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Background: Evidence about early cardiac mechanics abnormalities in patients with mitochondrial diseases (MDs) before overt cardiomyopathy is limited., Methods: In this prospective study, we performed a comparative analysis of conventional and speckle tracking echocardiographic parameters between patients with genetically identified MDs and no overt cardiomyopathy vs controls matched for age, sex and cardiovascular risk factors. The Newcastle mitochondrial disease adult scale (NMDAS) was calculated, using a threshold of > 21 as indicator of high disease severity., Results: We enrolled 24 MDs patients (50 % males, mean age 47.2 ± 14.3 years), the most prevalent mutation was the MT-TL1 m.3243A>G (37.5 %). In MDs patients all dimensional echocardiographic parameters were similar to controls. Conversely, albeit normal, Tissue Doppler septal systolic (p = 0.002) and early diastolic velocities (p = 0.016) were significantly lower and E/e' ratio was higher (p = 0.032) in MDs. Moreover, LV-GLS was significantly reduced in MDs as compared to their counterparties (20.2 ± 1.6 vs 22.6 ± 1.5, p < 0.001). Similarly, LA reservoir and conduit strain were significantly lower in MDs (31.7 ± 7.0 vs 35.9 ± 6.6, p = 0.038; 19.7 ± 5.6 vs 23.1 ± 6.0, p = 0.049 respectively), while LA contractile strain was similar between the two groups. Lower values of LV-GLS were observed in patients with NMDAS > 21 vs patients with NMDAS ≤ 21 (19.0 ± 1.2 vs 21.0 ± 1.3, p = 0.001)., Conclusions: In patients with MDs and no overt cardiomyopathy Tissue Doppler and speckle tracking analysis unveil worse LV systolic and diastolic function indices as compared to controls. Reduced LV-GLS values were found especially in those with worse disease burden., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

Aims: This study aims to explore the presence of left ventricular (LV) and left atrial (LA) morphological and functional abnormalities in patients with Barlow's disease (BD) without significant mitral regurgitation (MR) and to investigate whether these abnormalities may predict MR progression., Methods and Results: Consecutive patients with BD were retrospectively identified from two tertiary centres; those with MR graded from trivial to mild-to-moderate were selected and matched with healthy controls in a 1:1 ratio. Conventional and speckle-tracking echocardiographic data were collected. The development of moderate-to-severe or greater MR was evaluated on follow-up echocardiograms. Patients with BD (n = 231) showed increased LV dimensions and indexed LV mass (LVMi) in comparison with controls (P < 0.001); LV remodelling worsened with higher MR severity and was accompanied by an increased prevalence of eccentric LV hypertrophy (eLVH). Moreover, BD patients had larger LA volumes and more impaired LA reservoir strain vs. controls (P < 0.001), while LV strain was similar between the two groups. Multivariable linear regression analyses in the overall population identified BD and MR grade as independent predictors of remodelling markers (LV dimensions, LVMi, and LA volume) and BD as independent correlate of LA strain. MR progression was observed in 51 BD subjects (out of 170 patients with available follow-up). On Cox regression analysis, age, eLVH, mild-to-moderate MR, and mitral annular disjunction (MAD) emerged as independent predictors of MR progression., Conclusion: BD patients without significant MR show early LV and LA remodelling, together with reduced LA strain. MR progression was associated with eccentric LV remodelling, MAD, and MR severity., Competing Interests: Conflict of interest: The Department of Cardiology, Heart Lung Center, Leiden University Medical Center, received research grants from Abbott Vascular, Alnylam, Bayer, BioVentrix, Biotronik, Boston Scientific, Edwards Lifesciences, GE Healthcare, Medtronic, Medis, Novartis, Pfizer, and Pie Medical. J.J.B. received speaker fees from Abbott Vascular. N.A.M. received speaker fees from Abbott Vascular, GE Healthcare, Philips Ultrasound, and Omnor., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Clinical and echocardiographic results of valve repair for mitral regurgitation in the setting of atrial fibrillation are poorly studied., Methods: Between January 2008 and December 2020, 89 patients underwent valve repair for mitral regurgitation in the setting of atrial fibrillation. Clinical and echocardiographic follow-up data were collected and studied. The primary composite endpoint consisted of all-cause mortality or hospitalization for heart failure., Results: Valve repair with true-sized annuloplasty was performed in 83 (93 %) and restrictive annuloplasty in 6 (7 %) patients. Early mortality occurred in 3 (3 %) and residual mitral regurgitation in 1 (1 %) patient. During a median follow-up of 5.4 years (interquartile range 3.4-9.5), 25 patients died, 6 due to end-stage heart failure. Ten patients were hospitalized for heart failure. The estimated event-free survival rate at 10 years was 48.2 % (95 % CI 33.5 %-62.9 %). Recurrent mitral regurgitation was observed in 14 patients and most often caused by leaflet tethering. When analyzed as a time-dependent variable, recurrent regurgitation was related to the occurrence of the primary endpoint (hazard ratio 3.192, 95 % CI 1.219-8.359, p = 0.018). On exploratory sub-analyses, no recurrent regurgitation was observed after restrictive annuloplasty or in patients with paroxysmal atrial fibrillation. Moreover, recurrent regurgitation was observed more often when signs of left ventricular impairment were present preoperatively., Conclusions: Despite good initial results, recurrent regurgitation was a frequent observation after valve repair for mitral regurgitation in atrial fibrillation and had an effect on heart failure related morbidity and mortality. Refinements in the timing of surgery and surgical technique might help improve outcomes., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: Lung ultrasound (LUS) is a sensitive tool to assess pulmonary congestion (PC). Few data are available on LUS-PC evaluation in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). The aim of this study was to assess the prevalence and prognostic impact of LUS-PC in patients with severe AS before and after TAVI., Methods and Results: We designed a single-centre prospective study in patients referred for TAVI for severe AS (ClinicalTrials.gov identification number: NCT05024942). All patients underwent echocardiography and LUS (according to a simplified 8-zone scanning protocol) the day before and within 72 h after the procedure. The primary endpoint was the composite of all-cause mortality, hospitalization for heart failure and urgent medical visits for worsening dyspnoea at 12-month follow-up. A total of 127 patients were enrolled (mean age 81.1 ± 5.8 years; 54.3% female). Pre-TAVI LUS-PC was documented in 65 patients (51%). After TAVI, the prevalence of LUS-PC significantly decreased as compared to pre-TAVI evaluation, being documented in only 28 patients (22% vs. 51%, p < 0.001) with a median B-lines score of 4 (interquartile range [IQR] 0-11) versus 11 (IQR 6-19) pre-TAVI (p < 0.001). During a median follow-up of 12 (12-17) months, 25 patients (19.6%) met the composite endpoint. On multivariable Cox regression analysis, pre-TAVI LUS-PC was independently associated with cardiovascular events (hazard ratio 2.764, 95% confidence interval 1.114-6.857; p = 0.028)., Conclusions: Lung ultrasonography reveals a high prevalence of PC in patients with severe AS undergoing TAVI, which is significantly reduced by the procedure. Pre-TAVI PC, measured by LUS, is an independent predictor of 1-year clinical outcome., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: To evaluate the prognostic implications of left atrial reservoir strain-defined diastolic dysfunction (LARS-DD) grade in patients undergoing TAVI for severe aortic stenosis (AS) and to determine if post-TAVI LARS was more closely associated with new-onset atrial fibrillation than pre-TAVI LARS., Methods and Results: Pre-TAVI LARS-DD was evaluated by speckle-tracking echocardiography and was assigned as grade 0 to 1 (LARS≥24%), grade 2 (LARS≥19 to <24%) and grade 3 (LARS<19%). Patients were followed-up for the primary endpoint of all-cause mortality from the date of TAVI. For the secondary endpoint, patients with pre- and post-TAVI LARS measurements and no history of atrial fibrillation were evaluated for the occurrence of new-onset atrial fibrillation. A total of 601 patients (median age 81 [76-85] years, 53% male) were included. Overall, 169 patients (28%) were LARS-DD grade 0/1, 96 patients (16%) were LARS-DD grade 2 and 336 (56%) were LARS-DD grade 3. Over a median follow-up of 40 (IQR 26-58) months, a total of 258 (43%) patients died. In a comprehensive multivariable Cox regression model, LARS-DD grade was independently associated with all-cause mortality (adjusted HR 1.28 per one-grade increase, 95%CI 1.07-1.53, P=0.007). For the secondary endpoint of new-onset atrial fibrillation, a total of 285 patients were evaluated. Post-TAVI LARS (SDHR 1.14 per 1%<20%, 95%CI 1.05-1.23, P=0.0009), but not pre-TAVI LARS (P=0.93) was independently associated with new-onset atrial fibrillation., Conclusions: Increasing LARS-DD grade was independently associated with long-term post-TAVI survival in patients with severe AS. Post-TAVI LARS was closely related to the occurrence of new-onset atrial fibrillation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Previous studies demonstrated the prognostic value of baseline cardiac damage staging as well as left ventricular global longitudinal strain (LVGLS) in patients undergoing transcatheter aortic valve implantation (TAVI). The aim of the present study was to evaluate the changes in cardiac damage stage and LVGLS after TAVI and to investigate their prognostic values when integrated into the follow-up assessment. Methods: Patients with severe aortic stenosis undergoing TAVI were hierarchically classified into cardiac damage stages based on echocardiographic criteria before TAVI and at a 6-month follow-up. At the same time, LVGLS was measured. The staging system included stage 0 = no signs of cardiac damage; stage 1 = LV damage; stage 2 = mitral or left atrial damage; stage 3 = pulmonary vasculature or tricuspid damage; and stage 4 = right ventricular damage. The primary endpoint was all-cause mortality. Results: A total of 620 patients were included. At follow-up, LVGLS significantly improved, and the improvement was similar among each baseline cardiac damage stage. Follow-up LVGLS values were divided into quintiles, and each quintile was integrated into the cardiac damage staging, leading to a reclassification of 308 (50%) patients. At the time of a median follow-up at 48 (IQR 31-71) months starting from the 6-month follow-up after TAVI, 262 (38%) patients had died. A multivariable Cox regression model showed that LVGLS-integrated cardiac damage staging at follow-up had an incremental prognostic value over the baseline assessment (HR per 1-stage increase 1.384; 95% CI 1.152-1.663; p < 0.001). Conclusions: The integration of LVGLS with conventional echocardiographic parameters of cardiac damage at a 6-month follow-up after TAVI can improve patient risk-stratification.

Introduction: After ST-segment elevation myocardial infarction (STEMI), follow-up imaging is currently recommended only in patients with left ventricular ejection fraction (LVEF) <40%. Left ventricular global longitudinal strain (LVGLS) was shown to improve risk stratification over LVEF in these patients but has not been thoroughly studied during follow-up. The aim of this study was to explore the changes in LVGLS after STEMI and their potential prognostic value., Materials and Methods: Data were analyzed from an ongoing STEMI registry. Echocardiography was performed during the index hospitalization and 1 year after STEMI; LVGLS was expressed as an absolute value and the relative LVGLS change (ΔGLS) was calculated. The study end point was all-cause mortality., Results: A total of 1,409 STEMI patients (age 60 ± 11 years; 75% men) who survived at least 1 year after STEMI and underwent echocardiography at follow-up were included. At 1-year follow-up, LVEF improved from 50% ± 8% to 53% ± 8% (P < .001) and LVGLS from 14% ± 4% to 16% ± 3% (P < .001). Median ΔGLS was 14% (interquartile range, 0.5%-32%) relative improvement. Starting 1 year after STEMI, a total of 87 patients died after a median follow-up of 69 (interquartile range, 38-103) months. The optimal ΔGLS threshold associated with the end point (derived by spline curve analysis) was a relative decrease >7%. Cumulative 10-year survival was 91% in patients with ΔGLS improvement or a nonsignificant decrease, versus 85% in patients with ΔGLS decrease of >7% (P = .001). On multivariate Cox regression analysis, ΔGLS decrease >7% remained independently associated with the end point (hazard ratio, 2.5 [95% CI, 1.5-4.1]; P < .001) after adjustment for clinical and echocardiographic parameters., Conclusions: A significant decrease in LVGLS 1 year after STEMI was independently associated with long-term all-cause mortality and might help further risk stratification and management of these patients during follow-up., Competing Interests: Conflicts of Interest This study is supported by a Novartis AG research grant. J.J.B. has received speaker fees from Abbott Vascular, Edwards Lifesciences, and Omron. N.A.M. has received speaker fees from Philips Ultrasound, Abbott Vascular, Omron, and GE Healthcare. K.T. has received speaker fees from Astra Zeneca, Bayer, Berlin Menarini, Boehringer-Ingelheim, Biotronik, Novo-Nordisk, and Servier. The Department of Cardiology of the Leiden University Medical Centre has received unrestricted research grants from Abbott Vascular, Alnylam, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Medis, Pfizer, Pie Medical, and Medtronic. All other authors have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Functional tricuspid regurgitation (TR) can develop either because of right ventricular (RV) remodeling (ventricular functional TR) and/or right atrial dilation (atrial functional TR)., Objectives: This meta-analysis aimed to investigate the association between right heart remodeling and long-term (>1 year) all-cause mortality in patients with significant TR (at least moderate, ≥2+)., Methods: MEDLINE, ISI Web of Science, and SCOPUS databases were searched. Studies reporting data on at least 1 RV functional parameter and long-term all-cause mortality in patients with significant TR were included. This study was designed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) requirements., Results: Out of 8,902 studies, a total of 14 were included, enrolling 4,394 subjects. The duration of follow-up across the studies varied, ranging from a minimum of 15.5 months to a maximum of 73.2 months. Overall, long-term all-cause mortality was 31% (95% CI: 20%-41%; P ≤ 0.001). By means of meta-regression analyses, an inverse relation was found between tricuspid annular plane systolic excursion (11 studies enrolling 3,551 subjects, -6.3% [95% CI: -11.1% to -1.4%]; P = 0.011), RV fractional area change (9 studies, 2,975 subjects, -4.4% [95% CI: -5.9% to -2.9%]; P < 0.001), tricuspid annular dimension (7 studies, 2,986 subjects, -4.1% [95% CI: -7.6% to -0.5%]; P = 0.026), right atrial area (6 studies, 1,920 subjects, -1.9% [95% CI: -2.5% to -1.3%]; P < 0.001) and mortality., Conclusions: RV dysfunction parameters are associated to worse clinical outcomes in patients with TR, whereas right atrial dilatation is linked to a better prognostic outcome. Further studies are needed to unravel the pathophysiological differences within the functional TR spectrum. (Right heart remodeling and outcomes in patients with tricuspid regurgitation; CRD42023418667)., Competing Interests: Funding Support and Author Disclosures Dr von Roeder has received an institutional research grant from Deutsche Stiftung für Herzforschung. Dr Grayburn has received grant support from Abbott Vascular, Boston Scientific, 4C Medical, Edwards Lifesciences, Medtronic, Restore Medical, and W.L. Gore; and has received consulting fees/honoraria from Abbott Vascular, 4C Medical, Edwards Lifesciences, Medtronic, and W.L. Gore. Dr Sannino has received grant support from Cardiovalve and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Fabry disease (FD) and transthyretin cardiac amyloidosis (TTR CA) are cardiomyopathies with hypertrophic phenotype that share several features, including left atrial (LA) enlargement and dysfunction, but direct comparative data are lacking. Aim of the present study was to perform a comparative analysis of LA remodelling between the two diseases., Methods and Results: In this prospective study, a total of 114 patients (31 FD and 83 TTR CA) were included; all of them had left ventricular hypertrophy (LVH), defined as left ventricular (LV) wall thickness ≥ 12 mm. Despite similar degree of LVH, patients with TTR CA showed worse LV systolic and diastolic function. LA maximal volume index