Transcatheter Aortic-Valve Replacement for Inoperable Severe Aortic Stenosis
Reporter: Aviva Lev-Ari, PhD, RN
Transcatheter Aortic-Valve Replacement for Inoperable Severe Aortic Stenosis
Raj R. Makkar, M.D., Gregory P. Fontana, M.D., Hasan Jilaihawi, M.D., Samir Kapadia, M.D., Augusto D. Pichard, M.D., Pamela S. Douglas, M.D., Vinod H. Thourani, M.D., Vasilis C. Babaliaros, M.D., John G. Webb, M.D., Howard C. Herrmann, M.D., Joseph E. Bavaria, M.D., Susheel Kodali, M.D., David L. Brown, M.D., Bruce Bowers, M.D., Todd M. Dewey, M.D., Lars G. Svensson, M.D., Ph.D., Murat Tuzcu, M.D., Jeffrey W. Moses, M.D., Matthew R. Williams, M.D., Robert J. Siegel, M.D., Jodi J. Akin, M.S., William N. Anderson, Ph.D., Stuart Pocock, Ph.D., Craig R. Smith, M.D., and Martin B. Leon, M.D. for the PARTNER Trial Investigators
N Engl J Med 2012; 366:1696-1704 May 3, 2012
Background
Transcatheter aortic-valve replacement (TAVR) is the recommended therapy for patients with severe aortic stenosis who are not suitable candidates for surgery. The outcomes beyond 1 year in such patients are not known.
Methods
We randomly assigned patients to transfemoral TAVR or to standard therapy (which often included balloon aortic valvuloplasty). Data on 2-year outcomes were analyzed.
Results
A total of 358 patients underwent randomization at 21 centers. The rates of death at 2 years were 43.3% in the TAVR group and 68.0% in the standard-therapy group (P<0.001), and the corresponding rates of cardiac death were 31.0% and 62.4% (P<0.001). The survival advantage associated with TAVR that was seen at 1 year remained significant among patients who survived beyond the first year (hazard ratio, 0.58; 95% confidence interval [CI], 0.36 to 0.92; P=0.02 with the use of the log-rank test). The rate of stroke was higher after TAVR than with standard therapy (13.8% vs. 5.5%, P=0.01), owing, in the first 30 days, to the occurrence of more ischemic events in the TAVR group (6.7% vs. 1.7%, P=0.02) and, beyond 30 days, to the occurrence of more hemorrhagic strokes in the TAVR group (2.2% vs. 0.6%, P=0.16). At 2 years, the rate of rehospitalization was 35.0% in the TAVR group and 72.5% in the standard-therapy group (P<0.001). TAVR, as compared with standard therapy, was also associated with improved functional status (P<0.001). The data suggest that the mortality benefit after TAVR may be limited to patients who do not have extensive coexisting conditions. Echocardiographic analysis showed a sustained increase in aortic-valve area and a decrease in aortic-valve gradient, with no worsening of paravalvular aortic regurgitation.
Conclusions
Among appropriately selected patients with severe aortic stenosis who were not suitable candidates for surgery, TAVR reduced the rates of death and hospitalization, with a decrease in symptoms and an improvement in valve hemodynamics that were sustained at 2 years of follow-up. The presence of extensive coexisting conditions may attenuate the survival benefit of TAVR. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.)
Supported by Edwards Lifesciences.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
This article (10.1056/NEJMoa1202277) was published on March 26, 2012, and updated on August 30, 2012, at NEJM.org.
Source Information
From Cedars–Sinai Heart Institute, Los Angeles (R.R.M., H.J., R.J.S.); Lenox Hill Heart and Vascular Institute (G.P.F.) and Columbia University Medical Center and New York Presbyterian Hospital (S. Kodali, J.W.M., M.R.W., C.R.S., M.B.L.) — both in New York; Cleveland Clinic Foundation, Cleveland (S. Kapadia, L.G.S., M.T.); Washington Hospital Center, Washington, DC (A.D.P.); Duke University School of Medicine, Durham, NC (P.S.D.); Emory University School of Medicine, Atlanta (V.H.T., V.C.B.), University of British Columbia and St. Paul’s Hospital, Vancouver, Canada (J.G.W.); Hospital of the University of Pennsylvania, Philadelphia (H.C.H., J.E.B.); Baylor Healthcare System (D.L.B., B.B.) and Medical City Dallas (T.M.D.) — both in Dallas; Edwards Lifesciences, Irvine, CA (J.J.A., W.N.A.); and London School of Hygiene and Tropical Medicine, London (S.P.).
Address reprint requests to Dr. Leon at Columbia University Medical Center, Center for Interventional Vascular Therapy, 161 Fort Washington Ave., 6th Fl., New York, NY 10032, or at mleon@crf.org.
The investigators, institutions, and research organizations participating in the Placement of Aortic Transcatheter Valves (PARTNERS) trial are listed in the Supplementary Appendix, available at NEJM.org.
http://www.nejm.org/doi/full/10.1056/nejmoa1202277
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A few years later, I was an Associate Professor at a new Medical School and I submitted a proposal that was reviewed by the Chairman of Pharmacology, who was a former Director of NSF. He thought it was good enough. I was a pathologist and it went to a Biochemistry Review Committee. It was approved, but not funded. The verdict was that I would not be able to carry out the studies needed, and they would have approached it differently. A thousand young investigators are out there now with similar letters. I was told that the Department Chairmen have to build up their faculty. It’s harder now than then. So I filed for and received 3 patents based on my work at the suggestion of my brother-in-law. When I took it to Boehringer-Mannheim, they were actually clueless.
This is very insightful. There is no doubt that there is the bias you refer to. 42 years ago, when I was postdocing in biochemistry/enzymology before completing my residency in pathology, I knew that there were very influential mambers of the faculty, who also had large programs, and attracted exceptional students. My mentor, it was said (although he was a great writer), could draft a project on toilet paper and call the NIH. It can’t be true, but it was a time in our history preceding a great explosion. It is bizarre for me to read now about eNOS and iNOS, and about CaMKII-á, â, ã, ä – isoenzymes. They were overlooked during the search for the genome, so intermediary metabolism took a back seat. But the work on protein conformation, and on the mechanism of action of enzymes and ligand and coenzyme was just out there, and became more important with the research on signaling pathways. The work on the mechanism of pyridine nucleotide isoenzymes preceded the work by Burton Sobel on the MB isoenzyme in heart. The Vietnam War cut into the funding, and it has actually declined linearly since.
A few years later, I was an Associate Professor at a new Medical School and I submitted a proposal that was reviewed by the Chairman of Pharmacology, who was a former Director of NSF. He thought it was good enough. I was a pathologist and it went to a Biochemistry Review Committee. It was approved, but not funded. The verdict was that I would not be able to carry out the studies needed, and they would have approached it differently. A thousand young investigators are out there now with similar letters. I was told that the Department Chairmen have to build up their faculty. It’s harder now than then. So I filed for and received 3 patents based on my work at the suggestion of my brother-in-law. When I took it to Boehringer-Mannheim, they were actually clueless.