Citations

Abstract Objectives The progression of extra-mitral valve (MV) cardiac damage in patients with primary mitral regurgitation (MR) following surgical repair has not been described. We aimed to investigate the evolution of extra-MV cardiac damage after MV repair and to assess its prognostic significance. Methods Patients with severe primary MR undergoing surgical repair at 5 referral centres were included when echocardiographic follow-up assessment was available. Based on echocardiographic parameters at baseline and at a median follow-up of 7 (interquartile range [IQR] 4-11) months after MV repair, patients were hierarchically classified as follows: stage 0: no cardiac damage; stage 1: left ventricular dilatation and/or dysfunction; stage 2: left atrial dilatation and/or atrial fibrillation; stage 3: pulmonary hypertension and/or significant tricuspid regurgitation. The primary outcome was all-cause mortality. Results A total of 764 patients (mean age 62 ± 13 years, 70% men) were included. Compared to baseline, 43% improved at least 1 stage, 49% remained unchanged, and 8% worsened at least 1 stage during follow-up after MV repair. At a median follow-up of 91 months after MV repair, 94 patients (12%) died. By multivariate Cox regression analysis, after adjusting for potential confounders, extra-MV cardiac damage staging at follow-up (HR per-1-stage-increase = 1.571; P = .009) and cardiac damage evolution (improved group, HR = 0.467; P = .034; worsened group, HR = 2.481, P = .037) were independently associated with all-cause mortality and had incremental prognostic value over preprocedural assessment. Conclusions Extra-MV cardiac damage improves significantly after MV repair, and its evolution is independently associated with all-cause mortality, suggesting the importance of comparative echocardiographic assessment following MV repair to improve risk stratification.

Background Mitral valve prolapse (MVP) can be associated with ventricular arrhythmias (VA), but little is known about the relationship between VA and exercise in these patients. The aim of this study was to assess the occurrence and severity of VA during exercise tests in patients with MVP, and to explore the association between VA during exercise and the occurrence of arrhythmic events during follow-up. Methods In this multicentre study, 375 patients with MVP (58 (48–69) years, 53% male) who underwent a clinically indicated exercise test were included. Severity of VA during exercise was defined as: (1) no VA, (2) minor VA (premature ventricular contractions ≥5% or non-sustained ventricular tachycardia (nsVT) <120 beats per minute) and (3) major VA (nsVTs ≥120 beats per minute). Results During exercise test, 242 (65%) patients showed no VA, 88 (24%) minor VA and 45 (12%) major VA. Patients with minor and major VAs showed more often bileaflet prolapse and mitral annular disjunction (MAD) than patients with no VA (p<0.001). Over a median follow-up of 101 months (IQR 58–138 months), 35 patients (9%) developed a severe arrhythmic event, defined as sustained VA or ventricular fibrillation, implantation of an implantable cardioverter-defibrillator and VA ablation. At the Kaplan-Meier curve analysis, patients with major VA showed the worst arrhythmic event-free survival (log-rank p<0.001). On multivariable analysis, left ventricular end-systolic diameter, MAD and VA severity during exercise were independently associated with this outcome. Conclusions In patients with MVP, the occurrence of VA during exercise is associated with more advanced mitral valve abnormalities, including MAD, and with higher rates of severe arrhythmic events during follow-up. Performing an exercise test, combined with the clinical and echocardiographic assessments, may therefore offer important complementary information useful for patient management.

Background Left ventricular (LV) end‐systolic enlargement in severe degenerative mitral‐regurgitation (MR) is a class I surgical trigger. Whether it occurs disproportionately to less‐than‐severe MR due to mitral valve prolapse and is associated with mortality are unknown. We aimed to analyze prevalence and association with survival of disproportionate LV enlargement in less‐than‐severe MR. Methods A multicenter cohort international study enrolled 2848 consecutive patients (52% women, 69±16 years) with degenerative MR prospectively quantified and graded mild or moderate. Primary end point was survival under medical management. Secondary outcome was survival throughout follow‐up stratified by performance of early mitral surgery within 3 months postdiagnosis. Results Among LV remodeling parameters (abnormal end‐diastolic diameter, LV end‐systolic diameter [LVESD] absolute and indexed), LVESD ≥40 mm (present in 12.4%) was the sole independent associate of reduced survival (5‐year 70±3 versus 76±9%; P =0.009). LVESD ≥40 mm was independently linked to larger body surface area, effective regurgitant orifice, and left atrium, and to male sex and diabetes. With multivariable comprehensive adjustment, LVESD ≥40 mm (adjusted hazard ratio [aHR], 1.25 [95% CI, 1.005–1.53]; P =0.04) remained associated with excess mortality under medical management, even after adjustment for lowered ejection fraction (aHR, 1.49 [95% CI, 1.13–1.95]; P =0.004) and in all patient subsets. Among patients with moderate degenerative MR and LVESD ≥40 mm, 22% underwent mitral surgery within 3 months, which was associated with superior survival, even after comprehensive adjustment (aHR, 0.11 [95% CI, 0.005–0.51]; P =0.002). Conclusions Disproportionate LV enlargement in patients with less‐than‐severe degenerative MR is common, particularly with larger bodies, regurgitation, and overall cardiac remodeling. LVESD ≥40 mm is associated with worse survival independent of all baseline characteristics, even lowered ejection fraction, and represents a marker for risk stratification of patients who are generally not yet considered for medical or surgical/interventional treatment.

