Aortic Valvular Disease in Active Patients
Overcoming Diagnostic and Management Challenges
Paul D. Thompson, MD
Exercise and Sports Cardiology Series Editor
THE PHYSICIAN AND SPORTSMEDICINE - VOL 30 - NO. 12 - DECEMBER 2002
In Brief: Valvular heart disease in physically active patients can present a diagnostic challenge, because adaptations to exercise may mimic abnormalities. Electrocardiograms may be used to follow asymptomatic or mildly symptomatic athletes but are not very useful for those with valve disorders. Moderate-to-severe aortic insufficiency requires careful follow-up and periodic echocardiograms to monitor changes. Athletes with mild aortic stenosis can participate in all sports if they are asymptomatic and have a normal exercise response. Those with moderate disease should be restricted to sports with low static and dynamic requirements. Symptoms of severe aortic stenosis include exercise-induced syncope, angina, heart attack, and, rarely, sudden death; these athletes should not compete and should have aortic valve replacement.
Aortic stenosis was implicated in 8% of the nontraumatic, exertion-related deaths reported by Jokl and Melzer1 in their review of medical reports published between 1921 and 1939. Unfortunately, despite the widespread appreciation of the dangers of exertion with valvular aortic stenosis, this entity remains an important cause of exercise-related cardiac deaths and still accounts for 4% of sudden deaths among young athletes.2,3 Furthermore, the evaluation of cardiac murmurs and valvular abnormalities remains a frequent reason for cardiology consultation.
Exercise Adaptations or Cardiac Abnormalities?
Evaluating valvular heart disease in athletes is not easy. The physiologic cardiac adaptations to exercise training create innocent flow murmurs that are difficult to differentiate from those that are abnormal. Blood flow is laminar and without turbulence until a critical Reynolds number (Re) is exceeded. Re is determined by the following formula4:
Laminar flow is disrupted above an Re of 2,000, creating turbulence and murmurs. Endurance exercise training reduces resting heart rate but enhances cardiac performance. Since oxygen demand determines cardiac output and since resting oxygen demand remains relatively constant before and after exercise training, resting cardiac output is also relatively constant. This means that the same cardiac output is delivered via a slower than normal heart rate and a larger stroke volume. Much of the larger stroke volume is delivered more vigorously in early systole by a more dynamic ventricle. This increases blood velocity.
Neither the pulmonic nor aortic valve orifice increases with exercise training, and reductions in blood density with training are not sufficient to prevent the development of turbulence and cardiac "flow murmurs." Such flow murmurs in young athletes are due to flow across the pulmonic valve and often vary with respiration. Athletes age 50 or older may have mild sclerosis of the aortic valve leaflets. Flow murmurs in older endurance athletes are often due to aortic valve turbulence from the physiologic changes of exercise training and aortic valve sclerosis. These murmurs in senior athletes are less "innocent," because they may progress to important aortic stenosis, especially in athletes with other risk factors for atherosclerosis such as hypercholesterolemia.5,6
Treatment of these risk factors may reduce the development of important aortic stenosis, but this has not been studied. Nevertheless, I often recommend 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in adults with noncritical aortic stenosis in the hope of preventing such progression.
Further complicating the treatment of valvular disease in athletes is the lack of studies evaluating various management strategies in such patients. Indeed, there are few trials of valvular heart disease treatment approaches in nonathletic populations, and much of the available literature is based on single-center reports.7 An additional problem is that athletes, because of their exercise activity, may present at earlier disease stages than other patients. This is a major issue, because the appearance of symptoms is an important indicator that valvular repair or replacement may be necessary. Physicians do not want to intervene too soon in athletes with symptoms produced by extreme exertion because of the immediate risk of surgery, the finite life of many valvular prostheses, and the need for life-long anticoagulant therapy after some valve replacements.
