Recently, there have been exciting developments involving new technologies for the surgical treatment of valvular heart disease associated with coronary artery disease (CAD). Interventional therapies for coronary artery obstruction have been extended to multivessel disease with hybrid procedures (targeted percutaneous interventions staged with limited access surgical coronary bypass surgery) and continues to change the number and nature of patients referred for surgery.¹ Similarly, the surgical treatment of structural valvular heart disease has continued to expand with advances in techniques for repair, as well as total valve replacement and valve-sparing repair options for both aortic and mitral valve abnormalities.² Most recently, bioprosthetic valve manufacturing advances in regard to calcium mitigation, tissue processing, and hemodynamically superior prosthetic valve stent designs have improved prosthetic valve durability, thereby broadening the valve replacement options for young and old alike.³ The advent of transcatheter valve replacement (TAVR procedures) has also quickly become a commercial reality and has proven to be safe and efficacious in numerous studies. The stunning early success of the TAVR approach has allowed this remarkable new option to become commonplace in many institutions in hospitals around the world.⁴ Most importantly, perhaps, is that transcatheter valvular interventions have provided very high-risk patients, such as the elderly or those with a myriad of threatening comorbidities, a viable new option to consider.

There are numerous issues the surgeon must consider when planning treatment strategies in the patient with combined valvular and CAD. It is uncommon for today’s surgeon to see a patient with simple aortic or mitral valvular disease who also has straightforward proximal CAD. Indeed, it is more often a patient presents with complex, acute valvular/ventricular pathology, with superimposed diffuse, CAD. The prevalence of presurgical interventional options means that patients now undergo more aggressive medical therapy and multiple intracoronary dilation attempts before being referred for surgical evaluation. As a result, they are often referred at an older age and with more complex comorbidities, with more diffuse disease, persistent dysrhythmias, and worsening ventricular function. This older, sicker cohort of patients now referred for surgery are understandably at much higher risk for postoperative morbidity and mortality than in previous eras. Consequently, contemporary surgeons often face difficult therapeutic dilemmas that usually requires a more flexible, systematic, and thoughtful approach. In fact, current decision-making is more often a result of multidisciplinary heart teams, utilizing broad, evidence-based data as a foundation for complex medical decisions.⁵

The pathophysiologic combination and interaction between valvular heart disease and associated CAD is complex. Progressive valvular heart disease clearly impacts ventricular function. The additional impact of CAD has synergistic potential to further affect ventricular morphology and physiology. In particular, the deterioration in contractile strength caused by myocardial infarction and subsequent regional wall motion injury causes progressive distortion of ventricular shape as the infarcted muscle compensates through tissue remodeling. Loss of contractile strength and remodeling after ischemic injury eventually leads to cavitary dilation, with resulting effects not only on ventricular function, but also on mitral valve performance. As valvular and subvalvular elements lose their important geometric relationships, functional valvular incompetence develops. In patients with valvular heart disease, coronary obstructions may be symptomatic or asymptomatic, but the decision to intervene surgically is often made regardless of the presence of ischemic symptoms, in order to have a protective effect toward the additive pathophysiology of concomitant cardiac diseases.

Under most circumstances, surgeons attempt to treat both valvular and CAD simultaneously. However, a combined approach leads to a prolonged and potentially complicated procedure. Accordingly, the increased risks of a combined operation demand a defined and focused operative strategy. Historically, combined coronary artery and valve operations have had an increased risk for early and late mortality compared to operations for isolated valvular heart disease (Fig. 45-1). This complexity increases the need for careful preoperative assessment of myocardial function and an understanding of the impact on ventricular function of the changing afterload and pre-load associated with valve surgery. Therefore, in adult patients with combined valvular and ischemic heart disease, the assessment of intrinsic left ventricular function assumes paramount importance during the initial consultative process. Clinical signs and symptoms of left ventricular failure should be diligently sought. In addition to history, physical examination, and routine laboratory tests, preoperative echocardiography is mandatory. Intraoperative transesophageal echocardiography (TEE) is used to correlate preanesthetic imaging and is utilized for accurate planning of all valvular interventions, and has become standard of care in most institutions. Immediately after weaning from cardiopulmonary bypass support, intraoperative TEE is carefully reviewed by the surgeon, anesthesiologist, and imaging team to evaluate the repair. If necessary, resumption of cardiopulmonary bypass support can then be done to perform additional repair efforts; the post-bypass TEE is critical for this evaluation, and requires a commitment from the entire team to be sure that the reparative efforts are optimal before the operation is terminated.

