European Heart Journal Advance Access originally published online on October 16, 2006
European Heart Journal 2006 27(22):2615-2616; doi:10.1093/eurheartj/ehl320
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Functional mitral regurgitation in acute coronary syndrome: what determines its prognostic impact?
Division of Cardiology, University Hospital Sart Tilman, Liège, Belgium
Corresponding author. Tel: +32 4 366 71 94; fax: +32 4 366 71 95. E-mail address: lpierard{at}chu.ulg.ac.be
This editorial refers to ‘Prognostic significance of functional mitral regurgitation after a first non-ST-segment elevation acute coronary syndrome’
by L.P. de Isla et al., on page 2655
Functional mitral regurgitation (MR) is frequently present in patients with acute coronary syndrome and can be observed by contrast ventriculography or Doppler echocardiography.1–5 It is, however, poorly detected by auscultation.1,6 Ischaemic MR results from either tethering force that restricts the ability of the mitral leaflets to close, reduced left ventricular (LV)-generated closing force, or both.7 Tethering is produced by global LV remodelling—increased LV sphericity and annular dilation—or more frequently by mitral valve distortion, characterized by systolic valvular tenting due to apical and outward displacement of the posterior papillary muscle or of both papillary muscles. Reduced closing force can be determined by reduced LV contractility or LV regional dyssynchrony. In the acute phase of myocardial infarction (MI), MR may pre-exist or result from the acute event through regional LV dilation and loss of contraction. Most studies have shown that functional MR in early MI is associated with a worse prognosis and is an important, independent predictor of cardiovascular mortality. The incidence of functional MR in the prospective studies is highly dependent on the method used to document it. The lowest frequency (9%) is observed when the detection of the MR relies only on cardiac auscultation.8 The frequency varies from 13 to 19% when MR is diagnosed by contrast ventriculography.1–3 The highest incidence is found, not surprisingly, in the trials using Doppler echocardiography.4,5
Several clinical parameters characterize patients with acute MI and MR when compared with patients without MR. The patients with MR are older in all series, more frequently female in most trials and more likely to have diabetes in some but not all studies. In all cohorts that did not only include patients with a first acute coronary event, a history of previous MI and a more severe coronary disease were more frequently found in the groups of patients with MR. The site of infarction varies in the different studies. Patients with MR were more likely to have sustained an anterior infarction in some trials, but in other investigations, an inferior MI, a posterolateral MI, a combined anterior–inferior, or an MI of indeterminate location were predominant. When the information is available, the size of dyssynergy is usually larger: a higher number of akinetic chords, a significantly larger hypokinetic segment, more segments with contraction defect. All studies demonstrated that functional MR in acute MI portends a guarded prognosis with the exception of the trial in which MR was detected only by physical examination.8 Multivariate analysis revealed that the presence of MR was an independent predictor of cardiovascular death, the relative risk varying from 1.48 to 7.5. Even mild MR was found to be independently associated with increased mortality.4
In this issue of the Journal, Perez de Isla et al.9 show that the presence and degree of MR confer a worse long-term prognosis also to patients with a first non-ST segment elevation acute coronary syndrome. They studied 300 consecutive patients admitted for a first event. Age and LV ejection fraction were independent markers of the development of MR. In-hospital cardiac death was more frequent in the group with MR, but no independent predictor of in-hospital mortality was found by multivariate analysis. In contrast, MR was the sole independent predictor of poor long-term prognosis. This observation contrasts with a previous study by the same investigators in patients with non-Q wave acute MI. In that study, the presence of MR did not add any independent prognostic importance, but the number of enrolled patients was only one-third of the population in the present study.10
Which factors determine the prognostic impact of functional MR?
The worse prognosis may relate to the MR and its consequences, to the myocardial state associated with functional MR, or to the combination of these two determinants.