The athlete's attitude can also complicate the decision. Some athletes deny symptoms and try to avoid surgery even with life-threatening conditions. Others prefer early intervention if waiting would mean restricted physical activity or reduced athletic performance. The latter patients need to understand the immediate risks of surgery versus its long-term benefits and also that few valvular repair procedures produce the performance characteristics of a normal native valve. In the final analysis, there is no substitute for a sympathetic explanation and definitive recommendations as to how and why athletes should proceed for their best interest. Second opinions should be recommended if athletes seem reluctant to follow a recommended plan. Referrals and scheduling assistance should be provided to ensure that athletes are evaluated by reputable physicians at recognized institutions.
The American College of Cardiology and the American Heart Association published "Guidelines for the Management of Patients with Valvular Heart Disease" in 1998.7 This document provides an excellent summary on how to manage this problem in the general patient. "Recommendations for Determining Eligibility for Competition in Athletes with Cardiovascular Abnormalities, the 26th Bethesda Conference" were published by the same two organizations in 1994 and included a section on athletes with acquired valvular heart disease.8
Valvular Aortic Stenosis
Valvular aortic stenosis remains a frequent cause of exertion-related sudden death in young athletes and an occasional cause of exercise-related deaths in adults. The normal aortic valve orifice is approximately 3 to 4 cm2 and must be reduced by 75% of normal before causing significant hemodynamic obstruction.7 Mild aortic stenosis is classified as an aortic valve area greater than 1.5 cm2, moderate as 1 to 1.5 cm2, and severe as less than 1.0 cm2. Severe aortic stenosis should produce a mean resting gradient of at least 50 mm Hg if cardiac output is normal. These values are not normalized for body surface area.
The hemodynamic significance of any specified aortic valve area depends on the cardiac output. Since muscle mass is a determinant of resting cardiac output, larger individuals may have more severe hemodynamic impairment despite a larger absolute aortic valve area. This may be an issue in athletes with an increased body size and muscle mass. Consequently, the calculated aortic valve area and classification of the severity of disease should be considered as only estimates and must be correlated with other findings.
Symptoms and progression. Aortic stenosis is typified by a long asymptomatic period. Common symptoms of severe aortic stenosis when they do occur include angina, syncope or near-syncope, and heart failure. Sudden cardiac death may also be the first symptom, but this is rare (see "Cardiovascular Risks of Exercise: Avoiding Sudden Death and Myocardial Infarction"). This presentation is more frequent in younger subjects with congenital aortic stenosis but does occur in adults. The incidence of sudden death without prior symptoms is estimated to be less than 1% of aortic stenosis patients per year.7
The rate of narrowing of the aortic valve in individual patients is highly variable and unpredictable. More than 50% of patients with aortic stenosis show little or no progression over 3 to 9 years, but the average rate of aortic valve narrowing is 0.12 cm2 per year.7 Consequently, patients with aortic stenosis, once identified, require careful follow-up.
Evaluating patients. The initial evaluation of aortic stenosis patients requires a physical examination, electrocardiogram (ECG), and Doppler echocardiographic study. Estimation of the severity of aortic stenosis is based on an evaluation of the results from all three examination modalities, although the aortic valve area is based primarily on Doppler echocardiographic results. Cardiac catheterization is required to help clarify the severity of the aortic stenosis if the noninvasive testing and clinical evaluations are contradictory. Even cardiac catheterization can incorrectly assess the aortic valve area, especially if the oxygen uptake value used to calculate the Fick cardiac output is estimated from body size and not directly measured by expired gas collection. In addition, the degree of stenosis can be overestimated by gradient calculations with concomitant aortic insufficiency, since the regurgitant volume increases stroke volume beyond that measured by the Fick calculation as forward flow. Coronary angiography is required before valve surgery to detect any coronary artery disease.
Athletic participation and valve replacement. Athletes with mild aortic stenosis can participate in all competitive sports if they are asymptomatic and have a normal exercise response.8 Athletes with moderate aortic stenosis should be restricted to sports with low static (isometric) and dynamic (isotonic) requirements (table 1), although selected athletes can participate in moderate static and dynamic intensity sports provided they have a normal ST segment, cardiac rhythm, and blood pressure response to exercise testing and they are not symptomatic.