Abstract Aims Functional tricuspid regurgitation (FTR) associated with degenerative mitral regurgitation (DMR) accentuates the severity of heart failure and is a marker of poor prognosis. Little is known about FTR associated with asymptomatic DMR. Methods and results The study included 1249 asymptomatic patients with moderate or severe DMR from the Mitral Regurgitation International Database-Quantitative (MIDA-Q) registry (mean age 64 ± 15 years, 25% female). Despite the asymptomatic status, absent/trivial FTR was noted in only 42%, mild in 34.5%, moderate in 11%, and severe FTR in 12.5%. Patients with higher FTR grades were older and more often female and had higher EuroScore II, larger left atrial volumes, and more atrial fibrillation (all P &lt; 0.05). Patients with moderate or severe FTR had comparable 5-year survival (64 ± 4% and 65 ± 4%) and lower than patients with no/trivial FTR(96 ± 1%, P &lt; 0.001). After adjustment for key prognostic factors, including age, left ventricular dilatation and dysfunction, DMR severity, left atrial dilatation, and pulmonary hypertension, ≥moderate FTR remained a strong predictor of mortality (HR = 2.08 [1.17–3.72], P = 0.013). Sensitivity analysis showed stable impact of ≥moderate FTR among patients with/without pulmonary hypertension, in women and men and for any other subset. For patients who underwent mitral valve surgery, post-operative survival rates were similar between those with no/trivial FTR and those with ≥moderate or severe FTR (P = 0.76), suggesting that surgery could reduce the excess mortality related to preoperative FTR. Conclusions Among asymptomatic patients with significant DMR, ≥moderate FTR is frequent and independently associated with higher mortality, independently of traditional guideline-based risk factors. These findings suggest that ≥moderate FTR should lead to consideration of early mitral surgery to improve outcomes.

BACKGROUND: Patients with arrhythmogenic mitral valve prolapse syndrome are at increased risk for life-threatening ventricular arrhythmias, but studies have been limited by small sample sizes. We sought to assemble an international arrhythmogenic mitral valve prolapse syndrome registry to delineate the clinical, imaging, and treatment characteristics of patients with arrhythmogenic mitral valve prolapse syndrome who survived sudden cardiac arrest (SCA) or had sustained ventricular tachycardia (VT) or ventricular fibrillation. METHODS: In this descriptive registry, we characterized patients with arrhythmogenic mitral valve prolapse syndrome who survived SCA, sustained VT, or ventricular fibrillation. Deidentified data were abstracted locally and combined centrally. RESULTS: We included 148 patients who had SCA or VT/ventricular fibrillation. Patients had a mean age of 43.7±15.4 years; 68% were women, 73% had bileaflet prolapse, 65% had mitral annular disjunction, 67% had nonsustained VT, and 59% had inferolateral T-wave inversions. Syncope (n=54, 48%) and anterolateral T-wave inversion (n=26, 22%) were relatively common. Catheter ablation was performed in 50 (35%) patients for premature ventricular complexes and in 18 (17.7%) patients for VT. Sites of origin for arrhythmias were commonly in the papillary muscles, fascicles, mitral annulus, and inferior/inferolateral left ventricle. CONCLUSIONS: In this international descriptive registry of patients with arrhythmogenic mitral valve prolapse syndrome and SCA, patients were young, women, and had bileaflet mitral valve prolapse, mitral annular disjunction, inferolateral T-wave inversions, and nonsustained VT. A history of syncope and anterolateral T-wave inversions was relatively common in patients who survived SCA or sustained VT/ventricular fibrillation.

