Valvular Heart Disease
Primary valvular heart disease ranks well below coronary heart disease, stroke, hypertension, obesity, and diabetes as major threats to the public health. Nevertheless, it is the source of significant morbidity and mortality. Rheumatic fever is the dominant cause of valvular heart disease in developing countries. Its prevalence has been estimated to range from as low as 1.0 per 100,000 school-age children in
Fig. Heart anatomy
TS, a relatively uncommon valvular lesion in North America and Western Europe, is more common in tropical and subtropical climates, especially in southern Asia and in
As of the year 2000, worldwide death rates for rheumatic heart disease approximated 5.5 per 100,000 population (n = 332,000), with the highest rates reported from
The incidence of infective endocarditis has increased with the aging of the population, the more widespread prevalence of vascular grafts and intracardiac devices, the emergence of more virulent multidrug-resistant microorganisms, and the growing epidemic of diabetes. Infective endocarditis has become a more frequent cause of acute valvular regurgitation.
Bicuspid aortic valve disease affects as many as 1–2% of the population, and an increasing number of childhood survivors of congenital heart disease present later in life with valvular dysfunction. The past several years have witnessed significant improvements in surgical outcomes with progressive refinement of relatively less-invasive techniques. Percutaneous heart valve replacement or repair is under active clinical investigation.
Major Causes of Valvular Heart Diseases
Valve Lesion Etiologies
Mitral stenosis Rheumatic fever
Congenital
Severe mitral annular calcification
SLE, RA
Mitral regurgitation Acute
Endocarditis
Papillary muscle rupture (post-MI)
Trauma
Chordal rupture/Leaflet flail (MVP, IE)
Chronic
Myxomatous (MVP)
Rheumatic fever
Endocarditis (healed)
Mitral annular calcification
Congenital (cleft, AV canal)
HOCM with SAM
Ischemic (
Dilated cardiomyopathy
Aortic atenosis Congenital (bicuspid, unicuspid)
Degenerative calcific
Rheumatic fever
Aortic regurgitation Valvular
Congenital (bicuspid)
Endocarditis
Rheumatic fever
Myxomatous (prolapse)
Traumatic
Syphilis
Ankylosing spondylitis
Root disease
Aortic dissection
Cystic medial degeneration
Marfan syndrome
Bicuspid aortic valve
Nonsyndromic familial aneurysm
Aortitis
Hypertension
Tricuspid stenosis Rheumatic
Congenital
Tricuspid regurgitation Primary
Rheumatic
Endocarditis
Myxomatous (TVP)
Carcinoid
Congenital (Ebstein’s)
Trauma
Papillary muscle injury (post-MI)
Secondary
RV and tricuspid annular dilatation
Multiple causes of RV enlargement (e.g., long-standing pulmonary HTN)
Chronic RV apical pacing
Pulmonic stenosis Congenital
Carcinoid
Pulmonic regurgitation Valve disease
Congenital
Postvalvotomy
Endocarditis
Annular enlargement
Pulmonary hypertension
Idiopathic dilatation
Marfan syndrome
Mitral regurgitation
Mitral regurgitation affects more than 2 million people in the
Mitral regurgitation is defined as systolic retrograde flow from the left ventricle into the left atrium. Although a trivial form of this valve disease is often seen in healthy people, epidemiological data show that moderate or severe regurgitation is the most frequent valve disease in the
All lesions that cause mitral regurgitation do so by reduction or elimination of the normal systolic coaptation between anterior and posterior mitral leaflets, which normally ensures mitral competence. Consistent anatomical and functional descriptors of mitral lesions are essential to assess surgical reparability but overlapping and poorly defined terminology has caused confusion. Causes and mechanisms are not synonymous and a particular cause might produce regurgitation by different mechanisms (table). Surgical correction of this valve disease is dependent on both cause and mechanism, which affect reparability. Causes are generally classified as ischaemic (mitral regurgitation due to consequences of coronary disease, not fortuitous association of both) and non-ischaemic (all other causes). Mechanisms are grossly classified as functional (mitral valve is structurally normal and disease results from valve deformation caused by ventricular remodelling) or organic (intrinsic valve lesions). They can be subclassified by leaflet movement (Carpentier’s classification)—type I (normal valve movement, such as annular dilatation or leaflet perforation); type II (excessive movement); and type III (restrictive movement: IIIa—diastolic restriction such as rheumatic disease; IIIb—systolic restriction as in functional disease). Carpentier also proposed a simple lesion localisation classification.
Schematic anatomical mitral-valve presentation
(A) Atrial view of a healthy mitral valve. Posterior leaflet has a shorter length but occupies a longer circumference than the anterior leaflet. Mitral annulus around the leaflet is part of the aortic-mitral fibrosa superiorly, is asymmetric, and short in its anteroposterior dimension. Leaflet segmentation starts with A1—P1 close to the anterolateral commissure, with A2—P2 centrally, and A3—P3 close to the posteromedial commissure. The normally apposing leaflets make up the mitral smile. (B) Example of a flail posterior leaflet affecting the P2 segment with ruptured chordae. Note the bulge and excess tissue of the flail segment and the annular enlargement mostly along the posterior part of its circumference. (C) Initial step of surgical valve repair. Resection of the flail segment can be triangular (as shown) or quadrangular and leaves the healthy P1 and P3 segments available for reattachment and repair. (D) Posterior leaflet has been restored by approximation of the remaining segment after resection of the flail segment and the mitral annular dimensions have been restored by an annuloplasty ring. In this example an incomplete ring has been used with its extremities sutured to the trigonal regions of the aortic-mitral fibrosa. The mitral smile and competence have been restored.
Major causes of surgical mitral regurgitation in western countries are degenerative (primary myxomatous disease, primary flail leaflets, annular calcification), representing 60—70% of cases, followed by ischaemic mitral regurgitation (20%), endocarditis (2—5%), rheumatic (2—5%), and miscellaneous causes (cardiomyopathies, inflammatory diseases, drug-induced, traumatic, congenital). Ischaemic disease probably represents a large proportion of the non-surgical disease burden. Nomenclature and mechanisms of major causes are summarised below.
Degenerative mitral regurgitation is usually related to mitral-valve prolapse and rarely to isolated mitral annular calcification. Mitral-valve prolapse is an abnormal systolic valve movement into the left atrium (≥2 mm beyond saddle-shaped annular level). This excessive movement can be seen with other causes such as endocarditis. Prolapse might be of moderate magnitude (leaflet tips remain in the left ventricle—ie, billowing mitral valve) or can be severe (eversion of leaflet tip into left atrium—ie, flail leaflet—usually caused by ruptured chordae). The main phenotypes of mitral prolapse are diffuse myxomatous degeneration (mitral-valve prolapse syndrome or Barlow’s disease, sometimes with posterior annular translocation into left atrium) or primary flail leaflets with ruptured chordae affecting the posterior leaflet in 70% of cases, and accompanied by myxomatous degeneration localised to the flail segment and generally normal valve morphology elsewhere. Myxomatous degeneration remodels valve tissue by increasing the spongiosa layer and valve water content and thickness, with mucopolysaccharide and matrix changes, as a functional manifestation of metalloproteinase alterations. These mitral tissue changes and prolapse might be genetically transmitted and X-chromosome linked. Degenerative mitral regurgitation is the most reparable form, warranting early and careful assessment.
Echocardiographic appearance of the two main anatomical types of mitral regurgitation from apical views centred on the mitral valve
(A) An example of a flail posterior leaflet with the tip of the leaflet floating in the left atrium. Note the otherwise grossly normal anterior leaflet. (B) An example of functional mitral regurgitation. Strut chordae (long arrows) to the anterior and posterior leaflets exert an abnormal traction on the body of the leaflets, which displaces (arrowheads) the leaflets towards the ventricular apex, creating an area of tenting above the mitral annulus and an incomplete coaptation. LA=left atrium.
The ischaemic form of this disease rarely results from an organic mechanism (papillary-muscle rupture) and is rarely acute. Frequently, it is functional (structurally normal leaflets) and chronic, epitomising left-ventricular disease that causes valvular dysfunction. Papillary-muscle dysfunction plays little part in the generation of functional mitral regurgitation, which is mostly caused by apical and inferior-papillary-muscle displacement due to ischaemic left-ventricular remodelling. Because chordae are non-extensible, papillary-muscle displacement exerts traction on leaflets through strut chordae implanted on the body of leaflets, resulting in tethered and apically displaced leaflets (tenting). Coupled with annular flattening, enlargement, and decreased contraction, mitral valve tenting results in coaptation loss that yields functional mitral regurgitation. Asymmetric tenting due to regional scarring (inferior infarction) might explain commissural jets of ischaemic disease. Rheumatic mitral regurgitation—past the acute phase—causes chordal and leaflet retraction, which, amplified by annular dilatation, results in coaptation loss. Postinflammatory and postradiation mitral regurgitations have similar mechanisms. Retraction of tissue is a major limitation to successful valve repair.
Endocarditic mitral regurgitation might be caused by ruptured chordae or perforations. In all causes, annular enlargement is common, is located mostly or exclusively on the posterior part of the annular circumference, and surgical repair almost always requires annuloplasty.
Pathophysiology and progression
The degree of mitral regurgitation is defined by lesion severity (measured as effective regurgitant orifice [ERO] area) and the yielding volume overload (measured as regurgitant volume[RVol]), but it is also affected by the driving force (left-ventricular systolic pressure) and left-atrial compliance.5 Thus, in acute disease, the large regurgitant orifice converts ventricular energy mostly into potential energy (left-atrial pressure V-wave) due to non-compliant left atrium. In chronic regurgitation, the enlarged left atrium is compliant, the V-wave is often small, and ventricular energy is converted mostly into kinetic energy (large RVol). This process of atrial enlargement and increased compliance probably explains atrial pressure reduction and clinical improvement after initial heart failure caused by acute mitral regurgitation.
The ERO area is not necessarily fixed and can be dynamic. Increased loading or contractility can cause the ERO area to increase or decrease slightly. With valve prolapse, the area is very dynamic, increasing progressively during systole, and is sometimes purely end-systolic. In functional mitral regurgitation, ERO area is dynamic during systole, with large area during short isovolumic contraction and relaxation phases caused by lesser ventricular pressure apposing leaflets. This type of regurgitation is also dynamic with decreased loading or inotrope administration, and might disappear with these interventions, whereas exercise most often results in augmentation of ERO area. Long-term progression of organic disease is about 5—7 mL per year for RVol and is determined by ERO area progression caused by new lesions or annular enlargement. Thus, mitral regurgitation is self-sustained, causing atrial and annular enlargement, which in turn leads to increased ERO area.
The ventricular and atrial consequences of organic mitral regurgitation are initiated by volume overload with increased preload and left-ventricular and left-atrial enlargement. Impedance to ejection is reduced despite normal or increased vascular resistances, whereas myocardial afterload (end-systolic wall stress) is normal with an end-systolic volume that is normal to slightly increased. Thus, in organic disease, altered left-ventricular function might coexist with normal or high ejection fraction. Borderline normal ejection fraction, between 50—60%, already implies overt left-ventricular dysfunction. Ventricular dysfunction should be suspected when end-systolic dimensions are large but is often masked by a large ejection volume and is revealed after surgical elimination of mitral regurgitation, with a postoperative average immediate ejection fraction drop of about 10%. Diastolic ventricular dysfunction is difficult to characterise, but seems to reduce exercise capacity.
Physiology of functional mitral regurgitation is even more complex than that of organic mitral regurgitation since ventricular dysfunction predates the regurgitation. Nevertheless, functional mitral regurgitation further increases atrial pressure, which leads to pulmonary hypertension and heart failure. With increased atrial pressure and low driving force, functional regurgitation often has low RVol and can be silent.
Whether functional regurgitation affects remodelling and dysfunction is uncertain but is suspected because of the high mortality associated with increased severity of mitral regurgitation.
Progression or recurrence after annuloplasty is weakly related to annular enlargement but strongly to increased mitral tenting caused by ventricular remodelling, papillary-muscle displacement, and increased chordal traction; however, rates of progression are unknown.
Assessment
Initial clinical assessment looks for symptoms, signs of heart failure, and physical signs of severe mitral regurgitation—ie, displaced apical impulse, systolic thrill, loud systolic murmur, S3, early diastolic rumble, and cardiomegaly with left-atrial enlargement on chest radiography and atrial fibrillation. These signs are important but not specific enough to rely solely on them to suggest surgery.
Doppler echocardiography is the main method for assessment of patients with mitral regurgitation. Transthoracic or transoesophageal echocardiography provides functional anatomical information that is crucial for assessment of reparability by defining cause, mechanism, presence of calcification, and localisation of lesions. Transoesophageal echocardiography provides better imaging quality than transthoracic echocardiography but its ability to detect details such as ruptured chordae rarely changes management. Transoesophageal echocardiography essentially provides incremental clinically meaningful information (such as reparability) when transthoracic echocardiography is of poor quality or when complex, calcified, or endocarditic lesions are suspected. Thus, transoesophageal echocardiography is rarely used on an outpatient basis and is mostly used intraoperatively for lesion verification and to monitor surgical results. Real-time three-dimensional echocardiography has at present insufficient image resolution but pilot data suggest that it allows quantitative assessment of structures that are not easily measurable by two-dimensional echocardiography, such as mitral annulus. Although emerging technologies such as transoesophageal echocardiography three-dimensional imaging have great potential, they need to be rigorously tested.
Doppler echocardiography provides crucial information about mitral regurgitation severity (table). Comprehensive integration of colour-flow imaging and pulsed and continuous wave doppler echocardiography is necessary because jet-based assessment has major limitations (figure). Quantitative assessment of regurgitation is feasible by three methods—quantitative doppler echocardiography based on mitral and aortic stroke volumes, quantitative two-dimensional echocardiography based on left-ventricular volumes, and flow-convergence analysis measuring flow with colour-flow imaging proximal to the regurgitant orifice (proximal isovelocity surface area method; figure ). These methods allow measurement of ERO area and RVol and have important prognostic value. Severe mitral regurgitation is diagnosed with an ERO area of at least 40 mm2 and RVol of at least 60 mL per beat; and moderate regurgitation with ERO area 20—39 mm2 and RVol 30—59 mL per beat. Outcome data suggest that a smaller volume mitral regurgitation and smaller ERO area (≥30 mL and ≥20 mm2, respectively) are associated with severe outcome in patients with ischaemic disease; therefore, thresholds for severe disease are cause-dependent. Consistency in all measures of mitral regurgitation severity is essential to appropriately grade disease severity (table ). Haemodynamic assessment is completed with doppler measurement of cardiac index and pulmonary pressure.
Use of colour-flow imaging for assessment of mitral regurgitation
(A) Jet imaging in left atrium. The jet is eccentric and is displayed with mosaic colours, whereas the normal flow is of uniform colour. It fills only part of the left atrium and might underestimate the regurgitation. The observation of a large flow convergence should lead to suspicion of severe regurgitation. (B) Measurement of the flow convergence with colour-flow imaging. The baseline of the colour scale has been brought down to decrease the aliasing velocity to 53 cm/s (velocity at the blue-yellow border), which allows the flow convergence (yellow) to be seen. The radius (r) of the flow convergence is used in the formula for calculation of the instantaneous regurgitant flow (258 mL/s). Flow=6·28×Valiasing×r2=6·28×53×0·882=258 mL/s. Division of this value by the jet velocity allows calculation of the effective regurgitant orifice of mitral regurgitation. LA=left atrium.
