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Exercise-induced pulmonary hypertension (exPHT) is a hemodynamic condition linked to increased morbidity and mortality across various cardiopulmonary diseases. Traditional definitions of exPHT rely on absolute cut-offs, such as mean pulmonary artery pressure (mPAP) above 30 mmHg during exercise. However, recent research suggests that these cut-offs may not accurately reflect pathophysiological changes, leading to false positives and false negatives. Instead, the mPAP over cardiac output (CO) slope, which incorporates both pressure and flow measurements, has emerged as a more reliable indicator. A slope exceeding 3 mmHg/L/min is now considered diagnostic for exPHT and strongly correlates with adverse outcomes. Stress echocardiography serves as a viable alternative to invasive assessment, enabling broader implementation. This review discusses the physiological basis of pulmonary hemodynamics during exercise, the advantages of the mPAP/CO slope over absolute pressure measurements, the evidence supporting its inclusion in clinical guidelines, and provides a practical guide for non-invasive determining the mPAP/CO slope in clinical practice., (© 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: Half of patients with heart failure with preserved ejection fraction (HFpEF) remain undiagnosed by resting evaluation alone. Therefore, exercise testing is proposed. The diastolic stress test (DST), however, has limited sensitivity. We aimed to determine the clinical significance of adding the mean pulmonary artery pressure over cardiac output (mPAP/CO) slope to the DST in suspected HFpEF., Methods and Results: In this prospective cohort study, consecutive patients (n=1936) with suspected HFpEF underwent exercise echocardiography with simultaneous respiratory gas analysis. These patients were stratified by exercise E over e ' (exE/ e ') and mPAP/CO slope, and peak oxygen uptake, natriuretic peptides (NT-proBNP [N-terminal pro-B-type natriuretic peptide]), and score-based HFpEF likelihood were compared. Twenty-two percent of patients (n=428) had exE/ e '<15 despite a mPAP/CO slope>3 mm Hg/L per min, 24% (n=464) had a positive DST (exE/ e '≥15), and 54% (n=1044) had a normal DST and slope. Percentage of predicted oxygen uptake was similar in the group with exE/ e '<15 but high mPAP/CO slope and the positive DST group (-2% [-5% to +1%]), yet worse than in those with normal DST and slope (-12% [-14% to -9%]). Patients with exE/ e '<15 but a high slope had NT-proBNP levels and H 2 FPEF (heavy, hypertensive, atrial fibrillation, pulmonary hypertension, elder; filling pressure) scores intermediate to the positive DST group and the group with both a normal DST and slope., Conclusions: Twenty-two percent of patients with suspected HFpEF presented with a mPAP/CO slope>3 mm Hg/L per min despite a negative DST. These patients had HFpEF characteristics and a peak oxygen uptake as low as patients with a positive DST. Therefore, an elevated mPAP/CO slope might indicate HFpEF irrespective of the DST result.

Background: In patients with low-gradient aortic stenosis (AS) and low transvalvular flow, dobutamine stress echocardiography (DSE) is recommended to determine AS severity, whereas the degree of aortic valve calcification (AVC) supposedly correlates with AS severity according to current European and American guidelines., Objectives: The purpose of this study was to assess the relationship between AVC and AS severity as determined using echocardiography and DSE in patients with aortic valve area <1 cm 2 and peak aortic valve velocity <4.0 m/s., Methods: All patients underwent DSE to determine AS severity and multislice computed tomography to quantify AVC. Receiver-operating characteristics curve analysis was used to assess the diagnostic value of AVC for AS severity grading as determined using echocardiography and DSE in men and women., Results: A total of 214 patients were included. Median age was 78 years (25th-75th percentile: 71-84 years) and 25% were women. Left ventricular ejection fraction was reduced (<50%) in 197 (92.1%) patients. Severe AS was diagnosed in 106 patients (49.5%). Moderate AS was diagnosed in 108 patients (50.5%; in 77 based on resting transthoracic echocardiography, in 31 confirmed using DSE). AVC score was high (≥2,000 for men or ≥1,200 for women) in 47 (44.3%) patients with severe AS and in 47 (43.5%) patients with moderate AS. AVC sensitivity was 44.3%, specificity was 56.5%, and positive and negative predictive values for severe AS were 50.0% and 50.8%, respectively. Area under the receiver-operating characteristics curve was 0.508 for men and 0.524 for women., Conclusions: Multi-slice computed tomography-derived AVC scores showed poor discrimination between grades of AS severity using DSE and cannot replace DSE in the diagnostic work-up of low-gradient severe AS., Competing Interests: Funding Support and Author Disclosures Dr Van Mieghem has received grant support/research contracts from Abbott Vascular, Boston Scientific, Medtronic, Edwards Lifesciences, Daiichy Sankyo, AstraZeneca, and PulseCath BV; and has received consulting/speaker fees from Abbot Vascular, Boston Scientific Corporation, Medtronic, Daiichy Sankyo, PulseCath BV, JenaValve, and Amgen. Dr Mehran has received grant support/research contracts from Abbott, Abiomed, Alleviant Medical, Amgen, AM-Pharma, Arena Pharmaceuticals, AstraZeneca, Atricure Inc, Biosensors, Biotronik, Boston Scientific, Bristol-Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, Cytsorbents, Daiichy-Sankyo, Element Science, Faraday, Humacyte, Idorsia Pharmaceuticals, Janssen Pharmaceuticals, Magenta, MedAlliance, Mediasphere, Medtelligence, Medtronic, MJH Healthcare, Novartis, OrbusNeich, Penumbra, PhaseBio, Philips, Pi-Cardia, PLx Pharma, Protembis, RenalPro, RM Global, Shockwave Medical, Vivasure, and Zoll; has received consulting/speaker fees from AstraZeneca, E.R. Squibb and Sons LLC, Esperion Science/Innovativa Biopharma, Ionis Pharmaceuticals, IQVIA, J-Calc, McVeigh Global, Novartis, Novo Nordisk, Overcome, Primer Healthcare of New Jersey, Radcliffe, SL Solutions, TARSUS Cardiology, Vectura, and WebMD; and she has equity in Applied Therapeutics, Elixir, and STEL. Dr Mehran’s spouse has equity in ControlRad. Dr Kodali has received grant support/research contracts from Admedus, Dura Biotech, Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve; has received consulting/speaker fees from Admedus, Dura Biotech, TriCares, X-Dot, Tioga, Helix Valve Repair, and Moray Medical; and has equity in Dura Biotech, Microinterventional Devices, Thubrika Aortic Valve Inc, Supira, Admedus, Triflo, and Adona. Dr Hahn has received consulting/speaker fees from Abbott Structural, Medtronic, Edwards Lifesciences, Boston Scientific, Baylis Medical, Navigate, Philips Healthcare, Siemens Healthcare, and 3mensio; and has equity in Navigate. Dr Bax has received grant support/research contracts from Biotronic, Boston Scientific, Medtronic, Bayer AG, and Edwards Lifesciences; and has received consulting/speaker fees from Abbott Vascular and Edwards Lifesciences. Drs Veulemans and Zeus have received consulting fees, travel expenses, or study honoraria from Medtronic, Edwards Lifesciences, and Boston Scientific. 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.)