Background The prevalence and impact of right ventricular dysfunction (RVD) in degenerative mitral regurgitation (DMR) is unknown. We aimed to determine whether RVD assessed by echocardiography in routine clinical practice is independently associated with mortality in patients with DMR. Methods and Results We used data from the MIDA‐Q (Mitral Regurgitation International DAtabase‐Quantitative) registry, which included patients with isolated DMR due to mitral valve prolapse from January 2003 to January 2020 from 5 tertiary centers across North America, Europe, and the Middle East. A cohort of 2917 (mean age: 66 years, 70.8% male patients, follow‐up: 5.2 [3.3–8.3] years) consecutive patients with severe DMR was included and long‐term mortality was analyzed. RVD, identified in 426 (14.6%) patients, was associated with reduced 8‐year survival (55%±3% versus 77%±1%; P <0.001), overall and in all subgroups of patients, even after comprehensive adjustment including left ventricular dilatation and dysfunction, DMR severity, pulmonary pressures, and surgery (adjusted hazard ratio, 1.44 [95% CI, 1.17–1.77]; P <0.001). This excess mortality was observed under medical management (adjusted hazard ratio, 1.57 [95% CI, 1.20–2.05]; P =0.001) and after surgical correction of mitral regurgitation (adjusted hazard ratio, 1.45 [95% CI, 1.02–2.05]; P =0.039). Patients with RVD undergoing surgery within 3 months of diagnosis experienced a better 8‐year survival (73%±4% versus 43%±4%; P <0.001), even after adjustment (adjusted hazard ratio, 0.44 [95% CI, 0.29–0.67]; P <0.001) despite an increase of 1‐month postoperative mortality (7.1% versus 0.5% for patients without RVD; P <0.001). Conclusions RVD is observed in 14.6% of severe DMR and exhibits a powerful and independent association with excess mortality partially attenuated by mitral surgery. Therefore, assessment of right ventricular systolic function should be included in routine DMR evaluation and in the clinical decision‐making process.

Abstract Background The prevalence and impact of right ventricular dysfunction (RVD) in degenerative mitral regurgitation (DMR) is unknown. We aimed to determine whether RVD assessed by echocardiography in routine clinical practice is independently associated with survival in patients with DMR. Methods We used data from the Mitral Regurgitation International DAtabase-Quantitative (MIDA-Q) which included patients with isolated DMR due to mitral valve prolapse from January 2003 to January 2020 from 5 tertiary centers across North America, Europe, and the Middle East. A cohort of 4,379 (mean age: 67 years, 64.6% males, follow-up:5.3[3.3-8.2]years) consecutive patients with significant (≥moderate) DMR was included and long-term survival was analyzed. Results RVD, identified in 584(13.3%) patients, was associated with reduced 10-year survival (49±3% vs. 67±1%; p&lt;0.001), overall and in all subgroups of patients, even after comprehensive adjustment including left ventricular dilatation and dysfunction, DMR severity, pulmonary pressures and surgery (adjusted HR[95%CI]=1.55[1.31-1.84]; p&lt;0.001). This excess mortality was observed under medical management (adjusted HR[95%CI]=1.39[1.12-1.72]; p=0.003) and after surgical correction of mitral regurgitation (adjusted HR[95%CI]=1.56[1.08-2.27]; p=0.019). Patients with RVD undergoing surgery within 3 months of diagnosis experienced a better 10-year survival (73±4% vs. 38±4%; p&lt;0.001), even after adjustment (adjusted HR[95%CI]=0.53[0.35-0.81]; p=0.003) despite an increase of 1-month post-operative mortality (5% vs 2.2% for patients without RVD; p&lt;0.001). Conclusions RVD is observed in 13.3% of significant DMR and exhibits a powerful and independent association with excess mortality partially attenuated by mitral surgery. Therefore, assessment of right ventricular systolic function should be included in routine DMR evaluation and in the clinical decision-making process.determinant ans prognosis of RVD in MR

