Hospital Medicine

Mitral regurgitation

I. Problem/Condition.

Mitral regurgitation (or mitral insufficiency) is the most common valve disorder and may result from dysfunction of the leaflets, annulus, chordae tendinae, or papillary muscles. Patients with this disorder most commonly present with symptoms of congestive heart failure and reduced cardiac output (hypotension, vasoconstriction, tachycardia).

A. What is the differential diagnosis for this problem?

Primary causes of mitral regurgitation (MR):

a.) mitral valve prolapse (myxomatous disease) - the most common cause of MR in the developed world

b.) infective endocarditis

c.) trauma, leading to ruptured chordae tendineae

d.) rheumatic heart disease (uncommon in the developed world but remains prevalent in the developing world)

e.) collagen vascular disease (Marfan syndrome)

f.) congenital

g.) annular calcification/calcification of the leaflets

h.) anorectic drugs

Secondary (functional) causes of mitral regurgitation:

a.) ischemic heart disease

b.) left ventricular systolic dysfunction

c.) hypertrophic cardiomyopathy

d.) pacemaker induced, usually right-sided pacemaker

B. Describe a diagnostic approach/method to the patient with this problem.

If mitral regurgitation is suspected, careful auscultation, chest x-ray, electrocardiogram (EKG) and transthoracic echocardiography with doppler should help to confirm the diagnosis. If the transthoracic echo (TTE) is not conclusive, a transesophageal echo (TEE) may provide more conclusive confirmation of the diagnosis. Unfortunately, patients with mitral regurgitation may be misdiagnosed and mistreated for primary lung disease or congestive heart failure due to systolic dysfunction for some time before the proper diagnosis is made.

1. Historical information important in the diagnosis of this problem.

A detailed history may aid in determining the etiology of the mitral regurgitation. Generally, acute mitral regurgitation presents with sudden dyspnea and often severe hemodynamic compromise, requiring immediate intervention. Chronic mitral regurgitation may present with a slower, more indolent course or progressive shortness of breath, orthopnea, fatigue, and paroxysmal nocturnal dyspnea. Other findings on history may also provide some insight to the diagnosis including:

a.) history of mitral valve prolapse, or history of a 'murmur'

b.) fevers, chills, weight loss, rashes/skin changes, recent dental work or infection

c.) multiple strep infections or history of rheumatic fever

d.) concurrent collagen vascular disease or personal/family history of Marfan's disease

e.) history of diet aids (which are now off the market) or prolonged use of ergotamine

f.) history of prior heart attack, coronary artery disease

g.) pacemaker dependence and presence of a single right ventricular (RV) lead

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

Acute mitral regurgitation and chronic mitral regurgitation may differ somewhat in their exam findings, but often it is challenging to differentiate the two based on exam alone.

Acute mitral regurgitation:

a.) Pulmonary edema, jugular venous distention, and RV heave due to pulmonary venous congestion and right ventricular overload.

b.) Cool, clammy, pale due to poor cardiac output and subsequent vasoconstriction.

c.) Cardiac Auscultation:

i.) Murmur may be early systolic, holosystolic or mid-systolic, and may radiate to axilla or back. Absence of a murmur does not exclude MR as nearly 50% of people with moderate to severe MR have no audible murmur (high left atrial pressure in systole decreases the pressure gradient between ventricle and atrium and thus lessens the murmur).

ii.) some maneuvers may help differentiate MR from other valvular disorders:

-abrupt standing (decrease blood return to right heart) DECREASES MR murmur intensity

-squatting (increases systemic vascular resistance and blood return to heart) INCREASES MR murmur intensity

-valsalva (decreases venous blood return) DECREASES MR murmur intensity

-hand grip (increases systemic vascular resistance and LV filling pressures) INCREASES MR murmur intensity

iii.) S3 gallop is often present, but may not be audible if patient is tachycardic.