Non-invasive imaging plays an increasingly important role in emergency medicine, given the trend towards smaller, portable ultrasound devices, the integration of ultrasound imaging across diverse medical disciplines, and the growing evidence supporting its clinical benefits for the patient. Heart failure with preserved ejection fraction (HFpEF) provides a compelling illustration of the impactful role that imaging plays in distinguishing diverse clinical presentations of heart failure with numerous associated comorbidities, including pulmonary, renal, or hepatic diseases. While a preserved left ventricular ejection fraction might misguide the clinician away from diagnosing cardiac disease, there are several clues provided by cardiac, vascular, and lung ultrasonography, as well as other imaging modalities, to rapidly identify (decompensated) HFpEF. Congestion remains the primary reason why patients with heart failure (irrespective of ejection fraction) seek emergency care. Furthermore, comprehensive phenotyping is becoming increasingly important, considering the development of targeted treatments for conditions exhibiting HFpEF physiology, such as cardiac amyloidosis. Timely recognition in such cases has lasting implications for long-term outcomes., Competing Interests: Conflict of interest: none declared., (© 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.)

Competing Interests: Conflicts of Interest None.

Mitral regurgitation (MR) is highly prevalent among patients with heart failure and preserved ejection fraction (HFpEF). Despite this combination being closely associated with unfavourable outcomes, it remains relatively understudied. This is partly due to the inherent heterogeneity of patients with HFpEF. To address this gap, dissecting HFpEF into mechanism-based phenotypes may offer a promising avenue for advancing our comprehension of these complex intertwined conditions. This review employs the validated CircAdapt model to explore the haemodynamic implications of moderate to severe MR across a well-defined spectrum of myocardial disease, characterized by impaired relaxation and reduced myocardial compliance. Both heart failure and mitral valve disease share overlapping symptomatology, primarily attributed to elevated pulmonary pressures. The intricate mechanisms contributing to these elevated pressures are multifaceted, potentially influenced by diastolic dysfunction, left atrial myopathy, and MR. Accurate evaluation of the haemodynamic and clinical impact of MR necessitates a comprehensive approach, taking into account the characteristics of both the left atrium and left ventricle, as well as their intricate interactions, which may currently be underemphasized in diagnostic practice. This holistic assessment is imperative for enhancing our understanding and refining therapeutic strategies within this patient cohort., (© 2024 European Society of Cardiology.)

Aims: Exercise-induced pulmonary hypertension (PH), defined by a mean pulmonary arterial pressure over cardiac output (mPAP/CO) slope >3 mmHg/L/min, has important diagnostic and prognostic implications. The aim of this study is to investigate the value of the mPAP/CO slope in patients with more than moderate primary mitral regurgitation (MR) with preserved ejection fraction and no or discordant symptoms., Methods and Results: A total of 128 consecutive patients were evaluated with exercise echocardiography and cardiopulmonary testing. Clinical outcome was defined as the composite of mitral valve intervention, new-onset atrial fibrillation, cardiovascular hospitalization, and all-cause mortality. The mean age was 63 years, 61% were male, and the mean LVEF was 66 ± 6%. The mPAP/CO slope correlated with peak VO2 (r = -0.52, P < 0.001), while the peak systolic pulmonary artery pressure (sPAP) did not (r = -0.06, P = 0.584). Forty-six per cent (n = 59) had peak exercise sPAP ≥60 mmHg, and 37% (n = 47) had mPAP/CO slope >3 mmHg/L/min. Event-free survival was 55% at 1 year and 46% at 2 years, with reduced survival in patients with mPAP/CO slope >3 mmHg/L/min (hazard ratio, 4.9; 95% confidence interval, 2.9-8.2; P < 0.001). In 53 cases (41%), mPAP/CO slope and peak sPAP were discordant: patients with slope >3 mmHg/L/mmHg and sPAP <60 mmHg (n = 21) had worse outcome vs. peak sPAP ≥60 mmHg and normal slope (n = 32, log-rank P = 0.003). The mPAP/CO slope improved predictive models for outcome, incremental to resting and exercise sPAP, and peak VO2., Conclusion: Exercise PH defined by the mPAP/CO slope >3 mmHg/L/min is associated with decreased exercise capacity and a higher risk of adverse events in significant primary MR and no or discordant symptoms. The slope provides a greater prognostic value than single sPAP measures and peak VO2., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Surgical correction of severe mitral regurgitation (MR) can reverse left ventricular (LV) remodeling in patients with mitral valve prolapse (MVP). However, whether this process is similar to the case in Barlow's Disease (BD) and Fibro-elastic Deficiency (FED) is currently unknown. The aim of this study is to evaluate post-operative LV reverse remodeling and function in patients with BD versus FED. In this study, 100 MVP patients (BD = 37 and FED = 63) with severe MR who underwent mitral valve surgery at three Belgian centers were retrospectively included. Transthoracic echocardiography was used to assess MR severity, LV volumes and function before surgery and 6 months thereafter. Baseline MR severity, LV ejection fraction (LVEF), indexed LV end-diastolic (LVEDVi) and end-systolic volumes (LVESVi) were not different between the groups. After a median follow-up of 278 days, there was a similar decrease in LVEDVi, but a trend towards a smaller decrease in LVESVi in BD compared to FED (-3.0 ± 11.2 mL/m 2 vs. -5.3 ± 9.0 mL/m 2 ; p = 0.154). This resulted in a significantly larger decrease in LVEF in BD (-8.3 ± 9.6%) versus FED (-3.9 ± 6.9%) after adjusting for baseline LVEF ( p < 0.001) and type of surgical intervention ( p = 0.01). These findings suggest that LV (reverse) remodeling in BD could be affected by other mechanisms beyond volume overload, potentially involving concomitant cardiomyopathy.

