Computed Simulation of Transcatheter Edge-to-Edge Mitral Valve Repair - A Proof of Concept Study.

AIMS: As transcatheter mitral valve (MV) interventions are expanding and more device types and sizes become available, a tool supporting operators in preprocedural planning and the clinical decision-making process is highly desirable. We sought to develop a finite element (FE) computational simulation model to predict results of transcatheter edge-to-edge (TEER) interventions. METHODS AND RESULTS: We prospectively enrolled patients with secondary mitral regurgitation (MR) referred for a clinically indicated TEER. Three-dimensional (3D) transesophageal echocardiograms performed at the beginning of the procedure were used to perform the simulation. On the 3D dynamic model of the MV that was first obtained, we simulated the clip implantation using the same clip(s) type, size, number, and implantation location that was used during the intervention. The 3D model of the MV obtained after simulation of the clip implantation was compared to the clinical results obtained at the end of the intervention. We analyzed the degree and location of residual MR and the shape and area of the diastolic mitral valve area. We performed computational simulation on 5 patients. Overall, the simulated models predicted well the degree and location of the residual regurgitant orifice(s) but tended to underestimate the diastolic mitral orifice area. CONCLUSIONS: In this proof-of-concept study, we present preliminary results on our algorithm simulating clip implantation in 5 patients with functional MR. We show promising results regarding the feasibility and accuracy in terms of predicting residual MR and the need to improve the estimation of the diastolic mitral valve area.

Is there a role for cardiovascular magnetic resonance imaging in the assessment of biological aortic valves?

Patients with biological aortic valves (following either surgical aortic valve replacement [SAVR] or trans catheter aortic valve implantation [TAVI]) require lifelong follow-up with an imaging modality to assess prosthetic valve function and dysfunction. Echocardiography is currently the first-line imaging modality to assess biological aortic valves. In this review, we discuss the potential role of cardiac magnetic resonance imaging (CMR) as an additional imaging modality in situations of inconclusive or equivocal echocardiography. Planimetry of the prosthetic orifice can theoretically be measured, as well as the effective orifice area, with potential limitations, such as CMR valve-related artefacts and calcifications in degenerated prostheses. The true benefit of CMR is its ability to accurately quantify aortic regurgitation (paravalvular and intra-valvular) with a direct and reproducible method independent of regurgitant jet morphology to accurately assess reverse remodelling and non-invasively detect focal and interstitial diffuse myocardial fibrosis. Following SAVR or TAVI for aortic stenosis, interstitial diffuse fibrosis can regress, accompanied by structural and functional improvement that CMR can accurately assess.

Is "moderate" aortic stenosis still the right name? A review of the literature.

Current guidelines recommend aortic valve replacement for symptomatic or selected asymptomatic high-risk patients with severe aortic stenosis. Conversely, a watchful waiting attitude applies to patients with moderate aortic stenosis, regardless of their risk profile and symptoms, until the echocardiographic thresholds of severe aortic stenosis are reached. This strategy is based on data reporting high mortality in untreated severe symptomatic aortic stenosis, whereas moderate aortic stenosis has always been perceived as a non-threatening condition, with a benefit-risk balance against surgery. Meanwhile, numerous studies have reported a worrying event rate in these patients, surgical techniques and outcomes have improved significantly and the use of transcatheter aortic valve replacement has become more widespread and extended to lower-risk patients, leaving this strategy open to question, especially for patients with moderate aortic stenosis and left ventricular dysfunction. In this review, we summarize the current state of knowledge about moderate aortic stenosis progression and prognosis. We also discuss the particular case of moderate aortic stenosis associated with left ventricular dysfunction, and the ongoing trials that that might change our paradigm for the management of this "moderate" valvular heart disease.

The evolving role of cardiovascular magnetic resonance in the assessment of mitral valve prolapse.

