By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center
Dr. Zimmet reports no financial relationships relevant to this field of study.
SOURCE: Taniguchi T, et al. Initial surgical vs conservative strategies in patients with asymptomatic severe aortic stenosis. J Am Coll Cardiol 2015 Oct 6. pii: S0735-1097(15)06789-3.
The role of aortic valve replacement (AVR) in relieving symptoms and improving mortality in symptomatic severe aortic stenosis is clear. However, the landscape is murkier in treating patients with severe aortic stenosis (AS) without symptoms. Prior studies have shown that in truly asymptomatic AS patients with otherwise normal cardiac function, survival is similar to age-matched controls if physicians follow the recommended frequency of clinical and echocardiographic monitoring. These studies suggest a low risk of sudden cardiac death (< 1% per year) in such patients. The 2014 American College of Cardiology/American Heart Association guidelines, therefore, recommend a watchful waiting approach for the majority of patients with severe AS and no symptoms, with a recommendation for surgery carved out for certain subsets. For example, asymptomatic patients with reduced ejection fraction and those with other indications for cardiac surgery maintain a Class I indication for AVR. Patients at low risk for surgery with very high gradients or with rapid progression of disease receive a Class II indication. To date, however, no large trial has adequately addressed the question of what to do with the majority of asymptomatic patients with severe AS.
Thus, the study by Taniguchi et al is of interest. The CURRENT AS registry retrospectively enrolled patients with severe AS at 27 centers in Japan. Between 2003 and 2011, researchers enrolled 3815 patients. Of these, 1808 patients showed no specific symptoms at the time of the qualifying echocardiogram and were the basis for the current study. In 291 asymptomatic patients, surgical AVR was the initial strategy; 98% of these actually underwent AVR, at a median of 44 days after the initial echo. The conservatively managed group of 1517 patients was winnowed by propensity-score matching to 291 patients, which, along with the initial surgery group, formed the main analysis set. The primary outcome measures were all-cause mortality and heart failure hospitalization at 5 years of follow-up.
Compared with patients in the conservative group, patients in the initial AVR group had a lower incidence of all-cause mortality (15.4% vs 26.4%, P = 0.009), cardiovascular death and aortic valve-related death (9.9% vs 18.6%, P = 0.01, and 5.3% vs 13.5%, P = 0.003, respectively). The cumulative 5-year incidence of heart failure hospitalization was similarly lower in the initial AVR group (3.8% vs 19.9%, P < 0.001). Of 46 patients in the conservative group who suffered cardiovascular death, the main causes identified were heart failure (9 patients) and sudden death (18 patients, including 10 without symptoms at the time of death). The authors concluded that patients with severe asymptomatic AS managed conservatively have “dismal” outcomes in real-world practice. They reported that an initial strategy of surgery vs conservative therapy was associated with lower 5-year risks for all-cause death and heart failure exacerbation. While calling for randomized trials, they strongly suggested the superiority of an initial surgical strategy based on these data.
Registry data rarely provide an adequate substitute for randomized, controlled trials, and this is no exception. Also, even seemingly simple things, such as the determination of symptom status, are often more complex than they appear.
In this study, the non-randomized surgical and conservative groups were substantially different from one another at baseline. Patients managed with an initial conservative strategy were much older and more frequently had a history of stroke, atrial fibrillation or flutter, malignancy, chronic lung disease, and coronary disease. Even after propensity matching, the initial AVR group was significantly younger, had a greater severity of AS, and had lower surgical risk as estimated by the Society of Thoracic Surgeons score. It’s no wonder that these patients were sent more readily to surgery.
Among the patients managed initially with AVR, a full 67% had formal indications that would in any case meet current guidelines for surgery. Forty-one percent had very severe AS, which is a group known to have a higher event rate during follow-up. Seven percent had reduced left ventricular ejection fraction. Eight percent had other indications for cardiac surgery. Eleven percent showed rapid hemodynamic progression.
What, then, can we safely conclude from this study? The authors make a strong case that such “real-world” patients with asymptomatic severe AS who are managed conservatively perform more poorly than has previously been acknowledged. For example, they note a 1.5% per year sudden death rate, compared with the < 1% rate that is commonly quoted in the guidelines. This is important to recognize in order to make good clinical decisions. Overall, the clinicians in this registry did an excellent job selecting patients who would do well with early surgery, balancing the potential benefits with risks that are not always captured in a registry. Until we have randomized data on this question, such tailored decision-making using current guidelines will remain the rule.