ACC 2003 ANNUAL SESSION HIGHLIGHTS
Valvular heart disease
Thomas M. Bashore, MD, FACC*,* and
Timothy J. Gardner, MD, FACC
* Division of Cardiology, Duke University Medical Center, Durham, North Carolina, USA
Division of Cardiothoracic Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
* Correspondence: Dr. Thomas M. Bashore, Box 3012, Duke University Medical Center, Durham, North Carolina 27710, USA.
thomas.bashore{at}duke.edu
Valvular heart disease was the focus of many exciting presentations at the American College of Cardiology Scientific Sessions in 2003. Traditional concepts related to "degenerative" native and prosthetic valve disease are being challenged, our surgical approaches are improving, and we are beginning to see over the horizon at the possibilities for percutaneous approaches to valve replacement and repair.
The role for cholesterol and inflammation in the development of calcific aortic stenosis (AS) continues to evolve. An estimated 2% to 9% of the elderly have calcific AS (1,2), and they share both similar risk factors with those suffering from atherosclerosis (3,4) and pathophysiologic mechanisms that result in calcification (5). Of the many abstracts investigating this, Fondard et al. (6) presented evidence for an increase in matrix metalloproteins in AS. Matrix metalloproteins are proteolytic enzymes that lead to the degradation of the extracellular matrix; overexpression has been associated with a variety of processes, most notably osteoarthritis (7). That tumor necrosis factor (TNF)-alpha may also be implicated was suggested by Kaden et al. (8). In this latter study, explanted aortic valve cells grown in culture treated with TNF-alpha resulted in an increase in the expression of osteoblast-associated genes and calcification.
There remains hope that medical therapy may slow the progression of, or prevent, AS. A recent editorial in the Journal addresses the issue (9). The AS valvular tissue harbors chronic infiltrations of macrophages, T lymphocytes, low-density lipoproteins, lipoprotein(a), osteopontin (a mediator of calcification), angiotensin-converting enzyme (ACE), and angiotensin II (10). Retrospective studies (11–15) have provided encouraging results regarding the effects of statins. However, in another retrospective echocardiographic study (16), 95 patients with AS on statins were compared with a similar AS cohort not on statins at a mean follow-up of 51 months, and no difference in the rate of change of the valve gradient, aortic valve area, symptoms, or need for aortic valve replacement (AVR) was found between the groups. Because ACE has been identified in AS valvular lesions, Olsen et al. (17) reviewed the effect of losartan compared with atenolol in 960 patients randomized in the Losartan Intervention for Endpoint reduction in hypertension (LIFE) study. Unfortunately, AS progressed regardless of the treatment arm.
There were many interesting surgical presentations regarding valvular disease. What to do with the mitral regurgitation (MR) in patients undergoing isolated AVR was addressed by Diodato et al. (18). In a retrospective echocardiographic review, with a mean follow-up of 16 months after AVR, the MR often persisted regardless of the baseline severity. The authors concluded that even mild to moderate MR should be repaired at the time of AVR, though no other supportive evidence was presented in this regard.
The risk associated with MR surgery in patients undergoing coronary artery bypass graft surgery (CABG) was reviewed using the Society of Thoracic Surgery’s database (19). The 30-day data from 4,137 patients with an ejection fraction  35% and associated MR revealed that mortality for CABG alone was 9.2%. Mortality from CABG plus mitral annuloplasty was 8.4%, CABG plus mitral repair was 7.7%, and CABG plus mitral valve replacement (MVR) was 14.3%. Thus, in these patients, mitral annuloplasty or repair added no additional risk to CABG, but MVR worsened early survival. Longer term follow-up data were not presented.
There remains an interest in novel prosthetic material for valve replacement. In a study of 11 patients undergoing the Ross procedure (20), excellent hemodynamic results using a tissue-engineered valve in the pulmonic position were reported. Four weeks before surgery, forearm or saphenous venous cells were harvested and grown in a tissue laboratory. These cells then seeded a decellularized pulmonary allograft coated with basal membrane glycoproteins. The patients were followed for two years with no evidence for early pulmonary homograft restenosis found.
Finally, Cribier et al. (21) reviewed the data that led to the first human percutaneous AVR reported in 2002 (22) describing two additional patients in whom the procedure had been successful. The valve consisted of three bovine pericardial leaflets mounted into a stainless steel balloon expandable stent. A different approach taking advantage of the valve in the bovine jugular vein has been described by Boudjemline and Bonhoeffer (23).
Percutaneous approaches to MR were the subject of a session with Drs. Pandian and Fitzgerald. They noted that Dr. Jose Candado from Venezuela had successfully performed the first human insertion of a coronary sinus MR reduction device.
