Refining the prognostic impact of functional mitral regurgitation in chronic heart failure

Goliasch, Georg; Pávó, Noémi; Neuhold, Stephanie; Wurm, Raphael; Mascherbauer, Julia; Lang, Irene M.; Strunk, Guido; Hülsmann, Martin

doi:10.1093/eurheartj/ehx402

Cited by 285 publications

(239 citation statements)

References 30 publications

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“…An increasing body of evidence consolidates the impact of sMR on the failing LV and long‐term outcome even in patients under GDT . Importantly, recent data illustrate the progressive nature of sMR to be a key feature that drives mortality in HFrEF patients .…”

Section: Discussionmentioning

confidence: 94%

“…Importantly, recent data illustrate the progressive nature of sMR to be a key feature that drives mortality in HFrEF patients . In fact, progressive sMR occurs in 20%‐30% of patients with nonsevere sMR despite GDT and is independently associated with a more than twofold increased risk of death . Defining patients at risk for progression is mandatory as in this patient subpopulation more invasive early treatment strategies are available but the level of evidence in guideline recommendations is weak .…”

Section: Discussionmentioning

confidence: 99%

“…Baseline examination included medical history, detailed assessment of current medication and an electrocardiogram. Cardiovascular risk factors were recorded according to the respective guidelines as previously described . All patients underwent a comprehensive echocardiographic examination at our institution at baseline and yearly thereafter within 3 years after study inclusion.…”

Section: Methodsmentioning

confidence: 99%

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Phenotyping progression of secondary mitral regurgitation in chronic systolic heart failure

Arfsten

Bartko

Pávó

et al. 2019

Eur J Clin Investigation

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BackgroundSecondary mitral regurgitation (sMR) drives adverse cardiac remodelling in patients with heart failure with reduced ejection fraction (HFrEF). Progression in severity over time contributes to a transition towards more advanced HF stages. Early identification of patients at risk for sMR progression remains challenging. We therefore sought to assess a broad spectrum of neurohumoral biomarkers in patients with HFrEF to explore their ability to predict progression of sMR.MethodsA total of 249 HFrEF patients were enrolled. Biomarkers encompassing key neurohumoral pathways in heart failure were sampled at baseline, and sMR progression was assessed over 3 years of follow‐up.ResultsOf 191 patients with nonsevere sMR at baseline, 18% showed progressive sMR within three years after study enrolment. Progression of sMR was associated with higher levels of MR‐proADM (adj.OR 2.25, 95% CI 1.29‐3.93; P = .004), MR‐proANP (adj.OR 1.84, 95% CI 1.14‐3.00; P = .012), copeptin (adj.OR 1.66, 95% CI 1.04‐2.67; P = .035) and CT‐pro‐ET1 (adj.OR 1.68, 95% CI 1.06‐2.68; P = .027) but not with NT‐proBNP (P = .54).ConclusionIncreased plasma levels of neurohumoral cardiac biomarkers are predictors of sMR progression in patients with HFrEF and add easily available incremental prognostic information for risk stratification. Importantly, NT‐proBNP was not useful to predict progressive sMR in the present analysis. On the contrary, MR‐proANP, primarily produced in the atria, copeptin partly triggered by intra‐cardiac and intra‐arterial pressures and MR‐proADM, a marker of forward failure and peripheral released vasoactive CT‐proET1, increase based on a progressive loading burden by sMR and may thus serve as better predictors of sMR progression.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Phenotyping progression of secondary mitral regurgitation in chronic systolic heart failure

Arfsten

Bartko

Pávó

et al. 2019

Eur J Clin Investigation

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“…Mild or even moderate functional mitral regurgitation (MR) is commonly observed in patients with HFpEF, but is often considered to be a bystander rather than contributor to pathophysiology. In HF with reduced ejection fraction (HFrEF), increasing MR severity is associated with greater symptom burden, hospitalization risk, and mortality . In these patients functional MR develops secondary to tethering of the mitral leaflets caused by dislocation of the papillary muscles and chordae tendinae, with impaired closing due to contractile dysfunction, and annular enlargement caused by left ventricular (LV) dilatation .…”

Section: Introductionmentioning

confidence: 99%

Functional mitral regurgitation and left atrial myopathy in heart failure with preserved ejection fraction

