Sunday, January 29, 2012

Aortic Stenosis


Aortic stenosis (AS) is defined as obstruction to blood flow from the left ventricle (LV) to the aorta (AO), whether at the aortic valve, or the subvalvular or the supravalvular level.

Etiology and Pathology:
  • Senile calcific aortic stenosis:
  • Rheumatic aortic stenosis.
  • Congenital aortic stenosis.
  • Radiation-induced aortic stenosis.

Senile calcific aortic stenosis:

Senile calcific AS is the most common cause in developed countries.  

It occurs in the form of a chronic inflammation, sclerosis & calcification of the aortic valve.  

The pathology is accelerated in the presence of one or more of the major risk factors for atherosclerotic disease, namely; diabetes mellitus, hypertension, Dyslipidemia and smoking.  

Male gender is another independent risk factor for this disease. 

If the aortic valve is bicuspid (a condition found in 1% of the population), the pathology tends to occur earlier in life than in a trileaflet aortic valve.  

About one third of bicuspid aortic valves will gradually get stenotic, usually in the fifth or sixth decade of life.  

Trileaflet aortic valve stenosis usually presents in the seventh or eighth decade of life. 

Rheumatic aortic stenosis: 

Rheumatic AS constitutes about 20% of all cases of AS in the developed countries, but is more common in the developing countries.  

Rheumatic AS usually becomes symptomatic in the fourth decade, and is associated with rheumatic mitral valve disease in most cases.

Congenital aortic stenosis: 

Congenital AS usually becomes symptomatic in the first to third decades.  

It may occur at valvular, subvalvular, or supravalvular levels.

Congenital valvular AS: 

Congenital valvular AS usually occurs in the form of a stenotic unicuspid aortic valve, or cusp fusion of a bicuspid aortic valve, without dense calcification, but often with extensive LV hypertrophy, and a high incidence of sudden cardiac death.  

Subvalvular AS occurs in one of three types:
  • Membranous subvalvular AS; caused by a subaortic membranous ring.
  • Fibromuscular tunnel-shaped stenosis of the LV outflow tract.
  • Hypertrophic Obstructive Cardio-Myopathy (HOCM): caused by muscular Asymmetric Septal Hypertrophy (ASH) of the basal part of the interventricular septum; which is more hypertrophied than the rest of the LV myocardium.

HOCM also presents, however, in other forms such as concentric LV hypertrophy, or localized hypertrophy in regions other than the basal septum, e.g. the cardiac apex. Some authorities consider HOCM only under Cardiomyopathies, and do not include this disease as a variety of congenital AS.

Supravalvular AS also occurs in one of three types:
  • Supravalvular membranous ring in the ascending aorta.
  • Tunnel-shaped stenosis of the aortic root.
  • Hour-glass localized constriction in any part of the ascending aorta.

Williams syndrome consists of:
  • Supravalvular AS.
  • Elfin facies: broad forehead, a short nose with a broad tip, full cheeks, and a wide mouth with full lips. Many affected people have dental problems such as small, widely spaced teeth.
  • Hypercalcemia.
  • Sometimes associated with peripheral pulmonary arterial stenosis, hypoplasia of the aorta, and stenosis in renal, celiac, and superior mesenteric arteries.
  • Intellectual disabilities and learning difficulties.
  • Connective tissue and joint abnormalities.

Williams syndrome facial features.

Radiation-induced aortic stenosis: 

AS may follow mediastinal radiation; ≥20 years after therapy. Radiation may also affect the coronary arteries, pericardium, myocardium, lungs, esophagus, and thyroid gland.

Clinical Manifestations and Natural History of aortic stenosis:

Symptoms of AS: 

Even with severe AS; the patient may remain asymptomatic for a long period, during which progressive fibrosis, inflammation, and calcification occur. Once symptomatic, however, survival is dramatically reduced. 

Three main symptoms of AS are recognized:
  • Angina: about 35% of patients present with angina; 50% of them survive for only 5 years, unless treated.
  • Syncope: about 15% of patients present with syncope; 50% of them survive for only 3 years, unless treated.
  • Congestive heart failure (CHF): about 50% present with symptoms of CHF; their mean survival is <2 years, unless treated.

Sudden cardiac death in asymptomatic patients is rare (occurs in about 0.5% per year), but dramatically increases to 2% per month after the development of symptoms.

Factors associated with rapid progression of AS:
  • Moderate or severe aortic valve calcification.
  • Elevated serum calcium levels.
  • Rapid increase in the Doppler-derived aortic systolic gradient.
  • Smoking.
  • Hypercholesterolemia.
  • Elevated serum Creatinine.

