Acute mitral regurgitation in adults: Clinical presentation and diagnosis

INTRODUCTION — 

Patients with acute mitral regurgitation (MR) are often gravely ill with significant hemodynamic abnormalities that require urgent medical and, usually, surgical treatment [1-5].

The pathophysiology, clinical features, and management of acute native MR will be reviewed here.

The pathophysiology, clinical features, and management of chronic MR are discussed separately:

●(See "Pathophysiology and natural history of chronic mitral regurgitation".)

●(See "Clinical manifestations and diagnosis of chronic mitral regurgitation".)

●(See "Chronic primary mitral regurgitation: General management".)

●(See "Chronic primary mitral regurgitation: Indications for intervention".)

●(See "Chronic secondary mitral regurgitation: General management and prognosis".)

●(See "Chronic secondary mitral regurgitation: Intervention".)

The clinical presentation, diagnosis, and management of prosthetic MR are discussed separately. (See "Clinical manifestations and diagnosis of surgical aortic and mitral prosthetic valve regurgitation".)

ETIOLOGY — 

There are two main categories of causes of acute native valve MR: ischemic and nonischemic (figure 1). These two categories have partially overlapping mechanisms.

Ischemic causes — Acute coronary syndromes (acute myocardial infarction [MI] or unstable angina) are causes of acute MR resulting from either of the following mechanisms:

●Ischemic papillary muscle (or chordae tendinae) rupture – Papillary muscle rupture due to acute MI is a cause of acute MR, as discussed separately [6]. A less commonly reported cause of acute MR in the setting of acute MI is chordae tendinae rupture [6,7]. (See "Acute myocardial infarction: Mechanical complications", section on 'Papillary muscle rupture'.)

●Ischemic mitral leaflet tethering – Another cause of acute MR in patients with ischemic heart disease is mitral leaflet tethering (due to papillary muscle displacement or altered angulation) with acute regional dilation and regional left ventricular (LV) dysfunction due to MI or myocardial ischemia [8-10]. A relatively small degree of leaflet tenting and small area of mitral leaflet lacking coaptation in the setting of acute MI can cause clinically significant MR [8].

Of note, the term "ischemic MR" is commonly applied to patients with chronic MR and mitral leaflet tethering associated with chronic coronary artery disease (CAD) and prior MI, as discussed separately. (See "Pathophysiology and natural history of chronic mitral regurgitation", section on 'Secondary MR'.)

Nonischemic causes — There are a number of nonischemic processes that can cause acute MR.

●Nontraumatic leaflet destruction – Infective endocarditis (and, less commonly, Libman-Sacks endocarditis associated with systemic lupus erythematosus) can cause leaflet destruction with perforation and/or inadequate leaflet coaptation [4,11,12].

●Nontraumatic nonischemic chordae tendinae or papillary muscle rupture

•Preexisting conditions – Conditions that predispose to ruptured chordae tendinea include mitral valve prolapse (diffuse myxomatous degeneration or fibroelastic deficiency) [13] and rheumatic mitral valve disease (acute rheumatic fever or rheumatic heart disease) [14-16].

•Precipitants

-Chordae tendinae rupture may occur spontaneously (without an apparent precipitating event) or in the setting of a precipitant (such as infective endocarditis) in patients with or without known preexisting mitral valve conditions [16-19].

-Papillary muscle rupture is rarely caused by nonischemic causes such as infective endocarditis, myocarditis, stress cardiomyopathy, myxomatous mitral valve disease, or severe mitral annular calcification [17,19-23].

●Systolic anterior motion of the mitral valve (SAM) – Acute MR associated with dynamic LV outflow obstruction with SAM occurs in some patients with hypertrophic cardiomyopathy (HCM), stress cardiomyopathy, or other non-HCM conditions such as hypertensive LV hypertrophy or sigmoid septum [24-28]. In this setting, SAM with acute MR may be provoked or worsened with inotropic agents or with the onset of atrial fibrillation and rapid ventricular response. (See "Management and prognosis of stress (takotsubo) cardiomyopathy", section on 'With left ventricular outflow tract obstruction' and "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction".)

MR with SAM following mitral valve repair for primary MR is discussed separately. (See "Anesthesia for patients with mitral regurgitation", section on 'Postbypass TEE assessment'.)