Athletes with severe aortic stenosis should be restricted from competitive athletics even if they are asymptomatic. Exercise testing in these athletes is useful in documenting that they are truly without symptoms and in ensuring that they do not develop exercise-induced hypotension. Exercise-induced hypotension is a bad prognostic sign and should prompt consideration for aortic valve surgery even in the absence of symptoms.
Aortic valve replacement is advocated for patients with severe aortic stenosis once symptoms appear. This decision can be more difficult in athletes; they are at an undefined, but definite risk of sudden death during exercise, and they may present with symptoms earlier in their disease course, because vigorous exercise provokes symptoms. There are no studies to address the issue as to whether valve replacement can be delayed if symptoms occur only with extreme exertion.
Clinicians must balance the immediate and delayed risk of valve replacement against the risks of not proceeding. Despite such considerations, our bias is to proceed fairly promptly to surgery in athletes with severe aortic stenosis at the onset of symptoms. There is little additional benefit to waiting since surgery is inevitable in this situation. Also, there is the risk inherent in waiting and the possibility that left ventricular hypertrophy will develop or worsen. Left ventricular hypertrophy is in its own right a risk factor for sudden cardiac death in the general population and among athletes.9
More complex decisions. The decision is considerably more complex in athletes who are asymptomatic and yet have severe aortic stenosis. It is generally thought that the immediate risk of surgery and the risks associated with a valvular prosthesis, such as anticoagulation, outweigh the benefits of proceeding. Among the asymptomatic patient group, those with exercise-induced hypotension, systolic dysfunction, and marked left ventricular hypertrophy are probably at increased risk and should be considered for valve replacement. Some experts also consider exercise ST depression to represent an additional risk factor and suggest that sudden death is extremely rare in children with aortic stenosis who have no ST depression with exercise.10
Asymptomatic athletes with severe aortic stenosis should undergo exercise testing to document their lack of symptoms and should be restricted from competing and training. My bias, even in these asymptomatic athletes, is to proceed to aortic valve replacement in the near future for the following reasons: Surgery has relatively low risk in healthy subjects, prolonged pressure overload has deleterious effects on the left ventricle, and many active patients are reluctant to avoid vigorous exercise for a prolonged period of time.
Chronic Aortic Insufficiency
Chronic aortic insufficiency can be well tolerated for decades, but many patients with moderate and severe regurgitation experience a gradual progression from normal to abnormal left ventricular function characterized by left ventricular enlargement, reduced contractility, and decreased ejection fraction. Most patients developing left ventricular dysfunction present with early symptoms of heart failure, including exercise intolerance, dyspnea, and exercise-induced presyncope before left ventricular function is severe. Some patients, however, do not develop sentinel symptoms and present with marked left ventricular enlargement and a severely dysfunctional left ventricle.7
Early in the course of left ventricular dysfunction, the left ventricle can recover after aortic valve replacement, probably because the dysfunction was primarily due to volume overload. If the volume overload has been persistent and produced severe chamber enlargement with left ventricular dysfunction, the myocardial dysfunction is not wholly reversible despite correction of the valvular lesion. Consequently, the severity of left ventricular dilatation and dysfunction are the key determinants of postoperative ventricular function and survival.
What to look for. Athletes with aortic insufficiency should be carefully questioned for exercise-induced signs of early heart failure. The physical examination should include a search for the stigmata of Marfan syndrome since many Marfan patients have important aortic insufficiency. They should also have a baseline ECG, echocardiogram with careful measurement of left ventricular and left atrial diameters, and an exercise stress test. The baseline ECG is used to evaluate left ventricular voltage and T-wave changes over time. The exercise test is to document functional capacity and the absence of symptoms and exercise-induced arrhythmia. It is useful to chart the ECG voltage and T waves in leads II, aVL, V5, and V6, as well as the echocardiographic left ventricular and left atrial dimensions. These can then be followed sequentially for evidence of early left ventricular dysfunction.