Gastrointestinal Bleeding:

Patients with AS have an increased risk of gastrointestinal bleeding, due to associated angiodysplasia, or arteriovenous malformations of the intestines (Heyde syndrome).

Physical Examination of the patient with AS:

Arterial pulse:

Palpation of the carotid pulse is more accurate in the assessment of the severity of AS than the radial pulse.

In severe AS; the carotid upstroke is reduced in amplitude and delayed in timing (pulsus parvus et tardus).

Atherosclerotic stiffness of the carotid arteries in the elderly may, however, maintain a more brisk upstroke, thus underestimating the severity of AS.

Palpation of the heart:

The apical impulse is not much displaced from the normal position (left fifth intercostal space in the mid clavicular line), and is heaving (forceful and sustained) in character.

The aortic stenosis murmur is often associated with a systolic thrill at the aortic area.

Auscultation of the heat:

Heart sounds and added sounds:

Aortic component of the second heart sound (A2) in moderate to severe acquired valvular AS is diminished in intensity due to reduced leaflet mobility.

In congenital AS, even severe, A2 is usually normal because leaflet mobility is preserved.

A fourth heart sound is common.

Ejection systolic click usually precedes the AS murmur.

Aortic stenosis murmur:
  • The murmur of AS is a harsh blowing murmur, but lower in pitch than that of mitral regurgitation.
  • Often loudest at the aortic area (the second right intercostal space near the sternum).
  • Often radiates to the neck.
  • Frequently well heard in the aortic area, then disappears over the sternum, and becomes louder again over the apex, thus mimicking coexisting mitral regurgitation (Gallivardin phenomenon).
  • Early in the course of disease, the murmur typically peaks in early to mid systole, but peaks progressively later until it becomes loudest in the latter half of systole in severe AS.
  • It becomes softer as the cardiac output decreases.

Clinical manifestations of pulmonary arterial hypertension and right ventricular failure may occur in very advanced cases with LV failure.

Clinical differentiation between AS and HOCM:

Conditions which reduce LV volume, e.g. Valsalva maneuver, will decrease the flow across the aortic valve, and reduce the intensity of the murmur of AS.

On the other hand, these conditions worsen the obstruction in patients with HOCM, due to more contact between the anterior mitral leaflet and the hypertrophied interventricular septum, thus increasing the intensity of the murmur of HOCM.

Pathophysiology of Aortic Stenosis:

Aortic stenosis creates a pressure overload on the left ventricle, with increased LV systolic wall stress, which induces concentric LV hypertrophy (LVH), in a trial to generate more pressure, overcome the outflow obstruction, and normalize the wall stress (remember the Laplace equation; wall stress = PR/2H, where P: pressure, R: radius & H: wall thickness).

LVH is accompanied by:
  • Increased myocardium stiffness & reduced compliance.
  • Diastolic LV dysfunction with impaired LV filling.
  • Dissociation and complex modulation of the genes responsible for contraction and relaxation.
  • Modulation of the Rennin-Angiotensin-Aldosterone System (RAAS)).
  • Alteration of the myocardial matrix metalloproteinase activity and expression.
  • Increased collagen deposition which further reduces muscle compliance.
  • Development of symptoms particularly of subendocardial ischemia and arrhythmias, with worsening of the condition and finally a vicious circle is created.
  • Reduced coronary flow reserve, from its normal 5-8 fold increase during stress above baseline, to 2-3 fold increase only, due to endocardial compression by increased LV pressure, and probably inadequate capillary growth.
  • Outflow obstruction increases the systolic ejection time and reduces the diastolic perfusion time, thus reducing coronary filling. Meanwhile, myocardial oxygen demand is increased by increased LV systolic pressure and wall stress.
  • Densification of microtubules comprising the myocardial cytoskeleton.
  • Increased afterload eventually decreases contractile function and cardiac output, with frank LV systolic failure.

Depressed contractility may be explained at least partially by impaired calcium handling and subendocardial ischemia.

Reduced cerebral blood flow may result from:
  • Inability to increase the cardiac output during exercise.
  • Decreased blood pressure due to a vasodepressor response from increased intraventricular pressure.
  • Supraventricular or ventricular arrhythmias may also precipitate hypotension.

Both systolic and diastolic LV functions correlate strongly with the prognosis of patients with AS.


ECG) in AS usually demonstrates:
  • Left ventricular hypertrophy (LVH).
  • Left atrial abnormality.

ECG signs of LVH may be absent in patients with AS even though severe LVH exists.

Left ventricular hypertrophy.

Chest X-Ray:

One or more of the following may be present:
  • The cardiac shadow is usually normal in size, but may demonstrate manifestations of LV enlargement.
  • Prominent ascending aorta.
  • Calcification in the aortic valve, particularly seen in the lateral view.
  • Pulmonary venous congestion may occur later.