was not significantly different between the two groups (p = 0.084), while patients with TTR CA showed larger LA minimal volume index (p = 0.001). Moreover, all phases of LA mechanics were more impaired in the TTR CA group vs FD (reservoir: 6.9[4.2-15.5] vs 19.0[15.5-29.5], p < 0.001). After excluding patients with atrial fibrillation (AF), these differences remained clearly significant. In multivariable regression analyses, LA reservoir strain showed an independent correlation with TTR CA, controlling for demographic characteristics, AF and LV systolic and diastolic performance (p ≤ 0.001), whereas LV global longitudinal strain did not. Finally, among echocardiographic parameters, LA function demonstrated the highest accuracy in discriminating the two diseases., Conclusions: TTR CA is characterized by a more advanced LA structural and functional remodelling in comparison to patients with FD and similar degree of LVH. The association between TTR CA and LA dysfunction remains consistent after adjustment for potential confounders., Competing Interests: Declaration of competing interest M.C.M. has received travel support from Alnylam. R.L. has received advisory board fees from Sanofi Genzyme, Takeda and Shire; she has also received travel support from Amicus Therapeutics. F.G. has received research grants from Takeda and Pfizer; she has also received advisory board/speaker fees from Amicus Therapeutics, Sanofi Genzyme, Shire and Alnylam and travel support from Pfizer. M.L. has received financial grants (honoraria and speaking) from Ackea, Alnylam, Sobi and Pfizer and travel support from Ackea, Alnylam, Sobi, Pfizer, Kedrion and Grifols. E.B. has received speaker fees from Takeda, Sanofi Genzyme, Amicus Therapeutics. The remaining authors have nothing to disclose in relation to this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

(1) Background: Left ventricular global longitudinal (LVGLS) and right ventricular free wall strain (RVFWS) demonstrated separate prognostic values in patients with severe aortic stenosis (AS). However, studies evaluating the combined assessment of LVGLS and RVFWS have shown contradictory results. This study explored the prognostic value of combining LVGLS and RVFWS in a large group of severe AS patients referred for transcatheter aortic valve implantation. (2) Methods: Patients were classified into three groups: preserved (LVGLS ≥ 15% AND RVFWS > 20%), single-ventricle impaired (LVGLS < 15% OR RVFWS ≤ 20%), or biventricular-impaired strain group (LVGLS < 15% AND RVFWS ≤ 20%). The cut-off values were based on previously published data and spline analyses. The endpoint was all-cause mortality. (3) Results: Of the 712 patients included (age 80 ± 7 years, 53% men), 248 (35%) died. The single-ventricle impaired and biventricular-impaired (vs. preserved) strain groups showed significantly lower 5-year survival rates (68% and 55% vs. 77%, respectively, p < 0.001). Through multivariable analysis, single-ventricle impaired (HR 1.762; 95% CI: 1.114-2.788; p = 0.015) and biventricular-impaired strain groups (HR 1.920; 95% CI: 1.134-3.250; p = 0.015) were independently associated with all-cause mortality. These findings were confirmed with a sensitivity analysis in patients with preserved LV ejection fraction. (4) Conclusions: In patients with severe AS, biventricular strain allows better risk stratification, even if LV ejection fraction is preserved.

As a slowly progressive form of hypertrophic cardiomyopathy (HCM), Anderson-Fabry disease (FD) resembles the phenotype of the most common sarcomeric forms, although significant differences in presentation and long-term progression may help determine the correct diagnosis. A variety of electrocardiographic and imaging features of FD cardiomyopathy have been described at different times in the course of the disease, and considerable discrepancies remain regarding the assessment of disease severity by individual physicians. Therefore, we here propose a practical staging of FD cardiomyopathy, in hopes it may represent the standard for cardiac evaluation and facilitate communication between specialized FD centres and primary care physicians. We identified 4 main stages of FD cardiomyopathy of increasing severity, based on available evidence from clinical and imaging studies: non-hypertrophic, hypertrophic - pre-fibrotic, hypertrophic - fibrotic, and overt dysfunction. Each stage is described and discussed in detail, following the principle that speaking a common language is critical when managing such complex patients in a multi-disciplinary and sometimes multi-centre setting., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Severe secondary tricuspid regurgitation (STR) causes significant right atrial (RA) volume overload, resulting in structural and functional RA-remodelling. This study evaluated whether patients with severe STR and reduced RA function, as assessed by RA-reservoir-strain (RASr), show lower long-term prognosis., Methods: Consecutive patients, from a single centre, with first diagnosis of severe STR and RASr measure available, were included. Extensive echocardiographic analysis comprised measures of cardiac chamber size and function, assessed also by two-dimensional speckle-tracking strain analysis. Primary outcome was all-cause mortality, analysed from inclusion until death or last follow-up. The association of RASr with the outcome was evaluated by Cox regression analysis and Akaike information criterion., Results: A total of 586 patients with severe STR (age 68±13 years; 52% male) were included. Patients presented with mild right ventricular (RV) dilatation (end-diastolic area 13.8±6.5 cm 2 /m 2 ) and dysfunction (free-wall strain 16.2±7.2%), and with moderate-to-severe RA dilatation (max area 15.0±5.3 cm 2 /m 2 ); the median value of RASr was 13%. In the overall population, 10-year overall survival was low (40%, 349 deaths), and was significantly lower in patients with lower RASr (defined by the median value): 36% (195 deaths) for RASr ≤13% compared with 45% (154 deaths) for RASr >13% (log-rank p=0.016). With a median follow-up of 6.6 years, RASr was independently associated with all-cause mortality (HR per 5% RASr increase:0.928; 95% CI 0.864 to 0.996; p=0.038), providing additional value over relevant clinical and echocardiographic covariates (including RA size and RV function/size)., Conclusions: Patients with severe STR presented with significant RA remodelling, and lower RA function, as measured by RASr, was independently associated with all-cause mortality, potentially improving risk stratification in these patients., Competing Interests: Competing interests: The Department of Cardiology, Heart Lung Centre, Leiden University Medical Centre has received unrestricted research grants from Abbott Vascular, Alnylam, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Medtronic, Medis, Pie Medical, Pfizer, and Novartis. VD received speaker fees from Abbott Vascular, Edwards Lifesciences, GE Healthcare, Medtronic, MSD and Novartis. JJB received speaker fees from Abbott Vascular, Edwards Lifesciences and Omron. NAM received speaker fees from Abbott Vascular, Philips Ultrasound and GE Healthcare. The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Cardiomyopathies and valvular heart diseases are typically considered distinct diagnostic categories with dedicated guidelines for their management. However, the interplay between these conditions is increasingly being recognized and they frequently coexist, as in the paradigmatic examples of dilated cardiomyopathy and hypertrophic cardiomyopathy, which are often complicated by the occurrence of mitral regurgitation. Moreover, cardiomyopathies and valvular heart diseases can have a shared aetiology because several genetic or acquired diseases can affect both the cardiac valves and the myocardium. In addition, the association between cardiomyopathies and valvular heart diseases has important prognostic and therapeutic implications. Therefore, a better understanding of their shared pathophysiological mechanisms, as well as of the prevalence and predisposing factors to their association, might lead to a different approach in the risk stratification and management of these diseases. In this Review, we discuss the different scenarios in which valvular heart diseases and cardiomyopathies coexist, highlighting the need for an improved classification and clustering of these diseases with potential repercussions in the clinical management and, particularly, personalized therapeutic approaches., (© 2023. Springer Nature Limited.)