Background: Imaging evaluation of arrhythmogenic right ventricular cardiomyopathy (ARVC) remains challenging. Myocardial strain assessment by echocardiography is an increasingly utilized technique for detecting subclinical left ventricular (LV) and right ventricular (RV) dysfunction. We aimed to evaluate the diagnostic and prognostic utility of LV and RV strain in ARVC., Methods: Patients with suspected ARVC (n = 109) from a multicenter registry were clinically phenotyped using the 2010 ARVC Revised Task Force Criteria and underwent baseline strain echocardiography. Diagnostic performance of LV and RV strain was evaluated using the area under the receiver operating characteristic curve analysis against the 2010 ARVC Revised Task Force Criteria, and the prognostic value was assessed using the Kaplan-Meier analysis., Results: Mean age was 45.3±14.7 years, and 48% of patients were female. Estimation of RV strain was feasible in 99/109 (91%), and LV strain was feasible in 85/109 (78%) patients. ARVC prevalence by 2010 ARVC Revised Task Force Criteria is 91/109 (83%) and 83/99 (84%) in those with RV strain measurements. RV global longitudinal strain and RV free wall strain had diagnostic area under the receiver operating characteristic curve of 0.76 and 0.77, respectively (both P <0.001; difference NS). Abnormal RV global longitudinal strain phenotype (RV global longitudinal strain > -17.9%) and RV free wall strain phenotype (RV free wall strain > -21.2%) were identified in 41/69 (59%) and 56/69 (81%) of subjects, respectively, who were not identified by conventional echocardiographic criteria but still met the overall 2010 ARVC Revised Task Force Criteria for ARVC. LV global longitudinal strain did not add diagnostic value but was prognostic for composite end points of death, heart transplantation, or ventricular arrhythmia (log-rank P =0.04)., Conclusions: In a prospective, multicenter registry of ARVC, RV strain assessment added diagnostic value to current echocardiographic criteria by identifying patients who are missed by current echocardiographic criteria yet still fulfill the diagnosis of ARVC. LV strain, by contrast, did not add incremental diagnostic value but was prognostic for identification of high-risk patients., Competing Interests: Disclosures Dr Namasivayam received support from the Nvidia Corporation Academic Hardware Grant for work unrelated to this article. The other authors report no conflicts.

Background: Hemostasis within the left atrial appendage (LAA) is a common cause of stroke, especially in patients with atrial fibrillation (AF). Although LAA flow provides insights into LAA function, its potential for predicting AF has yet to be established. The aim of this study was to explore whether LAA peak flow velocities early after cryptogenic stroke are associated with future AF on prolonged rhythm monitoring., Methods: A total of 110 patients with cryptogenic stroke were consecutively enrolled and underwent LAA pulsed-wave Doppler flow assessment using transesophageal echocardiography within the early poststroke period. Velocity measurements were analyzed offline by an investigator blinded to the results. Prolonged rhythm monitoring was conducted on all participants via 7-day Holter and implantable cardiac monitoring devices, with follow-up conducted over a period of 1.5 years to determine the incidence of AF. The end point of AF was defined as irregular supraventricular rhythm with variable RR interval and no detectable P waves lasting ≥30 sec during rhythm monitoring., Results: During a median follow-up period of 539 days (interquartile range, 169-857 days), 42 patients (38%) developed AF, with a median time to AF diagnosis of 94 days (interquartile range, 51-487 days). Both LAA filling velocity and LAA emptying velocity (LAAev) were lower in patients with AF (44.3 ± 14.2 and 50.7 ± 13.3 cm/s, respectively) compared with patients without AF (59.8 ± 14.0 and 76.8 ± 17.3 cm/sec, respectively; P < .001 for both). LAAev was most strongly associated with future AF, with an area under the receiver operating characteristic curve of 0.88 and an optimal cutoff value of 55 cm/sec. Age and mitral regurgitation were independent determinants of reduced LAAev., Conclusions: Impaired LAA peak flow velocities (LAAev < 55 cm/sec) in patients with cryptogenic stroke are associated with future AF. This may facilitate the selection of appropriate candidates for prolonged rhythm monitoring to improve its diagnostic accuracy and implementation., (Copyright © 2023 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Three-dimensional transoesophageal echocardiography (3D TOE) has been rapidly developed in the last 15 years. Currently, 3D TOE is particularly useful as an additional imaging modality for the cardiac echocardiographers in the echo-lab, for cardiac interventionalists as a tool to guide complex catheter-based procedures cardiac, for surgeons to plan surgical strategies, and for cardiac anaesthesiologists and/or cardiologists, to assess intra-operative results. The authors of this document believe that acquiring 3D data set should become a 'standard part' of the TOE examination. This document provides (i) a basic understanding of the physic of 3D TOE technology which enables the echocardiographer to obtain new skills necessary to acquire, manipulate, and interpret 3D data sets, (ii) a description of valvular pathologies, and (iii) a description of non-valvular pathologies in which 3D TOE has shown to be a diagnostic tool particularly valuable. This document has a new format: instead of figures randomly positioned through the text, it has been organized in tables which include figures. We believe that this arrangement makes easier the lecture by clinical cardiologists and practising echocardiographers., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The aging population is rising at record pace worldwide. Along with it, a steep increase in the prevalence of atrial fibrillation and heart failure with preserved ejection fraction is to be expected. Similarly, both atrial functional mitral and tricuspid regurgitation (AFMR and AFTR) are increasingly observed in daily clinical practice. This article summarizes all current evidence regarding the epidemiology, prognosis, pathophysiology, and therapeutic options. Specific attention is addressed to discern AFMR and AFTR from their ventricular counterparts, given their different pathophysiology and therapeutic needs., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Mitral annular calcification (MAC)-related mitral valve (MV) dysfunction is an increasingly recognized entity, which confers a high burden of morbidity and mortality. Although more common among women, there is a paucity of data regarding how the phenotype of MAC and the associated adverse clinical implications may differ between women and men. A total of 3,524 patients with extensive MAC and significant MAC-related MV dysfunction (i.e., transmitral gradient ≥3 mm Hg) were retrospectively analyzed from a large institutional database, with the goal of defining gender differences in clinical and echocardiographic characteristics and the prognostic importance of MAC-related MV dysfunction. We stratified patients into low- (3 to 5 mm Hg), moderate- (5 to 10 mm Hg), and high- (≥10 mm Hg) gradient groups and analyzed the gender differences in phenotype and outcome. The primary outcome was all-cause mortality, assessed using adjusted Cox regression models. Women represented the majority (67%) of subjects, were older (79.3 ± 10.4 vs 75.5 ± 10.9 years, p <0.001) and had a lower burden of cardiovascular co-morbidities than men. Women had higher transmitral gradients (5.7 ± 2.7 vs 5.3 ± 2.6 mm Hg, p <0.001), more concentric hypertrophy (49% vs 33%), and more mitral regurgitation. The median survival was 3.4 years (95% confidence interval 3.0 to 3.6) among women and 3.0 years (95% confidence interval 2.6 to 4.5) among men. The adjusted survival was worse among men, and the prognostic impact of the transmitral gradient did not differ overall by gender. In conclusion, we describe important gender differences among patients with MAC-related MV dysfunction and show worse adjusted survival among men; although, the adverse prognostic impact of the transmitral gradient was similar between men and women., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The relation between ventricular arrhythmia and fibrosis in mitral valve prolapse (MVP) is reported, but underlying valve-induced mechanisms remain unknown. We evaluated the association between abnormal MVP-related mechanics and myocardial fibrosis, and their association with arrhythmia., Methods: We studied 113 patients with MVP with both echocardiogram and gadolinium cardiac magnetic resonance imaging for myocardial fibrosis. Two-dimensional and speckle-tracking echocardiography evaluated mitral regurgitation, superior leaflet and papillary muscle displacement with associated exaggerated basal myocardial systolic curling, and myocardial longitudinal strain. Follow-up assessed arrhythmic events (nonsustained or sustained ventricular tachycardia or ventricular fibrillation)., Results: Myocardial fibrosis was observed in 43 patients with MVP, predominantly in the basal-midventricular inferior-lateral wall and papillary muscles. Patients with MVP with fibrosis had greater mitral regurgitation, prolapse, and superior papillary muscle displacement with basal curling and more impaired inferior-posterior basal strain than those without fibrosis ( P <0.001). An abnormal strain pattern with distinct peaks pre-end-systole and post-end-systole in inferior-lateral wall was frequent in patients with fibrosis (81 versus 26%, P <0.001) but absent in patients without MVP with basal inferior-lateral wall fibrosis (n=20). During median follow-up of 1008 days, 36 of 87 patients with MVP with >6-month follow-up developed ventricular arrhythmias associated (univariable) with fibrosis, greater prolapse, mitral annular disjunction, and double-peak strain. In multivariable analysis, double-peak strain showed incremental risk of arrhythmia over fibrosis., Conclusions: Basal inferior-posterior myocardial fibrosis in MVP is associated with abnormal MVP-related myocardial mechanics, which are potentially associated with ventricular arrhythmia. These associations suggest pathophysiological links between MVP-related mechanical abnormalities and myocardial fibrosis, which also may relate to ventricular arrhythmia and offer potential imaging markers of increased arrhythmic risk.

