Factors influencing post-surgical survival in degenerative mitral regurgitation.

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 < 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.

The MIDA-Q Mortality Risk Score: A Quantitative Prognostic Tool for the Mitral Valve Prolapse Spectrum.

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 mm2) in 50%, moderate (ERO 20-40 mm2) in 25%, and severe or higher (ERO ≥40 mm2) in 25%, with mean ERO 24±24 mm2, 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 (R2 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.

Incremental Prognosis by Left Atrial Functional Assessment: The Left Atrial Coupling Index in Patients With Floppy Mitral Valves.

Background Emerging data suggest important prognostic value to left atrial (LA) characteristics, but the independent impact of LA function on outcome remains unsubstantiated. Thus, we aimed to define the incremental prognostic value of LA coupling index (LACI), coupling volumetric and mechanical LA characteristics and calculated as the ratio of left atrial volume index to tissue Doppler imaging a', in a large cohort of patients with isolated floppy mitral valve. Methods and Results All consecutive 4792 patients (61±16 years, 48% women) with isolated floppy mitral valve in sinus rhythm diagnosed at Mayo Clinic from 2003 to 2011, comprehensively characterized and with prospectively measured left atrial volume index and tissue Doppler imaging a' in routine practice, were enrolled, and their long-term survival analyzed. Overall, LACI was 5.8±3.7 and was <5 in 2422 versus ≥5 in 2370 patients. LACI was independently higher with older age, more mitral regurgitation (no 3.8±2.3, mild 5.1±3.0, moderate 6.5±3.8, and severe 7.8±4.3), and with diastolic (higher E/e') and systolic (higher end-systolic dimension) left ventricular dysfunction (all P≤0.0001). At diagnosis, higher LACI was associated with more severe presentation (more dyspnea, more severe functional tricuspid regurgitation, and elevated pulmonary artery pressure, all P≤0.0001) independently of age, sex, comorbidity index, ventricular function, and mitral regurgitation severity. During 7.0±3.0 years follow-up, 1146 patients underwent mitral valve surgery (94% repair, 6% replacement), and 880 died, 780 under medical management. In spline curve analysis, LACI ≥5 was identified as the threshold for excess mortality, with much reduced 10-year survival under medical management (60±2% versus 85±1% for LACI <5, P<0.0001), even after comprehensive adjustment (adjusted hazard ratio, 1.30 [95% CI, 1.10-1.53] for LACI ≥5; P=0.002). Association of LACI ≥5 with higher mortality persisted, stratifying by mitral regurgitation severity of LA enlargement grade (all P<0.001) and after propensity-score matching (P=0.02). Multiple statistical methods confirmed the significant incremental predictive power of LACI over left atrial volume index (all P<0.0001). Conclusions LA functional assessment by LACI in routine practice is achievable in a large number of patients with floppy mitral valve using conventional Doppler echocardiographic measurements. Higher LACI is associated with worse clinical presentation, but irrespective of baseline characteristics, LACI is strongly, independently, and incrementally determinant of outcome, demonstrating the crucial importance of LA functional response to mitral valve disease.

Functional Mitral Regurgitation Outcome and Grading in Heart Failure With Reduced Ejection Fraction.

