Atrial Functional Mitral Regurgitation Research Articles

The Clinical Outcome of Maze Procedure in Atrial Functional Mitral Regurgitation

The Clinical Outcome of Maze Procedure in Atrial Functional Mitral Regurgitation

Atrial functional mitral regurgitation as a marker of atrial remodeling and ablation outcomes in atrial fibrillation patients

Abstract Background Atrial fibrillation (AF) triggers a cascade of atrial remodeling processes, significantly impacting atrial function and the efficacy of ablation therapies. This remodeling fosters the development of atrial cardiomyopathy and atrial dilation, which is linked to the emergence of mitral regurgitation, paving the way for the concept of atrial functional mitral regurgitation (aFMR). Our study delves into the intricate relationship between aFMR and the electrical architecture of the atrium, specifically focusing on left atrial bipolar voltage and the prevalence and extent of low-voltage areas (LVAs) in AF patients. By exploring these associations, this research aims to deepen our understanding of the interplay between the atrial substrate alterations and the development of aFMR. Methods A total of 282 patients were enrolled, who had presented for a redo PVI procedure after experiencing AF recurrence following a previous PVI. All patients received echocardiography prior to the electrophysiological procedure. All procedures were performed using 3D mapping and radiofrequency ablation. Reconnected pulmonary veins were detected in all patients and were re-isolated. The voltage of the electroanatomical points was documented on each of the atrial walls. LVAs were calculated in selected HD maps. Patients were followed-up for one year after the blanking period. Results Our cohort comprised 282 patients, predominantly male (69.4%), with a mean age of 64 years. 56% of the patients presented with persistent AF. LA area was larger in patients with aFMR ≥ 1+ as compared to aFMR < 1+ (17.0 [14.6-19.7] vs 20.6 [16.6-24.7] cm2, p<0.001). We observed significant differences in left atrial voltage and LVA extent between patients with varying degrees of aFMR (Table 1). Upon further investigation Patients with aFMR = 1+ showed significantly lower atrial voltage compared with aFMR < 1+ yet no significant increase in LVAs area. Patients with aFMR = 2 exhibited lower average voltage amplitudes in all atrial regions and larger LVA in the posterior wall, atrial roof, and septum compared to their aFMR < 1+ counterparts. Notably, the recurrence of AF was significantly higher in the AFMR ≥ 1+ (59% vs 46% p=0.027) group within one year of follow-up. aFMR was associated with AF recurrence even after adjusting for sex, age and AF types (HR:1.517, 95% CI: 1.057-2.184, p=0.025). Conclusion The presence of aFMR in AF patients may serve as a marker of progressive atrial remodeling and the onset of left atrial cardiomyopathy, characterized by reduced atrial voltage and increased LVAs. Additionally, aFMR is linked to the outcomes of PVI, suggesting that aFMR should be considered in the decision-making process for AF therapy. Further research is needed to explore the potential reversibility of these changes.Left atrial voltage and low voltage area

A case of mitral regurgitation due to bilateral undifferentiated papillary muscles with detailed preoperative diagnosis of associated morphological abnormalities

Incomplete differentiation of the mitral valve structures during fetal life results in the papillary muscles and tendon cords becoming hypoplastic, a condition termed undifferentiated papillary muscles (UDPM). This fetal abnormality causes a group of diseases that cause mitral valve dysfunction in adult life. Here, we report a case of UDPM centered on the medial posterior apex in which detailed morphological abnormalities were diagnosed preoperatively using echocardiography and three-dimensional computed tomography (3DCT) analysis, contributing to plastic surgery.The patient was a 64-year-old man who was followed up for several years for atrial functional mitral regurgitation (MR), ultimately developing heart failure. His MR was severe, and he was referred for surgery.Echocardiography revealed restrictive tendon cords primarily in the posterior apex, abnormal muscle bundles in the lower part of the valve, and findings indicative of UDPM; this was considered the main cause of MR. The patient had surgery findings similar to the preoperative diagnosis, which greatly aided the surgery. Postoperatively, the MR was well-controlled and mild.UDPM may present as various morphologic and functional abnormalities, including partial club-shaped tendinous MR and rheumatoid mitral stenosis, which are rarely accurately diagnosed preoperatively. Detailed analysis of morphological abnormalities using 3DCT or other methods may be beneficial for a successful plasty.

Paradox of disproportionate atrial functional mitral regurgitation and survival after transcatheter edge-to-edge repair.