Tamargo

Obokata

Reddy

et al. 2020

European J of Heart Fail

110

112

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Aims Mild to moderate functional mitral regurgitation (MR) is common in patients with heart failure and preserved ejection fraction (HFpEF) where it is usually considered as an innocent bystander. We hypothesized that MR in HFpEF reflects greater left atrial (LA) myopathy, leading to more adverse haemodynamics and poorer exercise reserve. Methods and results Patients with HFpEF (n = 280) with and without MR underwent echocardiography, invasive haemodynamic exercise testing, and expired gas analysis. As compared to non‐MR‐HFpEF (n = 163), patients with MR‐HFpEF (n = 117; 78 mild and 39 moderate, central jet in 90%) were older, more likely female, with lower body mass and higher prevalence of atrial fibrillation (AF). HFpEF patients with MR displayed greater LA volume, reduced LA strain and compliance, and greater mitral annular dilatation, which was strongly correlated with LA dilatation (r = 0.63, P < 0.0001) but was only weakly related to left ventricular remodelling (r = 0.37). Patients with MR‐HFpEF displayed worse biventricular function, more adverse pulmonary haemodynamics, impaired pulmonary vasodilatation, blunted right ventricular reserve, and reduced cardiac output with exercise as compared to non‐MR‐HFpEF. Importantly, these findings were maintained after excluding patients with HFpEF and AF, suggesting a role for LA myopathy in contributing to MR in HFpEF, independent of rhythm. Conclusions Functional MR in patients with HFpEF reflects LA myopathy, even in the absence of AF, and is associated with greater haemodynamic severity of disease and poorer functional capacity. Further study is required to better define causal mechanisms and potential treatments for MR and LA dysfunction in patients with HFpEF.

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“…FMR results from various LV remodelling mechanisms that prevent coaptation of structurally normal valve leaflets . FMR multiplies the risk of HF decompensation and death by roughly two depending on the HF patient population . Because of its volatile nature in time and the variety of underlying mechanisms causing mitral regurgitation (MR), the management of HF patients with FMR is complex.…”

Section: Main Differences Between Coapt and Mitra‐fr To Explain The Cmentioning

confidence: 99%

To clip, or not to clip heart failure patients, that is the question

Mewton

Cucherat

2020

European J of Heart Fail

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Functional mitral regurgitation (FMR) occurs in up to 60% of heart failure (HF) patients with reduced left ventricular (LV) ejection fraction. Its frequency and severity depend on the clinical stage of advancement of HF as well as the immediate haemodynamic and therapeutic patient status at presentation. 1,2 FMR results from various LV remodelling mechanisms that prevent coaptation of structurally normal valve leaflets. 3 FMR multiplies the risk of HF decompensation and death by roughly two depending on the HF patient population. 1,4,5 Because of its volatile nature in time and the variety of underlying mechanisms causing mitral regurgitation (MR), the management of HF patients with FMR is complex. This is in clear contrast with organic MR, where MR is the primary cause of symptoms and the benefits of surgical repair/replacement are clearly demonstrated. Percutaneous mitral valve repair (PMVR) has recently emerged as an efficient technique to correct or significantly reduce FMR. 6 Whether this repair translates in significant clinical benefit on HF rehospitalizations and death remained to be demonstrated in randomized clinical trials. Now, two randomized controlled trials have been performed with contradictory results. 7The MITRA-FR study was the first randomized controlled trial assessing efficacy of PMVR against medical therapy in chronic HF patients. It showed no significant difference between the device and control groups for the composite of death and HF hospitalization or for all-cause death at 1 year (P = 0.53 and P = 0.66, respectively). 8 The industry-sponsored COAPT trial was the second and conversely shed an incredible reduction in the repeat-event of all consecutive HF hospitalizations at 2 years (P < 0.001). 9 Some might say MITRA-FR is a false-negative, but they could be biased. In the light of all previous trials performed in this setting, 10,11 others might suggest COAPT is a false-positive, but they could also be biased.Therefore, in this peculiar situation of two trials with different results, without any overlap in confidence intervals for the primary endpoint, it is of upmost importance to go beyond the emotions triggered by the COAPT survival curves and keep our wits together! That is, if you have any.

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Refining the prognostic impact of functional mitral regurgitation in chronic heart failure

Abstract: In a patient cohort under OMT, the adverse prognostic impact of FMR is given predominantly in a sub-cohort of a specific intermediate-failure phenotype-well-defined functionally, haemodynamically, biochemically, and morphologically.

Cited by 285 publications

References 30 publications

Phenotyping progression of secondary mitral regurgitation in chronic systolic heart failure

Phenotyping progression of secondary mitral regurgitation in chronic systolic heart failure

Functional mitral regurgitation and left atrial myopathy in heart failure with preserved ejection fraction

To clip, or not to clip heart failure patients, that is the question

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