain and GLS were more reduced in the group with the presence of MF. Both atria were more dilated (only volume index) and had the worse function in the group with MF . The patients with MF had more dilated LV (difference between groups with p < 0.001). A weak correlation was found with RV strain parameters, RA reservoir strain , and RA contractile strain . A moderate correlation was observed between MF and RA conduit strains . The relationships between myocardial mechanics and MF are shown in Binary logistic regression analysis showed that only LV GLS, LV GCS, and LASr were independently associated with the presence of MF . p < 0.001), LV GLS , and LASr  were the strongest 2D echocardiographic predictors in the prognostication of MF. A cut-off value of −14.4 of LV GCS could prognosticate the presence of MF with a sensitivity of 100% and specificity of 85%. A LV GLS cut-off value of −9.5% could prognosticate the presence of MF with a sensitivity of 100% and specificity of 83%. The optimal cut-off value of LASr for the detection of MF was 11.7%, with a sensitivity of 86% and specificity of 82%.To evaluate the performance of the independent echocardiographic variables, we compared the area under the curve (AUC) of the ROC curves of LV GCS A, LV GLSThe findings of this study can be summarized as follows: (1) In patients with NIDCM, myocardial mechanics are more impaired in patients with the presence of MF; (2) LV GCS, LV GLS, and LASr are the best 2D echocardiographic deformation parameters to prognosticate the presence of MF.Cardiac fibrosis occurs early in the progression of NIDCM, increasing cardiac rigidity, decreasing myocardial performance, and enhancing the risk of sudden cardiac death and life-threatening arrhythmias. Cardiac fibrogenesis is a multistep process initiated in response to pro-inflammatory stimuli and cytokines. Many cells, such as macrophages, monocytes, T lymphocytes, mast cells, and endothelial cells, are involved in the development of MF . Early studies using LGE by CMR to assess for the presence of MF have reported that one-third to two-thirds of DCM patients have focal MF ,15. In rWe did not find an association between the clinical data of patients, such as age and gender, and the presence of MF. The data are lacking on the influence of gender or age on the prevalence and extent of LGE in NIDCM in other studies also. Some authors have reported that only the male sex predicts the presence of MF , and thePrevious data have suggested a strong correlation between MF and the worsening of HF ,20. Our Lisi et al. reported that RV-free wall longitudinal strain was independently associated with RV fibrosis and was the main determinant of MF . HoweverDespite the well-established focus on LV deformation parameters as predictors of outcomes in many cardiac diseases, the prognostic value of LA function has been recently gaining attention as well . Some studies have revealed that the LA reservoir strain is a sensitive prognostic marker ,27. LA lUnlike LASr, RA strain values showed only a weak correlation with the presence of MF. This could be explained by the fact that NIDCM more often affects the left-sided chambers of the heart. Additionally, RA strain is technically difficult to measure due to the difficulty in contouring thin walls and unusual chamber geometry . Our data support that LV GLS, LV GCS, and LASr are the most important prognostic factors for the presence of MF.There are several limitations to our study. First, this is a single-center cohort study with a small sample size. Secondly, our cohort mainly consisted of white men, which is not necessarily representative of all patients with NIDCM. Further studies in multi-center cohorts with extended follow-up are needed to verify the results of this study. Thirdly, we did not quantify the extent of LGE in this cohort, as we thought that the cohort was too small for further differentiation to yield results from which reliable conclusions could be drawn. Additionally, we only used 2D echocardiographic strain parameters for the assessment of myocardial mechanics. Finally, no follow-up data were available; thus, the prognostic value of our findings is not known.In patients with NIDCM, MF is correlated with reduced mechanical parameters in both ventricles and atria. However, it is more closely related to the reduced strain values of LV and LA. LV GLS, GCS, and LARs are the strongest predictive factors for the prediction of MF. Clinicians should consider the routine use of these markers for early suspicion of MF and potential referral to CMR.


