Title: Papillary muscle free strain- promising parameter to predict sudden cardiac death in hypertrophic cardiomyopathy?Author:Dr Aslannif Roslan (MBBS, MRCP)Institut Jantung Negara,50400 Kuala Lumpur,MalaysiaE-mail: [email protected] author:Dr Aslannif Roslan (MBBS, MRCP)Institut Jantung Negara,50400 Kuala Lumpur,MalaysiaE-mail:[email protected] Cardiomyopathy (HCM) generally have a good prognosis. In the long follow-up study over 5 decades annual overall HCM-related mortality was 1.3%/y (0.7% first decade to 1.8% in second and third decades). The sudden cardiac death (SCD) mortality rate was also low (0.1%/y first decade to 0.44% in second and third decades)1. SCD is the most feared HCM complication and the only effective treatment for this is Implantable Cardioverter Defibrillator (ICD) that is responsible for >10-fold decrease in HCM related mortality2. In 2014,the European Society of Cardiology (ESC) come out with risk score comprising 7 variables but this risk score have low sensitivity3,4. This led to the search for additional risk factors such as percentage of late gadolinium enhancement (LGE) in the left ventricle, presence of apical aneurysm and left ventricle ejection fraction <50% .The American Society of Cardiology/American Heart Association (ACC/AHA) incorporate this for their guidelines in 20205.Eventhough this guidelines have high sensitivity, it have low ability to identify low risk patients which can lead to inappropriate ICD implantation4. The ongoing challenge is to identify the small yet significant group of patients who are at risk of sudden cardiac death, heart failure, and death resulting from heart failure.Neither the 2014 nor the 2020 SCD risk calculators/predictors, nor even the latest 2022 ESC guidelines, have incorporated the relatively new echocardiography technique of speckle-tracking strain measurements. This technique is non-doppler oriented, angle independent and have been shown to be highly reproducible with high sensitivity and specificity6. These techniques can measure Global longitudinal strain (GLS), left atrial reservoir (LArS), conduit (LAcS) and booster (LAbS) strain and right ventricle global (RVGLS) and free wall strain (RVFWS). The most studied of these is Global Longitudinal Strain (GLS) and a recent study showed GLS have the highest accuracy to predict fatal arrhythmia and accurate ICD indication compare to all the other echocardiographic parameters that was previously considered important like diastolic left atrial (LA) diameter, left ventricular wall thickness and ejection fraction7.This is consistent with another study of large cohort of 427 HCM patients showing independent association between GLS and all cause mortality, heart transplantation, aborted SCD, and appropriate ICD therapy8. Furthermore, the latest meta-analysis of 13 studies with 2441 HCM patients showed significant correlation between impaired GLS and major adverse cardiovascular outcomes (MACE). The same correlation was also found with LA strain. A recent meta-analysis in 2023 shows significant association between all aspect of LA strain (reservoir, conduit and booster) with MACE as well as development of new atrial fibrillation (AF)9. This is not only true with echocardiography derived strain. In a Cardiac MRI (CMR) strain study published in 2024, the combination of left ventricle circumferential strain and left atrial reservoir strain model shows high diagnostic value of SCD with staggeringly high area under the curve (AUC) of 0.9510. All of these studies show how powerful is strain study in HCM SCD prognosis and it is natural to then look at papillary muscle (PM) strain as this structure is frequently abnormal in HCM11.It is widely known that papillary muscle abnormalities are part of HCM phenotypes, in addition to elongated mitral valve leaflets and hypertrophied muscle with excessive contractility (the sine qua non of HCM)11. Abnormal papillary muscle morphology is independently associated with increase left ventricular outflow tract (LVOT) obstruction with anteroapically displaced PM and double bifid PM patients having higher resting LVOT gradients than control independent of septal thickness, use of rate control medications and resting heart rate12. The variations of papillary muscle abnormalities are anterior and apical displacement of the PM usually involving ALPM, bifid PM characterized by the presence of more than one muscle head (If both PM involved it is called double bifid morphology), accessory PM that extend from the LV apex and inserted to basal myocardium without insertion into the mitral leaflets and anomalous insertion of the PM itself12,13,14.In HCM, the PM are frequently hypertrophied, with a mass measuring roughly twice the healthy controls. HCM patients also tend to have larger number of PM (2.5 muscles vs 2.1 in control) with half of the patients demonstrating multiple (3 or 4) PM15.In this issue of Echocardiography Atilla Koyuncu et al look at 79 patients with HCM that were divided into low/intermediate-risk (n=57, ESC risk score <6 points) and high risk (n=22, ESC risk score ≥6 points) groups based on the ESC risk calculator. Their mean follow-up duration is 6.2 years. They specifically look for PM abnormalities and measured anterolateral papillary muscle (ALPM) and posteromedial papillary muscle (PMPM) free strain in addition to other conventional 2-dimensional echocardiographic parameters and GLS. They enrolled all HCM phenotypic groups with or without obstruction and they exclude patients with hypertension, valvular heart diseases, hepatic/renal failure or inflammatory diseases. Of note, they did not perform left atrium (LA) or right ventricle (RV) strain. Papillary muscle strain is a relatively