Aortic stenosis (AS) is the most common valvular disease in the western hemisphere. Currently, 4% of the North American population above 75 years of age has AS, and approximately 50% of patients with mild to moderate AS will progress to hemodynamically severe AS in their lifetime.1
The natural history of the disease, which is largely unchanged since its initial description by Braunwald and Ross in 1968, includes a ‘latent period’ in which progressing aortic valvular obstruction leads to myocardial pressure overload followed by an abrupt and precipitous decline in survival after the onset of symptoms is manifested.2 The classic symptoms include angina, syncope, and heart failure, which develop primarily from the inability of the cardiac output to meet peripheral demands. The severity of the valvular stenosis at which these symptoms occur varies from patient to patient.
Despite several trials examining medical therapy for these patients, the only proven and accepted therapy is surgical replacement of the aortic valve.3,4 The operative mortality rate for aortic valve replacement (AVR) is around 4%, with long-term survival of 80% at three years.5 Although the operative mortality rate is relatively low, the American College of Cardiology (ACC)/American Heart Association (AHA)/American Society of Echocardiography (ASE) guidelines provide a class I indication for AVR in patients with severe AS only after the onset of symptoms.6 This recommendation is based on observational studies that demonstrate that patients with severe AS who are truly asymptomatic have only a 1% risk for undergoing sudden death.7
In this study we sought to ascertain the reasons why patients with severe AS were not referred for AVR in a university hospital setting. The study population included all patients who received a transthoracic echocardiogram at the University of Chicago Medical Center during calendar year 2007 and who met echocardiographic criteria for severe AS. We followed the ACC/AHA/ASE criteria for classifying severe AS, including all patients with an aortic valve area <1.0cm2, an aortic valve gradient ≥40mmHg, and an aortic jet velocity ≥4m/s.
Medical records were reviewed and test results for exercise stress and coronary computed tomography (CT) were collected when performed. Clinic notes and hospitalization summaries were reviewed for presence of symptoms including chest pain, dyspnea, heart failure, dizziness, and syncope. It was noted whether or not the physician attributed the symptoms to AS. Referral to surgery and subsequent date of AVR was also recorded. Operative risk was calculated using the online Society of Thoracic Surgeons (STS) Risk Calculator and logistic EuroSCORE, both of which are validated risk assessment tools.8,9
Medical records for all patients were reviewed every month for the occurrence of symptoms, symptom progression, AVR, and death. Date of death was recorded and confirmed by the social security death index (SSDI). Cause of death was collected whenever possible. The last follow-up for all patients took place in March 2009. The study protocol was approved by the institutional review board. A detailed version of this study has been previously reported in a recent issue of the American Journal of Cardiology.10
Results
A total of 11,000 transthoracic echocardiograms were performed between January and December 2007. Of these echocardiograms, 106 patients met the pre-specified echocardiographic criteria for severe AS and were included in the study. Of the 106 patients with severe AS, 33 (31%) underwent AVR, while 73 (69%) did not. The baseline characteristics of the patients who underwent surgery included 58% female patients with a mean age of 73 years (range 25–90 years). Forty-six percent of patients in this group had left ventricular (LV) dysfunction with a mean ejection fraction of 36% (range 4–54%). Every patient who underwent surgery had a minimum of one comorbidity. Of the patients who did not undergo AVR, 75% were female with a mean age of 76 years (range 45–108 years). Only 21% of the patients in this group had LV dysfunction, with a mean ejection fraction of 38% (range 24–53%). Eighty-nine percent of patients who did not have surgery also had a minimum of one comorbidity (see Table 1).
The most common comorbidity in the group of patients who had AVR was hypertension (88%), followed by coronary artery disease (64%), congestive heart failure (48%), diabetes (36%), chronic kidney disease (21%), and cancer (18%). In the group of patients who did not receive AVR, hypertension was also the most common comorbidity (76%), followed by coronary artery disease (36%), chronic kidney disease (31%), diabetes (24%), cancer (21%), and congestive heart failure (19%).