Doppler echocardiography also measures left-ventricular and left-atrial consequences of mitral regurgitation. End-diastolic left-ventricular diameter and volume indicate volume overload whereas end-systolic dimension shows volume overload and ventricular function. Patients with left-ventricular ejection fraction less than 60% or end-systolic diameter of at least 40—45 mm are regarded as having overt left-ventricular dysfunction. Left-atrial diameter indicates volume overload but also conveys important prognostic information. Left-atrial volume was recommended as the preferred measure of atrial overload, (at least 40 mL/m2 for severe dilatation) and predicts the occurrence of atrial fibrillation.
Exercise tests are used to define functional capacity. One in five asymptomatic patients shows severe functional limitations during cardiopulmonary exercise. Peak oxygen consumption compared with that expected for age, sex, and weight objectively measures functional limitations versus normal reference values. Other exercise modalities, such as supine-bike exercise, examine changes in severity of mitral regurgitation with activity, especially seen in ischaemic and functional disease and might reveal poor prognosis when ERO area increases. Standard postexercise echocardiography was used to detect exertional ventricular volume increase as a predictor of postoperative left-ventricular dysfunction, but difficulties in measurement of monoplane ventricular volumes hinder this approach. Other stress tests are rarely used. Dobutamine echocardiography reduces mitral regurgitation universally, but in selected patients with ischaemic disease it might reveal viability and ischaemia.
MRI shows mitral regurgitation jets, with limitations similar to those of colour-flow imaging; quantitative measurements are possible but validation studies are few. This imaging method is unique in revealing ventricular scars and in assessment of viability in ischaemic disease and is useful in measurement of ventricular volumes but its incremental diagnostic role remains unknown.
Detection of hormonal activation is important in many cardiac diseases. Atrial natriuretic peptide has little specificity for mitral regurgitation and is strongly activated by arrhythmias, irrespective of mitral regurgitation severity. B-type natriuretic peptide is of greater value than atrial natriuretic peptide in patients with regurgitation. Its activation in organic disease is determined by the consequences—mostly left-atrial enlargement, symptoms, rhythm, and left-ventricular function—rather than the severity of regurgitation. Importantly, its activation is associated with poor outcome and should alert clinicians. Strong B-type natriuretic peptide activation is noted in functional mitral regurgitation linked to the severity of end-systolic ventricular changes and of mitral regurgitation. Subtle sympathetic activation and altered β receptors in organic disease might indicate left-ventricular dysfunction but are usually less prominent than in functional disease.
Cardiac catheterisation is not consistently used by institutions and might be overused in some.3 In academic centres, it is rarely used to define haemodynamics, which are usually provided by doppler echocardiography. Left ventriculography and right-heart catheterisation are rarely needed for assessment of mitral regurgitation. Conversely, in most patients aged 45 years or older, coronary angiography is routinely done preoperatively.
Natural history and clinical outcome
Although a few prospective studies are available, most data for mitral regurgitation outcome are extracted from observational series. Clinical outcome under medical management and after surgery is different in organic and functional disease.
Natural history of organic regurgitation has been poorly defined, largely because of limitations in severity assessment. Old studies, before echocardiography, showed a wide range in 5-year survival rates from 27% to 97%, probably related to variations in severity. Most data (table) were from studies of patients diagnosed with mitral regurgitation due to flail leaflets, most of whom had severe regurgitation. Such patients have ventricular enlargement causing the notable volume overload and incur excess mortality overall; mortality was especially high in patients with class III—IV symptoms but also notable in those with no or minimum symptoms. A sudden death rate of 1·8% per year overall varied from as high as 12·0% per year in patients with class III—IV symptoms who had not undergone surgery to 0·8% per year in asymptomatic patients with normal ejection fraction and sinus rhythm. Patients in some mitral regurgitation subsets have low mortality, such as young patients (<50 years) even with severe mitral regurgitationor those of all ages with initially a moderate disorder. Conversely, in a prospective study of asymptomatic patients with long-term follow-up, those with severe regurgitation proven by quantitative measurements showed increased mortality under medical management.9 Thus, older patients (≥50 years) with severe (defined as ERO area ≥40 mm2) organic mitral regurgitation are at increased risk of mortality (yearly rates of about 3% for moderate regurgitation vs 6% for the severe organic form). For morbid complications, all studies substantiated the adverse effect of severe regurgitation. Patients with flail leaflet and in general those with severe mitral regurgitation had, under medical management, yearly cardiac event rates of 10—12%—including about 9% for heart failure and 5% for atrial fibrillation. Within 10 years of diagnosis, cardiac events arise in most patients with severe mitral regurgitation, and death occurs or cardiac surgery is needed in at least 90%, making surgery an almost unavoidable consideration in such patients. The risk of stroke is low, but in excess of that expected in old patients and is strongly linked to occurrence of atrial fibrillation, and thus to left-atrial size. Predictors of reduced survival under medical management are symptoms (class III or IV), even if transient, reduced ejection fraction, severe mitral regurgitation with ERO area of 40 mm2 or more, and hormonal activation, although not as well substantiated. Predictors of cardiac events are atrial fibrillation, left-atrial enlargement of at least 40—50 mm diameter, , flail leaflet or large ERO area—all markers of severe mitral regurgitation—and, during exercise, reduced peak oxygen consumption and possibly reduced right ventricular function.
Clinical outcome after surgery depends on patient-specific, disease-related, and surgery-related factors. Early postoperative mortality is largely affected by age, but improvement of surgical results reduced the risk to about 1% for patients younger than 65 years, 2% for those aged 65—75 years, and 4—5% for older than 75 years. Increased surgical risk is also linked to preoperative severe symptoms or heart failure whereas ejection fraction has less effect. Surgery-related determinants of operative risk are governed by mitral reparability, which ensures reduced risk, whereas risk is increased with concomitant coronary artery bypass grafting. Other associated procedures, such as tricuspid repair or replacement, or those aimed at treatment or prevention of atrial fibrillatioeed a longer bypass time, which can increase risk. Long-term, patient-related factors continue to affect outcome, particularly coronary disease or reduced renal function. Age determines mortality but restoration of life expectancy is similar in young and old patients. After surgery, patients with severe symptoms before surgery continue to have increased mortality despite symptom relief, whereas in those with no or few symptoms, restoration of life expectancy can be achieved. Similarly, patients with overt preoperative ventricular dysfunction have increased postoperative mortality, especially with ejection fraction less than 50%. Generally, a 10% early postoperative reduction in ejection fraction happens after elimination of volume overload, whereas end-systolic characteristics (volume, wall stress) are unchanged. This reduction is lowest after valve repairand is minimised by preservation of subvalvular apparatus during valve replacement. Nevertheless, 25—30% of patients with mitral regurgitation present with postoperative left-ventricular dysfunction, especially those with preoperative ejection fraction of less than 60% or end-systolic diameter at least of 40—45 mm. Occasional unexpected ventricular dysfunctions arise in patients with ejection fraction greater than 60% and no perfect predictor has been identified. Hence, in some centres, prevention of postoperative left-ventricular dysfunction relies on performance of early surgery wheo sign of left-ventricular alteration is present.
Coronary disease (even in the absence of angina) increases the risk of left-ventricular dysfunction despite the performance of coronary artery bypass grafting. Although no clinical trial has compared outcomes of patients randomised to repair versus replacement, observational evidence suggests that the major surgical determinant of improved long-term outcome is valve repair, which allows restoration of life expectancy and reduces the risk of heart failure after surgery. Although mitral regurgitation can recur after repair, reoperation rates do not differ after repair compared with replacement. Thus, mitral valve repair is widely regarded as the preferred mode of correction of organic mitral regurgitation, especially degenerative.
For ischaemic mitral regurgitation, the natural history of the functional form is incompletely definedwhereas that of papillary-muscle rupture is known to be rapidly fatal. Whether functional regurgitation intrinsically causes poor outcome, or whether it indicates left-ventricular alterations, is still disputed. However, association of severe ischaemic mitral regurgitation with severe outcomes, independent of ejection fraction, age, and presentation, suggests that the regurgitation is indeed causal of the poor outcome. This prognostic role of mitral regurgitation is now substantiated by results from studies of patients with acute or chronic myocardial infarction, by clinical trials and by population studies. Another important concept is that even modest regurgitation is associated with substantially increased mortality, a fact proved by quantitative data. ERO area of ischaemic mitral regurgitation independently predicts excess mortality. Patients with an area larger than 20 mm2 incur about a two-fold increase in mortality risk and about a four-fold increase in the risk of heart failure compared with those with a similar ischaemic left-ventricular dysfunction but no mitral regurgitation. The better predictive value of ERO area than that of RVol is explained by the strong link between ERO area and filling pressure. Increase in ERO area with exercise might additionally affect clinical outcome, survival, and heart failure. Nevertheless, a clinical trial is needed to determine whether surgical correction of the valvular consequence (ischaemic mitral regurgitation) improves mortality and heart failure in this mainly ventricular disease. Clinical outcome of functional disease caused by cardiomyopathy is not well defined but few data suggest that mitral regurgitation yields poor outcomes.
Fig Mitral regurgitation
Outcomes after surgery for functional disease remain suboptimum. Operative mortality is still high despite definite surgical improvements. Long-term mortality and heart failure rates are high, although not unexpected in patients with coronary disease, previous myocardial infarction, reduced ventricular function, and vascular comorbidity. These suboptimum outcomes explain uncertainties in surgical indications. However, with low operative mortality, postoperative heart failure and symptomatic improvements are possible.
The natural history of untreated organic and functional mitral regurgitation emphasises the importance of treatment of patients with severe regurgitation. Because the effects of various treatments on survival have not been tested in randomised clinical trials, the value of any approach is estimated on the basis of outcome studies.
Fig Management strategy for patients with chronic severe mitral regurgitation. *Mitral valve (MV) repair may be performed in asymptomatic patients with normal left ventricular (
Medical treatment aims to prevent progression of organic disease. Prevention of endocarditis is directed at forestalling catastrophic infectious complications and sudden mitral regurgitation progression associated with endocarditis. Diuretics often reduce or eliminate symptoms of disease but such improvement should not unduly reassure physicians. Patients who had transiently severe symptoms and improved with treatment continue to be at high risk and should be promptly assessed for surgery.
Treatment of organic mitral regurgitation with vasodilators has been advocated on the basis of experimental studies showing reductions in acute RVol and even ERO area with blood pressure reduction. Acutely ill patients with mitral regurgitation benefit from vasodilator treatment. However, despite some encouraging data, translation to chronic treatment of organic disease is unresolved because reported series were small, rarely randomised, and contradictory in conclusions. Activation of the tissue (not systemic) renin-angiotensin myocardial system was shown in organic mitral regurgitation. Consistent pilot studies suggest potential of drugs blocking tissue renin-angiotensin system to stabilise organic disease severity and consequences. The effect of such treatments on clinical outcome remains to be shown. β blockade in organic mitral regurgitation has only been tested in animal models and remains conjectural. Conversely, in functional disease, medical treatment has been better studied than in organic disease. Maximum medical treatment of patients with heart failure and left-ventricular dysfunction reduces functional mitral regurgitation. Specifically β blockade—with carvedilol or long-acting metoprolol—and inhibition of angiotensin-converting enzyme reduce functional mitral regurgitation severity. These therapies are recommended for treatment of left-ventricular dysfunction. Thus, non-urgent surgical indications should be reviewed after maximum medical treatment has taken effect.
Interventional treatment is not yet approved for clinical use and remains investigational. Percutaneous revascularisation of patients with ischaemic regurgitation is possible but patients are often left with residual regurgitation that affects prognosis so that more effective treatment is necessary. Resynchronisation treatment in left-ventricular dysfunction with delayed conduction might improve functional mitral regurgitation. Two specific interventional approaches to treatment are discussed here.
Valvular edge-to-edge attachment mimics the surgical procedure proposed by Alfieri and colleagues, creating a tissue bridge between anterior and posterior leaflets. Percutaneously, this technique uses a clip or sutures deployed through trans-septal catheterisation. Experimental studies have shown success and reliable clip or suture placement through the trans-septal approach (figure). Early trials also suggest safety and feasibility with close echocardiographic guidance in centres with much experience of interventional valvular procedures. Data for how well this intervention works are preliminary but encouraging,128 suggesting that more than 80% of patients can be discharged from hospital with a clip, and mild or little mitral regurgitation. A randomised trial comparing percutaneous clip and surgery is in progress. The edge-to-edge technique has important limitations. First, the application of this technique is restricted to localised prolapse of the central segment of the anterior and posterior leaflets. Second, annular dilatation is not addressed by the procedure and might cause residual regurgitation.
Percutaneous devices used for treatment of mitral regurgitation
(A) Percutaneous clip introduced by venous and trans-septal approach into the left atrium and through the mitral orifice. The clip then grabs both leaflets, resuspending them with prolapse. (B) Percutaneous coronary sinus cinching device introduced through the jugular vein into the coronary sinus. The distal stent (smallest) then the proximal stent are deployed. With time the bridge shrinks and cinches the annulus.
Annuloplasty aimed at reduction of annular dilatation is under investigation mostly with coronary sinus cinching. Technically, stabilisation of material with sufficient constraining force to obtain more than 20% diameter reduction is a challenge. Most devices are composed of anchoring devices placed in the distal and proximal coronary sinus and an intermediate tensioning or supporting element. Experimentally, reduction of mitral regurgitation is achievable, but clinical results are preliminary. Feasibility through a jugular approach and safety seem to be acceptable. Potential limitations are those of annuloplasty (incomplete valve tenting correction) and those of coronary sinus approach that might reduce only part of the annular circumference with an effectiveness limited by the 1—2 cm sinus-annular distance. Because of safety concerns related to proximity of the coronary sinus and circumflex artery with potential artery compression, non-coronary sinus approaches to annuloplasty and percutaneous ventricular remodelling-constraint devices are being investigated.
On the basis of the success of balloon valvuloplasty for mitral stenosis, percutaneous treatment of mitral regurgitation is expected to be successful but this success will necessitate complex development that needs strong cardiologist—engineer collaboration and rigorous assessment.
Surgical treatment of mitral regurgitation is the only approach with defined clinical success, providing sustained relief of symptoms or heart failure. However, no randomised trial has been done to prove mortality or cardiac event reduction. The standard surgical approach is a median sternotomy, but sometimes only partial sternotomy or minimally invasive surgery through thoracoscopic approach can be used.
