Echocardiographic diagnosis of left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM) often requires extensive provocative manoeuvers. We investigated, whether echocardiography-derived parameters obtained at rest can aid to determine the presence of LVOTO in persons with HCM.Consecutive patients with HCM admitted to a referral centre underwent standardized transthoracic echocardiographic examination including provocative manoeuvers. Under resting conditions, the length of mitral leaflets and distances between mitral valve coordinates and ventricular walls were blindly measured in parasternal long axis (PLAX) and apical three-chamber (3ch) views, both at early and late systole. Among 142 patients , 68 (42%) had resting or provocable LVOTO with maximal LVOT gradients ≥30 mmHg. Late-systolic distance between mitral leaflet tip and ventricular septum (TIS) was measurable in 137 participants (96%) in 3ch view and independently associated with LVOTO in multivariable logistic regression analysis. The area under the ROC curve of TIS for the identification of LVOTO was 0.91 [95% confidence interval (CI) 0.87–0.96]. TIS ≤ 14 mm yielded 97% sensitivity and 57% specificity regarding LVOTO. TIS >14 mm ruled out LVOTO with a negative predictive value of 95%. TIS ≤9 mm ruled in LVOTO with a positive predictive value of 92% . Among 43 patients with TIS between 10 and 14 mm, 35% had LVOTO.In our study, the novel echocardiographic parameter TIS showed high negative and positive predictive values for LVOTO in HCM. These exploratory results await confirmation in larger collectives and prospective investigations.  Spirito and L. Boni, 1 Left ventricular outflow tract obstruction (LVOTO) is present in up to 70% of patients with HCM and increases the risk of heart failure and death.3 Once LVOTO is diagnosed, pharmacological and invasive therapies are available for its treatment.4–7 Also after septal reduction therapy (SRT), residual LVOTO can be present.8 The severity of LVOTO is affected by pre- and afterload conditions, ventricular morphology, alterations of the mitral valve apparatus, and ventricular contractility, and about 50% of LVOTO patients exhibit a significant obstruction only during provocative manoeuvers.3 Therefore, an extensive sequence of examination steps including standardized provocative manoeuvers is recommended during echocardiography in patients with HCM and a left ventricular outflow tract (LVOT) gradient <30 mmHg to reliably exclude or identify LVOTO.9 Given that awareness of the dynamic component of LVOTO and experience with provocative manoeuvers are often limited in clinical practice, there is substantial underdiagnosis of LVOTO with an unacceptably high proportion of patients being withheld from optimal treatment.10 An easily applicable echocardiographic parameter to discriminate between obstructive and non-obstructive HCM is therefore desirable.Hypertrophic cardiomyopathy (HCM) is a hereditary cardiomyopathy with an estimated prevalence of up to 0.6% in the general population.11 Previous studies suggested that both elongation of the post-coaptational portion of the mitral leaflet and the spatial relationship between mitral valve and ventricular walls may determine the presence of LVOTO.11–13Systolic anterior motion (SAM) of the post-coaptational portion of the mitral valve is considered the predominant mechanism leading to LVOTO. However, SAM as semi-quantitative echocardiography-derived parameter is of limited use, due to its high inter-observer variability and poor diagnostic accuracy for identification of LVOTO, particularly regarding provocable LVOTO.We therefore aimed (i) to establish echocardiography-derived parameters reflecting the interaction between the mitral leaflet and the ventricular walls during systole and (ii) to identify the echocardiographic markers with the best diagnostic properties for exclusion and detection of LVOTO in a sample of consecutive patients with HCM including patients with and without previous SRT.14 Patients with previous mitral valve surgery (n = 2) and concomitant presence of subaortic membrane (n = 3) were excluded. Laboratory analysis, physical examination, medical history, vital parameters, and 12-lead electrocardiogram were assessed at the day of echocardiographic examination.This is a cross-sectional analysis of the HyperCard Registry. This registry is a single-centre prospective cohort study conducted at the Comprehensive Heart Failure Centre (CHFC), Würzburg, a referral centre for HCM. The registry includes consecutive patients with diagnosed or suspected HCM, with and without previous SRT. It has been approved by the local Ethics Committee  and adheres to the principles of Good Clinical Practice and the Declaration of Helsinki. Between October 2020 and September 2021, 183 patients consented for participation in the HyperCard Registry. For the present report, we analysed 147 patients fulfilling diagnostic criteria of HCM with complete digitally stored standardized transthoracic echocardiograms.15 Echocardiography followed a standardized protocol with acquisition of cine loops over three cardiac cycles in parasternal, apical, and subcostal views using ECG gating.16 Still images and loops with a mandated frame rate of at least 55 frames per second were stored digitally. LVOT gradient was measured in apical three- (3ch) and five-chamber (5ch) view at rest and during the strain phase of Valsalva manoeuver in every patient. Continuous-wave Doppler cursor was positioned parallel to the LVOT long axis, and LVOT flow velocity was measured under simultaneous B-mode visualization to facilitate differentiation from mid-cavitary gradients. As recommended, further provocative manoeuvers in addition to Valsalva manoeuver  were conducted in any patient, in whom provocable LVOTO was clinically suspected, e.g. in case of systolic murmur after exercise manoeuver, or if typical symptoms were reported, such as worsening of symptoms after heavy meals or alcohol intake.9 Basic echocardiographic parameters were measured offline from digitally stored images and loops by an experienced sonographer of the Academic Core Lab Ultrasound-based Cardiovascular Imaging at the CHFC. The Simpson’s biplane method was used to compute left ventricular ejection fraction (LVEF) and left ventricular stroke volume. Left atrial volume index was determined using the method of discs, and the Dubois formula was applied to calculate body surface area (BSA). Peak early velocities of transmitral filling (E) and lateral mitral annulus  were measured using Doppler imaging, and their ratio was used to calculate E/e’ lateral.18Transthoracic echocardiography was performed at the CHFC by trained and internally certified sonographers using a Vivid E95 machine and a 4Vc-D probe .14 Maximal end-diastolic thickness of the ventricular septum was measured in parasternal long axis. HCM phenotype was categorized into reverse curve, sigmoid, apical, and neutral hypertrophy pattern as defined by Binder and colleagues.19 SAM was assessed at rest and was defined as partial or total motion of one of the mitral valve leaflets towards the ventricular septum during systole. SAM was categorized into Grade 0 , Grade I , Grade II , and Grade III . SAM was classified as complete if contact between the mitral valve and the septum was documented in at least one view. We did not differentiate, whether SAM originated from anterior mitral leaflet (AML) or posterior mitral leaflet (PML). Apical papillary muscle displacement was defined as present if the base of the respective papillary muscle originated from the apical third of the left ventricle.20Resting LVOTO was defined as maximal peak LVOT gradient ≥30 mmHg at rest. Provocable LVOTO was defined as a resting gradient <30 mmHg and peak LVOT gradient ≥30 mmHg under provocative manoeuvers.Figure 1). Distance measures were performed originating from the coaptation point  and from the mitral leaflet tip , respectively.Parameters were measured off-line from digitally stored images and loops using EchoPAC , by a cardiologist certified in transthoracic echocardiography by the European Association of Cardiovascular Imaging (NV). Parameters reflecting spatial relationship between mitral valve and ventricular walls were acquired at rest (without provocative manoeuvers) both in 3ch view and in parasternal long axis (PLAX), both at early and late systole. Frames capturing first mitral leaflet coaptation and closest distance between the mitral leaflet tip and the ventricular septum were considered for early-systolic and late-systolic measurements, respectively. Lengths of AML and PML were measured at end diastole. The residual leaflet of the mitral valve  was defined as the portion of the mitral valve extending distant the mitral valve coaptation point  curve analyses were applied. Diagnostic accuracy of continuous spatial relationship parameters was expressed as area under the ROC curve (AUC) with 95% confidence interval (CI). Reference thresholds based on optimized sensitivity and specificity were derived from AUC, and diagnostic accuracies of these cut-offs were expressed as diagnostic effectiveness . Diagnostic accuracy analyses were repeated in subgroups  and with adjustment for BSA and stroke volume. Intra- and inter-observer variabilities were assessed in a random sample of 20 patients calculating intra-class correlation coefficients with 95% CI, and Cohen’s κ for categorical variables. SPSS Statistics Version 27  was used for statistical analyses. The significance level was set at 5%.Patient characteristics were described in the whole sample and stratified by presence of LVOTO. Normal distribution of variables was checked by Q–Q_plots, concordance between mean and median, and skewness. Categorical variables were expressed as count with percentage. Continuous measures were described as mean ± standard deviation or median with quartiles, as appropriate. For group comparisons between presence and absence of LVOTO, we used Mann–Whitney Table S1). Mean age was 59 ± 13 years (range 23 to 84 years), and 59 (42%) were women. Of the total sample, 74 patients (52%) had no LVOTO, and 68 (48%) had LVOTO . SRT had been performed in 59 patients (42%) and 121 patients (85%) were on a beta-blocker therapy.We identified 142 consecutive patients with HCM eligible for the present analysis  