Jacc vol 74 no 7 2019 Mitral regurgitation Mitral regurgitation MR is the most frequent valvular heart disease Degenerative MR DMR is the predominant MR cause requiring surgical correction ID: 813480
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Slide1
Prognostic implications of left atrial enlargement in degenerative mitral regurgitation
Jacc
vol 74, no 7, 2019
Slide2Mitral regurgitation
Mitral regurgitation (MR) is the most frequent valvular heart disease.
Degenerative MR (DMR) is the predominant MR cause requiring surgical correction.
When left unoperated, DMR is associated with serious outcome consequence.
To indicate mitral surgery, guidelines provide limited numbers of individual triggers such as Class I symptoms or signs of LV dysfunction.
However, indications based on these triggers are associated with increased post-op mortality, while marked MR undertreatment is linked to excess mortality after diagnosis.
Slide3dmr
Most frequent organic MR and most frequent indication for MV surgery in western countries.
Surgical valve repair restores life expectancy with very low operative mortality and MR recurrent rates.
Recent evidence suggests that a minority of patients with MR ultimately undergo lifesaving interventions.
May be due to difficulties interpreting subjective symptoms and their cause in elderly patients and to the rarity of Class I objective triggers for surgery.
Slide4MR severity
Slide5Guidelines for mitral valve replacement/repair
Slide6Left atrial enlargement
Has long been considered a pure MR consequence.
However, recent studies have provided proof-of-concept evidence that LA enlargement, measured by LA volume index may predict new arrhythmias and mortality, possibly independently and incrementally to DMR severity.
Whether LAVI measured by multiple physicians/sonographers in routine clinical practice carries independent prediction of outcome remains unproven.
Consequently, LAVI measurement does not appear in US guidelines, and is only involved in Class II indications in European guidelines.
Slide7Left atrial enlargement
LA in DMR is the receptacle of the regurgitant volume (
RVol
)
Has long been considered a passive bystander, reflecting volume overload.
Progressively expanding in response to MR progression.
This 2˚ LA dilatation in turn results in increased LA compliance
Known to maintain lower atrial and pulmonary pressures
Thus yielding the long, asymptomatic phase of severe MR.
Slide8Left atrial enlargement
Mechanisms modulating the LA enlargement response to MR are not well understood.
Neuro-hormonal activation
Patterns of atrial protein expression
Cytokine/fibroblast interaction
Genetics
+
mutations
Slide9To fill this gap of knowledge, an unselected cohort representing the entire consecutive experience with a single isolated diagnosis of DMR in a large routine clinical practice, with prospective LAVI measurement regardless of rhythm would be required
Also with comprehensive clinical and echo characterization and with long-term outcome defined.
Slide10Aim
The aim of this study was to examine the hypothesis that LAVI measured in routine clinical practice is an independent and incremental determinant of DMR outcome.
Slide11methods
All consecutive inpatients and outpatients at the Mayo Clinic, with
Diagnosis of DMR, defined as MVP or flail leaflet by first Doppler echo from 2003 to 2011
Age
>
18 years
With LAVI measured prospectively at diagnosis in routine clinical practice
With comprehensive diagnostic evaluation of symptoms, clinical history, comorbidities, and rhythm status.
Slide12methods
Did
not
attempt to measure LAVI retrospectively.
Exclusions:
Patients without LAVI measurements.
Denied research authorization.
Had any of the following:
>
moderate AR or AS or MS
Previous valvular surgery
Congenital heart disease
Hypertrophic, restrictive, or constrictive cardiomyopathies.
PFOs and TRs were
not
excluded.
Slide13Echo evaluation
Performed by multiple trained sonographers (>100) and reviewed by cardiologists (>30).
Imaging protocols included all views from standard windows and systematic measurement of LV dimensions, LVEF, cardiac index, LV filling, and systolic pulmonary pressures as per ASE guidelines.
DMR was classified (per guidelines) to
None/trivial
Mild
Moderate
Severe
LAVI was measured using ASE-guided formulas, area-length, or modified Simpson biplane.
Shown to provide similar results.
Slide14Clinical evaluation
AF was classified based on the presence of overt AF on ECG or with clinical notes demonstrating a history of proven AF.
Clinical notes were analyzed for symptoms (dyspnea, chest pain, palpitations and oedema) at diagnosis.
