Degenerative Mitral Regurgitation Outcomes in Asian Compared With European-American Institutions.

Background: Clinical outcome and interventional thresholds for degenerative mitral regurgitation (DMR) were developed in studies of patients at European and American institutions (EAIs), but little is known about patients at Asian institutions (AsIs). Objectives: This study sought to contrast DMR presentation/management/outcomes of AsI patients vs EAI patients. Methods: Patients with DMR due to flail leaflet from Hong Kong and Singapore (AsI cohort, n = 737) were compared with EAI patients (n = 682) enrolled in the MIDA (Mitral regurgitation International Database) registry with similar eligibility criteria. Results: AsI patients presented similar DMR lesion/consequences vs EAI patients, but they were younger, with fewer symptoms (74% vs 44% Class I), more sinus rhythm (83% vs 69%), and lower EuroSCORE II (European System for Cardiac Operative Risk Evaluation II) (0.9 ± 0.5 vs 1.4 ± 1.5; all P < 0.0001). Imaging showed smaller absolute left atrial/ventricular dimensions in AsI patients, belying cardiac dilatation with larger body surface area-indexed diameters (all P < 0.01). Surgical/interventional mitral repair was similarly predominant (90% vs 91%; P = 0.47), and early repair was similarly beneficial (for AsI patients, adjusted HR: 0.28; 95% CI: 0.16-0.49; for EAI patients, HR: 0.32; 95% CI: 0.20-0.49; both P < 0.0001). However, AsI patients underwent fewer interventions (55% ± 2% vs 77% ± 2% at 1 year; P < 0.0001) and incurred excess mortality (adjusted HR: 1.60 [95% CI: 1.13-2.27] vs EAI patients; P = 0.008) at long-term postdiagnosis. Propensity score matching (434 patient pairs), which balanced all clinical characteristics, confirmed that there was undertreatment and excess mortality in the long term in AsI patients with DMR (P < 0.0001). Conclusions: Imaging may underestimate volume overload in AsI patients due to smaller cardiac cavities related to smaller body size compared with EAI patients with similar mitral lesions and DMR severity. AsI patients enjoy similar mitral repair predominance and early intervention benefits but undergo fewer mitral interventions than EAI patients and incur subsequent excess mortality, suggesting the need to account for imaging and cultural specificity to improve DMR outcomes worldwide.

Survival loss linked to guideline-based indications for degenerative mitral regurgitation surgery.

AIMS: Operating on patients with severe degenerative mitral regurgitation (DMR) is based on ACC/AHA or ESC/EACTS-guidelines. Doubts persist on best surgical indications and their potential association with postoperative survival loss. We sought to investigate whether guideline-based indications lead to late postoperative survival loss in DMR-patients. METHODS AND RESULTS: : We analyzed outcome of 2833 patients from the MIDA-registry undergoing surgical correction of DMR. Patients were stratified by surgical indications: Class-I-trigger (symptoms, left ventricular end-systolic diameter≥40mm, or left ventricular ejection fraction<60%, n=1677), isolated-Class-IIa-trigger (atrial fibrillation [AF], pulmonary hypertension [PH], or left atrial diameter≥55mm, n=568), or no-trigger (n=588). Postoperative survival was compared after matching for clinical differences. Restricted-mean-survival time (RMST) was analyzed. During a median 8.5-year follow-up, 603 deaths occurred. Long-term postoperative survival was lower with Class-I-trigger than in Class-IIa-trigger and no-trigger (71.4±1.9%, 84.3±2.3%, 88.9±1.9% at 10 years, p<0.001). Having at least one Class-I-criterion led to excess mortality (p<0.001), while several Class-I-criteria conferred additional death-risk (HR:1.53, 95%CI:1.42-1.66). Isolated-Class-IIa-triggers conferred an excess mortality risk versus those without (HR:1.46, 95%CI:1.00-2.13, p=0.05). Among these patients, isolated-PH led to decreased postoperative-survival versus those without (83.7%±2.8% vs. 89.3%±1.6%, p=0.011), with the same pattern observed for AF (81.8%±5.0% vs. 88.3%±1.5%, p=0.023). According to RMST-analysis, compare to those operated on without triggers, operating on Class-I-trigger patients led to 9.4-month survival-loss (p<0.001) and operating on isolated-Class-IIa-trigger patients displayed 4.9-month survival loss (p=0.001) after 10-years. CONCLUSIONS: : Waiting for the onset of Class-I or isolated-Class-IIa-triggers before operating on DMR patients is associated with postoperative survival loss. These data encourage an early surgical-strategy.