and in PLAX in 115 patients (81%). In all cases with missing parameters, this was due to inadequate spatial resolution. Due to higher feasibility, we report 3ch view-derived parameters, only.Table 1. In multivariable logistic regression analyses, LVOTO was associated with longer residual mitral leaflets (for both early- and late-systolic measurements), shorter TIS (for both early- and late-systolic measurements), and longer distances between mitral leaflet tip and the posterior wall (only for late-systolic measurement), as shown in Table 2. Analyses were adjusted for sex, NYHA functional class, atrial fibrillation, device therapy, LVEF, degree of SAM, maximal septal thickness, apical displacement of anterolateral papillary muscle, and apical displacement of posteromedial papillary muscle.LVOTO was associated with higher LVEF, higher septal thickness, the degree of SAM, and apical displacement of both anterolateral and posteromedial papillary muscle. Basic echocardiographic parameters stratified by LVOTO are shown in Table 3). TIS was measurable in 137 patients (feasibility 96%). From AUC, optimized TIS thresholds of 14 and 9 mm were derived . Among 63 patients with LVOTO and available TIS, 2 (5%) had TIS >14 mm, 15 (35%) had TIS between 10 and 14 mm, and 46 (92%) had TIS ≤9 mm. TIS ≤ 14 mm yielded 97% sensitivity and 57% specificity regarding LVOTO (diagnostic effectiveness 75%). TIS was >14 mm in 44 patients (31%) and ruled out LVOTO with a negative predictive value of 95% (Table 4). TIS was ≤9 mm in 50 patients (35%) and ruled in LVOTO with a positive predictive value of 92% . Among 43 patients with TIS between 10 and 14 mm, 15 (35%) had LVOTO (n = 9 with previous SRT).Among spatial relationship parameters, late-systolic TIS showed the highest diagnostic accuracy for identification of LVOTO, with AUC of 0.91 . Among 35 patients with provocable LVOTO and available TIS, 2 (6%) had TIS >14 mm, 14 (40%) had TIS between 10 and 14 mm, and 19 (54%) had TIS ≤9 mm. Diagnostic accuracy read-outs for TIS thresholds of 9 and 14 mm regarding provocable LVOTO are illustrated in Table 5.The AUC of TIS to identify provocable LVOTO—omitting patients with resting LVOTO—was 0.87 . When confining analyses to those without previous SRT, TIS yielded an AUC of 0.95 (95% CI 0.91–0.99). The diagnostic accuracy of TIS was similar for both sexes: for women, AUC 0.92 (95% CI 0.85–0.99); for men, AUC 0.93 (95% CI 0.87–0.98). Indexing TIS for BSA minimally improved diagnostic accuracy: AUC 0.92 (95% CI 0.88–0.96). Indexing TIS for left ventricular stroke volume also slightly improved diagnostic accuracy: AUC 0.93 (95% CI 0.88–0.97). Representative measurements of TIS are shown in TIS was re-measured in 20 randomly selected patients by two cardiologists in a blinded fashion  to assess intra- and inter-observer agreement. TIS measurement required on average less than 1 min per patient. TIS showed very favourable intra- and inter-observer variability, with intra-class correlation coefficients of 0.96 (95% CI 0.82–0.99) and 0.95 (0.83–0.98), respectively. Expressing TIS in categories, intra-observer agreement was good regarding both thresholds: > 14 mm yielded κ=0.79 and agreement in 90%, while ≤9 mm yielded κ=0.70 and agreement in 85%. Further, there was good inter-observer agreement regarding the threshold >14 mm with κ=0.79 (agreement in 90%) and moderate inter-observer agreement regarding the threshold ≤9 mm with κ=0.50 (agreement in 75%).In a well-characterized cohort of consecutive patients with HCM, we identified late-systolic TIS as an echocardiographic parameter that can be obtained under resting conditions and has high negative and positive predictive values for LVOTO in HCM. TIS has high feasibility when acquired in apical 3ch view and can be measured easily and with high reproducibility during routine echocardiography work-up.2 Both pharmacological therapies and SRT are effective in relieving LVOTO and associated symptoms.21–23 Of note, whereas provocable obstruction is as common as resting obstruction, it frequently remains undiagnosed. The execution of provocative manoeuvers for its correct diagnosis is time-consuming and requires experienced investigators.3 Although specific symptom assessment  and physical examination  can be helpful, such derived diagnostic information is subjective by nature and depends on the experience of the individual physician.24 Yet, a diagnostic parameter excluding or indicating LVOTO and prompting provocative manoeuvers is lacking.In patients with HCM, LVOTO at rest increases morbidity and mortality.9 Since the 1960s, the intricate interaction between ventricular septum and the mitral valve has been investigated. Authors combining mechanographic, haemodynamic, and angiographic methods and M-mode echocardiography described this interaction as SAM.25 Recent HCM guidelines, however, do not provide clear definitions how to quantify SAM.14 Also after SRT, residual LVOTO can be present.8 Spirito and colleagues showed that the diagnostic accuracy of semi-quantified SAM was low, as eight out of 10 patients with post-operatively provocable LVOTO had no SAM.11 Also in untreated HCM patients, SAM was not associated with presence of LVOTO in another study.3Systolic motion of the mitral valve leaflets towards the ventricular septum is the central mechanism underlying LVOTO in patients with HCM.12 Mitral valve alterations are well established as surgical treatment targets, but their quantitative assessment during the diagnostic work-up of HCM has not yet been implemented. Patients with HCM exhibit on average longer mitral leaflets than healthy persons, but the contributing role of total mitral leaflet length to LVOTO has been discussed controversially.26 Therefore, it was suggested to focus on the post-coaptational leaflet portion describing the residual leaflet portion distant to the mitral valve coaptation point.12 In line with this concept, patients admitted with acute takotsubo syndrome and LVOTO during the ballooning event exhibited significantly longer residual leaflets compared to those not developing LVOTO.27 In pivotal studies by Sherrid and colleagues, echocardiographic assessment of the post-coaptational portion relied on early-systolic measurements of residual leaflet length and distances between the mitral valve coaptation point and ventricular walls, all acquired in PLAX.27 Of note, the mobility of the tip of the residual leaflet makes it susceptible to systolic hydrodynamic forces. Therefore, we measured distances between mitral leaflet tip and ventricular walls, on top of measurements at the coaptation point, acquired both at early and late systole. Taking into account that SAM and LVOT gradients are often best visualized in 3ch view, we measured all parameters in 3ch view on top of PLAX. We identified late-systolic TIS measured at rest in 3ch view as an echocardiography-derived predictor of LVOTO with favourable diagnostic properties. This novel echocardiographic parameter advances the former concept and can be easily derived in clinical routine 2D echocardiography within less than min, either instantly or using post-processing software. Interestingly, a recent retrospective study applying machine learning algorithms in a large dataset of HCM patients with available cardiac magnetic resonance imaging reported concordant results.28 They found that among several anatomical parameters, distance between anterior mitral valve leaflet tip and basal septum best predicted presence of resting LVOTO. Our study further extends these findings involving also patients with provocable LVOTO and providing an easily applicable echocardiographic parameter.In the context of septal hypertrophy and ventricular hypercontractility, both mitral leaflet elongation and apical papillary displacement are considered as most important factors permitting the mitral valve to protrude into the LVOT.Our study indicates that TIS between 10 and 14 mm represents an area of diagnostic uncertainty. Interestingly, all but one patient with LVOTO and TIS in this area had provocable LVOTO, and 60% had a previous SRT. Given our relatively small study population, subgroup analyses should be interpreted cautiously. Yet, our study suggests that TIS may perform substantially better in patients without previous SRT. The diagnostic accuracy of TIS in SRT-naïve patients with HCM and also the effect of SRT on the spatial relationship between mitral valve and ventricular septum should be addressed more specifically in prospective studies.Our results may have important implications on diagnostic and therapeutic strategies. In HCM patients with a TIS >14 mm, the probability of an LVOTO appears so low that further provocation manoeuvers may be omitted and the search for alternative causes of symptoms should be initiated. Approximately 40% of patients with provocable LVOTO had TIS in the range of 9–14 mm. Therefore, in patients with TIS in this ‘grey zone’ and symptoms indicative of LVOTO, particular attention needs to be paid to provocation manoeuvers in order to uncover a potentially latent LVOTO. A TIS of ≤9 mm appears to raise the likelihood for the presence of a clinically relevant LVOTO close to 100%.post hoc, the performance of the identified TIS thresholds await verification in prospective larger studies. However, effect sizes were large, with fairly narrow confidence intervals and in line with a sound pathophysiologic concept. The mono-centric character may limit generalizability of our findings. Measurements were performed by a single experienced investigator, but TIS showed good inter-observer variability when re-assessed for validation purposes in a subset of patients.Due to the exploratory nature of the study design and analyses carried out In our study, the novel echocardiographic parameter TIS showed high negative and positive predictive values regarding the presence LVOTO in HCM. Application of TIS in resting echocardiography protocols may help in tailoring the diagnostic work-up in HCM and identifying those patients who should or should not undergo echocardiography with extensive provocative manoeuvers. These exploratory results need to be confirmed in larger collectives and prospective investigations.European Heart Journal - Cardiovascular Imaging online.jead036_Supplementary_DataClick here for additional data file.