Aims: To assess the level of transesophageal echocardiography (TOE) knowledge and skills of young cardiologists., Methods and Results: A European Association of Cardiovascular Imaging (EACVI) online study using the first fully virtual simulation-based software was conducted in two periods (9-12 December 2021 and 10-13 April 2022). All young cardiologists eligible to participate (<40 years) across the world were invited to participate. After a short survey, each participant completed two tests: a theoretical test to assess TOE knowledge and a practical test using an online TOE simulator to investigate TOE skills. Among 716 young cardiologists from 81 countries, the mean theoretical test score was 56.8 ± 20.9 points, and the mean practical test score was 47.4 ± 7.2 points (/100 points max each), including 18.4 ± 8.7 points for the acquisition test score and 29.0 ± 6.7 points for the anatomy test score (/50 points max each). Acquisition test scores were higher for four-chamber (2.3 ± 1.5 points), two-chamber (2.2 ± 1.4 points) and three-chamber views (2.3 ± 1.4 points) than for other views (all P < 0.001). Prior participation to a TOE simulation-based training session, a higher number of TOE exams performed per week, and EACVI certification for TOE were independently associated with a higher global score (all P < 0.001)., Conclusion: Online evaluation of young cardiologists around the world showed a relatively low level of TOE skills and knowledge. Prior participation to a TOE simulation-based training session, a higher number of TOE exams performed per week, and the EACVI certification for TOE were independently associated with a higher global score., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Mitral annular calcification (MAC) is a common clinical finding and is associated with adverse clinical outcomes, but the clinical impact of MAC-related mitral valve (MV) dysfunction remains underappreciated. Patients with MAC frequently have stenotic, regurgitant, or mixed valvular disease, and this valvular dysfunction is increasingly recognized to be independently associated with worse prognosis. MAC-related MV dysfunction is a distinct pathophysiologic entity, and importantly much of the diagnostic and therapeutic paradigm from published rheumatic MV disease research cannot be applied in this context, leaving important gaps in our knowledge. This review summarizes the current epidemiology, pathophysiology, diagnosis, and classification of MAC-related MV dysfunction and proposes both an integrative definition and an overarching approach to this important and increasingly recognized clinical condition., Competing Interests: Funding Support and Author Disclosures This study was supported in part by a grant from the Ellison Foundation and by National Institutes of Health grant R01 HL141917 (Drs Levine and Hung). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Acute valvular emergencies represent an important cause of cardiogenic shock. However, their clinical presentation and initial diagnostic testing are often non-specific, resulting in delayed diagnosis. Moreover, metabolic disarray or haemodynamic instability may result in too great a risk for emergent surgery. This review will focus on the aetiology, clinical presentation, diagnostic findings, and treatment options for patients presenting with native acute left-sided valvular emergencies. In addition to surgery, options for medical therapy, mechanical circulatory support, and novel percutaneous interventions are discussed., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: Ferric carboxymaltose (FCM) improves left ventricular function in heart failure with reduced ejection fraction (HFrEF). Yet, the effect of FCM on right ventricular (RV) function remains insufficiently elucidated., Methods and Results: This is a pre-defined analysis of the IRON-CRT trial in which symptomatic HFrEF patients with iron deficiency and reduced left ventricular ejection fraction (LVEF) despite optimal medical therapy and cardiac resynchronization therapy (CRT) underwent 1:1 randomization to FCM or placebo in a double-blind fashion. RV function was measured as the change from baseline to 3-month follow-up in RV fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE) and pulsed Doppler peak velocity at the RV lateral annulus (RV S'), systolic pulmonary artery pressure (SPAP) and its coupling to the right ventricle (TAPSE/SPAP ratio). The RV contractile reserve was measured as the change in TAPSE during incremental pacing at 70, 90 and 110 bpm. A total of 75 patients underwent randomization and received FCM (n = 37) or placebo (n = 38). At baseline 72.5% had RV dysfunction and 70% had RV dilatation. At 3-month follow-up, patients receiving FCM had a significant improvement in RV FAC (+4.1% [+1.4% - +6.9%] vs. -2.2% [-4.9% - +0.6%] in the placebo group, p = 0.002) and TAPSE (+0.98 mm [+0.28 mm - +1.62 mm] vs. -0.19 mm [-0.85 mm - +0.48 mm] in the placebo group, p = 0.020), but not RV S'. Patients receiving FCM had a numerically lower SPAP (p = 0.073) and significant improvement in TAPSE/SPAP ratio (+0.097 [+0.048 - +0.146] vs. +0.002 [-0.046 - +0.051] in the placebo group, p = 0.008). At baseline both groups had diminished RV contractile reserve during incremental pacing, which was attenuated at 3-month follow-up in the FCM group (p = 0.004). Patients manifesting more RV function improvement were more likely to exhibit higher degrees of LVEF improvement (p < 0.05 for all)., Conclusions: Treatment with FCM in HFrEF patients results in an improvement in RV function and structure and improves the RV contractile reserve., (© 2022 European Society of Cardiology.)