Background: Pressure-strain loop (PSL) analysis provides a novel, less load-dependent non-invasive method to quantify myocardial work and demonstrates a significant correlation with the contractile reserve in adult athletes. We aim to validate PSL-derived markers in characterizing LV function in pre-adolescent basketball players by comparing results before and after the cardiopulmonary exercise test (CPX) and explore its association with CPX-derived aerobic capacity.Methods: Cardiac morphology and function in 20 pre-adolescent basketball players were assessed at 9.7 years old (9.7 ± 1.1 year) before and after cardiopulmonary exercise testing. Echocardiography was performed in all subjects, including two-dimensional speckle-tracking echocardiography (STE). Simultaneous brachial-cuff-measured blood pressure was recorded to perform PSL analysis.Results: Nineteen subjects were included in the final analysis. Exercise training in pre-adolescent males was associated with lower global work index (GWI) and global work efficiency (GWE) at rest. GWE at stress was significantly correlated with VO2max and peak O2 pulse . When indexed by body mass, GWI and GWE both significantly correlated with relative VO2max ; GWI and GWE at baseline and stress were all significantly correlated with peak O2 pulse .Conclusion: PSL-analysis-derived GWI and GWE at rest indexed by body mass are associated with cardiopulmonary exercise test-derived peak oxygen consumption and oxygen pulse in pre-adolescent athletes. Cardiac morphological and functional remodeling in response to long-term training includes increased left ventricular (LV) wall thickness, LV mass, increased LV and RV right ventricular (RV) chamber size  and low-2max) in adult athletes and were suggested to be good predictors of the contractile reserve under stress (2max and VO2max/kg).Pressure-strain loop (PSL) analysis provides a novel non-invasive method to quantify myocardial work, which takes into consideration the impact of afterload when evaluating LV mechanics  and thusr stress . The aimIn August 2019, 20 basketball players between 8 and 10 years old were recruited during their routine cardiopulmonary exercise test (CPX). They have been practicing basketball 5 times a week for 2 h each time for 18 months. They trained on a children’s basketball court, which was 22 m long and 12 m wide, with 2.6 m high baskets and a size five ball (22 cm diameter) for training. They train mainly with games and individual technical training with medium intensity. From Monday to Thursday afternoons are training and Friday afternoons are games, where there is no position differentiation between players on the court. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the “Science Research Ethics Committee at the Shanghai University of Sport.” All athletes’ parents were informed about the protocol of this study, which was outlined in an information letter. No data collection took place without parents’ consent.Participants underwent a complete two-dimensional echocardiographic study (2DE) at baseline and a focused scan immediately after CPX on Vivid iq  with a 2.5 MHz phased array transducer (M5Sc). Cuff-measured blood pressure was recorded concomitantly with the scanning session. Data were digitally stored for offline analysis . From 2DE, LV dimensions, ejection fraction by Simpson’s biplane method, and LV diastolic function parameters were assessed. Left atrial (LA) volume was measured using the biplane method. Right atrial (RA) area and RV function parameters were assessed in the RV-focused apical four-chamber view. Parameters were measured according to the latest recommendations . LV massLV myocardial work was calculated by integrating longitudinal strain and brachial-cuff-measured blood pressure, as previously described by Russel et al. . LV longGlobal myocardial work index (GWI): the total work within the area of the LV PSL between mitral valve closure and mitral valve opening.Constructive myocardial work (CW): shortening of the myocytes during systole adding lengthening of the myocytes during isovolumic relaxation.Wasted myocardial work (WW): lengthening of myocytes during systole (absorbing work done by other segments) adding shortening during the isovolumic relaxation phase (not contributing to ejection).Global cardiac work efficiency (GWE): Cardiac work efficiency was expressed as CW/(CW + WW) × 100% per segment and GWE as an average of all segmental values .2max) was determined by a ramp incremental exercise test . The exercise test was accepted as maximal if the majority of the following termination criteria were met: respiratory exchange ratio greater than 1.0, heart rate greater than 200 beats/minute, display of indicators of a maximal effort such as sweating and, despite strong verbal encouragement, the participant was unable or unwilling to continue.t-test or Wilcoxon signed rank test depending on data distribution. Z-test for single sample was performed to compare echocardiographic indices and relative VO2max of this cohort with reference data of normal children whose population mean and variance was known , and a value of p < 0.05 was considered statistically significant.The Shapiro-Wilk test for normality was performed on all data sets. Continuous data were expressed as mean ± SD or as median (interquartile range) according to data distribution. CPX data were compared with their predicted values through either paired as known . Specifias known . The conas known . The conas known . CompariAll