OBJECTIVES: This study aims to define excess-mortality linked to functional mitral regurgitation (FMR) quantified in routine-practice. BACKGROUND: Appraisal of FMR in heart failure with reduced ejection fraction (HFrEF) is challenging because risks of excess mortality remain uncertain and guidelines diverge. METHODS: Cases of HFrEF (ejection-fraction <50%) Stage B-C that were diagnosed between 2003 and 2011 and had routine-practice FMR quantitation (FMR cohort, n = 6,381) were analyzed for excess mortality thresholds/rates within the cohort and in comparison to the general population. These were also compared to those of a degenerative mitral regurgitation (DMR) simultaneous cohort (DMR cohort, n = 2,416). RESULTS: In the FMR cohort (age: 70 ± 11 years, ejection fraction: 36 ± 10%, effective regurgitant orifice area [EROA]: 0.09 ± 0.13 cm2), EROA distribution was skewed towards low-values (≥0.40 cm2 in only 8% vs 38% for the DMR cohort; P < 0.0001). One-year mortality was high (15.6%), increasing steeply from 13.3% without FMR to 28.5% with EROA ≥0.30 cm2 (adjusted odds ratio: 1.57 [95% CI: 1.19-2.97]; P = 0.001). In the long term, 3,538 FMR cohort patients died with excess mortality threshold ∼0.10 cm2 (vs ∼0.20 cm2 in the DMR cohort), with 0.10 cm2 EROA increments independently associated with considerable mortality increment (adjusted HR: 1.11 [95% CI: 1.08-1.15]; P < 0.0001) and with no detectable interaction. Compared to the general population, FMR excess mortality increased exponentially with higher EROA (risk ratio point estimates 2.8, 3.8, and 5.1 at EROA 0.20, 0.30, and 0.40 cm2, respectively), and was much steeper than that of the DMR cohort (P < 0.0001). In nested models, individualized EROA was the strongest FMR survival marker, and a new expanded FMR grading scale based on 0.10 cm2 EROA increments provided incremental power over current American Heart Association-American College of Cardiology/European Society of Cardiology guidelines (all P < 0.03). CONCLUSIONS: In HFrEF, FMR is skewed towards smaller EROA. Nevertheless, when measured in routine practice, EROA is the strongest independent FMR determinant of survival after diagnosis. Excess mortality increases exponentially above the threshold of 0.10 cm2, with a much steeper slope than in DMR, for any EROA increment. An expanded EROA-based stratification, superior to existing grading schemes in determining survival, should allow guideline harmonization.

The Mitral Annular Disjunction of Mitral Valve Prolapse: Presentation and Outcome.

OBJECTIVES: The aim of this study was to assess in patients with mitral valve prolapse (MVP) mitral annular disjunction (MAD) prevalence, phenotypic characteristics, and long-term outcomes (clinical arrhythmic events and excess mortality). BACKGROUND: Clinical knowledge regarding MAD of MVP remains limited and controversial, and its potential link with untoward outcomes is unsubstantiated. METHODS: A cohort of 595 (278 women, mean age 61 ± 16 years) consecutive patients with isolated MVP, with comprehensive clinical, rhythmic, Doppler echocardiographic, and consistent MAD assessment, were examined. MAD prevalence, associated MVP phenotypes, and outcomes (survival, clinical arrhythmic events) starting at diagnostic echocardiography were analyzed. To balance important baseline differences, propensity scoring matching was conducted among patients with and those without MAD. RESULTS: The presence of MAD was common (n = 186 [31%]) in patients with MVP, generally in younger patients, and was not random but was independently associated with severe myxomatous disease involving bileaflet MVP and marked leaflet redundancy (both P ≤ 0.0002). The presence of MAD was also independently associated with a larger left ventricle (P = 0.005). Age-matched cohort survival after MVP diagnosis was not worse with MAD (10-year survival 93% ± 2% for patients without MAD and 97% ± 1% for those with MAD; P = 0.40), even adjusted comprehensively for MVP characteristics (P = 0.80) and accounting for time-dependent mitral surgery (P = 0.60). During follow-up, 170 patients had clinical arrhythmic events (ventricular tachycardia, n = 159; arrhythmia ablation, n = 14; cardioverter-defibrillator implantation, n = 14; sudden cardiac death, n = 3). MAD was independently associated with higher risk for arrhythmic events (adjusted HR: 2.60; 95% CI: 1.87-3.62; P < 0.0001). The link between MAD and arrhythmic events persisted with time-dependent mitral surgery (adjusted HR: 2.54; 95% CI: 1.84-3.50; P < 0.0001), was strong under medical management (adjusted HR: 3.21; 95% CI: 2.03-5.06; P < 0.0001) but was weaker after mitral surgery (adjusted HR: 2.07; 95% CI: 1.24-3.43; P = 0.005). CONCLUSIONS: This large cohort with MVP comprehensively characterized shows that MAD is frequent at MVP diagnosis and is strongly linked to advanced myxomatous degeneration. The presence of MAD was independently associated with long-term excess incidence of clinical arrhythmic events. However, within the first 10 years post-diagnosis, MAD was not linked to excess mortality, and although reassurance should be provided from the survival point of view, careful monitoring for arrhythmias is in order for MAD.

Diffuse 18F-FDG PET/CT Uptake of the Bilateral Atrial Walls in Atrioventricular Nodal Re-entrant Tachycardia.

