Transcatheter aortic valve replacement is an effective option for treating severe aortic valve stenosis in high-risk patients.
Cian P. McCarthy, MB, BCh, BAO
School of Medicine, University College Cork, Cork, Ireland
Dermot Phelan, MD, PhD
Director of Sports Cardiology, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic; Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH
Brian Griffin, MD
Section Head of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic
Address: Dermot Phelan, MD, PhD, Director of Sports Cardiology, Department of Cardiovascular Medicine, Heart and Vascular Institute, J1-5, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; firstname.lastname@example.org
ABSTRACTAsymptomatic but hemodynamically severe aortic stenosis often poses a dilemma: should the aortic valve be replaced, or is watchful waiting acceptable? Patients with this condition are a diverse group with varying prognoses. Here, we review the guidelines for valve replacement in this situation and highlight the variables useful in establishing which patients should be considered for early intervention even if they have no symptoms.
Aortic stenosis is the most common valvular heart condition in the developed world, affecting 3% of people between ages 75 and 851 and 4% of people over age 85.2 Aortic valve replacement remains the only treatment proven to reduce the rates of mortality and morbidity in this condition.3 Under current guidelines,4,5 the onset of symptoms of exertional angina, syncope, or dyspnea in a patient who has severe aortic stenosis is a class I indication for surgery—ie, surgery should be performed.
However, high-gradient, severe aortic stenosis that is asymptomatic often poses a dilemma. The annual rate of sudden death in patients with this condition is estimated at 1% to 3%,6–9 but the surgical mortality rate in aortic valve replacement has been as high as 6% in Medicare patients (varying by center and comorbidities).10 Therefore, the traditional teaching was to not surgically replace the valve in asymptomatic patients, based on an adverse risk-benefit ratio. But with improvements in surgical techniques and prostheses, these rates have been reduced to 2.41% at high-volume centers11 (and to less than 1% at some hospitals),12 arguing in favor of earlier intervention.
Complicating the issue, transcatheter aortic valve replacement has become widely available, but further investigation into its use in this patient cohort is warranted.
Furthermore, many patients with severe but apparently asymptomatic aortic stenosis and normal left ventricular ejection fraction may actually have impaired exercise capacity, or they may have structural left ventricular changes such as severe hypertrophy or reduction in global strain, which may worsen the long-term survival rate.13,14
A prospective trial in patients with severe aortic stenosis found that mortality rates were significantly lower in those who underwent surgery early than in those who received conventional treatment, ie, watchful waiting (no specific medical treatment for aortic stenosis is available).15
Patients with asymptomatic severe aortic stenosis are a diverse group; some have a far worse prognosis than others, with or without surgery.
This paper reviews the guidelines for valve replacement in this patient group and the factors useful in establishing who should be considered for early intervention even if they have no classic symptoms (Figure 1).
SIGNS AND SYMPTOMS OF STENOSIS
Aortic stenosis is often first suspected when a patient presents with angina, dyspnea, and syncope, or when an ejection systolic murmur is heard incidentally on physical examination—typically a high-pitched, crescendo-decrescendo, midsystolic ejection murmur that is best heard at the right upper sternal border and that radiates to the carotid arteries.
Several physical findings may help in assessing the severity of aortic stenosis. In mild stenosis, the murmur peaks in early systole, but as the disease progresses the peak moves later into systole. The corollary of this phenomenon is a weak and delayed carotid upstroke known as “pulsus parvus et tardus.” This can be assessed by palpating the carotid artery while auscultating the heart.
Aortic stenosis is often first suspected when a patient has angina, dyspnea, and syncope or an ejection systolic murmur
The second heart sound becomes progressively softer as the stenosis advances until it is no longer audible. If a fourth heart sound is present, it may be due to concentric left ventricular hypertrophy with reduced left ventricular compliance, and a third heart sound indicates severe left ventricular dysfunction. Both of these findings suggest severe aortic stenosis.