Mitral valve prolapse (MVP), characterized by a displacement > 2 mm above the mitral annulus of one or both bileaflets, with or without leaflet thickening, is a common valvular heart disease, with a prevalence of approximately 2% in western countries. Although this population has a generally good overall prognosis, MVP can be associated with mitral regurgitation (MR), left ventricular (LV) remodeling leading to heart failure, ventricular arrhythmia, and, the most devastating complication, sudden cardiac death, especially in myxomatous bileaflet prolapse (Barlow's disease). Among several prognostic factors reported in the literature, LV fibrosis and mitral annular disjunction may act as an arrhythmogenic substrate in this population. Cardiac magnetic resonance (CMR) has emerged as a reliable tool for assessing MVP, MR severity, LV remodeling, and fibrosis. Indeed, CMR is the gold standard imaging modality to assess ventricular volume, function, and wall motion abnormalities; it allows accurate calculation of the regurgitant volume and regurgitant fraction in MR using a combination of LV volumetric measurement and aortic flow quantification, independent of regurgitant jet morphology and valid in cases of multiple valvulopathies. Moreover, CMR is a unique imaging modality that can assess non-invasively focal and diffuse fibrosis using late gadolinium enhancement sequences and, more recently, T1 mapping. This review describes the use of CMR in patients with MVP and its role in identifying patients at high risk of ventricular arrhythmia.

Quantification of primary mitral regurgitation by echocardiography: A practical appraisal.

The accurate quantification of primary mitral regurgitation (MR) and its consequences on cardiac remodeling is of paramount importance to determine the best timing for surgery in these patients. The recommended echocardiographic grading of primary MR severity relies on an integrated multiparametric approach. It is expected that the large number of echocardiographic parameters collected would offer the possibility to check the measured values regarding their congruence in order to conclude reliably on MR severity. However, the use of multiple parameters to grade MR can result in potential discrepancies between one or more of them. Importantly, many factors beyond MR severity impact the values obtained for these parameters including technical settings, anatomic and hemodynamic considerations, patient's characteristics and echocardiographer' skills. Hence, clinicians involved in valvular diseases should be well aware of the respective strengths and pitfalls of each of MR grading methods by echocardiography. Recent literature highlighted the need for a reappraisal of the severity of primary MR from a hemodynamic perspective. The estimation of MR regurgitation fraction by indirect quantitative methods, whenever possible, should be central when grading the severity of these patients. The assessment of the MR effective regurgitant orifice area by the proximal flow convergence method should be used in a semi-quantitative manner. Furthermore, it is crucial to acknowledge specific clinical situations in MR at risk of misevaluation when grading severity such as late-systolic MR, bi-leaflet prolapse with multiple jets or extensive leak, wall-constrained eccentric jet or in older patients with complex MR mechanism. Finally, it is debatable whether the 4-grades classification of MR severity would be still relevant nowadays, since the indication for mitral valve (MV) surgery is discussed in clinical practice for patients with 3+ and 4+ primary MR based on symptoms, specific markers of adverse outcome and MV repair probability. Primary MR grading should be seen as a continuum integrating both quantification of MR and its consequences, even for patients with presumed "moderate" MR.

Role of Cardiovascular Magnetic Resonance in Native Valvular Regurgitation: A Comprehensive Review of Protocols, Grading of Severity, and Prediction of Valve Surgery.

Valvular regurgitation is common in developed countries with an increasing prevalence due to the aging of the population and more accurate diagnostic imaging methods. Echocardiography is the gold standard method for the assessment of the severity of valvular heart regurgitation. Nonetheless, cardiovascular magnetic resonance (CMR) has emerged as an additional tool for assessing mainly the severity of aortic and mitral valve regurgitation in the setting of indeterminate findings by echocardiography. Moreover, CMR is a valuable imaging modality to assess ventricular volume and flow, which are useful in the calculation of regurgitant volume and regurgitant fraction of mitral valve regurgitation, aortic valve regurgitation, tricuspid valve regurgitation, and pulmonary valve regurgitation. Notwithstanding this, reference values and optimal thresholds to determine the severity and prognosis of valvular heart regurgitation have been studied lesser by CMR than by echocardiography. Hence, further larger studies are warranted to validate the potential prognostic relevance of the severity of valvular heart regurgitation determined by CMR. The present review describes, analyzes, and discusses the use of CMR to determine the severity of valvular heart regurgitation in clinical practice.

Extensive intra-myocardial calcifications: Value of multimodality imaging.

BACKGROUND: Massive myocardial calcification is a very rare finding. INTRODUCTION: Accurate identification and characteriation may help the clinicians to determine the etiology and clinical significance. RESULTS: In this case, the diagnostic pathway excluded previous myocardial infarction, myocarditis, and calcium-phosphate disorders. A possible dystrophic etiology was considered. DISCUSSION: There are no standardized imaging features available to classify specific subtypes of intra-myocardial calcifications. The relative merits of computed tomography and cardiac magnetic resonance (CMR) in providing complimentary diagnostic information in the evaluation of calcific myocardial lesions are shown. CONCLUSION: Knowledge of the potential etiology and their imging patterns are important to provide a concise and accurate differential diagnosis.