Purposes: Predicting hemodynamic changes of stenotic mitral valve (MV) lesions with mitral annular calcification (MAC) following transcatheter aortic valve implantation (TAVI) may inform clinical decision-making. This study aimed to investigate the association between the MAC severity quantified by computed tomography (CT) and changes in mean transmitral gradient (mTMG), mitral valve area (MVA) and stroke volume index (SVi) following TAVI., Methods and Results: A total of 708 patients (median age 81, 52% male) with severe aortic stenosis (AS) underwent pre-procedural CT and pre- and post-TAVI transthoracic echocardiography. According to the classification of MAC severity determined by CT, 299 (42.2%) patients had no MAC, 229 (32.3%) mild MAC, 102 (14.4%) moderate MAC, and 78 (11.0%) severe MAC. After adjusting for age and sex, there was no significant change in mTMG following TAVI (Δ mTMG = 0.07 mmHg, 95% CI -0.10 to 0.23, P = 0.92) for patients with no MAC. In contrast, patients with mild MAC (Δ mTMG = 0.21 mmHg, 95% CI 0.01 to 0.40, P = 0.018), moderate MAC (Δ mTMG = 0.31 mmHg, 95% CI 0.02 to 0.60, P = 0.019) and severe MAC (Δ mTMG = 0.43 mmHg, 95% CI 0.10 to 0.76, P = 0.0012) had significant increases in mTMG following TAVI, with greater changes associated with increasing MAC severity. In contrast, there was no significant change in MVA or SVi following TAVI., Conclusion: In patients with severe AS undergoing TAVI, MAC severity was associated with greater increases in post-procedural mTMG whereas MVA or SVi remained unchanged. MAC severity should be considered for potential subsequent MV interventions if TAVI does not improve symptoms., (© 2023. The Author(s).)

Background: There is limited evidence on the risk stratification of cardiovascular outcomes in patients with Fabry disease (FD)., Objectives: This study sought to classify FD patients into disease stages, based on the extent of the cardiac damage evaluated by echocardiography, and to assess their prognostic impact in a multicenter cohort., Methods: Patients with FD from 5 Italian referral centers were categorized into 4 stages: stage 0, no cardiac involvement; stage 1, left ventricular (LV) hypertrophy (LV maximal wall thickness >12 mm); stage 2, left atrium (LA) enlargement (LA volume index >34 mL/m 2 ); stage 3, ventricular impairment (LV ejection fraction <50% or E/e' ≥15 or TAPSE <17 mm). The study endpoint was the composite of all-cause death, hospitalization for heart failure, new-onset atrial fibrillation, major bradyarrhythmias or tachyarrhythmias, and ischemic stroke., Results: A total of 314 patients were included. Among them, 174 (56%) were classified as stage 0, 41 (13%) as stage 1, 57 (18%) as stage 2 and 42 (13%) as stage 3. A progressive increase in the composite event rate at 8 years was observed with worsening stages of cardiac damage (log-rank P < 0.001). On multivariable Cox regression analysis, the staging was independently associated with the risk of cardiovascular events (HR: 2.086 per 1-stage increase; 95% CI: 1.487-2.927; P < 0.001). Notably, cardiac staging demonstrated a stronger and additive prognostic value, as compared with the degree of LV hypertrophy., Conclusions: In FD patients, a novel staging classification of cardiac damage, evaluated by echocardiography, is strongly associated with cardiovascular outcomes and may be helpful to refine risk stratification., Competing Interests: Funding Support and Author Disclosures Dr Lillo has received advisory board fees from Amicus Therapeutics, Sanofi Genzyme, Takeda, and Shire. Dr Biagini has received speaker fees from Amicus Therapeutics, Sanofi Genzyme, Takeda, and Bristol Myers Squibb. Dr Pieroni has received speaker and/or advisory board fees from Sanofi Genzyme, Pfizer, and Bristol Myers Squibb. Dr Crea has received personal fees from Amgen, AstraZeneca, Abbott, Menarini, Chiesi, and Daiichi-Sankyo. Dr Limongelli has received advisory board fees from Amicus Therapeutics; and has received an unrestricted grant from Sanofi. Dr Olivotto has received research grants from Bristol Myers Squibb, Cytokinetics, Sanofi Genzyme, Shire, Bayer, Amicus, Chiesi, and Menarini International; and has received speaker and/or advisory board fees from Bristol Myers Squibb, Cytokinetics, Sanofi Genzyme, Amicus, Shire, Tenaya, and Rocket Pharma. Dr Graziani has received research grants from Takeda and Pfizer; and has received advisory board fees from Amicus Therapeutics, Sanofi Genzyme, and Shire. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Management of patients affected by heart failure with reduced ejection fraction (HFrEF) has deeply changed thanks to novel pharmacological therapies, such as Sacubitril/Valsartan, which assured morbidity and mortality advantages in this population. These effects may be mediated by both left atrial (LA) and ventricular reverse remodeling, although left ventricular ejection fraction (LVEF) recovery still represents the main parameter of treatment response., Methods: In this prospective, observational study, 66 patients with HFrEF and naïve from Sacubitril/Valsartan were enrolled. All patients were evaluated at baseline, at 3 months and 12 months from therapy initiation. Echocardiographic parameters, including speckle tracking analysis, LA functional and structural metrics, were collected at three timepoints. The endpoints of our study were: (1) to evaluate the effects of Sacubitril/Valsartan on echo measurements; (2) to assess the predictive role of early modifications of these parameters (expressed as ∆ 3-0 months) on long-term LVEF significant recovery, defined as >15% improvement from baseline., Results: The majority of echocardiographic parameters evaluated progressively improved during the observation period, including LVEF, ventricular volumes and LA metrics. ∆(3-0 months) of LV Global Longitudinal Strain (LVGLS) and LA Reservoir Strain (LARS) were associated with significant LVEF improvement at 12 months (p < 0.001 and p = 0.019 respectively). A cut-off of ∆(3-0 months) LVGLS of 3% and of ∆(3-0 months) LARS of 2% could predict LVEF recovery with satisfactory sensitivity and specificity., Conclusions: LV and LA strain analysis may identify patients who adequately respond to HFrEF medical treatment and should be routinely used in the evaluation of these patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: The clinical importance of optimal post-repair mitral valve diastolic performance is increasingly being recognized. The haemodynamic effect of a partial annuloplasty band implantation, in comparison to a full ring, remains insufficiently explored., Methods: Patients undergoing mitral valve repair for pure degenerative disease between 2011 and 2019 at 2 experienced heart valve centres were eligible for inclusion. Exclusion criteria were concomitant procedures other than tricuspid valve repair and ablation procedures for atrial fibrillation. Pre-discharge and follow-up echocardiograms (1-4 years after surgery) were analysed to assess haemodynamic mitral valve performance., Results: Of 535 patients meeting the inclusion criteria, 364 (68.0%) patients underwent full annuloplasty ring and 171 (31.0%) partial band implantation. On predischarge echocardiogram, post-repair mitral valve gradient and area did not differ between groups [2.89 mmHg (IQR 2.26-3.72) vs 2.60 mmHg (IQR 1.91-3.55), P = 0.19 and 1.98 cm2 (IQR 1.66-2.46) vs 2.03 cm2 (IQR 1.55-3.06), P = 0.15]. However, multivariable linear regression analysis demonstrated band annuloplasty as a determinant of larger valve area (coefficient 0.467 cm2, standard error 0.105, P < 0.001). On multivariable analysis, no significant impact on post-repair gradient was observed (-0.370 mmHg, standard error 0.167, P = 0.36). At follow-up, the differences between groups disappeared and multivariable regression