Using easy-to-determine bedside measurements, we developed an echocardiographic algorithm for predicting left ventricular ejection fraction (LVEF) and longitudinal strain (LVLS) in patients with septic shock.We measured septal and lateral mitral annular plane systolic excursion (MAPSE), septal and lateral mitral S-wave velocity, and the left ventricular longitudinal wall fractional shortening in patients with septic shock. We used a conditional inference tree method to build a stratification algorithm. The left ventricular systolic dysfunction was defined as an LVEF <50%, an LVLS greater than −17%, or both.We included 71 patients . Septal MAPSE (cut-off: 1.2 cm) was the best predictor of left ventricular systolic dysfunction. The level of agreement between the septal MAPSE and the left ventricular systolic dysfunction was 0.525 [0.299–0.751]. A septal MAPSE ≥1.2 cm predicted normal LVEF in 17/18 patients, or 94%. In contrast, a septal MAPSE <1.2 cm predicted left ventricular systolic dysfunction with impaired LVLS in 46/53 patients (87%), although 32/53 (60%) patients had a preserved LVEF.Septal MAPSE is easily measured at the bedside and might help clinicians to detect left ventricular systolic dysfunction early—especially when myocardial strain measurements are not feasible. Experts have prompted clinicians to report markers of systolic function other than LVEF and GLS, such as the mitral annular plane systolic excursion (MAPSE) and the systolic myocardial velocity (S-wave) at the mitral annulus.Myocardial strain  might facilitate the early diagnosis of SCM by detecting early LV systolic dysfunction (i.e. before a decrease in LVEF). A recent meta-analysis by Sanfilippo and colleaguesThe objective of the present study was to use echocardiographic variables  that are easily and reproducibly measured at the bedside to develop an algorithm for predicting LV systolic dysfunction  in patients with septic shock.This prospective study was conducted in the intensive care unit (ICU) at Amiens University Hospital . We included all consecutive patients on mechanical ventilation and admitted with septic shock or having developed septic shock during their stay in the ICU between March 2015 and January 2017. Septic shock was defined according to the Sepsis-2 criteria.Commission Nationale de l'Informatique et des Libertés, Paris, France: registration number 2208336). Informed consent was obtained from the patient's family or (after recovery) the patient.The study protocol was approved by an independent ethics committee  and registered with the French National Data Protection Commission  system with a 1.5–4.5 MHz transducer . The depth and sector angle were adjusted to capture the entire left ventricle, including the septal and lateral mitral annuli. All measurements complied with the European Association of Cardiovascular Imaging/American Society of Echocardiography guidelines and were averaged over five consecutive cardiac cycles.−1. In the present study, LV systolic dysfunction was defined as an LVEF <50%, an LVLS greater than −17% (i.e. less negative than −17%), or both.,Based on the LV end-diastolic and end-systolic volumes, we calculated the LVEF (in %) according to Simpson's modified method.1.MAPSE: in conventional M-mode, we measured the longitudinal excursion of the septal and lateral mitral annuli. Given that M-mode is angle dependent, we made sure that the M-mode line was parallel to the LV walls and that the deviation was below 15 degrees. MAPSE (cm) was measured as the distance between the peak (i.e. end-systole) and bottom (i.e. end-diastole) of the M-mode tracing curve.2.−1) in both septal and lateral mitral annuli.Mitral S-wave: we placed the sample volume in the ventricular myocardium, immediately adjacent to the mitral annulus. We then used pulsed-wave tissue Doppler imaging to measure the peak systolic velocity , median (inter-quartile range [IQR]), or frequency (%), as appropriate. Spearman's correlation coefficient was used to analyse the correlation between LV systolic function as estimated by different methods. Correlation analysis (Pearson's correlation coefficient) and Bland–Altman plots were used to assess intra- and inter-observer reliabilities of echocardiographic variables in a sample of 20 patients. Next, we used a conditional inference tree method to build our stratification algorithm; recursive partitioning was used to stratify the population of interest into subgroups.P-values. The tree-building process continued as long as a predictor led to significantly different child nodes. The final sets of subgroups were referred to as terminal nodes. Diagnostic properties  were calculated. Cohen's kappa statistic was used to measure the level of agreement between LV systolic function predicted by echocardiography and that measured using the LVEF and the LVLS. The threshold for statistical significance was set to P<0.05. All statistical analyses were performed using GraphPad Prism software  and R version 4.0.5  through the RStudio interface Version 1.4.1106.Data were expressed as the mean (standard deviation [sd) age: 61 [15]; mean [sd] Simplified Acute Physiology Score: 60 [19])  dose of 0.7 (0.7) μg kg−1 min−1. The median (IQR) heart rate and mean arterial pressure were 97 (79–111) beats min−1 and 73 (67–77) mm Hg, respectively  . Most ofectively .Figure 1Intra- and inter-observer reliabilities of echocardiographic variables are shown in −1 (n=64) and 12.0 (4.1) cm s−1 (n=69), respectively. Lastly, the mean LV-LWFS was 11.8% (3.6%) (n=55)  cm and 1.25 (0.37) cm, respectively. The mean septal and lateral mitral S-wave velocities were 9.8 (3.3) cm s) (n=55) .r=0.521 [0.321–0.676]; P<0.001), whereas septal MAPSE had the strongest correlation with LVLS   with LVEF (P<0.001) .Table 2CSeptal MAPSE (with a cut-off of 1.2 cm) was the best TTE predictor of LV systolic function as measured by LVEF and LVLS . The incAmong the patients with abnormal predicted LV systolic function , 21 (40%) had both abnormal LVEF and abnormal LVLS. Interestingly, 25 patients (47%) had abnormal LVLS even though the LVEF was normal. Only seven patients (13%) had normal LVEF and normal LVLS .n=12, 67%). Only five patients (27%) had normal LVEF with abnormal LVLS, whereas one patient (6%) had both abnormal LVEF and abnormal LVLS  had both normal LVEF and normal LVLS —because the atrioventricular plane is strongly echogenic.per se.,MAPSE, S-wave velocity, LV-LWFS, LVEF, and LVLS analyse different mechanistic aspects of LV systolic function. For instance, LVEF is the sum of the contraction of circumferential, longitudinal, and oblique myocardial fibres, and is associated with a cardiac twist. Taken individually, these variables might not accurately reflect the true complexity of LV contractility. In physiological terms, myocardial contractility is related to the extent of shortening, the shortening velocity, and the contraction strength. Although ultrasound techniques cannot assess the contraction strength, MAPSE is a reliable index of longitudinal shortening. However, MAPSE and LV-LWFS are weakly related to LVEF, because only 60% of the LV ejection results from longitudinal contraction ,,Neither LVEF nor mitral S-wave velocity are valid indicators of mortality in patients with septic shock.Our study had several limitations, most of which concerned the stratification algorithm. Firstly, we did not include all surrogates of LV systolic function . Moreover, we only measured septal and lateral MAPSE from the four-apical chamber view, regardless of the anterior and inferior walls  and the anteroseptal and inferolateral walls .Septal MAPSE with a cut-off of 1.2 cm was the best TTE variable for predicting LV systolic function in patients with septic shock. Since MAPSE corresponds to longitudinal LV shortening, it reflects LVLS more faithfully than LVEF. Hence, septal MAPSE might be a simple bedside tool for helping clinicians with the early detection of LV systolic dysfunction in a septic patient with conserved LVEF, especially when strain measurements are not available or feasible (e.g. in cases with poor echogenicity).Designed the study: CB, YZ, JM, MS.Collected the data: PM, JM, MS.Analysed the data: CB, YZ, AM, MD.Wrote the manuscript: CB, YZ, MS.Critically reviewed the manuscript: PM, CT, JM.Approved the final version of the manuscript: all authors.Have agreed to be accountable for all aspects of the work by ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: all authors.The authors declare that they have no conflicts of interest.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.


This cohort study assesses whether native T1 mapping can measure the cardiac light-chain amyloidosis treatment response and the association between changes in native T1 and prognosis. Can changes in myocardial native T1, derived without the need for contrast, track the treatment response in cardiac light-chain amyloidosis?In this cohort study, 221 patients had repeat cardiac magnetic resonance imaging 6 and/or 12 months after initiating chemotherapy. Changes in myocardial native T1 in response to treatment reflect a composite of changes in myocardial T2 and extracellular volume; changes in native T1 are also associated with in changes in traditional validated markers of the cardiac response and are independently associated with mortality.Changes in myocardial native T1 may be used in the clinical setting to track treatment response in cardiac light-chain amyloidosis. Cardiac magnetic resonance (CMR) imaging–derived extracellular volume (ECV) mapping, generated from precontrast and postcontrast T1, accurately determines treatment response in cardiac light-chain amyloidosis. Native T1 mapping, which can be derived without the need for contrast, has demonstrated accuracy in diagnosis and prognostication, but it is unclear whether serial native T1 measurements could also track the cardiac treatment response.To assess whether native T1 mapping can measure the cardiac treatment response and the association between changes in native T1 and prognosis.This single-center cohort study evaluated patients diagnosed with cardiac light-chain amyloidosis (January 2016 to December 2020) who underwent CMR scans at diagnosis and a repeat scan following chemotherapy. Analysis took place between January 2016 and October 2022.Comparison of biomarkers and cardiac imaging parameters between patients with a reduced, stable, or increased native T1 and association between changes in native T1 and mortality.P < .001), maximal wall thickness , and E/e' , improved longitudinal strain , and reduction in both myocardial T2  and ECV . At 12 months, an increased native T1 occurred in 24 patients (15%), most of whom had a poor hematological response (17 [71%]), and was associated with an increased N-terminal pro-brain natriuretic peptide , reduced left ventricular ejection fraction , and an increase in both myocardial T2  and ECV . Change in myocardial native T1 at 6 months was independently associated with mortality .The study comprised 221 patients . At 6 months, 183 patients  underwent repeat CMR imaging. Reduced native T1 of 50 milliseconds or more occurred in 8 patients (4%), all of whom had a good hematological response; by contrast, an increased native T1 of 50 milliseconds or more occurred in 42 patients (23%), most of whom had a poor hematological response (27 [68%]). At 12 months, 160 patients  had a repeat CMR scan. A reduced native T1 occurred in 24 patients (15%), all of whom had a good hematological response, and was associated with a reduction in N-terminal pro-brain natriuretic peptide (median [IQR], 2638 [913-5767] vs 423 [128-1777] ng/L; Changes in native T1 in response to treatment, reflecting a composite of changes in T2 and ECV, are associated with in changes in traditional markers of cardiac response and associated with mortality. However, as a single-center study, these results require external validation in a larger cohort. Although native T1 has demonstrated accuracy in diagnosis and prognostication, it is unclear whether serial measurements could track the cardiac response to treatment.8Cardiac light-chain (AL) amyloidosis is caused by monoclonal immunoglobulin light-chains that misfold into pathogenic amyloid fibrils and deposit in the myocardial interstitial space.The aims of this study were to assess the ability of CMR with native T1 mapping to measure the cardiac response to treatment and the association between changes in native T1 and prognosis.5 Data on ethnicity were self-reported.Study participants comprised individuals with cardiac AL amyloidosis diagnosed at the National Amyloidosis Centre (January 2016 to December 2020). Data from 176 patients had been included within a prior publication from our center, but the current study includes an updated analysis.9 and provided written informed consent for analysis and publication of their data. Comparisons were made between baseline and follow-up CMR scans to calculate the absolute change in native T1. Patients were classified as having a reduced native T1 (native T1 reduction ≥50 milliseconds), a stable native T1 (change in native T1 <50 milliseconds), or an increased native T1 (native T1 increase ≥50 milliseconds)  and compared using the χ2 test. Correlation between parameters were assessed using Pearson r or Spearman ρ.Continuous variables are presented as mean (SD) or median (IQR), other than N-terminal pro-brain natriuretic peptide (NT-proBNP), which was natural log transformed for parametric testing. Continuous variables were analyzed using the independent P values were 2-sided, and statistical significance was defined as P < .05, except for paired tests where significance was defined as P < .01. Analysis took place between January 2016 and October 2022.All mortality data were obtained via the UK Office