Purpose of Review: The purpose of this review is to explore the prevalence and risk factors for a malignant phenotype in mitral valve prolapse (MVP) characterized by life-threatening ventricular arrhythmias and sudden cardiac arrest and death (SCD), including mechanistic and pathophysiologic findings and mechanism-based potential therapies., Recent Findings: A malignant phenotype in MVP characterized by life-threatening arrhythmias has long been recognized, although MVP is often benign. Efforts to identify this malignant phenotype have revealed potential risk factors for SCD that include elongated, myxomatous leaflets, ECG changes and complex ventricular ectopy. More recently, malignant MVP has been associated with myocardial fibrosis in the papillary muscles and inferobasal left ventricular wall. This localization suggests a central role of prolapse-induced mechanical forces on the myocardium in creating an arrhythmogenic substrate and triggering life-threatening arrhythmias. This mechanism for fibrosis is also consistent with imaging evidence of prolapse-induced mechanical changes in the papillary muscles and inferobasal left ventricular wall. Currently, no therapy to prevent SCD in malignant MVP has been established and limited clinical data are available. Mechanistic information and prospective study have the potential to identify patients at risk of SCD and preventive strategies., Summary: Malignant MVP relates to unique properties and mechanical abnormalities in the mitral valve apparatus and adjacent myocardium. Increased understanding of disease mechanisms and determinants of arrhythmias is needed to establish effective therapies., Competing Interests: CONFLICT OF INTEREST Yasufumi Nagata, Philippe B. Bertrand, and Robert A. Levine declare that they have no conflict of interest.

Mitral valve prolapse (MVP) is a common valvular disorder that can be associated with mitral regurgitation (MR), heart failure, ventricular arrhythmias and sudden cardiac death. Given the prognostic impact of these conditions, it is important to evaluate not only mitral valve morphology and regurgitation, but also the presence of left ventricular (LV) function and remodeling. To date, several possible hypotheses have been proposed regarding the underlying mechanisms of LV remodeling in the context of non-syndromic MVP, but the exact pathophysiological explanation remains elusive. Overall, volume overload related to severe MR is considered the main cause of LV dilatation in MVP. However, significant LV remodeling has been observed in patients with MVP and no/mild MR, particularly in patients with bileaflet MVP or Barlow's disease, generating several new hypotheses. Recently, the concept of "prolapse volume" was introduced, adding a significant volume load to the LV on top of the transvalvular MR volume. Another possible hypothesis is the existence of a concomitant cardiomyopathy, supported by the link between MVP and myocardial fibrosis. The origin of this cardiomyopathy could be either genetic, a second hit (e.g., on top of genetic predisposition) and/or frequent ventricular ectopic beats. This review provides an overview of the different mechanisms and remaining questions regarding LV remodeling in non-syndromic MVP. Since technical specifications of imaging modalities impact the evaluation of MR severity and LV remodeling, and therefore might influence clinical decision making in these patients, this review will also discuss assessment of MVP using different imaging modalities., 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 Pype, Bertrand, Paelinck, Heidbuchel, Van Craenenbroeck and Van De Heyning.)