Quantification of anatomical aortic valve area by multi-detector computed tomography: A pilot 3D-morphological modeling of the stenotic aortic valve.

BACKGROUND: Aortic-valve-stenosis (AS) is a frequent degenerative valvular-disease and carries dismal outcome under-medical-treatment. Transvalvular pressure gradient reflects severity of the valve-disease but is highly dependent on flow-conditions and on other valvular/aortic characteristics. Alternatively, aortic-valve-area (AVA) represents a measure of aortic-valve lesion severity conceptually essential and practically widely-recognized but exhibits multiple-limitations. METHODS: We analyzed the 4D multi-detector computed tomography(MDCT) of 20 randomly selected patients with severe AS. For each-patient, we generated the 3D-model of the valve and of its calcifications, and we computed the anatomical AVA accounting for the 3D-morphology of the leaflets in three-different-ways. Finally, we compared our results vs. Doppler-based AVAE measurements and vs. 2D-planimetric AVA-measurements. RESULTS: 3D-reconstruction and identification of the cusps were successful in 90% of the cases. The calcification patterns where highly-variable over patients, ranging from multiple small deposits to wide and c-shaped deposits running from commissure-to-commissure. AVAE was 82 ± 15 mm2. When segmenting 18 image planes, AVATight, AVAProj-Ann, AVAProj-Tip and their average AVAAve were equal to 80 ± 16, 88 ± 20, 93 ± 21 and 87 ± 19 mm2, respectively, while AVAPlan was equal to 143 ± 50 mm2. Linear-regression of the three measurements vs. AVAE yielded regression slopes equal to 1.26, 1.13 and 0.93 for AVAProj-Ann, AVAProj-Tip and AVATight, respectively. The respective Pearson-coefficients were 0.85,0.86 and 0.90. Conversely, when comparing AVAPlan vs. AVAE, linear regression yielded a slope of 1.73 and a Pearson coefficient of 0.53. CONCLUSIONS: We described a new-method to obtain a set of flow-independent quantifications that complement pressure gradient measurements and combine the advantages of previously proposed methods, while bypassing the corresponding-limitations.

Indexing left ventricular end-systolic dimension to body size: Association with mortality in patients with degenerative mitral regurgitation.

AIMS: In patients with degenerative mitral regurgitation (DMR), left ventricular (LV) dysfunction is associated with increased risk of heart failure and excess mortality. LV end-systolic diameter (LVESD) is an established trigger for intervention, yet recommended LVESD thresholds apply poorly to patients with small body size. Whether LV normalization to body surface area (BSA) may be used as a trigger for DMR correction is unknown. We examined the link between LVESD index (LVESDi) and outcome in DMR to identify appropriate thresholds for excess mortality. METHODS AND RESULTS: This study focuses on 2753 consecutive patients with DMR due to flail leaflets diagnosed in tertiary centres from Europe and the United States, with prospective echocardiographic measurement of LVESD and BSA and long-term follow-up. The primary endpoint was mortality after diagnosis under conservative management. Secondary endpoints were mortality under conservative and surgical management and postoperative mortality of patients who underwent surgery. The optimal LVESDi cut-off for mortality prediction was 20 mm/m2. Irrespective of management type, 10-year survival was lower with LVESDi ≥20 mm/m2 than with LVESDi <20 mm/m2 (both p < 0.001). After covariate adjustment, LVESDi ≥20 mm/m2 was independently predictive of mortality under conservative management (adjusted hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.15-1.75), and with conservative and surgical management (adjusted HR 1.34, 95% CI 1.17-1.54). LVESDi remained associated with poorer postoperative outcome in patients who underwent intervention. LVESDi showed higher incremental predictive value over the baseline model compared to LVESD. The association between LVESDi ≥20 mm/m2 and outcome was consistent in subgroups of patients with DMR. CONCLUSIONS: In severe DMR due to flail leaflets, LVESDi is a marker of risk additive and incremental to LVESD. Its use in clinical practice should lead to earlier referral to mitral valve surgery and improved long-term outcome.