It is also important preoperatively to attempt to distinguish heart failure resulting from valvular disease from myocardial dysfunction owing to coronary ischemia. Myocardial viability assessment may be useful in eliciting ventricular size and functional changes that are exacerbated under stress conditions and may help delineate the underlying pathology, especially of the mitral valve. At cardiac catheterization, in addition to coronary artery angiography, left ventricular end-diastolic pressure and pulmonary pressures measurements may yield additional information about left- and right ventricular function and supplement noninvasive assessments of valve function and coronary anatomy. In centers where it is available, positron emission tomography (PET) scans and other radioisotope imaging studies can help determine the viability of myocardium with potential reversible ischemia.⁶ These assessments are critically important before embarking on concomitant valve and coronary artery surgery; both for determining the operative risk, as well as planning the scope and extent of the surgical approach.

The assessment of valve pathology is covered in detail in previous chapters on isolated valvular heart disease. As has been noted, coronary angiography is not mandatory in all patients with valvular pathology who are about to undergo valve surgery. However, given the prevalence of CAD in aging Western populations, coronary angiography is usually performed in all patients greater than 40 years of age, and selects younger patients with suggestive symptoms or significant risk factors. More recently, patients felt to be at low risk for coronary occlusive disease may be adequately screened with coronary computed tomographic angiography.⁷

Because of the wide pathophysiologic spectrum of valvular and CAD, several frequently encountered valve and coronary artery combinations are considered in this chapter, including: (1) aortic stenosis (AS) with CAD, including strategies for moderate AS, (2) aortic regurgitation plus CAD, (3) mitral regurgitation plus CAD, (4) mitral stenosis plus CAD, (5) AS and mitral regurgitation plus CAD, and (6) aortic regurgitation and mitral regurgitation plus CAD.

Patients may have combined pathology of stenosis and insufficiency, but to avoid unproductive complexity, and because one lesion usually dominates, the somewhat arbitrary categorization noted above will be maintained during the ensuing discussion. For each entity, the clinical presentation, the pathophysiology of the disease state and its correction, the operative and management approach, short- and long-term results are discussed. Today’s surgeon must also be familiar with evolving hybrid techniques, such as staged coronary artery stenting and percutaneous aortic valve replacement (AVR) in the management of patients with combined valve and CAD.⁸ Since these new innovative strategies are rapidly gaining acceptance as appropriate options in highly select patients, this chapter will also briefly review some of the more common hybrid approaches where applicable.^9-12

Aortic stenosis is one of the more frequently encountered valvular lesions in adult populations and will continue to increase in prevalence due to our aging population. Degenerative calcific AS is most common in patients in their sixties, seventies, and eighties^13-15 and often is associated with CAD.¹⁶ This disease combination is usually gratifying to treat because the response to surgical relief of AS and coronary artery obstructions is significant, immediate, and relatively durable.

Clinical Presentation

Patients with AS are asymptomatic initially due to compensatory mechanisms within the left ventricle. Eventually patients can present with angina pectoris, congestive heart failure, syncope, or some combination of these as the stenosis progresses and the compensatory mechanisms begin to fail. When significant coronary artery obstruction is present, in addition to valvular obstruction, angina pectoris is almost always manifest. However, angina pectoris can occur in the absence of significant coronary artery obstructions due to insufficient diastolic coronary flow across a severely stenotic valve. Identifying symptoms of myocardial ischemia or congestive heart failure in patients with concomitant AS and significant CAD is generally straightforward. Accurate discrimination of subtle neurologic symptoms, such as syncope, presyncope, transient ischemic symptoms, or orthostatic hypotension, may be more difficult to elicit, and careful questioning regarding transient symptomatology is required. Symptoms suggestive of carotid artery obstruction should be sought and appropriately evaluated with carotid artery ultrasound and Doppler scanning, since the murmur of AS often radiates into the neck and can obscure the detection of bruits.

