Chapter 47. Multiple Valve Disease

Pathologic changes in the cardiac valves requiring surgical correction of more than one valve can result from rheumatic heart disease, degenerative valve diseases, infective endocarditis, and a number of miscellaneous causes. Further, valve dysfunction may be primary; that is, a direct result of a disease process, or secondary; that is, caused by cardiac enlargement and/or pulmonary hypertension. Surgical management is influenced both by the underlying cause of valve dysfunction and, when valves are involved secondarily, by the anticipated response to replacement or repair of the primary valve lesion. In addition, the consequences of various combinations of diseased valves on left and right ventricular geometry and function frequently are different from the remodeling as a result of single-valve disease. This chapter addresses pathophysiologic considerations in multivalvular heart disease, surgical techniques, and management of commonly encountered etiologies.

Repair of multiple lesions was necessary even in the early development of operative management of valvular heart disease (Table 47-1). The first triple-valve replacement during a single operation was reported in 1960, and simultaneous replacement of all four valves was reported in 1992.1

Experience from clinical practice indicates that multiple valve disease requiring surgical correction occurs in a few common combinations. As seen in Table 47-2, multiple procedures account for approximately 15% of all operations on cardiac valves; 80% of these operations involve the aortic and mitral positions. Replacement of the mitral and tricuspid valves (with or without aortic replacement) accounts for 20% of operations. Only rarely is the combination of aortic and tricuspid disease encountered.

Valvular regurgitation may result from the pathologic process affecting the valve directly or may be secondary to alterations in ventricular morphology caused by other valve lesions; this secondary or functional regurgitation affects the atrioventricular valves. In some patients, secondary valvular regurgitation may be expected to improve with repair or replacement of the primarily diseased valve. In other patients, the secondary disease process may have advanced to the stage that valve function will not improve following correction of the primary lesion, and thus simultaneous surgical correction should be considered.

Primary Aortic Valve Disease with Secondary Mitral Regurgitation

Isolated aortic valve lesions can cause secondary regurgitation of the mitral valve and rarely, the tricuspid valve. Severe aortic valve stenosis with or without left ventricular dilatation frequently is associated with some degree of mitral valve regurgitation. In one series, 67% of patients with severe aortic valve stenosis had associated mitral valve leakage.2

When the mitral valve is structurally normal, its regurgitation would be expected to improve with relief of left ventricular outflow obstruction3; mild mitral valve regurgitation would be expected to resolve almost completely after aortic valve replacement. Improvement in mitral valve regurgitation results from both decreased intraventricular pressure and ventricular remodeling.4 If mitral valve regurgitation is severe, some degree of persistent regurgitation is expected after aortic valve replacement, and mitral valve annuloplasty may be required. In contrast, with aortic valve stenosis and mitral valve regurgitation associated with a structurally abnormal mitral valve, repair or replacement of the mitral valve usually is necessary. A recent report alleges that moderate mitral regurgitation has an adverse impact on survival in elderly patients undergoing aortic valve replacement and suggests that those with intrinsic mitral valve disease should be considered for concurrent correction.5

Thus determination of the morphology and pathophysiologic severity of each valve lesion is critically important in planning surgical management, and preoperative and intraoperative echocardiographic studies are necessary in all patients suspected of having multiple valve disease. Often, transthoracic echocardiography can define the etiology of mitral and tricuspid valvular regurgitation. When valve regurgitation is entirely secondary, the mitral valve leaflets will appear thin and freely mobile, without prolapsing segments. Mitral (and tricuspid) valve regurgitation secondary to rheumatic disease is readily identified when leaflets are thickened and chordae are shortened; fibrosis of these structures restricts leaflet mobility. Leaflet prolapse with or without ruptured chordae tendineae also may cause atrioventricular valve regurgitation.

Transesophageal echocardiography images the heart from a retrocardiac position, which avoids interference from interposed ribs, lungs, and subcutaneous tissue. A high-frequency (5-MHz) transducer is employed, which yields better resolution than that of images obtained with routine transthoracic imaging with 2.25- to 3.5-MHz transducers.6 Thus transesophageal echocardiography provides the best image of the mitral and tricuspid valves and may be obtained preoperatively. Intraoperative transesophageal Doppler echocardiography should be employed in all patients having valve repair or replacement, and the technique is especially important for assessment of response of mitral regurgitation to relief of left ventricular outflow obstruction.7 In some cases, preoperative left ventriculography may help to quantify left atrioventricular valve leakage. Right ventricular angiocardiography also can be useful in determining the degree of tricuspid valve dysfunction, but it is rarely employed in current practice.8

Tricuspid Valve Regurgitation Secondary to Other Valvular Disease

Secondary tricuspid valve regurgitation commonly is associated with rheumatic mitral valve stenosis, and the exact cause is unknown.9,10 Some authors believe that secondary tricuspid valve regurgitation is a result of pulmonary artery hypertension and right ventricular dilatation.11 As with the mitral valve, tricuspid valve annular dilatation in those with severe TR is asymmetric. Most enlargement occurs in the annulus subtended by the free wall of the right ventricle, and there is little dilation of the annulus adjacent to the septal leaflet of the tricuspid valve.12,13 Although pulmonary artery hypertension with secondary enlargement of the right ventricle and tricuspid valve annulus may be an important contributing factor in secondary tricuspid regurgitation, it is not the sole mechanism. For example, congenital heart lesions such as tetralogy of Fallot produce systemic pressure in the right ventricle, yet severe tricuspid valve regurgitation rarely is seen in these patients. Similarly, important tricuspid valve regurgitation is uncommon in children with ventricular septal defects who have enlargement of the right ventricle associated with variable degrees of pulmonary hypertension.

Furthermore, clinical experience suggests that other mechanisms must play a role in development of secondary tricuspid valve regurgitation. Patients who have had mitral valve replacement for rheumatic mitral valve stenosis may develop regurgitation of their native tricuspid valve years after initial operation, and many patients have only modest elevation of pulmonary artery pressure.14,15 Recent evidence points to a progressive immunologic process in rheumatic valve disease, which can lead to severe TR many years after successful percutaneous or surgical management of the mitral valve.16

It is useful to classify secondary mitral and tricuspid valve regurgitation as mild, moderate, and severe.13 Usually, patients with mild tricuspid valve regurgitation do not have clinical signs and symptoms of right-sided heart failure. Also, mild tricuspid regurgitation demonstrated by preoperative echocardiography may appear even less severe in the operating room under general anesthesia. In most instances, mild secondary tricuspid regurgitation does not require intervention.