ABSTRACT: An 84-year-old man was referred for the evaluation of a suspected gastrointestinal neoplasia. 18F-FDG PET/CT scan was performed showing, in addition to the physiological myocardial FDG uptake in the left ventricular wall, an unusual diffuse FDG uptake of the bilateral atrial walls. During his visit to the nuclear medicine unit, the patient became unwell, and an ECG was performed, suggestive of an atrioventricular nodal re-entrant tachycardia. Our case highlights the importance of including supraventricular arrhythmia such as atrioventricular nodal re-entrant tachycardia in the differential diagnosis of atrial FDG uptake.

Presentation and Outcome of Arrhythmic Mitral Valve Prolapse.

BACKGROUND: Mitral valve prolapse (MVP) is often considered benign but recent suggestion of an arrhythmic MVP (AMVP) form remains incompletely defined and uncertain. OBJECTIVES: This study determined ventricular arrhythmia prevalence, severity, phenotypical context, and independent impact on outcome in patients with MVP. METHODS: A cohort of 595 (age 65 ± 16 years; 278 women) consecutive patients with MVP and comprehensive clinical, arrhythmia (24-h Holter monitoring) and Doppler-echocardiographic characterization, was identified. Long-term outcomes were analyzed. RESULTS: Ventricular arrhythmia was frequent (43% with at least ventricular ectopy ≥5%), most often moderate (ventricular tachycardia [VT]; 120 to 179 beats/min) in 27%, and rarely severe (VT ≥180 beats/min) in 9%. Presence of ventricular arrhythmia was associated with male sex, bileaflet prolapse, marked leaflet redundancy, mitral annulus disjunction (MAD), a larger left atrium and left ventricular end-systolic diameter, and T-wave inversion/ST-segment depression (all p ≤ 0.001). Severe ventricular arrhythmia was independently associated with presence of MAD, leaflet redundancy, and T-wave inversion/ST-segment depression (all p < 0.0001) but not with mitral regurgitation severity or ejection fraction. Overall mortality after arrhythmia diagnosis (8 years; 13 ± 2%) was strongly associated with arrhythmia severity (8 years; 10 ± 2% for no/trivial, 15 ± 3% for mild and/or moderate, and 24 ± 7% for severe arrhythmia; p = 0.02). Excess mortality was substantial for severe arrhythmia (univariate hazard ratio [HR]: 2.70; 95% confidence interval [CI]: 1.27 to 5.77; p = 0.01 vs. no/trivial arrhythmia), even after it was comprehensively adjusted, including for MVP characteristics (adjusted HR: 2.94; 95% CI: 1.36 to 6.36; p = 0.006) and by time-dependent analysis (adjusted HR: 3.25; 95% CI: 1.56 to 6.78; p = 0.002). Severe arrhythmia was also associated with higher rates of mortality, defibrillator implantation, VT ablation (adjusted HR: 4.68; 95% CI: 2.45 to 8.92; p < 0.0001), particularly under medical management (adjusted HR: 5.80; 95% CI: 2.75 to 12.23; p < 0.0001), and weakly post-mitral surgery (adjusted HR: 3.69; 95% CI: 0.93 to 14.74; p = 0.06). CONCLUSIONS: In this large cohort of patients with MVP, ventricular arrhythmia by Holter monitoring was frequent but rarely severe. AMVP was independently associated with phenotype dominated by MAD, marked leaflet redundancy, and repolarization abnormalities. Long-term severe arrhythmia was independently associated with notable excess mortality and reduced event-free survival, particularly under medical management. Therefore, AMVP is a clinical entity strongly associated with outcome and warrants careful risk assessment and well-designed clinical trials.

Functional tricuspid regurgitation of degenerative mitral valve disease: a crucial determinant of survival.