This study aims to assess the applicability of the mitral regurgitation (MR) proportionality concept in patients with atrial functional mitral regurgitation (aFMR) treated with transcatheter edge-to-edge repair (M-TEER). We hypothesized that patients with disproportionate MR (higher MR relative to left ventricular size) would exhibit different outcomes compared to those with proportionate MR, despite undergoing M-TEER. We retrospectively analysed 98 patients with aFMR from the EuroSMR registry who underwent M-TEER between 2008 and 2019. Patients met criteria for aFMR (normal indexed left ventricular end-diastolic volume [LVEDV], preserved left ventricular ejection fraction [LVEF]≥50% without regional wall motion abnormalities, and structurally normal mitral valves). We excluded patients with missing effective regurgitant orifice area (EROA) or LVEDV data. The primary endpoint was 2-year mortality, with an EROA/LVEDV ratio employed to differentiate disproportionate from proportionate MR. Procedural success and baseline characteristics were analysed, and multivariate Cox proportional hazards models were used to identify mortality predictors. The mean patient age was 79±7.3years, with 68.8% female, and 79% had a history of atrial fibrillation. The mean EROA was 0.27±0.14cm2, and LVEDV was 95.6±33.7mL. Disproportionate MR was identified with an EROA/LVEDV ratio >0.339cm2/100mL. While procedural success was similar in both groups, disproportionate MR was associated with a numerically higher estimate of systolic pulmonary artery pressures (sPAP) and rates of NYHA ≥III and TR≥3+. Disproportionate MR had a significant association with increased 2-year mortality (P<0.001). The EROA/LVEDV ratio and tricuspid annular plane systolic excursion (TAPSE) were independent predictors of 2-year mortality (EROA/LVEDV: HR: 1.35, P=0.010; TAPSE: HR: 0.85, P=0.020). This analysis introduces the MR proportionality concept in aFMR patients and its potential prognostic value. Paradoxically, disproportionate MR in aFMR was linked to a 1.35-fold increase in 2-year mortality post-M-TEER, emphasizing the importance of accurate preprocedural FMR characterization. Our findings in patients with disproportionate MR indicate that a high degree of aFMR with high regurgitant volumes may lead to aggravated symptoms, which is a known contributor to increased mortality following M-TEER. These results underline the need for further research into the pathophysiology of aFMR to inform potential preventative and therapeutic strategies, ensuring optimal patient outcomes.

Assessing emerging causes of mitral regurgitation: atrial functional mitral regurgitation.

Functional or secondary mitral regurgitation is linked to increased cardiovascular morbidity and mortality. From a mechanical perspective, secondary mitral regurgitation occurs due to an imbalance between the forces that tether the mitral leaflets and those that close them. This results in incomplete coaptation. Most commonly, functional mitral regurgitation, which occurs in both ischaemic and non-ischaemic disease states, is usually caused by dysfunction and changes in the left ventricle. Atrial functional mitral regurgitation (AFMR) is a disease state that has been more recently recognized. It occurs when mitral annular enlargement is associated with left atrial dilatation, preserving left ventricular geometry and function. AFMR is typically seen in patients with chronic atrial fibrillation or heart failure who have a conserved ejection fraction. Published reports and ongoing investigations vary in how they define AFMR. This publication examines the pathophysiology of AFMR and highlights the importance of having a common working standard for the definition of AFMR to ensure consistency in the data reported and to drive forward the much needed research into the outcomes and treatment strategies in this area. Several studies have reported that restrictive annuloplasty and transcatheter edge-to-edge repair can reduce mitral regurgitation and improve symptoms. This narrative review will explore the pathophysiology, echocardiographic diagnosis and treatment of AFMR.