Patients with echocardiographic evidence of significant regurgitation who do not have symptoms or have their symptoms controlled by medical treatment can be classified as having moderate tricuspid regurgitation. These patients usually are managed with a DeVega suture annuloplasty or a partial-ring annuloplasty.17 Patients with severe secondary tricuspid regurgitation and clinical evidence of right-sided heart failure (eg, pulsatile liver, distended neck veins, and peripheral edema with or without ascites) are most frequently managed by concomitant ring annuloplasty or tricuspid valve replacement.

The degree of pulmonary hypertension may influence surgical management of secondary tricuspid valve regurgitation. Kaul and colleagues18 grouped 86 patients with functional tricuspid regurgitation in association with rheumatic mitral valve disease according to the degree of pulmonary hypertension. One group had severe pulmonary hypertension (mean pulmonary pressure 78 mm Hg), and a second group had moderate pulmonary hypertension (mean pulmonary artery pressure 41 mm Hg). Patients with moderate pulmonary hypertension preoperatively had more advanced right-sided heart failure and right ventricular dilatation, and many of these patients continued to have tricuspid valve regurgitation following mitral valve surgery without tricuspid valve surgery. The patients with severe pulmonary hypertension all showed regression of tricuspid regurgitation, and 28% had complete resolution following mitral valve surgery without operation on the tricuspid valve.

Excluding hospital mortality, about 40% of patients undergoing tricuspid valve surgery have premature death.8 It is also important to understand that mild to moderate (2+) regurgitation is a risk factor for late failure of tricuspid valve repair, and severe (4+) regurgitation preoperatively is a predictor of early residual regurgitation.19 Finally, there is recent evidence to suggest that remodeling annuloplasty in the setting of tricuspid annular dilatation (≥70 mm) at the time of mitral repair significantly decreases the risk of subsequent functional deterioration as compared with those not having annular correction.20

The difficulty with interpretation and generalization of current literature guiding management of secondary functional TR is the significant heterogeneity in both patient disease substrate and surgical procedure performed. The incidence of severe late TR has been reported to be approximately 68% up to 30 years following mitral replacement for rheumatic disease.21 The risk of significant late secondary TR is as high as 74% 3 years following repair of ischemic MR.22 The most frequently identified risk factors for TR progression from these series include older age, female gender, rheumatic etiology, atrial fibrillation, the absence of a Maze operation.21–24 Therefore, most would agree that correction of moderate or greater TR at the time of surgery for rheumatic mitral disease is indicated to prevent the development of symptoms associated with TR progression.25 Less clear however is whether long-term survival is improved by such intervention.24 Furthermore, reliance on tricuspid annular dilation alone as suggested by Dreyfus and coworkers20 has recently been challenged.26

In contrast, although mitral valve prolapse is the most frequent cause of mitral regurgitation in the developed world, there are few reports addressing the incidence and fate of functional TR following successful mitral valve repair. Recent data suggest that moderate or less functional TR does not progress as aggressively following repair of leaflet prolapse as in rheumatic or ischemic mitral disease subsets.27 Outcomes following isolated mitral valve repair for degenerative MR with less than severe coexistent functional TR at Mayo Clinic support this assertion; with only one patient out of 699 requiring tricuspid valve reoperation during long-term follow up.

When multiple valve replacement is confined to the left ventricle, replacement valves should be chosen from the same class with respect to the need for anticoagulation and projected longevity. There are no theoretical or practical advantages to use of a tissue valve and a mechanical valve for mitral and aortic valve replacement, and studies show no reduction in the risk of thromboembolism, valve-related morbidity, or late death.29,30 In addition, a lower reoperation rate is reported for patients with two mechanical valves in the left ventricle compared with patients with one mechanical and one tissue valve.29

For tricuspid valve replacement, alone or in conjunction with other valve procedures, use of a bioprosthesis may have advantages in regard to minimizing risk of valve thrombosis.31,32 Furthermore, there are few hemodynamic considerations in selecting a tricuspid prosthesis; the greater hemodynamic efficiency of mechanical valves compared with bioprostheses rarely is an issue in atrioventricular valve replacement, especially the tricuspid valve, in which the annulus diameter in adults is often 33 mm or more. In vitro studies demonstrate only minimal hemodynamic improvement with atrioventricular valves larger than 25 mm.33

Aortic and Mitral Valve Replacement

Cannulation

Arterial inflow is established by cannulation of the distal ascending aorta near the pericardial reflection just to the left of the origin of the innominate artery (Fig. 47-1A). Venous cannulation is simplified by using a two-stage cannula in the right atrium for venous return. Individual cannulation of the superior and inferior venae cavae is reserved for operations that require right atrial or ventricular incisions (Fig. 47-2A). Provisions for intraoperative autotransfusion are used routinely, and antifibrinolytic drugs such as aprotinin or epsilon-aminocaproic acid (Amicar) may be useful, especially in reoperations, in which pericardial adhesions may worsen bleeding.34

Cardioplegia

If the aortic valve is competent, myocardial protection during aortic cross-clamping is achieved by initial infusion of cold (4 to 8°C) blood cardioplegia through a tack vent placed in the aorta proximal to the clamp. The volume of cardioplegia needed to achieve diastolic arrest and uniform hypothermia depends on the heart size and the presence of aortic valve regurgitation. Generally, the initial volume of cardioplegia required for hearts with multiple valve disease is higher than that required for coronary revascularization because of myocardial hypertrophy. For patients without cardiac enlargement, we infuse approximately 10 mL/kg of body weight, whereas 15 mL/kg of body weight is used for patients with significant degrees of myocardial hypertrophy. Repeat infusions of 400 mL of cardioplegia are given directly into the coronary ostia at 20-minute intervals during aortic occlusion. We use custom-designed, soft-tipped coronary perfusion catheters to minimize the potential for trauma to the coronary ostia during intubation and infusion.35

If aortic valve regurgitation is moderate or severe, cardioplegia is infused directly into the coronary ostia. Initial aortotomy is facilitated by emptying the heart using suction on an aortic tack vent and temporarily reducing the cardiopulmonary bypass flow rate to maximize venous return. Some surgeons prefer retrograde infusion of cardioplegia,36 and if this method is used, even larger volumes are necessary because of nonnutritive flow through the coronary venous system and variation in coronary venous anatomy.37,38

Procedure

After cardioplegia, the aortic valve is inspected through an oblique aortotomy extended into the noncoronary aortic sinus (see Fig. 47-1B). Aortic valve regurgitation caused by cuspal perforation or prolapse of a congenitally bicuspid valve often can be repaired,39 but the decision for or against aortic valve repair should take into consideration whether or not a mitral valve prosthesis will be needed. For example, even though aortic valve repair might seem technically possible, prosthetic replacement may be the best option for a patient who requires mitral valve replacement and will be maintained on warfarin for long-term anticoagulation.