Prognosis and advice. The general population of patients with moderate-to-severe aortic insufficiency, no symptoms, and normal left ventricular function has a reasonably good near-term prognosis. Among seven studies including 490 patients who were followed for a mean of 6.4 years, sudden death occurred in only 6, and progression to symptoms or left ventricular dysfunction occurred at a rate of 4.3% per annum.7 This is not a trivial rate of progression, however, since 21% of patients worsened over 5 years.
It is not clear how exercise training would affect these results. Dynamic exercise acutely increases heart rate, which shortens diastole and the time available for aortic regurgitation. In contrast, exercise training in normal people induces bradycardia, which prolongs aortic insufficiency and theoretically hastens left ventricular dysfunction. I am unaware of studies that have examined the effects of endurance training in aortic insufficiency patients, so the ultimate effect of athletic training and competition on aortic insufficiency has not been determined. Patients with important aortic insufficiency are routinely advised to avoid static exertion, because the increased afterload acutely increases aortic regurgitation, although whether static effort actually affects prognosis has not been examined.
Athletic participation. Athletes with mild or moderate aortic insufficiency, minimal left ventricular enlargement, and normal left ventricular function can participate in all sports.8 They should be cautioned to report any new symptoms. They should have a repeat echocardiogram 6 to 12 months after the initial visit to document disease stability and then every 2 to 3 years thereafter.7
Selected athletes with moderate aortic insufficiency and moderate left ventricular enlargement can participate in sports requiring moderate static and high dynamic effort (see table 1).8 These patients should also be cautioned to report new symptoms, have a repeat echocardiogram 6 months after the initial visit to document stability, and have repeat evaluations yearly thereafter.7
Asymptomatic athletes with severe aortic insufficiency should be restricted from competition and training and followed closely.8 They should have a repeat echocardiogram 3 months after the initial visit and every 6 to 12 months subsequently. Asymptomatic athletes with moderate-to-severe aortic insufficiency and left ventricular dysfunction or marked dilatation due to the aortic insufficiency should undergo valve replacement.7 Left ventricular dysfunction is defined as an ejection fraction (LVEF) of less than 50%.7 Marked enlargement is defined as a left ventricular end-diastolic volume greater than 75 mm or an end-systolic volume greater than 55 mm.7 Women with aortic insufficiency develop symptoms with less severe left ventricular dysfunction and enlargement than do men,7 suggesting that smaller individuals may require valve replacement at smaller ventricular volumes.
Aortic valve replacement should be strongly considered if there is progressive left ventricular dilation and dysfunction in asymptomatic patients, even if the left ventricle does not achieve the preceding parameters. An LVEF of 50% already represents considerable left ventricular dysfunction in aortic insufficiency patients, because the normal ventricular response to aortic insufficiency is to increase the LVEF above the normal 55% to 65%. Also, once the patient's left ventricle is markedly dilated, there is the possibility that the left ventricle has been permanently altered and will not return to normal function.
Athletes with severe aortic insufficiency who are symptomatic should undergo aortic valve replacement. The timing of the aortic valve replacement can be varied depending on the effort level required to produce symptoms, as well as left ventricular function and dimensions.
It is generally recommended that patients with moderate-to-severe aortic insufficiency and systolic hypertension should be treated with afterload-reducing agents such as hydralazine, nifedipine, or angiotensin-converting enzyme (ACE) inhibitors to achieve a normal systolic pressure. There is no conclusive evidence that treating normotensive patients who have aortic insufficiency is beneficial. Nevertheless, I routinely place patients with moderate-to-severe aortic insufficiency on ACE inhibitors in the hope of delaying the development of left ventricular dysfunction.