new tool and the measurements of ALPM strain is done in apical 4 chamber view and measurement for PMPM strain is done in apical 3 chamber view. The majority of patients have sigmoid or reverse curvature phenotype (70.9%). Interestingly 5 patients (6.3%) had anteriorly displaced papillary muscles, 7(8.8%) had bifid ALPM, 5(6.3%) had bifid PMPM and 2 patients have both bifid ALPM and PMPM (double bifid morphology).They found that the high SCD-risk group had greater wall thickness, interventricular septum thickness, posterior wall thickness and left ventricle mass index and lower GLS, ALPM (-16.88 ± 4.41% vs. -14.34 ± 3.68%, p = .028) and PMPM (-18.48 ± 6.31% vs. -15.28 ± 6.88%, p = .042) free strain. Furthermore, the SCD risk score was positively correlated with GLS, ALPM (r=0.658, p<0.001) and PMPM (r=0.600, p<0.001) strain. Also important is the fact that patient who have papillary muscle abnormalities had significantly worse ALPM and PMPM free strain. Finally, in multivariate analysis, LVMI, presence of syncope, worse GLS and ALPM-free strain were predictors of death. In terms of PM free strain value in normal healthy populations, one study done in 2016 shows between -32.5% to -48% for ALPM and -34.5% to -39.5% for PMPM but for the moment at least there are no guidelines for normal values16.What is the relevance of this paper for our understanding of HCM? It introduces an additional parameter that is easy to measure and reproducible alongside GLS and LA strain, aiding in the prediction of SCD. Although the technique is new and the sample size is limited, further studies with larger populations are necessary to establish its predictive value for SCD, similar to GLS. As strain measurements are generally robust and reproducible, papillary muscle strain has the potential to replace traditional parameters like left atrial dimension, wall thickness, and ejection fraction. Moreover, this paper highlights the importance of considering papillary muscle involvement in HCM, drawing attention to abnormalities such as bifid papillary muscles and anterior displacement during strain measurement. Ultimately, by integrating papillary muscle free strain with GLS, RV, and LA strain, we can enhance our ability to predict sudden cardiac death and ensure more appropriate ICD implantation. For clinicians focused on managing HCM, these are exciting times, and this paper provides valuable insights into the field.Maurizi N, Olivotto I, Maron M, et al. Lifetime clinical course of hypertrophic cardiomyopathy: Outcome of the historical Florence cohort over five decades. JACC Adv. 2023;2(4). doi:10.1016/j.jacadv.2023.100337Maron MS, Rowin EJ, Maron BJ. The paradigm of sudden death prevention in hypertrophic cardiomyopathy. Am J Cardiol. 2024;212S:S64-S76. doi:10.1016/j.amjcard.2023.10.076Zeppenfeld K, Tfelt-Hansen J, de Riva M, et al. 2022 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2022;26:ehac262. doi:10.1093/eurheartj/ehac262Monda E, Limongelli G. Integrated sudden cardiac death risk prediction model for patients with hypertrophic cardiomyopathy. Circulation. 2023;147(4):281-283. doi:10.1161/CIRCULATIONAHA.122.063019Ommen SR, Mital S, Burke MA, et al. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2020;142:e558–e631. doi:10.1161/CIR.0000000000000937Shirani J, Pick R, Roberts WC, Maron BJ. Morphology and significance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death. J Am Coll Cardiol. 2000;35(1):36-44. doi:10.1016/s0735-1097(99)00492-1Nikoo MH, Zarrabi M, Moaref A, Razeghian-Jahromi I. Global longitudinal strain may be the one that appropriately identifies candidates for ICD implantation. Cardiol Res Pract. 2024;2024:2214072. doi:10.1155/2024/2214072Hiemstra YL, Debonnaire P, Bootsma M, et al. Global longitudinal strain and left atrial volume index provide incremental prognostic value in patients with hypertrophic cardiomyopathy. Circ Cardiovasc Imaging. 2017;10(7): e005706. doi:10.1161/CIRCIMAGING.116.005706Hussain K, Nso N, Tsourdinis G, et al. A systematic review and meta-analysis of left atrial strain in hypertrophic cardiomyopathy and its prognostic utility. Curr Probl Cardiol. 2024;49(1 Pt C):102146. doi:10.1016/j.cpcardiol.2023.102146Zhu X, Shi Y, Lian J, et al. Left atrial and left ventricular strain in feature-tracking cardiac magnetic resonance for predicting patients at high risk of sudden cardiac death in hypertrophic cardiomyopathy. Quant Imaging Med Surg. 2024;14(5):3544-3556. doi:10.21037/qims-23-1615Sherrid MV, Adams DH. The mitral valve in hypertrophic cardiomyopathy: Other side of the outflow tract. J Am Coll Cardiol. 2020;76(19):2248-2251. doi:10.1016/j.jacc.2020.09.580Kwon DH, Setser RM, Thamilarasan M, et al. Abnormal papillary muscle morphology is independently associated with increased left ventricular outflow tract obstruction in hypertrophic cardiomyopathy. Heart. 2008;94(10):1295-1301. doi:10.1136/hrt.2007.118018Klues HG, Maron BJ, Dollar AL, Roberts WC. Diversity of structural mitral valve alterations in hypertrophic cardiomyopathy. Circulation. 1992;85(5):1651-1660. doi:10.1161/01.cir.85.5.1651Gruner C, Chan RH, Crean A, et al. Significance of left ventricular apical-basal muscle bundle identified by cardiovascular magnetic resonance imaging in patients with hypertrophic cardiomyopathy. Eur Heart J. 2014;Rajiah P, Fulton NL, Bolen M. Magnetic resonance imaging of the papillary muscles of the left ventricle: Normal anatomy, variants, and abnormalities. Insights Imaging. 2019;10(1):83. doi:10.1186/s13244-019-0761-3Kılıcgedik A, Kahveci G, Gurbuz AS, et al. Papillary muscle free strain in patients with severe degenerative and functional mitral regurgitation. Arq Bras Cardiol. 2017;108(4):339-346. doi:10.5935/abc.20170035