analysis failed to demonstrate a significant impact of annuloplasty device type on mitral valve gradient (coefficient -0.095 mmHg, standard error 0.171, P = 1.00) or area (coefficient -0.085 cm2, standard error 0.120, P = 1.00). These results were confirmed with a linear mixed model analysis., Conclusions: Partial band annuloplasty was related to an improved haemodynamic profile directly after valve repair for degenerative disease but the effect was short-lived. Our results suggest that the type of annuloplasty device has no durable impact on diastolic valve performance., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Patients with heart failure (HF) and reduced ejection fraction (HFrEF) are complex patients who often have a high prevalence of co-morbidities and risk factors. In the present study, we investigated the prognostic significance of left ventricular (LV) global longitudinal strain (GLS) along with important clinical and echocardiographic variables in patients with HFrEF. Patients who had a first echocardiographic diagnosis of LV systolic dysfunction, defined as LV ejection fraction ≤45%, were selected. The study population was subdivided into 2 groups based on a spline curve analysis derived optimal threshold value of LV GLS (≤10%). The primary end point was occurrence of worsening HF, whereas the composite of worsening HF and all-cause death was chosen for the secondary end point. A total of 1,873 patients (mean age 63 ± 12 years, 75% men) were analyzed. During a median follow-up of 60 months (interquartile range 27 to 60 months), 256 patients (14%) experienced worsening HF and the composite end point of worsening HF and all-cause mortality occurred in 573 patients (31%). The 5-year event-free survival rates for the primary and secondary end point were significantly lower in the LV GLS ≤10% group compared with the LV GLS >10% group. After adjustment for important clinical and echocardiographic variables, baseline LV GLS remained independently associated with a higher risk of worsening HF (hazard ratio 0.95, 95% confidence interval 0.90 to 0.99, p = 0.032) and the composite of worsening HF and all-cause mortality (hazard ratio 0.94, 95% confidence interval 0.90 to 0.97, p = 0.001). In conclusion, baseline LV GLS is associated with long-term prognosis in patients with HFrEF, independent of various clinical and echocardiographic predictors., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Risk stratification of patients with ischemic heart disease (IHD) still depends mainly on the left ventricular ejection fraction (LVEF). LV inward displacement (InD) is a novel parameter of LV systolic function, derived from feature tracking cardiac magnetic resonance (CMR) imaging. We aimed to investigate the prognostic impact of InD in patients with IHD and prior myocardial infarction. A total of 111 patients (mean age 57 ± 10, 86% male) with a history of myocardial infarction who underwent CMR were included. LV InD was quantified by measuring the displacement of endocardially tracked points towards the centreline of the LV during systole with feature tracking CMR. The endpoint was a composite of all-cause mortality, heart failure hospitalization and arrhythmic events. During a median follow-up of 142 (IQR 107-159) months, 31 (27.9%) combined events occurred. Kaplan-Meier analysis demonstrated that patients with LV InD below the study population median value (23.0%) had a significantly lower event-free survival (P < 0.001). LV InD remained independently associated with outcomes (HR 0.90, 95% CI 0.84-0.98, P = 0.010) on multivariate Cox regression analysis. InD also provided incremental prognostic value to LVEF, LV global radial strain and CMR scar burden. LV InD, measured with feature tracking CMR, was independently associated with outcomes in patients with IHD and prior myocardial infarction. LV InD also provided incremental prognostic value, in addition to LVEF and LV global radial strain. LV InD holds promise as a pragmatic imaging biomarker for post-infarct risk stratification., (© 2023. The Author(s).)

Background: There is limited evidence regarding the association between right ventricular-to-pulmonary artery (RV-PA) coupling and outcomes after transcatheter aortic valve replacement (TAVR)., Objectives: This study aimed to explore the evolution of RV-PA coupling in patients with severe aortic stenosis undergoing TAVR and its prognostic impact., Methods: A total of 900 patients who underwent TAVR in 2 tertiary centers and with echocardiographic analysis performed within 3 months before and after the procedure were included. RV-PA coupling was measured as the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP). RV-PA uncoupling was defined by TAPSE/PASP <0.55, whereas a TAPSE/PASP <0.32 identified a severe uncoupling. The primary endpoint was all-cause mortality., Results: A total of 520 patients (58%) showed RV-PA uncoupling before TAVR, whereas post-TAVR RV-PA uncoupling was observed in 407 patients (45%). During a median follow-up of 40 months, 250 deaths (28%) occurred. Post-TAVR RV-PA uncoupling was independently associated with an increased risk of mortality (adjusted HR: 1.474; 95% CI: 1.115-1.948; P = 0.006), whereas pre-TAVR uncoupling did not. Among patients with post-TAVR RV-PA uncoupling, the presence of severe uncoupling identified a subgroup with the worst survival (P = 0.008). Patients with RV-PA coupling recovery after TAVR showed similar outcomes as compared with patients with normal coupling. Conversely, the presence of either persistent or new-onset RV-PA uncoupling following TAVR was associated with an increased mortality risk., Conclusions: Post-TAVR RV-PA uncoupling is an independent predictor of long-term mortality, irrespective of coupling before intervention. Assessment of TAPSE/PASP response after TAVR may be helpful to improve risk stratification., Competing Interests: Funding Support and Author Disclosures The Department of Cardiology, Heart Lung Center, Leiden University Medical Center, received research grants from Abbott Vascular, Bioventrix, Medtronic, Biotronik, Boston Scientific, GE Healthcare and Edwards Lifesciences. Dr Bax has received speaker fees from Abbott Vascular. Dr Ajmone Marsan has received speaker fees from Abbott Vascular and GE Healthcare; and has served on the medical advisory board of Philips Ultrasound. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aortic stenosis (AS) can often coexist with other valvular diseases or be combined with aortic regurgitation (AR), leading to unique pathophysiological conditions. The combination of affected valves can vary widely, resulting in a lack of standardized diagnostic or therapeutic approaches. Echocardiography is crucial in assessing patients with valvular heart disease (VHD), but careful consideration of the hemodynamic interactions between combined valvular defects is necessary. This is important as it may affect the reliability of commonly used echocardiographic parameters, making the diagnosis challenging. Therefore, a multimodality imaging approach, including computed tomography or cardiac magnetic resonance, is often not just beneficial but crucial. It represents the future of diagnostics in this intricate field due to its unprecedented capacity to quantify and comprehend valvular pathology. The absence of definitive data and guidelines for the therapeutic management of AS in the context of multiple valve lesions makes this condition particularly challenging. As a result, an individualized, case-by-case approach is necessary, guided primarily by the recommendations for the predominant valve lesion. This review aims to summarize the pathophysiology of AS in the context of multiple and mixed valve disease, with a focus on the hemodynamic implications, diagnostic challenges, and therapeutic options.