Echocardiography is the most important diagnostic tool for:
  • Confirming the diagnosis of AS.
  • Quantifying the disease severity.

M-mode and Two-dimensional echocardiography may demonstrate:
  • Distinction between bicuspid and tricuspid anatomy.
  • Thickened and calcified aortic valve leaflets.
  • Reduced leaflet motion.
  • Calcification of the aortic annulus.
  • The extent of concentric LVH.
  • Calculating LV mass.
  • Calculation of LV ejection fraction (EF).

Trans-thoracic parasternal short axis view showing bicuspid aortic valve.

Doppler echocardiography can accurately quantify:
  • Transvalvular systolic pressure gradient.
  • Aortic valve area. Diastolic dysfunction.

Estimation of the severity of AS by Doppler echocardiography:

Echocardiographic follow-up of asymptomatic patients is essential, yearly in patients with severe AS, every 2 years in patients with moderate AS, and every 5 years in patients with mild AS, to detect:
  • LV systolic dysfunction.
  • Worsening LVH.
  • Development of mitral regurgitation.

Stress Testing:

Stress testing should be avoided in symptomatic patients with AS. It is particularly useful in asymptomatic patients to assess exercise tolerance, and when symptoms are uncertain.

Dobutamine stress echocardiography (DSE) is especially useful in patients with AS who have a low gradient but a small aortic valve area (AVA) and a depressed LV systolic function.
  • If the gradient does not change but the AVA rises >0.3 cm2, the myocardial impairment is the main issue, the valve is probably not severely stenotic (pseudo-stenosis), and AVR will be questionable.
  • If the gradient increases, but the AVA remains small, severe AS probably exists, and AVR is probably useful.

Nuclear imaging: 

Nuclear imaging has been used to evaluate the presence of associated coronary artery disease.

Cardiac Catheterization:

Indications for cardiac catheterization in patients with AS:
  • For definition of coronary anatomy:
    • Patients >40 years of age.
    • Patients with angina pectoris.
    • Patients with major cardiovascular risk factors, namely: diabetes mellitus, hypertension, Dyslipidemia and smoking.
  • If echocardiographic imaging is inadequate, or there is a discrepancy between clinical findings and echocardiography.
  • Other associated cardiac disease that indicates the need for cardiac catheterization.

Management of aortic stenosis:

Medical Therapy:

  • Aggressive management of atherosclerotic risk factors in patients with senile calcific AS.
  • Medical control of congestive heart failure (CHF) might help.
  • Medical control of angina might help.
  • Antibiotic prophylaxis for infective endocarditis, whenever indicated.
  • Vasodilators, e.g. ACE inhibitors, are relatively contraindicated, since they reduce the peripheral vascular resistance and thus increase the systolic pressure gradient across the aortic valve. 

Balloon Aortic Valvuloplasty (BAV): 

BAV may be effective in patients with congenital AS.

In adults with AS, however, the results have been disappointing, and as well 50% will get re-stenosis within 6 months.

BAV has not reduced the high mortality seen in patients who do not undergo surgery for symptomatic AS.

Accordingly, BAV is reserved for patients with AS and advanced CHF who are not candidates for surgery due to other co-morbid conditions and/or high perioperative mortality.

Palliative BAV may be used in patients with treatable acute illnesses until resolution, to be followed by aortic valve replacement.

Aortic Valve Replacement (AVR): 

AVR is performed through a median sternotomy incision, or a minimally invasive procedure with 8-10 cm incision in the lower sternum only, using a bioprosthetic or mechanical valve or a homograft.  

Replacement of the aortic valve as well as the aortic root may be performed, with re-implantation of the coronary arteries into the neo-aortic root. 

Aortic Valve Replacement with Pulmonary Autograft (Ross Procedure): 

Another complex operation described by Ross is to excise the patient's own pulmonary valve and root & re-implant them into the aortic position. A pulmonary homograft is then implanted to replace the pulmonary valve and the main pulmonary artery.  


Perioperative mortality is around 1-3%, but is higher in the presence of:
  • Elderly patients.
  • Debilitated patients.
  • Significantly impaired LV systolic function.
  • Extensive coronary artery disease.
  • Other valvular disease.
  • Non-cardiac co-morbidities. 

Postoperative Valve-Related Complications:
  • Deterioration of the prosthetic valve, with prosthetic dysfunction, particularly with tissue valves and after Ross operation.
  • Prosthetic valve thrombosis and systemic thromboembolism.
  • Anticoagulant-related bleeding.
  • Infection; most seriously is prosthetic valve endocarditis.
  • Hemolysis.
  • Heart block.