Fusion imaging (FI) technology using Echo-Navigator that integrates live transesophageal echocardiogram (TEE) and overlays on real-time fluoroscopy. We present our experience placing a right ventricular (RV) support device, a ProtekDuo, in our patient with post-operative RV failure using FI to guide the implantation.

Concomitant inferior sinus venosus atrial septal defect and hypoplasia of the posterior mitral valve leaflet in a 65-year-old female with a history of surgical ostium secundum atrial septal defect repair decades ago. Transesophageal echocardiography with bubble study using agitated saline contrast and cardiac magnetic resonance confirmed the previously undetected diagnosis

Mitral valve prolapse is a common valve disorder that usually has a benign prognosis unless there is significant regurgitation or left ventricular impairment. However, a subset of patients are at an increased risk of ventricular arrhythmias and sudden cardiac death, which has led to the recognition of ‘arrhythmic mitral valve prolapse’ as a clinical entity. Emerging risk factors include mitral annular disjunction and myocardial fibrosis. While echocardiography remains the primary method of evaluation, cardiac magnetic resonance has become crucial in managing this condition. Cine-MR sequences provide accurate characterization of prolapse and annular disjunction, assessment of ventricular volumes and function, identification of early dysfunction and remodeling, and quantitative assessment of mitral regurgitation when integrated with flow imaging. However, the unique strength of magnetic resonance lies in its ability to identify tissue changes. T1 mapping sequences identify diffuse fibrosis, in turn related to early ventricular dysfunction and remodeling. Late gadolinium enhancement sequences detect replacement fibrosis, an independent risk factor for ventricular arrhythmias and sudden cardiac death. There are consensus documents and reviews on the use of cardiac magnetic resonance specifically in arrhythmic mitral valve prolapse. However, in this article, we propose an algorithm for the broader use of cardiac magnetic resonance in managing this condition in various scenarios. Future advancements may involve implementing techniques for tissue characterization and flow analysis, such as 4D flow imaging, to identify patients with ventricular dysfunction and remodeling, increased arrhythmic risk, and more accurate grading of mitral regurgitation, ultimately benefiting patient selection for surgical therapy.

Type Ⅲ redundancy of the foramen ovale flap (RFOF) mimics hemodynamic changes of mitral stenosis(MS), which has not been particularly highlighted in previous literature. This type of MS carries a favorable prognosis.

Congenitally correct transposition of the great arteries (cc-TGA) is an extremely rare congenital cardiac malposition. They are usually detected by echocardiography in the fetal period. This case report describes a 58-year-old female patient who presented with tachycardia. The combination of cc-TGA and isolated levocardia is incidentally diagnosed by transthoracic echocardiography and cardiac magnetic resonance imaging.

Purpose: Point-of-care cardiovascular left ventricle ejection fraction (LVEF) quantification is established, but automatic tablet-based stroke volume (SV) quantification with handheld ultrasound devices is unexplored. We evaluated a tablet-based monoplane LVEF and LV volume quantification tool (AutoEF) against a computer-based tool (Tomtec) for LVEF and SV quantification. Methods: Patients underwent handheld ultrasound scans, and LVEF and SV were quantified using AutoEF and computer-based software that utilized either apical four-chamber views (AS-mono) or both apical four-chamber and apical two-chamber views (AS-bi). Correlation and Bland-Altman analysis were used to compare AutoEF with AS-mono and AS-bi. Results: Out of 43 participants, 8 were excluded. AutoEF showed a correlation of 0.83 [0.69:0.91] with AS-mono for LVEF and 0.68 [0.44:0.82] for SV. The correlation with AS-bi was 0.79 [0.62:0.89] for LVEF and 0.66 [0.42:0.81] for SV. The bias between AutoEF and AS-mono was 4.88% [3.15:6.61] for LVEF and 17.46 ml [12.99:21.92] for SV. The limits of agreement (LOA) were [-5.50:15.26]% for LVEF and [-8.02:42.94] ml for SV. The bias between AutoEF and AS-bi was 6.63% [5.31:7.94] for LVEF and 20.62 ml [16.18:25.05] for SV, with LOA of [-1.20:14.47]% for LVEF and [-4.71:45.94] ml for SV. Conclusion: LVEF quantification with AutoEF software was accurate and reliable, but SV quantification showed limitations, indicating non-interchangeability with neither AS-mono nor AS-bi. Further refinement of AutoEF is needed for reliable SV quantification at the point of care.

We are grateful to the authors for sharing the results of this very precise and detailed analysis of the diagnostic performance of apical myocardial perfusion by combining high-frequency linear probe and contrast enhanced ultrasound (CEUS) for the detection of left anterior descending artery (LAD) stenosis. there are many imaging modalities to assess coronary artery stenosis. For example, invasive coronary angiography, coronary computed tomography angiography (CCTA), myocardial nuclear perfusion imaging, cardiac magnetic resonance (CMR)[1], it’s crucial to choose the most appropriate imaging modality for diagnosis, treatment and procedural planning. In previous studies, the quantitative analysis of myocardial perfusion by CEUS were based on 17-segment model to assess the stenosis of the relevant vessels[2], it is relatively cumbersome to perform. Since most of the apical LV is supplied by LAD, the authors quantitative analysis of myocardial blood flow in the apical LV to evaluate the stenosis of the LAD vessels by combining high-frequency linear probe and CEUS, overcoming insufficient near-field resolution and artifacts by the conventional phased-array probe. The authors found that it is feasible and convenient to to assess apical perfusion to reflect LAD stenosis by combining high-frequency linear probe and CEUS with high Area under the curve of β, T, A, and MBF (0.880, 0.881, 0.761, and 0.880 respectively). And the best cut-off of β, T, A, and MBF were 10.32, 3.28, 9.39, and 4.99 respectively. What is more, compared with phased-array probe, the quantitative analysis of high-frequency linear probe is of high reproducibility and could get good curve fitting

