Elsevier

International Journal of Cardiology

Volume 315, 15 September 2020, Pages 15-21
International Journal of Cardiology

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?

https://doi.org/10.1016/j.ijcard.2020.03.071Get rights and content

Highlights

  • Patients with left ventricle dyssinchrony (LVD) have often concomitant mitral regurgitation (MR).

  • Management of LVD and MR are based on a fix-step algorithm (“3 months”).

  • This review summarizes the evidence regarding FMR and LVD.

  • A new algorithm is proposed for therapeutic approach.

Abstract

Cardiac resynchronization therapy (CRT) has been associated to left ventricle (LV) remodelling, reduction of functional mitral regurgitation (FMR) and clinical improvement in patients with heart failure and reduced ejection fraction (HFrEF). The prevalence of significant FMR in patients with LV dyssynchrony that are candidate to CRT is up to 40%. Current approach in patients with FMR undergoing CRT consists of re-evaluation of the amount of FMR following a waiting period of at least 3 months after the implant. In case of persistent significant FMR despite CRT and guideline directed medical therapy, trancatheter Mitral Valve repair (TMVR) is an important option to improve quality of life and prognosis. This stepwise approach does not take into account the probability of the individual response to CRT and the availability of TMVR solutions that are safe and effective in high risk patients. We reviewed the effects of CRT on FMR, the prognostic role of persistence of FMR after CRT treatment and the impact of treatment of FMR in patients CRT non responders. We aimed to point out the limits of current step-wised approach in light on more recent evidence regarding FMR treatment. A new, “tailored” approached is proposed.

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.

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