Reappraisal of the Concept and Implications of Pulmonary Hypertension in Degenerative Mitral Regurgitation.

BACKGROUND: European and U.S. clinical guidelines diverge regarding pulmonary hypertension (PHTN) in degenerative mitral regurgitation (DMR). Gaps in knowledge underpinning these divergences affect risk assessment and management recommendations attached to systolic pulmonary pressure (SPAP) in DMR. OBJECTIVES: This study sought to define PHTN links to DMR severity, prognostic thresholds, and independent outcome impact in a large quantitative DMR registry. METHODS: This study gathered a large multicentric registry of consecutive patients with isolated moderate-to-severe DMR, with DMR and SPAP quantified prospectively at diagnosis. RESULTS: In 3,712 patients (67 ± 15 years, 36% women) with ≥ moderate-to-severe DMR, effective regurgitant orifice (ERO) was 0.42 ± 0.19 cm2, regurgitant volume 66 ± 327 mL/beat and SPAP 41 ± 16 mm Hg. Spline-curve analysis showed excess mortality under medical management emerging around SPAP 35 mm Hg and doubling around SPAP 50 mm Hg. Accordingly, severe pulmonary hypertension (sPHTN) (SPAP ≥50 mm Hg) was detected in 916 patients, moderate pulmonary hypertension (mPHTN) (SPAP 35-49 mm Hg) in 1,128, and no-PHTN (SPAP <35 mm Hg) in 1,668. Whereas SPAP was strongly associated with DMR-ERO, nevertheless excess mortality with sPHTN (adjusted HR: 1.65; 95% CI: 1.24-2.20) and mPHTN (adjusted HR: 1.44; 95% CI: 1.11-1.85; both P ≤ 0.005) was observed independently of ERO and all baseline characteristics and in all patient subsets. Nested models demonstrated incremental prognostic value of mPHTN and sPHTN (all P < 0.0001). Despite higher operative risk with mPHTN and sPHTN, DMR surgical correction was followed by higher survival in all PHTN ranges with strong survival benefit of early surgery (<3 months). Postoperatively, excess mortality was abolished (P ≥ 0.30) in mPHTN, but only abated in sPHTN. CONCLUSIONS: This large international registry, with prospectively quantified DMR and SPAP, demonstrates a Doppler-defined PHTN impact on mortality, independent of DMR severity. Crucially, it defines objectively the new and frequent mPHTN range, independently linked to excess mortality under medical management, which is abolished by DMR correction. Thus, at DMR diagnosis, Doppler-SPAP measurement defining these new PHTN ranges, is crucial to guiding DMR management.

Prognostic Value of Aortic Valve Calcification in Nonsevere Aortic Stenosis with Preserved Ejection Fraction.

BACKGROUND: Aortic valve calcification(AVC) is prognostic in patients with aortic stenosis(AS). We assessed the AVC prognostic value in nonsevere AS patients. METHODS AND RESULTS: We conducted a retrospective study of 395 patients with nonsevere AS, LV ejection fraction ≥50%. The Agatston method was used for computed tomography AVC assessment. The log-rank test determined the best AVC cutoffs for survival under medical surveillance: 1185 AU in men and 850 in women, lower than the established-cutoffs for severe AS(2064AU in men and 1274 in women). Patients were divided into three AVC groups based on these cutoffs: low(<1185 AU men and <850 women), sub-severe(1185-2064AU men and 850-1274 women) and severe(>2064AU men and >1274 women). Of 395 patients(mean age 73 ± 12 years, 60.5% men, aortic valve area 1.23 ± 0.30cm2, mean pressure gradient 28 ± 8 mmHg), 218 underwent aortic valve intervention(AVI) and 158 deaths occurred during follow-up, 82 before AVI. Median survival time under medical surveillance was 2.1[0.7-4.9]years. Compared to the low AVC group, both sub-severe and severe AVC groups had higher risk for all-cause death under medical surveillance after comprehensive adjustment including echocardiographic AS severity and coronary artery calcium score(all p ≤ 0.006); while mortality risk was similar between sub-severe and severe AVC groups(all p ≥ 0.2). This mortality risk pattern persisted in the overall survival analysis after adjustment for AVI. AVI was protective of all-cause death in the sub-severe and severe AVC(all p ≤ 0.01), but not in the low AVC groups. CONCLUSIONS: Sub-severe AVC is a robust risk-stratification parameter in patients with nonsevere AS and may inform AVI timing.