Objectives: To assess the ability of left atrial(LA) strain parameters to discriminate patients with elevated left atrial pressure(LAP) from patients with atrial fibrillation(AF). Methods and results: A total of 142 patients with non-valvular AF who underwent first catheter ablation(CA) between November 2022 and November 2023 were enrolled in the study. Conventional and speckle-tracking echocardiography（STE）were performed in all patients within 24 hours before CA，and LAP was invasively measured during the ablation procedure. According to mean LAP,the study population was classified into 2 groups of normal LAP(LAP＜ 15 mmHg, n=101) and elevated LAP（LAP≥15 mmHg, n=41)．Compared with the normal LAP group, elevated LAP group showed significantly reduced LA reservoir strain (LASr) [9.14 ( 7.97 -11.80 ) vs 20(13.59-26.96), p < 0.001], and increased LA filling index[9.60 ( 7.15 -12.20 ) vs 3.72 ( 2.17 -5.82 )，p<0.001], LA stiffness index[1.13 ( 0.82-1.46 ) vs 0.47( 0.30 -0.70 )，p<0.001]. LASr, LA filling index and LA stiffness index were independent predictors of elevated LAP after adjusted by the type of AF, EDT, E/e’, mitral E and Peak acceleration rate of mitral E velocity. The receiver-operating characteristic curve (ROC) analysis showed LA strain parameters (area under curve [AUC] 0.794 to 0.819) could provide similar or greater diagnostic accuracy for elevated LAP, as compared to conventional echocardiographic parameters. Furthermore, the novel algorithms built by LASr, LA stiffness index, LA filling index and LA emptying fraction（LAEF）, was used to discriminate elevated LAP in AF with good accuracy (AUC 0.880, accuracy of 81.69%, sensitivity of 80.49%, specificity of 82.18%), and much better than 2016 ASE/EACVI algorithms in AF. Conclusion: In patients with AF，LA strain parameters could be useful to predict elevated LAP and non-inferior to conventional echocardiographic parameters. Besides, the novel algorithm built by LA strain parameters combined with conventional parameters would improve the diagnostic efficiency.

Background Device-related thrombosis (DRT) is a common finding after left atrial appendage closure (LAAC) and is associated with worse outcomes. As women are underrepresented in clinical studies, further understanding of sex differences in DRT patients is warranted. Methods and Results This sub-analysis from the EUROC-DRT-registry compromises 176 patients with diagnosis of DRT after LAAC. Women, who accounted for 34.7% (61/176) of patients, were older (78.0±6.7 vs. 74.9±9.1 years, p=0.06) with lower rates of comorbidities. While DRT were detected significantly later in women (173±267 vs. 127±192 days, p=0.01), anticoagulation therapy was escalated similarly, mainly with initiation of novel oral anticoagulant (NOAC), vitamin K antagonist (VKA) or heparin. DRT resolution was achieved in 67.5% (27/40) of women and in 75.0% (54/72) of men (p=0.40). In the remaining cases, an intensification/switch of anticoagulation was conducted in 50% (9/18) of men and in 41.7% (5/12) of women. Final resolution was achieved in 72.5% (29/40) cases in women, and in 81.9% (59/72) cases in men (p=0.24). Women were followed-up for a similar time as men (779±520 vs. 908±687 days, p=0.51). Kaplan-Meier analysis revealed no difference in mortality rates in women (Hazard Ratio [HR]: 1.73, 95%-Confidence interval [95%-CI]: 0.68-4.37, p=0.25) and no differences in stroke (HR: 0.83, 95%-CI: 0.30-2.32, p=0.72) within two years after LAAC. Conclusion Evaluation of risk factors and outcome revealed no differences between men and women, with DRT in women being diagnosed significantly later. Women should be monitored closely to assess for DRT formation/resolution. Treatment strategies appear to be equally effective.

Left Atrial Strain

Background: Systemic Sclerosis (SSc), an intricate autoimmune disease causing tissue fibrosis, introduces cardiovascular complexities, notably pulmonary hypertension (PH), affecting both survival and quality of life. This study centers on evaluating echocardiographic parameters and endothelial function using Flow Mediated Dilatation (FMD) in SSc patients, aiming to differentiate those with and without pulmonary arterial hypertension (PAH). The emphasis lies in early detection, given the heightened vulnerability of the right ventricle in the presence of PH. Methods: 59 SSc patients and 48 healthy subjects participated, undergoing clinical examinations, echocardiography, FMD assessments, blood analyses, and, when necessary, right heart catheterization (RHC). Results: SSc-PAH patients displayed lower FMD, increased TAPSE <18 mm, RA area >18 cm2, and TRV >280 cm/sec compared to those without PAH and healthy controls. Resting Resistivity Index (RI) was higher in SSc patients, with no significant difference between those with and without PAH. Lower FMD% serves as a predictive marker for adverse cardiovascular outcomes in both SSc and SSc-PAH patients. Stratification by TRV levels and PAH presence reveals notable FMD% variations, emphasizing its potential utility. Conclusions: Early identification of endothelial dysfunction and echocardiographic parameters, such as TAPSE and TRV, could aid in predicting right ventricular dysfunction and PAH in SSc patients.