Prominent findings on physical examination include the typical late-packing mid-systolic crescendo murmur heard in the aortic area, radiating into the right neck. Signs of congestive heart failure with rales on chest auscultation or peripheral extremity edema may be present in later stages. The electrocardiogram may show left ventricular strain and increased QRS height due to left ventricular hypertrophy. If the patient has suffered a recent or remote myocardial infarction, then typical ischemic electrocardiographic changes may also be present. The echocardiogram usually shows calcified and immobile aortic valve leaflets producing a contracted aortic orifice with the resultant compensatory hypertrophied left ventricle. Evidence of calcifications extending into the sinuses of Valsalva and/or the left ventricular outflow tract should be carefully evaluated. Significant acceleration of trans-valvular flow velocities, estimates of reduced outflow areas, and flow turbulence with Doppler confirms the reduced outflow area. The transaortic valvular gradient also can be determined at catheterization and is often helpful, though modern m-mode echocardiography and Doppler imaging analysis has supplanted catheter gradient assessments in many hospitals due to correlated accuracy.

The preoperative evaluation of patients with AS, CAD, and poor ventricular function is complicated. Patients with poor ventricular function often generate relatively low transaortic valve gradients. This renders the calculation of valve area for the assessment of critical AS less accurate. In those cases where poor cardiac output from left ventricular failure leads to a less-than-expected gradient across the left ventricular outflow tract, the morphologic demonstration of valve immobility and heavy leaflet calcification is an important confirmatory sign that hemodynamically significant AS is present. Fortunately, even in the presence of a low gradient, if echocardiographic signs of significant valve stenosis are present, and if left ventricular intracavitary pressure exceeds 120 mm Hg in systole, mortality rates for valve replacement are acceptable, and the clinical response to surgery is typically good.¹⁷ In stark contrast, however, a poorly contractile, thinned-out left ventricle with low transvalvular gradients in the presence of low intracavitary systolic pressures, usually suggests that the operation carries high risks, and due to inadequate ventricular reserve, may be of very limited benefit. On the other hand, a poorly contractile ventricle that has normal, or even increased wall thickness, will usually recover significant contractile force if a substantial amount of reversible ischemic myocardium is demonstrated, and if the degree of AS is significant. In addition to ventricular function, other important determinants of the risks and advisability of surgery include patient age, functional status (ie, “frailty index”), presence of previous cardiac operations, and the presence of other comorbidities that affect end-organ function, especially renal and pulmonary function.

Pathophysiology

Aortic stenosis produces impairment of left ventricular emptying during systole, which ultimately is the source of all the symptoms and signs of AS. Most patients with AS have hypertrophied and thick-walled left ventricles to overcome the obstructive valve orifice. Contractile function is initially good, and ejection fraction is usually maintained because of these compensatory mechanisms for some time. In later stages of the disease, the ventricle begins to fail due to persistently severe afterload resistance, with enlargement and global diminution of contractile function as the patient progress up the Starling curve of heart failure (Fig. 45-2). At any stage of the disease, the additional presence of critical coronary artery obstruction can cause specific regional wall motion abnormalities that may be exacerbated by stenosis of the aortic valve. Significant three-vessel CAD may itself lead to temporary global ventricular dysfunction, which may be reversible with revascularization apart from any valve replacement effects.

In patients with critical AS and good ventricular function, valve replacement immediately reduces left ventricular afterload. Because most patients with AS have thick-walled hypertrophied ventricles, intraoperative subendocardial ischemia may be more difficult to avoid during aortic cross-clamping and subsequent cardioplegic arrest. Although revascularization should not decrease left ventricular contractility, and should actually improve it long-term, some myocardial stunning with a temporary decrease in global and regional left ventricular contractility inevitably results from the surgical procedure.^18-21 This, of course, assumes even more important pathophysiologic significance in patients with poor ventricular function preoperatively. Diastolic dysfunction may also occur postoperatively, causing a less compliant left ventricle. The most extreme example of this was the so-called “stone heart”²² that occasionally plagued early cardiac surgery pioneers who first attempted AVR surgery. Fortunately, modern myocardial preservation strategies have eliminated this feared complication through the liberal use of antegrade and retrograde delivery techniques and more physiologic cardioplegic solutions that optimally protects myocardial cellular integrity and tissue function.

