HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Varadarajan, P. Articles by Pai, R. G. Search for Related Content PubMed PubMed Citation Articles by Varadarajan, P. Articles by Pai, R. G. Related Collections Valve disease Related Articles

Ann Thorac Surg 2006;82:2111-2115
© 2006 The Society of Thoracic Surgeons

---

Original Articles: Cardiovascular

Clinical Profile and Natural History of 453 Nonsurgically Managed Patients With Severe Aortic Stenosis

Division of Cardiology, Loma Linda University Medical Center, Loma Linda, California

Accepted for publication July 6, 2006.

^_* Address correspondence to Dr Pai, Division of Cardiology, USC/Keck School of Medicine, 1510 San Pablo St, Suite 322, Los Angeles, CA 90033. (Email: rpai{at}usc.edu).

	Abstract

Top Abstract Introduction Patients and Methods Results Comment References

 
BACKGROUND: Severe aortic stenosis (AS) is a surgically correctable condition. However, aortic valve replacement (AVR) is not offered to many patients with severe AS for various reasons. We investigated the profile and survival patterns of patients with severe AS who did not have AVR.

METHODS: Our echocardiographic database was screened for patients with severe AS, defined as a Doppler estimated aortic valve area of 0.8 cm² or less between 1993 and 2003. Seven hundred and forty patients with severe AS were identified, of whom 453 patients had no AVR through the follow-up period, forming the study cohort. These patients were comprehensively characterized by obtaining clinical, pharmacologic, and surgical data through a comprehensive chart review and extracting survival data from the National Death Index.

RESULTS: Patient characteristics were as follows: age 75 ± 13 years, 48% male, left ventricular (LV) ejection fraction 52 ± 21%, coronary artery disease in 34%, hypertension in 35%, serum creatinine level greater than 2 mg/dL in 11%, and diabetes mellitus in 14%. The survival at 1 year, 5 years, and 10 years was 62%, 32%, and 18%, respectively. The univariate predictors of reduced survival were advanced age, low LV ejection fraction, heart failure, elevated serum creatinine level, severe mitral regurgitation, and pulmonary hypertension; and the independent predictors were advanced age, low LV ejection fraction, heart failure, elevated serum creatinine level, and systemic hypertension. Concomitant pharmacotherapy had no impact on survival.

CONCLUSIONS: Conservatively treated patients with severe AS have a grave prognosis, and it is worse in the presence of advanced age, LV dysfunction, heart failure, and renal failure.

	Introduction

Top Abstract Introduction Patients and Methods Results Comment References

 
Aortic stenosis (AS) is common with aging and is the most common valve condition for which aortic valve replacement (AVR) is performed in the United States. Standard indications for AVR include severe AS in the presence of symptoms such as exertional chest pain, syncope, and dyspnea [1]. Once these symptoms develop, the average survival is 5, 3, and 2 years, respectively [2]. After symptoms develop, the only effective therapy is AVR. Aortic valve replacement is not offered to many of the patients with severe AS for reasons such as "lack of symptoms" or patient refusal or when surgery is deemed to entail high risk. Studies have reported a dismal prognosis for severe AS patients managed nonsurgically [3–5]. However, these studies included small numbers of patients (n = 13 to 55), and the natural history of medically managed patients with severe AS in the modern era is unclear.

The goal of this study was to characterize the survival of nonsurgically managed patients with severe AS, and to identify the variables that affect prognosis in these patients.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment References

 
Patient Population
This is a retrospective cohort study from a large university medical center. This study was approved by our Institutional Review Board. Informed consent was waived by our Institutional Review Board owing to the retrospective nature of our study.

Our echocardiographic database was searched for patients with severe aortic stenosis defined as a valve area of 0.8 cm² or less. This yielded a total of 740 patients. Complete clinical, echocardiographic, and pharmacologic data were compiled on these patients from comprehensive chart review. During the follow-up, 287 patients had AVR, and 453 patients did not undergo AVR for various reasons. The latter group formed the study cohort. Although precise reasons for lack of surgical therapy were difficult to establish from chart review, the predominant reasons included lack of symptoms, patient refusal, and high estimated surgical risk. Decision for AVR was made by treating physicians in conjunction with the patients and not by the investigators. Mean duration of follow-up for patients with AVR was 3.8 years, and for those without AVR it was 1.5 years; the short duration of follow-up for the no AVR group principally is due to a high short-term mortality rate. Of the 453 patients who did not undergo AVR, 102 patients had follow-up echocardiograms after a mean of 1.6 years.