Chronic mitral regurgitation:

a.) Often patients are asymptomatic until there is left ventricular (LV) dilatation and systolic dysfunction leading to congestive heart failure, poor cardiac output or atrial fibrillation.

b.) Cardiac auscultation:

i.) S1 is quiet due to failure of the mitral leaflets to close with contact

ii.) Wide splitting of S2

iii.) S3 gallop is often prominent due to the common occurrence of LV dysfunction in this case

iv.) murmur most often holosystolic with radiation to axilla or back. It begins shortly after S1 and often overlaps A2

v.) location of the murmur may provide further insight into the etiology of the MR

-if murmur radiates anteriorally towards the sternum it may reflect damage to the posterior leaflet seen in prolapse and chordal rupture

-if murmur radiates to the back (and even the top of the head) it may reflect damage to the anterior leaflet seen in prolapse and chordal rupture

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

Pro-BNP (Brain natriuretic peptide)

a.) BNP is most useful in asymptomatic MR. Serial BNP measurements may help to improve timing for surgery. Low plasma levels in low-risk patients generally is the most helpful clinically.

Electrocardiogram:

a.) Acute MR: no specific EKG findings, although look for underlying p mitrale - a sign of left atrial enlargement (a double humped or notched p wave in lead II or a biphasic p wave in lead V1 in which the downward deflection is at least one box wide and deep)

b.) Chronic MR: may find left atrial enlargement (LAE) as above, left ventricular hypertrophy (LVH) or evidence of right heart strain (stemming from pulmonary venous hypertension) including R/S > 1 in V1 or rSR' in V1

Chest x-ray:

a.) Acute MR: pulmonary edema with cephalization +/- Kerley B lines, normal cardiac silhouette unless there is underlying chronic MR

b.) Chronic MR: cardiomegaly stemming from LV enlargement and LAE, straightening of left heart border due to LAE, may see calcification of mitral annulus

TTE and TEE:

This is essential for determining the diagnosis, etiology and severity of MR. If TTE does not confirm the diagnosis, a TEE may be warranted. Diagnostic accuracy is higher for TEE as compared to TTE.

a.) Acute MR: usually the anatomy of the left atrium and, left ventricle appear normal as well as the LV systolic function.

i.) Flail mitral leaflet with papillary or chordal rupture. A disrupted anterior leaflet most often stems from chordal rupture from rheumatic disease. A disrupted posterior leaflet most often stems from chordal rupture from myxomatous disease.

ii.) Vegetations may appear on leaflets with endocarditis.

iii.) Doppler studies help to clarify the severity of the regurgitation.

b.) Chronic MR: usually the left atrium size is increased, but the left ventricular size and systolic function may be normal (initially). All worsen as the disease progresses. CHRONIC MR CANNOT BE DIAGNOSED WITHOUT THE PRESENCE OF LEFT ATRIAL ENLARGEMENT OR LEFT VENTRICULAR ENLARGEMENT.

i.) Posterior flail leaflets into the atrium during systole occur with mitral prolapse.

ii.) Vegetations may appear on leaflets with endocarditis.

iii.) Regurgitated jet of blood through a perforated mitral valve leaflet.

iv.) Flail mitral leaflet with papillary or chordal rupture. A disrupted anterior leaflet most often stems from chordal rupture from rheumatic disease. A disrupted posterior leaflet most often stems from chordal rupture from myxomatous disease.

v.) Thickening and dysfunction of the leaflets or chordal shortening occur with rheumatic heart disease.

vi.) Secondary MR occurs due to excessive dilatation of the left atrium and ventricle leading to poor coaptation of the valve leaflets. If ischemic disease is the etiology most often it is due to posterior leaflet dysfunction.

Stress testing:

Exercise stress testing is often going to exacerbate an already symptomatic patient with mitral regurgitation and should be avoided. However, if a patient has symptoms consistent with mitral regurgitation that worsen with exertion, but only mild insufficiency on a resting TTE, exercise may be essential to the diagnosis. If ischemic, especially in the vascular territory of the posterior wall, there may be a component of dynamic mitral regurgitation, i.e. as the patient becomes more ischemic the chordae tendineae experience dysfunction and lead to worsened regurgitation.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

N/A

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

Cardiovascular magnetic resonance imaging

May be helpful when there is a discrepancy between the clinical presentation and echocardiography, however this holds a very limited role in the diagnosis of MR, especially given the expense.