AIMS: To assess functional tricuspid regurgitation (FTR) determinants, consequences, and independent impact on outcome in degenerative mitral regurgitation (DMR). METHODS AND RESULTS: All patients diagnosed with isolated DMR 2003-2011, with structurally normal tricuspid leaflets, prospective FTR grading and systolic pulmonary artery pressure (sPAP) estimation by Doppler echocardiography at diagnosis were identified and long-term outcome analysed. The 5083 DMR eligible patients [63 ± 16 years, 47% female, ejection fraction (EF) 63 ± 7%, and sPAP 35 ± 13 mmHg] presented with FTR graded trivial in 45%, mild in 37%, moderate in 15%, and severe in 3%. While pulmonary hypertension (PHTN-sPAP ≥ 50 mmHg) was the most powerful FTR severity determinant, other strong FTR determinants were older age, female sex, lower left ventricle EF, DMR, and particularly atrial fibrillation (AFib) (all P ≤ 0.002). Functional tricuspid regurgitation moderate/severe was independently linked to more severe clinical presentation, more oedema, lower stroke volume, and impaired renal function (P ≤ 0.01). Survival (95% confidence interval) throughout follow-up [70% (69-72%) at 10 years] was strongly associated with FTR severity [82% (80-84%) for trivial, 69% (66-71%) for mild, 51% (47-57%) for moderate, and 26% (19-35%) for severe, P < 0.0001]. Excess mortality persisted after comprehensive adjustment [adjusted hazard ratio 1.40 (1.18-1.67) for moderate FTR and 2.10 (1.63-2.70) for severe FTR, P ≤ 0.01]. Excess mortality persisted adjusting for sPAP/right ventricular function (P < 0.0001), by matching [adjusted hazard ratios 2.08 (1.50-2.89), P < 0.0001] and vs. expected survival [risk ratio 1.79 (1.48-2.16), P < 0.0001]. Within 5-year of diagnosis valve surgery was performed in 73% (70-75%) and 15% (13-17%) of severe and moderate DMR and in only 26% (19-34%) and 6% (4-8%) of severe and moderate FTR. Valvular surgery improved outcome without alleviating completely higher mortality associated with FTR (P < 0.0001). CONCLUSION: In this large DMR cohort, FTR was frequent and causally, not only linked to PHTN but also to other factors, particularly AFib. Higher FTR severity is associated at diagnosis with more severe clinical presentation. Long term, FTR is independently of all confounders, associated with considerably worse mortality. Functional tricuspid regurgitation moderate and even severe is profoundly undertreated. Thus careful assessment, consideration for tricuspid surgery, and testing of new transcatheter therapy is warranted.

Prognostic Implications of Left Atrial Enlargement in Degenerative Mitral Regurgitation.

BACKGROUND: Left atrial enlargement is frequent in degenerative mitral regurgitation (DMR), but its link to outcomes remains unproven in routine clinical practice. OBJECTIVES: The purpose of this study was to assess whether left atrial volume index (LAVI) measured in routine clinical practice of multiple sonographers/cardiologists is associated independently with DMR survival. METHODS: A cohort of 5,769 (63 ± 16 years, 47% women) consecutive patients with degenerative mitral valve disease, in whom LAVI was prospectively measured, was enrolled and the long-term survival was analyzed. RESULTS: LAVI (43 ± 24 ml/m2) was widely distributed (<40 ml/m2 in 3,154 patients, 40 to 59 ml/m2 in 1,606, and ≥60 ml/m2 in 1,009). Overall survival throughout follow-up (10-year 66 ± 1%) was strongly associated with LAVI (79 ± 1% vs. 65 ± 2% and 54 ± 2% for LAVI <40, 40 to 59, and ≥60 ml/m2, respectively; p < 0.0001) even after comprehensive adjustment, including for DMR severity (adjusted hazard ratio [HR]: 1.05 [95% confidence interval (CI): 1.03 to 1.08] per 10 ml/m2; p < 0.0001). Mortality under medical management was profoundly affected by LAVI (adjusted HR: 1.07 [95% CI: 1.04 to 1.10] per 10 ml/mm2 and 1.55 [95% CI: 1.31 to 1.84] for LAVI ≥60 ml/m2 vs. <40 ml/m2; both p < 0.0001) incrementally to adjusting variables (p < 0.0001) and in all subgroups, particularly sinus rhythm (adjusted HR: 1.25 [95% CI: 1.21 to 1.28]) or atrial fibrillation (adjusted HR: 1.10 [95% CI: 1.06 to 1.13] per 10 ml/m2; both p < 0.0001). Thresholds of excess mortality in spline curve analysis were approximated at 40 ml/m2 in all subgroups. Survival markedly improved after mitral surgery (time-dependent adjusted HR: 0.43 [95% CI: 0.36 to 0.53]; p < 0.0001) but remained modestly linked to LAVI (10-year survival 85 ± 3% vs. 86 ± 2% and 75 ± 3% for LAVI <40, 40 to 59, and ≥60 ml/m2, respectively; p < 0.0001). CONCLUSIONS: The frequent left atrial enlargement of DMR as measured by LAVI in routine practice displays, overall and in all subsets, a powerful, incremental, and independent link to excess mortality, which is partially alleviated by mitral surgery. Hence, LAVI measurement should be part of routine DMR evaluation and the clinical decision-making process.