Objective: The non-invasive right ventricular pressure-strain loop (PSL) represents a novel method for the quantitative assessment of right ventricular myocardial function. Given that atrial septal defect (ASD) is a prevalent congenital heart anomaly associated with right ventricular volume overload, this study aims to quantitatively assess the myocardial function of the right ventricle in ASD patients pre- and post-occlusion by noninvasive right ventricular PSL. Methods: This study included thirty-six patients diagnosed with secundum atrial septal defect (ASD group) and thirty healthy adults (control group). We compared conventional right ventricular echocardiographic parameters, right ventricular strain, and myocardial work in the ASD group before occlusion, two days post-occlusion, and three months post-occlusion, with those in the control group. Results: Prior to and two days following occlusion, the ASD group exhibited higher right ventricular global work index (RVGWI), right ventricular global wasted work (RVGWW), and right ventricular global constructive work (RVGCW) compared to the control group ( P < 0.05). Within the ASD group, post-occlusion, RVGWI, RVGCW, and RVGWW values were significantly reduced compared to pre-occlusion values ( P < 0.001). Furthermore, RVGWI and RVGCW showed a significant decrease three months after occlusion compared to two days post-occlusion ( P < 0.05). Multivariate regression analysis identified ASD diameter and pulmonary artery systolic pressure (PASP) as independent predictors of RVGWI( β = 0.405, P < 0.001; β=2.307， P=0.037) and RVGCW（β=0.350, P＜0.001; β=1.967, P=0.023). Conclusions: The non-invasive right ventricular PSL effectively demonstrates the alterations in right ventricular myocardial function in ASD patients, pre- and post-occlusion. The metrics of right ventricular myocardial work (RVMW) offer a novel indicator for evaluating right ventricular myocardial function in these patients. Moreover, ASD diameter and PASP emerge as independent determinants of RVGWI and RVGCW.

Advancing Transcatheter Valve Replacement for Severe Aortic Regurgitation: Innovations in Devices and Multi-Modality ImagingJulien Dreyfus, MD, PhD1; David Messika-Zeitoun, MD, PhD21: Cardiology Department, Centre Cardiologique du Nord, 32-36 rue des moulins gémeaux, 93200 Saint-Denis, France2: Division of Cardiology, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, CanadaWord Count : 912 wordsAddress for correspondence :Julien Dreyfus, Department of Cardiology, Centre Cardiologique du Nord, Saint-Denis, France. Tel: +33149334803, Fax: +33149334143, E-mail: [email protected] patients with severe symptomatic aortic regurgitation (AR) who are deemed at high surgical risk, off-label use of transcatheter aortic valve replacement (TAVR) is increasingly performed. However, the rate of complications is high in this subset, including migration, paravalvular regurgitation, pacemaker implantation, stroke, bleeding, vascular complication, acute renal failure, surgical conversion and mortality.(1)In this issue of Echocardiography , Hu et al (ref) present their findings on 70 patients (56% of males, mean age=74±8 years) with severe symptomatic AR (all in NYHA functional class III or IV) on native or bioprosthetic valves who underwent a TAVR using the Vita-Flow valves (Microport), a novel self-expanding valve (Figure). The population was divided into two groups: group A consisted of 40 patients with aortic root dilatation or valve prolapse and no valvular calcifications, while group B comprised 30 patients with aortic valve degeneration and/or mild senile calcifications (Agatston score ranging from 0 to 100). All interventions were performed under general anesthesia, with procedural guidance provided by both fluoroscopy and real-time three-dimensional echocardiography. A comprehensive pre-procedural assessment of the anatomy was conducted using both transesophageal echocardiography (TEE) and computed tomography (MSCT) and dedicated software. The study focuses on the utility of echocardiography in the pre-procedural screening, intra-procedural monitoring, and 30-day post-procedural follow-up, while also identifying potential predictors for post-procedural complications.The main results from the study can be summarized as follow:Multimodality imaging analysis demonstrated significant concordance between TEE and MSCT especially in the assessment of the annulus and aorta dimensions, as well as left and right coronary artery height, enabling accurate device sizing.The procedural success rate was high (96%) and there were no deaths at 30 days.Multiple underlying mechanisms of AR were successfully treated.Mild peri-valvular leakage was observed in 16% of cases but no moderate or greater peri-valvular leakage was reported.Incidence of significant complications was low, with 3% experiencing iliac artery dissection, 4% encountering stroke, and 3% developing acute renal insufficiency within 30 days post-procedure. No migration was reported.A noteworthy 22% of patients required new pacemaker implantation due to complete atrioventricular block, with a median implantation time of 6 days with right bundle branch block as the only independent predictor.Procedural success correlated with a positive left ventricular and atrial remodeling at 30 days (reductions in left atrial and left ventricular diameters, and improvement of the left ventricular ejection fraction).The main limitations of this study include its retrospective single-center design, small sample size (although relatively large for a single center), mix of TAVR on native valves and valve-in-valve procedures, and a short follow-up period.A significant proportion of patients with surgical indications for severe AR are not referred, often due to high surgical risk or comorbidities(2,3). Transcatheter treatment of AR is currently on the rise but is much more challenging than for aortic stenosis, notably due to the absence of calcifications.TAVR is currently mostly performed using prostheses developed for aortic stenosis. A recent multicenter registry (PANTHEON) including 201 patients treated with commercially available devices (self-expandable and balloon expendable valves developed for AS) showed that with improvements in TAVR devices, in experienced centers and in selected patients, satisfactory outcomes can be achieved in a majority of patients, but that complications rates remained high (12% of embolization or migration at 1 month and 10% of moderate or greater residual leakage), regardless of prosthesis type. Critically, these complications were associated with high mortality or hospitalization for heart failure rates at 1 year (approximately 25%). Rates of permanent pacemaker implantation were also high (approximately 22%), often associated with device oversizing.(1)Several devices designed for the management of AR are currently available or under evaluation. Presently, the JenaValve Trilogy system (JenaValve Technology) is the only dedicated device to have received Conformité Européenne (CE) mark approval for the transcatheter treatment of patients with AR. A recent multicenter registry, comprising 58 consecutive patients from 6 centers across Germany, demonstrated excellent outcomes with a 98% implantation success rate, the absence of moderate or severe paravalvular regurgitation, a 30-day mortality rate of 1.7%, and a 19.6% rate of new permanent pacemaker implantation.(4) The Jena-Valve ALIGN-AR Pivotal Trial (NCT04415047) included 177 patients with 91% of procedures performed under general anesthesia. The trial yielded a procedural success rate of 95%, with 3% of patients necessitating subsequent surgery. Only 0.6% experienced moderate or severe paravalvular regurgitation, and 30-day mortality rate was 2.2%. Additionally, 24% of patients received new pacemaker implantation, a rate that tended to decrease with experience, particularly with refined strategies for device sizing and positioning.The J-Valve (JC Medical), specifically designed for the treatment of patients with AR, is another alternative. A recent study including 27 patients for compassionate use found a procedural success rate of 81% overall and 100% in the last 15 cases, with no patient having residual AR of moderate or greater degree at 30 days and a 13% rate of new pacemaker implantation.(5)In conclusion, there is a genuine enthusiasm for transcatheter AR management, driven by both industry innovation and clinical demand. Dedicated devices seem to perform better than devices commercially used for aortic stenosis, but pacemaker implantation rate remains high. Multimodal imaging plays a pivotal role in patient and device selection, procedural guidance, and follow-up. Although echocardiography seems accurate, as for aortic stenosis, MSCT will remain the method of choice for pre-intervention procedural planning. As the landscape rapidly evolves, refining patient selection, procedural techniques, and postprocedural care will be paramount to ensuring optimal outcomes in this challenging patient population.