of National Statistics, which is the national government registry for all deaths. Survival was evaluated with Cox proportional hazards regression analysis. Multivariable models were used to investigate the association between the change in native T1 or change in ECV with mortality. Akaike information criterion and Harrell C statistics were calculated for each model, and Harrell C statistics were compared using the Wald test. Kaplan-Meier curves were constructed, with statistical significance being assessed with a log-rank test. 2. Overall, 6 patients (2.7%) were Asian, 14 (6.3%) were Black, and 201 (91.0%) were White. The median (interquartile range) NT-proBNP was 2443 (926-5230) ng/L, median (IQR) troponin T was 0.052 (0.028-0.100) ng/mL , and 102 (46.2%) had Mayo stage IIIa biomarkers at diagnosis  age of 64.7 (10.6) years, 130 (58.8%) were male, and the mean (SD) body surface area was 1.88 (0.25) mA reduced native T1 was detectible in 8 patients (4.4%), 130 patients (71.0%) had a stable native T1, and 45 (24.6%) had an increased native T1. All 8 patients with a reduced native T1 achieved a good hematological response , whereas the majority of patients with an increased native T1 had a poor hematological response  (eTable 3 in P = .002) and ECV . Those who received contrast demonstrated ECV regression (4 [57.1%]) or a stable ECV (3 [42.9%]). All patients with a reduced native T1, but a stable ECV, demonstrated a reduction in T2 of 3 milliseconds or more.Patients with a reduced native T1 had a significant reduction in T2  and ECV . The majority who received contrast demonstrated ECV progression (28 [71.8%]), while the remaining patients had a stable ECV (11 [28.2%]). Subgroup analysis of patients with an increased native T1, but stable ECV, demonstrated these patients had a significant increase in T2  and no significant change in ECV  , 112 patients (70.0%) had a stable native T1, and 24 (15.0%) had an increased native T1. All 24 patients with a reduced native T1 achieved a good hematological response , whereas the majority of patients with an increased native T1 had a poor hematological response  (eTable 5 in P < .001), maximal wall thickness , and E/e'  and improved longitudinal strain . There was also a significant reduction in both T2  and ECV . The majority who received gadolinium contrast had ECV regression (18 [78.3%]), while the remaining patients had a stable ECV (5 [21.7%]). All patients with a reduced native T1 but a stable ECV demonstrated a reduction in T2 of 3 milliseconds or more.Patients with a reduced native T1 had a significant reduction in NT-proBNP  and reduction in left ventricular ejection fraction . There was also a significant increase in both T2  and ECV . The majority who received gadolinium contrast demonstrated ECV progression (22 [95.6%]), while the remaining patient had a stable ECV but an increase in T2 of 3 milliseconds or more , while the percentage change in NT-proBNP had a weak positive correlation with the change in native T1  and a moderate positive correlation with the change in ECV .Change in native T1 and change in ECV had a strong positive correlation . The multivariable model containing change in ECV had a lower Akaike information criterion than the model containing native T1, but the Harrell C statistics of both models were not significantly different (eTable 7 in At median (IQR) follow-up of 60 (37-71) months from the time of diagnosis, 62 patients (28.1%) had died. Patients with an increased native T1 at 6 or 12 months had a worse prognosis  C and D.In this prospective study, we demonstrate that native T1 can track the treatment response in cardiac AL amyloidosis. Change in native T1 reflects the composite change of ECV and T2 and is independently associated with mortality.10 Native T1 complements conventional methods of monitoring treatment response, with change in native T1 being independently associated with mortality and hence redefining the treatment response beyond traditional markers.Cardiac response is commonly measured using NT-proBNP, with a reduction thought to reflect diminished cardiotoxicity and being associated with favorable outcomes.11 As expected, change in ECV correlated with change in native T1, but change in ECV demonstrated a stronger correlation with change in NT-proBNP and the multivariable model containing change in ECV had a lower Akaike information criterion than the model containing native T1. Despite this, the multivariable model containing ECV had a similar Harrell C statistic to the model containing native T1, confirming the role of native T1 as an effective marker of treatment response.Native T1 is closely related to ECV, with ECV maps being generated from precontrast and postcontrast T1.13These differences may represent the different biological data being measured. Amyloid fibril accumulation causes ECV expansion as well as myocardial damage and edema secondary to light-chain toxicity and rapid amyloid accumulation reflected by increased T2. ECV measurements most likely quantify the degree of amyloid deposition, whereas native T1 provides a composite signal influenced by amyloid accumulation (ECV) and myocardial edema (T2) (eFigure 5 in 5 Concerns have been raised regarding the risk of contrast administration in the setting of chronic kidney disease and also regarding accumulation of gadolinium deposits in the brain. These concerns resulted in the removal of linear agents for most indications, macrocylic agents being used at the lowest possible dose, and only when noncontrast scans are not suitable. Serial native T1 measurements are able to track the cardiac treatment response while simultaneously avoiding contrast exposure. Use of native T1 without the need for contrast also reduces acquisition time by up to two-thirds, with noncontrast studies that include native T1 mapping, volume, and functional assessments being performed in less than 15 minutes. This additional advantage has implications on diagnostic workflow, with reductions in scan time resulting in improvements in efficiency and a greater capacity for more CMR scans to take place.8Serial native T1 measurements represent an important addition to the standard armamentarium of amyloid assessment. Changes in ECV are able to track the cardiac treatment response, but ECV mapping requires gadolinium contrast administration.Serial CMR scans were only available for patients with follow-up imaging, which invariably introduced survival bias. Rapid amyloid accumulation may have resulted in mortality before the 6-month interval CMR scan could take place. This is a single-center study and therefore requires validation in a larger cohort of patients.In summary, changes in native T1 in response to treatment are reflected in changes in the traditional markers of the cardiac response; importantly, changes in native T1 are independently associated with mortality. However, this is a single-center study, and therefore these results require external validation in a larger cohort of patients.


Ivabradine improves cardiac function in patients with heart failure, but its effect on dilated cardiomyopathy (DCM) remains unclear. We performed a systematic review and meta-analysis to study the efficacy and potential mechanisms of ivabradine's effect on cardiac function and prognosis in patients with DCM.We searched PubMed, Cochrane Library, Embase, Web of Science, and four registers through September 28, 2022. All controlled trials of ivabradine for the treatment of DCM with congestive heart failure were included. Articles were limited to English, with the full text and necessary data available. We performed random- or fixed effects meta-analyses for all included outcome measures and compared the effect sizes for outcomes in patients treated with and without ivabradine. The quality of the studies was assessed using the Cochrane risk-of-bias tool for randomized trials (RoB2.0).Five trials with 357 participants were included. The pooled risk ratio was 0.48 [95% confidence interval (CI) ] for all-cause mortality and 0.38 [95% CI ] for cardiac mortality. The pooled mean difference was −15.95 [95% CI ] for resting heart rate, 3.96 [95% CI ] for systolic blood pressure, 2.93 [95% CI ] for left ventricular ejection fraction, −5.90 [95% CI ] for left ventricular end-systolic diameter, −3.41 [95% CI ] for left ventricular end-diastolic diameter, −0.81 [95% CI ] for left ventricular end-systolic volume, −0.67 [95% CI ] for left ventricular end-diastolic volume, −11.01 [95% CI ] for Minnesota Living with Heart Failure score, and −0.52 [95% CI ] for New York Heart Association class.Ivabradine reduces heart rate and ventricular volume, and improves cardiac function in patients with DCM, but showed no significant effect on the prognosis of patients. Dilated cardiomyopathy (DCM) is a non-ischemic myocardial disease with structural and functional abnormalities characterized by left or bilateral ventricular dilation and systolic dysfunction in the absence of coronary heart disease (CHD), hypertension, valvular disease, and congenital heart disease . DCM shoIf current inhibitor that lowers heart rate by reducing the rate of phase 4 spontaneous depolarization of autorhythmic cells  2020 statement , 14.www.clinicaltrials.gov), Chinese Clinical Trials Registry (www.chictr.org.cn), EU Clinical Trials Register  and University Hospital Medical Information Network Clinical Trials Registry (www.umin.ac.jp/ctr)] for ongoing trials until September 28, 2022, to identify potential studies of ivabradine in treating DCM. Medical Subject Headings and Emtree were used for search terms. The following terms were included in the title or abstract:  and (“ivabradine” or “corlanor”). Reviews and conference abstracts were also searched. The search was limited to English language and human studies. If there were articles and studies for which complete information was not available, we asked the authors for unpublished content via email. When the systematic review was completed, we ran a search again to ensure that no new studies were missed. The literature search strategy was formulated according to the PRISMA-S   for published literature and four clinical trial registries  and in patients with a higher baseline LVEF  . Sensitiion bias .I2 = 63%] ; 2 = 10%] , indicatTo investigate whether patient age, baseline LVEF, and follow-up duration were sources of heterogeneity, and whether they affected the effect of ivabradine on increasing LVEF, we performed subgroup analyses. When grouped by baseline LVEF and age, there was no heterogeneity within the subgroups, suggesting that these two factors may be responsible for minor heterogeneity. It could be that minors could obtain more LVEF elevation  and patients with a higher baseline LVEF could also achieve more LVEF elevation . However, the follow-up duration did not contribute to potential heterogeneity and was not significantly associated with the effect of ivabradine on increasing LVEF . Sensiti, 9.45 vsp = 0.034) revealed a significant publication bias  and cardiac mortality (p = 0.11) was not statistically significant.In total, four , 18–20 sI2 = 2%]  and 0.38ectively  and therectively   and quality of life, but had no significant effect on SBP and prognosis  in patients with DCM.f Inhibitor Ivabradine Trial) support the conclusion that ivabradine improves HF-related quality of life, clinical outcomes of HF, and cardiac function  Ivabradine is more effective in reducing heart rate in juvenile patients, as well as in patients with a higher baseline LVEF; (2) Juvenile patients and patients with higher baseline LVEF can obtain more LVEF improvement. We believe that, although as mentioned earlier, other factors may play a potential role, heart rate reduction is the primary reason for ivabradine's improvement of cardiac function. The heart rate of minors, especially children aged 0–3 years, is significantly higher than that of adults , and theOur systematic review explores the effectiveness and possible mechanisms of ivabradine in the treatment of DCM. And also compared prognostic outcome measures with those from previous SHIFT trials and corresponding systematic reviews in the expectation of finding uniqueness of ivabradine in the treatment of DCM, although no meaningful conclusions can be drawn due to negative results. In general, this study provides some guidance for the clinical use of ivabradine to some extent.This study had several limitations. First, the small number of studies included not only reduced the validity of the pooled statistics but also limited subsequent subgroup and cumulative analyses. Second, objective statistical sample size of prognosis outcome measures is limited; therefore, larger and better-designed randomized controlled trials are needed to determine the prognostic impact of ivabradine on patients. Third, both the risk of bias in our included studies and the quality of the evidence on the outcome measures were less than satisfactory, which somewhat reduced the credibility of our conclusions. Fourth, there was significant heterogeneity across the included studies in WMD for RHR, left ventricular diameter, NYHA class, and MLWHF score. Although sensitivity and subgroup analyses were used, the source of heterogeneity could not be completely identified. Fifth, in the statistical analysis of LVEF we found that each comparison accounted for a significantly uneven weight. If the study quality and publication bias of the two comparisons  accountiOur systematic review suggests that ivabradine can reduce heart rate and ventricular volume, and improve cardiac function in patients with DCM. Moreover, it may be more effective in juvenile patients and patients with higher baseline LVEF. However, more high-quality clinical studies are still needed to explore the efficacy of ivabradine in DCM.