Valve repair includes an array of valvular, subvalvular, and annular procedures aimed at restoration of leaflet coaptation (ie, valvular normal function) and elimination of mitral regurgitation. These surgical techniques are more successful with redundant than with retracted or calcified leaflets. For valve prolapse, typical repair is resection (triangular or quadrangular) of the prolapsed posterior leaflet segment whereas the anterior leaflet is rarely resected. Subvalvular support can be obtained by chordal transfer or artificial chords rather than chordal shortening. Annuloplasty is routinely used with annular bands or flexible or rigid rings. Many additional technical procedures might be used at the surgeon’s discretion to restore coaptation and valve competence. Conversely, in functional mitral regurgitation, valve repair is rather uniform with restrictive annuloplasty substantially reducing the anteroposterior annular diameter. New rings aimed at annular reshaping, specific to each cause of functional regurgitation (ischaemic disease or cardiomyopathy) are now available but their incremental value (compared with traditional rings) is not defined. Valve repair is done in about half of patients who undergo surgery for mitral regurgitation in the
Valve replacement involves insertion of a biological or mechanical prosthesis. Bioprosthetic valve replacement is associated with low embolic risk but shorter durability, whereas mechanical valve replacement is associated with high risk of embolism and haemorrhagic complications (due to intensive warfarin treatment) but has potential for long-lasting durability. Results of randomised trials showed that within 10 years of surgery these risks are balanced. Older age determines the probability that bioprosthetic durability will be longer than life expectancy, and is the main bioprosthesis insertion indication (usually >65 years of age). Ability to achieve high-quality anticoagulation and patient’s desire also affect the choice of prosthesis. Irrespective of the prosthesis selected, conservation of subvalvular apparatus is essential for preservation of ventricular function. The risk of prosthetic complications makes surgical indications more restrictive when valve replacement is likely.
Controversies and guidelines for treatment
In view of the experimental nature of medical and interventional treatments for mitral regurgitation, surgery is the only treatment recommended by management guidelines. Because surgery is associated with small but definite risks, those patients with a higher risk of spontaneous complications than of surgery-related complications are selected. Guidelines should, in our opinion, be interpreted as a minimum to be applied by all physicians but should not deter centres with better results than those of other centres from providing advanced care to patients with mitral regurgitation. Furthermore, the absence of clinical trials and few prospective studies create ample controversy, which should be addressed in future studies.
Although approaches to surgical indications are detailed in clinical guidelines, they are summarised here. Rescue surgical indications—class I by guidelines—are compulsory. Patients with organic mitral regurgitation who have developed severe symptoms (class III or IV), heart failure, or signs of overt left-ventricular dysfunction (ejection fraction <60% or end-systolic dimension ≥40—45 mm) have an immediate high risk and therefore prompt surgery—repair (preferable) or replacement—is indicated. Even with advanced heart failure or ventricular dysfunction, contraindications to surgery are rare as long as mitral regurgitation remains severe, emphasising the importance of quantitative assessment of disease. Such rescue surgery is indispensable, but is not the preferred timing for surgery in organic disease. Indeed, patients who need to be operated on at such a late stage of their disease have increased mortality after surgery. This outcome emphasises the importance of early detection and assessment of mitral regurgitation. In functional regurgitation, rescue surgery is the most frequent surgical indication, but consideration should be given to surgery in symptomatic patients before heart failure becomes intractable.
Restorative surgical indications—class II by guidelines—are optional. Patients with no or minimum symptoms at baseline cannot expect substantial symptomatic improvement. Those with functional mitral regurgitation are rarely candidates for restorative surgery while asymptomatic but might be suitable for valve repair if coronary artery bypass grafting is necessary independently of the mitral regurgitation. In organic regurgitation, postoperative outcome studies in patients with no or minimum symptoms before surgery show restoration of life expectancy, emphasising the importance of this approach. Patients who are asymptomatic but had either reduced functional capacity by objective exercise testing, hormonal activation, or paroxysmal atrial fibrillation are specific but not exclusive candidates for restorative surgery.
Mitral stenosis
Etiology and Pathology
Rheumatic fever is the leading cause of mitral stenosis (MS) (Table). Other less common etiologies of obstruction to left atrial outflow include congenital mitral valve stenosis, cor triatriatum, mitral annular calcification with extension onto the leaflets, systemic lupus erythematosus, rheumatoid arthritis, left atrial myxoma, and infective endocarditis with large vegetations.
Pure or predominant MS occurs in approximately 40% of all patients with rheumatic heart disease and a history of rheumatic fever. In other patients with rheumatic heart disease, lesser degrees of MS may accompany mitral regurgitation (MR) and aortic valve disease. With reductions in the incidence of acute rheumatic fever, particularly in temperate climates and developed countries, the incidence of MS has declined considerably over the past few decades. However, it remains a major problem in developing nations, especially in tropical and semitropical climates.
In rheumatic MS, the valve leaflets are diffusely thickened by fibrous tissue and/or calcific deposits. The mitral commissures fuse, the chordae tendineae fuse and shorten, the valvular cusps become rigid, and these changes, in turn, lead to narrowing at the apex of the funnel-shaped (“fish-mouth”) valve. Although the initial insult to the mitral valve is rheumatic, the later changes may be a nonspecific process resulting from trauma to the valve caused by altered flow patterns due to the initial deformity. Calcification of the stenotic mitral valve immobilizes the leaflets and narrows the orifice further. Thrombus formation and arterial embolization may arise from the calcific valve itself, but in patients with atrial fibrillation (AF), thrombi arise more frequently from the dilated left atrium (LA), particularly the left atrial appendage.
Pathophysiology
Iormal adults, the area of the mitral valve orifice is 4–6 cm2. In the presence of significant obstruction, i.e., when the orifice area is reduced to < ~2 cm2, blood can flow from the LA to the left ventricle (LV) only if propelled by an abnormally elevated left atrioventricular pressure gradient, the hemodynamic hallmark of MS.
When the mitral valve opening is reduced to <1 cm2, often referred to as “severe” MS, a LA pressure of ~25 mmHg is required to maintain a normal cardiac output (CO). The elevated pulmonary venous and pulmonary arterial (PA) wedge pressures reduce pulmonary compliance, contributing to exertional dyspnea. The first bouts of dyspnea are usually precipitated by clinical events that increase the rate of blood flow across the mitral orifice, resulting in further elevation of the LA pressure (see below).
Fig. Pathophysiology of MS
To assess the severity of obstruction hemodynamically, both the transvalvular pressure gradient and the flow rate must be measured. The latter depends not only on the CO but on the heart rate as well. An increase in heart rate shortens diastole proportionately more than systole and diminishes the time available for flow across the mitral valve. Therefore, at any given level of CO, tachycardia including that associated with AF augments the transvalvular pressure gradient and elevates further the LA pressure. Similar considerations apply to the pathophysiology of tricuspid stenosis.
In patients with moderate MS (mitral valve orifice 1.0 cm2–1.5 cm2), the CO is normal or almost so at rest but rises subnormally during exertion. In patients with severe MS (valve area <1.0 cm2), particularly those in whom pulmonary vascular resistance is markedly elevated, the CO is subnormal at rest and may fail to rise or may even decline during activity.
The clinical and hemodynamic features of MS are influenced importantly by the level of the PAP. Pulmonary hypertension results from: (1) passive backward transmission of the elevated LA pressure; (2) pulmonary arteriolar constriction, which presumably is triggered by LA and pulmonary venous hypertension (reactive pulmonary hypertension); (3) interstitial edema in the walls of the small pulmonary vessels; and (4) organic obliterative changes in the pulmonary vascular bed. Severe pulmonary hypertension results in RV enlargement, secondary tricuspid regurgitation (TR) and pulmonic regurgitation (PR), as well as right-sided heart failure.
In temperate climates, the latent period between the initial attack of rheumatic carditis (in the increasingly rare circumstances in which a history of one can be elicited) and the development of symptoms due to MS is generally about two decades; most patients begin to experience disability in the fourth decade of life. Studies carried out before the development of mitral valvotomy revealed that once a patient with MS became seriously symptomatic, the disease progressed continuously to death within 2–5 years.
In patients whose mitral orifices are large enough to accommodate a normal blood flow with only mild elevations of LA pressure, marked elevations of this pressure leading to dyspnea and cough may be precipitated by sudden changes in the heart rate, volume status, or CO, as for example with severe exertion, excitement, fever, severe anemia, paroxysmal AF and other tachycardias, sexual intercourse, pregnancy, and thyrotoxicosis. As MS progresses, lesser stresses precipitate dyspnea, and the patient becomes limited in daily activities, and orthopnea and paroxysmal nocturnal dyspnea develop. The development of permanent AF often marks a turning point in the patient’s course and is generally associated with acceleration of the rate at which symptoms progress.
In addition to the aforementioned changes in the pulmonary vascular bed, fibrous thickening of the walls of the alveoli and pulmonary capillaries occurs commonly in MS. The vital capacity, total lung capacity, maximal breathing capacity, and oxygen uptake per unit of ventilation are reduced. Pulmonary compliance falls further as pulmonary capillary pressure rises during exercise.
In patients with severe MS, there may be a malar flush with pinched and blue facies. In patients with sinus rhythm and severe pulmonary hypertension or associated tricuspid stenosis (TS), the jugular venous pulse reveals prominent a waves due to vigorous right atrial systole. The systemic arterial pressure is usually normal or slightly low. An RV tap along the left sternal border signifies an enlarged RV. A diastolic thrill may be present at the cardiac apex, with the patient in the left lateral recumbent position.
The first heart sound (S1) is usually accentuated and slightly delayed. The pulmonic component of the second heart sound (P2) also is often accentuated, and the two components of the second heart sound (S2) are closely split. The opening snap (OS) of the mitral valve is most readily audible in expiration at, or just medial to the cardiac apex. This sound generally follows the sound of aortic valve closure (A2) by 0.05–0.12 s. The time interval between A2 and OS varies inversely with the severity of the MS. The OS is followed by a low-pitched, rumbling, diastolic murmur, heard best at the apex with the patient in the left lateral recumbent position. It is accentuated by mild exercise (e.g., a few rapid sit-ups) carried out just before auscultation. In general, the duration of this murmur correlates with the severity of the stenosis in patients with preserved CO. In patients with sinus rhythm, the murmur often reappears or becomes louder during atrial systole (presystolic accentuation). Soft grade I or II/VI systolic murmurs are commonly heard at the apex or along the left sternal border in patients with pure MS and do not necessarily signify the presence of MR. Hepatomegaly, ankle edema, ascites, and pleural effusion, particularly in the right pleural cavity, may occur in patients with MS and RV failure.
With severe pulmonary hypertension, a pansystolic murmur produced by functional TR may be audible along the left sternal border. This murmur is usually louder during inspiration and diminishes during forced expiration (Carvallo’s sign). When the CO is markedly reduced in MS, the typical auscultatory findings, including the diastolic rumbling murmur, may not be detectable (silent MS), but they may reappear as compensation is restored. The Graham Steell murmur of PR, a high-pitched, diastolic, decrescendo blowing murmur along the left sternal border, results from dilatation of the pulmonary valve ring and occurs in patients with mitral valve disease and severe pulmonary hypertension. This murmur may be indistinguishable from the more common murmur produced by aortic regurgitation (AR), though it may increase in intensity with inspiration and is accompanied by a loud P2.
In MS and sinus rhythm, the P wave usually suggests LA enlargement . It may become tall and peaked in lead II and upright in lead V1 when severe pulmonary hypertension or TS complicates MS and right atrial (RA) enlargement occurs. The QRS complex is usually normal. However, with severe pulmonary hypertension, right axis deviation and RV hypertrophy are often present.
Transthoracic two-dimensional echocardiography (TTE) with color flow Doppler imaging provides critical information, including an estimate of the transvalvular peak and mean gradients and of mitral orifice size, the presence and severity of accompanying MR, the extent of restriction of valve leaflets and their thickness, the degree of distortion of the subvalvular apparatus, and the anatomic suitability for percutaneous mitral balloon valvotomy (PMBV; see below). In addition, TTE provides an assessment of the size of the cardiac chambers, an estimation of
The earliest changes are straightening of the upper left border of the cardiac silhouette, prominence of the main pulmonary arteries, dilatation of the upper lobe pulmonary veins, and posterior displacement of the esophagus by an enlarged LA. Kerley B lines are fine, dense, opaque, horizontal lines that are most prominent in the lower and mid-lung fields and that result from distention of interlobular septae and lymphatics with edema when the resting mean LA pressure exceeds approximately 20 mmHg.
Like MS, significant MR may also be associated with a prominent diastolic murmur at the apex due to increased flow, but in MR this diastolic murmur commences slightly later than in patients with MS, and there is often clear-cut evidence of
Penicillin prophylaxis of Group A -hemolytic streptococcal infections to prevent rheumatic fever is important for at-risk patients with MS. Recommendations for infective endocarditis prophylaxis have recently changed. In symptomatic patients, some improvement usually occurs with restriction of sodium intake and maintenance doses of oral diuretics. Digitalis glycosides usually do not benefit patients with MS and sinus rhythm, but they are helpful in slowing the ventricular rate of patients with AF. Beta blockers and nondihydropyridine calcium channel blockers (e.g., verapamil or diltiazem) are also useful in this regard.
Warfarin to an international normalized ration (INR) of 2–3 should be administered indefinitely to patients with MS who have AF or a history of thromboembolism. The routine use of warfarin in patients in sinus rhythm with LA enlargement (maximal dimension >
Management strategy for patients with mitral stenosis (MS) and mild symptoms. There is controversy as to whether patients with severe MS (MVA <1.0 cm2) and severe pulmonary hypertension(PH) (PASP >60 mmHg) should undergo percutaneous mitral balloon valvotomy (PMBV) or mitral valve replacement (MVR) to prevent right ventricular failure. CXR, chest x-ray; ECG, electrocardiogram; echo, echocardiography; LA, left atrial; MR, mitral regurgitation; MVA, mitral valve area; MVG, mean mitral valve pressure gradient; NYHA, New York Heart Association; PASP, pulmonary artery systolic pressure; PAWP, pulmonary artery wedge pressure; 2D, 2-dimensional. (From Bonow et al.)
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Note: Antibiotic prophylaxis is recommended according to current American Heart Association guidelines. For patients with these forms of valvular heart disease, prophylaxis is indicated for a prior history of endocarditis. HF is an indication for surgical or percutaneous treatment, and the recommendations here pertain to short-term therapy prior to definitive correction of the valve lesion. For patients whose comorbidities prohibit surgery, the medical therapies listed can be continued according to available guidelines for the management of HF. See text. Abbreviations: AF, atrial fibrillation; HF, heart failure; HTN, systemic hypertension; PCN, penicillin; RF, rheumatic fever. Source: Adapted from NA Boon, P Bloomfield: The medical management of valvular heart disease. Heart 87:395, 2002 |
If AF is of relatively recent onset in a patient whose MS is not severe enough to warrant PMBV or surgical commissurotomy, reversion to sinus rhythm pharmacologically or by means of electrical countershock is indicated. Usually, cardioversion should be undertaken after the patient has had at least 3 consecutive weeks of anticoagulant treatment to a therapeutic INR. If cardioversion is indicated more urgently, then intravenous heparin should be provided and a TEE performed to exclude the presence of left atrial thrombus before the procedure. Conversion to sinus rhythm is rarely successful or sustained in patients with severe MS, particularly those in whom the LA is especially enlarged or in whom AF has been present for more than 1 year.
Unless there is a contraindication, mitral valvotomy is indicated in symptomatic [New York Heart Association (NYHA) Functional Class II–IV] patients with isolated MS whose effective orifice (valve area) is < ~1.0 cm2/m2 body surface area, or <1.5 cm2 iormal-sized adults. Mitral valvotomy can be carried out by two techniques: PMBV and surgical valvotomy. In PMBV a catheter is directed into the LA after transseptal puncture, and a single balloon is directed across the valve and inflated in the valvular orifice. Ideal patients have relatively pliable leaflets with little or no commissural calcium. In addition, the subvalvular structures should not be significantly scarred or thickened and there should be no left atrial thombus. The short- and long-term results of this procedure in appropriate patients are similar to those of surgical valvotomy, but with less morbidity and a lower periprocedural mortality rate. Event-free survival in younger (<45 years) patients with pliable valves is excellent, with rates as high as 80–90% over 3–7 years. Therefore, PMBV has become the procedure of choice for such patients when it can be performed by a skilled operator in a high-volume center.