●Nonischemic mitral leaflet tethering – Mitral leaflet tethering caused by nonischemic LV dysfunction is an uncommon cause of acute MR. Etiologies include myocarditis [29] and stress cardiomyopathy [30]. SAM is another cause of acute MR with stress cardiomyopathy, as discussed above. (See "Clinical manifestations and diagnosis of stress (takotsubo) cardiomyopathy", section on 'Symptoms and signs'.)

●Mechanical causes

•Chest trauma – Blunt or penetrating chest trauma with injury of mitral chordae tendinae, leaflets, and/or papillary muscles is a rare cause of acute MR [31-34].

•Iatrogenic – Acute MR caused by injury to mitral leaflets, chordae, and/or papillary muscle [35], or caused indirectly by injury to the conduction system (causing LV dyssynchrony) and/or impairment of coronary artery flow (causing LV dysfunction resulting in mitral leaflet tethering) has been rarely reported as a complication of medical procedures (eg, transcatheter aortic valve implantation [36] or implantation or removal of a mechanical circulatory support device [37,38]).

PATHOPHYSIOLOGY — 

The hemodynamic changes in acute MR are often more severe than those in chronic MR, largely due to the lack of time for the left atrium and LV to adapt to the volume load caused by MR [8,39].

This is in contrast to subacute or chronic MR with which adaptations (eg, increased left atrial compliance) have time to develop and typically preserve hemodynamic stability (figure 2). (See "Pathophysiology and natural history of chronic mitral regurgitation".)

The degree of hemodynamic deterioration in acute MR depends upon the degree and acuity of MR, which is often severe with rapid onset, resulting in the following hemodynamic consequences:

●Pulmonary edema – In the absence of chronic volume overload (as with chronic MR), the left atrium is not compliant, so the sudden and marked increase in left atrial volume caused by acute MR results in abrupt elevation in left atrial pressure. This pressure is immediately transmitted back into the pulmonary circulation, often resulting in pulmonary edema.

●Cardiogenic shock – Because the LV is not dilated and severe MR causes a large fraction of the blood ejected by the ventricle to go backward across the mitral valve, effective forward flow is limited. Despite a compensatory increase in heart rate, forward cardiac output falls, which can precipitate cardiogenic shock. The neurohumoral response to the reduction in cardiac output is an increase in vascular resistance, which exacerbates the regurgitation. (See "Hemodynamics of valvular disorders as measured by cardiac catheterization", section on 'Acute mitral regurgitation'.)

Given the hemodynamic consequences of acute severe MR, urgent intervention is required. (See "Acute mitral regurgitation: Management".)

CLINICAL MANIFESTATIONS

Acuity of presentation — Acute severe MR usually presents as a cardiovascular emergency with the sudden onset and rapid progression of pulmonary edema, hypotension, a hyperdynamic apical impulse, and signs and symptoms of cardiogenic shock. In some cases, the pulmonary hypertension leads to acute right-sided heart failure (HF).

The presentation may not be as dramatic if acute MR is less severe, superimposed upon chronic MR, or occurs in a young physically fit individual. Such patients may present subacutely in the office or clinic, rather than in the emergency department. They may note increasing shortness of breath, dyspnea on exertion, fatigue, and weakness with little or no overt HF.

Cardiovascular examination — Patients with acute MR often present with pulmonary edema and evidence of poor tissue perfusion with peripheral vasoconstriction, pallor, and diaphoresis. The arterial pulse is often rapid and of low amplitude or thready due to the reduction in forward stroke volume. When there is an associated increase in right-sided pressure, the neck veins become distended; they may also become pulsatile with a marked "v" wave if the elevated right ventricular pressure leads to significant tricuspid regurgitation. (See "Examination of the arterial pulse" and "Assessment of the jugular venous pressure".)

The cardiac apical impulse is hyperdynamic but is usually normal in location because LV size is normal. If, however, acute regurgitation is superimposed upon chronic MR, the cardiac impulse may be displaced due to the underlying LV enlargement. A right ventricular lift may be present due to the acute increase in pressure within this chamber and the development of tricuspid regurgitation.

Murmur — Patients with acute MR may or may not have an audible murmur. Approximately 50 percent of patients with moderate to severe acute ischemic MR have no audible murmur [40-45].