Severe calcification of the valve, whether it is bicuspid or tricuspid, necessitates replacement;40 therefore, the cusps are excised and annular calcium debrided carefully. The aortic annulus then is calibrated; experience has shown that subsequent replacement of the mitral valve usually reduces the aortic annular diameter by shortening the circumference that is in continuity with the attachment of the anterior mitral valve leaflet. Therefore, we routinely identify (but do not break the sterile packaging of) two aortic prostheses: One corresponds to the calibrated dimension, and the other is the next size smaller. Final selection of the aortic prosthesis is made after mitral valve replacement or repair.

Although exposed first, the aortic valve usually is replaced after mitral valve repair or insertion of the mitral valve prosthesis. Sutures placed in the portion of the aortic valve annulus that is continuous with the anterior leaflet of the mitral valve pull the anterior leaflet superiorly toward the left ventricular outflow area and thus hinder exposure of this area as viewed through the left atriotomy.

If the aortic annulus is small, it can be enlarged with a patch of pericardium.41 This technique increases annular diameter by 2 to 4 mm or more, and only rarely are more radical techniques necessary.42–44 Another maneuver to accommodate as large a prosthesis as possible is to place the necessary sutures for the mitral valve repair or replacement but not secure the mitral prosthesis until the aortic valve is implanted. This eliminates downsizing of the aortic prosthesis but does not compromise insertion of sutures in the superior portion of the mitral valve annulus.

After removal of the aortic valve, the right atrial cannula is repositioned, and the mitral valve is exposed through an incision posterior to the interatrial groove (see Fig. 47-1B). The presence or absence of thrombi in the left atrium is noted, and the mitral valve is inspected. When there is rheumatic disease of the aortic valve, the mitral valve almost always will be involved to some extent. If aortic valve replacement is necessary, the surgeon should have a low threshold for replacing a diseased mitral valve because scarring and fibrosis of the rheumatic process are progressive, and mitral valve repair (commissurotomy for stenosis or leaflet repair and annuloplasty for regurgitation) is less durable than repair for degenerative disease.45–47 In contrast, when aortic valve replacement is necessary because of calcification of a bicuspid valve or senescent calcification, repair of mitral valve regurgitation owing to degenerative causes can be expected to give predictably good long-term results. Repair of the mitral valve is described in Chapter 41.

In preparation for replacement, the anterior leaflet of the mitral valve is excised, and when possible, a portion of the posterior leaflet with its chordal attachments is preserved to maintain left ventricular papillary muscle–annular continuity.48–50 Some surgeons make a special effort to preserve the anterior leaflet and its chordal attachments, believing that this has a further beneficial effect on ventricular performance.51 The mitral prosthesis is implanted using interrupted mattress sutures of 2-0 braided polyester reinforced with felt pledgets, which can be situated on the atrial or ventricular side of the valve annulus (see Fig. 47-1C). The leaflets of mechanical valves should be tested for free mobility following valve seating.

When atrial fibrillation is present preoperatively, we obliterate the left atrial appendage by oversewing its orifice from within the left atrium or ligating it externally. The left atriotomy is closed from each end with running polypropylene sutures. Vent tubing is inserted through the partially closed left atriotomy and left in place while the aortic valve is being replaced (see Fig. 47-1D).

After appropriate exposure, the aortic prosthesis is sewn in place with interrupted 2-0 polyester mattress sutures backed with felt pledgets, and the aortotomy is closed, usually with two layers of 4-0 polypropylene. Any remaining air is evacuated from the heart with the usual maneuvers, and a tack vent in the ascending aorta is placed on suction as the aortic clamp is removed. The vent is removed from the left atrium, and closure of the left atriotomy is secured.

In patients with annuloaortic ectasia, the mitral valve sometimes can be visualized and replaced through the enlarged aortic annulus.52

Aortic Valve Replacement and Mitral Valve Repair

Intraoperative transesophageal echocardiography is useful in assessing the degree of mitral regurgitation and, importantly, in identifying the cause of valve leakage. When mitral valve regurgitation is only moderate and leaflet morphology is normal, we expect mitral valve function to improve following relief of severe aortic stenosis. In all other instances, the valve should be inspected directly to determine the need for repair or replacement.

Sternotomy, cannulation, and assessment of the aortic valve proceed as described previously. When there is no indication of tricuspid valve disease and no other right atrial procedures are planned, venous return is obtained through a single two-staged cannula (Fig. 47-3A). Specific techniques of mitral valve repair depend on operative findings.53 Localized prolapse of a portion of the posterior leaflet with or without ruptured chordae usually is managed by triangular excision of that segment and repair with continuous 4-0 polypropylene suture.54 Ruptured chordae to the anterior leaflet are replaced with 4-0 or 5-0 polytetrafluoroethylene (PTFE) sutures inserted into papillary muscle and through the free edge of the prolapsing leaflet.55

Almost all leaflet repairs are supplemented with a posterior annuloplasty. Interrupted 2-0 braided polyester mattress sutures are placed along the posterior circumference of the annulus ending at the right and left fibrous trigones (see Fig. 47-3A). Sutures then are spaced evenly through a flexible 6.0- to 6.5-cm–long partial ring; this standard length can be obtained by using a flexible 63-mm posterior annuloplasty band.47,56 Following annuloplasty, competence of the mitral valve is tested by filling the ventricle with saline or blood; the atrium then is closed, and the aortic valve prosthesis is sewn into place.

Mitral Valve Replacement and Tricuspid Valve Replacement or Repair

In most instances, tricuspid valve regurgitation is caused by annular dilatation.57 The severity of tricuspid valve leakage can be determined by transesophageal echocardiography before bypass and by digital exploration of the right atrium just before venous cannulation. Under general anesthesia, changes in blood volume and cardiac output can cause significant fluctuation in the amount of regurgitation, and most often the severity of tricuspid valve leakage is lessened in the immediate prebypass period.