Aortic Valve Replacement in Athletes
The management of athletes after valvular replacement was discussed in the 26th Bethesda Conference.8 In general, athletes with normal left ventricular function after aortic valve replacement can participate in low-intensity sports, with selected athletes participating in moderate-intensity static and dynamic sports. Athletes taking anticoagulants should not engage in sports with any risk of bodily contact. These recommendations8 reflect concern about the aortic valve replacement techniques commonly available at that time. Until recently, nearly all aortic valve replacements were performed using a porcine heterograft, a cadaveric homograft, or a mechanical prosthesis. The mechanical prostheses required lifelong anticoagulation and had an effective valve area of only 1.2 to 3.2 cm2.11 Both heterografts and homografts required anticoagulation for only 3 months unless there were other factors predisposing to systemic embolization. Unfortunately, the techniques to preserve these bioprostheses affected their durability, and 30% of heterografts and 10% to 20% of homografts had to be replaced in 10 to 20 years.11 Bioprosthesis failure was most frequent in patients under age 40 years.11
Autografts. In 1967, Ross described an autograft approach to aortic valve replacement in which the normal pulmonic valve was used to replace the diseased aortic valve. There was a fairly high early mortality rate to the operation of 7.4% over the first 24 years of its use.12 Ross attributed this to the steep learning curve required for the operation.12 In 1976, the procedure was altered to using the pulmonic valve with the pulmonic trunk in the replacement. This advancement eliminated many of the technical problems inherent in the earlier technique and helped reduce the current mortality rate to less than 1%.7
The Ross procedure has multiple advantages over other aortic valve replacement techniques. The tissue used is viable because it is not subjected to sterilization and preservation procedures required for heterografts and homografts. This viability means that the replacement should last indefinitely, and the new aortic root can actually enlarge with somatic growth of the child.13 As with heterografts and homografts, long-term anticoagulation is not required, and the hemodynamic performance of the autograft is equal or superior to all other replacements.12 These advantages have led many surgeons to conclude that the Ross procedure is the treatment of choice in otherwise healthy subjects with more than a 20-year life expectancy.12 The procedure is especially attractive in athletes. Several high-profile athletes have competed successfully after a Ross replacement, including Jesse Sapolu, the center of the San Francisco 49ers football team in 1997.14
Limitations. There are limitations to this operation. It is not indicated for Marfan syndrome patients or other patients with connective tissue disorders, since the same process could affect the pulmonic valve in the aortic position. The operation is complicated and quite often long since it is really a "double valve procedure for a single valve disease"12 and, in addition, requires reimplantation of the coronary arteries into the autograft. Finally, it has not been widely used, and few surgeons have extensive experience with the technique. It is not clear that the excellent published mortality results will be replicated by less experienced surgeons. Nevertheless, if performed by an experienced operating team, the Ross procedure is probably the aortic valve replacement of choice for children, physiologically young adults, and athletes.
Knowledge of the evaluation and management of active individuals with valvular heart disease is a critical component of sports cardiology. Valvular aortic stenosis continues to account for approximately 4% of exercise-related sudden deaths among young athletes. The presence of a cardiac murmur or the possibility of cardiac symptoms among young athletes is a frequent reason for cardiac referral. The most common cause of cardiac murmurs in athletes is a flow murmur across the pulmonic valve related to the cardiovascular adaptations that occur with exercise training. In adults, physiologic flow murmurs are often related to aortic sclerosis, but this condition may not be as benign as flow murmurs in children, because aortic sclerosis is accompanied by other risk factors for atherosclerosis, such as hyperlipidemia.
Severe aortic stenosis may be associated with exercise-induced syncope, angina, heart failure, and, rarely, sudden death. Athletes with severe aortic stenosis should be restricted from competition and encouraged to undergo aortic valve replacement. Active subjects with moderate-to-severe aortic insufficiency require careful follow-up and periodic echocardiograms to detect early signs of heart failure or progressive left ventricular dilatation. Surgical repair should be performed with the onset of symptoms, marked cardiac enlargement, or progressive left ventricular dilatation.
This article was adapted from the recently published book: Thompson PD (ed): Exercise and Sports Cardiology, New York City, McGraw-Hill Medical Publishing, 2001 (to order: 1-800-262-4729 [ISBN:0-07-134773-9]).
Dr Thompson is the director of preventive cardiology at the Hartford Hospital in Hartford, Connecticut. Address correspondence to Paul D. Thompson, MD, 80 Seymour St, Hartford, CT 06102; e-mail to [email protected].
Disclosure information: Dr Thompson discloses no significant relationship with any manufacturer of any commercial product mentioned in this article. No drug is mentioned in this article for an unlabeled use.