Aims: To perform a comparative analysis of right ventricle (RV) myocardial mechanics, assessed by 2D speckle-tracking echocardiography (2D-STE), between patients with Fabry disease and patients with sarcomeric disease., Methods and Results: Patients with Fabry cardiomyopathy (FC) (n = 28) were compared with patients with sarcomeric hypertrophic cardiomyopathy (HCM), matched for degree of left ventricle hypertrophy (LVH) and demographic characteristics (n = 112). In addition, patients with Fabry disease and no LVH [phenotype-negative carriers of pathogenic α-galactosidase gene mutations (GLA LVH-)] (n = 28) were compared with age and sex-matched carriers of sarcomeric gene mutations without LVH [Phenotype-negative carriers of pathogenic sarcomeric gene mutations (Sarc LVH-)] (n = 56). Standard echocardiography and 2D-STE were performed in all participants. Despite a subtle impairment of RV global longitudinal strain (RV-GLS) was common in both groups, patients with FC showed a more prominent reduction of RV free wall longitudinal strain (RV-FWS) and lower values of difference between RV-FWS and RV-GLS (ΔRV strain), in comparison to individuals with HCM (P < 0.001 and P = 0.002, respectively). RV-FWS and ΔRV strain demonstrated an independent and additive value in discriminating FC from HCM, over the presence of symmetric LVH, systolic anterior motion of the mitral valve and RV hypertrophy. Similar results were found in GLA LVH- patients: they had worse RV-FWS and lower values of ΔRV strain as compared to Sarc LVH- patients (both P < 0.001)., Conclusion: Patients with FC show a specific pattern of RV myocardial mechanics, characterized by a larger impairment of RV-FWS and lower ΔRV strain in comparison to patients with HCM, which may be helpful in the differential diagnosis between these two diseases., Competing Interests: Conflict of interest: The Department of Cardiology, Heart Lung Center, Leiden University Medical Center, received research grants from Abbott Vascular, Bayer, Bioventrix, Medtronic, Biotronik, Boston Scientific, GE Healthcare and Edwards Lifesciences. J.B. received speaker fees from Abbott Vascular and Edwards Lifesciences. N.A.M. received speaker fees from Abbott Vascular and GE Healthcare and has been in the Medical Advisory Board of Philips Ultrasound. F.G. and R.L. received board meetings and speaker honoraria from Sanofi-Genzyme and Takeda. The remaining authors have nothing to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: Left ventricular (LV) hypertrophy is the main feature of cardiac involvement in Anderson-Fabry disease (FD), but the right ventricle (RV) is also frequently affected. Previous studies failed to demonstrate an independent association between conventional parameters of RV performance and outcomes in FD. Nevertheless, if RV free wall strain (RV-FWS), assessed by 2D speckle tracking analysis, may provide a better prognostication is currently unknown., Methods: We retrospectively evaluated the association between RV-FWS and the occurrence of cardiovascular events in a cohort of 56 patients with FD. The study endpoint comprises cardiovascular mortality, severe heart failure symptoms, new-onset atrial fibrillation and major arrhythmias requiring device implantation., Results: Reduced RV-FWS, defined by values lower than 23%, was found in 25 (45%) patients. During a median follow-up of 47 months, 16 (29%) patients met the study endpoint. A ROC-curve analysis confirmed the threshold of reduced RV-FWS (<23%) as the best cut-off for predicting cardiovascular events, but with a lower power compared to left-sided parameters. On univariable Cox regression analysis, RV-FWS, expressed as continuous variable, was significantly associated with the study endpoint (HR: 0.795, 95% CI: 0.710-0.889, p < 0.001). However, RV-FWS did not retain a significant association with outcomes, after adjustment for LV global longitudinal strain or indexed left atrial volume (p = 0.340 and p = 0.289 respectively)., Conclusions: RV-FWS was not independently associated with the occurrence of cardiovascular events in FD, confirming previous observations that prognosis is mainly driven by the severity of LV cardiomyopathy., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Left atrial (LA) and left ventricular (LV) mechanics are impaired in patients with atrial functional mitral regurgitation (AFMR), but their prognostic value in this subset of patients remains unknown. The present study aimed to evaluate the association between LA and LV longitudinal strain and clinical outcomes in patients with AFMR., Methods: A total of 197 patients (mean age 73±10 years, 44% men) with at least moderate AFMR were retrospectively identified. LV global longitudinal strain (GLS) and left atrial reservoir strain (LAS) were calculated by two-dimensional speckle tracking echocardiography. All-cause mortality was the primary endpoint of the study. The threshold value of LV GLS (≤16.3%) to identify impaired LV mechanics was defined based on the risk excess of the primary endpoint described with a spline curve analysis., Results: Impaired LV GLS (≤16.3%) was found in 89 (45%) patients. During a median follow-up of 69 months, 45 (23%) subjects experienced the primary endpoint. Patients with impaired LV GLS (≤16.3%) had a significantly lower cumulative survival rate at 5 years, as compared with patients with LV GLS (>16.3%) (74% vs 93%, p<0.001). On multivariable Cox regression analysis, LV GLS expressed as continuous variable was independently associated with the occurrence of all-cause mortality (HR 0.856, 95% CI 0.763 to 0.960; p=0.008) after adjustment for age, LAS, pulmonary artery systolic pressure and severe tricuspid regurgitation. Conversely, LAS was not significantly associated with patients' outcome., Conclusions: In patients with significant AFMR, the impairment of LV GLS was independently associated with worse outcomes., Competing Interests: Competing interests: the Department of Cardiology, Heart Lung Center, Leiden University Medical Center, received research grants from Abbott Vascular, Bayer, Bioventrix, Medtronic, Biotronik, Boston Scientific, GE Healthcare and Edwards Lifesciences. JJB received speaking fees from Abbott Vascular. NAM received speaking fees from Abbott Vascular and GE Healthcare and has been in the Medical Advisory Board of Philips Ultrasound. VD received speaker fees from Abbott Vascular, Medtronic, Edwards Lifesciences, MSD and GE Healthcare. The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Autologous bone marrow-derived mesenchymal stromal cell (MSC) therapy and withdrawal of calcineurin inhibitors (CNIs) has been shown to improve systemic blood pressure control and left ventricular hypertrophy regression in kidney transplant recipients. In the current subanalysis, we aimed to evaluate the impact of this novel immunosuppressive regimen on the longitudinal changes of left atrial (LA) structure and function after kidney transplantation., Methods: Kidney transplant recipients randomized to MSC therapy-infused at weeks 6 and 7 after transplantation, with complete discontinuation at week 8 of tacrolimus (MSC group)-or standard tacrolimus dose (control group) were evaluated with transthoracic echocardiography at weeks 4 and 24 after kidney transplantation. The changes in echocardiographic parameters were compared between