Echocardiographic characteristics of non-resectional ring-only valve repair in mitral valve prolapse.

BACKGROUND: Simple mitral valve repair (MVR) using a ring-only approach (ROA) was recently proposed for some complex forms of bileaflet myxomatous mitral valve prolapse (MVP). Nevertheless, few data are available concerning the characteristics of MVP patients that may benefit from this simple repair technique. METHODS: Based on 39 consecutive patients (28 men; mean age 57 ± 15) with severe primary Mitral regurgitation (MR) caused by bileaflet MVP referred for MVR, we sought to identify the preoperative echocardiographic parameters associated with successful ROA repair. RESULTS: Twenty-three patients (59%) underwent standard resectional MVR (SMVR) while 16 (41%) underwent ROA. Cardiopulmonary bypass and cross clamp times were lower in ROA than in SMVR (74 ± 27 min vs 99 ± 42 min and 49 ± 19 min vs 70 ± 25 min, respectively, p = 0.03 and p = 0.005). ROA patients were more frequently women (50% vs 13%, p = 0.027). Echocardiographic characteristics of successful ROA were mid-late systolic MR, a paradoxical systolic papillary muscle displacement, and paradoxical systolic annulus expansion (PAE). A prolapsing depth <10 mm, the absence of flail leaflet and ruptured chordae, the presence of multiple jets, more often in the central part of the valve were also associated with ROA. Non hemodynamic systolic anterior motion and residual trivial MR tended to be more frequent in ROA than in SMVR. CONCLUSION: Simple and fast MVR using a ROA is feasible in 4/10 patients with complex forms of bileaflet MVP. Successful ROA patients were more frequently women, with mid-late systolic central multiple jet, low prolapse depth, absence of chordal rupture or flail leaflet and PAE.

Comparison of Mitral Regurgitant Volume Assessment between Proximal Flow Convergence and Volumetric Methods in Patients with Significant Primary Mitral Regurgitation: An Echocardiographic and Cardiac Magnetic Resonance Imaging Study.

BACKGROUND: Discrepancies have been observed between transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) severity grading in primary mitral regurgitation (MR). OBJECTIVES: We sought to compare mitral regurgitant volume (RVol) determined by the TTE proximal flow convergence (proximal isovelocity surface area [PISA]) method and by volumetric methods (TTE and CMR) and to study the relationship between left ventricle (LV) size and RVol obtained by either the PISA or volumetric methods. METHODS: Two centers prospectively recruited 188 patients with at least moderate to severe primary MR due to prolapse in sinus rhythm who underwent TTE and CMR examinations. Regurgitant volume was estimated by either PISA (PISA-RVol) or volumetric methods (LV total stroke volume-systolic aortic forward outflow volume) using either CMR (CMR-RVol) or TTE (TTE-RVol). RESULTS: The PISA-RVol was weakly correlated with CMR-RVol and TTE-RVol (r = 0.29 and 0.30, respectively; P < .001 for both). On multivariable analysis, smaller CMR-left ventricular end-diastolic volume (LVEDV) and absence of mitral annular disjunction independently correlated with increased magnitude of RVol difference between PISA and volumetric methods. While PISA-RVol and LVEDV were unrelated, CMR-RVol and TTE-RVol moderately correlated with LVEDV (r = 0.66 and 0.68, respectively; P < .001 for both). In contrast, LVEDV and regurgitant fraction (RVol/LV total stroke volume), assessed with either TTE or CMR, were poorly correlated (r = 0.17, P = .02; and r = 0.12, P = .10, respectively). CONCLUSIONS: Mitral RVol values estimated by PISA and volumetric methods are not directly comparable. The expected proportional relationship between volumetric RVol and LV size, which was not observed with PISA-RVol, suggests that PISA-RVol would be inaccurate. Given that RVol assessed with volumetric methods depends on LV size, determination of a unique RVol threshold for severe MR is challenging. In contrast to RVol, calculating regurgitant fraction by volumetric methods allows the quantification of MR severity independently from LV size.

