Calcific aortic stenosis is the most common valve lesion in the United States. Severe aortic stenosis can present with shortness of breath, angina, syncope, or a combination of these symptoms. The prognosis for calcific aortic stenosis, if left untreated, is poor, with almost 50 percent of patients dying within one year.
A study from Mayo Clinic in Rochester, Minn., followed 622 patients with severe aortic stenosis (mean age, 72 years) for more than five years. Sudden death without preceding symptoms occurred at a rate of 1 percent per year in unoperated patients. After five years, only 33 percent remained symptom-free. A peak aortic valve velocity greater than 4.5 m/s by Doppler echocardiography predicted symptoms, need for aortic valve replacement (AVR) and cardiac death.
A number of series have shown that patients treated with surgical AVR have a more favorable prognosis than those who do not undergo AVR. Five-year survival was 90 percent with AVR and only 38 percent without AVR in a cohort of patients with severe asymptomatic aortic stenosis.
Despite the grim prognosis of severe aortic stenosis, multiple series have demonstrated that 40 to 50 percent of elderly patients with severe aortic stenosis are untreated, primarily because of high surgical risk due to multiple medical comorbid conditions.
Recently, technology for implanting aortic valve prostheses in a minimally invasive manner has been developed. The randomized controlled PARTNER Cohort B trial prospectively compared the transcutaneous aortic valve implantation (TAVI) of the Edwards Sapien prosthesis delivered via the transfemoral route with standard medical therapy with or without valvuloplasty.
By design, a high-risk cohort of patients was enrolled, with the mean age of 83 years and a mean Society of Thoracic Surgeons score of 11 to 12, indicative of very high surgical risk. Patients had frequent comorbid conditions, including:
At one year, 50 percent of patients treated medically had died compared with 30 percent of those treated with TAVI. "This absolute risk reduction of 20 percent represents 200 lives saved per 1,000 patients treated and is reflected in a very small number-needed-to-treat of only five patients per life saved," according to Charanjit S. Rihal, M.D., an interventional cardiologist and chair of the Division of Cardiovascular Diseases at Mayo Clinic in Rochester. Similarly, mortality or repeat hospitalization was greatly reduced from 71 to 42 percent in the TAVI cohort.
Although the results of the PARTNER Cohort B trial were favorable, TAVI is not without procedural risk. Stroke occurred in 5 percent of patients undergoing TAVI by 30 days compared with stroke in only 1 percent of patients treated medically. Stroke may be attributable to embolization, hypotension or a combination of both.
Since the native valve leaflets are left in situ, paravalvular regurgitation around the cage of the stented valve was observed in more than half the patients. Ten percent of patients had moderate to severe paravalvular regurgitation. Mean gradients and aortic valve areas remained stable during the first year of follow-up, and the majority of patients reported their symptoms were improved.
In the PARTNER Cohort A trial, patients with severe aortic stenosis were randomly assigned to undergo either TAVI or conventional valve replacement surgery. The results of this arm of the PARTNER trial were presented at the recent American College of Cardiology meeting and published in The New England Journal of Medicine.
This cohort of patients, like those in Cohort B, was elderly, with a mean age of 84 years. Approximately two-thirds of the TAVI group valves were implanted via the transfemoral route, and approximately one-third were implanted transapically.
Although 30-day mortality was superior in the TAVI group, one-year mortality was similar, demonstrating noninferiority of TAVI compared with operative AVR. As in Cohort B, the concern centered on the stroke rate, which was significantly higher in the TAVI group than in the surgical group at one year. When the combined endpoint of major stroke and death is considered, however, there is no significant event difference between the two groups at 30 days and at one year.
Kevin L. Greason, M.D., a cardiovascular surgeon at Mayo Clinic in Rochester, points out that both cohorts had significant rates of vascular complications associated with TAVI. "Given the risk of stroke and major vascular complications associated with TAVI, standard AVR should still be strongly considered for those patients with normal operative risk."
Furthermore, the long-term durability of operative AVR has been demonstrated, although the long-term outcomes of TAVI have yet to be determined. Additionally, the procedure has thus far been evaluated only in elderly patients; outcomes and complication rates may differ in other patient groups.
These outcomes need to be considered in the context of the trial, according to David R. Holmes Jr., M.D., a cardiologist at Mayo Clinic in Rochester and president of the American College of Cardiology. "The valve used in this trial was a first-generation device; current valves have a smaller profile delivery system that will facilitate implantation," notes Dr. Holmes. "Additionally, operators were by definition inexperienced, as this is an investigational device, while experienced cardiovascular surgeons were implanting valves in the conventional manner."
Dr. Holmes expects TAVI outcomes to improve and complication rates to decrease with newer devices and as operators gain skill.
"An improved ability to match the right patient to the right treatment may be one of the most important outcomes of the trial," says Rakesh M. Suri, M.D., D.Phil., a cardiovascular surgeon at Mayo Clinic in Rochester.
At Mayo Clinic, a multidisciplinary TAVI program has been established through collaboration of the Valvular Heart Clinic, the Division of Cardiovascular Surgery, and the Interventional Cardiology Laboratory.
Patients see a medical cardiologist, a clinical and research nurse, and a cardiovascular surgeon, who review patients' status in twice-weekly team conferences. All agree that these integrated working relationships add greatly to the collective knowledge base that members of the team draw on to decide best patient practices. The team determines the costs (such as increased morbidity) and benefits (such as reduced mortality) of TAVI for each patient.
Currently, the valve is investigational, and all patients provide informed consent when they are enrolled in a prospective research study under the auspices of a U.S. Food and Drug Administration-approved protocol.