Wednesday, January 18, 2012

Mitral regurgitation


Mitral regurgitation (MR) refers to the backward flow of blood from the left ventricle (LV) to the left atrium (LA), across the mitral valve (MV), during systole, due to inadequate mitral valve closure. MR may be acute or chronic.


The prevalence of chronic MR varies inversely with its severity:
  • Trivial (Physiologic) MR: is detectable with sensitive Doppler techniques in up to 70% of healthy adults.
  • Mild MR: is found in about 19% of the population.
  • Moderate MR: in about 1.9 % of the population.
  • Severe MR: in about 0.2 % of the population.
Etiology and pathology of chronic MR:

MR can arise from abnormalities of any part of the mitral valve apparatus and other structures, including;
  • MV leaflets.
  • MV annulus.
  • MV chordae tendineae.
  • MV papillary muscles.
  • LA wall.
  • LV myocardium adjacent to the papillary muscles.

The mitral valve.

The mitral valve has two papillary muscles: The anterolateral papillary muscle originates from the anterolateral LV wall and provides chordae to the anterolateral half of anterior and posterior mitral leaflets. The posteromedial papillary muscle originates from the posterior LV wall and provides chordae to the posteromedial half of both leaflets.

Mitral regurgitation may be due to:
  • A primary abnormality of the valve apparatus; or
  • Secondary to another cardiac disease.
Primary causes of chronic MR include:
  • Mitral valve prolapse.
  • Rheumatic heart disease.
  • Drugs.
  • Congenital MR.
Mitral valve prolapse (MVP) is the most common cause in developed countries.

Rheumatic heart disease is uncommon in developed countries but still common in the rest of the world.
Whether rheumatic mitral affection causes mitral stenosis (MS) or mitral regurgitation (MR) depends on physical orientation of the leaflets.

Rheumatic MR is characterized by:
  • Commissural fusion due to fibrosis & calcification.
  • Leaflet contracture.
  • Valve distortion & loss of normal coaptation of the leaflets, due to:
    • Fibrosis
    • Calcification; which extends from one leaflet to the other.
    • Secondary distortion caused by progressive LA & LV dilatation, which restricts posterior leaflet motion, dilates the mitral annulus & aggravates MR. In this manner, MR begets MR.

Drugs: prolonged use of certain drugs may result in MR e.g. the anorectic drugs: Ergotamine, Pergolide, and Cabergoline.

Congenital primary MR may be due, for example, to a valve cleft.

Secondary (functional) causes of MR include:
  • Ischemic heart disease.
  • Cardiomyopathies.
  • Collagen diseases.
  • Mitral annular calcification.
  • Congenital MR.

Ischemic heart disease:
Myocardial ischemia or infarction can cause MR by:
  • LV dilatation, with dilatation of the mitral ring.
  • Papillary muscle dysfunction, usually associated with infarction of the adjacent LV wall. Asynergic contraction of the infarct area adds to mitral leaflet distortion & MR.

Cardiomyopathies (CM):
  • Idiopathic dilated CM: MR results from:
    • Mitral annular dilatation.
    • Distortion of the orientation of the leaflets, chordae & papillary muscles.
  • Endocardial fibroelastosis: similar to dilated CM.
  • Hypertrophic CM: MR is probably caused by systolic anterior motion (SAM) of the anterior mitral leaflet, which occurs in this disease.

Collagen diseases:
Collagen diseases produce MR by restraint of the leaflets & chordae tendineae; Such as:
  • Marfan’s syndrome.
  • Ehlers Danlos syndrome.
  • Pseudo xanthoma elasticum.
  • Systemic lupus erythematosus.
  • Loffler’s endomyocardial fibrosis.
  • Osteogenesis imperfecta.
  • Scleroderma.

Mitral annular calcification:
Mitral annular calcification does not usually cause valve dysfunction, but MR may result from adhesion of the posterior leaflet to the calcific area.

Congenital MR:
Congenital MR can result from:
  • Primary mitral valve anomalies:
    • Clefts of the mitral leaflets.
    • Fenestrations.
    • Double orifice.
    • Absence of leaflets tissue.
    • Malformations of chordae & papillary muscles.
  • MR associated with other congenital heart diseases such as:
    • A–V canal defects.
    • Corrected transposition of the great arteries (TGA): In this case the left-sided tricuspid valve frequently shows Ebstein’s anomaly and is regurgitant.
    • MR may be part of the congenital polyvalvular disease.
    • Coarctation of the aorta.
    • Aortic stenosis (AS).
    • Anomalous left coronary artery from the pulmonary artery.
    • Endocardial fibroelastosis.
  • MR associated with congenital systemic diseases: e.g. Mucopolysaccharidosis.

