Impact of Sex on Severity Assessment and Cardiac Remodeling in Primary Mitral Regurgitation.

Background: Women with severe primary mitral regurgitation (MR) have lower surgery rates than men and could suffer from delayed referral for mitral valve (MV) intervention, exposing them to an increased risk of postoperative adverse outcomes. Objectives: The purpose of this study was to assess the sex-based differences in patients with primary MR. Methods: The study sample consisted of 420 patients (median age: 62 years, 26% women) with primary MR due to valve prolapse referred for preoperative assessment who underwent transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) imaging. Multiple endpoints (abnormally increased left ventricular size, NYHA functional class III/IV, severe left atrial [LA] dilatation, pulmonary hypertension) were studied using areas under the curves and logistic regression models. Results: Women were older than men, had higher NYHA functional class and larger indexed LA volumes (all P ≤ 0.031), despite displaying lower MR effective regurgitant orifice area, regurgitant volumes (RegVol), and ventricular volumes than men (all P ≤ 0.002). The optimal cut-off values of RegVol associated with abnormally increased left ventricular size according to reference normal values were lower in women (TTE: 67 ml, CMR: 50 ml) than in men (TTE: 77 ml, CMR: 65 ml). MR regurgitant fraction, but not RegVol, was associated in women and men with NYHA functional class III/IV, severe LA dilatation, and pulmonary hypertension (all areas under the curves, P ≤ 0.024). Conclusions: Despite having hallmarks of more advanced valvular heart disease, women with significant primary MR demonstrate lower mitral RegVol and ventricular volumes than men. In contrast, the systematic calculation of MR regurgitant fraction could standardize MR quantification irrespective of sex.

Integrating Echocardiography Parameters With Explainable Artificial Intelligence for Data-Driven Clustering of Primary Mitral Regurgitation Phenotypes.

BACKGROUND: Primary mitral regurgitation (MR) is a heterogeneous clinical disease requiring integration of echocardiographic parameters using guideline-driven recommendations to identify severe disease. OBJECTIVES: The purpose of this preliminary study was to explore novel data-driven approaches to delineate phenotypes of MR severity that benefit from surgery. METHODS: The authors used unsupervised and supervised machine learning and explainable artificial intelligence (AI) to integrate 24 echocardiographic parameters in 400 primary MR subjects from France (n = 243; development cohort) and Canada (n = 157; validation cohort) followed up during a median time of 3.2 years (IQR: 1.3-5.3 years) and 6.8 (IQR: 4.0-8.5 years), respectively. The authors compared the phenogroups' incremental prognostic value over conventional MR profiles and for the primary endpoint of all-cause mortality incorporating time-to-mitral valve repair/replacement surgery as a covariate for survival analysis (time-dependent exposure). RESULTS: High-severity (HS) phenogroups from the French cohort (HS: n = 117; low-severity [LS]: n = 126) and the Canadian cohort (HS: n = 87; LS: n = 70) showed improved event-free survival in surgical HS subjects over nonsurgical subjects (P = 0.047 and P = 0.020, respectively). A similar benefit of surgery was not seen in the LS phenogroup in both cohorts (P = 0.70 and P = 0.50, respectively). Phenogrouping showed incremental prognostic value in conventionally severe or moderate-severe MR subjects (Harrell C statistic improvement; P = 0.480; and categorical net reclassification improvement; P = 0.002). Explainable AI specified how each echocardiographic parameter contributed to phenogroup distribution. CONCLUSIONS: Novel data-driven phenogrouping and explainable AI aided in improved integration of echocardiographic data to identify patients with primary MR and improved event-free survival after mitral valve repair/replacement surgery.

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.

Clinical significance of myocardial contraction fraction in significant primary mitral regurgitation.