Resumen: Consenso internacional para la nomenclatura y clasificación de la válvula aórtica bicúspide congénita y su aortopatía, con fines clínicos, quirúrgicos, intervencionistas y de investigación / Summary: International consensus statement on nomenclature and classification of the congenital bicuspid aortic valve and its aortopathy, for clinical, surgical, interventional and research purposes

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Abstract This consensus of nomenclature and classification for congenital bicuspid aortic valve and its aortopathy is evidence-based and intended for universal use by physicians (both pediatricians and adults), echocardiographers, advanced cardiovascular imaging specialists, interventional cardiologists, cardiovascular surgeons, pathologists, geneticists, and researchers spanning these areas of clinical and basic research. In addition, as long as new key and reference research is available, this international consensus may be subject to change based on evidence-based data1.

Technical and Clinical Outcomes After Transcatheter Edge-to-Edge Repair of Mitral Regurgitation in Male and Female Patients: Is Equality Achieved?

BACKGROUND: Currently, no clear impact of sex on short- and long-term survival following transcatheter edge-to-edge mitral valve repair (TEER) is evident, although no data are available on postprocedural life expectancy. Our aim was to assess sex-specific differences in outcomes of patients with mitral regurgitation (MR) treated by TEER. METHODS AND RESULTS: Short-term and 5-year outcomes in men and women undergoing TEER between 2011 and 2018 who were included in the large, multicenter, real-world MitraSwiss registry were analyzed. Outcomes were compared stratified by sex and according to MR cause (primary versus secondary). The impact of TEER on postprocedural life expectancy was estimated by relative survival analysis. Among 1142 patients aged 60 to 89 years, 39.8% were women. They were older, with fewer cardiovascular risk factors and lower functional capacity compared with men. Thirty-day mortality was higher in men than in women (3.3% versus 1.1%; odds ratio, 3.16 [95% CI, 1.16-10.7]; P=0.020). Five-year survival was comparable in both sexes (adjusted hazard ratio for 5-year mortality in men, 1.14 [95% CI, 0.90-1.44], P=0.275). Both men and women with either primary or secondary MR showed similar clinical efficacy over time. TEER provided high relative survival estimates among all groups, and fully restored predicted life expectancy in women with primary MR (5-year relative survival estimate, 97.4% [95% CI, 85.5-107.0]). CONCLUSIONS: TEER is not associated with increased short-term mortality in women, whereas 5-year outcomes are comparable between sexes. Moreover, TEER completely restored normal life expectancy in women with primary MR. A residual excess mortality persists in secondary MR, independently of sex.

Degenerative mitral regurgitation due to flail leaflet: sex-related differences in presentation, management, and outcomes.