The patient's clinical condition must be correlated with echocardiographic findings and intraoperative assessment of the tricuspid valve. Patients with an enlarged, pulsatile liver, peripheral edema, and jugular venous distention are likely to require tricuspid valvuloplasty following mitral valve replacement or repair. Patients without the stigmata of right-sided heart failure usually have less severe valve leakage, and tricuspid valve function may improve without direct repair or replacement after left-sided valvular lesions are corrected.

The decision for repair or replacement of functional tricuspid valve regurgitation at the time of mitral valve replacement is important because the risk of subsequent reoperation is high. In our earlier experience, operative mortality was 25% in patients who required later reoperation for tricuspid valve regurgitation. Further, tricuspid regurgitation progresses in 10 to 15% of patients after replacement of rheumatic mitral valves.58 Therefore, we maintain a liberal policy for annuloplasty or prosthetic replacement at initial operation.59

Procedure

For operations on the tricuspid valve, insertion of a Swan-Ganz catheter is optional; if one is used, the catheter is withdrawn from the right heart chambers during inspection and assessment of the tricuspid valve. We prefer direct cannulation of the inferior and superior venae cavae.60 After commencement of cardiopulmonary bypass and cardioplegia, the cavae are snared around the venous cannulae, and the interatrial septum and tricuspid valve are exposed through a right atriotomy (see Fig. 47-2A). A decision for repair or replacement of the tricuspid valve is made, and the necessary prosthesis is identified.

When the tricuspid valve is also addressed, we tend to expose the mitral valve through an incision in the interatrial septum, which crosses the fossa ovalis and can be extended superiorly (see Fig. 47-2B). Care should be taken during retraction to avoid tearing the septum inferiorly toward the coronary sinus and triangle of Koch. Alternatively, the mitral valve can be exposed through a standard left atriotomy posterior to the interatrial groove.

After repair or replacement of the mitral valve (see Fig. 47-2C), the septal or left atrial incision is closed, and the tricuspid valve is repaired or replaced. For tricuspid valve repair, we use either the DeVega method or ring annuloplasty.11,17,61,62 Both techniques are based on the observation that the anterior and posterior valve portions of the tricuspid valve annulus are more prone to dilatation than the septal leaflet portion of the annulus, as described previously. When ring annuloplasty is indicated, we prefer a flexible device such as the Cosgrove-Edwards prosthesis63 or a partial Duran ring (see Fig. 47-3B). The use of a partial ring avoids placement of sutures in the annulus near the penetrating bundle of His and reduces risk of injury to conduction tissue. There have been conflicting reports regarding the superiority of DeVega procedure versus prosthetic annuloplasty in improving freedom from recurrent TR.64–66

Minimally Invasive Approaches

Although addressed elsewhere in this textbook, minimally invasive approaches to primary and reoperative left and right-sided valvular heart disease have been proposed. Various cannulation and cardioplegia techniques have been described as determined by the pattern of valve disease and patient anatomy.67

Tricuspid Valve Replacement and Pulmonary Valve Replacement for Carcinoid Heart Disease

If there is no involvement of the mitral and aortic valves,57,68 tricuspid and pulmonary valve replacement usually can be performed without the need for aortic occlusion and cardioplegic arrest. It is important to exclude the presence of a patent foramen ovale to eliminate the risk of air entering the left atrium, and if a defect in the atrial septum is identified, it is closed using a brief period of aortic occlusion. In the past, our strategy for patients with carcinoid heart disease was to replace the tricuspid valve and excise the diseased pulmonary valve.

Subsequent experience has suggested that right ventricular function is better preserved with a competent pulmonary valve, so we now favor pulmonary valve replacement rather than valvectomy.69 Tricuspid valve replacement always is indicated, and it is usually necessary only to remove the anterior leaflet. A recent review of 200 patients with carcinoid heart disease at our institution demonstrated that prognosis has improved in the current era and that valve replacement surgery was independently associated with prolonged survival.70

Carcinoid disease produces fibrosis and retraction of the leaflets, so anchoring sutures (interrupted mattress sutures of 2-0 braided polyester backed with felt pledgets) can be inserted into the remaining septal and posterior leaflets. We prefer to position the pledgets on the ventricular side of the valve annulus. If exposure is difficult, a brief period of aortic clamping and cardioplegic arrest is used during placement of sutures in the posterior and septal leaflets; the aortic cross-clamp is removed, and the heart is allowed to beat rhythmically. The remaining sutures are placed, and all sutures are secured with observation of the electrocardiogram. If atrioventricular block develops, the sutures in the area of the penetrating bundle of His are removed and reinserted in a more superficial location.

Pulmonary valve replacement is performed through a longitudinal incision across the valve annulus onto the outflow portion of the right ventricle. We prefer to insert the prosthetic valve using a continuous 3-0 polypropylene suture, anchoring the sewing ring to the native valve annulus for approximately two-thirds of the valve annulus and then anteriorly to a pericardial patch that is used routinely to augment the valve annulus and facilitate closure of the pulmonary artery and right ventricle.

Triple-Valve Replacement

Operative preparation is similar to that described previously. Usually left-sided valvular lesions are corrected before tricuspid valve procedures. Again, if there is aortic valve regurgitation, the aortotomy is performed first, and cardioplegia is administered; simultaneously, we snare the cavae and open the right atrium. After excision of the aortic valve and calibration of the annulus, the interatrial septum is incised, and the mitral valve is repaired or replaced. Next, the aortic valve is implanted, and after closure of the aortotomy and septotomy, the tricuspid valvuloplasty or prosthetic replacement can be performed without aortic cross-clamping.71

As shown in Table 47-3, rheumatic valvulitis is a common cause of multiple valve disease. Autopsy studies show that almost all patients with rheumatic heart disease have some involvement of the mitral valve, although it is not always evident clinically.72 The percentages of multiple valve involvement in two autopsy studies of patients with rheumatic heart disease are shown in Table 47-4.