The Natural History of Atrial Functional Mitral Regurgitation

BackgroundThe natural history of moderate/severe atrial functional mitral regurgitation (AFMR) is unknown. ObjectivesThe authors sought to study the incidence of left ventricular (LV) systolic dysfunction (LVSD), progression or regression of ≥mild-moderate AFMR, and impact on mortality. MethodsAdults with left atrial (LA) volume index ≥40 mL/m2, ≥mild-moderate AFMR, and follow-up echocardiogram were followed for incident LVSD (ejection fraction <50% and ≥10% lower than baseline), progression of mild-moderate/moderate AFMR to severe, and persistent regression of AFMR to no/trivial. Relation of AFMR progression or regression as time-dependent covariates with all-cause mortality was studied. Incidence of LVSD was compared with patients with no/mild AFMR matched on age, sex, comorbidities and ejection fraction. Patients were followed until mitral intervention, myocardial infarction, or last follow-up. ResultsA total of 635 patients (median age 75 years, 51% female, 96% mild-moderate/moderate AFMR, 4% severe AFMR) were included. Over a median 2.2 years (Q1-Q3: 1.0-4.3 years), incidence rates per 100 person-years were 3.2 for LVSD (P = 0.52 vs patients with no/mild AFMR), 1.9 for progression of AFMR, and 3.9 for regression. Female sex and larger LA volume index were independently associated with progression, whereas younger age, male sex, absent atrial fibrillation, and higher LA emptying fraction were independently associated with regression. Neither AFMR progression nor regression was independently associated with mortality. Instead, independent risk factors for mortality included older age, concentric LV geometry, and higher estimated LV filling and pulmonary pressures. ConclusionsIn patients with predominantly mild-moderate/moderate AFMR, regression of MR was more common than progression, but neither was associated with mortality. Instead, diastolic function abnormalities were more important. Over a median 2-year follow-up, LVSD risk was not increased.

Prevalence and clinical outcomes of isolated or combined moderate to severe mitral and tricuspid regurgitation in patients with cardiac amyloidosis.

Evidence on the epidemiology and prognostic significance of mitral regurgitation (MR) and tricuspid regurgitation (TR) in patients with cardiac amyloidosis (CA) is scarce. Overall, 538 patients with either transthyretin (ATTR, n = 359) or immunoglobulin light-chain (AL, n = 179) CA were included at three Italian referral centres. Patients were stratified according to isolated or combined moderate/severe MR and TR. Overall, 240 patients (44.6%) had no significant MR/TR, 112 (20.8%) isolated MR, 66 (12.3%) isolated TR, and 120 (22.3%) combined MR/TR. The most common aetiologies were atrial functional MR, followed by primary infiltrative MR, and secondary TR due to right ventricular (RV) overload followed by atrial functional TR. Patients with isolated or combined MR/TR had a more frequent history of heart failure (HF) hospitalization and atrial fibrillation, worse symptoms, and higher levels of NT-proBNP as compared to those without MR/TR. They also presented more severe atrial enlargement, atrial peak longitudinal strain impairment, left ventricular (LV) and RV systolic dysfunction, and higher pulmonary artery systolic pressures. TR carried the most advanced features. After adjustment for age, sex, CA subtypes, laboratory, and echocardiographic markers of CA severity, isolated TR and combined MR/TR were independently associated with an increased risk of all-cause death or worsening HF events, compared to no significant MR/TR [adjusted HR 2.75 (1.78-4.24) and 2.31 (1.44-3.70), respectively]. In a large cohort of patients with CA, MR, and TR were common. Isolated TR and combined MR/TR were associated with worse prognosis regardless of CA aetiology, LV, and RV function, with TR carrying the highest risk.

Functional tricuspid regurgitation and efficacy of electrical cardioversion in patients with atrial fibrillation and atrial functional mitral regurgitation.

Atrial functional mitral regurgitation (afMR) is common in patients with atrial fibrillation (AF). The presence of functional tricuspid regurgitation (fTR), which arises as a secondary effect of afMR, has the potential to impact the effectiveness of procedures aimed at restoring normal heart rhythm. In this study, we sought to evaluate the efficacy of electrical cardioversion (CVE) in AF regarding the presence and degree of fTR in patients with afMR. Retrospective analysis included 521 patients with persistent AF on optimal medical therapy undergoing CVE. 157 (30.1%) patients had afMR (characterized by left ventricle ejection fraction ≥ 50% and LA dilatation) and were divided into 2 groups: the group with fTR (107, 68.2%) and the group without fTR (50, 31.9%). Patients with afMR and fTR had a higher prevalence of metabolic syndrome (p = 0.02) and greater right atrial area (p < 0.01) compared to patients without fTR. The efficacy of CVE was lower in the group with fTR in comparison to patients with isolated afMR (82.2% vs. 94%; p = 0.048) and it was unrelated to the degree of fTR (p = 0.15) and RVSP (p = 0.56). The energy required for successful CVE was comparable regardless of the presence (p = 0.26) or severity of fTR (p = 0.94). The fTR frequently coexists with afMR and it significantly diminishes the effectiveness of CVE for treating AF. The degree of fTR does not appear to influence the efficacy of CVE.

Outcomes of transcatheter edge-to-edge repair for atrial functional mitral regurgitation.

