Clinical Significance of Exercise Pulmonary Hypertension With a Negative Diastolic Stress Test for Suspected Heart Failure With Preserved Ejection Fraction.

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 H2FPEF (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.

Diagnostic Value of Aortic Valve Calcification Levels in the Assessment of Low-Gradient Aortic Stenosis.

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 cm2 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.

Mitral regurgitation in heart failure with preserved ejection fraction: The interplay of valve, ventricle, and atrium.

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.

Non-invasive imaging in acute decompensated heart failure with preserved ejection fraction.

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.

Mitral Valve Surgery for Mitral Regurgitation Results in Reduced Left Ventricular Ejection Fraction in Barlow's Disease as Compared with Fibro-Elastic Deficiency.

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/m2 vs. -5.3 ± 9.0 mL/m2; 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.

Exercise pulmonary hypertension by the mPAP/CO slope in primary mitral regurgitation.

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.

Utility of Left and Right Ventricular Strain in Arrhythmogenic Right Ventricular Cardiomyopathy: A Prospective Multicenter Registry.

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.

Reduced Left Atrial Appendage Flow Is Associated With Future Atrial Fibrillation After Cryptogenic Stroke.

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.

Arrythmia-Mediated Valvular Heart Disease.

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.

Three-dimensional transoesophageal echocardiography: how to use and when to use-a clinical consensus statement from the European Association of Cardiovascular Imaging of the European Society of Cardiology.

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.

Abnormal Mechanics Relate to Myocardial Fibrosis and Ventricular Arrhythmias in Patients With Mitral Valve Prolapse.

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.

Sex Differences in Extensive Mitral Annular Calcification With Associated Mitral Valve Dysfunction.

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.

EACVI SIMULATOR-online study: evaluation of transoesophageal echocardiography knowledge and skills of young cardiologists.

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.

Acute valvular emergencies.

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.

Mitral Valve Dysfunction in Patients With Annular Calcification: JACC Review Topic of the Week.

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.

Malignant Mitral Valve Prolapse: Risk and Prevention of Sudden Cardiac Death.

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.