Clinical Variables
Hypertension was defined as blood pressure greater than 130/90 mm Hg or a history of hypertension and being on antihypertensive medications. Diabetes mellitus was defined as fasting blood sugar greater than 125 mg/dL or being on a regimen of antidiabetic agents. Renal insufficiency was defined as serum creatinine of 2 mg/dL or greater. Coronary artery disease was deemed to be present if any of the following were present: a history of angina pectoris, myocardial infarction, a positive stress test, angiographic evidence of coronary artery disease, coronary intervention, coronary artery bypass surgery, or presence of significant Q waves on the surface electrocardiogram. In the absence of angiographic data on all patients, it is likely that the prevalence of coronary artery disease could be underestimated.

Pharmacologic Data
Pharmacotherapy at the time of echocardiography was recorded. This was broadly categorized into ß-blockers, calcium-channel blockers, diuretics, angiotensin-converting enzyme inhibitors, digoxin, and statins.

Echocardiographic Data
All patients had standard two-dimensional echocardiographic examinations. Left ventricular (LV) ejection fraction was assessed visually by a level 3 trained echocardiographer and entered into a database at the time of the examination. That has been proved to be reliable and has been validated against contrast and radionuclide LV angiography [6, 7]. Anatomic and Doppler examinations and measurements were performed according to the recommendations of the American Society of Echocardiography [8]. Severe pulmonary hypertension was defined as a pulmonary artery systolic pressure of 60 mm Hg or greater.

Mortality Data
The endpoint of the study was all-cause mortality. Mortality data were obtained from the National Death Index using the social security numbers.

Statistical Analysis
All the data were initially entered into Microsoft Excel program. The data were then imported into Stat View 5.01 (SAS Institute, Cary, North Carolina) program for statistical analysis. Kaplan-Meier survival curves were computed for patients with and without AVR and were compared using the log-rank statistic. Characteristics of patients with and without AVR were compared using the Student t test for continuous variables and the ² test for categorical variables. A logistic regression model was used to adjust for the effect of group difference on survival. A p value of 0.05 or less was considered significant.

	Results

Top Abstract Introduction Patients and Methods Results Comment References

 
Baseline Patient Characteristics
The baseline features of patients are summarized in Table 1. In brief, the age was 75 ± 13 years, 48% were males, LV ejection fraction was 52% ± 21%, coronary artery disease was present in 34%, hypertension in 35%, serum creatinine level greater than 2 mg/dL in 11%, and diabetes mellitus in 14%. The LV ejection fraction was 40% or less in 35%, 30% or less in 24%, and 20% or less in 12%. Forty-five percent of the patients were 80 years or older, 47% had symptoms in the form of chest pain (10%) or dyspnea (42%), 11% had a prior stroke, and 18% had a pulmonary artery systolic pressure of 60 mm Hg or greater, indicating severe pulmonary hypertension.

View larger version (21K): [in this window] [in a new window]   Fig 1. (A–G) Kaplan-Meier survival curves in conservatively treated severe aortic stenosis patients stratified by age, ejection fraction (EF), congestive heart failure (CHF), chronic renal insufficiency (CRI), severe pulmonary artery hypertension (PASP), and severe mitral regurgitation (MR).

Cox Proportional Hazard
All variables significant on univariate analysis were entered into Cox proportional hazard model for the prediction of survival (Tables 3 and 4). Using this, age, presence of severe pulmonary hypertension, LV ejection fraction, and chronic obstructive pulmonary disease were independent predictors of survival. Only 315 patients had measurable tricuspid regurgitation velocities for estimation of pulmonary artery pressure. When all patients were included in the model (hence, excluding pulmonary artery pressure as a predictor variable), age, LV ejection fraction, congestive heart failure, chronic obstructive pulmonary disease, and hypertension emerged as independent predictors of survival.

	Comment

Top Abstract Introduction Patients and Methods Results Comment References

 
Our study confirms that severe AS, left untreated surgically, carries a dismal prognosis. Our series is larger than all the other reported series and has additional comprehensive echocardiographic and pharmacologic data that have potential prognostic implications.