Other causes of chronic MR:
  • Hypereosinophilic syndrome.
  • Carcinoid disease.
  • Tumors, e.g. LA myxoma.
  • Infiltrative diseases, e.g. amyloidosis, sarcoidosis.
  • Paravalvular prosthetic leak.

Causes of acute MR:
The following conditions produce acute MR by chordal and/or papillary muscle rupture, or by erosion, destruction & perforation of the leaflets:
  • Mitral valve prolapse.
  • Acute myocardial infarction.
  • Infective endocarditis.
  • Trauma.

In view of this huge list of causes of acute and chronic MR; it is really astonishing that MR does not occur more frequently than it is actually present.


Chronic MR pathophysiology:

Chronic MR creates left ventricular volume overload, with progressive LV dilatation. The dilated LV is well compliant & suited to deliver a larger stroke volume.

LV dilatation accommodates the increased end-diastolic volume trying to keep the end-diastolic pressure within normal.

According to Laplace priciple; LV wall stress = PR/2H, where P: pressure, R: radius, and H: wall thickness.
In chronic MR; LV pressure is kept normal in the compensated stage, with some increase in radius, thus wall stress incraeses, but not markedy. 

The backward flow of blood, from LV into the low-pressure LA, reduces LV afterload, since the low-pressure LA offers an easy runoff to LV, much easier than the forward flow into the much higher-pressure aorta. Thus LV systolic function looks better than it actually is, and the measured LV ejection fraction (EF) in these patients is actually over-estimated.

The regurgitant volume is determined by:
  • Regurgitant orifice area.
  • The systolic pressure gradient across the mitral valve.
  • The duration of systole.

MR increases with bigger regurgitant orifice area, higher systolic gradient, and/or longer duration of systole, and vice versa.

With progressive increase in the regurgitant volume & LV dilatation, the Frank-Starling mechanism is overcome, and LV systolic dysfunction starts, with progressive decline in EF.

When the end-diastolic dimension is ≥70 mm, the end-systolic dimension is ≥40 mm, and/or the EF is ≤0.6, systolic dysfunction is already significant, and mitral valve surgery is indicated, even if there are no symptoms related to the valve disease, to avoid the transition into an irreversible state.

Acute MR pathophysiology:

Acute MR creates:
  • Acute pressure overload on the LA & the pulmonary circulation; which often leads to acute pulmonary edema.
  • Acute volume overload on the LV; and the left ventricular end diastolic volume (LVEDV) increases due to the increased preload created by the regurgitant volume.

As in chronic MR; LV contraction is augmented due to myocardial stretch (Frank-Starling mechanism). Meanwhile; the rapid run off of blood into the LA reduces LV afterload. Stronger contraction and reduced afterload result in increased stroke volume, thus reducing the left ventricular end systolic volume (LVESV). The result is an increase of LV ejection fraction.

Because of the decrease in LV systolic volume (radius) & pressure, the systolic wall stress is actually reduced in acute MR.

Clinical manifestations of chronic MR:


Patients with isolated chronic mild, moderate, or even severe MR are asymptomatic until there is LV failure, pulmonary hypertension, or the onset of atrial fibrillation (AF).

In patients with rheumatic MR, symptoms may not appear except two decades after the initial attack of rheumatic carditis.

In the natural history of MR, the first symptoms to appear are usually those due to low cardiac output; particularly easy fatigue, due to backward flow of blood to the extent of reducing forward aortic flow.

Next are pulmonary congestive manifestations, due to LV systolic failure; with dyspnea, orthopnea and paroxysmal nocturnal dyspnea. At this stage, myocardial dysfunction might have become already irreversible due to the long standing MR.

In exceptional cases, irreversible LV systolic dysfunction occurs in the absence of symptoms. Thus; some of the asymptomatic patients with chronic MR will really need mitral valve surgery, when one or more of the indices of significant LV systolic dysfunction mentioned above are fulfilled. This fact clearly illustrates the crucial need for clinical & echocardiographic regular follow up of all patients with MR.

Other symptoms include: thromboembolism, hemoptysis, and right-sided heart failure, but these symptoms are less common than in MS.

There is a high risk for infective endocarditis, with its clinical manifestations & complications, in patients with moderate to severe MR.

Symptoms related to the etiology of MR may be present, e.g. symptoms of ischemic heart disease (IHD), MVP …etc.

Physical examination:

Arterial pulse is usually brisk in upstroke, when the ejection fraction is normal, and usually falls-off rapidly, giving the impression of bounding pulse, but the pulse volume is usually normal.

Sings of LV dilatation & volume overload: with hyperdynamic apical impulse that is displaced outward & downward.