Inoue balloon technique for mitral balloon valvotomy. A. After transseptal puncture, the deflated balloon catheter is advanced across the inter-atrial septum, then across the mitral valve and into the left ventricle. B-D. The balloon is then inflated stepwise within the mitral orifice.
Successful valvotomy is defined by a 50% reduction in the mean mitral valve gradient and a doubling of the mitral valve area. Successful valvotomy, whether balloon or surgical, usually results in striking symptomatic and hemodynamic improvement and prolongs survival. However, there is no evidence that the procedure improves the prognosis of patients with slight or no functional impairment. Therefore, unless recurrent systemic embolization or severe pulmonary hypertension has occurred (PA systolic pressures >50 mmHg at rest or >60 mmHg with exercise), valvotomy is not recommended for patients who are entirely asymptomatic and/or who have mild stenosis (mitral valve area >1/5 cm2). When there is little symptomatic improvement after valvotomy, it is likely that the procedure was ineffective, that it induced MR, or that associated valvular or myocardial disease was present. About half of all patients undergoing surgical mitral valvotomy require reoperation by 10 years. In the pregnant patient with MS, valvotomy should be carried out if pulmonary congestion occurs despite intensive medical treatment. PMBV is the preferred strategy in this setting and is performed with TEE and no or minimal x-ray exposure.
Mitral valve replacement (MVR) is necessary in patients with MS and significant associated MR, those in whom the valve has been severely distorted by previous transcatheter or operative manipulation, or those in whom the surgeon does not find it possible to improve valve function significantly. MVR is now routinely performed with preservation of the chordal attachments to optimize 1 cm2—and are in NYHA Class III, i.e., symptomatic with ordinary activity despite optimal medical therapy. The overall 10-year survival of surgical survivors is ~70%. Long-term prognosis is worse in older patients and those with marked disability and marked depression of the CO preoperatively. Pulmonary hypertension and RV dysfunction are additional risk factors for poor outcome.
Aortic stenosis
Aortic stenosis (AS) most often is due to calcification of a congenitally bicuspid or normal trileaflet valve. Calcific changes are due to an active disease process characterized by lipid accumulation, inflammation, and calcification. Once initiated, progressive leaflet calcification and fibrosis eventually result in reduced leaflet motion with obstruction to left ventricular (
AS occurs in about one-fourth of all patients with chronic valvular heart disease; approximately 80% of adult patients with symptomatic valvular AS are male.
AS in adults may be due to degenerative calcification of the aortic cusps. It may be congenital in origin or it may be secondary to rheumatic inflammation. Age-related degenerative calcific AS (also known as senile or sclerocalcific AS) is now the most common cause of AS in adults in North America and 2.5 m/s. Aortic sclerosis appears to be a marker for an increased risk of coronary heart disease events. On histologic examination these valves frequently exhibit changes similar to those seen with atherosclerosis and vascular inflammation. Interestingly, risk factors for atherosclerosis, such as age, male sex, smoking, diabetes mellitus, hypertension, chronic kidney disease, increased LDL, reduced HDL cholesterol, and elevated C-reactive protein are all risk factors for aortic valve calcification.
Fig. Aortic stenosis
The congenitally affected valve may be stenotic at birth and may become progressively more fibrotic, calcified, and stenotic. In other cases the valve may be congenitally deformed, usually bicuspid [bicuspid aortic valve (BAV)], without serious narrowing of the aortic orifice during childhood; its abnormal architecture makes its leaflets susceptible to otherwise ordinary hemodynamic stresses, which ultimately lead to valvular thickening, calcification, increased rigidity, and narrowing of the aortic orifice.
Rheumatic disease of the aortic leaflets produces commissural fusion, sometimes resulting in a bicuspid-appearing valve. This condition in turn makes the leaflets more susceptible to trauma and ultimately leads to fibrosis, calcification, and further narrowing. By the time the obstruction to
The obstruction to
A mean systolic pressure gradient >40 mmHg with a normal CO or an effective aortic orifice area < ~1.0 cm2 (or ~<0.6 cm2/m2 body surface area in a normal-sized adult)—i.e., less than approximately one-third of the normal orifice—is generally considered to represent severe obstruction to
The hypertrophied
AS is rarely of clinical importance until the valve orifice has narrowed to approximately 1.0 cm2. Even severe AS may exist for many years without producing any symptoms because of the ability of the hypertrophied
Most patients with pure or predominant AS have gradually increasing obstruction for years but do not become symptomatic until the sixth to eighth decades. Exertional dyspnea, angina pectoris, and syncope are the three cardinal symptoms. Often there is a history of insidious progression of fatigue and dyspnea associated with gradual curtailment of activities. Dyspnea results primarily from elevation of the pulmonary capillary pressure caused by elevations of
Since the CO at rest is usually well maintained until late in the course, marked fatigability, weakness, peripheral cyanosis, cachexia, and other clinical manifestations of a low CO are usually not prominent until this stage is reached. Orthopnea, paroxysmal nocturnal dyspnea, and pulmonary edema, i.e., symptoms of
When AS and MS coexist, the reduction in CO induced by MS lowers the pressure gradient across the aortic valve and thereby masks many of the clinical findings produced by AS.
The rhythm is generally regular until late in the course; at other times, AF should suggest the possibility of associated mitral valve disease. The systemic arterial pressure is usually withiormal limits. In the late stages, however, when stroke volume declines, the systolic pressure may fall and the pulse pressure narrow. The peripheral arterial pulse rises slowly to a delayed sustained peak (pulsus parvus et tardus. In the elderly, the stiffening of the arterial wall may mask this important physical sign. In many patients the a wave in the jugular venous pulse is accentuated. This results from the diminished distensibility of the RV cavity caused by the bulging, hypertrophied interventricular septum.
An early systolic ejection sound is frequently audible in children and adolescents with congenital noncalcific valvular AS. This sound usually disappears when the valve becomes calcified and rigid. As AS increases in severity,
A. Schematic representation of ECG, aortic pressure (AOP), left ventricular pressure (LVP), and left atrial pressure (LAP). The shaded areas indicate a transvalvular pressure difference during systole. HSM, holosystolic murmur; MSM, midsystolic murmur. B. Graphic representation of ECG, aortic pressure (AOP), left ventricular pressure (LVP), and left atrial pressure (LAP) with shaded areas indicating transvalvular diastolic pressure difference. EDM, early diastolic murmur; PSM, presystolic murmur; MDM, middiastolic murmur.
The murmur of AS is characteristically an ejection (mid) systolic murmur that commences shortly after the S1, increases in intensity to reach a peak toward the middle of ejection, and ends just before aortic valve closure. It is characteristically low-pitched, rough and rasping in character, and loudest at the base of the heart, most commonly in the second right intercostal space. It is transmitted upward along the carotid arteries. Occasionally it is transmitted downward and to the apex, where it may be confused with the systolic murmur of MR (Gallavardin effect). In almost all patients with severe obstruction and preserved CO, the murmur is at least grade III/VI. In patients with mild degrees of obstruction or in those with severe stenosis with heart failure in whom the stroke volume and therefore the transvalvular flow rate are reduced, the murmur may be relatively soft and brief.
In most patients with severe AS there is
Left ventricular hypertrophy (LVH) increases the amplitude of electrical forces directed to the left and posteriorly.
In advanced cases, ST-segment depression and T-wave inversion (
The key findings are
Still frame two-dimensional echocardiographic image from the parasternal long axis view of a patient with aortic stenosis. The aortic valve is calcified with restricted opening during systole. Ao, aorta; RV, right ventricle; LA, left atrium;
Standard evaluation of aortic stenosis (AS) severity is based on measurement of left ventricular outflow tract (LVOT) diameter (D) in a parasternal long-axis view for calculation of a circular cross-sectional area (CSA), outflow tract velocity (V) from an apical approach using pulsed Doppler, and the maximum aortic jet (AS-Jet, Vmax) from the continuous-wave Doppler recording. Either velocity-time integrals (VTIs) or maximum velocities can be used in the continuity equation for aortic valve area (AVA).
. The valve gradient and aortic valve area can be estimated by Doppler measurement of the transaortic velocity. Severe AS is defined by a valve area <1.0 cm2, whereas moderate AS is defined by a valve area of 1.0–1.5 cm2 and mild AS by a valve area of 1.5–2.0 cm2.
Echocardiography is useful for identifying coexisting valvular abnormalities such as MS and AR, which sometimes accompany AS; for differentiating valvular AS from other forms of outflow obstruction; and for measurement of the aortic root. Aneurysmal enlargement (maximal dimension >
The chest x-ray may show no or little overall cardiac enlargement for many years. Hypertrophy without dilatation may produce some rounding of the cardiac apex in the frontal projection and slight backward displacement in the lateral view; severe AS is often associated with poststenotic dilatation of the ascending aorta. As noted above, however, aortic enlargement may be an independent process and mediated by the same type of structural changes that occur in patients with Marfan syndrome. Aortic calcification is usually readily apparent on fluoroscopic examination or by echocardiography; the absence of valvular calcification in an adult suggests that severe valvular AS is not present. In later stages of the disease, as the
Management strategy for patients with severe aortic stenosis. Preoperative coronary angiography should be performed routinely as determined by age, symptoms, and coronary risk factors. Cardiac catheterization and angiography may also be helpful when there is discordance between clinical findings and echocardiography. AVA, aortic valve area; BP, blood pressure; CABG, coronary artery bypass graft surgery; echo, echocardiography; LV, left ventricle; Vmax, maximal velocity across aortic valve by Doppler echocardiography. (From Bonow et al. Modified from CM Otto: J Am Coll Cardiol 47:2141, 2006.)
In patients with severe AS (<1.0 cm2), strenuous physical activity should be avoided, even in the asymptomatic stage. Care must be taken to avoid dehydration and hypovolemia to protect against a significant reduction in CO. Medications used for the treatment of hypertension or CAD, including beta blockers and ACE inhibitors, are generally safe for asymptomatic patients with preserved left ventricular systolic function. Nitroglycerin is helpful in relieving angina pectoris. Retrospective studies have shown that patients with degenerative calcific AS who receive HMG-CoA reductase inhibitors (“statins”) exhibit slower progression of leaflet calcification and aortic valve area reduction than those who do not. One prospective randomized clinical trial using high-dose atorvastatin failed to show a measurable benefit, although a more recent trial using rosuvastatin did show a beneficial effect. The role of statin medications may be more clearly defined with further study.
Asymptomatic patients with calcific AS and severe obstruction should be followed carefully for the development of symptoms and by serial echocardiograms for evidence of deteriorating
Operation should, if possible, be carried out before frank 20% in stroke volume after dobutamine challenge). In patients in whom severe AS and CAD coexist, relief of the AS and revascularization of the myocardium by means of aortocoronary bypass grafting may result in striking clinical and hemodynamic improvement.
Because many patients with calcific AS are elderly, particular attention must be directed to the adequacy of hepatic, renal, and pulmonary function before AVR is recommended. Age alone is not a contraindication to AVR for AS. The mortality rate depends to a substantial extent on the patient’s preoperative clinical and hemodynamic state. The 10-year survival rate of patients with AVR is approximately 60%. Approximately 30% of bioprosthetic valves evidence primary valve failure in 10 years, requiring re-replacement, and an approximately equal percentage of patients with mechanical prostheses develop significant hemorrhagic complications as a consequence of treatment with anticoagulants.
Percutaneous Balloon Aortic Valvuloplasty
This procedure is preferable to operation in children and young adults with congenital, noncalcific AS. It is not commonly used in adults with severe calcific AS because of a very high restenosis rate and the risk of procedural complications, but on occasion it has been used successfully as a “bridge to operation” in patients with severe
Aortic Regurgitation
In approximately two-thirds of patients with valvular AR, the disease is rheumatic in origin, resulting in thickening, deformity, and shortening of the individual aortic valve cusps, changes that prevent their proper opening during systole and closure during diastole. A rheumatic origin is much less common in patients with isolated AR who do not have associated mitral valve disease. Patients with congenital BAV disease may develop predominant AR. Congenital fenestrations of the aortic valve occasionally produce mild AR. Membranous subaortic stenosis often leads to thickening and scarring of the aortic valve leaflets with secondary AR. Prolapse of an aortic cusp, resulting in progressive chronic AR, occurs in approximately 15% of patients with ventricular septal defect but may also occur as an isolated phenomenon or as a consequence of myxomatous degeneration sometimes associated with mitral and/or tricuspid valve involvement.
AR may result from infective endocarditis, which can develop on a valve previously affected by rheumatic disease, a congenitally deformed valve, or, rarely, on a normal aortic valve, and may lead to perforation or erosion of one or more leaflets. The aortic valve leaflets may become scarred and retracted during the course of syphilis or ankylosing spondylitis and contribute further to the AR that derives primarily from the associated root disease. Although traumatic rupture or avulsion of the aortic valve is an uncommon cause of acute AR, it does represent the most frequent serious lesion in patients surviving nonpenetrating cardiac injuries. The coexistence of hemodynamically significant AS with AR usually excludes all the rarer forms of AR because it occurs almost exclusively in patients with rheumatic or congenital AR. In patients with AR due to primary valvular disease, dilatation of the aortic annulus may occur secondarily and intensify the regurgitation.
The total stroke volume ejected by the
The reverse pressure gradient from aorta to
In patients with chronic severe AR, the effective forward CO usually is normal or only slightly reduced at rest, but often it fails to rise normally during exertion. Early signs of
In chronic severe AR, the jarring of the entire body and the bobbing motion of the head with each systole can be appreciated, and the abrupt distention and collapse of the larger arteries are easily visible. The examination should be directed toward the detection of conditions predisposing to AR, such as Marfan syndrome, ankylosing spondylitis, and ventricular septal defect.
A rapidly rising “water-hammer” pulse, which collapses suddenly as arterial pressure falls rapidly during late systole and diastole (Corrigan’s pulse), and capillary pulsations, an alternate flushing and paling of the skin at the root of the nail while pressure is applied to the tip of the nail (Quincke’s pulse), are characteristic of free AR. A booming “pistol-shot” sound can be heard over the femoral arteries (Traube’s sign), and a to-and-fro murmur (Duroziez’s sign) is audible if the femoral artery is lightly compressed with a stethoscope.
The arterial pulse pressure is widened, and there is an elevation of the systolic pressure, sometimes to as high as 300 mmHg, and a depression of the diastolic pressure. The measurement of arterial diastolic pressure with a sphygmomanometer may be complicated by the fact that systolic sounds are frequently heard with the cuff completely deflated. However, the level of cuff pressure at the time of muffling of the Korotkoff sounds (Phase IV) generally corresponds fairly closely to the true intraarterial diastolic pressure. As the disease progresses and the
In patients with severe AR, the aortic valve closure sound (A2) is usually absent. An S3 and systolic ejection sound are frequently audible, and occasionally an S4 also may be heard. The murmur of chronic AR is typically a high-pitched, blowing, decrescendo diastolic murmur, heard best in the third intercostal space along the left sternal border.