The prevalence of mitral annular calcium (MAC) is increasing in our aging population. However, data regarding prognostication in MAC-related mitral valve (MV) disease remain limited. This retrospective observational study aims to explore the prognostic impact of systolic pulmonary artery pressure (SPAP) in MAC-related MV dysfunction and define its determinants. We identified 4,384 patients (mean age 78 ± 11 years and 69% female) with MAC-related MV dysfunction (documented transmitral gradient ≥3 mm Hg) from a large institutional echocardiographic database between 2001 and 2019. In Cox regression analysis, higher SPAP strongly associated with all-cause mortality, independent of cardiovascular risk factors and indices of MV dysfunction (adjusted hazard ratio 1.22 per 10 mm Hg SPAP increase, 95% confidence interval 1.17 to 1.27). Patients with SPAP ≥50 mm Hg had significantly higher mortality compared with SPAP <50 mm Hg (log-rank p <0.001), a finding that was consistent across different transmitral gradient subgroups (≤5, 5 to 10, and ≥10 mm Hg). Independent determinants of SPAP included the mean transmitral gradient, mitral regurgitation severity, left ventricular ejection fraction, and ≥moderate aortic stenosis (adjusted p <0.05), and atrial fibrillation and left atrial dimension. The impact of concomitant mitral regurgitation on SPAP decreased at higher transmitral gradients and was no longer significant at gradients ≥10 mm Hg (p = 0.100). In conclusion, SPAP strongly associates with mortality in MAC, independent of cardiovascular risk factors and indices of MAC-related MV dysfunction. These findings suggest an incremental role for SPAP in the risk stratification and prognostication in this increasingly prevalent condition with expanding the scope of possible interventions., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Heart failure (HF) is among the most important and frequent complications of diabetes mellitus (DM). The detection of subclinical dysfunction is a marker of HF risk and presents a potential target for reducing incident HF in DM. Left ventricular (LV) dysfunction secondary to DM is heterogeneous, with phenotypes including predominantly systolic, predominantly diastolic, and mixed dysfunction. Indeed, the pathogenesis of HF in this setting is heterogeneous. Effective management of this problem will require detailed phenotyping of the contributions of fibrosis, microcirculatory disturbance, abnormal metabolism, and sympathetic innervation, among other mechanisms. For this reason, an imaging strategy for the detection of HF risk needs to not only detect subclinical LV dysfunction (LVD) but also characterize its pathogenesis. At present, it is possible to identify individuals with DM at increased risk HF, and there is evidence that cardioprotection may be of benefit. However, there is insufficient justification for HF screening, because we need stronger evidence of the links between the detection of LVD, treatment, and improved outcome. This review discusses the options for screening for LVD, the potential means of identifying the underlying mechanisms, and the pathways to treatment., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Objectives: This study aimed to investigate mitral annular dynamics in atrial fibrillation (AF) and after sinus rhythm restoration, and to assess the relationship between annular dynamics and mitral regurgitation (MR)., Background: AF can be associated with MR that improves after sinus rhythm restoration. Mechanisms underlying this atrial functional MR (AFMR) are ill-understood and generally attributed to left atrial remodeling., Methods: Fifty-three patients with persistent AF and normal left ventricular ejection fraction were prospectively examined by means of 3-dimensional transesophageal echocardiography before, immediately after, and 6 weeks after electric cardioversion to sinus rhythm. Annular motion was assessed during AF and in sinus rhythm with the use of 3-dimensional analysis software, and the relationship with MR severity was explored., Results: During AF and immediately after sinus rhythm restoration, the mitral annulus behaved relatively adynamically, with an overall change in annular area of 10.3% (95% CI: 8.7%-11.8%) and 12.2% (95% CI: 10.6%-13.8%), respectively. At follow-up, a significant increase in annular dynamics (19.0%; 95% CI: 17.4%-20.6%; P < 0.001) was observed, owing predominantly to an increase in presystolic contraction (P < 0.001). The effective regurgitant orifice area decreased from 0.15 cm 2 (0.10-0.23 cm 2 ) during AF to 0.09 cm 2 (0.05-0.12 cm 2 ) at follow-up (P < 0.001) in the total cohort, and from 0.27 (0.23-0.33) to 0.16 (0.12-0.29) in the subgroup with effective regurgitant orifice area (EROA) ≥0.20 cm 2 . The change in presystolic annular motion was the only independent determinant of the decrease in MR severity (P = 0.027), by optimizing annular-leaflet imbalance. Patients with more pronounced blunting of presystolic dynamics had a higher EROA (P < 0.001), because of a lower total-to-closed leaflet area ratio (P < 0.001) at each point in time. This ratio was the strongest independent determinant of AFMR severity (adjusted P = 0.003)., Conclusions: Mitral annular dynamics are impaired in AF, with blunted presystolic narrowing that contributes to AFMR. Sinus rhythm restoration allows gradual recovery of presystolic annular dynamics. Improved annular dynamics decrease AFMR severity by optimizing annular-leaflet imbalance, regardless of LA remodeling., Competing Interests: Funding Support and Author Disclosures Drs Deferm and Vandervoort are researchers for the Limburg Clinical Research Program UHasselt-ZOL-Jessa, supported by the foundation Limburg Sterk Merk, Hasselt University, Ziekenhuis Oost-Limburg, and Jessa Hospital. Drs Deferm and Vandervoort are part of an Interreg project (Poly-Valve) aimed at providing tailor-made heart valve prostheses using coated biomedical polyurethane. Dr Verbrugge is supported by a Fellowship of the Belgian American Educational Foundation and by the Special Research Fund of Hasselt University (BOF19PD04). Dr Rega has been a consultant for Atricura and; LivaNova and has received research funding from Medtronic. Dr Thomas has been a consultant for and has received honoraria from Edwards, Abbott, GE, and Caption Health; and his spouse is an employee of Caption Health. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: Atrial secondary mitral regurgitation (ASMR) is a clinically distinct form of Carpentier type I mitral regurgitation (MR), rooted in excessive atrial and mitral annular dilation in the absence of left ventricular dysfunction. Mitral valve annuloplasty (MVA) is expected to provide a more durable solution for ASMR than for ventricular secondary MR (VSMR). Yet data on MR recurrence and outcome after MVA for ASMR are scarce. This study sought to investigate surgical outcomes and repair durability in patients with ASMR, as compared with a contemporary group of patients with VSMR., Methods: Clinical and echocardiographic data from consecutive patients who underwent MVA to treat ASMR or VSMR in an academic centre were retrospectively analysed. Patient characteristics, operative outcomes, time to recurrence of ≥moderate MR and all-cause mortality were compared between patients with ASMR versus VSMR., Results: Of the 216 patients analysed, 97 had ASMR opposed to 119 with VSMR and subvalvular leaflet tethering. Patients with ASMR were typically female (68.0% vs 33.6% in VSMR, p<0.001), with a history of atrial fibrillation (76.3% vs 33.6% in VSMR, p<0.001), paralleling a larger left atrial size (p<0.033). At a median follow-up of 3.3 (IQR 1.0-7.3) years, recurrence of ≥moderate MR was significantly lower in ASMR versus VSMR (7% vs 25% at 2 years, overall log-rank p=0.001), also when accounting for all-cause death as competing risk (subdistribution HR 0.50 in ASMR, 95% CI 0.29 to 0.88, p=0.016). Moreover, ASMR was associated with better overall survival compared with VSMR (adjusted HR 0.43 95% CI 0.22 to 0.82, p=0.011), independent from baseline European System for Cardiac Operative Risk Evaluation II surgical risk score., Conclusion: Prognosis following MVA to treat ASMR is better, compared with VSMR as reflected by lower all-cause mortality and MR recurrence. Early distinction of secondary MR towards underlying ventricular versus atrial disease has important therapeutic implications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Whether to repair nonsevere tricuspid regurgitation (TR) during surgery for ischemic mitral valve regurgitation (IMR) remains uncertain., Objectives: The goal of this study was to investigate the incidence, predictors, and clinical significance of TR progression and presence of ≥moderate TR after IMR surgery., Methods: Patients (n = 492) with untreated nonsevere TR within 2 prospectively randomized IMR trials were included. Key outcomes were TR progression (either progression by ≥2 grades, surgery for TR, or severe TR at 2 years) and presence of ≥moderate TR at 2 years., Results: Patients' mean age was 66 ± 10 years (67% male), and TR distribution was 60% ≤trace, 31% mild, and 9% moderate. Among 2-year survivors, TR progression occurred in 20 (6%) of 325 patients. Baseline tricuspid annular diameter (TAD) was not predictive of TR progression. At 2 years, 37 (11%) of 323 patients had ≥moderate TR. Baseline TR grade, indexed TAD, and surgical ablation for atrial fibrillation were independent predictors of ≥moderate TR. However, TAD alone had poor discrimination (area under the curve, ≤0.65). Presence of ≥moderate TR at 2 years was higher in patients with MR recurrence (20% vs. 9%; p = 0.02) and a permanent pacemaker/defibrillator (19% vs. 9%; p = 0.01). Clinical event rates (composite of ≥1 New York Heart Association functional class increase, heart failure hospitalization, mitral valve surgery, and stroke) were higher in patients with TR progression (55% vs. 23%; p = 0.003) and ≥moderate TR at 2 years (38% vs. 22%; p = 0.04)., Conclusions: After IMR surgery, progression of unrepaired nonsevere TR is uncommon. Baseline TAD is not predictive of TR progression and is poorly discriminative of ≥moderate TR at 2 years. TR progression and presence of ≥moderate TR are associated with clinical events. (Comparing the Effectiveness of a Mitral Valve Repair Procedure in Combination With Coronary Artery Bypass Grafting [CABG] Versus CABG Alone in People With Moderate Ischemic Mitral Regurgitation, NCT00806988; Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation, NCT00807040)., Competing Interests: Funding Support and Author Disclosures The Cardiothoracic Surgical Trials Network (CTSN) is supported by a cooperative agreement (U01 HL088942) funded by the National Heart, Lung, and Blood Institute and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health, and the Canadian Institutes for Health Research. The views expressed in this article are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, the National Institutes of Health, or the U.S. Department of Health and Human Services. Dr. Ailawadi has received honoraria (modest) from Medtronic, Edwards, Abbott, Admedus, and Gore. Dr. Thourani has served on the Advisory Board (modest) for Gore Vascular; and has received research grants (modest) from Abbott Vascular, Boston Scientific, Edwards Lifesciences, and Jenavalve. Dr. Mack has received honoraria (modest) from Gore; and has received research grants (modest) from Edwards Lifesciences, Medtronic, and Abbott. Dr. Gillinov has served as a consultant (significant) for Medtronic, AtriCure, Edwards Lifesciences, Abbott, CryoLife, and ClearFlow; and has an ownership interest (significant) in ClearFlow. Dr. Giustino has received honoraria (modest) from Bristol Myers Squibb. Dr. O’Gara has been a member of the Executive Committee for the Apollo Trial (TMVR) (modest) for Medtronic; has served as a member of the Executive Committee for the Early TAVR trial (modest) for Edwards Lifesciences; and has served as a member of the Scientific Advisory Board (modest) for MedTrace. Dr. Gammie has served as a consultant (modest) for Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Occult atrial fibrillation (AF) is an important contributor to cryptogenic stroke, yet remains difficult to unmask at presentation. This study investigated the predictive value of left atrial (LA) mechanics by strain echocardiography during stroke hospitalization for the presence of AF as detected on early 30-day monitoring and routine clinical follow-up., Methods: Left atrial mechanics were studied by strain echocardiography in a retrospective cohort of 191 patients with cryptogenic stroke and 30-day mobile cardiac outpatient telemetry poststroke to diagnose AF. After this, AF was diagnosed via routine clinical follow-up. The independent and incremental value of measures of LA size and mechanics (i.e., strain and strain rate in the reservoir, conduit, and booster pump phase) to predict AF on top of clinical characteristics was assessed., Results: Of 191 patients, 15% (n = 28) developed AF, of which 10 were observed during 30-day mobile cardiac outpatient telemetry and 18 were observed at a median follow-up of 25 (interquartile range, 10-43) months. Median time from embolic stroke to strain echocardiography was 1 day (interquartile range, 1-2 days). Left atrial mechanics were significantly worse in AF (P < .05 for all), despite largely similar baseline cardiovascular risk profile. Booster pump strain rate was the strongest predictor for AF, independent of age, LA volume index, E/e', and reservoir strain (odds ratio = 2.88 per SD increase; 95% confidence interval, 1.29-6.41; P = .010). Adding LA strain reservoir strain and booster pump function significantly enhanced a multivariate model to predict AF. Freedom from AF was significantly lower in subjects with a booster pump strain rate (at stroke presentation) worse than -0.67 sec -1 , as derived from receiver operator curve analysis (P < .001)., Conclusions: Left atrial mechanics and particularly the LA booster pump function assessed early during hospitalization for cryptogenic stroke can identify patients at greater likelihood of future diagnosis of AF. These findings could in part relate to LA mechanical stunning after spontaneous cardioversion, which-when identified by early strain echocardiography-can inform further risk stratification and decision-making., (Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Aims: The aim of this study was to define the natural history of patients with mitral annular calcification (MAC)-related mitral valve dysfunction and to assess the prognostic importance of mean transmitral pressure gradient (MG) and impact of concomitant mitral regurgitation (MR)., Methods and Results: The institutional echocardiography database was examined from 2001 to 2019 for all patients with MAC and MG ≥3 mmHg. A total of 5754 patients were stratified by MG in low (3-5 mmHg, n = 3927), mid (5-10 mmHg, n = 1476), and high (≥10 mmHg, n = 351) gradient. The mean age was 78 ± 11 years, and 67% were female. MR was none/trace in 32%, mild in 42%, moderate in 23%, and severe in 3%. Primary outcome was all-cause mortality, and outcome models were adjusted for age, sex, and MAC-related risk factors (hypertension, diabetes, coronary artery disease, chronic kidney disease). Survival at 1, 5, and 10 years was 77%, 42%, and 18% in the low-gradient group; 73%, 38%, and 17% in the mid-gradient group; and 67%, 25%, and 11% in the high-gradient group, respectively (log-rank P < 0.001 between groups). MG was independently associated with mortality (adjusted HR 1.064 per 1 mmHg increase, 95% CI 1.049-1.080). MR severity was associated with mortality at low gradients (P < 0.001) but not at higher gradients (P = 0.166 and 0.372 in the mid- and high-gradient groups, respectively)., Conclusion: In MAC-related mitral valve dysfunction, mean transmitral gradient is associated with increased mortality after adjustment for age, sex, and MAC-related risk factors. Concomitant MR is associated with excess mortality in low-gradient ranges (3-5 mmHg) but gradually loses prognostic importance at higher gradients, indicating prognostic utility of transmitral gradient in MAC regardless of MR severity., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Agitated saline contrast studies are an essential component of contemporary echocardiography. Agitated saline contrast plays a critical role in the elucidation of intracardiac versus intrapulmonary shunting and can have major therapeutic implications, particularly in light of the evolution of percutaneous treatment options for atrial septal defects or a patent foramen ovale. Despite their perceived simplicity, however, there are numerous pitfalls of these investigations that can occur during their performance and interpretation. As such, the authors review the "bubble study" in identifying intracardiac and extracardiac shunts, including the history of its development, the physics and physiology of contrast enhancement, how to optimally perform and interpret an agitated saline contrast study, and its safety in unique populations., (Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