ECHOCARDIOGRAPHIC MEASURES OF SEVERITY
Echocardiography is the best established and most important initial investigation in the assessment of a patient with suspected aortic stenosis. It usually provides accurate information on the severity and the mechanism of stenosis. The following findings indicate severe aortic stenosis:
RECOMMENDATIONS FOR SURGERY BASED ON SEVERITY AND SYMPTOMS
The American College of Cardiology and American Heart Association (ACC/AHA)4 have issued the following recommendations for aortic valve replacement, based on the severity of stenosis and on whether the patient has symptoms (Figure 2):
Severe stenosis, with symptoms: class I recommendation (surgery should be done). Without surgery, these patients have a very poor prognosis, with an overall mortality rate of 75% at 3 years.3
Severe stenosis, no symptoms, in patients undergoing cardiac surgery for another indication (eg, coronary artery bypass grafting, ascending aortic surgery, or surgery on other valves): class I recommendation for concomitant aortic valve replacement.
Moderate stenosis, no symptoms, in patients undergoing cardiac surgery for another indication: class IIa recommendation (ie, aortic valve replacement “is reasonable”).
Very severe stenosis (aortic peak velocity > 5.0 m/s or mean pressure gradient ≥ 60 mm Hg), no symptoms, and low risk of death during surgery: class IIa recommendation.
Severe stenosis, no symptoms, and an increase in transaortic velocity of 0.3 m/s or more per year on serial testing or in patients considered to be at high risk for rapid disease progression, such as elderly patients with severe calcification: class IIb recommendation (surgery “can be considered”). The threshold to replace the valve is lower for patients who cannot make serial follow-up appointments because they live far away or lack transportation, or because they have problems with compliance.
Echocardiography also provides information on left ventricular function, and patients with left ventricular dysfunction have significantly worse outcomes. Studies have shown substantial differences in survival in patients who had an ejection fraction of less than 50% before valve replacement compared with those with a normal ejection fraction.3
Thus, the ACC/AHA guidelines recommend immediate referral for aortic valve replacement in asymptomatic patients whose left ventricular ejection fraction is less than 50% (class I recommendation, level of evidence B) in the hope of preventing irreversible ventricular dysfunction.4
TREADMILL EXERCISE TESTING UNMASKS SYMPTOMS
Treadmill testing is absolutely contraindicated in patients with severe symptomatic aortic stenosis
In the past, severe aortic stenosis was considered a contraindication to stress testing because of concerns of precipitating severe, life-threatening complications. However, studies over the past 10 years have shown that a supervised modified Bruce protocol is safe in patients with severe asymptomatic aortic stenosis.16,17
However, treadmill exercise testing clearly is absolutely contraindicated in patients with severe symptomatic aortic stenosis because of the risk of syncope or of precipitating a malignant arrhythmia. Nevertheless, it may play an essential role in the workup of a physically active patient with no symptoms.
Symptoms can develop insidiously in patients with chronic valve disease and may often go unrecognized by patients and their physicians. Many patients who state they have no symptoms may actually be subconsciously limiting their exercise to avoid symptoms.
Amato et al13 examined the exercise capacity of 66 patients reported to have severe asymptomatic aortic stenosis. Treadmill exercise testing was considered positive in this study if the patient developed symptoms or complex ventricular arrhythmias, had blood pressure that failed to rise by 20 mm Hg, or developed horizontal or down-sloping ST depression (≥ 1 mm in men, ≥ 2 mm in women). Twenty (30.3%) of the 66 patients developed symptoms during exercise testing, and they had a significantly worse prognosis: the 2-year event-free survival rate was only 19% in those with a positive test compared with 85% in those with a negative test.13 This study highlights the problem of patients subconsciously reducing their level of activity, thereby masking their true symptoms.
A meta-analysis by Rafique et al18 found that asymptomatic patients with abnormal results on exercise testing had a risk of cardiac events during follow-up that was eight times higher than normal, and a risk of sudden death 5.5 times higher.