A. Schematic representation of ECG, aortic pressure (AOP), left ventricular pressure (LVP), and left atrial pressure (LAP). The shaded areas indicate a transvalvular pressure difference during systole. HSM, holosystolic murmur; MSM, midsystolic murmur. B. Graphic representation of ECG, aortic pressure (AOP), left ventricular pressure (LVP), and left atrial pressure (LAP) with shaded areas indicating transvalvular diastolic pressure difference. EDM, early diastolic murmur; PSM, presystolic murmur; MDM, middiastolic murmur.
In patients with mild AR, this murmur is brief but, as the severity increases, generally becomes louder and longer, indeed holodiastolic. When the murmur is soft, it can be heard best with the diaphragm of the stethoscope and with the patient sitting up, leaning forward, and with the breath held in forced expiration. In patients in whom the AR is caused by primary valvular disease, the diastolic murmur is usually louder along the left than the right sternal border. However, when the murmur is heard best along the right sternal border, it suggests that the AR is caused by aneurysmal dilatation of the aortic root. “Cooing” or musical diastolic murmurs suggest eversion of an aortic cusp vibrating in the regurgitant stream.
A mid-systolic ejection murmur is frequently audible in isolated AR. It is generally heard best at the base of the heart and is transmitted along the carotid vessels. This murmur may be quite loud without signifying aortic obstruction. A third murmur frequently heard in patients with severe AR is the Austin Flint murmur, a soft, low-pitched, rumbling mid-diastolic murmur. It is probably produced by the diastolic displacement of the anterior leaflet of the mitral valve by the AR stream but does not appear to be associated with hemodynamically significant mitral obstruction. The auscultatory features of AR are intensified by strenuous handgrip, which augments systemic resistance.
In acute severe AR, the elevation of
In patients with chronic severe AR, the ECG signs of
The extent and velocity of wall motion are normal or even supernormal, until myocardial contractility declines. A rapid, high-frequency fluttering of the anterior mitral leaflet produced by the impact of the regurgitant jet is a characteristic finding. The echocardiogram is also useful in determining the cause of AR, by detecting dilatation of the aortic annulus and root or aortic dissection. Thickening and failure of coaptation of the leaflets also may be noted. Color flow Doppler echocardiographic imaging is very sensitive in the detection of AR, and Doppler echocardiography is helpful in assessing its severity. With severe AR, the central jet width exceeds 65% of the left ventricular outflow tract, the regurgitant volume is 60 ml/beat, the regurgitant fraction is 50%, and there is diastolic flow reversal in the proximal descending thoracic aorta. The continuous wave Doppler profile shows a rapid deceleration time in patients with acute severe AR, due to the rapid increase in
In chronic severe AR, the apex is displaced downward and to the left in the frontal projection. In the left anterior oblique and lateral projections, the
Clinically, bounding arterial pulses, a widened pulse pressure, a loud diastolic murmur, and a third heart sound are signs of severe regurgitation but are not always specific. Doppler echocardiography has become the mainstay of the assessment of the severity of aortic regurgitation. Suggestive of severe regurgitation are signs of a broad jet width on color-flow imaging, steep jet velocity deceleration (reflecting equalization of aortic and ventricular pressure), and prolonged diastolic flow reversal in the aorta. The use of Doppler echocardiography makes it possible to quantify the effective regurgitant orifice (severe if 0.30 cm2) and regurgitant volume (severe if 60 ml per beat)
Echo-Doppler imaging of aortic regurgitation (video)
Example of a Jet of Aortic Regurgitation, as Shown by Color-Flow Imaging.
The three components of the regurgitant flow (flow convergence above the orifice, vena contracta through the orifice, and the jet below the orifice) are shown. The width of the vena contracta (as indicated by crosses) can be measured as a surrogate for the regurgitant orifice.
A simple, reliable measurement is the “vena contracta” — that is, the width of the regurgitant flow at the orifice, a surrogate measurement for the size of the orifice. Measurements that are
Example of Quantitation of Aortic Regurgitation by the Convergence of the Proximal Flow.
Panel A is a color-flow image of the aortic valve; the measured radius of the proximal flow convergence (R) is
Treatment
Acute Aortic Regurgitation
Patients with acute severe AR may respond to intravenous diuretics and vasodilators (such as sodium nitroprusside), but stabilization is usually short-lived and operation is indicated urgently. Intraaortic balloon counterpulsation is contraindicated. Beta-blockers are also best avoided so as not to reduce the CO further or slow the heart rate, which might allow proportionately more time in diastole for regurgitation to occur. Surgery is the treatment of choice.
Early symptoms of dyspnea and effort intolerance respond to treatment with diuretics and vasodilators (ACE inhibitors, dihydropyridine calcium channel blockers, or hydralazine) may be useful as well. Surgery can then be performed in more controlled circumstances. The use of vasodilators to extend the compensated phase of chronic severe AR before the onset of symptoms or the development of
In deciding on the advisability and proper timing of surgical treatment, two points should be kept in mind: (1) patients with chronic severe AR usually do not become symptomatic until after the development of myocardial dysfunction; and (2) when delayed too long (defined as >1 year from onset of symptoms or LV dysfunction), surgical treatment often does not restore normal LV function. Therefore, in patients with chronic severe AR, careful clinical follow-up and noninvasive testing with echocardiography at approximately 6-month intervals are necessary if operation is to be undertaken at the optimal time, i.e., after the onset of LV dysfunction but prior to the development of severe symptoms. Operation can be deferred as long as the patient both remains asymptomatic and retains normal
AVR is indicated for the treatment of severe AR in symptomatic patients irrespective of
Surgical options for management of aortic valve and root disease have expanded considerably over the past decade. AVR with a suitable mechanical or tissue prosthesis is generally necessary in patients with rheumatic AR and in many patients with other forms of regurgitation. Rarely, when a leaflet has been perforated during infective endocarditis or torn from its attachments to the aortic annulus by thoracic trauma, primary surgical repair may be possible. When AR is due to aneurysmal dilatation of the annulus and ascending aorta rather than to primary valvular involvement, it may be possible to reduce the regurgitation by narrowing the annulus or by excising a portion of the aortic root without replacing the valve. Resuspension of the native aortic valve leaflets is possible in approximately 50% of patients with acute AR in the setting of Type A aortic dissection. In other conditions, however, regurgitation can be eliminated only by replacing the aortic valve, excising the dilated or aneurysmal ascending aorta responsible for the regurgitation, and replacing it with a graft. This formidable procedure entails a higher risk than isolated AVR.
As in patients with other valvular abnormalities, both the operative risk and the late mortality are largely dependent on the stage of the disease and on myocardial function at the time of operation. The overall operative mortality for isolated AVR is about 3%. However, patients with marked cardiac enlargement and prolonged
Patients with acute severe AR require prompt surgical treatment, which may be lifesaving.
Tricuspid stenosis
TS, much less prevalent than MS in North America and
A diastolic pressure gradient between the RA and RV defines TS. It is augmented when the transvalvular blood flow increases during inspiration and declines during expiration. A mean diastolic pressure gradient of 4 mmHg is usually sufficient to elevate the mean RA pressure to levels that result in systemic venous congestion. Unless sodium intake has been restricted and diuretics administered, this venous congestion is associated with hepatomegaly, ascites, and edema, sometimes severe. In patients with sinus rhythm, the RA a wave may be extremely tall and may even approach the level of the RV systolic pressure. The y descent is prolonged. The CO at rest is usually depressed, and it fails to rise during exercise. The low CO is responsible for the normal or only slightly elevated LA, PA, and RV systolic pressures despite the presence of MS. Thus, the presence of TS can mask the hemodynamic and clinical features of the MS, which usually accompanies it.
Since the development of MS generally precedes that of TS, many patients initially have symptoms of pulmonary congestion. Spontaneous improvement of these symptoms should raise the possibility that TS may be developing. Characteristically, patients complain of relatively little dyspnea for the degree of hepatomegaly, ascites, and edema that they have. However, fatigue secondary to a low CO and discomfort due to refractory edema, ascites, and marked hepatomegaly are common in patients with TS and/or TR. In some patients, TS may be suspected for the first time when symptoms of right-sided failure persist after an adequate mitral valvotomy.
Severe TS is associated with marked hepatic congestion, often resulting in cirrhosis, jaundice, serious malnutrition, anasarca, and ascites. Congestive hepatomegaly and, in cases of severe tricuspid valve disease, splenomegaly are present.
On auscultation, an OS of the tricuspid valve may occasionally be heard approximately 0.06 s after pulmonic valve closure. The diastolic murmur of TS has many of the qualities of the diastolic murmur of MS, and since TS almost always occurs in the presence of MS, the less-common valvular lesion may be missed. However, the tricuspid murmur is generally heard best along the left lower sternal margin and over the xiphoid process, and it is most prominent during presystole in patients with sinus rhythm. The murmur of TS is augmented during inspiration, and it is reduced during expiration and particularly during the strain phase of the Valsalva maneuver, when tricuspid blood flow is reduced.
The ECG features of RA enlargement include tall, peaked P waves in lead II, as well as prominent, upright P waves in lead V1. The absence of ECG evidence of right ventricular hypertrophy (RVH) in a patient with right-sided heart failure who is believed to have MS should suggest associated tricuspid valve disease. The chest x-ray in patients with combined TS and MS shows particular prominence of the RA and superior vena cava without much enlargement of the PA and with less evidence of pulmonary vascular congestion than occurs in patients with isolated MS. On echocardiographic examination, the tricuspid valve is usually thickened and domes in diastole; the transvalvular gradient can be estimated by Doppler echocardiography. TTE provides additional information regarding mitral valve structure and function,
Patients with TS generally exhibit marked systemic venous congestion; intensive salt restriction, bed rest, and diuretic therapy are required during the preoperative period. Such a preparatory period may diminish hepatic congestion and thereby improve hepatic function sufficiently so that the risks of operation, particularly bleeding, are diminished. Surgical relief of the TS should be carried out, preferably at the time of surgical mitral valvotomy or MVR, in patients with moderate or severe TS who have mean diastolic pressure gradients exceeding ~4 mmHg and tricuspid orifice areas <1.5–2.0 cm2. TS is almost always accompanied by significant TR. Operative repair may permit substantial improvement of tricuspid valve function. If repair cannot be accomplished, the tricuspid valve may have to be replaced with a prosthesis, preferably a large bioprosthetic valve. Mechanical valves in the tricuspid position are more prone to thromboembolic complications than in other positions.
Tricuspid regurgitation
Most commonly, TR is functional and secondary to marked dilatation of the tricuspid annulus. Functional TR may complicate RV enlargement of any cause, including inferior wall infarcts that involve the RV. It is commonly seen in the late stages of heart failure due to rheumatic or congenital heart disease with severe pulmonary hypertension (pulmonary artery systolic pressure >55 mmHg), as well as in ischemic heart disease and dilated cardiomyopathy. It is reversible in part if pulmonary hypertension is relieved. Rheumatic fever may produce organic (primary) TR, often associated with TS. Infarction of RV papillary muscles, tricuspid valve prolapse, carcinoid heart disease, endomyocardial fibrosis, infective endocarditis, and trauma all may produce TR. Less commonly, TR results from congenitally deformed tricuspid valves, and it occurs with defects of the atrioventricular canal, as well as with Ebstein’s malformation of the tricuspid valve. TR also develops eventually in patients with chronic RV apical pacing.
As is the case for TS, the clinical features of TR result primarily from systemic venous congestion and reduction of CO. With the onset of TR in patients with pulmonary hypertension, symptoms of pulmonary congestion diminish, but the clinical manifestations of right-sided heart failure become intensified. The neck veins are distended with prominent v waves and rapid y descents, marked hepatomegaly, ascites, pleural effusions, edema, systolic pulsations of the liver, and a positive hepatojugular reflux. A prominent RV pulsation along the left parasternal region and a blowing holosystolic murmur along the lower left sternal margin, which may be intensified during inspiration and reduced during expiration or the strain of the Valsalva maneuver (Carvallo’s sign), are characteristic findings; AF is usually present.
The ECG usually shows changes characteristic of the lesion responsible for the enlargement of the RV that leads to TR, e.g., inferior wall myocardial infarction or severe RVH. Echocardiography may be helpful by demonstrating RV dilatation and prolapsing, flail, scarred, or displaced tricuspid leaflets; the diagnosis of TR can be made by color flow Doppler echocardiography, and its severity can be estimated by Doppler examination.
Continuous-wave Doppler of tricuspid regurgitation in a patient with pulmonary hypertension. There is an increase in the velocity of flow from the right ventricle into the right atrium to 5.4 m/s. Using the modified Bernoulli equation, the peak pressure gradient between the right ventricle and right atrium during systole is 120 mmHg. Assuming a right atrial pressure of 10 mmHg, the right ventricular systolic pressure is 130 mmHg. In the absence of right ventricular outflow tract obstruction, this indicates there is severe pulmonary hypertension with a pulmonary artery systolic pressure of 130 mmHg.
Severe TR is accompanied by hepatic vein systolic flow reversal. Continuous wave Doppler is also useful in estimating PA pressure. Roentgenographic examination usually reveals enlargement of both the RA and RV.
In patients with severe TR, the CO is usually markedly reduced, and the RA pressure pulse may exhibit no x descent during early systole but a prominent c-v wave with a rapid y descent. The mean RA and the RV end-diastolic pressures are often elevated.
Tricuspid Regurgitation: Treatment
Isolated TR, in the absence of pulmonary hypertension, such as that occurring as a consequence of infective endocarditis or trauma, is usually well tolerated and does not require operation. Indeed, even total excision of an infected tricuspid valve may be well tolerated for several years if the PA pressure is normal. Treatment of the underlying cause of heart failure usually reduces the severity of functional TR, by reducing the size of the tricuspid annulus. In patients with mitral valve disease and TR secondary to pulmonary hypertension and massive RV enlargement, effective surgical correction of the mitral valvular abnormality results in lowering of the PA pressures and gradual reduction or disappearance of the TR without direct treatment of the tricuspid valve. However, recovery may be much more rapid in patients with severe secondary TR if, at the time of mitral valve surgery, and especially when there is measurable enlargement of the tricuspid valve annulus, tricuspid annuloplasty (generally with the insertion of a plastic ring), open tricuspid valve repair, or, in the rare instance of severe organic tricuspid valve disease, tricuspid valve replacement is performed. Tricuspid annuloplasty or replacement may be required for severe TR with primary involvement of the valve.
Ebstein’s Anomaly
Ebstein’s anomaly is an abnormality of the tricuspid valve in which the septal leaflets and often the posterior leaflets are displaced into the right ventricle and the anterior leaflet is usually malformed, excessively large, and abnormally attached or adherent to the right ventricular free wall. Thus, a portion of the right ventricle is “atrialized” in that it is located on the atrial side of the tricuspid valve, and the remaining functional right ventricle is small (Figure 6). The tricuspid valve is usually regurgitant but may be stenotic. Eighty percent of patients with Ebstein’s anomaly have an interatrial communication (atrial septal defect or patent foramen ovale) through which right-to-left shunting of blood may occur.
Figure Ebstein’s Anomaly.
In patients with Ebstein’s anomaly, a portion of the right ventricle is atrialized (i.e., located on the atrial side of the tricuspid valve), and as a result, the functional right ventricle is small. In addition, most patients have an interatrial communication (atrial septal defect or patent foramen ovale), through which right-to-left shunting may occur.