Functional MR is more frequent in patients with LV dilation and abnormal, more spherical geometry. MR worsens the volume overload, producing additional LV dilatation, increased leaflet tethering, and a further increase in MR severity. The presence of non-ischaemic MR prior to a first MI was also found to be an independent prognostic marker, associated with a poor outcome in both the immediate and the long-term periods.11 In that study, atrial fibrillation prior to MI was more frequent in patients with pre-infarction MR, but was not an independent predictor of mortality.
Does the myocardial state resulting from the acute coronary syndrome play a role?
Transmural necrosis is frequently complicated by early infarct expansion, more often in the acute phase of anterior MI, leading to LV remodelling. Geometrical changes associated with LV dilation induce a stretching of the leaflets that result in apical displacement of the mitral coaptation. Transmural posterior necrosis determines posterior and apical displacement of the papillary muscles, leading to systolic mitral valvular tenting. Transmural necrosis results from thrombotic coronary occlusion without adequate collateral circulation and without rapid, successful adequate reperfusion. This situation usually occurs in patients with ST-segment elevation MI. In contrast, patients with a non-ST segment elevation acute coronary syndrome, have less frequently complete coronary occlusion or have collateral circulation developed in the presence of more severe stenoses and more diseased coronary arteries. This situation may produce myocardial ischaemia or hibernation. In some patients with acute MI, the absence of ST-elevation may relate to circumflex occlusion and posterolateral necrosis, a location found to be four times more frequent in patients with moderately severe and severe MR in the large series of 1480 patients described by Tcheng et al.2
In the study of Perez de Isla et al.,9 significant coronary lesions of the circumflex artery were not more frequent in the group with MR. The mean number of vessels with significant lesions was higher in patients with MR, the left anterior descending artery was more frequently involved, and there was twice more stenoses of the left main artery. The incidence of diffuse atherosclerosis is not described, but could have been more frequent in the group with MR which comprised more patients with diabetes mellitus. All these features suggest a higher frequency of myocardial hibernation in patients with MR who were not more frequently submitted to percutaneous coronary intervention or bypass grafting. Non-revascularized viable, hibernating myocardium has been found to be associated with a high risk of mortality.
The role of dynamic functional MR
Ischaemic functional MR is dynamic in nature and varies during exercise. Patients with a decrease in MR during exercise have a good long-term prognosis.12 This is more frequently observed when recruitable contractile reserve develops during exercise, producing temporary inverse remodelling in patients with stunned myocardium in the acute phase or non-transmural MI and good coronary flow reserve in the long term. In contrast, patients with a large increase in MR during exercise—increase in the effective regurgitant orifice 
13 mm2—have a five-fold increased risk of cardiac death at 3 years.12
Intermittent increases in MR can produce acute increase in pulmonary vascular pressure and result in acute pulmonary oedema.13 Patients with dynamic MR can experience a more rapid progression of LV remodelling possibly leading to end-stage heart failure. The increased volume overload in this condition may also predispose to severe arrhythmias.
Practically, functional MR should be identified in the acute phase of MI also in patients presenting without ST-segment elevation. Doppler echocardiography is the ideal tool as a murmur of MR is rarely heard. MR is a very simple marker of increased risk. The presence of jeopardized myocardium should be searched; the dynamic component of MR should be unmasked and quantified. These results should lead to consideration for complete revascularization and restoration of valvular competence.
Conflict of interest: none declared.
Footnotes
The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.
doi:10.1093/eurheartj/ehl287 
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[Abstract/Free Full Text]
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Related articles in EHJ:
- Prognostic significance of functional mitral regurgitation after a first non-ST-segment elevation acute coronary syndrome
- Leopoldo Perez de Isla, Jose Zamorano, Maribel Quezada, Carlos Almería, José Luis Rodrigo, Viviana Serra, Juan Carlos García Rubira, Antonio Fernandez Ortiz, and Carlos Macaya
EHJ 2006 27: 2655-2660.[Abstract] [FREE Full Text]
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