Functional mitral regurgitation and cardiac resynchronization therapy in the “era” of trans-catheter interventions: Is it time to move from a staged strategy to a tailored therapy?
Section snippets
Left ventricular dyssynchrony and functional mitral regurgitation: what is known and what is missing
The prevalence of Functional mitral regurgitation (FMR) in patients with heart failure and reduced ejection fraction (HFrEF), ranges from 20 to 50% [1], reaching 65% in patients with any type of LV dyssynchrony and 40% in those who have full indication to CRT.
Despite the relation between LV dyssynchrony (LVD), LV dysfunction and FMR has been largely described, in daily clinical practice the current approach to FMR in patients eligible to CRT is based only on recent observational studies [2]
Mechanisms of effects of CRT on FMR: acute and chronic effects
In patients with HFrEF rather than LV dimensions per se major determinants of secondary MR are: geometric changes of the LV, eccentricity index and position and dynamics of the papillary muscles (PM) [[6], [7], [8], [9]]. Fig. 1 summarized the relation between LV dysfunction, LV remodelling, LV dyssincrony and FMR and highlights the role of medical treatments and CRT in this context. The main mechanisms of action of CRT on FMR have been discussed in previous studies and can be summarized and
Amount of effects of CRT on FMR: Evidence from post hoc analysis of CRT- trials and ad-hoc studies
The amount of FMR reduction after CRT in this population of advanced heart failure was found to be 23–35% within the first 3–6 month in post-hoc analysis of some land-mark trials on CRT [[23], [24], [25], [26]]. In the echocardiographic analysis of MADIT CRT, including patients with less advanced heart failure (NYHA I and II), FMR was mostly of mild grade (“severe” only in 2% of patients before CRT); the majority of patients worsened in the ICD-only group and improved in the CRT-D group. These
Predictors of improvement of FMR after CRT
Other than all the echocardiographic predictors of LV response, that can ideally affect the amount of concomitant FMR [[30], [31], [32], [33]], other specific echocardiographic predictors of response have been searched. Goland et al. tested the amount of mechanical dyssynchrony and confirmed that significant time-to-peak delay between inferior and anterior LV segments, a preserved longitudinal and radial strain of posterior wall and MR jet area/left atrium area ratio < 40% are factors
Persistent FMR after CRT mitigates the effects of CRT
As well as CRT can affect FMR, the persistence of FMR after CRT is associated with worse outcomes [10]. Conversely the reduction of FMR and LV resynchronization can act in a synergistic fashion to improve long term outcome and LV remodelling. Verhaert et al. demonstrated that the amount of acute decrease of FMR was predicting larger decrease in LVESVi in the long-term follow up [29]. Similar results were obtained by Liang YJ et al. in a small study of 83 patients in which a cut off of 11%
Integrated approach to avoid futility of CRT and futility of MitraClip
Beyond the mere quantitative assessment of predicted/possible effects of CRT or TMVI, in the group of HFREF patients some concerns should be always pointed out for avoiding futility of interventions.
Right ventricle function and pulmonary hypertension have an independent additive role in determining the prognosis of patients with HFrEF, irrespective from the aetiology. The presence of a pre-capillary contribution to pulmonary hypertension can attenuate the benefit of CRT on prognosis in terms of
Conclusions
FMR has high prevalence in heart failure patients who are candidate to CRT. Integrated evaluation of patients with HF that are candidate to CRT should be carried out prior and after CRT to evaluate not only LV remodelling but also the amount of FMR. Transcatheter MV repair reduces events and improve LV remodelling on top of medical treatment and CRT, particularly when it is applied in a timely fashion and before the disease is too advanced. In order to reduce the delay in decisions, and to
CRediT authorship contribution statement
Mara Gavazzoni: Conceptualization, Writing - original draft. Maurizio Taramasso: Writing - review & editing. Michel Zuber: Writing - review & editing. Alberto Pozzoli: Writing - review & editing. Mizuki Miura: Writing - review & editing. Dinaldo Oliveira: Writing - review & editing. Francesco Maisano: Writing - review & editing.
Acknowledgements
The authors thank Dr.Victoria Del Gado for her contribution as reviewer of this paper.
References (55)
- et al.
Left ventricular shape is the primary determinant of functional mitral regurgitation in heart failure
J. Am. Coll. Cardiol.
(1992) - et al.
Temporal changes in interpapillary muscle dynamics as an active indicator of mitral valve and left ventricular interaction in ischemic mitral regurgitation
J. Am. Coll. Cardiol.
(2014) - et al.
Left ventricular structure and function: basic science for cardiac imaging
J. Am. Coll. Cardiol.
(2006 Nov 21) - et al.