the randomization arms using an analysis of covariance model adjusted for baseline variable., Results: Fifty-four participants (MSC therapy = 27; tacrolimus therapy = 27) were included. There was no significant interaction between the allocated treatment and the changes of indexed maximal LA volume (LAVImax) over the study period. Conversely, between 4 and 24 weeks post-transplantation, an increase in indexed minimal LA volume (LAVImin) was observed in control subjects, while it remained unchanged in the MSC group, leading to a significant difference between groups (P = .021). Additionally, patients treated with MSC therapy showed a benefit in LA function, assessed by a significant interaction between changes in LA emptying fraction and LA reservoir strain and the randomization arm (P = .012 and P = .027, respectively)., Conclusions: The combination of MSC therapy and CNIs withdrawal prevents progressive LA dilation and dysfunction in the first 6 months after kidney transplantation. LAVImin and LA reservoir strain may be more sensitive markers of LA reverse remodeling, compared with LAVImax., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Worsening heart failure (HF), defined as hospitalization for worsening signs and symptoms of HF or the need for urgent intravenous diuretics, is often considered a surrogate of poor prognosis in clinical trials. However, data on the prognostic implications of worsening HF in patients with HF and reduced ejection fraction is limited. Patients who had a first echocardiographic diagnosis of left ventricular systolic dysfunction, defined as left ventricular ejection fraction (LVEF) ≤45%, were identified. Worsening HF was defined as hospitalization for HF or urgent need for intravenous diuretics. All-cause mortality was chosen as the study end point. A total of 1,801 patients (mean age 64 ± 12 years, 74% men) were analyzed. Worsening HF was observed in 275 patients (15%) during a median follow-up of 20 months, while, 435 patients (24%) died during a median follow-up of 60 months (Interquartile range 28 to 60 months). The 5-year survival rate was significantly lower in the worsening HF cohort compared with the non-worsening HF cohort (Log-rank p <0.0001), and it was significantly different between the worsening HF cohort and the nonworsening HF cohort for LVEF ≤25% (log-rank p <0.0001) and LVEF 26% to 34% (log-rank p = 0.038) but not for LVEF 35% to 45% (log-rank p = 0.14). After adjustment for important clinical and echocardiographic predictors, worsening HF was independently associated with a higher risk of all-cause mortality (hazard ratio 1.46, 95% confidence interval 1.09 to 1.96, p = 0.011). In conclusion, worsening HF, defined by HF hospitalization or the urgent need for intravenous diuretics, is independently associated with poor long-term prognosis in patients with HF and reduced ejection fraction., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The clinical impact of valvular heart disease (VHD) in adult congenital heart disease (ACHD) patients is unascertained. Aim of our study was to assess the prevalence and clinical impact of severe VHD (S-VHD) in a real-world contemporary cohort of ACHD patients., Materials and Methods: Consecutive patients followed-up at our ACHD Outpatient Clinic from September 2014 to February 2021 were enrolled. Clinical characteristics and echocardiographic data were prospectively entered into a digitalized medical records database. VHD at the first evaluation was assessed and graded according to VHD guidelines. Clinical data at follow-up were collected. The study endpoint was the occurrence of cardiac mortality and/or unplanned cardiac hospitalization during follow-up., Results: A total of 390 patients (median age 34 years, 49% males) were included and S-VHD was present in 101 (25.9%) patients. Over a median follow-up time of 26 months (IQR: 12-48), the study composite endpoint occurred in 76 patients (19.5%). The cumulative endpoint-free survival was significantly lower in patients with S-VHD vs. patients with non-severe VHD (Log rank p < 0.001). At multivariable analysis, age and atrial fibrillation at first visit ( p = 0.029 and p = 0.006 respectively), lower %Sat O 2 , higher NYHA class ( p = 0.005 for both), lower LVEF ( p = 0.008), and S-VHD ( p = 0.015) were independently associated to the study endpoint. The likelihood ratio test demonstrated that S-VHD added significant prognostic value ( p = 0.017) to a multivariate model including age, severe CHD, atrial fibrillation, %Sat O2, NYHA, LVEF, and right ventricle systolic pressure > 45 mmHg., Conclusion: In ACHD patients, the presence of S-VHD is independently associated with the occurrence of cardiovascular mortality and hospitalization. The prognostic value of S-VHD is incremental above other established prognostic markers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Graziani, Iannaccone, Meucci, Lillo, Delogu, Grandinetti, Perri, Galletti, Amodeo, Butera, Secinaro, Lombardo, Lanza, Burzotta, Crea and Massetti.)

Background: Changes in right ventricular (RV) dimensions and function after tricuspid valve (TV) surgery and their association with long-term outcomes remain largely unexplored. The current study evaluated RV reverse remodeling, based on changes in RV dimensions and function, after TV surgery for significant (moderate or severe) tricuspid regurgitation (TR) and their association with outcome., Methods: A total of 121 patients (mean age 63 ± 12 years, 47% males) with significant TR treated with TV surgery were included in this analysis. The population was stratified by tertiles of percentage reduction of RV end-systolic area (RVESA) and absolute change of RV fractional area change (RVFAC). Five-year mortality rates were compared across the tertiles of RV remodeling and independent associates of mortality were investigated., Results: Tertile 3 consisted of patients presenting with a reduction in RVESA ≥17.2% and an improvement in RVFAC ≥2.3% after TV surgery. Cumulative survival rates were significantly better in patients within tertile 3 of RVESA reduction: 90% vs. 49% for tertile 1 and 69% for tertile 2 (log-rank p = 0.002) and within tertile 3 of RVFAC improvement: 87% vs. 57% for tertile 1 and 65% for tertile 2 (log-rank p = 0.02). Tertiles 3 of RVESA reduction and RVFAC improvement were both independently associated with better survival after TV surgery compared to tertiles 1 (hazard ratio: 0.221 [95% CI: 0.074-0.658] and 0.327 [95% CI: 0.118-0.907], respectively)., Conclusions: The extent of RV reverse remodeling, based on reduction in RVESA and improvement in RVFAC, was associated with better survival at 5-year follow-up of TV surgery for significant TR., Competing Interests: The Department of Cardiology, Heart Lung Center, Leiden University Medical Centre has received research grants from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Ionis, Medtronic, and Novartis. J.S. received funding from the European Society of Cardiology (ESC Training Grant App000064741). N.A.M. received speaker fees from Abbott Vascular and GE Healthcare. J.J.B. received speaker fees from Abbott Vascular and Edwards Lifesciences. V.D. received speaker fees from Abbott Vascular, Edwards Lifesciences, GE Healthcare, Medtronic, MSD, and Novartis. The other authors had no conflicts to declare., (© 2022 The Author(s).)