In summary, the pathophysiology of what is traditionally considered "degenerative" aortic valve disease remains of great interest. The desperate need for appropriately designed and executed randomized trials to investigate treatment options, such as statins and ACE inhibitors, remains obvious given the mixed results of retrospective trials. When AVR is being performed, the presence of associated MR may warrant concurrent repair. When CABG is performed in patients with poor left ventricular function and MR, mitral repair or annuloplasty does not add to early mortality, but MVR does. Tissue-engineered valves appear promising, at least when used in the pulmonary position in the Ross procedure. And finally, the meetings provided the first glimpse for the attendees at the possibilities for percutaneous valve replacement and repair.
 |
References
|
|---|
1. Lindroos M, Kupari M, Heikkila J, Tilvis R. Prevalence of aortic valve abnormalities in the elderly: an echocardiographic study of a random population sample. J Am Coll Cardiol. 1993;21:1220–1225[Abstract]
2. Stewart BF, Siscovick D, Lind BK, et al. Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study. J Am Coll Cardiol. 1997;29:630–634[Abstract]
3. Otto CM, Kitzman DW, Gersh BJ, Siscovick DS. Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. N Engl J Med. 1999;341:142–147[CrossRef][Medline]
4. Pohle K, Maffert R, Ropers D, et al. Progression of aortic valve calcification: association with coronary atherosclerosis and cardiovascular risk factors. Circulation. 2001;104:1927–1932[Abstract/Free Full Text]
5. Demer LL. Cholesterol in vascular and valvular calcification. Circulation. 2001;104:1881–1883[Free Full Text]
6. Fondard O, Detaint D, Adle H, et al. Matrix remodeling in human aortic valve disease. (abstr)J Am Coll Cardiol. 2003;41(Suppl A):508A
7. Hedbom E, Hauselmann HJ. Molecular aspects of pathogenesis in osteoarthritis: the role of inflammation. Cell Mol Life Sci. 2002;59:45–53[CrossRef][Medline]
8. Kaden JJ, Sarikoc A, Kilic R, Haase KK, Dempfle C-E, Borggrefe M. Tumor necrosis factor alpha induces calcification of aortic valve myofibroblasts. (abstr)J Am Coll Cardiol. 2003;41(Suppl A):507A
9. Pearlman AS. Medical treatment of aortic stenosis: promising, or wishful thinking? J Am Coll Cardiol. 2002;40:1723–1730[Abstract/Free Full Text]
10. O’Brien KD, Shavelle DM, Caulfield MT, et al. Association of angiotensin-converting enzyme with low-density lipoprotein in aortic valvular lesions and in human plasma. Circulation. 2002;106:2224–2230[Abstract/Free Full Text]
11. Aronow WS, Ahn C, Kronzon I, Goldman ME. Association of coronary risk factors and use of statins with progression of mild valvular aortic stenosis in older persons. Am J Cardiol. 2001;88:693–695[CrossRef][Medline]
12. Novaro GM, Tiong IY, Pearce GL, Lauer MS, Sprecher DL, Griffin BP. Effect of hydroxymethylglutaryl coenzyme A reductase inhibitors on the progression of calcific aortic stenosis. Circulation. 2001;104:2205–2209[Abstract/Free Full Text]
13. Bellamy MF, Pellikka PA, Klarich KW, Tajik AJ, Enriquez-Sarano M. Association of cholesterol levels, hydroxymethylglutaryl coenzyme-A reductase inhibitor treatment, and progression of aortic stenosis in the community. J Am Coll Cardiol. 2002;40:1723–1730[Abstract/Free Full Text]
14. Shavelle DM, Takasu J, Budoff MJ, Mao S, Zhao XQ, O’Brien KD. HMG CoA reductase inhibitor (statin) and aortic valve calcium. Lancet. 2002;359:1125–1126[CrossRef][Medline]
15. Pohle K, Maffert R, Ropers D, et al. Progression of aortic valve calcification: association with coronary atherosclerosis and cardiovascular risk factors. Circulation. 2001;104:1927–1932[Abstract/Free Full Text]
16. Antonini-Canterin F, Huang G, Cervesato E, et al. Do statins really slow the progression of aortic valve stenosis? A need for a prospective randomized trial. (abstr)J Am Coll Cardiol. 2003;41(Suppl A):497A
17. Olsen M, Wachtell K, Bella JN, et al. The effect of losartan versus atenolol on aortic valve sclerosis: a LIFE study. (abstr)J Am Coll Cardiol. 2003;41(Suppl A):505A
18. Diodato MD, Moazami N, Moon MR, et al. Does functional mitral regurgitation improve with isolated aortic valve replacement. (abstr)J Am Coll Cardiol. 2003;41(Suppl A):503A
19. Trichon BH, Coombs LP, O’Connor CM, Dullum M, Peterson ED. Outcomes after various surgical strategies for patients with severe ischemic cardiomyopathy and moderate mitral regurgitation. (abstr)J Am Coll Cardiol. 2003;41(Suppl A):504A
20. Dohmen PM, Lembcke A, Dushe S, Hotz H, Konertz W. Up to two year’s performance using a tissue engineered pulmonary graft during the Ross procedure. (abstr)J Am Coll Cardiol. 2003;41(Suppl A):514A
21. Cribier A, Eltchaninoff H, Tron C, et al. Percutaneous implantation of prosthetic heart valves: from animal model to first human implantation in calcific aortic stenosis. (abstr)J Am Coll Cardiol. 2003;41(Suppl A):508A
22. Cribier A, Eltchaninoff H, Bash A, et al. Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis: first human case description. Circulation. 2002;106:3006–3008[Abstract/Free Full Text]
23. Boudjemline Y, Bonhoeffer P. Steps toward percutaneous aortic valve replacement. Circulation. 2002;105:775–778[Abstract/Free Full Text]
This article has been cited by other articles:
|
|
|
|
 
V. Ripamonti, V. Racca, M. G. Calvo, P. Castiglioni, and M. Ferratini
Angiotensin-Converting Enzyme Inhibitors Slow Recovery From Anemia Following Cardiac Surgery
Chest,
July 1, 2006;
130(1):
79 - 84.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
Top
References