Forty-seven percent of those studied had involvement of more than one valve. Mitral and aortic valve disease was the most common combination and was present in 34% of patients; the second most common combination was mitral, aortic, and tricuspid valve disease (9%). A recent report has suggested that all four valves might be involved with the rheumatic process.73

Long-term follow-up of children with rheumatic heart disease suggests that approximately 50% of patients have multivalvular involvement.74,75 In a study of patients undergoing mitral valvotomy for rheumatic mitral stenosis (Table 47-5), 13% had clinical evidence of other rheumatic valve stenosis or regurgitation. Most of these patients had associated rheumatic aortic disease.76

Rheumatic heart disease can cause valve stenosis, regurgitation, or a combination of lesions. The percentages of 290 patients with specific valvular lesions from four studies of multiple valve disease are shown in Table 47-6. Mixed lesions producing stenosis and regurgitation were encountered most commonly in both aortic and mitral valves.

Rheumatic Mitral Stenosis with Rheumatic Aortic Regurgitation

Approximately 10% of patients with rheumatic mitral valve stenosis also have rheumatic aortic regurgitation.77,78 Clinical and laboratory characteristics of patients with mitral stenosis and aortic regurgitation are summarized in Table 47-7.

Pathophysiology

In patients with mitral valve stenosis and aortic valve regurgitation, decreased cardiac output minimizes the classic signs of aortic regurgitation (eg, waterhammer pulse, head bobbing, visibly pulsating capillaries). Also, concomitant mitral stenosis reduces left ventricular volume overload, which is a characteristic of isolated aortic regurgitation.79 The underfilling of the left ventricle characteristic of mitral stenosis is offset by overfilling secondary to aortic valve regurgitation. Pulmonary artery hypertension characteristic of mitral stenosis usually is present.

Operative Decision Making

Patients with rheumatic mitral stenosis and rheumatic aortic regurgitation of more than a mild degree usually require replacement of both valves. Aortic valve repair is possible using techniques such as cuspal extension with glutaraldehyde-treated bovine or autologous pericardium80 or the Trussler technique.81 Although early results with cuspal extension have been good, inexorable progression of valve fibrosis may necessitate later prosthetic replacement for many patients.82

Preoperative transthoracic and intraoperative transesophageal echocardiography aids in assessing function of the aortic valve in patients requiring surgery for mitral stenosis. At operation, the degree of ventricular filling and amount of aortic root distention with infusion of cardioplegia are clues to important aortic valve regurgitation. As stated previously, if mitral valve replacement is necessary, serious consideration should be given to replacement of the aortic valve when there is moderate or worse leakage owing to rheumatic valvulitis.

Great care should be exercised to avoid ventricular distention if ventricular fibrillation occurs before aortic clamping. If ventricular fibrillation develops, distention of the heart can be prevented by inserting a left ventricular vent and compressing the heart manually. Also, even mild or moderate degrees of aortic regurgitation can complicate cardioplegia delivery through the proximal aorta.

Rheumatic Mitral Stenosis with Rheumatic Aortic Stenosis

Pathophysiology

In contrast to isolated mitral stenosis, in which ventricular function frequently is preserved, the combination of mitral and aortic stenosis is associated with ventricular hypertrophy and diastolic dysfunction. The pressure load from the aortic stenosis causes a concentric hypertrophy with a small, noncompliant ventricular cavity.78 Mitral stenosis compromises the ventricle's ability to maintain cardiac output (in contrast to isolated aortic stenosis, in which cardiac output is maintained).83,84 The decrease in cardiac output minimizes the signs and symptoms of aortic stenosis and may make the diagnosis of aortic stenosis difficult.85 Other hemodynamic parameters are similar to those of isolated mitral stenosis, eg, elevation of left atrial and pulmonary arterial pressures.84,86

Operative Decision Making

Although mitral valve stenosis sometimes can be treated effectively with valvuloplasty, commissurotomy for rheumatic aortic stenosis is indicated rarely. Thus, for patients with both aortic and mitral valve stenoses caused by rheumatic heart disease, we favor prosthetic replacement with mechanical prostheses if patients can manage long-term anticoagulation. If aortic valve stenosis is only mild and the decision is made not to replace the aortic valve at the time of mitral valve replacement, then the patient should be followed carefully, because more than 50% will develop moderate to severe disease by 15 years postoperatively.87 The combination of aortic stenosis and mitral stenosis may present unique problems for the surgeon. First, concentric hypertrophy of the left ventricle may displace the mitral valve orifice anteriorly, producing poor exposure through a standard atriotomy; several maneuvers and alternative incisions are described for patients in whom mitral valve exposure is difficult.85,88–92 Also, the small left ventricular cavity may impinge on struts of a stent-mounted bioprosthesis. There is also the potential for left ventricular outflow obstruction from high-profile prostheses in the mitral position in patients with aortic and mitral valve stenoses and small left ventricular cavity size.

Rheumatic Mitral Regurgitation with Rheumatic Aortic Regurgitation

Pathophysiology

The combination of mitral and aortic valve regurgitation produces severe volume overload of the left ventricle. The reduction of impedance to ejection allows the ventricle to empty further, reducing ventricular wall tension with a resulting increase in the velocity of shortening.94 Chronic volume overload increases stroke volume and distention of the left ventricle so that a larger stroke volume can be achieved with less myocardial fiber shortening than in normal hearts.78 Patients who respond to increased volume load by left ventricular dilatation appear to tolerate surgical correction better than patients with left ventricular hypertrophy owing to an increased pressure load.78 Patients with aortic valve regurgitation have augmented stroke volume to maintain an adequate cardiac output, but when mitral regurgitation coexists, part of the augmented stroke regurgitates into the left atrium and pulmonary veins. For this reason, when aortic regurgitation is severe, concomitant mitral regurgitation greatly reduces systemic cardiac output and can produce severe pulmonary congestion.95

Operative Decision Making

As stated previously, aortic valves involved with rheumatic disease usually require replacement. When the mitral valve also has rheumatic involvement, we replace the mitral valve at the time of aortic valve operation. After the aortic valve is excised, the mitral valve is inspected visually if it is suspected of being diseased or the degree of regurgitation is severe.