The prognostic benefits of transcatheter edge-to-edge repair (TEER) remain unclear in patients with atrial functional mitral regurgitation (AFMR). We aimed to investigate the clinical outcomes of TEER for patients with AFMR. We retrospectively classified functional mitral regurgitation (FMR) patients undergoing TEER into those with AFMR or ventricular FMR (VFMR). A residual MR ≤1+ at discharge was considered optimal mitral regurgitation (MR) reduction, and an elevated mean mitral valve pressure gradient (MPG) was defined as an MPG ≥5 mmHg at discharge. The primary outcome was a composite of all-cause mortality and hospitalisation due to heart failure within one year. Of 441 FMR patients, 125 patients were considered as having AFMR. Residual MR ≤1+ was associated with a lower risk of the composite outcome in both AFMR and VFMR patients, while an MPG ≥5 mmHg was associated with a higher risk of the composite outcome in patients with AFMR but not with VFMR. AFMR patients with residual MR ≤1+ and an MPG ≥5 mmHg, as well as those with residual MR >1+, had a higher incidence of the composite outcome than those with residual MR ≤1+ and an MPG <5 mmHg (50.7%, 41.8%, and 14.3%, respectively; p<0.001). This association was consistent after adjustment for clinical and echocardiographic characteristics. An MR reduction to ≤1+ following TEER was associated with a lower risk of clinical outcomes in patients with AFMR, while an MPG ≥5 mmHg was related to a higher risk of clinical outcomes. Optimal MR reduction by TEER may have potential benefits on the prognosis of patients with AFMR, although the prognostic benefit may be attenuated by an elevated MPG.

Remodeling on Lateral Side of Posterior Mitral Leaflet in Recurrent Mitral Regurgitation after Mitral Annuloplasty for Patients with Atrial Functional Mitral Regurgitation

Objective. The high recurrence rate of mitral regurgitation (MR) in patients with atrial functional mitral regurgitation (AFMR) who underwent mitral annuloplasty (MAP) is reported. However, the mechanism of recurrence is not fully understood and appropriate surgical intervention remains unknown. Herein, we reviewed patients with AFMR who underwent MAP at our institution and investigated the preoperative geometric characteristics of the mitral valve in terms of MR recurrence after surgery. Methods. We retrospectively evaluated 20 patients with AFMR who underwent MAP between 2010 and 2022. The mean follow-up period was 3.2 ± 2.3 years. Preoperative three-dimensional transesophageal echocardiography (3D TEE) was available for all patients, and geometric analysis of the mitral valve was performed using the Philips Q-Lab software. Results. MR recurred in six patients. The rates of freedom from MR recurrence were 79% and 57% at one and three years, respectively. The lateral portion of the posterior mitral leaflet (PML) in patients with recurrent MR was longer and thicker than that in patients without recurrent MR (length of P1; 10 ± 3 vs. 15 ± 5 mm, p&lt;0.01, length of P2; 11 ± 4 vs. 14 ± 4 mm, p=0.23, length of P3; 8 ± 3 vs. 10 ± 3 mm, p=0.13). Conclusions. Patients with remodeling of the lateral portion of PML tended to have recurrent MR after MAP. This factor could indicate progressive remodeling, and MAP alone may not be a sufficient intervention for these patients.

Prevalence and prognostic impact of dynamic atrial functional mitral regurgitation assessed by isometric handgrip exercise.

In atrial functional mitral regurgitation (aFMR), a considerable proportion of patients displays a discrepancy between symptoms and echocardiographic findings at rest. Exercise testing plays a substantial role in assessing the haemodynamic relevance of mitral regurgitation (MR) and is recommended by current guidelines. Here, we aimed to assess the prevalence, extent, and prognostic impact of exercise-induced changes in patients with aFMR. Patients with at least mild MR who underwent handgrip exercise echocardiography at the University Hospital Duesseldorf between January 2019 and September 2021 were enrolled. Patients were followed up for 1 year to assess clinical outcomes. Eighty patients with aFMR were included [median age: 80 (77-83) years; 53.8% female]. The median N-terminal pro-brain natriuretic peptide level was 1756 (1034-3340) ng/L. At rest, half of the patients (53.8%) had mild MR, 20 patients (25.0%) had moderate MR, and 17 patients (21.2%) had severe MR. In approximately every fifth patient (17.5%) with non-severe MR at rest, the MR became severe during exercise. Handgrip exercise led to a reclassification of MR severity in 28 patients (35.0%). At 1-year follow-up, adverse events occurred more often in patients with severe MR at rest (76.5%) and exercise-induced dynamic severe MR (66.7%) than in those with non-severe MR (28.6%; P < 0.001). Handgrip exercise during echocardiography revealed exercise-induced changes in aFMR in every third patient. These data may have implications for therapeutic decision-making in symptomatic patients with non-severe aFMR at rest.