Abstract Aims Indications for surgery in patients with degenerative mitral regurgitation (DMR) are increasingly liberal in all clinical guidelines but the role of secondary outcome determinants (left atrial volume index ≥60 mL/m2, atrial fibrillation, pulmonary artery systolic pressure ≥50 mmHg and moderate to severe tricuspid regurgitation) and their impact on post-operative outcome remain disputed. Whether these secondary outcome markers are just reflective of the DMR severity or intrinsically affect survival after DMR surgery is uncertain and may have critical importance in the management of patients with DMR. To address these gaps of knowledge the present study gathered a large cohort of patients with quantified DMR, accounted for the number of secondary outcome markers and examined their independent impact on survival after surgical correction of the DMR. Methods and results The Mitral Regurgitation International DAtabase-Quantitative registry includes patients with isolated DMR from centres across North America, Europe, and the Middle East. Patient enrolment extended from January 2003 to January 2020. All patients undergoing mitral valve surgery within 1 year of registry enrolment were selected. A total of 2276 patients [65 (55–73) years, 32% male] across five centres met study eligibility criteria. Over a median follow-up of 5.6 (3.6 to 8.7) years, 278 patients (12.2%) died. In a comprehensive multivariable Cox regression model adjusted for age, EuroSCORE II, symptoms, left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LV ESD) and DMR severity, the number of secondary outcome determinants was independently associated with post-operative all-cause mortality, with adjusted hazard ratios of 1.56 [95% confidence interval (CI): 1.11–2.20, P = 0.011], 1.78 (95% CI: 1.23–2.58, P = 0.002) and 2.58 (95% CI: 1.73–3.83, P &lt; 0.0001) for patients with one, two, and three or four secondary outcome determinants, respectively. A model incorporating the number of secondary outcome determinants demonstrated a higher C-index and was significantly more concordant with post-operative mortality than models incorporating traditional Class I indications alone [the presence of symptoms (P = 0.0003), or LVEF ≤60% (P = 0.006), or LV ESD ≥40 mm (P = 0.014)], while there was no significant difference in concordance observed compared with a model that incorporated the number of Class I indications for surgery combined (P = 0.71). Conclusion In this large cohort of patients treated surgically for DMR, the presence and number of secondary outcome determinants was independently associated with post-surgical survival and demonstrated better outcome discrimination than traditional Class I indications for surgery. Randomised controlled trials are needed to determine if patients with severe DMR who demonstrate a cardiac phenotype with an increasing number of secondary outcome determinants would benefit from earlier surgery.

Background: Mitral valve prolapse (MVP) is responsible for a considerable disease burden but is widely heterogeneous. The lack of a comprehensive prognostic instrument covering the entire MVP spectrum, encompassing the quantified consequent degenerative mitral regurgitation (DMR), hinders clinical management and therapeutic trials. Methods: The new Mitral Regurgitation International Database Quantitative (MIDA-Q) registry enrolled 8187 consecutive patients (ages 63±16 years, 47% women, follow-up 5.5±3.3 years) first diagnosed with isolated MVP, without or with DMR quantified prospectively (measuring effective regurgitant orifice [ERO] and regurgitant volume) in routine practice of 5 tertiary care centers from North America, Europe, and the Middle East. The MIDA-Q score ranges from 0 to 15 by accumulating guideline-based risk factors and DMR severity. Long-term survival under medical management was the primary outcome end point. Results: MVP was associated with DMR absent/mild (ERO <20 mm 2 ) in 50%, moderate (ERO 20–40 mm 2 ) in 25%, and severe or higher (ERO ≥40 mm 2 ) in 25%, with mean ERO 24±24 mm 2 , regurgitant volume 37±35 mL. Median MIDA-Q score was 4 with a wide distribution (10%–90% range, 0–9). MIDA-Q score was higher in patients with EuroScore II ≥1% versus <1% (median, 7 versus 3; P < 0.0001) but with wide overlap (10%–90% range, 4–11 versus 0–7) and mediocre correlation ( R 2 0.18). Five-year survival under medical management was strongly associated with MIDA-Q score, 97±1% with score 0, 95±1% with score 1 to 2, 82±1% with score 3 to 4, 67±1% with score 5 to 6, 60±1% with score 7 to 8, 44±1% with score 9 to 10, 35±1% with score 11 to 12, and 5±4% with MIDA-Q score ≥13, with hazard ratio 1.31 [1.29–1.33] per 1-point increment. Excess mortality with higher MIDA-Q scores persisted after adjustment for age, sex, and EuroScore II (adjusted hazard ratio, 1.13 [1.11–1.15] per 1-point increment). Subgroup analysis showed persistent association of MIDA-Q score with mortality in all possible subsets, in particular, with EuroScore II<1% (hazard ratio, 1.08 [1.02–1.14]) or ≥1% (hazard ratio, 1.11 [1.08–1.13]) and with no/mild DMR (hazard ratio, 1.14 [1.10–1.19]) or moderate/severe DMR (hazard ratio, 1.13 [1.10–1.16], all per 1-point increment with P <0.0001). Nested-model and bootstrapping analyses demonstrated incremental prognostic power of MIDA-Q score (all P <0.0001). Conclusions: This large, international cohort of isolated MVP, with prospective DMR quantification in routine practice, demonstrates the wide range of risk factor accumulation and considerable heterogeneity of outcomes after MVP diagnosis. The MIDA-Q score is strongly, independently, and incrementally associated with long-term survival after MVP diagnosis, irrespective of presentation, and is therefore a crucial prognostic instrument for risk stratification, clinical trials, and management of patients diagnosed with all forms of MVP.