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J Am Coll Cardiol, 2005; 45:1025-1030, doi:10.1016/j.jacc.2004.06.081
© 2005 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: VALVULAR HEART DISEASE

Long-term survival and functional results after aortic valve replacement in asymptomatic patients with chronic severe aortic regurgitation and left ventricular dysfunction

Roldano Scognamiglio, MD*, Christian Negut, MD, Monica Palisi, MD, Giuseppe Fasoli, MD and Sergio Dalla-Volta, MD

Division of Cardiology, Department of Clinical and Experimental Medicine, University of Padua Medical School, Padua, Italy

Manuscript received April 14, 2004; accepted June 22, 2004.

* Reprint requests and correspondence: Dr. Roldano Scognamiglio, Cattedra e Divisione di Cardiologia, Policlinico Universitario, via Giustiniani 2, I-35128 Padova, Italy (Email: r.scognamiglio{at}unipd.it).


   Abstract
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 Abstract
Methods
 Results
 Discussion
 References
 
OBJECTIVES: We examined the influence of medical treatment on the results of surgery in terms of long-term survival and functional results in patients with chronic, severe aortic regurgitation (AR).

BACKGROUND: Asymptomatic patients with AR and a reduced left ventricular ejection fraction (LVEF) are at high risk because of a higher-than-expected long-term mortality. The influence of preoperative medical therapy on the outcome after aortic valve replacement (AVR) is not well known.

METHODS: Surgery was indicated for the appearance of a reduced LVEF (<50%). At the time of AVR, there were 134 patients treated with nifedipine (group A), and 132 received no medication (group B).

RESULTS: Operative mortality was similar in the two groups (0.75% vs. 0.76%, p = NS). The LVEF normalized in all of group A, whereas it remained abnormal in 36 group B patients (28%). At 10-year follow-up, LVEF persisted higher in group A (62 ± 5% vs. 48 ± 4%, p < 0.001). Five-year survival was similar in the two groups (94 ± 2% vs. 94 ± 3%, p = NS). Group A showed a 10-year survival not different from expected and significantly higher than that in group B (85 ± 4% vs. 78 ± 5%, p < 0.001), which had a worse survival than expected.

CONCLUSIONS: Unloading treatment with nifedipine in AR allows one to indicate AVR at the appearance of a reduced LVEF with a low operative mortality and an optimal long-term outcome. The concept of surgical correction of AR indicated for reduced LVEF may not be applied to all patients. Indeed, in a large amount of untreated patients, a reduced LVEF preoperatively is not reversed by prompt surgery, indicating irreversible myocardial damage, and 10-year survival is worse than expected.

Abbreviations and Acronyms
  AR = chronic, severe aortic regurgitation
  AVR = aortic valve replacement
  LV = left ventricle/ventricular
  LVEDVI = left ventricular end-diastolic volume index
  LVEF = left ventricular ejection fraction
  LVESVI = left ventricular end-systolic volume index

The decision to recommend operative intervention to the asymptomatic patient with chronic, severe aortic regurgitation (AR) is very difficult because aortic valve replacement (AVR) continues to entail immediate risk, and biologic and mechanical valves still have problems resulting in significant morbidity and mortality. On the other hand, the mortality rate in asymptomatic patients with AR is very low, and surgery does not improve the quality of life. Thus, the indication in asymptomatic patients must be delayed until changes occur that will predict an increased risk of operative or long-term death after AVR.

It is not clear whether the occurrence of a reduced left ventricular ejection fraction (LVEF) in asymptomatic patients with AR represents the right moment to recommend surgery or whether this is a parameter that will predict a less-than-optimal result. The issue of patients with AR after deterioration of LVEF has occurred offers an intriguing clinical and pathophysiologic problem. Particularly, controversies exist about the questions of whether the risks of surgery are too high, and whether any improvement in LVEF and survival can realistically be expected after successful AVR. Several studies support the idea that asymptomatic patients with normal LVEF should undergo surgery without waiting for the development of symptoms or reduced LVEF. This conclusion is based on the demonstration that reduced LVEF has a marked influence on survival after aortic valve replacement (1–5). However, other studies indicate that there is no reliable evidence that early valve replacement is beneficial in asymptomatic patients with normal LVEF (6–9), and in the absence of symptoms, the chief indication is the development of reduced LVEF (5,10–15). Recently, a long-term follow-up study (5) showed that asymptomatic patients with normal LVEF had a 10-year mortality rate not different from expected, whereas those with reduced LVEF constituted a subgroup with excess mortality rates with conservative management. The authors concluded that these patients should be considered at high risk and evaluated for prompt intervention. Unfortunately, data on postoperative survival derived from large series of these patients are not available. Moreover, the effects of medical treatment are largely unknown, because in these studies patients received, in variable proportion, calcium channel blockers, angiotensin-converting enzyme inhibitors, hydralazine, beta-blockers, digoxin, or none of these (1–12). In a previous study, unloading therapy with nifedipine in asymptomatic patients with normal LVEF delayed surgery (indicated by the appearance of reduced LVEF), and all patients responded favorably to aortic valve replacement with normalization of the ejection fraction (16).