A systolic expansion impulse along the lower left sternal border may be palpable, due to excess filling of the enlarged LA, which pushes the heart anteriorly.

Systolic thrill at the apex is usually detected in patients with significant MR.

Diminished intensity of the first heart sound (S1); reflecting failure of the mitral leaflets to close properly. When the initial mitral valve closure is uninterrupted, S1 intensity is often normal; as occurs in MR secondary to MVP or papillary muscle dysfunction.

Wide splitting of the second heart sound (S2) may occur, due to shortened LV ejection time & early aortic component (A2).

If pulmonary artery hypertension is present, the pulmonary component of the second heart sound (P2) will be accentuated and delayed, thus further widening the splitting of S2.

Third heart sound (S3) is present in hemodynamically significant MR, due to an augmented flow rate across the mitral valve orifice into a dilated left ventricle.

If S3 is accompanied by a harsh systolic murmur; LV systolic function is usually preserved. On the other hand, an S3 accompanied by a soft systolic murmur usually indicates depressed LV systolic function.

Fourth heart sound (S4) is rare, unless there is associated IHD with high left ventricular end diastolic pressure (LVEDP).

Mid systolic click may be heard if MR is due to MVP.

MR specific murmur;
  • In most cases, the murmur is pan systolic high-pitched and blowing, best heard at the apex, and radiated to the left axilla.
  • It may be only mid-to-late systolic when MR is due to MVP or papillary muscle dysfunction.
  • It may radiate to the back when very loud, or if the anterior leaflet is predominantly affected. 
  • It may radiate anteriorly to the sternum when the posterior leaflet is predominantly affected. In these cases it may be heard well at the cardiac base, and could be confused with the murmur of aortic stenosis (AS), but it does not radiate to the carotid arteries.
  • Late systolic accentuation of the murmur may be found in cases with MVP or IHD with papillary muscle dysfunction.
  • In most patients with primary MR; there is good correlation between the loudness of the murmur & the severity of MR, but this correlation is weak in patients with functional MR.
  • Usually there is little variation of the murmur of MR with respiration.

Mid-diastolic apical rumble may be heard if MR is significant, due to excess flow across the mitral valve (Relative stenosis).

Signs of right-sided congestive heart failure will be detected in long standing severe cases with CHF and pulmonary hypertension.

Dynamic auscultation in patients with chronic MR:

Dynamic auscultation is not usually used nowadays in clinical practice, because its interpretation is often difficult and may not be reproducible, and these maneuvers have rarely been validated. The best tool for evaluation of cardiac murmurs is echocardiography.

The murmur of MR may become louder with:
  • Increased preload with increased LV volume, as occurs in:
    • leg raising.
    • lying down.
  • Increased afterload, as occurs in:
    • Squatting.
    • Isometric hand grip.
    • Phenylephrine infusion.

On the other hand, there is a decrease in intensity of the murmur with:
  • Reduced preload, as occurs in:
    • Standing.
    • Valsalva maneuver.
  • Reduced afterload, as occurs in:
    • Amyl nitrate inhalation.

In patients with MVP; the disparity between the redundant mitral valve and the mitral annulus increases with smaller LV volume, thus aggravating MVP & MR. On the other hand; this disparity decreases with larger LV volume.

Thus; decreased preload or afterload, with decreased LV volume, may produce earlier systolic click, and longer but still fainter systolic murmur. On the other hand; increased preload or afterload may cause a delayed systolic click and shorter murmur, but its intensity is often louder.

Clinical manifestations of acute MR:

Acute MR almost always presents with acute heart failure & acute pulmonary edema.
Exceptionally; the acute phase may be well tolerated, with gradual transition into a sub-acute followed by a chronic state.
Normal heart size is usually found in the acute phase.
The systolic thrill may radiate to the base of the heart in presence of posterior leaflet prolapse.
The systolic murmur of MR is usually heard only in early & mid systole, because in late systole the regurgitant V-Wave in LA peaks rapidly & reduces the systolic gradient between LV & LA, thus reducing MR, and the murmur disappears. The murmur may radiate widely, to the axilla, back of the neck, and sacrum.
S3 & S4 are common.

Electrocardiogram in patients with chronic MR:

One or more of the following may be found:
  • LA enlargement similar to that seen in mitral stenosis.
  • LV hypertrophy.
  • RV hypertrophy, in late cases with pulmonary arterial hypertension.
  • Arrhythmia; e.g. AF.
  • Changes related to the etiology of MR, e.g. ischemia and/or infarction pattern in cases of IHD, loss of precordial R-waves in infiltrative cardiomyopathy, and non-specific ST-T changes in MVP.