The tricuspid valve (TV) is a complex anatomical structure that incorporates a saddle-shaped annulus, asymmetric leaflets, the subvalvular apparatus and the right ventricle and its loading conditions. In this paper, an appreciation of the normal anatomy and physiology of the TV is reviewed before discussing functional tricuspid regurgitation (TR), a disease that has garnered renewed interest due to increased awareness of adverse outcomes and novel transcatheter therapeutic options. Two and three-dimensional echocardiographic imaging of the TV using transthoracic and transesophageal windows are subsequently discussed. The future of cardiovascular medicine will have more to offer the "forgotten" right-sided chambers and valves, and this review aims to refresh knowledge and enthusiasm around the forgotten but crucially important TV., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd.2020.02.42). The series “Novel Concepts in Cardiopulmonary and Structural Heart Disease” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Objectives: The aim of this study was to assess the effect of congestion and decongestive therapy on left atrial (LA) mechanics and to determine the relationship between LA improvement after decongestive therapy and clinical outcome in immediate or chronic heart failure with reduced ejection fraction (HFrEF)., Background: LA mechanics are affected by volume/pressure overload in decompensated HFrEF., Methods: A total of 31 patients with HFrEF and immediate heart failure (age 64 ± 15 years, 74% male, left ventricular ejection fraction 20 ± 12%) underwent serial echocardiography during decongestive therapy with simultaneous hemodynamic monitoring. LA function was assessed by strain (rate) imaging. Patients were re-evaluated 6 weeks after discharge and prospectively followed up for the composite endpoint of heart failure readmission and all-cause mortality., Results: LA reservoir function was markedly reduced at baseline and improved with decongestion (peak atrial longitudinal strain from 6.4 ± 2.2% to 8.8 ± 3.0% and strain rate from 0.29 ± 0.11 s -1 to 0.38 ± 0.13 s -1 ), independent of changes in left ventricular global longitudinal strain, LA end-diastolic volume, and mitral regurgitation severity (p < 0.001). Both measures continued to rise at 6 weeks (up to 13.4 ± 6.1% and 0.50 ± 0.19 s -1 , respectively; p < 0.001). LA pump strain rate only increased 6 weeks after discharge (-0.25 ± 0.12 s -1 to -0.55 ± 0.29 s -1 ; p < 0.010). Changes in LA mechanics correlated with changes in wedge pressure (r = -0.61; p < 0.001). Lower peak atrial longitudinal strain values after decongestion were associated with increased risk for the composite endpoint of heart failure and mortality (p < 0.019)., Conclusions: LA reservoir and booster function, while severely impaired during immediate decompensation, significantly improve during and after decongestive therapy. Poor LA reservoir function after decongestion is associated with worse outcome., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study assessed the impact of right-atrial (RA) pacing on left-atrial (LA) physiology and clinical outcome., Background: Data for the effects of RA pacing on LA synchronicity, function, and structure after cardiac resynchronization therapy (CRT) are scarce., Methods: The effect of RA pacing on LA function, morphology, and synchronicity was assessed in a prospective imaging cohort of heart failure (HF) patients in sinus rhythm with a guideline-based indication for CRT. Additionally, in a retrospective outcome cohort of consecutive HF patients undergoing CRT implantation, the relationship to RA pacing was assessed using various outcome endpoints. High versus low atrial pacing burden was defined as atrial pacing above or below 50% in both cohorts., Results: A total of 36 patients were included in the imaging cohort (68 ± 11 years of age). Six months after CRT, patients with high RA pacing burden showed less improvement in LA maximum and minimum volumes and total emptying fraction (p < 0.05). Peak atrial longitudinal strain and reservoir and booster strain rates but not conduit strain rate improved after CRT in patients with low RA pacing burden but worsened in patients with high RA pacing burden (p < 0.05 for all). A high RA pacing burden induced significant intra-atrial dyssynchrony (maximum opposing wall delay: 44 ± 13 ms vs. 97 ± 17 ms, respectively; p = 0.022). A total of 569 patients were included in the outcome cohort. After covariate adjustments were made, a high RA pacing burden was associated with reduced LV reverse remodeling (β = 8.738; 95% confidence interval [CI]: 3.101 to 14.374; p = 0.002) and new-onset or recurrent atrial fibrillation (41% vs. 22%, respectively, at a median of 31 months [range 22 to 44 months follow-up]; p < 0.001). There were no differences in time to first HF hospitalization or all-cause mortality (p = 0.185) after covariate adjustment. However, in a recurrent event analysis, HF readmissions were more common in patients exposed to a high RA pacing burden (p = 0.003)., Conclusions: RA pacing in CRT patients negatively influences LA morphology, function, and synchronicity, which is associated with worse clinical outcome, including diminished LV reverse remodeling, increased risk for new-onset or recurrent AF and heart failure readmission. Strategies reducing RA pacing burden may be warranted., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The necessity of neurohumoral blockers in patients with heart failure who demonstrate normalized ejection fractions after cardiac resynchronization therapy remains unclear., Objectives: The aim of this study was to investigate the feasibility and safety of neurohumoral blocker withdrawal in patients with normalized ejection fractions after cardiac resynchronization therapy., Methods: In this prospective, open-label, randomized controlled pilot trial with a 2 × 2 factorial design, subjects were randomized to withdrawal of renin-angiotensin-aldosterone system inhibitors and/or beta-blockers versus continuation of treatment. The primary endpoint was a recurrence of negative remodeling, defined as an increase in left ventricular end-systolic volume index of >15% at 24 months. The secondary endpoint was a composite safety endpoint of all-cause mortality, heart failure-related hospitalizations, and incidence of sustained ventricular arrhythmias at 24 months., Results: Eighty subjects were consecutively enrolled and randomized among 4 groups (continuation of neurohumoral blocker therapy, n = 20; withdrawal of renin-angiotensin-aldosterone system inhibitors, n = 20; withdrawal of beta-blockers, n = 20; and withdrawal of renin-angiotensin-aldosterone system inhibitors and beta-blockers, n = 20). Of the 80 subjects, 6 (7.5%) met the primary and 4 (5%) the secondary endpoint. However, re-initiation of neurohumoral blockers occurred in 17 subjects because of hypertension or supraventricular arrhythmias., Conclusions: The incidence of the primary and secondary endpoints over a follow-up period of 2 years was low in both the control group and in the groups in which neurohumoral blockers were discontinued. However, neurohumoral blocker withdrawal was hampered by cardiac comorbidities. (Systematic Withdrawal of Neurohumoral Blocker Therapy in Optimally Responding CRT Patients [STOP-CRT]; NCT02200822)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