Strain imaging as a tool to engage in unravelling the secrets of cardiac motion in health and disease has opened a new horizon in the field of clinical cardiology beyond the standard algorithm for quantification of left ventricular function and dysfunction. As such, the wider application of strain can probably be compared with the ubiquitous application of the incretin molecule, glucagon like peptide 1 receptor agonist (GLP 1RA) first applied to manage type 2 diabetes, that is now indicated in many different conditions like obesity, heart failure, and Alzheimer’s disease! This commentary would focus on the role of automated strain imaging in heart failure, aortic stenosis, cardiac amyloidosis, atrial fibrillation, left atrial, and right ventricular strain, on a 2-dimensional domain of spacetime navigated, to some extent, by AI. This commentary thus argues that automated strain imaging is becoming an essential tool for comprehensive cardiac assessment across various conditions.

THE ADDED VALUE OF LEFT ATRIAL STRAIN IN CANCER-THERAPY-RELATED CARDIAC DYSFUNCTIONByLaura Romero, MD and Michele Nanna, MDAlbert Einstein Coll of Med/ Cardiac Care and Vascular Medicine, Bronx, NYCorrespondence:Michele Nanna, MD,Associate Professor of Medicine, Albert Einstein College of Medicine/ Cardiac Care and Vascular Medicine1461 Astor Ave, Bronx, NY 10469, USAEmail: [email protected] cardiac dysfunction (CTRCD) is an undesirable side effect of chemotherapy that occurs in approximately 10% of the patients [1]. Targeting early detection and advances in treatment increases cancer survivors [2]. The American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines recommend the use of Speckle-Tracking-derived LV Global Longitudinal Strain (LV-GLS) as a more objective and accurate method to identify subclinical LV deterioration in patient undergoing chemotherapy [3].In cancer patients, assessment of Left Atrium (LA) function by Speckle Tracking has emerged as a potential tool for predicting CTRCD and its associated morbid arrhythmias such as atrial fibrillation (AF), a frequent complication in this patient population [4-6].Early research work used volumetric approaches to derive LA function parameters. Volumetric parameters are widely used in standard clinical practice and current guidelines assigns prognostic value to end-systolic LA volume in patients with suspected LV diastolic dysfunction [3]. The relationship between LV filling and volumetric parameters is not linear and reduction in LV filling pressures reduces but rarely normalizes LA volumes. LA functional parameters, as measured by novel methods of deformation analysis, more reliably detect reductions in LV filling independent of LA volumes changes [7]. Speckle tracking echocardiography–derived analysis of LA strain provides quantitative parameters for all phases of LA function (reservoir, conduit, and booster pump) and carries similar prognostic significance to that provided by volumetric approaches, in different pathological conditions including cancer patients[5,8].Knowing the impact that LA functions has in detecting CTRCD the study by Lassen and colleagues has tested LA strain in the evaluation of CTRCD as a tool for early detection of myocardial damage induced by chemotherapy [9].In this retrospective cohort study a total of 170 women with HER2+ breast cancer (stage I-IV) undergoing treatment with trastuzumab were studied at baseline, 3 months into treatment and 1 year since treatment initiation. Of note, 77 (45.3%) of participants had prior exposure to anthracycline. Also of note, during the 1- year follow-up, 23 (13.5%) patients had trastuzumab held or stopped for either a decline in Left Ventricular Ejection Fraction (LVEF) in 82.6% of cases or other non-cardiac reasons in the remaining cases.A total of 36 patients developed CTRCD during follow-up. At 3-month follow-up, CTRCD patients had lower LVEF, LV-GLS, LA reservoir strain (LA εres), and LA conduit strain rate (LAεcon-sr) compared to patients that did not develop CTRCD. In the 36 patients developing CTRCD, there was a decline in LVEF from baseline to 3-months follow-up with partial recovery at 1-year follow- up. LV-GLS also declined at 3 months, however, contrary to LVEF a recovery did not occur at 1 year follow up. In the 134 patients who did not develop CTRCD during follow-up, LA Volume Index increased from baseline to 3-month follow-up and then modestly recovered at 1-year. LA strain parameters also declined during follow-up but to a lesser degree than in the CTRCD group suggesting its value as a more sensitive parameters of subtle functional changes. This study is one of the largest studies in patients with breast cancer that has assessed changes in LA strain parameters following treatment with transtuzumab.The new information provided by Lassen et al. is in demonstrating that cancer and its treatment with Transtuzumab may negatively affect atrial function and that measurements of LA strain can detect functional changes related to cardiotoxic effects of chemotherapy. Other studies also support the fact that cancer and chemotherapy can modified LA function earlier than LV function. For example, Laufer-Perl et al. identified that cancer itself caused LA εres to be 17% lower with a further 10% relative reduction in LA εres or a decrease in LA εres below 35% in half of a population of patients undergoing chemotherapy with anthracycline. [10]. Park et al. demonstrated that while both LA εres and LV-GLS were early markers in the detection of CTRCD, LA εres reduction was more sensitive and specific than LV-GLS in predicting CTRCD [6]. Similar abnormalities in LA function were demonstrated by Tadic et al. who showed that LA reservoir and conduit function were reduced, while booster pump function was increased in cancer patients [11]. Combined with the observation by Laufer- Perl and colleagues, this