Relationship Between the Ratio of Acceleration Time/Ejection Time and Mortality in Patients With High-Gradient Severe Aortic Stenosis.

Background The ratio of acceleration time/ejection time (AT/ET) is a simple and reproducible echocardiographic parameter that integrates aortic stenosis severity and its consequences on the left ventricle. No study has specifically assessed the prognostic impact of AT/ET on outcome in patients with high-gradient severe aortic stenosis (SAS) and no or mild symptoms. We sought to evaluate the relationship between AT/ET and mortality and determine the best predictive AT/ET cutoff value in these patients. Methods and Results A total of 353 patients (median age, 79 years; 46% women) with high-gradient (mean pressure gradient ≥40 mm Hg and/or aortic peak jet velocity ≥4 m/s) SAS, left ventricular ejection fraction ≥50%, and no or mild symptoms were studied. The impact of AT/ET ≤0.35 or >0.35 on all-cause mortality was retrospectively studied. During a median follow-up of 39 (25th-75th percentile, 23-62) months, 70 patients died. AT/ET >0.35 was associated with a considerable increased mortality risk after adjustment for established prognostic factors in SAS under medical and/or surgical management (adjusted hazard ratio [HR], 2.54; 95% CI, 1.47-4.37; P<0.001) or conservative management (adjusted HR, 3.29; 95% CI, 1.70-6.39; P<0.001). Moreover, AT/ET >0.35 improved the predictive performance of models including established risk factors in SAS with better global model fit, reclassification, and discrimination. After propensity matching, increased mortality risk persisted when AT/ET >0.35 (adjusted HR, 2.10; 95% CI, 1.12-3.90; P<0.001). Conclusions AT/ET >0.35 is a strong predictor of outcome in patients with SAS and no or only mild symptoms and identifies a subgroup of patients at higher risk of death who may derive benefit from earlier aortic valve replacement.

Influence of Prolapse Volume in Mitral Valve Prolapse.

Mitral valve prolapse (MVP) is characterized by excessive leaflet tissue leading to a wide spectrum of mitral regurgitation (MR) ranging from trivial to severe. The prolapse volume (PV) below the prolapsing leaflets in end-systole was suspected to impact both chamber remodeling and MR grading in MVP. Based on 157 consecutive patients (45 women; mean age 62±15) referred for CMR assessment of MR, either from MVP (n = 91; 58%) or fibroelastic disease (FED) (n = 66; 42%), we sought to study (i) the interaction between PV and cardiac chamber geometry (ii) to study the impact of PV on MR quantification in MVP. Despite similar left ventricular (LV) size, PV was larger in MVP (11±9ml) than in FED (2±2ml). PV progressively increased with the severity of MR in MVP but not in FED. Despite a low regurgitant volume (32±18ml), some MVP patients with less than moderate MR exhibit significant cardiac chambers remodeling compared to 52 age and sex-matched controls. PV correlated significantly (r = 0.52) with the LV dilatation in severe MR but also in less than moderate MR. In MVP, PV>14ml was associated with a significant underestimation (Bias=-26±32ml) of regurgitant volume by PISA compared to CMR. In conclusion, in MVP, PV may play a role in left cardiac chambers remodeling, even in patients without severe MR, and in discordant grading of MR between echocardiography and CMR.

Non-contrast myocardial T1 global and regional reference values at 3 Tesla cardiac magnetic resonance in aortic stenosis.

BACKGROUND: T1 mapping using cardiac magnetic resonance (CMR) was recently proposed as a promising non-contrast imaging technique for the assessment of diffuse myocardial fibrosis (MF) in aortic stenosis (AS). AIMS: To provide reference values for native T1 mapping at 3 Tesla magnetic field strength in subjects with moderate or severe AS and in control subjects; to identify factors associated with the presence of diffuse MF in severe AS; to assess the regional distribution of diffuse MF; and to compare the level of diffuse MF in the different types of AS, stratified by flow and gradient patterns. METHODS: Retrospective study based on 160 consecutive patients with moderate (n=11) to severe (n=149) AS and 47 control subjects referred for CMR. RESULTS: Mean native T1 increased progressively across controls (1221±23ms), moderate AS (1249±26ms) and severe AS (1273±43ms). T1 times correlated significantly with left ventricular (LV) remodelling (indexed LV mass and LV diastolic volume) and functional LV alterations (global longitudinal strain and LV ejection fraction). Native T1 appears to be elevated in the basal segments of the septum in moderate AS, and to extend to midventricular and apical segments in severe AS. Mean T1 time was higher in classical low-flow/low-gradient AS (1295±62ms) than in the other types of AS (P=0.006). The level of diffuse MF in paradoxical low-flow/low-gradient AS (1280±42ms) was higher than in moderate AS, but similar to that in high-gradient AS (1271±42ms) (P=0.07). CONCLUSIONS: Assessment of diffuse MF in AS using T1 mapping is feasible and reproducible in clinical practice. T1 value increases with AS severity, along with morphological and functional LV alterations, particularly in the basal segments of the septum.