BACKGROUND AND AIMS: Presentation, outcome, and management of females with degenerative mitral regurgitation (DMR) are undefined. We analysed sex-specific baseline clinical and echocardiographic characteristics at referral for DMR due to flail leaflets and subsequent management and outcomes. METHODS: In the Mitral Regurgitation International Database (MIDA) international registry, females were compared with males regarding presentation at referral, management, and outcome (survival/heart failure), under medical treatment, post-operatively, and encompassing all follow-up. RESULTS: At referral, females (n = 650) vs. males (n = 1660) were older with more severe symptoms and higher MIDA score. Smaller cavity diameters belied higher cardiac dimension indexed to body surface area. Under conservative management, excess mortality vs. expected was observed in males [standardized mortality ratio (SMR) 1.45 (1.27-1.65), P < .001] but was higher in females [SMR 2.00 (1.67-2.38), P < .001]. Female sex was independently associated with mortality [adjusted hazard ratio (HR) 1.29 (1.04-1.61), P = .02], cardiovascular mortality [adjusted HR 1.58 (1.14-2.18), P = .007], and heart failure [adjusted HR 1.36 (1.02-1.81), P = .04] under medical management. Females vs. males were less offered surgical correction (72% vs. 80%, P < .001); however, surgical outcome, adjusted for more severe presentation in females, was similar (P ≥ .09). Ultimately, overall outcome throughout follow-up was worse in females who displayed persistent excess mortality vs. expected [SMR 1.31 (1.16-1.47), P < .001], whereas males enjoyed normal life expectancy restoration [SMR 0.92 (0.85-0.99), P = .036]. CONCLUSIONS: Females with severe DMR were referred to tertiary centers at a more advanced stage, incurred higher mortality and morbidity under conservative management, and were offered surgery less and later after referral. Ultimately, these sex-related differences yielded persistent excess mortality despite surgery in females with DMR, while males enjoyed restoration of life expectancy, warranting imperative re-evaluation of sex-specific DMR management.

Tricuspid Valve Leaflets-Lead Interaction: Adjunctive Role of Functional Cardiac Computed Tomography for Clinical Decision Making.

The diagnostic approach toward the management of cardiac implantable electronic device-related tricuspid regurgitation is challenging and undefined. Functional cardiac computed tomography angiography provides a complementary role to echocardiography in the evaluation of lead-leaflet interaction which can help the clinical decision-making process, as presented in this case series.

Sex-Specific Left Ventricular and Aorta Size Cut-Off Values for Hemodynamically Significant Chronic Aortic Regurgitation　- Implications for Treatment in Asian Populations.

BACKGROUND: There are no sex-specific guidelines for chronic aortic regurgitation (AR). This retrospective study examined sex-specific differences and propose treatment criteria from an Asian AR cohort.Methods and Results: Consecutive 1,305 patients with moderate-severe AR or greater at 3 tertiary centers in Taiwan and Japan (2008-2022) were identified. Study endpoints were aortic valve surgery (AVS), all-cause death (ACD), and cardiovascular death (CVD). The median follow up was 3.9 years (interquartile range 1.3-7.1 years). Compared with men (n=968), women (n=337) were older, had more advanced symptoms, more comorbidities, larger indexed aorta size (iAortamax) and indexed left ventricular (LV) end-systolic dimension (LVESDi; P<0.001 for all). Symptomatic status was poorly correlated with the degree of LV remodeling in women (P≥0.18). Women received fewer AVS (P≤0.001) and men had better overall 10-year survival (P<0.01). Ten-year post-AVS survival (P=0.9) and the progression of LV remodeling were similar between sexes (P≥0.16). Multivariable determinants of ACD and CVD were age, advanced symptoms, iAortamax, LV ejection fraction (LVEF), LVESDi, LV end-systolic volume index (LVESVi), and Taiwanese ethnicity (all P<0.05), but not female sex (P≥0.05). AVS was associated with better survival (P<0.01). Adjusted LVEF, LVESDi, LVESVi, and iAortamaxcut-off values for ACD were 53%, 24.8 mm/m2, 44 mL/m2, and 25.5 mm/m2, respectively, in women and 52%, 23.4 mm/m2, 52 mL/m2, and 23.2 mm/m2, respectively, in men. CONCLUSIONS: Early detection and intervention using sex-specific cut-off values may improve survival in women with AR.

Prognostic Implications of Residual Tricuspid Regurgitation Grading After Transcatheter Tricuspid Valve Repair.