Diastolic Determinants of Excess Mortality in Heart Failure With Reduced Ejection Fraction.

OBJECTIVES: The objective of this study was to determine short- and long-term excess mortality associated with diastolic echocardiographic measures (primarily E/e' ratio) in patients with HF with reduced ejection fraction. BACKGROUND: In patients with heart failure (HF), Doppler echocardiography diastolic alterations are frequently but not convincingly linked to survival. Consequently, they are not included in risk-score algorithms or substantially mentioned in HF guidelines. METHODS: Consecutive patients with HF Stage B to C, diagnosed between 2003 and 2011, with ejection fraction <50%, Doppler diastolic characterization, complete clinical evaluation, and estimated pulmonary pressure, were analyzed. Outcome measure was mortality under medical management. RESULTS: The 12,421 eligible patients were 69 ± 14 years of age, 32% were women, 72% had Stage C HF, with ejection fraction 36 ± 10% and E/e' ratio of 17 ± 9. During median follow-up 4.0 (1.1 to 7.0) years, 1-year and 5-year mortality were 17 ± 0.4% and 42 ± 0.5%. E/e' ratio >20 was linked to elevated 1-year mortality (adjusted odds ratio: 1.45 [95% confidence interval (CI): 1.16 to 1.83]; p = 0.001). Long-term E/e' ratios >20 and >14 to 20 were associated with reduced survival (adjusted hazard ratio: 1.21 [95% CI: 1.07 to 1.37]; p = 0.003, and adjusted hazard ratio: 1.15 [95% CI: 1.02 to 1.29]; p = 0.02), independent of all HF characteristics and in all patients' subsets, including HF Stage B and Stage C. Guideline-based diastolic-grade algorithm also independently predicted mortality (p < 0.0001) but was definable less frequently (70%). CONCLUSIONS: In reduced ejection fraction HF, diastolic Doppler alterations entail considerable mortality independent of all presentation characteristics. Elevated E/e' ratio, associated with worse HF at diagnosis, is also, independent of presentation, linked to substantial short-term reduced survival and long-term sustained excess mortality and should be incorporated into HF risk assessment.

Excess Mortality Associated With Functional Tricuspid Regurgitation Complicating Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Functional tricuspid regurgitation (FTR) is common in heart failure with reduced ejection fraction and mostly consequent to pulmonary hypertension. However, the intrinsic clinical implications of FTR are not fully understood. METHODS: The cohort of all Mayo Clinic patients from 2003 to 2011 diagnosed with heart failure stage B-C and ejection fraction<50%, with FTR grading and systolic pulmonary artery pressure estimation by Doppler echocardiography was identified and outcomes were analyzed. Patients with pacemakers/defibrillators, organic valve disease, or previous valve surgery were excluded. The primary outcome measure was overall mortality (censored at implantation of a defibrillator, ventricular assist device, or cardiac transplantation), adjusting for clinical and echocardiographic associates with mortality and major comorbidities. RESULTS: Among 13 026 patients meeting inclusion criteria, FTR was detected in 88% (N=11 507: 33% trivial, 32% mild, 17% moderate, and 6% severe), aged 68±14 years, 35% women, ejection fraction 36±10%, systolic pulmonary artery pressure 41±14 mm Hg with 20% atrial fibrillation. Covariates independently associated with FTR included elevated systolic pulmonary artery pressure, older age, female sex, lower ejection fraction, mitral regurgitation, and atrial fibrillation (all P<0.0001). FTR was independently associated with more dyspnea, impaired kidney function, and lower cardiac output ( P<0.003 for all). For long-term outcome, higher FTR degree compared with trivial tricuspid regurgitation was independently associated with higher mortality (adjusted hazard ratios 1.09 [1.01-1.17] for mild FTR, 1.21 [1.11-1.33] for moderate FTR and 1.57 [1.39-1.78] for severe FTR); hence, 5-year survival was substantially lower with increasing severity of functional FTR, 68±1% for trivial FTR, 58±2% for mild FTR, 45±2% for moderate FTR, and 34±4% for severe FTR. CONCLUSIONS: In this large cohort of patients with heart failure with reduced ejection fraction, FTR was common and independently associated with pulmonary hypertension, atrial fibrillation, and more severe heart failure presentation. Long-term, higher FTR severity is associated with considerably worse survival, independently of baseline characteristics. Given these untoward outcomes associated with FTR in patients with heart failure with reduced ejection fraction, clinical trials should be directed at testing FTR treatment.