Myxomatous degeneration is the most common etiology of mitral regurgitation requiring surgical correction in North America, and myxomatous aortic valve disease with annular dilatation is perhaps the most common cause of aortic regurgitation.96–98 Most cases of isolated mitral or aortic valve prolapse are not associated with known connective tissue disorders. However, the coexistence of both mitral and aortic valvular prolapse together frequently can be seen in patients with connective tissue diseases such as Marfan's syndrome, Ehlers-Danlos syndrome, osteogenesis imperfecta, and others.95

Aortic valve regurgitation in patients with Marfan's syndrome is caused by progressive enlargement of the sinus portion of the aorta and the aortic valve annulus, ie, annuloaortic ectasia.99,100 The principal causes of mitral regurgitation in patients with Marfan's syndrome are mitral annular dilatation, floppy or prolapsing leaflets, and mitral annular calcification.100 The pathologic lesion in Marfan's syndrome is cystic medial necrosis, which is characterized by degeneration of elastic fibers and infrequent cysts.100 Alterations in the synthesis and cellular secretion of fibrillin are responsible for the phenotypic characteristics of many patients with Marfan's syndrome.101 Some patients have myxomatous cardiovascular lesions and annuloaortic ectasia without the other clinical characteristics of Marfan's syndrome.

Two-dimensional echocardiographic studies show that the frequency of aortic valve prolapse in patients with mitral valve prolapse varies between 3% and 24%102,103 (Table 47-8). In one necropsy study, the frequency of mitral regurgitation in Marfan patients with aortic aneurysms (most with aortic regurgitation) was 54% (7 of 13).100 About 17% of patients who undergo surgery for myxomatous aortic valve require surgical correction of mitral regurgitation (Table 47-9).

Although multiple valve involvement with myxomatous degeneration usually manifests as mitral regurgitation in combination with aortic regurgitation, in some cases, all four valves may be involved.105 It is not clear whether the underlying pathology of isolated mitral valve prolapse is the same as the cardiovascular lesions that occur in Marfan's syndrome and other multiple-floppy-valve syndromes.106,107

Diagnosis, Signs, and Symptoms

Signs and symptoms of aortic and mitral valve regurgitation are reviewed in the section on rheumatic valvular disease. In addition to complete evaluation of the aortic and mitral valves and proximal aorta, patients with Marfan's syndrome should have assessment of the descending aorta for aneurysm or chronic dissection.

Operative Decision Making

If annuloaortic ectasia is not present, patients with mitral and aortic valve regurgitation caused by myxomatous degeneration are candidates for repair of both valves. The aortic valve is inspected initially, and the decision for repair or prosthetic replacement is made depending on cuspal morphology. If tissue is sturdy and there is little prolapse or prolapse is limited to one cusp, repair can be undertaken with commissural narrowing and cusp resuspension. Often, aortic valve regurgitation is central, and simply narrowing the annulus by commissural plication restores valvular competence. Outcome of repair of both mitral and aortic valves has been good in terms of patient survival and freedom from valve-related complications, but reoperation is necessary in 35% of patients 10 years after the initial procedure; patients with most severe aortic valve regurgitation have an increased risk of late reoperation.108 If tissue is attenuated, or if multiple cusps have severe prolapse, the valve is replaced.

In most instances, patients with Marfan's syndrome and aortic regurgitation require composite replacement of the aortic valve and ascending aorta.109 Occasionally, moderate aortic regurgitation can be repaired at the time of aortic replacement by suspending the aortic valve inside a tube graft or remodeling the sinus portion of the aorta.110 Even if the aortic valve is replaced with a composite graft and mechanical valve, the surgeon should favor repair of associated mitral regurgitation.111 Gillinov and colleagues reported that valvuloplasty is possible in approximately 80% of patients with mitral regurgitation and Marfan's syndrome and that 5 years postoperatively 88% of patients are free of significant mitral valve insufficiency.112

Myxomatous Mitral Regurgitation with Tricuspid Regurgitation

Myxomatous degeneration also may involve the tricuspid valve, and presentation of mitral and tricuspid valve regurgitation owing to degenerative disease is not uncommon. In one study, 54% of patients with mitral valve prolapse also had tricuspid valve prolapse; however, most of these patients did not have significant regurgitation.95 As with tricuspid regurgitation associated with rheumatic mitral disease, preoperative and intraoperative echocardiography is important in evaluating tricuspid disease in patients with myxomatous mitral regurgitation. In contrast with rheumatic disease, myxomatous mitral and tricuspid regurgitation almost always lends itself to valve repair.

Unlike aortic stenosis caused by rheumatic disease, in which associated mitral valve disease is common, senile calcific aortic stenosis usually presents as an isolated lesion. Although the combination of mitral valve disease and senile calcific aortic stenosis is uncommon, senile aortic calcification is a frequent cause of aortic valve stenosis.97 The incidence of senile calcific aortic disease has increased steadily in the last 20 years. Therefore, although mitral valve disease associated with calcific aortic stenosis is less common than that seen with rheumatic disease of the aortic valve, as the incidence of calcific aortic stenosis increases, so does the likelihood of encountering patients with disease of both valves.

Patterns of Multiple Valve Involvement with Calcific Aortic Stenosis

Calcific Aortic Stenosis with Infective Endocarditis of the Mitral Valve

Stenotic aortic valves frequently are sites of infective endocarditis. As discussed in the section on endocarditis, the mitral valve may become involved with infective endocarditis by common abscess, by verrucous extension, or from a jet lesion, and infection may cause mitral valve aneurysm, perforation, and/or chordae disruption.113 Management of these patients usually requires aortic valve replacement and assessment of the mitral valve at the time of operation. Vegetations of the mitral valve sometimes can be removed and perforations patched if the remaining tissue is sturdy and appears healthy.

Calcific Aortic Stenosis with Functional Mitral Valve Disease

Senile calcification of the aortic valve may lead to mixed stenosis and regurgitation,97 and the volume load from regurgitation may lead to left ventricular dilatation and secondary mitral regurgitation of an otherwise normal mitral valve.97 Mitral regurgitation secondary to aortic valvular disease is discussed in the section on pathophysiology of multiple valve disease.

Calcific Aortic Stenosis with Calcification of the Mitral Valve

Degenerative calcification is an age-related process usually affecting the aortic and mitral valves. In a study of patients older than 75 years of age, one-third had degenerative aortic or mitral calcification.95 About 25 to 50% of patients with calcific aortic stenosis have calcification of the mitral valve annulus. Generally, patients with associated mitral annular calcification are older, have more severe aortic stenosis, and are more often female when compared with patients with aortic stenosis without mitral annular calcification.104 Mills reported 17 patients undergoing mitral valve replacement for valvular disease related to severe annular calcification. Four of these patients also had concomitant aortic valve replacement.114 Mitral annular calcification may exist in the setting of rheumatic or myxomatous disease.115 These patients may have increased incidence of conduction defects,116 aortic outflow murmurs, coronary artery disease,117 and stroke.118 Mitral repair or replacement is facilitated in some circumstances by removal of the annular calcium bar and pericardial reconstruction.119

Table 47-10 compares New York Heart Association (NYHA) class-matched groups that had multiple valve procedures for infective endocarditis and for other reasons.