The present study prospectively assessed operative mortality, long-term survival, and functional results in asymptomatic patients who underwent AVR after deterioration of LVEF. The effects of a preoperative unloading therapy with nifedipine or the absence of medical therapy were also evaluated.


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Patient selection.   In order to assess the effect of pretreatment unloading therapy on surgical outcome, in the 1980s and during the first half of the 1990s, the policy of the "Valve Heart Disease Unit" of our University randomly assigned asymptomatic patients with AR and normal LVEF to nifedipine unloading therapy or no medical treatment. In both groups of patients, no other cardioactive drugs were administered. At the moment of randomization to nifedipine or no medication, the age was comparable in the two study groups (42 ± 16 years vs. 43 ± 18 years, p = NS). Patients were followed up with a return visit and echocardiographic and color Doppler evaluations every six months. They were enrolled into the present study at the moment of the first appearance of reduced LVEF and then operated on within three months. Left ventricular (LV) dysfunction was defined as a reduced LVEF (<50%) confirmed by an echocardiographic study one month later. Moderately severe (grade III/IV) or severe (grade IV/IV) AR was diagnosed with color flow Doppler echocardiography (17). Exclusion criteria were the following: recent development or worsening of AR (within the preceding six months), diastolic blood pressure above 90 mm Hg, significant (≥50% diameter reduction) stenosis of coronary vessels demonstrated by coronary angiography, mixed aortic stenosis and regurgitation (mean valve gradient ≥20 mm Hg), and evidence of additional valvular or congenital heart disease.

The events and cause of death were established by a review of medical, coroner, and autopsy records and death certificates. To avoid biases due to concomitant diseases able to influence survival, associated co-morbid conditions were summated as a co-morbidity index (18). Informed consent was obtained in all patients, and the study was approved by the ethical committee of our institution.

Echocardiographic analysis.   Two-dimensional echocardiograms were recorded with a Hewlett-Packard (Andover, Massachusetts) ultrasonoscope (Sonos 2500, 4500, or 5500) and a 2.5- or 3.5-MHz or S3 transducer. Left ventricular echocardiograms in the apical four-chamber and parasternal short-axis views in at least three to five cardiac cycles were digitized at end diastole (peak of the R-wave) and at end systole (time when the cavity area was smallest). Each echocardiogram was read by two independent observers who did not know the patient's identity. If the readings differed by 10 ml or more for LV volume, data were analyzed by a third observer. Agreement was achieved by consensus. The degree of interobserver and intraobserver correlation for LV area (r = 0.98 and r = 0.97, respectively) and for LV length (r = 0.98 and r = 0.96, respectively) was reasonable.

The LV volumes were calculated by an ellipsoid biplane area-length method (19); LVEF was calculated as: (LVEDVI – LVESVI)/LVEDVI, where LVEDVI is left ventricular end-diastolic volume index and LVESVI is the left ventricular end-systolic volume index.

Aortic regurgitation was quantified in all patients by mapping of the regurgitant jet into the LV by color Doppler imaging. The severity of regurgitation was graded with use of the ratio of the height of the jet to that of LV outflow tract. The height of the regurgitant jet was measured at its origin, immediately beneath the aortic valve, in the parasternal long-axis view. Ratios >45% were categorized as indicating grade III/IV AR, and those >65% as grade IV/IV AR (17).

Echocardiographic study was repeated at the time of valve replacement, two months thereafter, and every year during follow-up.

