Marsan, Nina Ajmone

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.

Abstract Background Left ventricular (LV) remodeling in patients with valvular heart disease may vary according to the type of overload (pressure vs volume) as well as patients’ characteristics and comorbidities. Different LV remodeling patterns can be defined based on either an increase in LV mass index (LVMI), relative wall thickness (RWT), or both, and have been largely studied in patients with aortic valve disease but not in patients with primary mitral regurgitation (PMR). Purpose To describe the prevalence and baseline characteristics of the different LV remodeling patterns in PMR patients undergoing mitral valve (MV) surgery, and their association with outcome. Methods Four LV remodeling patterns were identified before MV surgery according to LVMI and RWT (Fig1-a). A cutoff of >115 g/m2 in males or >95 g/m2 in females was used to define high LVMI, and >0.42 was used to define high RWT. Patients with more than mild concomitant aortic stenosis were excluded. The study outcome was all-cause mortality. Results A total of 1538 patients were included, of which 362 (23.5%) had normal LV geometry (NG), 774 (50.3%) had eccentric hypertrophy (EH), 286 (18.6%) had concentric hypertrophy (CH), and 116 (7.5%) had concentric remodeling (Fig 1-a). Compared to the NG group (Fig 2), the EH group had more females, with larger LV size and left atrial volume index (LAVI). Compared to the NG group, patients in the CH group were significantly older and had more proportion of females. Moreover, they were more symptomatic, had higher prevalence of arterial hypertension, atrial fibrillation, and worse renal function, with smaller LV end-diastolic diameters and thicker LV walls.. Compared to the NG group, the CR group included patients with significantly smaller LV cavities and thicker LV walls, but interestingly similar LAVI and systolic pulmonary pressure, suggesting that this group might represent patients with a rather acute onset MR. Of note, there was no difference among the groups as regards LV systolic dysfunction (ejection fraction ≤ 60%, P=0.314). However, patients with CH and CR had significantly worse e’ and E/e’ ratio. After a median follow-up of 6.2 years, 211 (13.7%) patients died. Kaplan-Meier analysis showed similar survival between the NG and EH groups (91.4 vs 91.6%, P = 0.964), with significantly lower survival in the CH (76.6%, P<0.001) and CR (81.9%, P=0.028) groups, compared to NG (Fig 1-b). On multivariable analysis, after correcting for all the significant variables (Fig 1-c), CH and CR patterns carried higher risk of mortality (HR 1.7, P=0.024 and 2.0, P=0.017) compared to NG, while EH carried no additional risk (P=0.768). Conclusion LV remodeling patterns help in phenotyping patients with PMR undergoing MV surgery, and are independently associated with different risks of post-operative mortality.Figure 1:Prevalence and outcome Figure 2:Baseline characteristics

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.

ABSTRACT Aims The impact of treatment for tricuspid regurgitation (TR) across different levels of left ventricular ejection fraction (LVEF) remains uncertain. This study aimed to compare the outcomes of surgical and transcatheter tricuspid valve interventions (TTVI) to conservative (medical) management across LVEF categories. Methods and results Patients with severe isolated TR from the TRIGISTRY, a multicentre international registry, were categorized based on LVEF (preserved ejection fraction [pEF]: ≥50%, mildly reduced ejection fraction [mrEF]: 41–49%, and reduced ejection fraction [rEF]: ≤40%). We assessed the impact of treatment modality and procedural success (mild-to-moderate or lower residual TR) on 2-year survival within each LVEF category. Among 2384 patients, 1383 had pEF, 400 had mrEF, and 601 had rEF. Compared to conservative management, surgery (p &lt; 0.0005) and TTVI (p &lt; 0.0001) were associated with a survival benefit in patients with pEF. No significant survival advantage was observed in patients with mrEF (p = 0.28 for both), nor in those with rEF (p = 0.76 and p = 0.22, respectively). Similar results were obtained when surgical and transcatheter interventions were grouped (p &lt; 0.0001, p = 0.17 and p = 0.29 in patients with pEF, mrEF and rEF, respectively). Patients with residual TR after TTVI exhibited a trend toward worse survival compared to those managed conservatively across all LVEF categories (p = 0.47, p = 0.33 and p = 0.008 in pEF, mrEF and rEF, respectively). Conclusions Transcatheter tricuspid valve intervention, whether surgical or transcatheter-based, was associated with improved survival in patients with pEF but not in those with mrEF or rEF. Residual TR remained a significant prognostic factor across the entire LVEF spectrum. These findings highlight the need for careful patient selection when considering TTVI in individuals with rEF.

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 Background and Aims Severe tricuspid regurgitation is associated with increased mortality rates, but benefit of its correction and ideal timing are not clearly determined. This study aimed to identify patient subsets who might benefit from the surgery. Methods In TRIGISTRY, an international cohort study of consecutive patients with severe isolated functional tricuspid regurgitation (33 centres, 10 countries), survival rates up to 10 years were compared between patients who underwent isolated tricuspid valve surgery (repair or replacement) and those conservatively managed, overall and according to TRI-SCORE category (low: ≤3, intermediate: 4–5, and high: ≥6). Results One thousand and two hundred seventeen were managed conservatively, and 551 underwent isolated tricuspid valve surgery (200 repairs and 351 replacements). TRI-SCORE distribution was 33% low, 32% intermediate, and 35% high. At 10 years, survival rates were similar between surgical and conservative management [41% vs. 36%; hazard ratio (HR) .97; 95% confidence interval (CI) .88–1.08, P = .57]. Surgery improved survival compared with conservative management in the low TRI-SCORE category (72% vs. 44%; HR .27; 95% CI .20–.37, P &lt; .0001), but not in the intermediate (36% vs. 37%; HR 1.17; 95%CI .98–1.40, P = .09) or high categories (20% vs. 24%; HR 1.06; 95% CI .91–1.25, P = .45). Both repair and replacement improved survival in the low TRI-SCORE category (84% and 61% vs. 44%; HR .11; 95% CI .06–.19, P &lt; .0001, and HR .65; 95% CI .47–.90, P = .009). Repair showed benefit in the intermediate category (59% vs. 37%; HR .49; 95% CI .35–.68, P &lt; .0001) while replacement was possibly harmful (25% vs. 37%; HR 1.43; 95% CI 1.18–1.72, P = .0002). Conclusions Higher survival rates were observed with repair than replacement and benefit of intervention declined as TRI-SCORE increased with no benefit of any type of surgery in the high TRI-SCORE category. These results emphasize the importance of timely intervention and patient selection to achieve the best outcomes and the need for randomized controlled trials.