The presumed mechanism of silent MR is a relatively low systolic pressure gradient between the LV and left atrium due to the combination of a low systemic blood pressure and elevated left atrial pressure. Also, acute MR is often associated with tachycardia with associated shortened duration of systole, which may also make it more difficult to hear the murmur. In addition, acoustic transmission of the murmur may be obscured by adventitious sounds (including crackles) and obesity. Thus, the absence of a systolic murmur does not reliably exclude the diagnosis of acute severe MR.

When present, the murmur of acute MR is often best heard along the left sternal border and base of the heart, generally without a thrill, and may radiate to the back. It can be confused with the murmur of an acute ventricular septal defect, which, like acute MR, is a complication of an acute MI. (See "Acute myocardial infarction: Mechanical complications", section on 'Clinical manifestations'.)

The murmur of acute MR may be early systolic, midsystolic, or holosystolic. However, since the pressure within the left atrium markedly increases during ventricular systole and the pressure gradient between the left atrium and ventricle diminishes or disappears by the end of systole, the systolic murmur is often soft, low-pitched, and decrescendo, often ending well before A2 (early systolic). (See "Auscultation of diastolic and continuous murmurs in adults" and "Auscultation of heart sounds".)

Heart sounds — An S3 filling sound is commonly heard but may be difficult to appreciate if tachycardia is present. With the development of pulmonary hypertension, P2 is increased in intensity and the murmurs of pulmonary and tricuspid regurgitation may be appreciated. (See "Auscultation of heart sounds", section on 'Clinical significance of S3' and "Auscultation of heart sounds", section on 'Factors determining the intensity of S2' and "Auscultation of cardiac murmurs in adults: General concepts and systolic murmurs", section on 'Tricuspid regurgitation'.)

Initial tests — Initial testing in patients with acute MR includes an echocardiogram, electrocardiogram (ECG), and chest radiograph.

An urgent echocardiography is required for timely diagnosis and management, as described below. (See 'Echocardiography' below.)

Electrocardiogram — There are no ECG abnormalities specifically associated with acute MR. However, many of the causes or predisposing conditions associated with acute MR (such as an acute MI, stress [takotsubo] cardiomyopathy, hypertrophic cardiomyopathy [HCM], LV hypertrophy) have characteristic ECG findings including:

●Acute MI (or myocardial ischemia) (figure 3). (See "Electrocardiogram in the diagnosis of myocardial ischemia and infarction".)

●Stress cardiomyopathy. (See "Clinical manifestations and diagnosis of stress (takotsubo) cardiomyopathy", section on 'Electrocardiogram'.)

●ECG findings of LV hypertrophy are seen with HCM and with other causes of LV hypertrophy, such as hypertension (waveform 1 and waveform 2). (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation", section on 'Electrocardiography'.)

Chest radiograph — The chest radiograph usually shows a normal size cardiac silhouette and signs of pulmonary edema. Signs of interstitial and alveolar edema are most commonly bilateral and symmetric. Occasionally (9 percent in one study), the pulmonary edema is unilateral due to an eccentric MR jet, typically limited to the right upper lobe [46,47].

DIAGNOSIS

When to suspect acute MR — Acute valve regurgitation should be included in the differential diagnosis for any patient presenting with respiratory decompensation. If acute MR is suspected, early echocardiography is performed to confirm or exclude this diagnosis.

In clinical practice, acute MR may not be initially recognized because the clinical presentation mimics an acute pulmonary process or other cause of HF [48], and the physical examination findings are often subtle, with a soft or inaudible murmur of MR, as discussed above [2,48]. (See 'Murmur' above and 'Differential diagnosis' below.)

Echocardiography

Choice of test — A transthoracic echocardiogram (TTE) is often sufficient to confirm a diagnosis of acute MR and to identify its mechanism and etiology.

However, TTE may be inadequate to confirm or exclude a diagnosis of acute MR, since suboptimal imaging of the color flow jet may underestimate the severity of MR. When the TTE is nondiagnostic in patients with suspected acute native valve MR (eg, acute HF with a hyperdynamic LV and low cardiac output), transesophageal echocardiography (TEE) is performed to provide improved images of the mitral valve and assessment of regurgitation severity [49,50]. TEE is also indicated if additional imaging is required to determine the cause of acute MR to guide management. (See "Transesophageal echocardiography in the evaluation of mitral valve disease".)

Key findings — Key echocardiographic (transthoracic or transesophageal) findings in patients with acute MR include:

●Left atrial and LV sizes are generally normal. However, the left atrium and LV may be enlarged if chronic MR has been present prior to the acute event.