The severity of the hemodynamic derangements in patients with Ebstein’s anomaly depends on the degree of displacement and the functional status of the tricuspid-valve leaflets. Patients with mild apical displacement of the tricuspid leaflets have normal valvular function, whereas those with severe tricuspid-leaflet displacement or abnormal anterior leaflet attachment, with valvular dysfunction, have elevated right atrial pressure and right-to-left interatrial shunting. Similarly, the clinical presentation of Ebstein’s anomaly varies from severe heart failure in a fetus or neonate to the absence of symptoms in an adult in whom it is discovered incidentally.
When Ebstein’s anomaly is discovered during fetal life, the rate of intrauterine mortality is high. Neonates with severe disease have cyanosis, with heart failure and a murmur noted in the first days of life. Transient improvement may occur as pulmonary vascular resistance falls, but the condition worsens after the ductus arteriosus closes, thereby decreasing pulmonary blood flow. Older children with Ebstein’s anomaly often come to medical attention because of an incidental murmur, whereas adolescents and adults present with a supraventricular arrhythmia. In adults with Ebstein’s anomaly, the most important predictors of outcome are the New York Heart Association (NYHA) functional class, the heart size, the presence or absence of cyanosis, and the presence or absence of paroxysmal atrial tachycardias. Such tachycardias may lead to cardiac failure, worsening cyanosis, and even syncope. Patients with Ebstein’s anomaly and an interatrial communication are at risk for paradoxical embolization, brain abscess, and sudden death.
On physical examination, the severity of cyanosis depends on the magnitude of right-to-left shunting. The first and second heart sounds are widely split, and a third or fourth heart sound is often present, resulting in a “triple” or “quadruple” rhythm. A systolic murmur caused by tricuspid regurgitation is usually present at the left lower sternal border. Hepatomegaly (resulting from passive hepatic congestion due to elevated right atrial pressure) may be present.
Tall and broad P waves are common on the electrocardiogram, as is right bundle-branch block. First-degree atrioventricular block occurs frequently. Since about 20 percent of patients with Ebstein’s anomaly have ventricular preexcitation by way of an accessory electrical pathway between the atrium and ventricle (Wolff–Parkinson–White syndrome), a delta wave may be present. The radiographic findings depend on the severity of the anatomical abnormality. In mild cases, the heart size and pulmonary vasculature are normal. In more severe cases, marked cardiomegaly, which is largely due to right atrial enlargement, is present. In severe cases (with little functional right ventricle and marked right-to-left shunting), pulmonary vascular markings are decreased. Echocardiography is used to assess right atrial dilatation, anatomical displacement and distortion of the tricuspid-valve leaflets, and the severity of tricuspid regurgitation or stenosis; in addition, the presence and magnitude of interatrial shunting can be determined (by color Doppler imaging or bubble study), as can the presence of associated cardiac abnormalities. Electrophysiologic evaluation is warranted in patients with atrial tachyarrhythmias.
The management of Ebstein’s anomaly centers on the prevention and treatment of complications. Prophylaxis against infective endocarditis is recommended. Patients with symptomatic heart failure are given diuretic agents and digoxin. Those with atrial arrhythmias may be treated pharmacologically or with catheter ablation (if an accessory pathway is present). Ablation of accessory pathways has a lower rate of success in patients with Ebstein’s anomaly than in those with structurally normal hearts, and the risk of recurrence of arrhythmia is higher. In severely ill infants with Ebstein’s anomaly, an arterial shunt from the systemic circulation to the pulmonary circulation is created to increase pulmonary blood flow, thereby decreasing cyanosis. Further surgery to create a univentricular heart (i.e., by the Fontan procedure) may also be considered in neonates.
Repair or replacement of the tricuspid valve in conjunction with closure of the interatrial communication is recommended for older patients who have severe symptoms despite medical therapy. When possible, valve repair is preferable to valve replacement, because it is associated with lower mortality and has fewer long-term complications. The complications of surgery to correct Ebstein’s anomaly include complete heart block, persistence of supraventricular arrhythmias, residual tricuspid regurgitation after valve repair, and prosthetic-valve dysfunction.
Ebstein’s Anomaly
Ebstein’s anomaly is an abnormality of the tricuspid valve in which the septal leaflets and often the posterior leaflets are displaced into the right ventricle and the anterior leaflet is usually malformed, excessively large, and abnormally attached or adherent to the right ventricular free wall. Thus, a portion of the right ventricle is “atrialized” in that it is located on the atrial side of the tricuspid valve, and the remaining functional right ventricle is small (Figure 6). The tricuspid valve is usually regurgitant but may be stenotic. Eighty percent of patients with Ebstein’s anomaly have an interatrial communication (atrial septal defect or patent foramen ovale) through which right-to-left shunting of blood may occur.
Figure 6. Ebstein’s Anomaly.
In patients with Ebstein’s anomaly, a portion of the right ventricle is atrialized (i.e., located on the atrial side of the tricuspid valve), and as a result, the functional right ventricle is small. In addition, most patients have an interatrial communication (atrial septal defect or patent foramen ovale), through which right-to-left shunting may occur.
The severity of the hemodynamic derangements in patients with Ebstein’s anomaly depends on the degree of displacement and the functional status of the tricuspid-valve leaflets. Patients with mild apical displacement of the tricuspid leaflets have normal valvular function, whereas those with severe tricuspid-leaflet displacement or abnormal anterior leaflet attachment, with valvular dysfunction, have elevated right atrial pressure and right-to-left interatrial shunting. Similarly, the clinical presentation of Ebstein’s anomaly varies from severe heart failure in a fetus or neonate to the absence of symptoms in an adult in whom it is discovered incidentally.
When Ebstein’s anomaly is discovered during fetal life, the rate of intrauterine mortality is high. Neonates with severe disease have cyanosis, with heart failure and a murmur noted in the first days of life. Transient improvement may occur as pulmonary vascular resistance falls, but the condition worsens after the ductus arteriosus closes, thereby decreasing pulmonary blood flow. Older children with Ebstein’s anomaly often come to medical attention because of an incidental murmur, whereas adolescents and adults present with a supraventricular arrhythmia. In adults with Ebstein’s anomaly, the most important predictors of outcome are the New York Heart Association (NYHA) functional class, the heart size, the presence or absence of cyanosis, and the presence or absence of paroxysmal atrial tachycardias. Such tachycardias may lead to cardiac failure, worsening cyanosis, and even syncope. Patients with Ebstein’s anomaly and an interatrial communication are at risk for paradoxical embolization, brain abscess, and sudden death.
On physical examination, the severity of cyanosis depends on the magnitude of right-to-left shunting. The first and second heart sounds are widely split, and a third or fourth heart sound is often present, resulting in a “triple” or “quadruple” rhythm. A systolic murmur caused by tricuspid regurgitation is usually present at the left lower sternal border. Hepatomegaly (resulting from passive hepatic congestion due to elevated right atrial pressure) may be present.
Tall and broad P waves are common on the electrocardiogram, as is right bundle-branch block. First-degree atrioventricular block occurs frequently. Since about 20 percent of patients with Ebstein’s anomaly have ventricular preexcitation by way of an accessory electrical pathway between the atrium and ventricle (Wolff–Parkinson–White syndrome), a delta wave may be present. The radiographic findings depend on the severity of the anatomical abnormality. In mild cases, the heart size and pulmonary vasculature are normal. In more severe cases, marked cardiomegaly, which is largely due to right atrial enlargement, is present. In severe cases (with little functional right ventricle and marked right-to-left shunting), pulmonary vascular markings are decreased. Echocardiography is used to assess right atrial dilatation, anatomical displacement and distortion of the tricuspid-valve leaflets, and the severity of tricuspid regurgitation or stenosis; in addition, the presence and magnitude of interatrial shunting can be determined (by color Doppler imaging or bubble study), as can the presence of associated cardiac abnormalities. Electrophysiologic evaluation is warranted in patients with atrial tachyarrhythmias.
The management of Ebstein’s anomaly centers on the prevention and treatment of complications. Prophylaxis against infective endocarditis is recommended. Patients with symptomatic heart failure are given diuretic agents and digoxin. Those with atrial arrhythmias may be treated pharmacologically or with catheter ablation (if an accessory pathway is present). Ablation of accessory pathways has a lower rate of success in patients with Ebstein’s anomaly than in those with structurally normal hearts, and the risk of recurrence of arrhythmia is higher. In severely ill infants with Ebstein’s anomaly, an arterial shunt from the systemic circulation to the pulmonary circulation is created to increase pulmonary blood flow, thereby decreasing cyanosis. Further surgery to create a univentricular heart (i.e., by the Fontan procedure) may also be considered in neonates.
Repair or replacement of the tricuspid valve in conjunction with closure of the interatrial communication is recommended for older patients who have severe symptoms despite medical therapy. In addition, repair or replacement should be considered for patients with less severe symptoms who have cardiac enlargement, since this condition has a poor prognosis. When possible, valve repair is preferable to valve replacement, because it is associated with lower mortality and has fewer long-term complications. However, when valve replacement is required, a bioprosthesis is preferable to a mechanical prosthesis. The complications of surgery to correct Ebstein’s anomaly include complete heart block, persistence of supraventricular arrhythmias, residual tricuspid regurgitation after valve repair, and prosthetic-valve dysfunction.
Transposition of the Great Arteries
With d-transposition of the great arteries (also known as complete transposition), the aorta arises in an anterior position from the right ventricle and the pulmonary artery arises from the left ventricle (Figure 7A). Therefore, there is complete separation of the pulmonary and systemic circulations: systemic venous blood traverses the right atrium, right ventricle, aorta, and systemic circulation, whereas pulmonary venous blood traverses the left atrium, left ventricle, pulmonary artery, and pulmonary circulation. In order for an infant with this condition to survive, there must be a communication between the two circuits. In about two thirds of patients, no other associated cardiac defect is present, so that the ductus arteriosus and foramen ovale allow communication between the two circuits. Infants with this condition have severe cyanosis. The one third of patients with other associated defects that permit intracardiac mixing (e.g., atrial septal defect, ventricular septal defect, or patent ductus arteriosus) are less critically ill, since they have less severe cyanosis. However, they are at risk for left ventricular failure due to volume overload caused by left-to-right shunting.
Figure 7. Transposition and Switching of the Great Arteries.
In d-transposition of the great arteries (complete transposition) (Panel A), systemic venous blood returns to the right atrium, from which it goes to the right ventricle and then to the aorta. Pulmonary venous blood returns to the left atrium, from which it goes to the left ventricle and then to the pulmonary artery. Survival is possible only if there is a communication between the two circuits, such as a patent ductus arteriosus. With the “atrial switch” operation (Panel B), a pericardial baffle is created in the atria, so that blood returning from the systemic venous circulation is directed into the left ventricle and then the pulmonary artery (blue arrows), whereas blood returning from the pulmonary venous circulation is directed into the right ventricle and then the aorta (red arrow). With the “arterial switch” operation (Panel C), the pulmonary artery and ascending aorta are transected above the semilunar valves and coronary arteries, then switched (neoaortic and neopulmonary valves).
Patients with complete transposition have cyanosis from birth and often have heart failure in the newborn period. The findings on physical examination are nonspecific. Infants have cyanosis and tachypnea. The second heart sound is single and loud (due to the anterior position of the aorta). In patients with mild cyanosis, a holosystolic murmur caused by a ventricular septal defect may be heard. Likewise, a soft systolic ejection murmur (due to pulmonary stenosis, ejection into the anteriorly located aorta, or both) may be audible. The electrocardiogram shows right-axis deviation and right ventricular hypertrophy (since the right ventricle is the systemic ventricle). Patients with a large ventricular septal defect or patent ductus arteriosus, as well as those with pulmonary stenosis, have left ventricular hypertrophy. The chest radiograph shows cardiomegaly with increased pulmonary vascularity. Classically, the cardiac silhouette is described as being egg-shaped, with a narrow “stalk.”
Without intervention, patients with complete transposition have a poor prognosis. Unless intracardiac mixing is improved, progressive hypoxemia and acidosis develop; the mortality rate is 90 percent by six months of age. Infants who have less severe cyanosis (because of a sizable ventricular septal defect or patent ductus arteriosus) fare better in the neonatal period, but pulmonary vascular obstructive disease (due to increased pulmonary blood flow) is more likely to develop than in infants with more severe cyanosis; infants with less severe cyanosis are also more likely to have higher operative mortality and are less likely to have complete repair of their defect.
The immediate management of complete transposition involves creating intracardiac mixing or increasing its extent. This can be accomplished with an infusion of prostaglandin E (to maintain or restore patency of the ductus arteriosus), the creation of an atrial septal defect by means of balloon atrial septostomy (the Rashkind procedure), or both. In addition, oxygen is given to most patients (to decrease pulmonary vascular resistance and to increase pulmonary blood flow), as are digoxin and diuretic drugs (to treat heart failure).
Two surgical procedures have been used in patients with complete transposition of the great arteries. With the initial approach, known as the “atrial switch” operation (the Mustard or Senning operation), the atrial septum was excised, then a “baffle” within the atria was constructed to direct systemic venous blood across the mitral valve into the left ventricle and pulmonary venous blood across the tricuspid valve into the right ventricle (Figure 7B). Thus, physiologic circulation was restored; however, after this procedure was performed, the right ventricle continued to function as the “systemic ventricle.” This operation corrected cyanosis and improved survival. The complications associated with it were leakage of the atrial baffle (often clinically inconsequential); obstruction of the baffle (often insidious and frequently asymptomatic); sinus-node dysfunction and atrial arrhythmias, particularly atrial flutter; right (systemic) ventricular dysfunction; and an increased risk of sudden death.
The atrial-switch operation has been replaced by the arterial-switch operation, in which the pulmonary artery and ascending aorta are transected above the semilunar valves and coronary arteries and then switched, so that the aorta is connected to the neoaortic valve (formerly the pulmonary valve) arising from the left ventricle, and the pulmonary artery is connected to the neopulmonary valve (formerly the aortic valve) arising from the right ventricle (Figure
Eisenmenger’s Syndrome
A patient with Eisenmenger’s syndrome has a large left-to-right shunt that causes severe pulmonary vascular disease and pulmonary hypertension, with resultant reversal of the direction of shunting (Figure 8). With substantial left-to-right shunting, the exposure of the pulmonary vasculature to increased blood flow as well as increased pressure often results in pulmonary vascular obstructive disease. The initial morphologic alterations (medial hypertrophy of the pulmonary arterioles, intimal proliferation and fibrosis, and occlusion of capillaries and small arterioles) are potentially reversible. However, as the disease progresses, the more advanced morphologic changes (plexiform lesions and necrotizing arteritis) are irreversible. The result is obliteration of much of the pulmonary vascular bed, leading to increased pulmonary vascular resistance. As the pulmonary vascular resistance approaches or exceeds systemic resistance, the shunt is reversed.
Figure 8. Eisenmenger’s Syndrome.