Statistical analysis.   All data are expressed as the mean value ± SD. Comparisons of continuous variables in the two groups were made by repeated measures analysis of variance. Within each group, we compared preoperative and postoperative values by means of the paired t test. Long-term survival analysis was carried out using the Kaplan-Meier method, and the two-tailed k-sample log-rank test was used to compare groups. The one-sample log-rank test was used to compare survival with expected survival of the age- and gender-matched 1990s Italian census sample. Generally, the census data do not truly constitute a relevant matched control group, allowing a specific conclusion. To minimize the limits of this approach, we followed this design: background mortality and excess mortality were estimated from life-table data (Central Bureau for Statistics) contemporary to study population recruitment. Life-tables were compiled from the total population stratified by gender, three-year age group, and two-year calendar period; for each period that each patient was observed, mortality was calculated for the same period of the counterpart from the general population (matched with the patient for age, gender, and year of observation). By this method, whenever a patient was lost to follow-up, we withdrew his or her referent from the reference group. This rate adjustment procedure minimizes a lack of comparability at all times to the patient's group. A p value <0.05 by the two-tailed test was considered to indicate statistical significance.


   Results
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Baseline characteristics.   The clinical preoperative characteristics of the 266 patients who met the inclusion criteria are listed in Table 1. Patients were seen at the University of Padua, Italy, and at the moment of diagnosis, 134 patients (group A) had been randomly assigned to treatment with nifedipine and 132 to receive no medications (group B). All patients underwent AVR within three months of the appearance of reduced LVEF. The average duration of presurgical nifedipine therapy was 7.8 years. All patients in group A received nifedipine 20 mg twice daily.


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  		Table 1. Baseline Characteristics of 262 Patients With Chronic, Severe Aortic Regurgitation at the Time of Aortic Valve Replacement According to Study Group
 
Two patients in group A and two patients in group B were excluded from analysis because they did not return for the scheduled follow-up visits. Thus, the long-term analysis was performed in the remaining 262 patients (132 of group A and 130 of group B). The presumed cause of AR was rheumatic in 147 patients, degenerative in 67 patients, endocarditis in 14 patients, aortic valve prolapse in 8 patients, and bicuspid aortic valve in 26 patients, without significant differences between groups (Table 1). Although age was similar at drug treatment randomization in groups A and B, by the time of operation, patients in group A were significantly older, and the duration of disease was longer. Gender, comorbidity index, cardiothoracic ratio, systolic and diastolic blood pressure, and aortic root diameter were similar in the two study groups.

Aortic valve replacement.   All patients received a mechanical prosthesis. The overall operative mortality rate was 0.76% (2 of 262 patients). The operative mortality rate was similar in the two study groups: 0.75% (1 of 132 patients) for group A and 0.76% (1 of 130 patients) for group B (p = NS).

Two patients in group A (after 62 and 68 months) and two in group B (after 64 and 65 months) required re-operation. Operative deaths did not occur in these patients.

Survival at five years was similar in the two study groups: 94 ± 2% for group A and 93 ± 3% for group B patients (p = NS). In group A, these values were not different from expected (94 ± 4%), whereas in group B, five-year survival was worse than expected (95 ± 6%). At 10-year follow up, group A survival was not different from expected (group A: 85 ± 4%, expected 84 ± 5%) and significantly higher than group B (78 ± 5%, p < 0.001), which showed a worse survival than expected (88 ± 8%) (Fig. 1).



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  		Figure 1 Survival of patients with chronic severe aortic regurgitation after surgery according to study group and compared with expected survival (solid triangles = group A patients; open triangles = general population matched with group A; solid squares = group B patients; open squares = general population matched with group B). Survival at five years is similar in the two study groups and is not different from expected survival in group A. Ten-year survival of group A does not differ from expected and is significantly higher than that in group B (p < 0.001). Ten-year survival of group B is worse than expected.

 
Changes in LV dimension and function after AVR.   Group A and B patients had similar preoperative values of LVEDVI, LVESVI, and LVEF (Table 1). Changes in LVEF are shown in Figure 2. After AVR, LVEF increased significantly in both groups: from 46 ± 2% to 64 ± 8% (p < 0.001) in group A and from 45 ± 3% to 59 ± 9% (p < 0.001) in group B. After the procedure, LVEF was higher in group A patients (p < 0.001). In all nifedipine group patients (group A), LVEF returned to normal after AVR, whereas it remained abnormal in 36 patients (28%) who received no medication (group B) before surgery (p < 0.01). At five-year (65 ± 4% vs. 56 ± 8%, p < 0.001) and 10-year follow-up (62 ± 5% vs. 48 ± 4%, p < 0.001), LVEF was persistently higher in group A patients.



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  		Figure 2 Changes in left ventricular ejection fraction (LVEF) after surgical correction of chronic severe aortic regurgitation (solid triangles = group A patients; open triangles = group B patients). Group A and B patients have similar preoperative values (Pre-op). The LVEF is higher in group A patients after the procedure (Post-op) (p < 0.001) and at five-year (p < 0.001) and 10-year follow-up (p < 0.001).