●In the setting of severe MR, a reduced forward stroke volume shortens the duration aortic valve opening.

●The severity of regurgitation is evaluated with Doppler studies. (See "Echocardiographic evaluation of the mitral valve", section on 'Determination of severity'.)

●Other findings are related to the etiology of acute MR (figure 1) (see 'Etiology' above):

•Systolic function is often normal or hyperdynamic. However, in patients with ischemic heart disease, segmental wall motion abnormalities are commonly identified. In patients with stress (takotsubo) cardiomyopathy, focal LV dysfunction (most typically apical ballooning with basal hyperkinesis) is present. (See "Role of echocardiography in acute myocardial infarction" and "Clinical manifestations and diagnosis of stress (takotsubo) cardiomyopathy", section on 'Identification of wall motion abnormalities'.)

•Mitral valve leaflet tethering associated with papillary/segmental wall motion abnormalities may be identified when this is the cause of acute MR due to ischemic heart disease (myocardial infarction or ischemia) or nonischemic causes (eg, myocarditis or stress cardiomyopathy).

•With papillary muscle or chordae rupture, there is commonly flail mitral leaflet, in which the ruptured head is seen in the LV and prolapses back into the left atrium (movie 1 and movie 2). Chordal rupture with rheumatic disease more often affects the anterior leaflet, while chordal rupture with myxomatous disease more often involves the posterior leaflet [16].

•Systolic anterior motion (SAM) of the mitral valve leaflets may be identified in patients with SAM-associated acute MR, including patients with hypertrophic cardiomyopathy (HCM) or stress cardiomyopathy.

•In patients with endocarditis, findings may include mitral leaflet destruction with perforation, inadequate leaflet coaptation, and vegetations on the leaflets.

Doppler assessment of MR — The presence, severity, and jet characteristics of acute MR are identified by Doppler studies. The vena contracta width and density of the continuous-wave Doppler signal are key findings for identification of significant MR that are particularly helpful in acutely ill patients with limited image quality. When the MR jet is eccentric, the jet area is usually small and underestimates MR severity.

The spectral display of the continuous-wave Doppler mitral regurgitant flow velocity often shows a characteristic triangular shape (instead of the typical rounded shape of chronic MR) due to rapid decline in late systolic velocity in response to abruptly rising left atrial pressure. In patients with HCM with MR caused by SAM of mitral leaflets, the jet is generally posteriorly directed. If a patient with HCM has an anteriorly directed jet, an alternative cause of MR (such as mitral valve prolapse) should be sought. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation", section on 'Echocardiography'.)

Exercise echocardiography — There is no role for exercise testing for most patients with acute severe MR. However, in selected patients with ischemic MR that is not severe at rest, exercise echocardiography may be helpful in identifying exercise-induced severe MR.

The mechanism of worsening MR with exercise may be papillary muscle displacement (previously known as papillary muscle dysfunction) or alterations in papillary muscle orientation due to hypokinesis of the underlying LV wall. However, worsening of MR with exercise can occur in the absence of detectable ischemia, as evidenced by the absence of chest pain or typical ECG or echocardiographic findings [51]. Such patients can present with acute pulmonary edema and have a worse prognosis. These issues are discussed in detail separately. (See "Clinical manifestations and diagnosis of chronic mitral regurgitation", section on 'Stress testing'.)

Differential diagnosis — The differential diagnosis for acute MR includes other causes of acute hypoxic respiratory and/or cardiovascular decompensation, including:

●Other causes of acute HF. (See "Approach to diagnosis and evaluation of acute decompensated heart failure in adults".)

●Acute pulmonary conditions, such as pneumonia and acute respiratory distress syndrome. (See "Overview of community-acquired pneumonia in adults" and "Acute respiratory distress syndrome: Clinical features, diagnosis, and complications in adults".)

CARDIAC CATHETERIZATION — 

For patients with acute MR, cardiac catheterization with coronary angiography is indicated in patients with CAD or at risk for CAD who may require revascularization.

Contrast left ventriculography is generally avoided when acute MR is present, as it requires an additional contrast load and the information it provides is rarely necessary given the information provided by echocardiography.

●Patients presenting with acute coronary syndrome – Indications for urgent coronary angiography in patients with acute coronary syndrome are discussed separately. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department" and "Non-ST-elevation acute coronary syndromes: Selecting a management strategy".)

