Citations

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Mayo Clinic Foundation Background Left atrial (LA) volume is linked to outcome in degenerative mitral regurgitation (DMR) but does not encompass LA function assessment. Thus, we ought to determine the prognostic role of left atrial coupling-index (LACI), as left atrial volume-index (LAVI) by Tissue-Doppler-Imaging a’ (TDI-a’), in a large cohort of DMR. Methods All consecutive 4792 patients (61 ± 16 years, 48% women) with isolated degenerative mitral valve disease diagnosed at Mayo Clinic 2003-2011, comprehensively characterized, in whom LAVI and TDI-a’ in sinus rhythm was prospectively measured in routine practice, was enrolled and their long-term survival analyzed. Results LACI (5.8 ± 3.7–T1 < 3.8; T2 3.8-6.3; T3 > 6.3) was significantly higher through different DMR grades (no, mild, moderate, severe DMR: 3.77 ± 2.26, 5.08 ± 2.95, 6.54 ± 3.74 and 7.84 ±4.29 respectively; p < 0.0001). Independent determinants of LA dysfunction assessed by LACI were age, E/e’, left-ventricle (LV) end-systolic-diameter, mitral-regurgitation (MR) grade, and LV ejection-fraction (all P ≤ 0.0001). LACI > 6 was independently associated with dyspnea, edema, more severe functional tricuspid-regurgitation and elevated pulmonary artery pressure, irrespective of age, sex, Charlson-comorbidity-index, ventricular function and MR severity. Total follow-up was 7.03 ± 3.0 years, during which 1146 (24%) underwent mitral-valve surgery (94% repair-6% replacement) and 880 (18%) died, 780 under medical treatment and 100 after surgery. Overall survival throughout follow-up (10-year 76 ± 1%) was strongly associated with LACI (88 ± 1% vs. 78 ± 1% and 62 ± 2% for LACI <3.8, 3.8-6.3 and ≥6.3, P < 0.0001) even adjusting comprehensively, including for DMR severity (adjusted-hazard-ratio 1.23[1.07-1.43] for LACI > 5.79, P = 0.005). Mortality under medical management was profoundly affected by LACI (adjusted-hazard-ratio 1.11[1.05-1.18] per 3 unit increment; 1.35[1.15-1.58] for LACI > 5.79 vs. ≤5.79, both P = 0.0002). Survival improved after mitral surgery (time-dependent adjusted-hazard-ratio 0.40[0.28-0.65], P < 0.0001) but remained humbly linked to LACI (10-year 93 ± 3% vs. 90 ± 2% and 80 ± 3% for LACI tertiles, P = 0.0008). Most importantly, LACI provided incremental prognostic information over LAVI and other conventional determinants of survival (P < 0.0001) with Net-reclassification-improvement vs. LAVI of 0.21 ± 0.02, P < 0.0001. Conclusion LA function assessed by LACI in routine practice, by conventional echocardiographic measurements, displays incremental and independent link to excess-mortality, considerable under medical management and partially alleviated by mitral surgery. Thus, LACI is a simple tool of crucial interest in DMR risk-stratification. Abstract Figure. LACI in DMR