Among the different types of physician taking care of these patients, cardiologists were the subspecialty most likely not to refer patients with severe AS for AVR (64%), followed by generalists (22%) and vascular surgeons (3%). The specialty of 11% of the physicians was unknown. By stark contrast, all patients who were evaluated by cardiothoracic surgeons received AVR.
Symptoms such as chest pain, dizziness, syncope, dyspnea, and heart failure were prevalent both in patients who underwent surgery and in those who did not. Ninety-four percent of patients who underwent AVR were symptomatic. Of the patients who were not referred for surgery, 42% were found to be symptomatic (see Figure 1).
In symptomatic patients with severe AS, the most common reason for not performing AVR was the treating physician not attributing the symptoms to AS (29%). High operative risk was the reason in 15%, although the calculated STS risk and EuroSCORE were high in only 10% of the patients. The remaining reasons included patient refusal (15%), AS not being considered truly severe (11%), limited life expectancy (11%), advanced age (6%), the patient being transferred to another hospital (3%), the symptoms not being recognized by the physician (6%), and pseudo-AS (3%) (see Figure 2).
For the patients who were thought to be asymptomatic and accordingly not referred for AVR, the most common reason for not undergoing AVR was the lack of symptoms (70%), followed by the presence of comorbidities (7%), AS not being considered truly severe (4%), and high operative risk (2%) (see Figure 3). The calculated STS risk and EuroSCORE for the patients who were assumed to be at high operative risk was low to moderate due to age only. Seventeen percent of the reasons were not specified. Only 4% of these patients had an exercise stress test to determine whether or not they were objectively symptomatic.
Twenty-one percent of the patients have died since their echo-cardiography study in 2007. Six of these patients (6%) underwent AVR and 15 (15%) did not. Of the six patients who underwent AVR, three died from bacteremia within two months of AVR. Of the 15 patients who did not receive AVR, 10 were symptomatic and five were thought to be asymptomatic.
Since the initial data collection, seven more patients have undergone AVR. Three of these patients were symptomatic and were not initially referred for surgery: one was considered a high operative risk, one had symptoms not attributed to AS, and one was thought not to be truly symptomatic. The remaining patients were considered to be asymptomatic. All patients were alive and well during the last follow-up.
Discussion
In this study, we found that in a large academic medical center only 31% of patients with severe AS were referred for AVR. The mean age of patients who underwent surgery and those who did not was remarkably similar and, interestingly, the majority of patients in both groups were female. Since AVR is recommended when LV ejection fraction falls below 50%,6 it is not surprising that more patients who underwent AVR had moderate to severe LV dysfunction than those patients who did not undergo AVR. However, over 20% of patients who were not referred for surgery also had significant LV dysfunction.
The majority of patients in both groups had at least one comorbidity. A high percentage of patients in the group who did not undergo surgery had cancer and chronic kidney disease. The presence of these comorbidities was commonly the reason the patients were not ultimately referred for AVR.
Although the presence of symptoms in patients with severe AS signals worsening disease and the need for surgery, we found that almost half of the patients with symptoms were not referred for surgery. Certainly, there are legitimate reasons why some patients with symptomatic severe AS should not undergo surgery. However, the most common reason in this study was that symptoms, including dyspnea, chest pain, and syncope, were attributed to reasons other than severe AS. High operative risk was another frequent reason for not referring a subset of symptomatic patients with severe AS for surgery. However, using the STS risk and EuroSCORE, several of these patients were actually in the low to moderate operative risk range primarily because of advanced age.
Several studies have examined decision-making among physicians in referring elderly patients for valvular surgery. One study in particular reviewed the records of 216 patients over 75 years of age with severe symptomatic AS and found that 33% were not referred for AVR.11 In multivariable analysis, LV dysfunction and older age were the two most significant reasons patients did not undergo valve replacement. Although older age and LV dysfunction do increase operative risk, the natural history of AS indicates that these are the patients who would most benefit from AVR.
