Evolution of Functional Mitral Regurgitation and Prognosis in Medically Managed Heart Failure Patients With Reduced Ejection Fraction

Nasser, Riwa; Assche, Lauranne Van; Vorlat, Anne; Vermeulen, Tom; Craenenbroeck, Emeline Van; Conraads, Viviane M.; Meiren, Vicky Van der; Shivalkar, Bharati; Herck, Paul Van; Claeys, Marc J.

doi:10.1016/j.jchf.2017.06.015

Cited by 81 publications

(76 citation statements)

References 21 publications

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“…These agents can greatly minimize regurgitant flow, even when the MR is severe (EROA of 0.3–0.4 cm 2 ). However, intensive medical therapy is not sufficient to alleviate MR if there is meaningful ventricular dyssynchrony (e.g. as reflected by the presence of left bundle branch block), which is strongly associated with disproportionate MR.…”

Section: Identifying Patients With Disproportionate Functional Mitralmentioning

confidence: 99%

“…Second, MR can be caused by left ventricular (LV) dyssynchrony due to a localized electrical or mechanical disturbance that leads to uncoordinated support of the valve leaflets during systole. Although the degree of MR may be mild and of little consequence, one‐third of patients with chronic heart failure manifest severe MR, which is related to either LV enlargement or LV dyssynchony …”

mentioning

confidence: 99%

“…Although the degree of MR may be mild and of little consequence, one-third of patients with chronic heart failure manifest severe MR, which is related to either LV enlargement or LV dyssynchony. 2…”

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confidence: 99%

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Disproportionate functional mitral regurgitation: a new therapeutic target in patients with heart failure and a reduced ejection fraction

Packer

2019

European J of Heart Fail

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Patients with chronic heart failure and a reduced ejection fraction commonly show evidence of functional mitral regurgitation (MR), which may result from two distinct pathophysiological mechanisms. 1 First, MR can occur primarily as a result of enlargement of the left ventricle, which leads to mitral annular dilatation and the tethering of the valve leaflets by displaced papillary muscles. Second, MR can be caused by left ventricular (LV) dyssynchrony due to a localized electrical or mechanical disturbance that leads to uncoordinated support of the valve leaflets during systole. Although the degree of MR may be mild and of little consequence, one-third of patients with chronic heart failure manifest severe MR, which is related to either LV enlargement or LV dyssynchony. 2 Identifying patients with disproportionate functional mitral regurgitationThe two mechanisms leading to functional MR can be distinguished in the clinical setting. 3 When the principal reason for MR is LV enlargement, there is a predictable relationship between LV end-diastolic volume (LVEDV) and the effective regurgitant orifice area (EROA), assessed by Doppler echocardiography. An EROA of 0.1-0.2 cm 2 can be expected when the LVEDV is 150-200 mL, whereas an LVEDV of 250-300 mL generally leads to EROA of 0.3-0.4 cm 2 (i.e. severe MR). A patient who has severe MR in association with an LVEDV of 250-300 mL has a regurgitant lesion that is proportionate to the LVEDV, i.e. the MR can be explained entirely by LV enlargement. In contrast, when the EROA is of 0.3-0.4 cm 2 but the LVEDV is only 150-200 mL, the degree of MR is much greater than expected from the LV chamber size; i.e. the MR is disproportionate to LV dilatation, typically because it is related to LV dyssynchrony. Thus, distinguishing between proportionate and disproportionate MR allows

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Section: Identifying Patients With Disproportionate Functional Mitralmentioning

confidence: 99%

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confidence: 99%

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Disproportionate functional mitral regurgitation: a new therapeutic target in patients with heart failure and a reduced ejection fraction

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2019

European J of Heart Fail

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“…Both guideline‐directed medical therapy (on account of reverse remodeling and afterload reduction) and CRT therapy (in those meeting criteria) have been shown to improve the degree of FMR and consequently clinical outcomes including HF hospitalization and mortality. However, severe FMR improves, at best, in less than half of these patients . To date, mitral valve surgery is the most widely accepted strategy for the treatment of symptomatic severe MR, both for primary and functional mitral regurgitation.…”

Section: Introductionmentioning

confidence: 99%

“…However, severe FMR improves, at best, in less than half of these patients. 2 To date, mitral valve surgery is the most widely accepted strategy for the treatment of symptomatic severe MR, both for primary and functional mitral regurgitation. However, neither mitral valve repair nor replacement has demonstrated improvement in mortality or hospitalization rates in patients with functional mitral regurgitation.…”