Excess Mortality and Undertreatment of Women With Severe Aortic Stenosis.

Background Although women represent half of the population burden of aortic stenosis (AS), little is known whether sex affects the presentation, management, and outcome of patients with AS. Methods and Results In a cohort of 2429 patients with severe AS (49.5% women) we aimed to evaluate 5-year excess mortality and performance of aortic valve replacement (AVR) stratified by sex. At presentation, women were older (P<0.001), with less comorbidities (P=0.030) and more often symptomatic (P=0.007) than men. Women had smaller aortic valve area (P<0.001) than men but similar mean transaortic pressure gradient (P=0.18). The 5-year survival was lower compared with expected survival, especially for women (62±2% versus 71% for women and 69±1% versus 71% for men). Despite longer life expectancy in women than men, women had lower 5-year survival than men (66±2% [expected-75%] versus 68±2% [expected-70%], P<0.001) after matching for age. Overall, 5-year AVR incidence was 79±2% for men versus 70±2% for women (P<0.001) with male sex being independently associated with more frequent early AVR performance (odds ratio, 1.49; 1.18-1.97). After age matching, women remained more often symptomatic (P=0.004) but also displayed lower AVR use (64.4% versus 69.1%; P=0.018). Conclusions Women with severe AS are diagnosed at later ages and have more symptoms than men. Despite prevalent symptoms, AVR is less often performed in women and 5-year excess mortality is noted in women versus men, even after age matching. These imbalances should be addressed to ensure that both sexes receive equivalent care for severe AS.

Left atrial dysfunction as marker of poor outcome in patients with hypertrophic cardiomyopathy.

BACKGROUND: The incremental prognostic value of left atrial (LA) dysfunction, emerging in various clinical contexts, remains poorly explored in hypertrophic cardiomyopathy (HCM). OBJECTIVE: To assess LA strain correlation with outcome in HCM. METHODS: A cohort of all 307 consecutive patients presenting with HCM between 2007 and 2017 (54±17 years; 34% women), with comprehensive echocardiography at diagnosis and LA peak longitudinal strain (PALS) and LA peak contraction strain (PACS) measurement, was enrolled and occurrence of HCM related cardiac events analysed. RESULTS: Clinically, atrial fibrillation (AF) was present in 13%, New York Heart Association functional class II-III in 54%, and B-type natriuretic peptide (BNP) concentration was 199±278pg/mL. By echocardiography, left ventricular (LV) ejection fraction (EF) was 67±10%, LV thickness 21±5mm and European Society of Cardiology HCM risk score 3±3%, with 109 patients (36%) presenting obstructive HCM (LV outflow gradient 21±32mmHg). LA diameter was 41±8mm [with 109 (36%) presenting LA diameter ≥40mm], LA volume index 50±26mL/m2, PALS 24±13%, PACS 11±7% and LA peak systolic strain rate (LASRs) 1.7±0.6 s-1. In addition to AF, age, BNP, LVEF and LV thickness were all independent determinants of lower PALS, with odd ratios almost unchanged after adjustment (all P ≤0.0004). At a mean follow-up of 21 (range 18-23) months, patients with adverse cardiac events (n=65) presented with more impaired LA function (all P ≤0.0005), with a significant association between impaired PALS and worse outcome, hazard ratio 0.94 [95% confidence interval (CI) 0.92-0.97, P<0.0001]. After comprehensive adjustment, PALS remained strongly associated with worse outcome, adjusted hazard ratio 0.86 (95% CI 0.79-0.94; P=0.0008). CONCLUSIONS: The present study, by gathering a unique HCM cohort, suggests a strong link between LA dysfunction and poor outcome, to be further investigated.