Chest x-ray:

One or more of the following may be present:
  • Cardiomegaly; with LV configuration. LV size, however, does not correlate with the degree of MR.
  • LA enlargement. Again; LA size, however, does not correlate with the elevation of LA pressure.
  • RA & RV enlargement, with dilated central pulmonary arteries; in the presence of pulmonary hypertension.
  • Pulmonary congestion; in the presence of congestive heart failure (CHF).
  • Pulmonary edema with normal heart size is the usual finding in patients with acute MR.
  • Mitral annular calcification may be detected.
  • Thoracic cage abnormalities may be seen in patients with MVP.
Acute pulmonary edema in a 28-year-old woman with previously undiagnosed combined mitral stenosis and regurgitation who had just given birth to a full-term neonate. Frontal chest radiograph shows massive pulmonary edema with a bias for the perihilar and lower lung regions. The cardiac silhouette is moderately enlarged. Dilation of the main and central pulmonary arteries and cephalization of pulmonary vascular flow are evident. Note the splaying of the angle of tracheal bifurcation, a finding that is indicative of marked left atrial enlargement (arrow).
LA (black arrow) & LV (red arrow) enlargement, with hilar congestion.


Echocardiography is essential for establishing:
  • The diagnosis of the presence of MR.
  • Severity of MR.
  • Etiology of MR.
  • LA size, and exclusion of LA thrombus.
  • LV size and systolic function.
  • Pulmonary artery pressures.

Trans-Esophageal Echocardiography (TEE) is recommended if Trans-Thoracic Echocardiography (TTE) image quality is suboptimal.

Echocardiographic assessment of the severity of MR:

Accurate estimation of the severity of MR is of prime importance; since surgery is indicated only for severe MR.

Doppler and color flow Doppler can be used to evaluate the severity of MR, by measuring and calculating:
  • Vena contracta: the narrowest segment of the jet on color flow imaging.
  • Regurgitant volume.
  • Regurgitant fraction.
  • Regurgitant orifice area.
The following findings are consistent with severe MR, in the average-size adult patient:
  • Vena contracta width ≥0.7 cm.
  • Regurgitant orifice area ≥0.40 cm2.
  • Regurgitant volume ≥60 ml.
  • Regurgitant fraction ≥50%.
  • Regurgitant jet area >40% of LA area.
  • Systolic reversal of flow in a pulmonary vein.

These values are based on an average adult size and may need to be adjusted for body size in small or large patients. Unfortunately, however, there is no specific formula for this adjustment.

In the presence of more than one of these findings, severe MR is diagnosed with more certainty.

Although severe chronic MR may be asymptomatic, it is almost always associated with a clear evidence of LA and/or LV enlargement.

Parasternal short axis (SAX) view: showing the mitral valve ring and leaflets; with its fish-mouth appearance while opened.

In parasternal long axis view the jet can be either directed toward or away from the probe, then its color can be yellow-red (toward the probe) or green-blue (away from the probe).
In apical 4 or 2 chamber views, MR will appear as a blue-green systolic jet going away from the probe.
Apical four chamber view showing LV (left ventricle), RV (right ventricle), RA (right atrium), LA (left atrium) and AML (anterior mitral leaflet) with a small mitral regurgitation (MR) jet into LA. MR jet is seen as a mosaic (multi colour) area within the left atrium within the color flow mapping. Mosaic color is due to aliasing as the MR jet velocity is much above the aliasing velocity of the system. Severity of the mitral regurgitation can be assessed by the extent to which the jet extends into the left atrium. Other measures are the area of the jet, especially in comparison with the area of the left atrium. The larger the ratio, the more severe the mitral regurgitation. AML is seen in the closed position between the LA and LV indicating that it is a systolic frame.
Echocardiographic image in parasternal long axis (PLAX) view illustrating a combination of mitral stenosis and regurgitation. Right half shows the two dimensional image while the left half shows superimposed colour Doppler (color flow mapping) image. The bluish mosaic coloured jet within the Doppler sample volume is suggestive of mild mitral regurgitation. RV: right ventricle; LV: left ventricle; Ao: aorta; LV: left ventricle; LA: left atrium; AML: anterior mitral leaflet; PML: posterior mitral leaflet. The left atrium is dilated, when compared to the aorta, both of which are usually of equal size in this view in normals. Left ventricular size is normal. The anterior mitral leaflet is seen doming into the left ventricle in diastole. The posterior mitral leaflet is pulled along with it due to commissural fusion, causing the paradoxical anterior motion in diastole. Normally the anterior leaflet moves anteriorly and posterior leaflet moves posteriorly while opening in ventricular diastole, allowing free flow of blood from the left atrium to the left ventricle. Both doming of the anterior mitral leaflet and paradoxical anterior motion of the posterior mitral leaflet are characteristic echocardiographic features of rheumatic mitral stenosis.
Baseline transthoracic echocardiography showing a moderate organic mitral regurgitation due to the previous thoracic radiotherapy. (A) Parasternal long-axis view showing the thickening of aorto-mitral aponevrosis highly suggestive of radiation-associated valvular disease. (B) Four-chamber view showing a moderate mitral regurgitation using Colour Doppler. (C) Vena contracta was 4.5 mm. (D) Flow convergence of the regurgitant jet: the effective regurgitant orifice was 0.17 cm2 and the regurgitant volume 37 ml.