First-in-human experience with a novel transcatheter direct annuloplasty system for severe atrial functional mitral regurgitation.

First-in-human experience with a novel transcatheter direct annuloplasty system for severe atrial functional mitral regurgitation.

Atrial functional mitral regurgitation: the tip of the iceberg.

Atrial functional mitral regurgitation: the tip of the iceberg.

Handgrip echocardiography improves risk stratification in patients with atrial functional mitral regurgitation

Abstract Background In the last years, cardiologist increasingly recognize "atrial functional mitral regurgitation" (AFMR) frequently associated with heart failure with persevered ejection fraction and atrial fibrillation. Exercise echocardiography is recommended by current guidelines in patients with secondary mitral regurgitation (MR) in several clinical scenarios. However, there are no data on the prognostic impact of exercise induced AFMR yet. We hypothesise that handgrip exercise during echocardiography unravels dynamic changes of MR severity that may impact further clinical decision making. Purpose We aimed to assess the prognostic impact of isometric exercise-induced changes in patients with AFMR. Methods Patients with atrial fibrillation and at least mild AFMR who underwent handgrip exercise echocardiography between January 2019 and September 2021 were included. Patients were followed-up for one year to assess clinical outcomes. The combined endpoint included all-cause mortality, heart failure hospitalisation and mitral valve surgery/intervention. Results We included 80 patients with AFMR (median age was 80 (77-83) years; 53.8%were female). Echocardiography at rest showed mild MR in half of the patients (53.8%), moderate MR in 20 patients (25.0%), and severe MR in 17 patients (21.2%). In nearly every fifth patient (17.5%) with non-severe MR at rest, the MR became severe during exercise. Median follow-up duration was 12 months (IQR: 4-17 months). Follow-up was completed in 78 of the 80 patients (97.5%). Thirty-five patients (44.9%) experienced adverse events. Kaplan-Meier survival analysis revealed adverse clinical outcomes more often in patients with severe MR during exercise (76.9%) compared to patients with non-severe MR during exercise (33.3%)(p&amp;lt;0.001). Addition of handgrip exercise testing to echocardiographic assessment at rest improved the global chi-square (from 21.2 to 30.2) and the Harrell’s c-index (from 0.69 to 0.78) for prediction of mitral valve surgery/interventions during follow-up. Conclusions Isometric handgrip exercise testing unmasks severe MR in a significant proportion of patients with non-severe MR at rest and improves further risk stratification in these patients.

Incidence and predictors of the novo significant mitral and tricuspid regurgitation in patients with permanent atrial fibrillation

Abstract Introduction Atrial fibrillation (AF) is related to atrial remodeling and annular enlargement, which leads to functional mitral and tricuspid regurgitation. These two entities can derive in heart failure with preserved left ventricular ejection fraction (LVEF), the reason why it is becoming a rising concern in recent years. However, its incidence and predictors have not been well established. Purpose This study aimed to assess the incidence and predictors of significant atrial functional mitral and tricuspid regurgitation in patients with permanent AF. Methods The study population comprised 547 patients from a Spanish health area diagnosed with permanent AF between 2014 and 2019 (CardioCHUVI-AF registry; ClinicalTrials.gov identifier: NCT04364516). Individuals who presented with atrial enlargement at the diagnosis, primary moderate to severe valve disease, previous cardiac surgery (including valve replacement or repair), decreased LVEF, pulmonary hypertension, or right ventricular pacing that could interfere with tricuspid valve closure were excluded. The median age was 78.0 (IQ 70.4-85.6), and men represented 43% of the population (235 patients) compared to women, which represented 57% (312 patients). During a median follow-up of 3.5 years (IQ 2.03-4.95) we assessed the incidence of moderate to severe de novo mitral and tricuspid valve regurgitation and its predictors. Results The development of moderate to severe mitral and tricuspid valve regurgitation was higher after three years of diagnosis. The incidence of mitral regurgitation was 3.8 (3.0-4.9) per 100 persons/year. The incidence of tricuspid regurgitation was 5.5 (4.5-6.8) per 100 persons/year. In addition, multivariate analysis showed an association between the development of mitral regurgitation and older age (HR 1.05 [CI 95% 1.01-1.09]), female sex (HR 1.82 [CI 95% 1.1-3]) and prior admission for HF (HR 2.35 [CI 95% 1.18-4.7]). On the other hand, the development of tricuspid regurgitation did not show an association with age (HR 1.02 [CI 95% 0.97-1.05]), but it did with prior admission for HF (HR 2.11 [CI 95% 1.17-3.79]) and female sex (HR 2.17 [CI 95% 1.43-3.3]). Conclusion Permanent atrial fibrillation was associated with an increased risk of developing atrial functional mitral and tricuspid regurgitation, especially after three years of the diagnosis and in the female sex. Older age was associated with a higher incidence of mitral regurgitation. Prior admission for HF was associated with a higher incidence of tricuspid regurgitation. Based on the preceding, monitoring a specific profile of patients with atrial fibrillation may be especially important in preventing and early treating valve disease that can compromise their prognosis.Incidence of mitral regurgitationIncidence of tricuspid regurgitation