In patients with Eisenmenger’s syndrome, in response to substantial left-to-right shunting, morphologic alterations occur in the small pulmonary arteries and arterioles (inset), leading to pulmonary hypertension and the resultant reversal of the intracardiac shunt (arrow). In the small pulmonary arteries and arterioles, medial hypertrophy, intimal cellular proliferation, and fibrosis lead to narrowing or closure of the vessel lumen. With sustained pulmonary hypertension, extensive atherosclerosis and calcification often develop in the large pulmonary arteries. Eisenmenger’s syndrome may occur in association with a ventricular septal defect (as shown), but it also may occur in association with an atrial septal defect or patent ductus arteriosus.
The morphologic changes in the pulmonary vasculature that occur with Eisenmenger’s syndrome usually begin in childhood, but symptoms may not appear until late childhood or early adulthood. In many patients, pulmonary congestion in early infancy (a result of the large left-to-right shunt) resolves in later infancy or early childhood as pulmonary vascular resistance increases and the magnitude of shunting decreases. Likewise, the patient may have a murmur in early childhood that disappears (as the pulmonary disease progresses and the magnitude of shunting decreases), leading to the mistaken assumption that the intracardiac communication has closed. Occasionally, patients have no history of pulmonary congestion or a murmur in childhood.
As right-to-left shunting develops, cyanosis appears. Most patients will have impaired exercise tolerance and exertional dyspnea, but these symptoms may be well compensated for years. Palpitations are common and are most often due to atrial fibrillation or flutter. As erythrocytosis due to arterial desaturation develops in patients with Eisenmenger’s syndrome, symptoms of hyperviscosity (visual disturbances, fatigue, headache, dizziness, and paresthesias) may appear. Hemoptysis may occur, as a result of pulmonary infarction or rupture of dilated pulmonary arteries, arterioles, or aorticopulmonary collateral vessels. Since patients with arterial desaturation have abnormal hemostasis, they are at risk for both bleeding and thrombosis. Cerebrovascular accidents may occur as a result of paradoxical embolization, venous thrombosis of cerebral vessels, or intracranial hemorrhage. In addition, patients with this condition are at risk for brain abscess. Patients with Eisenmenger’s syndrome may have syncope owing to inadequate cardiac output or, less commonly, an arrhythmia. Symptoms of heart failure, which are uncommon until the disease is far advanced, portend a poor prognosis. Finally, these patients are at risk for sudden death.
On physical examination, patients have digital clubbing and cyanosis, the severity of which depends on the magnitude of right-to-left shunting. The jugular venous pressure may be normal or elevated, and prominent V waves are seen if tricuspid regurgitation is present. Arterial pulses are small in volume. A right parasternal heave (due to right ventricular hypertrophy) is present, and the pulmonary component of the second heart sound is loud (and often palpable). The murmur caused by a ventricular septal defect, patent ductus arteriosus, or atrial septal defect disappears when Eisenmenger’s syndrome develops. Many patients have a decrescendo diastolic murmur caused by pulmonary regurgitation or a holosystolic murmur caused by tricuspid regurgitation. A right-sided fourth heart sound is usually present. The lungs are clear. Peripheral edema and hepatic congestion are absent unless there is substantial right ventricular dysfunction.
The electrocardiogram shows right ventricular hypertrophy. Atrial arrhythmias may be present, particularly in patients with atrial septal defect. The chest film reveals prominent central pulmonary arteries and decreased vascular markings (“pruning”) of the peripheral vessels. The size of the heart is normal in patients with a ventricular septal defect or patent ductus arteriosus, but cardiomegaly (due to right ventricular enlargement) is usually seen in those with atrial septal defect. On transthoracic echocardiography, there is evidence of right ventricular pressure overload and pulmonary hypertension. The underlying cardiac defect can usually be visualized, although shunting across the defect may be difficult to demonstrate by color Doppler imaging because of the low velocity of the jet. Contrast echocardiography permits the location of the shunt to be determined. Catheterization should be performed in any patient with suspected Eisenmenger’s syndrome in order to assess the severity of pulmonary vascular disease and to quantify the magnitude of intracardiac shunting. Pulmonary vasodilators — such as oxygen, inhaled nitrous oxide, or intravenous adenosine or epoprostenol — should be administered to permit assessment of the reversibility of pulmonary hypertension.
The rate of survival among patients with Eisenmenger’s syndrome is 80 percent 10 years after diagnosis, 77 percent at 15 years, and 42 percent at 25 years. Death is usually sudden, presumably caused by arrhythmias, but some patients die of heart failure, hemoptysis, brain abscess, or stroke. A history of syncope, clinically evident right ventricular systolic dysfunction, low cardiac output, and severe hypoxemia portend a poor outcome.
Patients with Eisenmenger’s syndrome should avoid intravascular volume depletion, heavy exertion, high altitude, and the use of vasodilators. Because of high maternal and fetal morbidity and mortality, pregnancy should be avoided. Although no therapy has been proved to reduce pulmonary vascular resistance, intravenous epoprostenol may be beneficial. Phlebotomy with isovolumic replacement should be performed in patients with moderate or severe symptoms of hyperviscosity; it should not be performed in asymptomatic or mildly symptomatic patients (regardless of the hematocrit). Repeated phlebotomy may result in iron deficiency, which may worsen symptoms of hyperviscosity, since iron-deficient erythrocytes are less deformable than iron-replete erythrocytes.
Patients with Eisenmenger’s syndrome who are undergoing noncardiac surgery require meticulous management of anesthesia, with attention to the maintenance of systemic vascular resistance, the minimization of blood loss and intravascular volume depletion, and the prevention of iatrogenic paradoxical embolization. In preparation for noncardiac surgery, prophylactic phlebotomy (usually of 1 to 2 units of blood, with isovolumic replacement) is recommended for patients with a hematocrit above 65 percent in order to reduce the likelihood of perioperative hemorrhagic and thrombotic complications. In general, anticoagulants and antiplatelet agents should be avoided, since they exacerbate the hemorrhagic diathesis.
Lung transplantation with repair of the cardiac defect or combined heart–lung transplantation is an option for patients with Eisenmenger’s syndrome who have markers of a poor prognosis (syncope, refractory right-sided heart failure, a high NYHA functional class, or severe hypoxemia). Because of the somewhat limited success of transplantation and the reasonably good survival among patients treated medically, careful selection of patients for transplantation is imperative.
For Guidelines on the Management of Adults With Congenital Heart Disease, please visit here.
Atrial septal defect: case 1
A 43-year-old businessman presents to the accident and emergency department having had palpitations for 12 h. He admits to having increasing shortness of breath over the past two years, and having to rest after climbing three flights of stairs. On examination, his pulse was irregular at a rate of 110 beats per minute, and his jugular venous pulsation (JVP)
Atrial septal defects are some of the most common congenital cardiac malformations in adults, representing up to 40% of acyanotic shunt lesions in patients older than 40 years. They arise from either excessive resorption of the septum primum or from deficient growth of the septum secundum, and are occasionally associated with anomalous pulmonary venous connection (about 10%). The degree of left-to-right atrial shunting depends on the size of the defect and the diastolic filling properties of the two ventricles. A substantial shunt (Qp/Qs >1·5/1·0) will probably cause symptoms over time, and the movement of such patients will become progressively more restricted with age. Effort dyspnoea is seen in about 30% of patients by their third decade whereas supraventricular arrhythmias (atrial fibrillation or flutter) and right heart failure develop in about 10% of patients by age 40 years.
Treatment
Haemodynamically unimportant atrial septal defects (Qp/Qs <1·5) do not need closure, except for the prevention of paradoxical emboli in patients who have had cryptogenic stroke. In the absence of clinically significant pulmonary hypertension, closure is recommended for severe defects (Qp/Qs >1·5, or those associated with right ventricular volume overload). In patients without symptoms, indications for closure are somewhat controversial. In those younger than 40 years, severe defects should probably be closed. The appropriate treatment for patients who are older than 40 years is in some dispute, although results of one randomised clinical trial which showed an overall survival benefit among surgical patients would suggest that closure is advisable.
Surgical closure of these defects can be done by primary suture closure or by an autologous pericardial or synthetic patch. Surgical mortality in adults with no pulmonary hypertension should be less than 1%, with a low morbidity related mainly to the development of perioperative arrhythmias (atrial flutter or fibrillation, or junctional rhythm). The use of devices to close defects percutaneously under fluoroscopy and transoesophageal echocardiographic guidance is gaining popularity.
Transoesophageal echocardiographical image of a secundum atrial septal defect after closure with Amplatzer device
LA=left atrium. RA=right atrium. Arrows point at both sides of the Amplatzer device after insertion.
Indications for closure by devices are the same as for surgical closure but selection criteria are stricter than for surgery. Devices are available only for patients with one secundum atrial septal defect and with an adequate septal margin for proper device support. Anomalous pulmonary venous connection precludes the use of this technique. This procedure is safe and effective when done by a skilled cardiologist, and major complications (eg, device embolisation, atrial perforation) arise in less than 1% of patients. Complete closure is achieved in 80% or more of patients. Long-term follow-up data, however, are not available. Notwithstanding, closure by device can be appealing to a patient wishing to avoid the consequences of surgery (general anaesthesia, cardiopulmonary bypass, pain, scar, and time for convalescence), or to a patient believed to be at high surgical risk.
Patent ductus arteriosus: case 2
A 72-year-old woman is referred by her family doctor for atypical chest pain. Risk factors for coronary artery disease are few. Physical examination revealed a grade 1/6 continuous murmur in the left subclavian area. Transthoracic echo confirmed a small colour flow jet area seen between the aorta and the pulmonary artery in the suprastemal view, suggestive of a small patent ductus arteriosus. Left-heart chambers are of normal size and function.
The incidence of isolated persistent patency of the ductus arteriosus is estimated at one in 2000 to one in 5000 births. The ductus arteriosus derives from the left sixth primitive aortic arch and connects the proximal left pulmonary artery to the descending aorta, distal to the left subclavian artery. Occasionally, the ductus fails to close at birth and presents as a potential clinical problem.
Physiological consequences of a patent ductus arteriosus depend on the degree of left-to-right shunting, which is determined by both the size of the duct and the difference between systemic and pulmonary vascular resistances. A small ductus accompanied by a small shunt does not cause significant haemodynamic disruption but might predispose to endarteritis, especially if accompanied by an audible murmur. A moderate sized duct and shunt put a volume load on the left atrium and ventricle that results in dilation and often dysfunction of the left ventricle, and development of a trial fibrillation, or both. A large duct results initially in left-ventricular volume overload (which disappears after pulmonary hypertension develops), with a progressive rise in pulmonary artery pressure. This rise in pressure leads to high pulmonary vascular resistance and eventually, irreversible pulmonary vascular changes and systemic pulmonary pressures.
Treatment
Closure of a clinically detectable patent ductus arteriosus, in the absence of irreversible pulmonary hypertension, is usually recommended, although controversial, to avoid infective endarteritis. The risk of endarteritis in a patient with a small silent patent ductus arteriosus is regarded as negligible, and closure of such small ducts is therefore not recommended. Over the past 20 years, the effectiveness and safety of transcatheter device closure for ducts smaller than
Surgical closure, by ductal ligation or division, or both, has been done for over 50 years with a slightly better closure rate, but greater morbidity and mortality, than that for closure with device. Surgical closure of a duct should be reserved for patients with ducts larger than
Bicuspid aortic valve: case 3
A 25-year-old woman (Gravida one, pregnancy none, abortioone) is referred at 18 weeks’ pregnancy for a heart murmur. The patient is asymptomatic. Her blood pressure is 90/60 mm Hg. On examination she had an ejection click best heard at the apex, a grade 3/6 systolic ejection murmur best heard at the second right intercostal space, with radiation to the carotids with a soft diastolic murmur grade 2/6 heard clearest along the left sternal border. A transthoracic echocardiogram confirmed the presence of a bicuspid aortic valve with moderate aortic stenosis (aortic valve area 1·0 cm2), and mild-to-moderate aortic regurgitation. Cardiac MRI showed a dilated ascending aorta measuring
MRI of a dilated ascending aorta in a patient with a bicuspid aortic valve
Arrows indicate the sides of the dilated ascending aorta.
Bicuspid aortic valve has a male preponderance of 4 to 1. This lesion accounts for about half the cases of surgically important isolated aortic stenosis in adults. A bicuspid aortic valve consists of two cusps, often of unequal size, the larger usually containing a false raphe. This lesion generally arises in isolation but is associated with other abnormalities in 20% of patients, the most common of which is coarctation of the aorta and patent ductus arteriosus.
At least half the patients with a bicuspid aortic valve have no complications, although there is always the risk of endocarditis. Mild aortic stenosis or regurgitation from bicuspid aortic valve generally progresses as the patient ages, but the rate is variable. Enlargement of the aortic root resulting from cystic medial changes in patients with bicuspid aortic valve has a high prevalence, and occurs irrespective of altered haemodynamics or age. Aortic dissection is rare.
Treatment
Bicuspid aortic valves need intervention for stenosis when symptoms (exertional dyspnoea, angina, pre-syncope, or syncope) are present and should be considered before pregnancy when the stenosis is severe. Intervention for asymptomatic severe aortic stenosis to allow safe pregnancy is controversial, but severe aortic stenosis has proved to be a risk factor for cardiac decompensation during pregnancy.30 Bicuspid aortic stenosis can be treated with balloon valvuloplasty if the patient is younger than 30 years and if the valve is not calcified. Other treatment options include open aortic valvotomy, or valve replacement with a mechanical valve, a biological valve, or a pulmonary autograft (Ross procedure).
Prophylactic surgery for proximal aortic dilation (>
This patient would be best treated with close medical follow-up and echocardiography every 3 months or so, to look for signs of progressive aortic root dilation. Treatment with β blockers (if blood pressure is normal) and bedrest, with or without early delivery, should be considered when rapid progression of the ascending aortopathy is seen or the ascending aorta reaches more than
Coarctation of aorta: case 4
A 44-year-old man with a history of coarctation repair in his childhood is referred for persistent mild systolic hypertension. The patient is otherwise asymptomatic. The blood pressure is 145/80 mm Hg on the right arm, 120/80 mm Hg on the left arm, 120/80 mm Hg on the right leg with a mild radiofemoral delay. MRI confirms the presence of a mild discrete narrowing at the site of previous coarctation repair and cardiac catheter shows a withdrawal gradient of 20 mm Hg between the proximal and distal descending aorta.
Coarctation of the aorta is seen most frequently in men with a ratio of almost 3 to 1. It usually resides in the region of the ligamentum arteriosum. It might be discrete or associated with hypoplasia of the aortic arch and isthmus. Related abnormalities include bicuspid aortic valve in 50-85% of cases. Despite initial successful correction of coarctation, the risk of late systemic hypertension (due to residual or recurrent coarctation, or merely to abnormal aortic wall compliance) in these patients is fairly high. If inadequately controlled, hypertension leads to an increased risk of premature death from late heart failure. Other causes of premature death might be coronary artery disease with or without aortic rupture or dissection. Careful long-term follow-up and aggressive management of patients with hypertension is therefore recommended. Local complications such as re-coarctation and aneurysm formation at the site of previous transcatheter or surgical correction should be identified through periodic chest radiography, echocardiogram, MRI, or spiral CT examinations.