Impella 5.5 direct aorta implantation via right anterior thoracotomy is a useful technique for patients with limited peripheral vascular size and can be placed similarly to the axillary approach.The Impella 5.5 with SmartAssist system , is the latest-generation microaxial mechanical circulatory support (MCS) with longer support duration and greater pump flow. Although Im5.5 was designed for transaxillary implantation, the direct ascending aorta (DA) and transinnominate implantation via sternotomy have been employed in pediatric patients, patients with small-sized (<7 mm) axillary arteries, and in patients with peripheral vascular disease.2) with a history of percutaneous coronary intervention for anterior wall myocardial infarction was hospitalized due to dyspnea and leg edema. Echocardiography showed a left ventricular ejection fraction of 15%. Cardiac catheter examination revealed pulmonary artery wedge pressure of 40 mm Hg and a low cardiac index of 1.26 L/min/m2. He was on dobutamine at 3 μg/kg/min and norepinephrine at 0.12 μg/kg/min with arterial pressure of 95/72 mm Hg and serum lactate level of 3.8 mmol/L. He was diagnosed with cardiogenic shock due to ischemic cardiomyopathy but was not a candidate for a heart transplant and ventricular assist device in Japan. We considered the longer Im5.5 support required for the recovery and establishing appropriate medication. However, bilateral axillary arteries were measured 5.0 to 5.5 mm using computed tomography (A 65-year-old man (body surface area: 1.9 mmography . We perfA). Reflection of the pericardium was resected around distal AscAo to easily deliver the anastomosis site toward the center of wound (B). The second rib was disarticulated for clamp placement. After systemic heparinization, a 9-mm J-graft  was sewn end-to-side to the AscAo using 5-0 polypropylene running suture after partial clamping (C). The graft was clamped above the anastomosis. A separate 2-cm skin incision was made in the subclavicular space. The graft was tunneled through the first intercostal space in a gentle upward direction (D). Im5.5 was introduced using the standard insertion technique under fluoroscopic and transesophageal echocardiography guidance. The graft was trimmed to the skin level and pushed under the wound. The second and third ribs were fixed using a mesh plate  and steel wires. Im5.5 position was stable and similar to axillary implantation (E). Although the patient received slight sedation using dexmedetomidine hydrochloride during Im5.5 support, an additional pain regimen was not needed. Two weeks after surgery, Im5.5 was removed under local anesthesia in the intensive care unit. The surgical incision was opened, Im5.5 was withdrawn, and graft was ligated into the right thoracic cavity.We made a 6-cm transverse skin incision in the second intercostal space adjacent to the sternum under general anesthesia with bilateral lung ventilation . The thiof wound , B. The clamping , C. The irection , D. Im5.antation , E. AlthA greater flow, the lack of a pigtail catheter to reduce interference with the valvular chordae and thrombus, and the low incidence of hemolysis are specific improvements of Im5.5. Im5.5 is a useful temporary MCS for weeks as the bridge to recovery, ventricular assist device, and heart transplant for various cardiogenic shock,Although an alternative Im5.5 implantation via sternotomy is easily performed,Inadequate access to AscAo is a potential risk, and the short length of AscAo, atherosclerosis, and porcelain aorta are contraindications of this approach. Therefore, detailed preoperative planning using 3-dimensional computed tomography should be performed.We recommend disarticulation of ribs to obtain a surgical space and safety. Reliable rib fixation using a mesh plate and wire is useful to reduce postoperative pain.


We evaluated the early changes in left ventricular (LV) volumetric, functional, and tissue characteristics in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients treated with trastuzumab and/or pertuzumab at cardiac magnetic resonance imaging (MRI).HER2-positive breast cancer patients undergoing planned anti-HER2 therapy and nonanthracycline-based chemotherapy were enrolled and subdivided into dual anti-HER2 (trastuzumab plus pertuzumab) group and trastuzumab group. Cardiac MRI was performed before treatment and three months after starting, covering ventricular volumes, cardiac function, systolic myocardial strain, myocardial oedema, and T1 and T2 relaxation times. Cardiac dysfunction was primarily defined as a > 10% reduction in LV ejection fraction (LVEF) to < 55% and/or a > 15% global longitudinal strain (GLS) change at the follow-up MRI examination.p ≤ 0.031). Systolic dysfunction remained significant in the dual anti-HER2 group. The decrease in GLS in the trastuzumab group was not significant (p = 0.169). T1 and T2 relaxation times tended to increase, but this was not significant at subgroup analysis.Twenty-four HER2-positive patients were evaluated . Six patients developed cardiac dysfunction at follow-up, five of them in the dual anti-HER2 group. One patient developed symptomatic heart failure, and five patients developed asymptomatic cardiac dysfunction. Patients displayed significantly decreased systolic function and increased T1 and T2 relaxation time at follow-up  therapy.• The change in myocardial strain was more marked in patients treated with dual (trastuzumab plus pertuzumab) than with trastuzumab only anti-HER2 therapy.• Cardiotoxicity surveillance through MRI is an interesting option particularly in patients treated with dual anti-HER2 therapy. Approximately 20% of breast cancers (BCs) strongly overexpress human epidermal growth factor receptor 2 (HER2), whose overexpression has been associated with more aggressive disease and a higher risk of recurrence. Trastuzumab, an anti-HER2 extracellular domain IV binding antibody, significantly improves long-term prognosis in HER2-positive BC patients; pertuzumab, an antibody that binds to HER2 extracellular domain II, has demonstrated promising efficacy in both metastatic and early BC and is an integral part of HER2-positive BC therapy , 2. DespCardiac magnetic resonance imaging (MRI) is the imaging modality of choice in this setting, particularly due to its capabilities of accurate cardiac function measurement and advanced tissue characterisation. Therefore, many studies have aimed to explore the effect of anti-HER2 therapy on cardiac function using cardiac MRI. An early ≥ 10% deterioration in global longitudinal strain (GLS) has been associated with a lower left ventricular ejection fraction (LVEF) at 9 months . In one However, most prior studies used only one anti-HER2 target therapy (trastuzumab), and a large part of the participants had been previously treated with anthracyclines. Increasing use of trastuzumab plus pertuzumab has led to further evaluation of anti-HER2 therapy-related cardiotoxicity without being affected by anthracycline chemotherapy, which may also cause myocardial injury . In addiIn this prospective study, HER2-positive BC participants treated with trastuzumab and/or pertuzumab in combination with nonanthracycline-based chemotherapy underwent cardiac MRI immediately before treatment initiation as well as 3 months after the start of treatment. The purpose was to evaluate and compare the early changes in LV volumetric, functional, and tissue characteristics in patients following short-term exposure to trastuzumab and/or pertuzumab using cardiac MRI.Between January 2021 and May 2022, women (aged 18 years and older) with HER2-positive BC scheduled to receive anti-HER2 therapy were prospectively recruited at our hospital. Anticancer treatments were managed at the discretion of the oncologist. The chemotherapy and anti-HER2 regimen consisted of taxane plus carboplatin plus trastuzumab plus pertuzumab or taxane plus carboplatin plus trastuzumab every 3 weeks. The exclusion criteria were anthracycline-based chemotherapy, previous treatment with anticancer therapy, preexisting cardiac disease, contraindications to cardiac MRI and refusal to participate in the study.Patients were subdivided into two groups according to the anti-HER2 regimen: dual anti-HER2 group (trastuzumab plus pertuzumab) and trastuzumab alone group. The demographic characteristics, cardiovascular risk factors, adjuvant treatment regimens, and BC characteristics were collected at baseline in a standardised