Moderate functional mitral regurgitation: difference between atrial and ventricular mechanism of the regurgitation

Abstract Background/Introduction In severe functional mitral regurgitation (MR), further distinction of the mechanism of MR in atrial functional MR (aFMR) and ventricular functional MR (vFMR) has shown prognostic importance. However, no data are available on moderate functional MR, whose characteristics and prognosis are largely unknown. Purpose To assess clinical and echocardiographic characteristics of patients with moderate aFMR and vFMR and their potential difference in outcome. Methods Patients with moderate functional MR were retrospectively included. aFMR was defined as isolated mitral annulus dilatation in combination with preserved left ventricular ejection fraction (LVEF≥50%) without ischemic heart disease or LV dilatation. Patients were classified as vFMR when LVEF was reduced, LV was dilated and/or wall motion abnormalities were present. Mitral valve intervention and all-cause mortality were used as combined endpoint. Results In total 474 patients with moderate functional MR (mean age 67 ±12, 57% male) were evaluated, of which 136 (29%) had aFMR and 338 (71%) had vFMR as underlying mechanism. Among the clinical variables, patients with aFMR had more atrial fibrillation (77% vs. 35%; p&amp;lt;0.001), were less symptomatic (NYHA class ≥ III: 6% vs. 18%; p&amp;lt;0.001) and had better renal function (eGFR 73 ±23 ml/min/1,73m2 vs. 65 ±23 ml/min/1,73m2; p=0.005) as compared to vFMR. In the vFMR group, 49% of patients had ischemic heart disease. Among the echocardiographic variables, as expected in aFMR, LVEF was higher (42 ±14% vs. 55 ±13%; p&amp;lt;0.001), while LV volumes (LV end-diastolic volume index 55 ±13 mL/m2 vs. 82 ±38 mL/m2; p&amp;lt;0.001) and E/E’ ratio were smaller (10 ±4 vs. 15 ±4; p&amp;lt;0.001) as compared to vFMR. However left atrial (LA) volume index was similar between both groups (43 ±14 mL/m2 vs. 41 ±18 mL/m2; p=0.271). For the echocardiographic measures of the right heart, significant difference was observed only for TAPSE which was higher for the aFMR group (22 ±4mm vs. 20 ±5mm; p&amp;lt;0.001). During a median follow-up of 74 months [IQR: 46.8-107.0], 132 (30%) patients died and 30 (6%) underwent mitral valve intervention. Event-free survival analysis for the combined endpoint was significantly better for aFMR patients (Figure 1). Based on significant variables from the univariable Cox regression analysis, multivariable Cox regression analysis showed that the mechanism of functional MR (with aFMR being protective as compared to vFMR), age, male gender, impaired renal function, NYHA class, severe LA dilatation and TAPSE were independently associated with the combined endpoint (Table 1). Conclusion In patients with moderate functional MR, aFMR is independently associated with better event-free survival as compared to vFMR. Therefore, clear identification of the mechanism of MR implies a better risk stratification and may be helpful for the management of patients with moderate MR.

3D atrial stiffness in chronic mitral regurgitation: impact of sex, regurgitation mechanism and valve geometry - the 3D-PRIME study