Postoperatively, patients usually enjoy a dramatic improvement in symptoms. Relief of left ventricular outflow obstruction immediately leads to enhanced cardiac output and perfusion of vital organs. In addition, left ventricular remodeling and regression of hypertrophy usually occurs over time.²¹ Simultaneous correction of myocardial ischemia can lead to improved subendocardial perfusion, as well as recruitment of formerly hibernating myocardium. The optimal final result is regression of hypertrophied ventricular mass, improved diastolic relaxation, balanced transmyocardial coronary perfusion, and elimination of left ventricular outflow obstruction, culminating in recovery of normal ventricular function.

Moderate Aortic Stenosis and Coronary Artery Disease

Symptomatic, severe AS is universally agreed to benefit from AVR at the time of coronary revascularization, but the management of patients with CAD and either mild or moderate AS continues to remain a matter of controversy. The earliest debates centered on the anticipated risks of a future reoperation, particularly in a population of advanced age, versus the risks of imposing on a patient a more complex initial operation with subsequent lifelong prosthetic valve concerns that may not be immediately necessary. Given the relatively reduced 10-year survival in advanced age patients undergoing cardiac surgery, valve durability was not considered to be a central factor limiting the success of a combined initial AVR/coronary artery bypass graft (CABG) strategy. Thus, the initial opinion favored a liberal AVR/CABG combination approach in patients with moderate AS, as the reoperative risks were considered the more dangerous of the two options. However, the early STS data base for AVR/CABG outcomes clearly showed a mortality nearly double that for isolated CABG (6-7% and 2-3%, respectively)²³ challenging the belief that initial combined valve-CAD operations were generally safer in terms of primary mortality and morbidity risks. Moreover, as experience with reoperations has grown, more recent studies demonstrate much lower risks of reoperation for AVR in post-CABG patients that rival levels similar to initial AVR/CABG procedures.²⁴ In fact, the lowered risks of redo sternotomy for primary AVR after previous CABG (6-7%) has now shifted the debate from one of concerns over the risks of reoperation, to predicting the incremental progression in AS if it is withheld at the initial CAD surgery.^25-27

Although there is no clearly identified method of predicting valvular progression, and surgical expertise is critical in formulating a surgical strategy and timing of intervention, estimates of the rate of progression of AS may help provide support for valve replacement, even without hemodynamically critical disease.²⁸ For instance, it has been established that the rate of valvular progression is more rapid if the valve is heavily calcified, and if the patient has advanced atherosclerotic systemic disease or renal failure.²⁵ Studies also demonstrate that age and valvular gradient at the time of diagnosis are important criteria to consider.²⁷ Verhoye et al²⁹ found that using echocardiography on a serial basis, AVR is recommended to be added to the revascularization procedure for younger patients (<70 years) if their peak gradient is >25-30 mm Hg, on the assumption of reasonable longevity and the probability AS would bear future symptoms. In older patients (>80 years), competing causes of mortality rationally increases the thresholds for concomitant replacement, and AVR is added only if their peak gradient exceeds 50 mm Hg, as longevity is often related to other factors before AS progression occurs.²⁵ Furthermore, studies show that reoperation for AVR after CABG rarely occurs within 5 years of CABG.²⁶ Consequently, from a survival standpoint, little is gained from adding AVR to patients >80 to 85 years of age at the time of coronary revascularization unless the valve is symptomatic or has severe, but incidentally identified hemodynamics.^25,26 In certain extremely high-risk cohorts, a multidisciplinary team may decide on a “hybrid” approach, utilizing percutaneous coronary artery stenting for major coronary artery obstruction, followed by percutaneous AVR (TAVR).^30-32

