CHAPTER 54: MANAGEMENT OF MIXED VALVULAR HEART DISEASE

The 2006 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for the treatment of valvular heart disease (VHD) were notable for the paucity (0.3%) of the recommendations supported by a level of evidence A—that is, evidence supported by two or more randomized controlled trials (RCTs).¹ Although several RCTs have been published since then and the evidence level supporting the 2014 guidelines improved markedly,² there are no RCTs and indeed only limited data-driving management decisions in mixed VHD. In a 230-page document, the current guideline devotes scarcely two pages to the topic. The following chapter will summarize some of the modest data that are available.

Most tricuspid regurgitation (TR) is secondary to overload caused by left-sided heart disease or by lung disease. Causes of primary TR include blunt trauma such as might occur in a motor vehicle accident, direct trauma from errant myocardial biopsies, carcinoid syndrome (or use of drugs with serotonin similarities), rheumatic heart disease, infective endocarditis, and interference from transvalvular pacing electrodes.

The general rule for treating secondary TR is to optimize therapy for the primary cause. Thus, if left-sided heart failure has resulted in pulmonary hypertension with adverse effects on the right ventricle, treatment of heart failure will reduce pulmonary pressure and improve secondary TR. Or, if lung disease has created cor pulmonale, therapy to improve pulmonary function is apt. However, this rule may be inappropriate when secondary TR is caused by left-sided valve lesions. Although it has long been hoped that correction of the hemodynamic overload produced by mitral or aortic valve disease would improve secondary TR, the results are unpredictable, with TR sometimes improving, sometimes worsening, and sometimes even arising de novo following left-sided valve surgery.^3,4,5,6,7,8 Although there is general agreement that severe TR, irrespective of its cause, should be addressed during surgery for left-sided disease, the approach to less than severe secondary TR is the subject of intense controversy. If leaving moderate TR uncorrected results in worsening rather than improvement in TR following successful left-sided surgery, the patient is then consigned either to the consequences of right-sided heart failure, despite the correction of the primary valve lesion, or to a second operation to address the residual TR, which has had an unusually variable and sometimes high mortality in reports of small series.^3,9,10 The variable response of TR to correction of left-sided valve disease is in part related to the causes and effects of the left-sided disease and its correction. As noted in other chapters, if the left-sided disease is secondary mitral regurgitation, left ventricular (LV) dysfunction is almost surely present and is not addressed by mitral surgery, serving as a cause for persistently elevated left- and right-sided chamber pressures, perpetuating TR. Even if pulmonary pressure is reduced by left-sided surgery, left sided cardiac output may be improved in turn increasing right ventricular (RV) volume load.

As shown in Fig. 54–1, the severity of TR (90% of which was secondary) impacted survival in one study. This was true even in the absence of pulmonary hypertension and even when LV ejection fraction was normal.¹¹ Thus, it would seem logical that preventing TR following left-sided surgery would improve mortality; however, this contention is unproven.

Outcomes of TR Correction During Left-Sided Surgery

It seems clear that tricuspid intervention during left-sided surgery reduces postoperative TR and RV dilatation. However, it has been difficult to show that TR surgery reduces mortality (Table 54–1),^{7,12,13,14,15,16,17,18,19} although lack of mortality benefit might be predicated on surgery that was performed for secondary MR that inherently has a poor prognosis, or from retrospective series that were not designed to detect a mortality difference.

Although tricuspid repair reduces postoperative heart failure and TR, it has increased the risk of postoperative conduction abnormalities, requiring permanent pacemaker implantation in some but not all reports.^16,20

In summary, severe primary and secondary TR is usually corrected during left-sided valve surgery. Most,^{7,12,13,14,15,16,17} but not all,¹⁸ data support addressing less than severe TR during left-sided valve surgery. TR is corrected because of unpredictable changes in TR after successful correction of mitral and aortic lesions and for the fear of residual postoperative right-sided heart failure. It is most probably this concern that is driving an increased rate of tricuspid surgery in the United States today.²¹

Although no randomized trial exists, tricuspid valve repair is generally favored over replacement. However, in cases of tricuspid disease where repair is impossible, a prosthetic valve is inserted instead. In a large meta-analysis, 10-year survival (about 60%) was nearly identical for bioprostheses versus mechanical prostheses.²² As usual, bioprostheses inserted at an early age were more likely to suffer structural valve deterioration, and patients receiving mechanical valves were more likely to encounter thromboembolic or hemorrhagic complications from over- or under-anticoagulation with vitamin K antagonists.

In developed countries, aortic stenosis (AS) is usually the result of an atherosclerotic-like process that does not affect the mitral valve (see Chap. 47) and the pressure overload of AS is usually accompanied by concentric chamber remodeling. When mitral regurgitation (MR) coexists with AS, MR is usually secondary to LV remodeling in which there is also an element of ventricular dilatation or eccentric remodeling that accompanies concentric remodeling. The pressure (P) overload of AS is approximately equal to the transaortic gradient (LVP-AoP). The transmitral gradient is obviously affected by LVP and equals LV minus left atrial pressure. Correction of AS that decreases the transaortic pressure gradient and decreases LVP also decreases the transmitral gradient, reducing the driving pressure propelling blood backward across the mitral valve. Thus, it is hoped that correction of AS will concomitantly reduce coexisting MR. Unfortunately this is not always the case, especially when the mitral valve is structurally abnormal, as might occur in rheumatic disease or coincidentally from the presence of independent myxomatous mitral disease. However, although secondary MR often regresses after aortic valve replacement (AVR), sometimes MR fails to improve or even worsens after surgical aortic valve replacement (SAVR). There is general agreement that primary severe and even primary moderate MR should be addressed with either concomitant mitral repair or replacement at the time of SAVR. However, the management of less than severe secondary MR remains controversial. Absil and associates²³ and Wan and coworkers²⁴ matched patients with mild versus moderate MR who underwent isolated AVR and found no difference in midterm mortality, and Takeda and colleagues reported similar findings in a study of unmatched patients.²⁵ Conversely, Countinho and associates found that failure of MR to improve following AVR did impact late survival.²⁶ Because of the unpredictable behavior of moderate secondary MR following AVR, many surgeons prefer to address secondary MR with at least an annuloplasty at the time of AVR.