BACKGROUND: The optimal timing for mitral valve (MV) surgery in asymptomatic patients with primary mitral regurgitation (MR) remains a matter of debate. Myocardial contraction fraction (MCF) - the ratio of the left ventricular (LV) stroke volume to that of the myocardial volume - is a volumetric measure of LV myocardial shortening independent of size or geometry. AIM: To assess the relationship between MCF and outcome in patients with significant chronic primary MR due to prolapse managed in contemporary practice. METHODS: Clinical, Doppler-echocardiographic and outcome data prospectively collected in 174 patients (mean age 62 years, 27% women) with significant primary MR and no or mild symptoms were analysed. The impact of MCF< or ≥30% on cardiac events (cardiovascular death, acute heart failure or MV surgery) was studied. RESULTS: During an estimated median follow-up of 49 (22-77) months, cardiac events occurred in 115 (66%) patients. The 4-year estimates of survival free from cardiac events were 21±5% for patients with MCF <30% and 40±6% for those with ≥30% (P<0.001). MCF <30% was associated with a considerable increased risk of cardiac events after adjustment for established clinical risk factors, MR severity and current recommended class I triggers for MV surgery (adjusted hazard ratio: 2.33, 95% confidence interval: 1.51-3.58; P<0.001). Moreover, MCF<30% improved the predictive performance of models, with better global fit, reclassification and discrimination. CONCLUSIONS: MCF<30% is strongly associated with occurrence of cardiac events in patients with significant primary MR due to prolapse. Further studies are needed to assess the direct impact of MCF on patient management and outcomes.

Significance of Left Ventricular Ejection Time in Primary Mitral Regurgitation.

The optimal timing for mitral valve (MV) surgery in asymptomatic patients with primary mitral regurgitation (MR) remains controversial. We aimed at evaluating the relation between left ventricular ejection time (LVET) and outcome in patients with moderate or severe chronic primary MR because of prolapse. Clinical, Doppler echocardiographic, and outcome data prospectively collected from 302 patients (median age 61 [54 to 74] years, 34% women) with moderate or severe primary MR were analyzed. Patients were retrospectively stratified by quartiles of LVET. The primary end point of the study was the composite of need for MV surgery or all-cause mortality. During a median follow-up time of 66 (25th to 75th percentile, 33 to 95) months, 178 patients reached the primary end point. Patients in the lowest quartile of LVET (<260 ms) were at high risk for adverse events compared with those in the other quartiles of LVET (global p = 0.005), whereas the rate of events was similar for the other quartiles (p = NS for all). After adjustment for clinical predictors of outcome, including age, gender, history of atrial fibrillation, MR severity, and current recommended triggers for MV surgery in asymptomatic primary MR, LVET <260 ms was associated with an increased risk of events (adjusted hazard ratio 1.49, 95% confidence interval 1.03 to 2.16, p = 0.033). In conclusion, we observed that shorter LVET is associated with increased risk of adverse events in patients with moderate or severe primary MR because of prolapse. Further studies are required to investigate whether shorter LVET has a direct effect on outcomes or is solely a risk marker in primary MR.

Balloon aortic valvuloplasty for severe aortic stenosis before urgent non-cardiac surgery.

BACKGROUND: Balloon aortic valvuloplasty (BAV) has been proposed as a therapeutic option in patients suffering from severe aortic stenosis (SAS) who need urgent non-cardiac surgery (NCS). Whether this strategy is better than medical therapy in this very specific population is unknown. AIMS: We aimed to evaluate the clinical benefit of an invasive strategy (IS) with preoperative BAV in patients with SAS requiring urgent NCS. METHODS: From 2011 to 2019, a registry conducted in two centres included 133 patients with SAS undergoing urgent NCS, of whom 93 underwent preoperative BAV (IS) and 40 a conservative strategy (CS) without BAV. All analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW) (10 clinical and anatomical variables). RESULTS: The primary outcome was MACE at one-month follow-up after NCS including mortality, heart failure, and other cardiovascular outcomes. In patients managed conservatively, occurrence of MACE was 20.0% (n=8) and death was 10.0% (n=4) at 1 month. In patients undergoing BAV, the occurrence of MACE was 20.4% (n=19) and death was 5.4% (n=5) at 1 month. Among patients undergoing conservative management, all events were observed after NCS while, in patients undergoing BAV, 12.9% (n=12) had events between BAV and NCS including 3 deaths, and 7.5% (n=7) had events after NCS including 2 deaths. In IPTW propensity analyses, the incidence of the primary outcome (20.4% vs 20.0%; OR 0.93, 95% CI: 0.38-2.29) and three-month survival (89.2% vs 90.0%; IPTW-adjusted HR 0.90, 95% CI: 0.31-2.60) were similar in both groups. CONCLUSIONS: Patients with SAS managed conservatively before urgent NCS are at high risk of events. A systematic invasive strategy using BAV does not provide a significant improvement in clinical outcome.