Invasive cardiac catheterization and direct measurement of intracardiac pressures

This is rarely superior to echocardiography alone (especially in chronic MR). However, it does hold a role in the assessment of obstructive coronary disease warranting surgical revascularization at the time of surgical valve repair. Beware - the contrast load (especially when performing an left ventriculogram) may further decompensate a patient in acute mitral regurgitation, and should be avoided.

A. Management of Clinical Problem Acute and Chronic Mitral Regurgitation.

Acute mitral regurgitation

Acute Mitral Regurgitation is a medical and surgical emergency and is often sudden in onset and accompanied by pulmonary edema and hemodynamic instability/cardiogenic shock. Surgery, most often, is the definitive treatment. However, medical management is often necessary as a stabilizing bridge to surgery.

  • Medical management: Nitroprusside is the primary medical therapy. It is an arterial and venodilator and thus decreases afterload, allowing for a reduction in the systemic vascular resistance. Its venodilator properties decrease filling pressures, and in turn attempt to reduce pulmonary edema and the degree of left ventricular dilation. Unfortunately, hypotension and hemodynamic instability may preclude the use of a vasodilator alone. In this setting, an inotrope such as dobutamine or dopamine may be needed in combination.

    • Nitroprusside utilization in patients with mitral regurgitation due to hypertrophic cardiomyopathy or mitral valve prolapse might worsen the regurgitation as the ventricular size decreases and the gradient increases.

  • Surgical management: surgical management of acute mitral regurgitation carries very high risk - mortality rates as high as 50% for all cause MR. The timing and type of intervention depends upon the etiology of the MR.

    • mitral valve prolapse: in cases of pure chordal rupture, often the valve can simply be repaired rather than replaced. This prevents the need for anticoagulation long term and has better morbidity and mortality outcomes. Treat early for better outcomes.

    • endocarditis: emergent valve repair/replacement indicated in cases of hemodynamic instability. Generally, early surgery is preferred in all cases of endocarditis-related MR to prevent fistula formation and progressive valve damage. Urgent, rather than emergent, surgery is advised with symptomatic patients without hemodynamic instability.

      • surgical repair is always preferred over replacement if at all possible. This is a possibility depending on type of organism and extent of disease/valvular damage present.

    • ischemic mitral regurgitation: if a discrete ischemic territory is the cause of MR, percutaneous coronary intervention may treat the problem. Medical therapy and an intraaortic balloon pump may be utilized as well to transition the patient out of the acute event. Conversely, if the cause is papillary rupture from ischemia, surgery is indicated. Unfortunately, mortality is high in this setting, but even higher if medical management alone is used.

Chronic mitral regurgitation

Medical management is warranted as long as patient can be managed symptomatically. Once the patient is symptomatic despite medical therapy, or becomes unstable, more intensive therapy is indicated (see acute mitral regurgitation).

  • Medical management: although vasodilator therapy has symptomatic benefit in acute MR, there is little data to support any long term benefit of these therapies on LV size and function. Blood pressure control alone is likely to provide the best mechanical offloading of the regurgitant flow.

    • mitral valve prolapse: goal is to reduce systemic arterial pressure (afterload) rather than preload reduction. Thus arterial vasodilators are key: ACE inhibitors, angiotenson receptor blockers (ARB), hydralazine, vasodilating beta blockers (carvedilol and labetalol).

    • ischemic disease and/or systolic dysfunction: angiotension converting enzyme (ACE) inhibitor and angiotension receptor blocker (ARB) for afterload reduction, beta blocker therapy, combination therapy of arterial vasodilator and preload reduction (hydralazine + isordil). Nitrate therapy if chronic ischemic disease is prominent.