raises the question as to whether LV dysfunction is only the consequence of anti- cancer therapy or if cancer itself leads to abnormalities in function. Thus, both the pathology and the therapy for that pathology can lead to LA functional impairment, which is associated with a higher risk of AF, a frequent arrhythmia in cancer patients with an impact on prognosis [4, 12].Several limitations should be noted. CTRCD is a serious complication of anticancer therapy that can beclassified into Type I exemplified by anthracyline- induced cardiac dysfunction characterized by irreversible myocardial damage due to cumulative administered dose and type II exemplified bytrastuzumab- induced cardiac dysfunction that is dose independent and reversible. The mechanism of cardiac toxicity in both types is not well defined. Current ACC/AHA guidelines recommend that patients who develop Heart Failure (HF) while receiving potentially cardiotoxic therapies should have these therapies discontinued while a diagnostic workup is undertaken to ascertain the cause of HF [12, 13]. These guidelines acknowledge that, particularly in patients receiving trastuzumab, asymptomatic decreases in LVEF can occur in approximately 10% of patients, yet, a high recovery rate is observed and discontinuation of therapy is not always necessary. [13, 14].Accordingly, trastuzumab is often continued in patients deemed low risk while neurohormonal blockadeIs initiated usually with guideline directed medical therapy to improve LV function such as beta blockersand ACEi. While the authors report discontinuing or holding trastuzumab in 23 (13.5%) patients, they do not mention adjuvant treatment with neurohormonal blockade that might have influenced the results. Partial improvement of some parameters (LA εres and LVEF) at 12 months follow-up in patients who developed CTRCD raises the possibility that treatment with adjuvant therapy might be responsible for the beneficial changes. Another important limitation is the lack of additional echocardiographic parameters potentially related to LA function. A significant association exists between impaired LA strain and LV filling pressure (E/E′ ratio), pulmonary pressure (tricuspid regurgitation velocity), and RV systolic function (RVFAC) [15]. None of these parameters have been described in the manuscript.From a research perspective, future investigations should be mindful of the association between reduction in LV filling pressure and improvement in LA function as indicated by the improvement in LA strain and a more holistic approach should be used reporting echocardiographic parameters related toLV filling (i.e. E/E′ ratio, LA stiffness index or E/E′/LA reservoir strain). Although Strain and Strain Rate are increasingly used, deformation analysis of the LA offers unique challenges. Anatomic challenges as well as specific expertise and training required for accurate data acquisition and processing remain a significant impediment to a widespread clinical use. Advances in cardiac imaging in the field of speckle tracking echocardiography, including machine learning algorithms, may help overcome these obstacles and provide a more reliable and fast functional assessment of the LA.Despite the limitations the manuscript convincingly confirms previous reports that have demonstrated the added value of LA strain in the assessment of various pathologic conditions affecting LV function and reinforces the need for further work to establish its role in clinical applications such as risk stratification and decision-making strategies.BIBLIOGRAPHY1. Cardinale D, Colombo A, Bacchiani G, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015; 131(22):1981-8.2. de Moor JS, Mariotto AB, Parry C, et al. Cancer survivors in the United States: prevalence across the survivorship trajectory and implications for care. Cancer Epidemiol Biomarkers Prev. 2013; 22(4):561-70.3. Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016; 29(4):277-314.4. Galderisi M, Esposito R, Sorrentino R, et al. Atrial Fibrillation, Cancer and Echocardiography. J Cardiovasc Echogr. 2020; 30(Suppl 1):S33-S7.5. Sarvari SI, Haugaa KH, Stokke TM, et al. Strain echocardiographic assessment of left atrial function predicts recurrence of atrial fibrillation. Eur Heart J Cardiovasc Imaging. 2016; 17(6):660-7.6. Park H, Kim KH, Kim HY, et al. Left atrial longitudinal strain as a predictor of Cancer therapeutics-related cardiac dysfunction in patients with breast Cancer. Cardiovasc Ultrasound. 2020; 18(1):28.7. Huynh QL, Kalam K, Iannaccone A,et al. Functional and Anatomic Responses of the Left Atrium to Change in Estimated Left Ventricular Filling Pressure. J Am Soc Echocardiogr. 2015; 28(12):1428-33.e1.8. Donal E, Behagel A, Feneon D. Value of left atrial strain: a highly promising field of investigation. Eur Heart J Cardiovasc Imaging. 2015; 16(4):356-7.9. M C Lassen, F Arya, T Biering-Sørensen, et al. Left Atrial Strain is Reduced Following Trastuzumab in Breast Cancer Patients. Echocardiography (InPress).10. Laufer-Perl M, Arias O, Dorfman SS, et al. Left Atrial Strain changes in patients with breast cancer during anthracycline therapy. Int J Cardiol.2021; 330:238-44.11. Tadic M, Genger M, Cuspidi C, et al. Phasic Left Atrial Function in Cancer Patients Before Initiation of Anti-Cancer Therapy. J Clin Med.2019; 8(4).12. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022; 79(17):e263-e421.13. Guarneri V, Lenihan DJ, Valero V, et al. Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience. J Clin Oncol. 2006; 24(25):4107-15.14. Wang SY, Long JB, Hurria A, et al. Cardiovascular events, early discontinuation of trastuzumab, and their impact on survival. Breast Cancer ResTreat. 2014; 146(2):411-9.15. Santos AB, Roca GQ, Claggett B, et al. Prognostic Relevance of Left Atrial Dysfunction in Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2016; 9(4):e002763.