The present study aimed to investigate (1) the association between left ventricular diastolic dysfunction (LVDD), graded according to the algorithm proposed by the Cirrhotic Cardiomyopathy Consortium, and long-term survival in patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS) and (2) the additive prognostic value of left atrial (LA) function, as assessed by LA reservoir strain, using two-dimensional speckle-tracking echocardiography (2D-STE). A total of 129 TIPS candidates (mean ± SD, 61 ± 12 years; 61% men) underwent a comprehensive preprocedural echocardiography. LA dysfunction was defined by LA reservoir strain ≤35%, based on a previously suggested cut-off value. The outcome was all-cause mortality after TIPS. In the current cohort, 65 (50%) patients had normal diastolic function, 26 (20%) patients had grade 1 LVDD, 21 (16%) patients had grade 2 LVDD, and 17 (13%) patients had indeterminate diastolic function. Additionally, LA dysfunction (based on LA reservoir strain ≤35%) was noted in 67 (52%) patients. After a median follow-up of 36 months (range, 12-80), 65 (50%) patients died. All-cause mortality rates increased along worse grades of LVDD (log-rank p = 0.007) and with LA dysfunction (log-rank p = 0.001). On multivariable Cox regression analysis, Model for End-Stage Liver Disease score (hazard ratio [HR],1.06; p = 0.003), hemoglobin (HR, 0.74; p = 0.022), and LA strain, expressed as a continuous variable (HR, 0.96; p = 0.005) were independently associated with all-cause mortality. Notably, the addition of LA strain to the model provided incremental prognostic value over the established prognostic variables (delta χ 2  = 8.27, p = 0.004). Conclusion: LA dysfunction assessed with 2D-STE is independently associated with all-cause mortality in patients with cirrhosis treated by TIPS., (© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Backgrounds: This study aimed to investigate the association between left atrioventricular coupling index (LACI) and the occurrence of atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM)., Methods: A total of 373 patients with HCM and no history of AF were evaluated by transthoracic echocardiography. LACI was defined by the ratio of left atrial (LA) end-diastolic volume divided by left ventricular (LV) end-diastolic volume. The cut-off value for LACI (≥40%) to identify LA-LV uncoupling was chosen based on the risk excess of new-onset AF described with a spline curve analysis., Results: The median LACI was 37.5% (IQR: 24.4-56.7) and LA-LV uncoupling (LACI ≥40%) was observed in 171 (45.8%) patients. During a median follow-up of 11 (IQR 7-15) years, 118 (31.6%) subjects developed new-onset AF. The cumulative event-free survival at 10 years was 53% for patients with LA-LV uncoupling versus 94% for patients without LA-LV uncoupling (p < 0.001). Multivariable Cox regression analyses performed separately for each LA parameter showed an independent association between new-onset AF and LACI (hazard ratio [HR], 1.021; 95% CI, 1.017-1.026), LA maximum volume indexed (HR, 1.028; 95% CI, 1.017-1.039), LA minimum volume indexed (HR, 1.047; 95% CI, 1.037-1.060) and LA emptying fraction (HR, 0.967; 95% CI, 0.959-0.977, all p < 0.001). The inclusion of LACI in the multivariate model provided a larger improvement in the risk stratification for new-onset AF, as compared to conventional LA parameters., Conclusion: In patients with HCM, LACI was more predictive of the occurrence of new-onset AF than conventional LA parameters., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: This study evaluated the prognostic value of staging right heart failure in patients with significant tricuspid regurgitation (TR) undergoing tricuspid valve (TV) surgery., Methods: Patients with significant TR who underwent TV surgery were divided into 4 right heart failure stages according to the presence of right ventricular (RV) dysfunction and clinical signs of right heart failure: stage 1 was defined as no RV dysfunction and no signs of right heart failure; stage 2 indicated RV dysfunction without signs of right heart failure; stage 3 included RV dysfunction and signs of right heart failure; and stage 4 was defined as RV dysfunction and refractory signs of right heart failure at rest., Results: A total of 278 patients [mean age 64 (12), 49% males] were included, of whom 34 (12%) patients were classified as stages 1 and 2, 141 (51%) as stage 3 and 103 (37%) as stage 4 right heart failure. The majority of patients (91%) had TV surgery concomitant to left-sided valve surgery or coronary artery bypass grafting and 95% underwent TV annuloplasty. Cumulative survival rates were 89%, 78% and 61% at 1 month, 1 year and 5 years, respectively. Stages 1 and 2 and stage 3 were independently associated with better survival compared to stage 4 (hazard ratio: 0.391 [95% confidence interval: 0.186-0.823] and 0.548 [95% confidence interval: 0.369-0.813], respectively)., Conclusions: Patients with significant TR undergoing TV surgery and diagnosed without advanced right heart failure have better survival as compared to patients with right heart failure., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Left ventricular (LV) global longitudinal strain (GLS) has been proposed as a sensitive marker of myocardial damage in patients with chronic severe aortic regurgitation (AR) and preserved LV ejection fraction (LVEF). However, LV GLS does not take into account the afterload. Noninvasive LV myocardial work is a novel parameter of LV myocardial performance, which integrates measurements of myocardial deformation and noninvasive blood pressure (afterload). The aims of this study were (1) to assess noninvasive LV myocardial work in patients with chronic AR and preserved LVEF and its correlation with other echocardiographic parameters, (2) to evaluate changes of LV myocardial work after aortic valve replacement or repair (AVR), and (3) to assess the relationship between LV myocardial work and postoperative LV reverse remodeling., Methods: Fifty-seven patients (53 ± 16 years; 67% men) with moderate or severe chronic AR and preserved LVEF treated by AVR were included. Noninvasive LV myocardial work indices were measured at baseline and postoperatively (between 2 and 12 months after surgery) and compared with previously reported normal reference ranges., Results: Based on normal reference values, patients with chronic AR and preserved LVEF had preserved or increased values of LV global work index (GWI; 82% and 18%, respectively) and LV global constructive work (GCW; 74% and 25%, respectively) and preserved LV global work efficiency (GWE). Left ventricular GWI and GCW showed a positive correlation with markers of AR severity and parameters of LV systolic function. Left ventricular GWI, GCW, and GWE decreased after AVR (P < .001), without changes in LV global wasted work (P = .28). The postoperative impairment of LV GWI, observed in 28% of patients, was closely associated with reduced LV reverse remodeling., Conclusions: Noninvasive myocardial work may allow better understanding of myocardial function and energetics than afterload-dependent echocardiographic parameters in chronic AR with preserved LVEF., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background After renal transplantation, there is a need of immunosuppressive regimens that effectively prevent allograft rejection while minimizing cardiovascular complications. This substudy of the TRITON trial evaluated the cardiovascular effects of autologous bone marrow-derived mesenchymal stromal cells (MSCs) in renal transplant recipients. Methods and Results Renal transplant recipients were randomized to MSC therapy, infused at weeks 6 and 7 after transplantation, with withdrawal at week 8 of tacrolimus or standard tacrolimus dose. Fifty-four patients (MSC group=27; control group=27) underwent transthoracic echocardiography at weeks 4 and 24 after transplantation and were included in this substudy. Changes in clinical and echocardiographic variables were compared. The MSC group showed a benefit in blood pressure control, assessed by a significant interaction between changes in diastolic blood pressure and the treatment group ( P =0.005), and a higher proportion of patients achieving the predefined blood pressure target of <140/90 mm Hg compared with the control group (59.3% versus 29.6%, P =0.03). A significant reduction in left ventricular mass index was observed in the MSC group, whereas there were no changes in the control group ( P =0.002). The proportion of patients with left ventricular hypertrophy decreased at 24 weeks in the MSC group (33.3% versus 70.4%, P =0.006), whereas no changes were noted in the control group (63.0% versus 48.1%, P =0.29). Additionally, MSC therapy prevented progressive left ventricular diastolic dysfunction, as demonstrated by changes in mitral deceleration time and tricuspid regurgitant jet velocity. Conclusions MSC strategy is associated with improved blood pressure control, regression of left ventricular hypertrophy, and prevention of progressive diastolic dysfunction at 24 weeks after transplantation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03398681.

Background: Assessment of left ventricular (LV) function in patients with secondary mitral regurgitation (SMR) remains challenging but is an important parameter for risk stratification. The association of LV myocardial work components (work index [GWI], constructive [GCW] and wasted [GWW] work, and work efficiency) derived from pressure-strain loops obtained with speckle tracking echocardiography, and all-cause mortality in patients with SMR was investigated., Methods: LV myocardial GWI, GCW, GWW, and global work efficiency were measured with speckle tracking strain echocardiography in 373 patients (72% men, median age 68 years) with various grades of SMR. All-cause mortality was the primary end point., Results: Mild SMR was observed in 143 patients, 128 had moderate SMR, and 102 had severe SMR. Patients with severe SMR had the largest LV volumes and the worst LV ejection fraction and LV global longitudinal strain. In patients with severe SMR, LV GWI and GCW were more impaired (500 mm Hg% versus 680 mm Hg% P =0.024 and 678 mm Hg% versus 851 mm Hg% P =0.006, respectively), while GWW was lower (130 mm Hg% versus 260 mm Hg% P <0.001, respectively) and global work efficiency was significantly higher (82% versus 76%, P =0.001) compared with patients with mild SMR. After a median follow-up of 56 months, 161 patients died. LV GWI≤500 mm Hg%, LV GCW≤750 mm Hg%, and LV GWW<300 mm Hg% were independently associated with excess mortality., Conclusions: Patients with severe SMR had the worst LV GWI and LV GCW but better LV GWW and global work efficiency reflecting the unloading of the LV in the low-pressure left atrial chamber. These parameters were independently associated with worse long-term survival in patients with SMR.