Comparison With Other Studies
Chizner and colleagues [3] reported poor survival in their study of 42 patients with severe or moderate stenosis (32 symptomatic), who underwent cardiac catheterization and did not undergo early valve surgery. Mortality rates from onset of symptoms were 26% at 1 year, 48% at 2 years, and 57% at 3 years. Fifty-six percent of deaths occurred suddenly, within hours of new symptoms. Horstkotte and colleagues [4] showed a dismal prognosis for patients with severe AS. In their study, 55 patients with severe AS who had refused aortic valve replacement had a mean average survival of 23 months, and the 5-year probability of survival was 18% [4]. All these patients had died within 12 years of observation. Livanainen and colleagues [5] showed severe AS (n = 13) predicted a fourfold to sixfold relative risk for death even after adjustment for age, sex, and LV measurements. The 4-year survival in this study in severe AS, medically treated, was 24%. The mortality rate in this study in patients with severe AS started to increase after 18 months of follow-up. The 5-year mortality rate in these studies in patients with severe AS ranged between 18% and 50% [3–5]. Our study, comprising a large number of well-characterized, conservatively managed severe AS patients, revealed a dismal 5-year survival of 32%, which is similar to the other studies. In addition, our study identifies subgroups who are at higher risk of intermediate term mortality.

Reasons for Nonsurgical Management
Reasons for nonsurgical management were difficult to establish in many of the patients in view of the retrospective study nature. Some of the prominent reasons included lack of symptoms, patient refusal, high surgical risk, and noncardiac comorbidities such as stroke, dementia, and physical debility.

Predictors of Survival in Nonsurgically Managed Patients
Not surprisingly, advanced age, low ejection fraction, presence of heart failure, and renal failure were predictors of reduced survival. Although many of these patients had coronary artery disease, treatment with aspirin or statins did not improve survival, possibly indicating the overriding negative impact of severe AS on survival. Beta-blockers can potentially reduce the risk of atrial fibrillation or ventricular arrhythmias, but in this cohort did not affect survival. Although 35% of the patients had an ejection fraction less than 40%, neither the ß-blockers nor the angiotensin-converting enzyme inhibitors improved survival, either in the whole cohort or in the subset with reduced ejection fraction.

In conclusion, patients with severe AS have a dismal prognosis when managed conservatively. The mortality rate is increased with age, heart failure, and renal insufficiency. Medical therapy with ß-blockers, angiotensin-converting enzyme inhibitors, or statins does not seem to affect survival in the entire group of conservatively treated patients with severe AS.

	References

Top Abstract Introduction Patients and Methods Results Comment References

 

1. Bonow RO, Carabello B, de Leon Jr AC. Guidelines for the management of patients with valvular heart disease: executive summaryA report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients with Valvular Heart Disease). Circulation 1998;98:1949-1984.[Free Full Text]
2. Ross J, Braumwald E. Aortic stenosis Circulation 1968;38(Suppl 5):61-67.[Medline]
3. Chizner MA, Pearle DL, deLeon Jr AC. The natural history of aortic stenosis in adults Am Heart J 1980;99:419-424.[Medline]
4. Horstkotte D, Loogen F. The natural history of aortic stenosis Eur Heart J 1988;9(Suppl E):57-64.
5. Livanainen AM, Lindroos M, Tilvis R, Heikkila J, Kupari M. Natural history of aortic valve stenosis of varying severity in the elderly Am J Cardiol 1996;78:97-101.[Medline]
6. van Royen N, Jaffe CC, Krumholz HM, et al. Comparison and reproducibility of visual echocardiographic and quantitative radionuclide left ventricular ejection fractions Am J Cardiol 1996;77:843-850.[Medline]
7. Amico AF, Lichtenberg GS, Reisner SA, Stone CK, Schwartz RG, Meltzer RS. Superiority of visual versus computerized echocardiographic estimation of radionuclide left ventricular ejection fraction Am Heart J 1989;118:1259-1265.[Medline]
8. Schiller NB, Shah PM, Crawford M, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography J Am Soc Echocardiogr 1989;2:358-367.[Medline]

This article has been cited by other articles:

				B. Zingone, G. Gatti, E. Rauber, P. Tiziani, L. Dreas, A. Pappalardo, B. Benussi, and A. Spina Early and Late Outcomes of Cardiac Surgery in Octogenarians Ann. Thorac. Surg., January 1, 2009; 87(1): 71 - 78. [Abstract] [Full Text] [PDF]

				R. G. Pai, P. Varadarajan, and A. Razzouk Survival Benefit of Aortic Valve Replacement in Patients With Severe Aortic Stenosis With Low Ejection Fraction And Low Gradient With Normal Ejection Fraction. Ann. Thorac. Surg., December 1, 2008; 86(6): 1781 - 1789. [Abstract] [Full Text] [PDF]

				E. Grube, L. Buellesfeld, R. Mueller, B. Sauren, B. Zickmann, D. Nair, H. Beucher, T. Felderhoff, S. Iversen, and U. Gerckens Progress and Current Status of Percutaneous Aortic Valve Replacement: Results of Three Device Generations of the CoreValve Revalving System Circ Cardiovasc Intervent, December 1, 2008; 1(3): 167 - 175. [Abstract] [Full Text] [PDF]