Valvular heart disease develops in about 50% of patients with carcinoid tumors; patients with primary carcinoid tumor in the small intestine are more likely to have carcinoid heart disease than those with carcinoid tumors in other locations.1 In most cases, the tricuspid and pulmonary valves are involved. We have offered valvular surgery to patients with severe symptoms of right-sided heart failure caused by carcinoid heart disease whose systemic carcinoid symptoms are controlled by octreotide and/or hepatic dearterialization.123 Patients who are being considered for complete resection of hepatic metastases after control of the primary tumor are also candidates for extirpation of cardiac disease and valve replacement. A recent review of 200 patients with carcinoid heart disease from our institution revealed that survival has improved over the past decade. Multivariate analysis indicated that valve replacement surgery was associated with a risk reduction of 0.48.68

Diagnosis, Signs, and Symptoms

Jugular venous distention with v waves (from tricuspid regurgitation) and a waves (from tricuspid stenosis) can be evident. Right ventricular enlargement can produce a pericardial lift. Most patients have murmurs from the tricuspid and pulmonary valves.123 Patients often demonstrate ascites and liver enlargement as a result of either right-sided heart failure or hepatic metastases or both. Therefore, these findings are not necessarily indicative of severe tricuspid valve regurgitation.

The electrocardiogram of patients with carcinoid heart disease often shows low voltage (85%), right bundle-branch block (42%), and evidence of right atrial enlargement (35%).1,123 The chest x-ray characteristically shows cardiomegaly (69%), pleural effusions (58%), and pleural thickening (35%).123

Echocardiography

Echocardiographic findings of carcinoid heart disease include thickening and reduced motion of the tricuspid valve leaflets; the pulmonic valve cusps may be thickened and retracted. Fusion of the pulmonary valve commissures results in a stiff fibrotic ring that may cause a stricture in the entire pulmonary orifice. Pulmonary regurgitation and stenosis both may be present.124

Invasive Studies

Cardiac catheterization is not necessary unless ischemic symptoms or a history of myocardial infarction suggests coronary artery disease.

Pathophysiology

Carcinoid heart disease results from deposition of plaques on the endocardium of the valves and atria; this usually occurs on the right side of the heart. However, plaques can develop on the mitral and aortic valves when there is carcinoid tumor in the lungs or in the presence of intracardiac shunting that bypasses the lungs. Valves are damaged by exposure to circulating substances released from carcinoid tumors such as serotonin and bradykinin. Both these components are inactivated by the lungs and the liver; the relationship between tumor location and the location of cardiac lesions is summarized in Table 47-11.125 The plaques usually deposit on the downstream side of the cardiac valves, causing adherence of the leaflet to the underlying structures and producing functional regurgitation. Carcinoid plaque deposition also may constrict the valve annulus and produce stenosis.1

The dominant functional lesion of carcinoid heart disease is tricuspid valve regurgitation; the valve is fixed in a semiopen position so that some degree of stenosis is present. Fibrosis and plaque deposition also affect the pulmonary valve, causing mixed stenosis and regurgitation, which increases the degree of tricuspid regurgitation.1

Operative Decision Making

Timing of Operation

The primary indications for surgery are increasing symptoms of congestive failure with objective evidence of valvular disease.122 Again, it should be noted that some of the signs of right-sided heart failure, such as peripheral edema, ascites, and hepatomegaly, can be caused by the primary disease. Another indication for operation may be progressive right ventricular enlargement in the absence of symptoms. In a small series of carcinoid patients, right ventricular size and function did not correlate with operative or late mortality.123 Currently, we employ exercise testing to provide an objective assessment of the functional status and a guideline to the timing of cardiac surgery. If the primary cause for debilitation is right-sided heart failure, it is reasonable to offer valve replacement even though the prognosis may be guarded.126

Tricuspid Valve Operation

The tricuspid valve always requires replacement, and in our earlier experience, we used mechanical prostheses because of the possibility of carcinoid plaque formation on a bioprosthesis. However, review of our patients and those reported previously shows little difference in patient survival with mechanical or tissue valves. Bioprostheses are selected for patients who have liver dysfunction that would complicate anticoagulation with Coumadin and those who will undergo subsequent hepatic resection or hepatic artery embolization.

Pulmonary Valve Options

As stated previously, we now advise valve replacement rather than excision when the pulmonary valve is involved.

Management of the carcinoid syndrome during and early after operation is critically important, and this has been simplified greatly by treatment with long-acting octreotide; this is supplemented intraoperatively with intravenous administration of short-acting octreotide when there is evidence of flushing and vasodilatation.127 Preoperative steroids and antihistamines also can be used to prevent adverse effects from tumor-released mediators.127,128 We usually give octreotide, 500 μg intravenously, before induction of anesthesia, with additional intravenous doses given as needed at the onset and termination of cardiopulmonary bypass. Postoperatively, octreotide is continued, and the dose is adjusted according to the severity of the flushing and vasodilatation. Aprotinin, a kallikrein inhibitor, may mitigate the effects of substances released by carcinoid tumors during anesthesia and reduce intraoperative and postoperative bleeding.127

Table 47-12 lists some rare causes of multiple heart valve disease that require surgical correction.