Abstract Background Mitral-annulus-disjunction (MAD), often described in mitral-valve-prolapse (MVP) patients, remains incompletely defined and its clinical outcome consequences are unknown. Objectives To assess MAD prevalence, clinical and echocardiographic characteristics, and independent impact on outcome in patients with isolated-MVP. Methods A cohort of 595 (65±16 years, 278 female) consecutive patients with MVP and comprehensive clinical, rhythmic and Doppler-echocardiographic characterization, was identified. Primary-endpoint was overall-survival, or occurrence of ventricular-arrhythmia. To eliminate clinical differences, we matched MAD-patients 1:1 with no-MAD based on propensity score for overall survival analysis using a greedy 5-to-1 digit-matching algorithm. Results MAD was frequent, present in 186 (31%) of MVP-patients and independently associated to bileaflet-MVP, leaflet-redundancy, younger-age, female-sex, enlarged left-ventricle-endsystolic-diameter and higher left-ventricle-ejection-fraction (all P≤0.04). Outcome primary-endpoint of survival after MVP diagnosis in matched-cohort (10-year 95±1%) was not associated with MAD presence (10-year 93±2% for no-MAD and 97±1% for MAD, P=0.4). Mortality was comparable for MAD (univariate-hazard-ratio 0.64 [0.25–1.65], P=0.4 vs. no-MAD), even adjusted-comprehensively including for MVP-characteristics (adjusted-hazard-ratio 1.17 [0.39–3.50], P=0.8). However, 220 (51%) MVP-patients were diagnosed ventricular-arrhythmia (161 with ventricular-tachycardia only) and long-term, MAD was associated with lower arrhythmia- and ventricular-tachycardia- overall freedom (adjusted-hazard-ratio for MAD 2.35 [1.75–3.15], P<0.0001 vs. no-MAD and 2.71 [1.93–3.82], P<0.0001 respectively). Hence, 10-year freedom of significant ventricular-arrhythmia in overall-cohort was severely reduced with MAD (41±4% vs. 62±3% for no-MAD). Conclusion In this unique MVP cohort, with arrhythmia and MAD comprehensively-characterized, MAD presence was frequent and independently associated to bileaflet-MVP and leaflet-redundancy. Long-term, MAD compared to no-MAD is not independently associated with higher-mortality but to reduced arrhythmia-freedom occurrence. Survival overall and by V arrhythmia Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Mayo Foundation

Abstract Background The majority of patients with of Mitral-valve-prolapse (MVP) have a excellent prognosis. Until recently most cases of mortality were thought to be related to mitral regurgitation and left ventricular dysfunction. The concept of the arrhythmic MVP emerged to describe cases of sudden cardiac death (SCD) in the presence of isolated MVP yet it’s phonotype remains incompletely and inconsistently defined. Purpose To analyze the prevalence, severity and characteristics of ventricular-arrhythmia (VA), to determine it’s phenotypical context and independent impact on outcome in patients with MVP. Methods A cohort of 595 (65 ± 16 years, 278 female) consecutive patients with MVP and comprehensive clinical, arrhythmia (24hour-Holter) and Doppler-echocardiographic characterization, was identified and long-term outcome analyzed. Results VA was frequent, present in 43% of patients with at least ventricular ectopy≥5%, but was most often moderate (ventricular-tachycardia—VT 120-179bpm) in 27% and rarely severe (VT≥180/min) in 8.6%. Presence of VA was associated with older age, male sex, bileaflet-prolapse, marked leaflet redundancy, mitral-annulus-disjunction (MAD), larger left-atrium and left ventricular end-systolic diameter, and T-wave-inversion/ST-depression (all P ≤ 0.001). Severe VA was independently associated with presence of MAD, leaflet-redundancy and T-wave-inversion/ST-depression (all P < 0.0001) but not with mitral regurgitation severity or ejection-fraction. Outcome primary endpoint of overall survival after arrhythmia diagnosis (8-year 87 ± 2%) was strongly associated with arrhythmia-severity (8-year 90 ± 2% for no/trivial arrhythmia, 85 ± 3% for mild/moderate and 76 ± 7% for severe arrhythmia. P = 0.02, Figure). Excess-mortality was substantial for severe-arrhythmia (univariate-hazard-ratio 2.70[1.27-5.77], P = 0.01 vs. no/trivial arrhythmia), even adjusted comprehensively including for MVP-characteristics (adjusted-hazard-ratio 2.94[1.36-6.36], P = 0.006) ). Conclusions This large cohort of isolated consecutive MVP characterized with 24-hour-Holter monitoring, clinical and Echocardiographic assessment, demonstrates that VA are frequent with MVP but rarely severe. The arrhythmic MVP was independently and strongly associated with specific ECG and morphologic patterns, particularly ST-T changes, MAD presence and marked leaflet redundancy, suggestive of a specific arrhythmic MVP phenotype, independently of MR-severity. Arrhythmia, particularly severe, is associated with long-term excess-mortality, independently of any other characteristics, including MR severity and LVEF. These findings lay the foundation for novel risk-stratification of MVP for the conduct of prospective controlled studies evaluating the management of MVP high-risk patients. Figure – Impact on survival of ventricular arrhythmia Overall survival of MVP stratified by ventricular arrhythmia (Panel A) or ventricular arrhythmia severity (Panel B) throughout follow-up. Abstract Figure.

Abstract 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.