Some patients with acute MR have mitral leaflet tethering resulting from LV dysfunction caused by acute MI or myocardial ischemia. The role of revascularization in this setting is discussed separately. (See "Acute mitral regurgitation: Management", section on 'Secondary MR'.)

●Evaluation of coronary artery disease prior to cardiac surgery

•For hemodynamically stable patients – In selected patients with acute MR who are hemodynamically stable and undergoing mitral valve surgery, preoperative coronary angiography may be warranted to detect significant coronary obstruction. Although data supporting efficacy are limited, these lesions are usually revascularized at the time of mitral valve surgery since concurrent bypass surgery typically adds little morbidity or mortality to the procedure.

Coronary angiography is indicated prior to valve surgery in patients with one or more of the following: history of CAD, angina, evidence of myocardial ischemia, impaired LV systolic function, or presence of coronary risk factors (including males >40 years old and postmenopausal females, although these criteria from the 2020 American College of Cardiology/American Heart Association were developed for elective valve surgery [49]). In selected patients with a low to intermediate pretest probability of CAD, contrast-enhanced coronary computed tomographic angiography is reasonable to exclude the presence of significant obstructive CAD [49].

•For hemodynamically unstable patients without an acute coronary syndrome – For patients with acute MR without an acute coronary syndrome who require emergency mitral valve surgery, proceeding to valve surgery without coronary angiography may be reasonable.

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac valve disease".)

SUMMARY AND RECOMMENDATIONS

●Categories of acute mitral regurgitation – There are two primary categories of causes of acute native valve mitral regurgitation (MR) (see 'Etiology' above):

•Ischemic MR – Causes of acute MR in patients with coronary artery disease (CAD) include papillary muscle rupture due to acute myocardial infarction (MI), or papillary muscle displacement or altered angulation due to MI or myocardial ischemia. (See "Acute myocardial infarction: Mechanical complications" and "Chronic secondary mitral regurgitation: General management and prognosis".)

•Nonischemic MR – Causes of nonischemic MR include ruptured mitral chordae tendineae (flail leaflet); this occurs in the setting of myxomatous disease (mitral valve prolapse), infective endocarditis, trauma, rheumatic heart disease (acute rheumatic fever or chronic rheumatic mitral valve disease), or spontaneous rupture. Acute MR has also been reported in the setting of systolic anterior motion (SAM) of the mitral valve dynamic left ventricular (LV) outflow obstruction, particularly in patients with stress cardiomyopathy. (See "Management and prognosis of stress (takotsubo) cardiomyopathy", section on 'With left ventricular outflow tract obstruction'.)

●Clinical presentation

•Acuity – Acute severe MR usually presents as a cardiovascular emergency with the sudden onset and rapid progression of heart failure (HF) with pulmonary edema, hypotension, and symptoms and signs of cardiogenic shock. The presentation may not be as dramatic if acute MR is less severe, superimposed upon chronic MR, or occurs in a young, physically fit individual. Such patients may present subacutely with increasing shortness of breath, dyspnea on exertion, fatigue, and weakness with little or no overt HF.

•Murmur – Patients with acute MR may or may not have an audible murmur. When present, the murmur of acute MR is often early systolic, best heard along the left sternal border and base of the heart, generally without a thrill, and may radiate to the back. Approximately 50 percent of patients with moderate to severe acute ischemic MR have no audible murmur, particularly those with acute ischemic MR. (See 'Clinical manifestations' above.)

●Diagnosis – Acute valve regurgitation should be included in the differential diagnosis for any patient presenting with respiratory decompensation. If acute MR is suspected, early echocardiography is performed to confirm or exclude the diagnosis. (See 'Diagnosis' above.)

●Echocardiography – A transthoracic echocardiogram (TTE) is often sufficient to confirm a diagnosis of acute MR and to identify its mechanism and etiology. However, if TTE is nondiagnostic in patients with suspected acute native valve MR, transesophageal echocardiography (TEE) is performed to provide improved images of the mitral valve and assessment of regurgitation severity [49]. TEE is also indicated if additional imaging is required to determine the cause of acute MR to guide management.

●Differential diagnosis – The differential diagnosis for acute MR includes other causes of HF and primary pulmonary conditions. (See 'Differential diagnosis' above.)