 
Preoperative and follow-up values of LVEDVI are reported in Figure 3. After AVR, there was a decrease in LVEDVI from 148 ± 18 ml/m2 to 84 ± 16 ml/m2 (p < 0.001) in group A and from 149 ± 16 ml/m2 to 96 ± 24 ml/m2 (p < 0.001) in group B patients. After the procedure, significantly higher values of LVEDVI were present in patients of group B (p < 0.001) and persisted at five-year (100 ± 14 ml/m2 vs. 82 ± 14 ml/m2, p < 0.001) and 10-year follow-up study (108 ± 22 ml/m2 vs. 89 ± 12 ml/m2, p < 0.001).



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  		Figure 3 Changes in left ventricular end-diastolic volume index (LVEDVI) after aortic valve replacement in study groups of patients with chronic severe aortic regurgitation (solid squares = group A patients; solid triangles = group B patients). Group A and B patients have similar preoperative (Pre-op) values. After valve replacement, LVEDVI decreases significantly both in group A (p < 0.001) and group B (p < 0.001). After surgery (Post-op), significantly higher values of LVEDVI are present in group B (p < 0.001) and are still present at five-year (p < 0.001) and 10-year follow-up study (p < 0.001).

 

   Discussion
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 Abstract
 Methods
 Results
 Discussion
References
 
There is overwhelming evidence that patients with AR who become symptomatic require prompt AVR. Conversely, asymptomatic patients generally have an excellent prognosis without AVR, and controversies exist about the optimal timing for surgical correction. Severe AR produces a sustained overload on the LV, which compensates by a progressive increase in dimension and hypertrophy, whereas LVEF remains normal. Patients are asymptomatic for a long period of time. The hemodynamic and clinical history of AR is usually characterized by the onset of LV dysfunction (reduced LVEF), symptoms, or both. Numerous investigations (1–16,20–24) over the past three decades have provided important information on the effect of reduced LVEF on the natural history of AR and the results of AVR. Nevertheless, the issue of patients with AR after deterioration of LVEF continues to represent an intriguing clinical and pathophysiologic problem. In this setting, it is important to address the questions of whether the risks of surgery are too high and whether, even after successful AVR, any improvement in LVEF or survival can realistically be expected. The principle that the severity of LV dysfunction has a marked influence on survival after AVR was established in several publications supporting the conclusion that patients with reduced LVEF did much more poorly regarding long-term survival after AVR than those with preserved or normal preoperative LVEF (1,2,13–23). These findings indicated the need for AVR before the development of irreversible myocardial damage. However, other studies showed that there is no reliable evidence that early AVR is of benefit in asymptomatic patients with normal LVEF (3–5,9), and in the absence of symptoms, the chief indication is the development of reduced LVEF (5,10–12,14,15). An important contribution has been the recent demonstration that patients with reduced LVEF have an outcome with conservative management characterized by an excess mortality rate compared with expected mortality (5). The authors concluded that these patients should be considered at high risk and evaluated for prompt surgical intervention. Unfortunately, this study included only a small number of asymptomatic patients with reduced LVEF who underwent AVR, and postsurgical survival for this subgroup is not reported.

Moreover, it has been demonstrated that another factor able to influence the results of AVR after reduced LVEF has been detected is constituted by the medical treatment of patients in the years before. In a previous study (16), surgery was indicated when reproducible evidence of reduced LVEF developed. Unloading treatment with nifedipine exerted a beneficial effect on the natural history of the disorder by reducing the need for AVR. Of greater importance, patients in whom a reduced LVEF developed while they were being treated with nifedipine all responded favorably to AVR and had normalized LVEF.

The results of the present study confirmed that the first appearance of reduced LVEF in asymptomatic patients treated by an unloading therapy with nifedipine is not an irreversible process. All nifedipine-treated patients operated on at the appearance of reduced LVEF had normalized LVEF after AVR, and at 10-year follow-up, LVEF was still normal. In these patients, reduced LVEF presumably occurred without irreversible myocardial contractile damage, and this mechanism may explain the favorable effects of AVR on LVEF and long-term outcome (24–26). At this moment in the natural history of AR, the surgical procedure restores an adequate match between myocardial contractility and LV load by reversing the excessive load imposed by AR. Conversely, in some patients who were not receiving medication, the persistent LV damage after AVR was presumably resulting from irreversible myocardial contractile dysfunction before AVR (24,26). More generally, in these patients not receiving unloading therapy, the presence of myocardial dysfunction, of a different extent, may also explain the progressive postoperative deterioration in LVEF over time and the poor outcome (26,27). Thus, changes in LVEF after AVR might explain the difference in survival: patients treated with unloading therapy before AVR had a significant improvement of long-term survival in comparison to patients receiving no medication, who had a worse-than-expected 10-year survival. It is important to stress that the more advantageous results of surgery occurred despite patients treated with nifedipine being older and the duration of the disease longer, presumably as a result of the capacity of this therapy to delay surgery (16).