Section: Introductionmentioning

confidence: 99%

Clinical outcomes of percutaneous mitral valve repair with MitraClip for the management of functional mitral regurgitation

Marmagkiolis

Hakeem

Ebersole

et al. 2019

Cathet Cardio Intervent

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Objectives To evaluate the safety and efficacy of percutaneous mitral valve repair for the management of functional mitral insufficiency. Background Severe FMR is present in 25–30% of patients with heart failure and is an independent predictor of mortality and hospitalizations in patients with both ischemic and nonischemic cardiomyopathy. MitraClip therapy has been approved for high surgical risk patients with primary mitral regurgitation. Recent studies including two randomized trials have yielded conflicting results in terms of its clinical efficacy and outcomes for FMR. A quantitative evaluation and synthesis of this information are essential in elucidating the role of MitraClip repair for FMR. Methods We performed a literature search using PubMed, EMBASE, and Cochrane Central Register of Controlled Trials from September 2008 to September 2018. Studies comparing percutaneous mitral valve repair using the MitraClip device against conservative therapy for the management of functional mitral regurgitation were included. Results Seven studies with 1,174 patients in MitraClip group and 1,015 patients in medical therapy group met inclusion criteria. The 12‐month mortality in the MitraClip group was 18.4% compared with 25.9% in the medical therapy group (odds ratio [OR]: 0.65 [0.50, 0.86]; p < .002). The rate of readmission at 12 months was 29.9% in the MitraClip group compared with 54.1% in the medical therapy group (OR: 040 [0.32–0.49]; p < .0001. The prognostic efficacy of MitraClip repair appears to be more substantial over longer follow‐up period over medical therapy alone. Conclusions Based on the results of this meta‐analysis, percutaneous mitral valve repair with MitraClip appears to be superior to medical therapy for symptomatic moderate‐to‐severe functional mitral insufficiency. Further clinical research is needed to identify the ideal patient subgroups who receive maximum benefit with the MitraClip therapy.

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New Evidence Supporting a Novel Conceptual Framework for Distinguishing Proportionate and Disproportionate Functional Mitral Regurgitation

Packer

Grayburn

2020

JAMA Cardiol

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ImportanceTraditionally, physicians distinguished between mitral regurgitation (MR) as a determinant of outcomes and MR as a biomarker of left-ventricular (LV) dysfunction by designating the lesions as primary or secondary, respectively. In primary MR, leaflet abnormalities cause the MR, resulting in modest increases in LV end-diastolic volume over time, whereas in patients with classic secondary MR, LV dysfunction and dilatation lead to MR without structural leaflet abnormalities. However, certain patients with global LV disease (eg, those with left bundle branch block or regional wall motion abnormalities) have the features of primary MR and might respond favorably to interventions that aim to restore the proper functioning of the mitral valve apparatus.ObservationsA novel conceptual framework is proposed, which classifies patients with meaningful LV disease based on whether the severity of MR is proportionate or disproportionate to the LV end-diastolic volume. Treatments that reduce LV volumes (eg, neurohormonal antagonists) are effective in proportionate MR but not disproportionate MR. Conversely, procedures that restore mitral valve function (eg, cardiac resynchronization and mitral valve repair) are effective in patients with disproportionate MR but not in those with proportionate MR. The proposed framework explains the discordant findings in the Multicentre Randomized Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation (MITRA-FR) and the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trials; differences in procedural success and medical therapy in the 2 studies cannot explain the different results. In addition, the small group of patients in the COAPT trial who had the features of proportionate MR and were similar to those enrolled in the MITRA-FR trial did not respond favorably to transcatheter mitral valve repair.Conclusions and RelevanceThe characterization of patients with functional MR into proportionate and disproportionate subtypes may explain the diverse range of responses to drug and device interventions that have been observed.

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Evolution of Functional Mitral Regurgitation and Prognosis in Medically Managed Heart Failure Patients With Reduced Ejection Fraction

Abstract: Severe FMR was successfully treated with medication in almost 40% and was associated with prevention of left ventricular adverse remodeling and with an improved long-term prognosis.

Cited by 81 publications

References 21 publications

Disproportionate functional mitral regurgitation: a new therapeutic target in patients with heart failure and a reduced ejection fraction

Disproportionate functional mitral regurgitation: a new therapeutic target in patients with heart failure and a reduced ejection fraction

Clinical outcomes of percutaneous mitral valve repair with MitraClip for the management of functional mitral regurgitation

New Evidence Supporting a Novel Conceptual Framework for Distinguishing Proportionate and Disproportionate Functional Mitral Regurgitation

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