Abstract Objective: We sought to evaluate the left atrial (LA) strain parameters of maintenance hemodialysis (MHD) patients before and after dialysis by two dimensional speckle tracking imaging (2D- STI), and to explore the effect of volume load change on LA function. Methods: 76 patients with end stage renal disease (ESRD) on hemodialysis (HD) were enrolled in the study protocol. The median duration of dialysis was 24.0 (7.5, 59.5) months. In addition, 30 healthy subjects were selected as control group. Comprehensive echocardiography was performed immediately before and after hemodialysis to compare the changes in left atrial function. Results: Regarding LA strain parameters in patients of pre-HD, the median (25th, 75th) LA reservoir, LA conduit, and LA contractile reserve were 28.0 (23.0, 34.5), -15.5 (-10.0, -21.5),-12.0 (-9.0, -16.0) respectively; the post-HD were 26.0 (21.0, 29.0), -12.0 (-9, -15.5), -12.5 (-9, -15.5) respectively; and controls were 43.0 (36.0, 48.0), -24.0 (-18.0, -32.0), -17.0 (-15.0, -22.0) respectively. The left atrial strain parameters before HD were lower than controls, the differences were statistically significant (P < 0.05). The reservoir function and conduit function of LA strain decreased after hemodialysis, the differences were statistically significant (P < 0.05). Regarding the contraction of LA, the differences between pre- and post-HD were not statistically significant (p > 0.05). Conclusion: New echocardiographic parameters, such as left atrial strain, can quantitatively evaluate the changes in left atrial function before and after hemodialysis in ESRD patients, which can provide valuable information for the overall cardiac evaluation in this specific population.

Introduction: Doppler-derived pulmonary pulse transit time (pPTT) is an auspicious hemodynamic marker in chronic pulmonary diseases. The aim is to compare four distinct pPTT measurements and its relation to right cardiac and pulmonary function. Methods: Prospectively, 22 chronic obstructive pulmonary disease (COPD) patients (one patient excluded) and 32 healthy subjects underwent repeated distinct pPTT measurements, one standard echocardiography and pulmonary function testing on the same day. pPTT was defined as the interval from the R or Q-wave in the ECG to the corresponding pulse wave Doppler peak late systolic (S2) or diastolic (D) pulmonary vein flow velocity (pPTT R-S , Q-S, R-D, Q-D). Reproducibility was evaluated using Bland-Altman analysis, coefficient of variation (COV), intraclass correlation coefficient (ICC) and power calculations. Coherence to right ventricle RV tissue und pulse wave Doppler velocities (RV E´, RV S´, RV A’, RV E, RV A, RV E/E‘, RV E/A (cm/s)), tricuspid annular plane systolic excursion (TAPSE), forced expiratory volume in 1 second (FEV1), vital capacity (FVC) predicted (%) and in (l) were analyzed. Results: There was no significant difference and no bias between pPTT measures (p range: 0.1 - 0.9). COV was in COPD 1.2 - 2.3%, in healthy subjects 1.0 % - 3.1 %. ICC ranged from 0.92 (COPD) to 0.96 (healthy subjects). In COPD significant correlations were found for pPTT R-S , Q-S and R-D with RV E‘, (all >ρ: 0.49, ρ: 0.49, ρ: -0.39, Conclusions: All pPTT measures were highly reproducible and affected by diastolic RV performance. Defining Q as starting point seems clinically advantageous considering electromechanical desynchrony in patients with conduction disorders.