Left ventricular remodeling: common process in patients with different primary myocardial disorders
Int. J. Cardiol.
(1999) - et al.
A mechanism for immediate reduction in mitral regurgitation after cardiac resynchronization therapy: insights from mechanical activation strain mapping
J. Am. Coll. Cardiol.
(2004 Oct 19) - et al.
A unifying concept for the quantitative assessment o secondary mitral regurgitation
J. Am. Coll. Cardiol.
(2019 May 28) - et al.
Acute effects of cardiac resynchronization therapy on functional mitral regurgitation in advanced systolic heart failure
J. Am. Coll. Cardiol.
(2003) - et al.
Predicting the long-term effects of cardiac resynchronization therapy on mortality from baseline variables and the early response. A report from the CARE-HF? (cardiac resynchronization in heart failure) trial
J. Am. Coll. Cardiol.
(2008) - et al.
Long-term effect of cardiac resynchronization therapy on functional mitral valve regurgitation
Am. J. Cardiol.
(2009) - et al.
Correction of mitral regurgitation in nonresponders to cardiac resynchronization therapy by MitraClip improves symptoms and promotes reverse remodeling
J. Am. Coll. Cardiol.
(2011 Nov 15)
Right heart-pulmonary circulation unit and cardiac resynchronization therapy
Am. Heart J.
Right ventricular evaluation to improve survival outcome in patients with severe functional mitral regurgitation and advanced heart failure undergoing MitraClip therapy
Int. J. Cardiol.
A unifying concept for the quantitative assessment of secondary mitral regurgitation
J. Am. Coll. Cardiol.
Recommendations for noninvasive evaluation of native valvular regurgitation a report from the American Society of Echocardiography developed in collaboration with the society for cardiovascular magnetic resonance
JASE
Discordance between echocardiography and MRI in the assessment of mitral regurgitation severity: a prospective multicenter trial
J. Am. Coll. Cardiol.
Reproducibility of proximal isovelocity surface area, vena contracta, and regurgitant jet area for assessment of mitral regurgitation severity
JACC Cardiovasc. Imaging
Role of cardiac dyssynchrony and resynchronization therapy in functional mitral regurgitation
Eur. Heart J. Cardiovasc. Imaging
Impact of cardiac resynchronization therapy on the severity of mitral regurgitation
Europace
Cardiac resynchronization therapy: state-of-the-art of current applications, guidelines, ongoing trials, and areas of controversy
Circulation.
Transcatheter mitral-valve repair in patients with heart failure
N. Engl. J. Med.
Percutaneous repair or medical treatment for secondary mitral regurgitation
N. Engl. J. Med.
Integrated mechanism for functional mitral regurgitation: leaflet restriction versus coapting force: in vitro studies
Circulation.
Insights from threedimensional echocardiography into the mechanism of functional mitral regurgitation: direct in vivo demonstration of altered leaflet tethering geometry
Circulation.
Role of cardiac dyssynchrony and resynchronization therapy in functional mitral regurgitation
Eur. Heart J. Cardiovasc. Imaging
Effects of cardiac resynchronization therapy on disease progression in chronic heart failure
Eur. Heart J.
Asymmetric redirection of flow through the heart
Nature
Left ventricular or biventricular pacing improves cardiac function at diminished energy cost in patients with dilated cardiomyopathy and left bundle-branch block
Circulation
Cited by (4)
New Perspective on Pathophysiology and Management of Functional Mitral Regurgitation
2023, Trends in Cardiovascular MedicineCitation Excerpt :The acute effects, however, do not prevent against dynamic worsening of MR with exercise [13]. Long-term beneficial effects of CRT occur 3-6 months after implantation via the reversal of LV remodeling, improvement in LV systolic function, reduction in LV volumes and restoration of synchronous ventricular contraction [28]. Given the prognostic significance of residual FMR in CRT non-responders, it is imperative to identify CRT non-responders early on, so that residual FMR can be addressed before the disease is too advanced [31].
Atrial fibrillation in cardiac resynchronization therapy
2021, Heart Rhythm O2Citation Excerpt :This may be related to the effect of reverse LV remodeling on left atrial hemodynamics, and improved left atrial function has been demonstrated in CRT responders who are in sinus rhythm.41 Furthermore, up to 40% of patients indicated for CRT have significant functional mitral regurgitation, owing to combination of LV dyssynchrony and dilatation, and improvement in mitral regurgitation severity has been reported in 23%–49% of patients after CRT in clinical trials.42 Mitral regurgitation has a complex interaction with AF, and has been associated with poorer outcomes after ablation.