  • Surgical management: decision and timing for surgical repair or replacement depends on the patient (age, comorbidities, presence or absence of LV dysfunction), symptoms, presence or absence of atrial fibrillation, and the etiology of the mitral regurgitation. The decision to operate is generally based on the presence of symptoms (see above). Guidelines recommend surgery in 1) symptomatic patients with severe MR on echocardiography, 2) in asymptomatic patients with abnormal left ventricular function, or 3) in asymptomatic patients with normal left ventricular function if there is a high likelihood of successful repair. Comprehensive mitral valve repair, rather than replacement, has been shown to decrease subsequently left ventricular remodeling and is associated with superior outcomes, but is dependent on the anatomy of the valve and technical feasibility as determined by the surgeon.

    • cardiac resynchronization therapy (CRT) may be warranted in patients with systolic dysfunction and dyssynchrony (QRS > 120 milliseconds) contributing to a dilated ventricle and regurgitation.

  • Transcatheter therapy: an emerging method of treatment for acute and chronic mitral regurgitation which offers a less invasive and less morbid method of treatment for MR, particularly in higher-risk, elderly patients. Early methods include the most-studied “MitraClip” transcatheter operation which typically incorporates ring annuloplasty and effectively sutures together the middle of the posterior and anterior leaflets in order to produce a double-orifice mitral valve, reducing regurgitation. Several other methods are in development, but such therapies are in ongoing trials and are not yet widely available.

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem.

The greatest challenge for the health care provider is to diagnose mitral regurgitation early. Although management of acute mitral regurgitation rarely offers little option but surgery, chronic mitral regurgitation is much more complex. The decision to refer for surgery is best made when a patient presents with the symptoms of dyspnea, orthopnea or fatigue due to pulmonary edema, rather than based on the degree of MR seen on echocardiography. The hospitalist should involve cardiology early for optimal assessment and the guarantee of good follow-up in these patients.

Nitroprusside is the optimal vasodilator for the inpatient management of symptomatic mitral regurgitation. Patients who are already hemodynamically unstable with hypotension, however, may not be able to tolerate even the smallest doses of this medication. In that setting, combination therapy with an inotrope such as dobutamine with nitroprusside may be the best option until the patient can get to surgery.

Nitroprusside infusion: Warning - this medication can cause cyanide toxicity which can be lethal. Toxic dosing can occur from 0.5 – 5 micrograms/kilogram/minute (mcg/kg/min) intravenous (IV).

  • Initial dose 0.3 mcg/kg/min IV infusion, titrate every few minutes to desired effect. Average dose: 3 mcg/kg/min. Maximum dose: 10 mcg/kg/min.

or

  • Starting dose 0.1 to 0.2 mcg/kg/min (continuous infusion), titrate every 5 minutes to goal

Dobutamine infusion:

  • Initial dose 0.5 to 1 mcg/kg/min IV, maintenance 2-40 mcg/kg/min IV, titrate to response

IV. What's the evidence?

Gaasch, WH,, Meyer, TE. "Left ventricular response to mitral regurgitation: implications for management.". Circulation. vol. 118. 2008. pp. 2298.

"HFSA 2010 Comprehensive Heart Failure Practice Guideline.". J Card Fail 2010. vol. 16. pp. e1.

Hermann,, HC and, Maisano,, F,. "Contemporary Reviews in Cardiovascular Medicine: Transcatheter Therapy of Mitral Regurgitation.". vol. 130. 2014. pp. 1712-1722.

Nishimura,, RA,, Otto,, CM,, Bonow,, RO. "ACC/AHA 2014 Guideline for the Management of Patients with Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heat Association Task Force on Practice Guidelines.". J Am Coll Cardiol.. vol. 129. 2014. pp. e521-e643.

Nishimura,, RA,, Vahanian,, A,, Mack,, MJ. "Mitral valve disease – Current management and future challenges.". Lancet.. vol. 387. 2016. pp. 1324-34.

Stout, KK,, Verrier, ED. "Acute valvular regurgitation. Circulation". vol. 119. 2009. pp. 3232.

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