participants completed echocardiographic scans and CPX but one was excluded from the final analysis due to poor image quality. The basic demographic characteristics of the athletes are summarized in 2max of the study population was significantly higher than their age-matched peers  (The relative VO0.00001) , which wAll participants reported more than 9 h of weekly exercise and were classified as active athletes without further subdivision. Data from 2DE and the Z-test results are summarized in p < 0.0001) due to increased heart rate, while peak systolic strain was not significantly different after CPX, which could be explained by the heterogeneous stress status each participant reached. For myocardial work indices, GWE rather than GWI changed significantly (p = 0.035).Exercise training in pre-adolescent males was associated with lower GWI and GWE at rest . In Figu2max  but ejection fraction, global longitudinal strain and fractional shortening were not . GWE at stress was significantly correlated with VO2max . When indexed by body mass, GWI and GWE both significantly correlated with relative VO2max .Among conventional LV functional parameters, only stroke volume (SV) and cardiac output (CO) were significantly correlated with VO2 pulse)  but ejection fraction, global longitudinal strain and fractional shortening were not . GWE at stress was significantly correlated with peak O2 pulse . When indexed by body mass, GWI and GWE at baseline and stress were all significantly correlated with peak O2 pulse .SV and CO were significantly correlated with peak oxygen pulse  GWI and GWE indexed by body mass correlates with relative VO2max in addition to SV, CO, age and BSA; 3) GWI and GWE indexed by body mass correlates with oxygen pulse in addition to SV and CO.The main findings of the present study can be summarized as follows: 1) only GWE at stress but no conventional LV systolic parameters or MW indices at rest correlates with VOThe morphological cardiac remodelling in pre-adolescent athletes has been well documented and confirmed by pooled analysis . HoweverAs the “pre-adolescent athletic heart” is guaranteed to transform into the “adult athletic heart” at certain time point if there is no cessation of training, the heterogeneity of study population could be one reason for the inconsistency. The limits of conventional echocardiographic parameters of LV systolic function or GLS could be another reason as they may not be sensitive enough to detect the functional change in pre-adolescent athletes. GLS remains load dependent , which m2max in pre-adolescent athletes. Previous studies in adult athletes have reported the association between either GWI or GWE at rest and relative VO2max (2max or relative VO2max but the indexed ones did. The indexed GWI is easy to understand as GWI is a measure of all the work generated by the heart and thus is closely related to the metabolic need of the body while indexing could address the difference of body mass among individuals which may be especially important in children. However, the indexed GWE is hard to understand as it is expressed as a ratio and thus should not be subject to the difference in body mass. The current study provides evidence for predicting contractile reserve at rest with MV indices in pre-adolescent athletes but future studies with larger sample size should be performed to validate the results.A major finding of the current study is that GWI and GWE indexed by body mass correlate with relative VOe VO2max . The cur2 pulse has been suggested to represent maximal working capacity (2 pulse as an important measure obtained from CPX (2 pulse stronger than with relative VO2max. As the calculation of GWI and GWE is based on single heartbeat, the better correlation with peak O2 pulse could be achieved after excluding the effect of heart rate. This finding also adds to the evidence for predicting aerobic capacity with MV indices in pre-adolescent athletes.Another important finding is the correlation of MW indices to the peak oxygen pulse. Oxygen pulse expresses the volume of oxygen ejected from the ventricles with each cardiac contraction and peak Ocapacity . Currentfrom CPX . In the Another interesting finding in the current study is that GWI of pre-adolescent males was lower than normal children. GWI has been demonstrated to be similar or higher in athletes than in sedentary controls in adults. Jain et al.  performeA major limitation of the current study is its limited sample size despite active recruitment performed by the researchers. Sensitivity tests were made by randomly excluding one subject and the major finding of the current study remained unchanged. However, it would be better validated with larger sample size.The current study is also subject to its narrow spectrum of sport disciplines. Thus, the generalizability of the current results needs to be clarified in a larger study population. The time interval between peak stress and echocardiographic scan may cause error in peak systolic strain measurement and thus affect PSL analysis. However, given the simultaneous measurement of blood pressure and the intrinsic heterogeneity of individual stress load, such error would not significantly change our current findings.PSL-analysis-derived GWI and GWE at rest indexed by body mass are associated with cardiopulmonary exercise test-derived peak oxygen consumption and oxygen pulse in pre-adolescent athletes. Our findings support the use of PSL analysis in the evaluation of pre-adolescent athletes’ heart.