manner. Cardiac MRI examinations were performed at baseline and 3 months after initiation of anti-HER2 therapy. Only participants who completed the entire study protocol were included in the final analysis. The hospital research ethics committee approved this study , and all study participants provided written informed consent.The presence of CTRCD was primarily defined as a > 10% reduction in LVEF to < 55% or a > 15% GLS change at the follow-up MRI examination –10. A reCardiac MRI examinations were performed with a clinical 3-T scanner . A 30-channel coil was used for signal reception. All images were acquired in a breath-hold by using a three-lead vector cardiogram for cardiac synchronisation. Cine steady-state free-precession cine images  were obtained in the short axis, two-chamber, three-chamber and four-chamber views for functional analysis. T2-weighted dual inversion-recovery imaging  was used for visualisation of myocardial oedema. A modified look-locker inversion-recovery approach was used for T1 mapping; images were acquired with a 3(3)3(3)5 heartbeat pattern . T2 mapping was conducted using a double inversion-recovery multi-echo fast spin-echo sequence with four different echo times .All images were transferred to the commercially available software cvi42 (Circle Cardiovascular Imaging Inc.) for blinded analysis. The epicardial and endocardial borders of the LV myocardium were manually traced in all phases on short-axis cine images to calculate functional parameters . Papillary muscles were included in the volume. T1 and T2 values were measured using a region of interest placed in the septum of the mid short-axis slice. For feature-tracking strain analysis, endocardial and epicardial contours were manually traced from cine images in the end-diastolic phase. Three long-axis cine images  and global circumferential strain (GCS). All images were analysed by one radiologist with 7 years of experience in cardiac MRI who was blinded to all the clinical information. To assess reproducibility, LVEF, GRS, GCS, GLS, T1 and T2 relaxation time analyses were performed again in 12 randomly selected patients by a second observer (with 9 years of experience) and the first radiologist after an interval of at least 1 month.t test or Mann‒Whitney U test was used, as appropriate. Bland–Altman plots and intraclass correlation coefficients with 95% confidence intervals were used to assess inter- and intra-observer variabilities. Statistical analyses were performed with SPSS  and GraphPad Prism ; p-values lower than 0.05 were considered indicative of significant difference.Clinical and cardiac MRI characteristics were checked for normal distribution using the Shapiro‒Wilk test. Continuous data are shown as mean ± standard deviation for normally distributed values and medians with interquartile ranges (IQRs) for nonnormally distributed variables. Categorical variables are reported as numbers with percentages. For intraindividual comparison of variables between baseline and follow-up MRI examinations, the paired test or Wilcoxon signed-rank test was used, as appropriate. Analysis was carried out in each group separately as well as in the entire study group. For comparison of variables between groups, the unpaired A total of 24 patients were included   had developed CTRCD at the follow-up MRI examination . One patient developed symptomatic heart failure (LVEF 35%) during follow-up. The main symptoms were fatigue and dyspnoea. Five patients experienced an asymptomatic decrease in LVEF. Five of the six patients were on dual (trastuzumab and pertuzumab) anti-HER2 therapy, and one patient was on single (trastuzumab) anti-HER2 therapy (Table versus 59.0% (IQR 55.0–60.0%) (p < 0.001). The LV end-systolic volume index was higher at follow-up than at baseline MRI  versus 25.6 mL/m2 (IQR 21.6–31.9 mL/m2) (p = 0.001). The stroke volume index  and cardiac index  were lower at the follow-up than at the baseline MRI. We found no evident differences between baseline and follow-up MRI examinations in the LV end-diastolic volume index (p = 0.880) or LV mass index (p = 0.536).The median LVEF was significantly lower at follow-up than at baseline  versus 29.3% ± 6.0%, p < 0.001), GCS  and GLS  were observed at follow-up.At myocardial strain analysis, lower GRS  and T2 relaxation time  between the baseline and follow-up MRI examinations  were observed in each subgroup. The cardiac index and GLS decreased significantly at follow-up in the dual anti-HER2 group but not in the trastuzumab group. T1 and T2 relaxation times showed a tendency towards an increase, but this was not statistically significant. There was no significant change in the LV end-diastolic volume index or LV mass index in either group at follow-up Table .Table 3CWe found no evidence of a difference in any of the MRI parameters between the dual anti-HER2 group and the trastuzumab group at either baseline or follow-up.The interobserver correlation coefficient values were 0.90 for LVEF, 0.86 for GRS, 0.84 for GCS, 0.82 for GLS, 0.94 for T1 and 0.86 for T2. The intraobserver correlation coefficient values were 0.93 for LVEF, 0.92 for GRS, 0.86 for GCS, 0.83 for GLS, 0.96 for T1 and 0.90 for T2.In this preliminary prospective study, we focused on a cohort of BC patients treated with anti-HER2 targeted therapy and nonanthracycline-based chemotherapy. Our results support the evidence of cardiotoxicity as an early treatment effect of anti-HER2 therapy.Women with HER2-positive BC treated with anti-HER2 therapy are at high risk of cardiac dysfunction, which is considered the main anti-HER2 therapy-related cardiotoxicity in BC patients. Its overall incidence is highly variable, ranging from 7.6% to 28% , 13. DifThe reduction in LVEF followed by persistent LVEF decline or lack of recovery  is associated with a subsequent risk of major adverse cardiovascular events . DespitePatients with asymptomatic or subclinical cardiac dysfunction will still have cardiac functional reserve and therefore tolerate less additional injury before their symptoms of cardiotoxicity become clinically apparent . A previIn our study, the cine and strain analysis showed systolic functional impairment in both the dual anti-HER2 group and the trastuzumab group. The absolute change in LV end-systolic volume was a larger contributor to the change in LVEF than LV end-diastolic volume in both the dual anti-HER2 group and the trastuzumab group, in line with a previous study . No signGLS is considered a marker of early LV subclinical dysfunction . It can Native T1 relaxation times can identify myocardial fibrosis and T2 relaxation times can identify myocardial oedema. A few previous studies have investigated the anti-HER2 target therapeutic effect on myocardial T1 and T2 relaxation times. However, most of these studies had only one anti-HER2 target therapy (anthracycline), and some of the participants were previously treated with anthracycline, which may prolong T1 and T2 relaxation times. Jordan et al. showed that T1-weighted signal intensity was increased in participants previously treated with anthracycline chemotherapy, which could lead to acute, subacute, chronic myocellular injury . An expeCardiac MRI facilitates early diagnosis of cancer treatment-related cardiotoxicity, but it is not a routine assessment in patients undergoing cancer treatment. Although standard cardiotoxicity surveillance every 3 months is recommended during therapy , we and Several limitations of our study need to be addressed. First, our study included 24 participants and 48 cardiac MRI scans. Therefore, the statistical power was limited due to the small sample size in this preliminary study. Moreover, diastolic function and right ventricular function were not analysed. However, Gong et al.  found noThe aim of this preliminary study was to evaluate and compare early changes in LV function and tissue characterisation using cardiac MRI in BC patients treated with nonanthracycline-based anti-HER2 target therapy. Systolic dysfunction in this group of patients was quite frequent but had a modest clinical impact. The change of myocardial strain was more marked in patients treated with dual anti-HER2 therapy. Cardiotoxicity surveillance through MRI is an interesting option particularly in patients treated with dual anti-HER2 therapy, allowing clinicians to incorporate cardioprotective therapy and decrease the risk of therapy interruptions. Studies with larger sample sizes are warranted.