Despite the recent trend outlined above favoring isolated CABG when concomitant moderate AS exits, there is also evidence that favors concomitant valve replacement in some patients with moderate AS who are referred for surgical myocardial revascularization.^33-36 In one study,³³ survival rates at both 1 year and 8 years were superior for patients who underwent valve replacement for moderate AS (gradient >30 mm Hg or gradient <40 mm Hg with valve area between 1.0 and 1.5 cm²). One-year survival was 90% in those having valve replacement compared to 85% in patients having CABG alone. Similarly, 8-year survival (55 vs 39%) was statistically significantly better (p < .001). Although this data may reveal some bias in healthier patients receiving concomitant AVR/CABG than their more chronically ill peers who were felt not to tolerate more extensive surgery and were only offered isolated CABG, it remains true that this dichotomy of patient groups is commonly seen in clinical practice. Thus, support for both strategies is rational and expected, and can be used to maintain a flexible approach when faced with moderate AS and severe CAD in patients of wide-ranging clinical conditions.^25-29

In summary, given the absence of convincing data that unilaterally supports an operative strategy for the treatment of moderate AS, at the time of surgical coronary revascularization, it is best to individualize patient selection carefully, relative to surgeon and institutional expertise and practice. Significant patient comorbidities, and risk/benefit assessment, including an accurate estimate of expected rehabilitation potential (particularly in frail, elderly candidates), must be contemplated. Review of the initial and recent data and strategies derived from both experience, as well as available relevant data demonstrates that a flexible and individualized approach is warranted to yield the best patient outcomes.

Operative Management

Monitoring for surgery of the aortic valve and coronary arteries includes catheters and measurements that have become standard for most cardiac surgical operations. These include an arterial line (usually in the radial artery for blood pressure and blood gases) and an optional pulmonary artery catheter for measurement of pulmonary artery pressures, and cardiac output by thermodilution, with optical sensors for continuous estimation of mixed venous oxygen saturation. While the pulmonary artery catheter has a balloon at its tip, occlusion wedge pressure is rarely measured in the perioperative period because of the danger of pulmonary artery rupture. Particularly useful information is provided by continuous measurement of mixed venous oxygen saturation. Of late, use of arterial flow or central venous monitoring devices, along with TEE, provides satisfactory estimates of continuous cardiac outputs and monitoring of volume management. This has significantly reduced our reliance on traditional, but more invasive, pulmonary artery catheters.

The perfusion setup is standard and similar to that for isolated coronary artery bypass. A single aortic cannula is ordinarily placed in the distal ascending aorta. A single two-stage venous cannula is placed via the right atrial appendage with its tip positioned in the inferior vena cava. After establishment of cardiopulmonary bypass, the patient is usually cooled to 32 to 34°C, during which time a left ventricular vent is positioned via the right superior pulmonary vein. With the heart well emptied, the aortic cross-clamp is applied during a temporary reduction in pump flow. Thereafter, the heart is arrested with cold (4°C) potassium crystalloid or blood cardioplegia. Low aortotomy incisions are recommended for maximal visibility, with the incision directed toward the noncoronary sinus if annular or root enlargement is anticipated. After valve excision, implant techniques according to each surgeon’s preference is performed. In situations of low-lying coronary ostia, suture techniques may need to be varied to prevent ostial compression. Prior to closure, the valve and coronary ostia are carefully reinspected a final time for clearance and embolic debris, and the aorta is closed. Deairing maneuvers are routine, and TEE aids assurance of complete removal, as well as early detection of proper prosthetic function.

A combination of antegrade and retrograde cardioplegia is optimal. The initial dose of cardioplegia (15 mL/kg) is typically split into a two-thirds antegrade and one-third retrograde dose, with subsequent doses of 200 to 300 mL cardioplegia delivered via the retrograde catheter every 20 minutes throughout the duration of cardiac arrest during the operation. This is particularly convenient because retrograde cardioplegia can be given even after the aortic root is opened without disrupting exposure or flow of the operation. In patients with significant left ventricular hypertrophy, light ventricular and inferior septal protection by retrograde cardioplegia perfusion alone may be inadequate. Handheld direct antegrade perfusion directly into the coronary ostia may be helpful.

The combination of aortic valve disease and CAD in patients has historically been accepted to be a marker of significantly reduced longevity.³⁷ In the elderly, with reduced life expectancies, bioprosthetic valve durability remains the valve of choice, particularly when associated with concomitant CAD.³⁸ Currently, with the advent of new bioprosthetic valve technology with calcium mitigation processing, and proven structural longevity, there is a trend toward increased tissue valve utilization.^39,40 As a result, many younger age patients considering the obligation of lifelong anticoagulation and the improvements in valve design and durability are opting to receive bioprosthetic valves instead of mechanical prostheses.