Treatment
All patients with serious coarctation or recoarctation having proximal hypertension, a withdrawal gradient greater than 20 mm Hg at angiography or an echo peak gradient of more than 20 mm Hg in the absence of extensive collaterals or less than 20 mm Hg in their presence, warrant treatment to eliminate the gradient and reduce the risk of long-term complications. Balloon dilatation with stent insertion in patients with native coarctation and recoarctation can be done with good immediate and medium-term results in adolescents and adults and should probably be the procedure of choice when the anatomy is suitable and expert skills are available. If the anatomy is not suitable (ie, long tunnel-like stenosis) surgery might be needed. After surgical repair of isolated aortic coarctation, the obstruction is usually relieved with minimum mortality (<2%). However, mortality is increased for reoperation (5-15%).
Angiograms of mild re-coarctation of the aorta (A); balloon dilatation and stenting of the re-coarctation segment of the descending aorta (B); and stented descending aorta (C)
Arrow in (A) indicates re-coarctation segment.
This patient has mild re-coarctation of the aorta (peak gradient >20 mm Hg) at the site of previous surgical repair with superimposed mild systolic hypertension. Balloon dilatation and stenting of the re-coarctation segment (if the anatomy is suitable) should be done to reduce proximal systolic blood pressure. The procedure should only be done, however, by experienced cardiologists. Surgical revision or antihypertensive medication, or both, might also be appropriate.
Tetralogy of Fallot: case 5
A 46-year-old woman is brought to the emergency room by ambulance after a witnessed collapse. Sustained ventricular tachycardia was ended and the patient successfully revived.
Electrocardiogram showing ventricular tachycardia in a patient after repair of tetralogy of Fallot
The patient has a history of repaired tetralogy of Fallot in childhood. She was lost to follow-up. Physical examination showed a right ventricular impulse and a low-pitched diastolic murmur grade 3/6 best heard along the left sternal border. Transthoracic echo showed a dilated right ventricle and severe pulmonary regurgitation. Cardiac MRI confirmed a severely dilated right ventricle (right ventricular end-diastolic volume 350 mL—normal range up to 108 mL/m2), severe pulmonary regurgitation, and fairly normal right ventricular systolic function.
MRI showing right right ventricular dilation in a patient after repair of tetralogy of Fallot
LA=left atrium.
Electrophysiological studies confirmed the presence of easily inducible ventricular tachycardia from the right ventricular outflow tract, and angiography shows normal pulmonary and coronary arteries.
Tetralogy of Fallot is the most common form of cyanotic congenital heart disease after 1 year of age, with a frequency of almost 10% of all congenital heart disease. The defect is caused by anterocephalad deviation of the outlet septum resulting in four features: (1) a non-restrictive ventricular septal defect; (2) an overriding aorta (<50% override); (3) obstruction of the right ventricular outflow tract which may be infundibular, valvar, or (usually) both, with or without supravalvar or branch pulmonary artery stenosis; and (4) consequent right ventricular hypertrophy.
Reparative surgery is usually done early in infancy, by closure of the ventricular septal defect with a Dacron patch and relief of the right ventricular outflow tract obstruction. Obstruction relief might include resection of infundibular muscle and insertion of a right ventricular outflow tract or transannular patch—a patch across the pulmonary valve annulus that disrupts the integrity of the pulmonary valve and causes important pulmonary regurgitation. Significant pulmonary regurgitation is almost always encountered when the transannular patch repair technique is used. Pulmonary regurgitation is usually well-tolerated indefinitely, if mild to moderate. Severe chronic pulmonary regurgitation might be well tolerated for 20 years or more, but could then lead to symptomatic right ventricular dysfunction, and increase the susceptibility to ventricular tachycardia and sudden cardiac death.
Residual obstruction of the right ventricular outflow tract can arise in the infundibulum, the pulmonary valve, and the main pulmonary trunk or branches of the left and right pulmonary arteries, or both branches. Right ventricular dilation in this setting is usually due to longstanding free pulmonary regurgitation, but might result from operative injury. Substantial tricuspid regurgitation might occur because of right ventricular dilation, which then leads to further dilation of the right ventricle.
Atrial tachyarrhythmia arises in about a third of adults and contributes to late morbidity and even mortality. It usually takes the form of atrial flutter or intra-atrial re-entrant tachycardia. Often indicative of haemodynamic trouble (significant right ventricular dilation and dysfunction, increased tricuspid regurgitation), the substrate is most likely a surgical scar in the atria and the trigger, atrial dilation.
Sustained monomorphic ventricular tachycardia is rare, compared with other types, and is highly associated with pronounced right ventricular dilation. The QRS duration from the standard surface ECG has been shown to correlate well with right ventricle size in these patients. A maximum QRS duration of 180 ms or more is a highly sensitive marker for sustained ventricular tachycardia and sudden cardiac death in adults with previous tetralogy repair, although its positive predictive value is low. Dilation of the right ventricle is thought to trigger ventricular tachycardia, whereas surgical scars (near the right ventricular outflow tract or ventricular septal defect patch) form the arrhythmia substrate. The reported frequency of sudden death, presumably due to arrhythmia, in late follow-up series is 0·5—6% over 30 years, accounting for about a third to a half of late deaths. Older age at repair, severe left ventricular dysfunction, postoperative right ventricular hypertension, transannular patching (causing free pulmonary regurgitation), and an accelerated rate of QRS prolongation are all predictors of sudden death in these patients.
Treatment of complications
Replacement of the pulmonary valve (with either a homograft or porcine bioprosthesis) might be necessary for severe pulmonary regurgitation leading to right ventricular dilation, sustained arrhythmias or symptoms, or both. Such replacement might also be needed for a grossly calcified pulmonary valve. It has a low operative risk and leads to symptomatic improvement. Timely pulmonary valve replacement, before irreversible severe right ventricular dilation and systolic right ventricular dysfunction begins, is a major clinical goal. Concomitant tricuspid valve annuloplasty might also be necessary when at least moderate tricuspid regurgitation is present.
Patients presenting with sustained atrial flutter, atrial fibrillation, or ventricular tachycardia, should undergo a thorough assessment of their haemodynamics and should have residual haemodynamic lesions repaired—eg, significant right ventricular dilation from pulmonary regurgitation with resulting tricuspid regurgitation that needs pulmonary valve replacement and tricuspid valve annuloplasty50, 51. Radiofrequency ablation, after mapping for atrial re-entry tachycardia, now yields better results than before for classic atrial flutter or incisional atrial reentrant tachycardia, or both, and should be done either percutaneously (if there is no need for concomitant surgery) or intraoperatively at the time of surgical repair of underlying haemodynamic lesions. For atrial fibrillation, a biatrial maze procedure should also be considered, and ideally done at reoperation. Likewise, transcatheter (when surgery is unnecessary) or concomitant intraoperative ablative procedures of the ventricular tachycardial pathway should be done when appropriate. Antiarrhythmic medications and the new generation of atrial antitachycardia pacemakers (for supraventricular tachycardia) can be used as adjunct treatments. Patients who were resuscitated after sudden cardiac death and are ieed of surgery without a haemodynamic substrate should probably receive an automated implantable cardioverter defibrillator (AICD).
This patient should probably have pulmonary valve replacement since the right ventricle is severely dilated, with repair of the ventricular septal defect patch as well as cryoablation of the ventricular tachycardia focus at the time of surgery. Pulmonary valve replacement will lead to a smaller right ventricle and cryoablation of the ventricular tachycardia focus would eliminate the arrhythmia substrate and probably prevent a further episode of sudden cardiac death.
Transposition of the great arteries: case 6
A 32-year-old man who had the Mustard procedure for D-transposition of the great arteries presents with increasing exertional dyspnoea and fatigue. Cardiac examination revealed a right ventricular impulse, a loud single S2 (second heart sound) and a holosystolic murmur best heard at the left sternal border. Transthoracic echo confirmed the presence of severe systemic tricuspid regurgitation and severe systemic right ventricular systolic dysfunction (ejection fraction 15%).
In patients with complete transposition of the great arteries, the connections between the atria and ventricles are concordant (normal), and the connections between ventricles and great arteries are discordant. Thus, the pulmonary and systemic circulations are connected in parallel rather than the normal in-series connection. In one circuit, systemic venous blood passes to the right atrium, the right ventricle, and then to the aorta. In the other, pulmonary venous blood passes through the left atrium and ventricle to the pulmonary artery. This situation is fatal unless the two circuits mix. About half of patients with transposition of the great arteries have additional abnormalities, most often a ventricular septal defect.
The most common previously done surgical procedure seen in adults is the atrial switch operation. Patients will have had either a Mustard or a Senning procedure. Blood is redirected at atrial level with a baffle made of Dacron or pericardium (Mustard operation) or with atrial flaps (Senning operation), to achieve physiological correction. Systemic venous return is diverted through the mitral valve into the subpulmonary morphological left ventricle and the pulmonary venous return is rerouted via the tricuspid valve into the subaortic morphological right ventricle. This repair, however, leaves the morphological right ventricle to support the systemic circulation.
Diagram showing atrial baffle in a patient with D-transposition of the great arteries
RA=right atrium. RV=right ventricle. LA=left atrium.
After atrial baffle surgery, most patients reaching adulthood will be in New York Heart Association class I—II. During 25 years of follow-up, about half these patients will have moderate systemic dysfunction of the right ventricle with only a few presenting with symptoms of congestive heart failure. Severe systemic tricuspid regurgitation is present in about a third, which exacerbates right ventricular dysfunction. Atrial flutter arises in 20% of patients by age 20 and progressive sinus node dysfunction is seen in half the patients by that time. These rhythm disturbances are thought to be a result of atrial and sinus node damage at the time of atrial baffle surgery. Baffle leak or obstruction can also occur.
The atrial switch operation was gradually replaced by the arterial switch operation (Jatene) in the 1980s, but few of these patients have yet become adults. Blood is redirected at the great artery level by switching the aorta and pulmonary arteries such that the morphological left ventricle becomes the subaortic ventricle and the morphological right ventricle becomes the subpulmonary ventricle. Reliable data for the clinical outcome in adults after the arterial switch procedure should be available over the next decade. Clinical arrhythmia promises to be less of a problem in this group of patients, but concerns about the development of supra neopulmonary artery stenosis, ostial coronary artery disease, and progressive neoaortic valve regurgitation warrant serial follow-up
Treatment
The benefits of angiotensin-converting enzyme inhibitors in patients with systemic right ventricular dysfunction after an atrial switch have not been established, and are being investigated in a double-blind multicentre randomised trial of ramipril. Occasionally, patients with a failed Mustard or Senning operation might need heart transplantation. Alternatively, a conversion procedure to an arterial switch, after re-training of the left ventricle with a pulmonary artery band, could be considered, but few data for the outcome of such a procedure are available in adults.
The degree of right ventricular dilation and systolic dysfunction should be confirmed by MRI or multiple gated acquisition examinations. An angiotensin-converting enzyme inhibitor with or without other heart failure therapies could be tried in this patient. If no clinical improvement is noted, however, a switch conversion procedure (pulmonary artery banding with left ventricular training followed by pulmonary artery debanding, and arterial switch with take down of the atrial baffle) should be used. Tricuspid valve replacement in this patient would probably lead to worsening of right ventricular function and is not recommended. Cardiac transplantation could also be considered at an appropriate time.
Fontan procedure: case 7
A 26-year-old college student with a diagnosis of tricuspid atresia palliated by the Fontan procedure goes to her local emergency room because of 6 h of continuous rapid palpitations. The patient is haemodynamically stable, and a cardiac monitor reveals atrial fibrillation with a ventricular response of ten beats per minute.
The Fontan procedure is the palliative, non-curative, surgical treatment for patients with univentricular hearts. The principle is diversion of the systemic venous return directly to the pulmonary arteries without the need for a subpulmonary ventricle. Many modifications of this procedure have been described, eg—direct atrio-pulmonary connection, total cavopulmonary connection, and extracardiac conduit. Progressive deterioration of functional status with time is the rule, with survival at 10 years after the procedure reported to be 60—71%. The most common complications after a Fontan procedure include atrial flutter or fibrillation, right atrial thrombus formation, obstruction of the Fontan circuit, and ventricular dysfunction.
Atrial flutter or fibrillation are common (15—20% at 5-year follow-up), and increases with duration of follow-up. They are associated with serious morbidity (especially the development of atrial thrombi within hours), and can lead to profound haemodynamic deterioration. Such patients need prompt and expert medical attention. The combination of atrial incisions and multiple suture lines at the time of Fontan surgery with increased right atrial pressure and size probably accounts for the high frequency of atrial arrhythmias in these patients. Obstruction of the Fontan connection should be ruled out in all patients presenting with new onset atrial arrhythmias.
The reported frequency of thromboembolic complications in the Fontan circuit varies from 6% to 33%, dependent on the diagnostic method used and the length of follow-up. Right atrial thrombus formation relates to the presence of atrial flutter or fibrillation, right atrial dilation, right atrial smoke (spontaneous echo contrast), and the presence of artificial material used to construct the Fontan circuit.
Part obstruction of the Fontan connection leads to exercise intolerance, atrial tachyarrhythmias, and right-sided heart failure. Sudden total obstruction presents as sudden death. Protein-losing enteropathy is seen in about 2—3% of patients after the Fontan procedure. Patients present with generalised oedema, ascites, pleural effusion, or chronic diarrhoea. The diagnosis is confirmed by low serum albumin and protein and high α1-antitrypsin stool clearance. The prognosis is poor, with a 5-year survival of 46—59%.
Treatment of complications
In patients with atrial fibrillation or flutter, prompt anticoagulation and transoesophageal echo assessment to rule out atrial thrombi before cardioversion is recommended. Long-term management with antiarrhythmic therapy is successful in less than 50%. Transcatheter atrial ablation can be done in specialised centres, with a 50% success rate. For recalcitrant cases, surgical revision with antiarrhythmic surgery is recommended.
Transoesophageal echocardiogram showing a right atrial clot
LA=left atrium. RA=right atrium. Arrow indicates right atrial clot.
For established thrombus, thrombolytic therapy or surgical removal of the clot and conversion of the Fontan circuit have been described. Long-term anticoagulation is recommended for patients with known thrombi. Some centres anticoagulate all Fontan circuits for the rest of the patient’s life. For patients with Fontan obstruction, surgical revision of the Fontan connection is usually needed. Alternatively, balloon angioplasty with or without stenting can be used when appropriate. Patients with protein-losing enteropathy might be candidates for creation of a fenestration in the atrial septum or revision of the Fontan. Alternatively, subcutaneous heparin, octreotide treatment, and prednisone treatment have also been tried with variable success, No particular treatment seems more successful than any other.
In this patient, who is haemodynamically stable, ventricular rate should be controlled with digoxin or other agents, and prompt anticoagulation with heparin should be started. The patient should be transferred to a highly specialised hospital for transoesophageal echo to rule out right atrial clot before cardioversion. Fontan obstruction as the cause of atrial fibrillation (conduit obstruction with secondary right atrial stretch) should be ruled out either at the time of transoesophageal echo or by cardiac catheterisation. Long-term coumadin is recommended for all patients with Fontan obstruction who have a history of atrial fibrillation. Maintenance of sinus rhythm after cardioversion is probably best achieved with amiodarone, although the success rate is low at 50%. Antitachycardia pacing, catheter ablation or surgical revision, or both, with concomitant biatrial maze procedure are used as second-line treatment in patients with Fontan obstruction and chronic or paroxysmal atrial fibrillation that is unresponsive to medical management. Other causes of atrial fibrillation such as ethanol binge or hyperthyroidism should also be ruled out.
Підготував Доброродній А.В.