This study aims to evaluate: the difference of soluble suppression of tumorigenicity 2 (sST2) level, a biomarker for cardiac remodeling and echocardiography parameters value prior to and 1 month after implantation; and the association between pacemaker parameters and pacemaker mode along with delta sST2 levels.This prospective cohort study enrolled all symptomatic bradycardia patients aged >18 years with preserved ejection fraction who underwent permanent pacemaker (PPM) implantation.A total of 49 patients were included in this study. The sST2 level (ng/ml) were significantly different between prior and 1 month following PPM implantation .The early cardiac remodeling has occurred within 1 month after PPM implantation as indicated by increasing delta sST2 level. It is widely known that pacing induced cardiomyopathy, which results from the utilization of a permanent pacemaker (PPM) within a long-term duration, will increase the risk of mortality and morbidity. Hence, early detection of the cardiac remodeling process is warranted in order to prevent this course. In this study, the soluble suppression of tumorigenicity 2 level (ng/ml), known as an indicator of cardiac remodeling, was significantly higher in 1 month following PPM implantation compared with the baseline . Thus, it denotes that early cardiac remodeling might occur earlier than expected, within 1 month following PPM implantation. According to the most recent guideline, permanent pacemaker (PPM) with right ventricular (RV) pacing is still a mainstay therapy of bradycardia in patients with preserved ejection fraction (EF) . Howeveret al. showed that gene expression which regulates cardiomyocytes metabolism was altered within 1 month after PPM implantation [Although a long-term process is necessarily required to cause PICM, the early cardiac remodeling might occur within 1 month after PPM placement ,9. The tantation . MoreoveBased on the current guideline, the soluble suppression of tumorigenicity 2 (sST2) level measurement was recommended as a prognostic marker of heart failure (HF), which increased of this biomarker’s level was correlated with several detrimental outcomes . NonetheThis is a single-center prospective cohort study that enrolled all symptomatic bradycardia patients aged >18 years. Patients who underwent PPM implantation due to symptomatic bradycardia and had left ventricular ejection fraction (LVEF) prior implantation higher than 50% were included. Patients who presented with acute coronary syndrome, acute or chronic HF, valvular heart disease, congenital heart disease, congenital cardiac conduction abnormalities, poor echocardiography window, cardiomyopathy , myocarditis, infection disease, autoimmune disease, acute asthma exacerbation and loss of follow-up were excluded from this study.A decision of choosing PPM mode, either single or dual chamber (VVI or DDD) was made by physician according to current guidelines . We implAll PPM implantation was carried out by an experienced operator. Independent variables of the current study are collected . In this study, we only performed PPM implantation in two different locations such as RVOT pacing and RV apical pacing. The RVOT pacing was preferable rather than RV apical pacing whenever possible, unless the parameters RVOT pacing  was not satisfactory. High septal pacing was classified as RVOT pacing in this study. Either RVOT pacing or RV apical pacing was achieved with an active fixation lead. The appropriate positioning of the lead was fluoroscopically confirmed at the time of implantation and by the QRS axis (during pacing) from ECG which was recorded after implantation. Right ventricle apical pacing was considered when the QRS axis in inferior leads are predominantly negative, and RVOT pacing were considered when QRS axis in inferior leads of ECG are predominantly positive. The pacing burden (pacing percentage) and other PPM parameters were determined from stored data after 1 month of implantation. A standard 12 lead surface ECG was obtained at speed 25 mm/s. The paced QRS duration was defined as the length of time from the beginning of the pacing artifact (spike) to the end of the QRS complex during RV pacing. The QRS duration was measured using a digital calliper .® ST2 Assay according to manufacturer instructions. The delta sST2 is a comparison level of sST2 prior and 1 month after implantation. While the outcome of this study is delta sST2 which described as difference level of sST2 1 month following implantation and 1 week prior implantation.The sST2 were collected prior and after 1 month of implantation. In regard to measure sST2 level, a total of 3 cc of blood sample was taken from each included patient. Blood samples were collected in tubes containing EDTA. Samples were centrifuged for 15 min at 4°C and stored at 2–8°C. Level of sST2 were measured using the Presaget-test or Mann–Whitney U test to calculate the association between two numerical data. Furthermore, in order to compare the sST2 level, QRS duration and echocardiographic parameters prior and after implantation, paired Student’s t-test or Wilcoxon test were used. Student’s t-test was preferred to use if distribution data were normal, whereas Mann–Whitney U and Wilcoxon tests were obtained when distribution data was not normal. Univariate and multivariate analysis were performed using linear regression analysis to discover which variables who modified the sST2 level after implantation. All probability values were deemed statistically significant at a level of <0.05.All statistical analyses were performed using SPSS, version 25.0 . The Shapiro–Wilk test was used to assess data distribution . All numerical data were expressed as means ± standard deviations. Whereas categorical data were summarized as frequencies and percentages. Univariate analysis was performed wielding unpaired Student’s For starters, there are 68 symptomatic bradycardia patients aged >18 years who underwent PPM implantation in the beginning of study. Moreover, 19 of them were excluded due to LVEF <50% (n = 5), poor echocardiography window (n = 3), loss to follow-up (n = 8) and suffer infection disease (n = 3), subsequently 49 patients were finally included into analysis. Patients’ selection process is described in Most of the included patients were elderly (66.5 ± 11.5 years), male (57.1%), and non-smokers (65.3%). Hypertension (67.3%) was the most common comorbidities among included patients, following by dyslipidemia (51%), coronary artery disease (44.9%) and diabetes mellitus (26.5%). Concerning prior medication, the majority of patients received statin (57.1%), calcium channel blocker (46.9%) and antiplatelet (44.9%), whereas only 8.1% of patients took ACEI/ARB and 10.2% consumed beta-blocker.Among included patients, sinus node dysfunction was the main etiology of bradycardia, accounts to 59.2%. Dual chamber pacing (63.3%) was commonly performed in this study. The location of PPM was comparable between in RV apical (44.9%) and RVOT pacing (55.1%). Regarding ECG and echocardiography results, the mean of QRS duration and LVEF appears normal. Moreover, pacing percentage in our study showed a high burden pacing (1 month following implantation). Baseline characteristics are elaborated in The univariate analysis showed that sST2 level 1 month following implantation was significantly higher compared with sST2 level prior implantation (p = 0.001) . The staThe analysis revealed that delta sST2 was not significantly changed regardless of pacing location (p = 0.117) and pacing mode (p = 0.330) . UnivariBased on multivariate linear regression, these three pacing parameters including pacing location (p = 0.808), pacing cumulative percentage (p = 0.079), QRS duration after implantation (p = 0.348) and pacing mode  (p = 0.887) were not substantially correlated with delta sST2 .To the best of our knowledge, this is the first study to detect early cardiac remodelling by sST2 measurement in patient who underwent PPM implantation. This study yielded three main results. For starter, sST2 level was significantly increased within 1 month after PPM implantation, indicating that early cardiac remodeling process was occurred. Second, echocardiographic parameters including LVEF, left ventricle internal diameter at diastolic and left ventricle internal diameter at systolic remained unchanged after 1 month following pacing placement , denotinet al. study found that RV pacing  may alter gene expression Optic Atrophy 1 (OPA1) and Sarcoplasmic Reticulum Calcium ATPase2a (SERCA2a) within 1 month after pacing placement. These genes regulate cardiac mitochondrial energy metabolism and cardiac contractile function [It is generally known that long-term complications of prolong RV pacing is PICM, due to its capability to cause electrical dyssynchrony. The electrical dyssynchrony will triggered mechanical stretch and biomechanical stress and it will trigger cardiac remodeling cascade just soon after the pacing ,3. Xu etfunction . Early cfunction . Anotherfunction . TherefoThe sST2 has been known as a cardiac remodelling marker since 2002 . The secet al. showed that 12 months of RVOT pacing in patients with normal cardiac function has no benefit in term of preventing cardiac remodeling and preserving LV systolic function, despite the fact that RVOT pacing presented more synchronous LV contraction compared with RV apical pacing [et al. have demonstrated that in patients with preserved LVEF, the risk of HF after RV apical pacing was low [et al. also suggested that RV apical pacing provided no harmful effects to patients with normal LV systolic function [et al. study identified that RV septal pacing may offer more beneficial outcomes as opposed to RV apical pacing but only in patient with baseline LVEF <45%, and not in patients with LVEF >45% [The association between several pacing parameters including pacing sites, pacing percentage and paced QRS duration along with PICM have been described by several previous studies. Gong l pacing . Further was low  Similarlfunction . On the et al. study, it showed that pacing percentage >40% have a higher risk to develop PICM, regardless of the PPM mode  [et al. [et al. [Similar to pacing sites, numerous studies have described that number of pacing percentage may also predict the incidence of PICM in the future. According to Sweeney hambers)  Moreover [et al.  showed t [et al.  suggesteet al. showed that wider paced QRS duration was associated with worsening LV systolic function and increase the risk of HF in patients with pacemaker [et al. study has demonstrated that paced QRS duration >140 ms and >167 ms had sensitivity and specificity of 95 and 90%, respectively, to prognosticate the incidence of PICM [et al. and Miyoshi et al. pointed >150 and >190 ms, respectively, as ideal cutoffs for predicting PICM [et al. [et al. [et al. [Given to the paced QRS duration were directly indicated an electrical dyssynchrony, this parameter has been evaluated by several studies for its potential to predict the risk of PICM . A cohoracemaker . Accordiing PICM . However [et al. , the pacBased on two cohort studies, pacemaker mode  was not significantly correlated with PICM incidence ,23. SimiSince none of these pacemaker parameters and pacemaker mode were not associated with delta sST2 level, we speculated that the mechanism of electrical dyssynchrony due to RV pacing is more complicated. The pacing parameters  and AV synchrony may be not the only pathway which triggered the cardiac remodeling in RV pacing. Multiple factors may be involved in the progression of cardiac remodeling due to RV pacing, such as myocardial necrosis, cardiomyocytes traction, mechanical stress, apoptosis, autophagy, fibrosis, oxidative stress, inflammatory response and neurohumoral regulatory disorders ,25.The current guidelines still recommended the utilization of conventional pacemaker in symptomatic bradycardia patient with preserved LVEF . HoweverThis study has three main limitations. First, this study did not provide several laboratory data, including HbA1c and inflammation markers  that could affect the sST2 level, indicating an increased risk of bias. However, in the beginning of the study, we have excluded patient with inflammatory diseases, including myocarditis, infection disease and autoimmune disease, presupposing that included patients have normal inflammation markers. Second, this study did not collect other cardiac remodeling markers, including N-terminal pro-brain natriuretic peptide, galectin-3, GDF-15 and syndecan-1. Hence, the indicator of early cardiac remodeling is solely dependent on significant changes in sST2 levels. Hence, we highly suggest other cohort studies to evaluate the usefulness of other cardiac remodeling markers as an indicator of early cardiac remodeling in patients who underwent PPM therapy in order to support our hypothesis that early cardiac remodeling is initiated in short-term period after the procedure. Third, this study had short-term follow-ups within only 1 month and low sample size; thereby, it may address why several associations  in our analysis were insignificant. Therefore, several prospective cohort studies with a long-term follow-up period and larger sample size are needed to evaluate better the comparison of sST2 level and echocardiographic markers before and after implantation to confirm the occurrence of the early cardiac remodeling process, as well as the association between pacing parameters to delta sST2.In conclusion, this prospective cohort study revealed that early cardiac remodeling has occurred within 1 month after PPM implantation as indicated by increasing delta sST2 level significantly, even though the cardiac structure and function remains unchanged as shown by echocardiographic parameters. However, the pacemaker parameters including pacing sites, pacing percentage, paced QRS duration and pacemaker mode were not associated with early cardiac remodeling. Thus, several prospective cohort studies with long-term follow-up duration and large sample size are required to confirm our findings.Application of a permanent pacemaker (PPM) in bradycardia patients within a long-term period is associated with pacing induced cardiomyopathy.This is the first prospective cohort study that perform early detection of the cardiac remodeling process by measuring the soluble suppression of tumorigenicity 2 (sST2) level; thereby, it will enhance our prevention strategy in intercepting this progressive course.This study revealed that sST2 levels were significantly higher after 1 month following PPM implantation compared with the baseline, indicating that early cardiac remodeling occurred.Echocardiographic parameters, including left ventricular ejection fraction, left ventricle internal diameter at diastolic and left ventricle internal diameter at systolic, remained unchanged after 1 month following pacing placement, denoting that early cardiac remodeling was initiated despite of normal structure and function of the heart.Pacing parameters such as pacing location, pacing percentage, and paced QRS duration were not significantly linked with delta sST2 level, implying that the early cardiac remodeling process after PPM was inevitable.According to this study’s findings, we suggest that utilization of sST2 is needed to predict early cardiac remodeling in bradycardia patients undergoing PPM.