Long- and Short-Term Mortality

Survival following multiple valve surgery has improved along with refinements in myocardial protection; for example, mortality for multiple valve operations performed using normothermic ischemic arrest was approximately 40%129; the use of cardioplegic arrest reduced operative risk by three-fourths.78,129,130 In recent reports,131 operative mortality (30-day mortality or hospital mortality) ranges from about 6 to 17% (Table 47-13, part A). The 5-year actuarial survival is 60 to 88% (see Table 47-13, part B), and the 10-year actuarial survival is 43 to 81% (see Table 47-13, part C). Risk factors identified for morbidity and mortality following multiple valve surgery include advanced NYHA class,132–134 advanced age,132–136 current or prior myocardial revascularization,135 ejection fraction,132 presence of coronary artery disease,132,133 aortic stenosis,137 elevated pulmonary artery pressure,135 tricuspid regurgitation,137 and diabetes mellitus.135

Clearly, operative mortality is influenced by patient selection, 134 and comparisons among studies are of limited value.134 Causes of death after multiple valve surgery are low cardiac output,134,137–140 myocardial infarction,135 technical failure,140 multiple-organ failure,32 ventricular rupture,100,135,138 and mechanical obstruction of the prosthetic leaflet.100,139 Comparisons of late survival between patients having multiple valve versus single-valve replacement are inconsistent. Some studies show poorer survival133 after multiple valve replacement, and others report no significant difference in survival.32,126,129,136–141 The discrepancy in these results may be because the majority of deaths in many reports are secondary to progression of coronary artery disease and noncardiac causes rather than valve-related issues.130,132 The presence of coronary artery disease and concomitant coronary artery surgery increases mortality following multiple valve surgery.135,146,147

Some causes of early death following multiple valve surgery are perhaps less common today owing to changes in practice. In a necropsy study from 1963 to 1985 of patients who died early following double-valve replacement, prosthetic valve dysfunction secondary to mechanical interference was evident in almost 50%, and ventricular rupture had occurred in 15% of patients.100 Most of these patients received Starr-Edwards caged-ball prosthetic valves. Mechanical failure of low-profile tilting-disk prostheses that are in current use is rare, and early valve-related death with this type of prosthesis is very unusual.32,133,134,148 The current practice of preserving the posterior leaflet and chordal attachments of the mitral valve during prosthetic replacement may decrease the chance of ventricular disruption.149

Thromboembolism

Thromboembolic rates following multiple valve replacement are shown in Table 47-13, part D, and range from 1 to 7% per patient-year for double-valve replacement. Ten years postoperatively, freedom from thromboembolic events ranges from 77 to 89% (see Table 47-13, part E). Although the data presented in Table 47-13, part D, along with other sources,150 do not indicate significant differences between single and multiple valve replacement, some reports suggest that both mechanical151 and bioprosthetic152 valves have an increased risk of thromboembolism in the mitral position. This risk is present early (90 days after operation) in patients undergoing multiple valve replacement that includes a bioprosthetic mitral valve.152

Anticoagulation-Related Hemorrhage

Rates of anticoagulant-related hemorrhage following multiple valve replacement, as with single-valve surgery, depend on target international normalization ratio (INR).153 Risks of hemorrhage are reported to be 0.1 to 4.5% per patient-year following multiple valve surgery (see Table 47-13, part F). Alvarez reported a significantly higher rate of anticoagulant-related hemorrhage following multiple valve replacement than following single-valve replacement.137

Prosthetic Valve Infective Endocarditis

Rates of infective endocarditis following multiple valve surgery range from 0.2 to 2.5% per patient-year, as shown in Table 47-13, part G. In comparison with isolated valve surgery, Alvarez reports that prosthesis infection is more frequent following double valve replacement than following either isolated aortic (p < .05) or mitral valve replacement (p < .001).137

Valve Performance

Rates of bioprosthetic structural deterioration relate to valve position; tissue valves appear to fail earlier in the mitral position than in the aortic position. When multiple valve replacements include the mitral valve, the rates of deterioration are similar154 or even worse than150 isolated mitral valve replacement (see Table 47-13, part H).

Comparisons of outcomes of patients with two or more mechanical prostheses with those of patients with two or more bioprostheses show similar rates of thromboembolism,27,153 but freedom from operation favors those with multiple mechanical valves.29,155,159 As might be expected, anticoagulation-related hemorrhage is less in patients with two bioprosthetic valves,155,160 but there is no clear advantage of one prosthesis over the other in terms of early and late mortality.29,155,160

Results of Tricuspid Valve Procedures with Other Valve Procedures

Results of Mitral and Tricuspid Valve Surgeries

Reported operative mortality following mitral valve replacement and tricuspid valve repair or replacement is approximately 12 to 15%,161 and 65 to 75% of patients are alive 5 years postoperatively.135,161 Outlook for patients with lesser degrees of tricuspid regurgitation at the time of mitral valve replacement is good; 5-year actuarial survival for patients with tricuspid regurgitation who do not have tricuspid valve repair or replacement is 80 to 84%, and 10-year survival is 62 to 77%.162

Triple-Valve Replacement

The operative mortality following triple-valve replacement is higher than that for double-valve replacement and ranges from 5 to 25%.31,135 As with double-valve replacement, advanced age and higher NYHA class are associated risk factors for early mortality.31,163 Causes of perioperative death are similar to those following double-valve replacement and include low cardiac output, multiorgan failure, hemorrhage, and dysrhythmia.31

Five-year actuarial survival after triple-valve replacement is 53 to 78%, and 10- and 15-year survivals are 40% and 25%, respectively (Table 47-14).

Considering only perioperative survivors of triple-valve replacement, late survival is comparable with that of patients undergoing isolated valve replacement.31,164 Reports of thromboembolic rates following triple-valve replacement range from 5 to 12% per patient-year (see Table 47-14).

Double-Valve Replacement and Tricuspid Annuloplasty

Operative mortality for patients undergoing double-valve replacement with tricuspid valve repair is about 25%,60 and the 10- and 15-year survival rates are 35% and 27%, generally comparable with those of patients having triple-valve replacement.60 Rates of thromboembolism in this group are reported to be 5% per patient-year.60

Other Results

The operative mortality for double re-replacement is about 10 to 20%.133,165 Incidence of postoperative ventricular arrhythmias is higher in patients having combined valve surgery than in those having single-valve surgery.166 Hemolysis may be more common with multiple valve disease or following multiple valve replacement.167,168

The incidence of perivalvular leak following multiple valve surgery is about 4% per patient-year and may be more frequent following multiple valve surgery than following single-valve surgery.139,141

When multiple valve surgery is combined with myocardial revascularization, the morbidity and mortality are 12 to 24%.146,169 Early death in this group of patients is associated with prolonged perfusion time, the need for postoperative inotropic support, and high blood loss.165

The challenges of multiple valve replacement and repair include not only the technical maneuvers of operation but also the identification of associated valve lesions and correct judgment in surgical management. Echocardiography is the essential tool in preoperative diagnosis, and surgeons should become as familiar and facile with interpretation of ultrasound assessment of cardiac valves as with analysis of coronary angiograms. Finally, the various etiologies of multiple valve disease occur in certain combinations, and understanding the pathophysiology and pathologic anatomy is necessary to select the best procedure and to optimize early and late operative results.