BACKGROUND: The safety profile of transcatheter tricuspid valve (TTV) repair techniques is well established, but residual tricuspid regurgitation (TR) remains a concern. OBJECTIVES: The authors sought to assess the impact of residual TR severity post-TTV repair on survival. METHODS: We evaluated the survival rate at 2 years of 613 patients with severe isolated functional TR who underwent TTV repair in TRIGISTRY according to the severity of residual TR at discharge using a 3-grade (mild, moderate, and severe) or 4-grade scheme (mild, mild to moderate, moderate to severe, and severe). RESULTS: Residual TR was none/mild in 33%, moderate in 52%, and severe in 15%. The 2-year adjusted survival rates significantly differed between the 3 groups (85%, 70%, and 44%, respectively; restricted mean survival time [RMST]: P = 0.0001). When the 319 patients with moderate residual TR were subdivided into mild to moderate (n = 201, 33%) and moderate to severe (n = 118, 19%), the adjusted survival rate was also significantly different between groups (85%, 80%, 55%, and 44%, respectively; RMST: P = 0.001). Survival was significantly lower in patients with moderate to severe residual TR compared to patients with mild to moderate residual TR (P = 0.006). No difference in survival rates was observed between patients with no/mild and mild to moderate residual TR (P = 0.67) or between patients with moderate to severe and severe residual TR (P = 0.96). CONCLUSIONS: The moderate residual TR group was heterogeneous and encompassed patients with markedly different clinical outcomes. Refining TR grade classification with a more granular 4-grade scheme improved outcome prediction. Our results highlight the importance of achieving a mild to moderate or lower residual TR grade during TTV repair, which could define a successful intervention.

Mitral Annular Disjunction in the Context of Mitral Valve Prolapse: Identifying the At-Risk Patient.

Mitral annular disjunction (MAD), a separation between the left atrium/mitral valve annulus and the left ventricular myocardium, is frequently seen in patients with arrhythmic mitral valve prolapse. Although an association exists between MAD and ventricular arrhythmias, little is known regarding the identification of individuals at high risk. Multimodality imaging including echocardiography, computed tomography, cardiac magnetic resonance, and positron emission tomography can play an important role in both the diagnosis and risk stratification of MAD. Due to a paucity of data, clinical decision making in a patient with MAD is challenging and remains largely empirical. Although MAD itself can be corrected surgically, the prevention and treatment of associated arrhythmias may require medical therapy, catheter ablation, and an implantable cardioverter-defibrillator. Prospective data are required to define the role of implantable cardioverter-defibrillators, targeted catheter ablation, and surgical correction in selected, at-risk patients.

Atrial secondary tricuspid regurgitation: pathophysiology, definition, diagnosis, and treatment.

Atrial secondary tricuspid regurgitation (A-STR) is a distinct phenotype of secondary tricuspid regurgitation with predominant dilation of the right atrium and normal right and left ventricular function. Atrial secondary tricuspid regurgitation occurs most commonly in elderly women with atrial fibrillation and in heart failure with preserved ejection fraction in sinus rhythm. In A-STR, the main mechanism of leaflet malcoaptation is related to the presence of a significant dilation of the tricuspid annulus secondary to right atrial enlargement. In addition, there is an insufficient adaptive growth of tricuspid valve leaflets that become unable to cover the enlarged annular area. As opposed to the ventricular phenotype, in A-STR, the tricuspid valve leaflet tethering is typically trivial. The A-STR phenotype accounts for 10%-15% of clinically relevant tricuspid regurgitation and has better outcomes compared with the more prevalent ventricular phenotype. Recent data suggest that patients with A-STR may benefit from more aggressive rhythm control and timely valve interventions. However, little is mentioned in current guidelines on how to identify, evaluate, and manage these patients due to the lack of consistent evidence and variable definitions of this entity in recent investigations. This interdisciplinary expert opinion document focusing on A-STR is intended to help physicians understand this complex and rapidly evolving topic by reviewing its distinct pathophysiology, diagnosis, and multi-modality imaging characteristics. It first defines A-STR by proposing specific quantitative criteria for defining the atrial phenotype and for discriminating it from the ventricular phenotype, in order to facilitate standardization and consistency in research.