MW indices were evaluated before the procedure, at hospital discharge, and at 1-year follow-up. LV remodeling was described as the percentage variation in LVEDV between baseline and 1-year follow-up. Results: TEER caused an acute reduction in LVEF, global longitudinal strain (GLS), global MW index (GWI), work efficiency (GWE), and mechanical dispersion (MD) and a significant increase in wasted work (GWW). One year after the procedure, GLS, GWI, GWE, and MD recovered, whereas GWW remained significantly impaired. Baseline GWW  was an independent predictor of LV reverse remodeling at 1-year follow-up. Conclusions: In patients with severe PMR undergoing TEER, the acute reduction in LV preload causes significant impairment to all the parameters of LV performance. Baseline GWW was the only independent predictor of LV reverse remodeling, suggesting that a lower myocardial energetic efficiency in the context of chronic preload increase might impact the left ventricular response to mitral regurgitation correction.Background: The noninvasive assessment of myocardial work (MW) allows for the evaluation of left ventricular (LV) performance by considering the effect of LV afterload. This study aims to evaluate the acute and chronic impact of transcatheter edge-to-edge repair (TEER) on MW parameters and LV remodeling in patients with severe primary mitral regurgitation (PMR). Methods: A total of 71 patients  with moderate–to-severe or severe PMR (effective regurgitant orifice: 0.57 ± 0.31 cm Severe primary mitral regurgitation (PMR) is associated with a chronic increase in left ventricular (LV) preload, which causes progressive LV dilatation and dysfunction . The cor®, Abbott structural, Santa Clara, CA, USA) according to recommendations [Patients with severe PMR undergoing TEER (MitraClipndations  at the Utot) was defined by the sum of the RV and stroke volume [2, RV < 30 mL), 2+ , 3+  or 4+  as recommended [All patients underwent transthoracic 2D-echocardiography using standard equipment  equipped with a 3S or M5S 3.5-MHz transducer before TEER, at hospital discharge (3 ± 1 days after TEER), and 1-year FU FU (11 ± 2 months after TEER). Bidimensional, colour Doppler, pulsed-wave, and continuous-wave Doppler data were stored on a dedicated workstation for the offline analysis . Cardiac dimensions and function, especially LV volumes, were measured according to current recommendations, and LVEF was calculated using the Simpson biplane method . LV revee volume . PMR wasommended . As prevommended . For theommended . LV mechommended .Myocardial work (MW) and related indices were estimated using a vendor-specific module  by the combination of LV strain data and the noninvasive estimation of the LV pressure. Briefly, peak systolic LV pressure is assumed to be equal to the peak arterial pressure recorded from the brachial cuff systolic pressure before the echocardiographic study. In all patients, systolic and diastolic blood pressure were measured in a supine position after five minutes of rest before the echocardiographic examination. The mean of three consecutive measures was retained for the purpose of the study. The software then constructed a patient-specific LV pressure curve, adjusting the LV pressure curve to the duration of the isovolumic and ejection phases, defined by visual assessment of valvular timing events ,14. Stra® , coinciding with a per-procedural estimated MR reduction to a grade ≤ 2 [All procedures were performed under general anesthesia using transesophageal echocardiography and fluoroscopic guidance. Procedural success was defined as a noncomplicated placement of one or more Mitraclipsrade ≤ 2 .t-test. Nonnormally distributed variables were expressed as the median and interquartile range and compared using Wilcoxon’s test. Categorical data are expressed as numbers and percentages and compared by the χ2-test. Correlations between variables were assessed by the linear regression analysis, and multiple linear regression was used to identify the best correlates of LV remodeling. The Bland-Altman plot and interclass correlation coefficient (ICC) were used to assess inter- and intra-echocardiographers’ variability in a subgroup of 20 patients. All statistical analyses were performed using Statistical Package for Social Science version 20.0  and MedCalc Software Ltd v20.111 . The normality of the distribution of continuous variables was tested by the Shapiro-Wilk test. Normally distributed variables were expressed as mean and standard deviation and compared using the paired sample Student’s 2, regurgitant volume 80 ± 34 mL), and heart failure symptoms (NYHA 2.7 ± 7) were included in the study. Twenty-three (32%) patients had ischemic cardiomyopathy, and there was paroxysmal or persistent atrial fibrillation in 35 (49%) patients. All patients received optimized medical therapy before mitral TEER. TEER was successful in 68 (96%) patients. Only three patients had >2+ residual mitral regurgitation after TEER, corresponding to an ERO > 0.35 cm2 and RV > 0.45 mL. The severity of PMR decreased at hospital discharge and did not modify at 1-year follow-up. The main clinical characteristics of the patients are depicted in Seventy-one patients  with moderate–to-severe or severe PMR (ERO: 0.57 ± 0.31 cmp < 0.0001), a fair correlation with GWE , a moderate correlation with systolic blood pressure , LVESVi , and a weak correlation with total stroke volume . GWW was well correlated with GWE , modestly correlated with MD , GLS , and RF  , four (10%) had impaired GLS values. On the other hand, five (12%) and six (14%) patients had impaired GWI and GCW, and six (14%) patients had impaired GWW, whereas the alteration in GWE was evident in 10 (24%) patients. Before TEER, GCW and GWI showed an excellent correlation with GLS  , Table 2The evolution of LV size and function before TEER, at hospital discharge, and 1-year follow-up is depicted in p < 0.0001) and moderately correlated with GWE  and SBP . The strength of the correlation between GWI, GCW, and LVESVi increased . GWW was fairly correlated with GWE  and GLS . Interestingly, the strength of the correlation between GWW and MD increased   , Table 2p < 0.0001) and GWE . They were moderately associated with LVESVi  and SBP . On the other hand, GWW was still well correlated with GWE  and MD   , Table 2p = 0.03)  is feasible in TEER candidates and (2) might contribute to explaining some of the mechanisms of the afterload mismatch and LV reverse remodeling observed after the correction of MR. TEER is an effective procedure to treat severe PMR in patients who have a contraindication for conventional cardiac surgery and suitable valvular anatomy . HoweverPrevious studies have shown that a reduction in GLS might be observed in patients with severe primary mitral regurgitation and preserved LVEF and is associated with poor prognosis ,3. In ouIn these patients, the progressive LV dilatation due to the increased preload causes a significant increase in LV wall stress, which is directly proportional to LV systolic pressure and chamber size, according to the Laplace law . The assThe acute removal of the chronic overload condition through the clipping approach is associated with an immediate increase in stroke volume, an abrupt reduction in LV wall stress, and a decrease in systemic vascular resistance . These aAt 1-year follow-up, we observed a significant decrease in LV volumes and recovery in GCW, GWE, and MD. However, GWW remained significantly altered. The persistent increase in GWW might be attributable to the persistence of myocardial fibrosis ,22, despThe determinants of LV remodeling after TEER are objects of debate ,23,24,25The conventional assessment of LV performance is based on the evaluation of myocardial shortening and does not consider LV afterload. Mitral regurgitation is associated with a marked increase in LV preload. Nevertheless, in the presence of LV dilatation, both chamber enlargement and LV afterload contribute to the increased LV wall stress and oxygen demand . The nonThis is a retrospective, monocentric, hypothesis-generating study, including a small group of patients with PMR. We decided to include patients with atrial fibrillation, which did not prevent the assessment of GLS and MW and is quite a common finding in patients with severe mitral regurgitation. In our study, the estimation of MW in patients with atrial fibrillation was made possible by choosing beats with approximately the same average heart rate, but it might be challenging in the case of extreme R-R variability.The impact of atrial fibrillation ablation on LA and LV reverse remodeling and prognosis  has not Eventual modification in medications during follow-up might potentially influence blood pressure and, therefore, the assessment of myocardial work. However, these modifications were not considered in this study, which might represent a bias for myocardial work analysis.During follow-up, we focused on the assessment of LV volumes, and we did not assess LV diameter, so the impact of mitral TEER on LV diameters cannot be determined in our study.The noninvasive assessment of MW is proposed by a vendor only , and strain datasets coming from other vendors cannot be analyzed, which might represent a limitation for the wide application of MW in clinical practice. The estimation of the LV pressure curve from the systolic blood pressure assessed at an arm-cuff sphygmomanometer can be imperfect. Nevertheless, Hubert et al. have shown that small imprecisions in the noninvasive estimation of LV pressure do not affect the measure of myocardial work parameters . The prePatients included in the study had very severe cardiomyopathy and contraindication to conventional surgery. As a consequence, our results should be interpreted cautiously, particularly when transposed to a more classical population of patients undergoing surgery for severe PMR. Finally, the large variability of myocardial work parameters prevents their application in everyday practice to guide clinical management. However, our results might be useful on a population basis to disclose some of the mechanisms that are associated with LV remodeling and afterload mismatch in patients undergoing TEER.The noninvasive assessment of myocardial work parameters is feasible in patients with PMR undergoing TEER and might contribute to underscoring the mechanisms of afterload mismatch observed acutely after a reduction in mitral regurgitation. Moreover, baseline GWW is an independent predictor of the entity of LV reverse remodeling at 1-year follow-up. Further studies are mandatory for confirming these preliminary results in a larger population of patients, including those undergoing surgical mitral valve repair/replacement.