Magnetic Resonance Imaging (MRI):

MRI may be useful in selected patients with MR, if echocardiographic imaging is inadequate, or there is a discrepancy between clinical findings and echocardiography.
MRI enables accurate quantitation of LV volumes and ejection fraction.

MRI quantitation of the severity of MR:
  • Calculation of the difference between LV stroke volume and ascending aortic forward flow.
  • Planimetry of the regurgitant orifice.

Cardiac catheterization:

Nowadays; cardiac catheterization is no more needed in most patients with chronic MR.

Indications for cardiac catheterization in MR:
  • For definition of coronary anatomy:
    • Patients >40 years of age.
    • Patients with angina pectoris.
    • Patients with major cardiovascular risk factors, namely: diabetes mellitus, hypertension, Dyslipidemia and smoking.
  • If echocardiographic imaging is inadequate, or there is a discrepancy between clinical findings and echocardiography.
  • Other associated cardiac disease that indicates the need for cardiac catheterization.
  • Patients with acute MR in whom the etiology of MR cannot be accurately defined by non-invasive tests.
  • In infants & children with complex congenital anomaly associated with MR.

Quantitation of the severity of MR by cardiac catheterization:
  • Grade I/IV: When the dye is injected into the LV, the LA partially opacifies & completely clears with each cardiac cycle.
  • Grade II/IV: When the dye is injected into the LV, the LA completely opacifies after several cardiac cycles, but never attains the same opacity like the LV.
  • Grade III/IV: When the dye is injected into the LV, the LA completely opacifies after several cardiac cycles, and attains the same opacity like the LV.
  • Grade IV/IV: When the dye is injected into the LV, the LA completely opacifies within one cardiac cycle attaining the same opacity like the LV.

Management of chronic mitral regurgitation:

Medical management:
  • Vasodilators in asymptomatic patients with moderate-to-severe MR, e.g. angiotensin converting enzyme (ACE) inhibitors, are controversial, but may help delay the need for surgery, by reducing the afterload, thus encouraging forward flow into the aorta & reducing backward regurgitation into the left atrium.
  • Symptomatic heart failure patients need treatment with ACE inhibitors, diuretics, β-blockers, digitalis…etc.
  • Treatment of arrhythmia, accordingly.
  • Antibiotic prophylaxis against infective endocarditis whenever indicated.

Indications for surgery:
  • Symptomatic patients with congestive heart failure (NYHA class II, III or IV) with an ejection fraction >30%.
    • When the EF is ≤30%, LV systolic dysfunction is already irreversible and the surgical mortality is unacceptable.
  • Asymptomatic patients with:
    • LV Ejection fraction ≤60 %.
    • LV end systolic dimension ≥40 mm.
    • Pulmonary artery systolic pressure ≥50 mmHg.

Surgical procedures:
  • Mitral valve repair is the procedure of choice, whenever possible.
  • When valve repair is not possible; mitral valve replacement is done.

Percutaneous procedures:

The following percutaneous procedures might help:
  • Coronary sinus ring; to push the mitral annulus anteriorly and reduce MR.
  • Mitral valve clip; fastening the middle scallops of both mitral leaflets, thus creating a double-orifice mitral valve and reducing MR.
  • Cardiac Re-synchronization Therapy may help in patients with severe congestive heart failure (NYHA class III or IV) despite optimal medical therapy, who have a wide QRS complex >120 msec.

Management of acute MR:

Acute MR is usually a medical emergency. Most patients need urgent surgery with either mitral valve repair or replacement as the case implies.

Intravenous vasodilator therapy with sodium nitrprusside is often needed to control acute pulmonary edema.

Intraaortic balloon couterpulsation is needed in many patients for heomynamic support, as well as intrvenous inotropic support, to tide the ptient over until surgery is carried out as early as possible.

Some patients with hypoxic respiratory failure may require mechnical ventilation.

The indications for cardiac catheterization are the same as in chronic MR.

If cardiac catheterization is indicated, the patient may be taken to the catheterization laboratory with the intraaortic balloon in place and the ventilator connected, and transferred directley from there to the operting room.