Clinical Outcome of Degenerative Mitral Regurgitation: Critical Importance of Echocardiographic Quantitative Assessment in Routine Practice.

BACKGROUND: Echocardiographic quantitation of degenerative mitral regurgitation (DMR) is recommended whenever possible in clinical guidelines but is criticized and its scalability to routine clinical practice doubted. We hypothesized that echocardiographic DMR quantitation, performed in routine clinical practice by multiple practitioners, predicts independently long-term survival and thus is essential to DMR management. METHODS: We included patients diagnosed with isolated mitral valve prolapse from 2003 to 2011 and any degree of mitral regurgitation quantified by any physician/sonographer in routine clinical practice. Clinical/echocardiographic data acquired at diagnosis were retrieved electronically. The end point was mortality under medical treatment analyzed by Kaplan-Meier method and proportional hazard models. RESULTS: The cohort included 3914 patients (55% male) mean age (±standard deviation) 62±17 years with left ventricular ejection fraction 63±8% and median after routinely-measured effective regurgitant orifice area (EROA) [interquartile range], 19 [0-40] mm2. During follow-up (6.7±3.1 years), 696 patients died under medical management, and 1263 underwent mitral surgery. In multivariate analysis, routinely-measured EROA was associated with mortality (adjusted hazard ratio, 1.19; 95% confidence interval, 1.13-1.24; P<0.0001 per 10 mm2) independently of left ventricular ejection fraction and end-systolic diameter, symptoms, and age/comorbidities. The association between routinely-measured EROA and mortality persisted with competitive risk modeling (adjusted hazard ratio, 1.15; 95% confidence interval, 1.10-1.20; P<0.0001 per 10 mm2), or in patients without guideline-based class I/II surgical triggers (adjusted hazard ratio, 1.19; 95% confidence interval, 1.10-1.28; P<0.0001 per 10 mm2) and in all subgroups examined (all P<0.01). Spline curve analysis showed that, compared with general population mortality, excess mortality appears for moderate DMR (EROA ≥20 mm2), becomes notable at EROA ≥30 mm2, and steadily increases with higher EROA levels (eg, higher EROA levels beyond the 40 mm2 threshold). CONCLUSIONS: Echocardiographic DMR quantitation is scalable to routine practice and is independently associated with clinical outcome. Routinely-measured EROA is strongly associated with long-term survival under medical treatment. Excess mortality versus the general population appears in the moderate DMR range and steadily increases with higher EROA. Hence, individual EROA values should be integrated into therapeutic considerations, in addition to categorical DMR grading.

Pathophysiology of Degenerative Mitral Regurgitation: New 3-Dimensional Imaging Insights.

Despite its high prevalence, little is known about mechanisms of mitral regurgitation in degenerative mitral valve disease apart from the leaflet prolapse itself. Mitral valve is a complex structure, including mitral annulus, mitral leaflets, papillary muscles, chords, and left ventricular walls. All these structures are involved in physiological and pathological functioning of this valvuloventricular complex but up to now were difficult to analyze because of inherent limitations of 2-dimensional imaging. The advent of 3-dimensional echocardiography, computed tomography, and cardiac magnetic resonance imaging overcoming these limitations provides new insights into mechanistic analysis of degenerative mitral regurgitation. This review will detail the contribution of quantitative and qualitative dynamic analysis of mitral annulus and mitral leaflets by new imaging methods in the understanding of degenerative mitral regurgitation pathophysiology.