Prognostic Importance of Left Ventricular Global Longitudinal Strain in Patients with Severe Aortic Stenosis and Preserved Ejection Fraction.

BACKGROUND: Impaired left ventricular (LV) speckle-tracking-derived global longitudinal strain (GLS) magnitude (GLS worse than 14.7%) has been associated with poor outcome in patients with severe aortic stenosis (AS) and preserved LV ejection fraction (EF). OBJECTIVES: To test the hypothesis that GLS magnitude ≤ 15% obtained with vendor-independent speckle-tracking strain software may be able to identify patients with severe AS who are at higher risk of death, despite preserved LVEF and no or mild symptoms. METHODS: GLS was retrospectively obtained in 332 patients with severe AS (aortic valve area indexed [AVAi] < 0.6 cm2/m2), no or mild symptoms, and LVEF ≥ 50%. Absolute values of GLS were collected. Survival analyses were carried out to study the impact of GLS magnitude on all-cause mortality. RESULTS: During a median follow-up period of 42 (37-46) months, 105 patients died. On multivariate analysis, and after adjustment of known clinical and/or echocardiographic predictors of outcome and aortic valve replacement as a time-dependent covariate, GLS magnitude ≤ 15% was independently associated with mortality during follow-up (all P < .01). Adding GLS magnitude ≤ 15% (adjusted hazard ratio = 1.99 [1.17-3.38], P = .011) to a multivariate model including clinical and echocardiographic variables of prognostic importance (aortic valve replacement, aortic valve area, LV stroke volume index < 30 mL/m2, and LVEF<60%) improved the predictive performance with improved global model fit, reclassification, and better discrimination. After propensity score matching (n = 196), increased risk of mortality persisted among patients with GLS magnitude ≤ 15% compared with those with GLS > 15% (hazard ratio = 2.10; 95% confidence interval, 1.20-3.68; P = .009). CONCLUSIONS: In this series of patients with severe AS, no or mild symptoms, and LVEF ≥ 50%, GLS obtained with vendor-independent speckle-tracking strain software was an effective tool to identify patients with a poor outcome. Detection of myocardial dysfunction by identifying GLS magnitude < 15% in patients with severe AS, no or mild symptoms, and LVEF ≥ 50%, can aid in risk assessment.

Correlates of the ratio of acceleration time to ejection time in patients with aortic stenosis: An echocardiographic and computed tomography study.

BACKGROUND: An increased acceleration time to ejection time (AT/ET) ratio is associated with increased mortality in patients with aortic stenosis (AS). AIM: To identify the factors associated with an increased AT/ET ratio. METHODS: The relationships between the AT/ET ratio and clinical and Doppler echocardiographic variables of interest in the setting of AS were analysed retrospectively in 1107 patients with AS and preserved left ventricular (LV) ejection fraction (LVEF). The computed tomography aortic valve calcium (CT-AVC) score was studied in a subgroup of 342 patients. RESULTS: In the univariate analysis, the AT/ET ratio was found to correlate with peak aortic jet velocity (r=0.57; P<0.0001), mean pressure gradient (r=0.60; P<0.0001), aortic valve area (r=-0.50; P<0.0001) and CT-AVC score (r=0.24; P<0.0001). The AT/ET ratio had good accuracy in predicting a peak aortic jet velocity≥4 m/s, a mean pressure gradient≥40mmHg and an aortic valve area≤1.0cm2, with an optimal cut-off value of 0.34. Multivariable linear regression analysis showed that presence of AS-related symptoms, decreased LV stroke volume index, LVEF, absence of diabetes mellitus, systolic blood pressure, increased LV mass index, relative wall thickness and peak aortic jet velocity were independently associated with an increased AT/ET ratio (all P<0.05). In the subgroup of patients who underwent CT-AVC scoring, the CT-AVC score was independently associated with an increased AT/ET ratio (P<0.05). CONCLUSIONS: The AT/ET ratio is related to echocardiographic and CT-AVC indices of AS severity. However, multiple intricate factors beyond the haemodynamic and anatomical severity of AS influence the AT/ET ratio, including LV geometry, function and systolic blood pressure. These findings should be considered when assessing the AT/ET ratio in patients with AS and preserved LVEF.