Abstract Background Chronic mitral regurgitation (MR) is both a cause and a consequence of progressive left atrial (LA) remodeling. The degree of LA stiffness in relation to clinical risk factors as well as atrio-valvular remodeling has not been reported in patients with MR. Aims To assess the severity and determinants of 3D LA stiffness in chronic MR. Methods In the prospective 3D-PRIME (3D Echocardiography and Cardiovascular Prognosis in Mitral Regurgitation) study, 100 patients with chronic MR (70±13years, 38% women, 55% with a history of atrial fibrillation (AF), 42% with severe MR) recruited at one heart valve center were investigated with 2D and 3D transthoracic and transesophageal echocardiography. MR severity was quantified by the regurgitant fraction and MR classified as primary (54%), atrial functional (26%) or ventricular functional (20%). 3D LA volume (LAV) was measured at end-diastole (min LAV) and end-systole (max LAV), and 3D LA function assessed in by the emptying fraction (EF) and the peak strain in the reservoir phase (LASr). LA stiffness was estimated from the ratio: mitral peak E-wave velocity divided by the mitral annular e’ velocity (E/e´) / LASr and classified as high for age if ≥ 0.55. Results High LA stiffness for age was present in 58% of patients and more often in those with a history of AF (73% vs. 45%) and in severe vs moderate MR (70% vs. 42%) (both p &amp;lt;0.01). Patients with high LA stiffness had larger LAVs with lower LA EF, lower right ventricular ejection fraction, increased mitral annulus area, and larger mitral valve leaflets (all p&amp;lt;0.05). Men had considerably larger LAVs in all MR subgroups, and highly stiff LAs in atrial functional MR compared to women (p &amp;lt;0.05, Figure) despite similar MR severity (regurgitation fraction 50% vs 52%, respectively). In multiple regression analysis, after stepwise removal of the following factors: MR severity, mitral leaflet to ring area ratio, and right ventricular ejection fraction, increased LA stiffness was independently associated with male sex, history of AF, lower LA EF and lower mitral intertrigonal diameter (R2 0.40, p &amp;lt;0.001, Table). Conclusion LA is stiff for age in over half of patients with chronic MR, excessively stiff in men with atrial functional MR, and associated with specific changes in mitral valve geometry and LA function. This gives mechanistic insights into the complex atrio-valvular interplay in chronic MR.Figure.Table.

Impact of transcatheter edge-to-edge repair (TEER) of mitral valve on the clinical outcomes in the management of atrial functional mitral regurgitation

Abstract Background Atrial functional mitral regurgitation (aFMR) has become a novel topic of interest. Data on the safety and efficacy of transcatheter edge-to-edge repair (TEER) of mitral valve among patients with aFMR and ventricular functional mitral regurgitation (vFMR) is scarce and limited to single center studies. Purpose We conducted a systematic review and meta-analysis to assess the safety and efficacy of TEER in the management of aFMR vs vFMR and its impact on clinical outcomes. Methods PubMed/MEDLINE, Cochrane Library and EMBASE databases were queried to identify studies comparing the efficacy of TEER between aFMR and vFMR. The primary outcome of interest was mortality at 1 year and composite of all-cause mortality and heart failure (HF) hospitalizations. Secondary outcomes included mitral regurgitation (MR) reduction, presence of residual MR, improvement in NYHA functional class, postoperatively and at 1-year. Risk ratios (RR’s) and their corresponding 95% confidence intervals (CIs) were calculated using random-effects model. Results We included a total of 3,314 patients from 6 observational studies which met the inclusion criteria (mean age 63.8 ± 3.8 years, 43% male). There were 443 aFMR patients and 2871 vFMR patients with an average follow-up of 12 months. Mortality at 1-year and the composite outcome of all-cause mortality and heart failure hospitalizations were comparable between aFMR and vFMR groups (RR 1.06; 95% CI 0.64 - 1.75; p = 0.81 and RR 0.92; 95% CI 0.75 - 1.14; p = 0.47, respectively). There were no significant differences between aFMR and vFMR groups in terms of MR reduction postoperatively (RR 0.99; 95% CI 0.96 - 1.02; p = 0.53) or at 1-year (RR 1.15; 95% CI 0.96 - 1.38; p = 0.14). Moreover, the presence of residual MR grade ≥ 3+ postoperatively (RR 1.31; 95% CI 0.83 - 2.08; p = 0.25) and at 1-year (RR 0.96; 95% CI 0.44 - 2.11; p = 0.92) was similar between aFMR and vFMR cohorts. Overall, although there was a clinical improvement in symptoms in terms of NYHA functional class at 1 year (grade ≤ 2), there was no statistical significance between the two groups (RR 1.02; 95% CI 0.93 - 1.11; p = 0.74). Conclusion This meta-analysis suggests that transcatheter edge-to-edge repair is likely to be an efficacious and safe option in patients with aFMR and vFMR. Future randomized control trials are needed to fully assess the clinical impact of this procedure in the two MR etiologies.Figure 1Figure 2

