Transcatheter Aortic Valve Implantation for Aortic Stenosis
Abstract & Commentary
By Andrew J. Boyle, MBBS, PhD, Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco. Dr. Boyle reports no financial relationships relevant to this field of study.This article originally appeared in the November 2010 issue of Clinical Cardiology Alert. It was edited by Michael H. Crawford, MD, and peer reviewed by Ethan Weiss, MD. Dr. Crawford is Professor of Medicine, Chief of Cardiology, University of California, San Francisco, and Dr. Weiss is Assistant Professor of Medicine, Division of Cardiology and CVRI, University of California, San Francisco. Dr. Crawford is on the speaker's bureau for Pfizer, and Dr. Weiss reports no financial relationships relevant to this field of study.
Sources: Leon MB, et al. Transcatheter aortic valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010; online pre-print; Gurvitch R, et al. Transcatheter aortic valve implantation. Durability of clinical and hemodynamic outcomes beyond 3 years in a large patient cohort. Circulation. 2010;122:1319-1327.
There is no medical therapy for aortic stenosis (AS), and balloon aortic valvuloplasty (BAV) has sub-optimal long-term results. The incidence of AS increases with age and, thus, many patients have significant comorbidities. These patients are often denied surgical aortic valve replacement (AVR) because of the high risk of surgery when serious comorbidities are present, and there has been no other treatment option for them. Percutaneous transcatheter aortic valve implantation (TAVI) may represent an alternative treatment option for patients at prohibitively high risk to undergo surgical AVR. Recently, the results of the PARTNER trial were presented at the Transcatheter Cardiovascular Therapeutics meeting, and the longer-term results from a Canadian registry also were released. These studies provide data to support the use of TAVI in patients with severe AS who have are too high risk to undergo surgical AVR.
The PARTNER trial was a randomized, controlled trial performed at 21 centers (17 in the United States) of TAVI vs. standard care in patients with symptomatic severe AS who were not candidates for surgical AVR. Inclusion criteria were New York Heart Association class II-IV symptoms and an aortic valve area of < 0.8 cm2, a mean aortic valve gradient of > 40 mmHg, or a peak aortic valve velocity of > 4.0 m/sec. All were considered too high risk for surgical AVR by at least two cardiac surgeons. Exclusion criteria included a bicuspid or non-calcified aortic valve, reduced left ventricular ejection fraction (< 20%), acute myocardial infarction (MI), coronary artery disease requiring revascularization, severe mitral or aortic regurgitation, stroke or transient ischemic attack (TIA) in the prior six months, severe peripheral vascular disease, and aortic valve diameter that was not between 18 and 25 mm (therefore unsuitable for the currently available valve sizes). The trial was sponsored by Edwards, which manufacture the valve. The valve was implanted via the femoral artery after standard BAV in either the operating room or the cardiac catheterization laboratory. The valve consists of a bovine pericardial trileaflet valve mounted on a stainless steel frame that is balloon-expanded inside the existing aortic valve.
The baseline characteristics of the two treatment groups were similar, but the standard-care group had slightly higher rates of COPD (52.5% vs. 41.3%; p = 0.04), atrial fibrillation (48.8% vs. 32.9%; p = 0.04), and a higher logistic Euroscore (30.4 ± 19.1 vs. 26.4±17.2; p = 0.04). The mean age was 83 years in each group and the STS score (Society of Thoracic Surgeons score), a predictor of surgical mortality, was similar between groups (12.1 ± 6.1 vs. 11.2 ± 5.8, p = 0.14). TAVI resulted in immediate improvement in aortic valve area from 0.6 ± 0.2 cm2 to 1.5 ± 0.5 cm2, as well as a reduction in aortic mean valve gradient from 44.5 ± 15.7 mmHg to 11.1 ± 6.9 mmHg, and these improvements were maintained at one-year follow-up.