While it was not surprising that over 70% of patients who were asymptomatic did not undergo surgery because, according to the physician, no symptoms were present, only two patients (4%) underwent exercise stress testing. For these two patients, the stress test was positive and each subsequently underwent surgery. At the time of the last follow-up, both patients were alive and well.
The initial symptoms of AS can be subtle and are notoriously difficult to identify with certainty. Because exercise provokes greater peripheral demand, symptoms should manifest themselves during stress testing. Amato et al. showed that in asymptomatic patients with severe AS, the estimated risk for developing symptoms or sudden death was eight times higher over two years in patients with a positive stress test.12 Currently, the ACC/AHA has given a class IIb indication and the European Society of Cardiology (ESC) has given a class I indication for the use of exercise stress tests to objectively assess for symptoms.13
Our study shows a significant underutilization of objective testing such as exercise stress tests. When exercise stress testing was performed in our study, the patients thought to be asymptomatic were, indeed, symptomatic and appropriately referred for successful AVR. Although no complications were reported in any of the studies using exercise stress tests in patients with severe AS, one explanation of why so few objective tests are performed is that referring physicians might worry about having their patients exert themselves on the treadmill. Unfortunately, as highlighted in this study, this unfounded fear prevents many patients who would benefit from AVR from receiving it.
The results of this study are not unique to a single institution. The Euro Heart Survey, a multicenter European study conducted in 2001, examined the characteristics, treatment, and outcomes of 809 patients with severe AS.14 Although more patients were referred for AVR than in our study (47 versus 31%) and fewer patients with severe symptomatic single-valve disease were denied surgical intervention (32 versus 42%), both studies show that the majority of patients with severe AS are not undergoing AVR, contrary to the guidelines. Similar to our study, this low percentage was thought to be due to the age of the patients and the perception of increased surgical risk. In addition, much like in our study, objective testing for asymptomatic patients was seldom used, with only 5.7% of patients undergoing an exercise stress test. The Euro Heart Survey authors concluded that fear of complications and inexperience with exercise testing contributed to its gross underutilization.
Another recent survey, conducted by Bach et al. at the University of Michigan Medical Center, examined why similar patients in the US with severe AS did not undergo AVR.15 Of 155 patients with severe AS, 52% underwent AVR—a significantly higher rate than in our study. The remaining patients who did not undergo surgery were younger than the cohort in our study (mean age 68 versus 76 years), but had a similar percentage of comorbidities (88 versus 89%), including LV dysfunction (20 versus 21%). Almost three-quarters of these unoperated patients were symptomatic and were not referred for AVR because of comorbidities. Much like our study and the European study, of the remaining asymptomatic patients not referred for AVR, only one (4.5%) underwent exercise stress testing. Our study has several limitations. First, the study was retrospective and thus inherent biases are impossible to rule out. In addition, the study population came from a single academic center and it is therefore difficult to generalize the results to other medical institutions, including private centers. However, one might expect that in centers where referral to cardiothoracic surgery is more difficult, the percentage of patients with severe AS requiring surgery but not receiving it would be even higher. While this study followed patients for an average of 15 months, further follow-up of these patients would likely show a significant difference in mortality between those patients who received AVR and those who did not.
Conclusion
In summary, despite a class I indication to perform AVR in patients with severe symptomatic AS, the majority of these patients do not undergo surgery. Although not every one of these patients is a suitable candidate for surgery, many patients are refused potentially life-saving therapy because symptoms are thought not to be directly caused by AS, or patients are thought to be a high operative risk based on age or comorbidities.
Multiple studies examining the natural history of AS have repeatedly shown that the failure to recognize symptoms that are directly attributable to severe AS is costly. The mean survival in symptomatic patients with severe AS is 23±5 months, with a five-year probability of survival of 18%.16 Physicians frequently overestimate the operative risk of AVR (as they did in our study), but with an operative mortality of 4%, the chance of surviving surgery is much better than the survival rate if the valve is not replaced. Furthermore, with the recently reported successes of percutaneous AVR in higher-risk patients with severe AS, referring physicians need to re-consider surgery for many of their patients.