Slide15outcomes
Primary outcome:
Overall survival throughout follow-up in all patients.
Secondary outcomes:
Survival under medical treatment in all patients with censoring at mitral surgery.
Post-operative survival in operated patients.
Slide16Patient characteristics
All patients diagnosed at Mayo Clinic from 2003 to 2011 with isolated DMR and LAVI measured in routine practice were included in the cohort
5,769 patients.
2,684 were women.
Slide17long-term outcome after diagnosis
Total follow-up was 6.8
+
3.1 years.
1405 patients (24%) underwent MV surgery
At 5 years:
LAVI <40: 8%
LAVI 40 to 59: 33%
LAVI
>
60: 58%
92% repair, 8% replacement.
1304 (23%) died
1142 under medical treatment
162 after surgery
Slide18Overall survival
On average, overall survival was:
94% at 1 year
83% at 5 years
66% at 10 years
Slide19Slide20OVERALL SURVIVAL
LAVI remained independently associated with excess mortality even after additional adjustment for
AF – HR 1.03 per 10ml/m
2
Pulmonary HTN – HR 1.03 per 10ml/m
2
TR – HR 1.04 per 10ml/m
2
Slide21Survival under medical management
On average, survival under medical management was:
79% at 5 years
62% at 10 years
Slide22Slide23Slide24Survival under medical management
Slide25Survival after mitral surgery
On average, survival after mitral surgery was:
91% at 5 years
79% at 10 years
Slide26Slide27discussion
This present study gathered, for the first time in the context of isolated DMR, a considerable cohort of >5000 patients, with unified diagnosis, extensive characterization of potential cofounders/comorbidities, and long term follow-up.
Provides unique power to assess the independent link between LA enlargement and long-term mortality.
Slide28discussion
Consecutive eligible patients were all enrolled regardless of DMR severity to minimize bias.
Recommended LAVI was measured prospectively by multiple sonographers/cardiologists in routine clinical practice, so that the present results are widely applicable to routine clinical practice.
Found that LA enlargement is common at DMR diagnosis and is generally not isolated.
Observed more often in older patients with more severe MR.
Slide29discussion
However, wide-ranging LA enlargement is observed within each DMR grade, rhythm, or age.
Demonstrates that LA response to DMR is highly variable between patients.
The main outcome result of major statistical robustness is that higher LAVI is associated with higher mortality throughout follow-up, independently and incrementally to baseline characteristics.
Slide30discussion
Under medical management, considerable mortality is observed independently with LAVI
>
60ml/m2, but even with LAVI 40-59ml/m2, and in all subgroups, including rhythm and MR severity.
Novel spline curve analysis shows excess mortality appearing around 40ml/m2, and becoming considerable with LAVI
>
60ml/m2.
After surgery, excess mortality is mostly alleviated, but this study demonstrates for the first time that it remains detectable for patients with LAVI
>
60ml/m2.
Slide31discussion
As mitral surgery sizably downgrades mortality risks attached to LA enlargement, LA-associated excess mortality is strongly linked to DMR.
DMR is the central cause of mortality, and LA enlargement is the consequence.
However, mortality is modulated by the individual response to MR, which is not directly treated by surgery, but leads to a mitral surgery decision that improves prognosis.
Authors believe that LAVI measurement should be used consistently in patients with DMR.
Because some risk persists after mitral surgery with LAVI
>
60ml/m
2
, consideration may be given to mitral surgery with high-moderate LA enlargement (40-59ml/m
2
).
Slide32discussion
Therefore, LA enlargement measured by echo LAVI in routine practice has considerable, independent, and incremental prediction power for survival after DMR diagnosis.
Slide33Slide34conclusion
The present study demonstrates in a large, consecutive, isolated DMR cohort with prospectively measured LAVI in routine clinical practice that LA enlargement is frequent, displays marked individual variability, and has a powerful, incremental, and independent link to excess mortality after diagnosis, irrespective of rhythm, age, or MR severity at diagnosis.
The link between LA enlargement and mortality, particularly strong under medical management and for LAVI
>
60ml/m2, is greatly alleviated by mitral surgery, demonstrating its direct link to DMR.
Hence, LA enlargement measured by LAVI should be part of comprehensive DMR evaluation and clinical decision-making in routine clinical practice.