				L. G. SVENSSON Evolution and results of aortic valve surgery, and a 'disruptive' technology Cleveland Clinic Journal of Medicine, November 1, 2008; 75(11): 802 - 804. [Full Text] [PDF]

				T. M. Dewey, D. L. Brown, T. S. Das, W. H. Ryan, J. E. Fowler, S. D. Hoffman, S. L. Prince, M. A. Herbert, D. Culica, and M. J. Mack High-risk patients referred for transcatheter aortic valve implantation: management and outcomes. Ann. Thorac. Surg., November 1, 2008; 86(5): 1450 - 1457. [Abstract] [Full Text] [PDF]

				J. S. Gammie, L. S. Krowsoski, J. M. Brown, P. N. Odonkor, C. A. Young, M. J. Santos, J. S. Gottdiener, and B. P. Griffith Aortic Valve Bypass Surgery: Midterm Clinical Outcomes in a High-Risk Aortic Stenosis Population Circulation, September 30, 2008; 118(14): 1460 - 1466. [Abstract] [Full Text] [PDF]

				L. G. Svensson, T. Dewey, S. Kapadia, E. E. Roselli, A. Stewart, M. Williams, W. N. Anderson, D. Brown, M. Leon, B. Lytle, et al. United States feasibility study of transcatheter insertion of a stented aortic valve by the left ventricular apex. Ann. Thorac. Surg., July 1, 2008; 86(1): 46 - 55. [Abstract] [Full Text] [PDF]

				F. Maisano, I. Michev, P. Denti, O. Alfieri, and A. Colombo Transfemoral transcatheter aortic valve implantation using the balloon expandable SAPIEN transcatheter heart valve device MMCTS, June 26, 2008; 2008(0626): 3087. [Abstract] [Full Text] [PDF]

				T. Walther, V. Falk, J. Kempfert, M. A. Borger, J. Fassl, M. W.A. Chu, G. Schuler, and F. W. Mohr Transapical minimally invasive aortic valve implantation; the initial 50 patients Eur. J. Cardiothorac. Surg., June 1, 2008; 33(6): 983 - 988. [Abstract] [Full Text] [PDF]

				T. K. Rosengart, T. Feldman, M. A. Borger, T. A. Vassiliades Jr, A. M. Gillinov, K. J. Hoercher, A. Vahanian, R. O. Bonow, and W. O'Neill Percutaneous and Minimally Invasive Valve Procedures: A Scientific Statement From the American Heart Association Council on Cardiovascular Surgery and Anesthesia, Council on Clinical Cardiology, Functional Genomics and Translational Biology Interdisciplinary Working Group, and Quality of Care and Outcomes Research Interdisciplinary Working Group Circulation, April 1, 2008; 117(13): 1750 - 1767. [Abstract] [Full Text] [PDF]

				T. M. Dewey, D. Brown, W. H. Ryan, M. A. Herbert, S. L. Prince, and M. J. Mack Reliability of risk algorithms in predicting early and late operative outcomes in high-risk patients undergoing aortic valve replacement J. Thorac. Cardiovasc. Surg., January 1, 2008; 135(1): 180 - 187. [Abstract] [Full Text] [PDF]

				T. Feldman and M. B. Leon Prospects for Percutaneous Valve Therapies Circulation, December 11, 2007; 116(24): 2866 - 2877. [Full Text] [PDF]

				J. G. Webb, S. Pasupati, K. Humphries, C. Thompson, L. Altwegg, R. Moss, A. Sinhal, R. G. Carere, B. Munt, D. Ricci, et al. Percutaneous Transarterial Aortic Valve Replacement in Selected High-Risk Patients With Aortic Stenosis Circulation, August 14, 2007; 116(7): 755 - 763. [Abstract] [Full Text] [PDF]

				R. G. Pai, P. Varadarajan, N. Kapoor, and R. C. Bansal Aortic Valve Replacement Improves Survival in Severe Aortic Stenosis Associated With Severe Pulmonary Hypertension Ann. Thorac. Surg., July 1, 2007; 84(1): 80 - 85. [Abstract] [Full Text] [PDF]

				S. Large Invited commentary Ann. Thorac. Surg., December 1, 2006; 82(6): 2115 - 2115. [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Varadarajan, P. Articles by Pai, R. G. Search for Related Content PubMed PubMed Citation Articles by Varadarajan, P. Articles by Pai, R. G. Related Collections Valve disease Related Articles