Results

Early hospital mortality after concomitant AVR and CABG ranges from approximately 2 to 10%. In earlier studies, but more recent studies suggest that modern operative management reveals very similar outcomes and mortality risks in patients having isolated AVR and those having combine AVR/CABG^{26,35,36,48,42-47} Higher mortality is observed in patients with more severe symptoms of heart failure and impaired ventricular function preoperatively, as well as the elderly or other patients with numerous comorbidities. The most frequent causes of operative death are low-output cardiac failure, myocardial infarction, and arrhythmia. Incremental risk factors for hospital death include patient age, functional class, diffuse CAD, and poor preoperative ventricular function. In a number of studies, late survival has ranged from 60 to 80% at 5 years and 50 to 75% at 8 years postoperatively (Fig. 45-3).^33,42-47 By multivariate analysis, risk factors for reduced late survival include older age, cardiac enlargement, and more severe preoperative clinical symptoms. The use of a mechanical prosthesis at valve replacement has been associated with similar long-term survival though lower long-term event-free survival.³⁹ Nonetheless, many elderly patients still have acceptable results following relief of AS, even those undergoing redo valve surgery that is combined with coronary revascularization.⁴⁷ As discussed previously, choice of valve type is a complex issue that takes on even more importance in combined valve-coronary artery surgery. A frank discussion of the advantages and drawbacks of each valve option continues to be an important component of the preoperative evaluation and planning for this type of surgery. In some circumstances, consideration of alternative procedures such as coronary artery stenting followed by percutaneous valve replacement may be indicated and necessary in otherwise inoperable or extreme risk patients.^5,8,49

Significant isolated aortic regurgitation occurs less often in older populations, though it may be associated with AS when the valve becomes immobile. Aortic valvular regurgitation is also less often encountered with significant CAD than in patients with AS. Most series of patients undergoing AVR and CABG include a relatively small number (10 to 25%) of patients with aortic insufficiency as compared to AS.^36,42-44 Although the operative management of patients with aortic regurgitation and CAD is similar to that previously described, aortic insufficiency produces different pathophysiologic effects that have implications for perioperative management. Moreover, the presence of an incompetent aortic valve introduces nuances to the intraoperative management and myocardial protection of these patients, primarily due to preoperative ventricular decompensation.

Clinical Presentation

Patients with aortic regurgitation and CAD usually present in one of three ways. The aortic regurgitation may be asymptomatic and detected incidentally during evaluation for symptomatic coronary disease. Second, the patient may be asymptomatic, yet a routine physical examination reveals a murmur of aortic insufficiency that leads to cardiac evaluation and detection of coronary disease. Finally, patients may present relatively late in the course of valvular heart disease with congestive heart failure caused by decompensation of the volume-overloaded left ventricle from long-standing insufficiency or with superimposed ischemic ventricular damage from combined CAD. Insufficiency of the aortic valve may also occur with dilatation of the ascending aorta that often involves with the coronary sinuses, particularly in patients with bicuspid valvular anatomy. Patients, therefore, may present within a broad spectrum of clinical signs and symptoms ranging from no symptoms and essentially normal physiology, to classic ischemic syndromes and severe congestive heart failure. The physical signs also depend on the nature of the presentation. In general, all patients with significant aortic insufficiency have an audible early diastolic regurgitant murmur. In late stages, rales and peripheral edema and other advanced signs of congestive heart failure usually occur with a prominent diastolic murmur.

The preoperative evaluation of a patient with aortic insufficiency and CAD is no different from that previously described for patients with AS and ischemic heart disease. Echocardiography is particularly useful in detecting aortic regurgitation because a physiologically significant murmur can be difficult to detect. In addition, echocardiography gives important information regarding both ventricular contractile function and ventricular size. Because many patients with aortic regurgitation are usually asymptomatic until marked left ventricular dilation occurs, careful evaluation for changes in ventricular size or function is important. The presence of these changes may constitute an indication to proceed with surgical intervention in the absence of significant symptoms.