The primary endpoint was all-cause mortality at one year. Patients randomized to standard care (n = 358) had a higher one-year mortality of 50.7%, patients randomized to TAVI had a lower mortality (30.7%; hazard ratio 0.55, p < 0.001). Patients randomized to TAVI also had lower rates of cardiovascular death (20.5% vs. 44.6%, p < 0.001), death or repeat hospitalization (p < 0.001), and death or major stroke (33.1% vs. 51.3%, p < 0.001). Patients randomized to TAVI had improvement in symptoms and six-minute walk test. However, the improved mortality comes at a price. Patients randomized to TAVI had a higher rate of stroke or TIA (10.6% vs. 4.5%, p = 0.04), driven mainly by an increase in major stroke in the first 30 days (5.0% vs. 1.1%, p = 0.06). There was a higher incidence of vascular complications (32.4% vs. 7.3%, p < 0.001) and major bleeding (22.3% vs. 11.2%, p < 0.001) in the TAVI group. Importantly, there were no differences between groups in the rates of acute kidney injury, new atrial fibrillation, MI, new pacemaker requirement, or endocarditis. Despite all being considered unsuitable for surgical AVR, 17 patients in the standard-care group and two patients in the TAVI group underwent surgical AVR during the study. The authors concluded that in patients with severe AS who were not suitable for surgical AVR, TAVI significantly reduced the rates of death, the composite of death or repeat hospitalization, and cardiac symptoms, despite the higher incidence of strokes and major vascular events.
Gurvitch and colleagues present their data on a 3-year follow-up of patients undergoing TAVI in Canada. Unlike the PARTNER trial, this is not a randomized, controlled trial; it is a registry of 70 patients undergoing TAVI who were considered unsuitable for surgical AVR. The patients had a STS score 9.6 ± 3.5% and a mean age 80.7 ± 7.6 years, indicating a high-risk population. The patients received either the Edwards Sapien balloon expandable valve or the earlier generation Cribier-Edwards valve; 78.6% of cases were performed by the trans-femoral route and 21.4% via the trans-apical route. Patients were routinely prescribed aspirin for life and clopidogrel for six months after the procedure. All patients were followed for at least three years. The researchers excluded from their analysis those patients who died in the first 30 days, because these were thought to be due to procedural difficulties and the initial learning curve rather than problems with the device.
In those patients who survived the first 30 days after TAVI, survival at one, two, and three years was 81%, 74%, and 61%, respectively. One patient required re-operation from endocarditis, but no patients required re-operation for valve dysfunction. The aortic valve gradient decreased from 45 mmHg to 10 mmHg after the procedure (p < 0.01) and increased slightly to 12.1 mmHg after three years (p = 0.03). Valve area increased from 0.6 ± 0.2 cm2 to 1.7 ± 0.4 cm2 after the procedure (p < 0.01) and reduced to 1.4 ± 0.3 cm2 after three years (p < 0.01). At baseline, 1%, 3%, 69%, and 17% were in NYHA class I, II, III, and IV, respectively. At one-year follow-up, 93% of patients were in NYHA class I or II. This improvement was sustained with no change from 1-3 years post-procedure. After TAVI, aortic regurgitation (AR) was common: it was trivial in 40%, mild in 44%, and moderate in 6%; no patients had severe AR. One patient with mild AR worsened to moderate; of the patients with moderate AR, two improved to mild and two remained unchanged. This suggests that the degree of AR seen immediately post-procedure remains largely unchanged over three years. There were no cases of valve thrombosis, deterioration, or embolization. The authors conclude that TAVI demonstrates good medium- to long-term durability and preserved hemodynamic function, with no evidence of structural failure.
Surgical AVR remains the gold-standard treatment for severe symptomatic AS. However, there remain a group of patients who are at high surgical risk due to other co-morbidities, who are unable to undergo surgical AVR. As our population ages, this patient group is likely to increase in size substantially, and there is currently a very high mortality (50% at one year) and no definitive therapy for this group. The randomized, controlled PARTNER trial demonstrated a 20% absolute reduction (40% relative risk reduction) in mortality if these patients undergo TAVI instead of medical therapy. This is a staggering improvement in all-cause mortality compared to most cardiology trials. Importantly, quality of life also is improved. The additional three-year data from Gurvitch and colleagues shows us that this early benefit is likely to be sustained. Their cohort maintained their hemodynamic and symptomatic improvement for over three years.
However, this is no free lunch. It is important to note the significant procedural risks involved with TAVI. The procedure requires large arterial sheaths that can cause significant vascular complications and bleeding. Furthermore, there is a significant peri-procedural risk of stroke. Notably, over 80% of the standard-therapy patients received BAV, which is not usually the standard of care. BAV may have increased the rate of early stroke and vascular complications in the standard-therapy group, thus underestimating the difference between the groups. We should, thus, look at the absolute rates of stroke and vascular access site complications. Interestingly, many of the late complications in the Canadian registry occurred due to combination anti-platelet therapy and warfarin, or over-anti-coagulation. In future, it will be important to define the optimal anti-thrombotic therapy in this group. TAVI is not FDA-approved for use in the United States, but is already on the market in other countries, as well as Europe. This is a promising new treatment strategy, reducing the high mortality in this very high-risk population, but its benefits must be weighed against its early risks.