The advent of transcatheter aortic valve replacement (TAVR) offers further insights and challenges regarding coexistent MR. In high-risk but operable AS patients, the presence of MR must be considered in the decision of SAVR versus TAVR, because the MR is not addressed directly at the time of TAVR but can be repaired during SAVR. Thus, it would be important to be able to predict the fate of MR following TAVR in making AVR decisions. Nombela-Franco and colleagues reviewed the fate of MR in thousands of patients undergoing TAVR²⁷ (well summarized in Fig. 54–2).^{28,29,30,31,32,33,34,35,36,37,38,39,40} The most common response was for MR to remain the same following TAVR, although MR in some patients improved but worsened in others. Although Toggweiler and coworkers³⁵ found that MR was more likely to improve when it was secondary, when there was an aortic gradient >40 mm Hg, and when atrial fibrillation was absent, the outcome of MR following TAVR still remains difficult to predict. When surgery is feasible, severe MR should be addressed during the operation. Decisions about the management of moderate MR are more difficult. If SAVR is performed, primary moderate MR is usually corrected during surgery. For secondary moderate MR, the course of action is less clear and predicated upon the risk factors noted above and the overall operative risk. It must be recognized that many patients with AS also have systemic hypertension. Failure to treat hypertension following AVR may do little to relieve LV afterload, in turn lessening the probability that MR will improve despite successful surgery.⁴¹

Irrespective of etiology, it is unusual for mixed aortic valve disease to have equal components of aortic stenosis (AS) and regurgitation (AR). In rare cases, AR is dominant, and thus physical examination should favor AR, producing accentuated carotid upstrokes, a displaced apical beat, and a long diastolic murmur. Imaging should demonstrate ventricular dilatation and the patient should be followed using guideline-directed management for AR (see Chap. 47).

However, in cases of moderate combined AS/AR, the left ventricle behaves much more as it would in pure AS rather than AR, and outcomes resemble those of AS.⁴² AR causes increased systolic flow through the moderately stenotic valve, thereby increasing jet velocity, pressure gradient, and in tandem, pressure overload on the left ventricle. In turn, the patient and his or her left ventricle respond primarily to the pressure overload. Figure 54–3 demonstrates that outcome for mixed disease compares best with that of severe AS, and substantially worse than moderate AS or moderate AR.⁴³ Thus, management of mixed AS/AR should follow the guideline strategy for managing patients with pure AS. AVR should be performed at symptom onset and might be considered for patients with jet velocity exceeding 5 m/sec or patients with abnormal exercise tolerance tests (see Chap. 47).

Mixed mitral stenosis (MS) and MR usually occur in the context of rheumatic heart disease. The management dilemma often presented to clinicians is whether the presence of symptoms in a patient with moderate MS and moderate MR is the result of the valve disease, because neither lesion by itself would probably cause symptoms. Further, if the valve is causing symptoms, current guidelines are unclear with respect to management. Thus, although symptom onset in VHD is almost always cause for mechanical intervention, moderate disease is not. In such cases, invasive hemodynamics performed at rest or during exercise often clarifies the issue. If exercise generates filling pressures that are high enough to cause the patient’s symptoms, it is highly likely that MS/MR is the cause of both the clinical and hemodynamic consequences. Because mitral balloon valvotomy (MBV) is usually contraindicated because it may worsen MR, mitral valve replacement (MVR) is indicated (in the absence of contraindications) for relief of symptoms. Unfortunately, no series of such patients is large enough to assess whether MVR would increase longevity.

Seen almost always in the setting of rheumatic heart disease, the combination of MS and AR may be confusing, especially by understating the severity of AR.⁴⁴ Because MS limits LV in-flow, total LV volumes and the manifestations of volume overload for any degree of AR are lessened, potentially causing underestimation of AR severity both during physical examination and during imaging. If AR appears less than severe and the mitral valve anatomy is amenable to MBV, this procedure can be performed first, followed by standard reevaluation of the patient’s AR. Severe AR may become manifest at that time, in turn leading to AVR. If MBV is not feasible and surgery is contemplated, a full qualitative and quantitative assessment of AR severity should be performed and double valve replacement considered if the degree of AR is greater than mild.

The combination of AS and MS is caused by rheumatic disease in the developing world and by mitral annular calcification and calcific AS in the developed world. In the former, MBV and AVR is the preferred strategy when the mitral valve is suited for MBV. The latter combination is much more problematic. The calcified mitral annulus cannot be balloon-dilated. Therefore, double valve replacement with its attendant higher operative risk must be employed, weighing the obvious risks and benefits.⁴⁵

Treatment of the patient with mixed VHD is fraught by lack of randomized trials to give us guidance. When secondary TR complicates left-sided VHD, there is clearly a trend toward tricuspid annuloplasty at the time of surgery. The risk of performing the procedure in experienced hands is small and seems outweighed by the risk of postoperative TR causing persistent symptoms of heart failure. Likewise, although secondary MR should improve after AVR, it often does not, a fact that must be considered in management strategy when both SAVR and TAVR are feasible. Combined moderate AS/AR usually behaves like isolated AS and should be treated accordingly. However little data we have to guide us for treating those lesions, we have even less regarding other types of combined VHD. For those lesions, common sense and clinical judgment tempered by available hemodynamic data should determine therapy.