Artificial intelligence-enabled electrocardiogram in the detection of patients at risk of atrial functional mitral regurgitation

Abstract Background Atrial functional mitral regurgitation (AFMR) is an increasingly recognized cause of functional MR thought to result from left atrial enlargement and myopathy in the setting of preserved left ventricular geometry and function. AFMR mostly occurs in patients with atrial fibrillation (AF) and/or heart failure with preserved ejection fraction. Purpose We investigated whether the use of an artificial intelligence-based electrocardiogram (AI-ECG) can identify patients with new-onset AF and sinus rhythm (SR) who are at highest risk of developing AFMR. Methods Adults with a new diagnosis of AF between 2010 and 2021 who had a transthoracic echocardiogram (TTE) within 1 month after AF diagnosis were identified. Similarly, adults in SR who never had AF diagnosis and had a TTE during the same period were identified. Exclusion criteria from both groups included &amp;gt;mild MR at baseline, primary mitral valve disease, cardiomyopathy, ≥moderate aortic valve disease, current or previous low ejection fraction, enlarged left ventricle, cardiac devices, previous cardiac surgeries, and the absence of follow-up TTE ≥6 months from baseline. Only patients who had ECG within 10 days of the TTE were included. When multiple ECGs were available, the closest was considered. A previously trained AI-ECG algorithm to detect the probability of AF was utilized. Incident AFMR was defined as &amp;gt;mild functional MR in the absence of &amp;gt;mild left ventricle enlargement or dysfunction. Diastolic dysfunction was defined according to ASE/EACVI guidelines. Results Overall, 1,570 patients with new-onset AF (median age 67 years; 34% females) and 16,802 patients in SR (median age 59 years; 46% females) were included. The median AI ECG probability for AF was 43% (IQR 26%-59%) in the new-onset AF group and 2% (0.5%-7%) in the SR group, Figure 1. Incident AFMR occurred in 152 patients in the AF group over median 3.06 (IQR 1.5-5.2) years of follow-up and in 482 patients in the SR group over median 3.0 (1.5-5.6) years of follow-up. The probability of silent AF by the AI-ECG was associated with incident AFMR in the new-onset AF group [hazard ratio 1.19 (95% CI 1.11-1.28) per 10%, p &amp;lt;.001] and the SR group [hazard ratio 1.19 (95% CI 1.12-1.25) per 10%, p &amp;lt;.001]. The AI ECG-derived AF probability remained as an independent risk factor for AFMR in multivariable analysis in both AF and SR, Table 1. Conclusion The AI ECG for AF might be able to reflect the degree of left atrial myopathy and thus the risk of incident AFMR in patients with AF and SR.Distribution of AI ECG probability of AFMultivariable risk factors for AFMR

Impact of Transcatheter Edge-to-Edge Mitral Valve Repair on Atrial Functional Mitral Regurgitation from the GIOTTO Registry

Atrial functional mitral regurgitation (aFMR) has a peculiar pathophysiology that may have distinctive outcomes. We investigated the impact of transcatheter edge-to-edge repair in aFMR compared with other FMR etiologies. The GIOTTO (GIse registry Of Transcatheter treatment of MR) is a multicenter, prospective study enrolling patients with symptomatic MR treated with MitraClip up to 2020. We categorized patients with FMR as aFMR, ischemic FMR (iFMR), and nonischemic ventricular FMR (niFMR). The clinical end points were defined according to the Mitral Valve Academic Research Consortium. Of 1,153 patients, 6% had aFMR, 47% iFMR, and 47% niFMR. Patients with aFMR were older, mostly women, and had a higher atrial fibrillation rate. They had better left ventricular ejection fraction and smaller left ventricular volumes, with no difference in mitral effective regurgitant orifice area. The acute device and procedural success rates were similar among the groups. At the longest available follow-up (median 478days, interquartile range 91 to 741 days), the rate of MR ≥2+ was similar among the groups. Patients with aFMR had a lower rate of cardiovascular death and heart failure than patients with iFMR (hazard ratio [HR] 0.43, p = 0.02) and niFMR (HR 0.45, p = 0.03). The aFMR etiology remained independently associated with the composite outcome, together with postprocedural MR ≤1+ (HR 0.63, p <0.01) and peripheral arteriopathy (HR 1.82, p = 0.003). The results of this GIOTTO subanalysis suggested that aFMR is less prevalent and associated with better outcomes compared with other causes of FMR treated by transcatheter edge-to-edge repair. Postprocedural MR >1+, peripheral vasculopathy, non-aFMR were independent predictors of worse outcomes.