With trials demonstrating that exercise testing is safe and prognostically useful in patients with aortic stenosis, the ACC/AHA guidelines emphasize its role, giving a class I recommendation for aortic valve replacement in patients who develop symptoms on exercise testing, and a class IIa recommendation in asymptomatic patients with decreased exercise tolerance or an exercise-related fall in blood pressure (Figure 2).4
Stress echocardiography has been used since the 1980s to assess the hemodynamic consequences of valvular heart disease, and many studies highlight its prognostic usefulness in patients with asymptomatic aortic stenosis.
In a 2005 study by Lancellotti et al,19 69 patients with severe asymptomatic aortic stenosis underwent a symptom-limited bicycle exercise stress test using quantitative Doppler echocardiography both at rest and at peak exercise, and a number of independent predictors of poor outcome (ie, symptoms, aortic valve replacement, death) were identified. These predictors included an abnormal test result, defined as any of the following: angina, dyspnea, ST-segment depression of 2 mm Hg or more, a fall or a small (< 20 mm Hg) rise in systolic blood pressure during the test, an aortic valve area of 0.75 cm2 or less, or a mean increase in valve gradient of 18 mm Hg or more.
Subsequently, a multicenter prospective trial assessed the value of exercise stress echocardiography in 186 patients with asymptomatic moderate or severe aortic stenosis.20 A mean increase in the aortic valve gradient of 20 mm Hg or more after exercise was associated with a rate of cardiovascular events (death, aortic valve replacement) 3.8 times higher, independent of other risk factors and whether moderate or severe stenosis was present (Table 1).20
Exercise-induced changes in systolic pulmonary artery pressure, which can be assessed using stress echocardiography, also have prognostic utility. Elevated systolic pulmonary artery pressure (> 50 mm Hg) seems to portend a poorer prognosis21,22 and a higher mortality rate after valve replacement,23 making it an independent predictor of hospital mortality and postoperative major adverse cardiovascular and cerebrovascular events (Table 1).
Exercise echocardiography also can be used to assess the patient’s contractile reserve. Left ventricular contractile reserve can be defined as an exercise-induced increase in left ventricular ejection fraction. In a study by Maréchaux et al24 in 50 patients with asymptomatic aortic stenosis and a normal resting left ventricular ejection fraction (> 50%), 40% of patients did not have left ventricular contractile reserve. In fact, their left ventricular ejection fraction decreased with exercise (from 64 ± 10% to 53 ± 12%). The subgroup of patients without contractile reserve developed symptoms more frequently during exercise and had lower event-free survival (Table 1).
Stress echocardiography has recently been introduced into the European Society of Cardiology guidelines, which give a class IIb indication for aortic valve replacement in asymptomatic patients who have severe aortic stenosis, a normal ejection fraction, and a greater than 20-mm Hg increase in mean gradient on exercise.5 But it has yet to be introduced into the ACC/AHA guidelines as a consideration for surgery.
LEFT VENTRICULAR FUNCTION: BEYOND EJECTION FRACTION
Left ventricular dysfunction is a bad sign for patients with aortic stenosis. Struggling to empty its contents through the narrowed aortic valve, the left ventricle is subjected to increased wall stress and eventually develops hypertrophy. The hypertrophied heart muscle requires more oxygen but receives less perfusion. Eventually, myocardial fibrosis develops, leading to systolic dysfunction and a reduction in the ejection fraction. As described above, patients with asymptomatic aortic stenosis and a left ventricular ejection fraction less than 50% have a poor prognosis,14 and therefore the ACC/AHA guidelines give this condition a class I recommendation for surgery.4
The ejection fraction has limitations as a marker of left ventricular function
However, the ejection fraction has limitations as a marker of left ventricular function. It reflects changes in left ventricular cavity volume but not in the complex structure of the left ventricle. Several studies show that up to one-third of patients with severe aortic stenosis have considerable impairment of intrinsic myocardial systolic function despite a preserved ejection fraction.8,25,26
Thus, other variables such as left atrial size, left ventricular hypertrophy, myocardial deformation (assessed using strain imaging), and B-type natriuretic peptide (BNP) level may also be considered in assessing the effect of severe aortic stenosis on left ventricular function in the context of a normal ejection fraction (Table 2).
Transcatheter aortic valve replacement is an effective option for treating severe aortic valve stenosis in high-risk patients.
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