A 77-year-old patient presented with a mobile structure on the anterior mitral valve leaflet and was diagnosed with endocarditis. Subsequent imaging demonstrated this finding was consistent with a left atrial mitral valve chord. Recognition of this rare mitral valve anomaly is key to avoid overdiagnostics and/or overtreatment. ( Level of Difficulty: Beginner. )., (© 2020 The Authors.)

Purpose of Review: Transcatheter edge-to-edge mitral valve repair (TMVr) has been increasingly used in the treatment of patients with severe symptomatic mitral regurgitation who are at high or prohibitive risk for surgical intervention. Pre-existing pulmonary hypertension is known to pertain worse prognosis for patients who are undergoing surgical intervention. The aim of this review is to discuss the current literature on the effects of pulmonary hypertension on the transcatheter edge-to-edge mitral valve repair outcomes., Recent Findings: Large registry data in patients undergoing TMVr for treatment of severe mitral regurgitation reveal a significant negative impact of baseline pulmonary hypertension on post-procedural outcomes. Pulmonary hypertension is associated with increased mortality and heart failure readmissions in patients undergoing TMVr using MitraClip. Further prospective studies are needed to determine whether earlier intervention will improve clinical outcomes.

Unlike secondary mitral regurgitation (MR) in the setting of left ventricular (LV) disease, the occurrence of functional MR in atrial fibrillation (AF) and/or heart failure with preserved ejection fraction (HFpEF) has remained largely unspoken. LV size and systolic function are typically normal, whereas isolated mitral annular dilation and inadequate leaflet adaptation are considered mechanistic culprits. Moreover, the role of left atrial and annular dynamics in provoking MR is often underappreciated. Because of this peculiar pathophysiology, atrial functional MR benefits from a different approach compared with secondary MR. Although both AF and HFpEF-two closely related disease epidemics of the 21st century-are held responsible, current guidelines do not emphasize the need to differentiate atrial functional MR from (ventricular) secondary MR. This review summarizes the prevalence and prognostic importance of atrial functional MR, providing mechanistic insights compared with those of secondary MR and suggesting potential therapeutic targets., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Mitral annular calcification (MAC) and associated calcific mitral stenosis (MS) are frequent in the aging population, although optimal management remains debated and outcomes are poor. This article summarizes challenges in the diagnosis and therapy of calcific MS, the indications for valve intervention, procedural concerns, and emerging treatment options., Recent Findings: Surgical mitral valve replacement is the procedure of choice in symptomatic patients at acceptable surgical risk, with transcatheter mitral valve replacement (TMVR) being evaluated in clinical trials as an alternative for patients at prohibitive surgical risk. Significant challenges exist with the currently available technology and outcomes have been suboptimal. Optimizing the patient-selection process by using multimodality imaging tools has proven to be essential. MAC and calcific MS is an increasingly prevalent, challenging issue with poor outcomes. While surgical valve replacement can be performed in patients with acceptable surgical risk, TMVR can be considered for patients at higher risk. Clinical trials are underway to optimize outcomes. Dedicated device designs and techniques to minimize risk of left ventricular outflow tract obstruction, paravalvular leakage, and device embolization are to be awaited.