Study limitations.   Systolic hypertension is a known risk factor for heart failure, and the risk of systolic hypertension in patients with AR was first demonstrated by Spagnuolo et al. (28). In our study, patients had moderately severe systolic hypertension at the time of operation. As a consequence, the study results do not allow to us advocate the use of nifedipine in patients with AR who are not hypertensive. Nevertheless, this use could possibly be reasonable and appropriate because afterload reduction in AR by nifedipine does not require systolic hypertension.

More than half of our patients in both groups had a rheumatic origin of their AR, and one-quarter had a degenerative origin. Hence, the results of this study are much more pertinent to this AR population and certainly less determinant in patient groups of AR with other causes (percentage of patients in our study: 10% with a bicuspid aortic valve, 5% with endocarditis, and 3% with aortic valve prolapse).

Conclusions.   Unloading therapy with nifedipine in asymptomatic patients with AR represents a pharmacologic strategy capable of delaying the need for surgery by prolonging the asymptomatic period while preserving LVEF. This treatment allows one to indicate AVR at the appearance of reduced LVEF with a low operative mortality and with significant improvement of long-term postoperative survival.

On the other hand, the concept of surgical correction of AR indicated for the appearance of reduced LVEF may not be applied in all patients. In fact, in the absence of an appropriate unloading therapy, reduced LVEF is not reversed by prompt surgery, indicating the presence of irreversible myocardial damage, and the 10-year survival is worse than expected.


   References
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 Abstract
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 References
 

  1. Forman R, Firth BF, Barnard MS. Prognostic significance of preoperative left ventricular ejection fraction and valve lesion in patients with aortic valve replacement Am J Cardiol 1980;45:1120-1125.[CrossRef][ISI][Medline]
  2. Acar J, Michel PL, Luxereau P, et al. How to manage patients with severe left ventricular dysfunction and valvular regurgitation J Heart Valve Dis 1996;5:421-429.[ISI][Medline]
  3. Carabello BA, Usher BW, Hendrix GH, Assey ME, Crawford FA, Leman RB. Predictors of outcome in patients with aortic regurgitation and left ventricular dysfunction J Am Coll Cardiol 1987;10:991-997.[Abstract]
  4. Klodas E, Enriquez-Sarano M, Tajik AJ, et al. Optimizing timing for surgical correction in patients with severe aortic regurgitation: role of symptoms J Am Coll Cardiol 1997;30:746-752.[Abstract]
  5. Dujardin KS, Enriquez-Sarano M, Hartzell V, et al. Mortality and morbidity of aortic regurgitation in clinical practiceA long-term follow-up study. Circulation 1999;99:1851-1857.[Abstract/Free Full Text]
  6. Gaasch WH, Andrias CW, Levine HJ. Chronic aortic regurgitation: the effect of aortic valve replacement on left ventricular volume, mass and function Circulation 1978;58:825-836.[Abstract/Free Full Text]
  7. Henry WL, Bonow RO, Rosing DR, Epstein SE. Observations on the optimum time for operative intervention for aortic regurgitationII: Serial echocardiographic evaluation of asymptomatic patients. Circulation 1980;61:484-492.[Free Full Text]
  8. Scognamiglio R, Fasoli G, Dalla-Volta S. Progression of myocardial dysfunction in asymptomatic patients with severe aortic insufficiency Clin Cardiol 1986;9:151-156.[ISI][Medline]
  9. Rahimtoola SH. Valve replacement should not be performed in all asymptomatic patients with severe aortic incompetence J Thorac Cardiovasc Surg 1980;79:163-172.[ISI][Medline]
  10. Bonow RO, Rosing DR, McIntosh CL, et al. The natural history of asymptomatic patients with aortic regurgitation and normal left ventricular function Circulation 1983;68:509-517.[Free Full Text]
  11. Bonow RO, Epstein SE. Is preoperative left ventricular function predictive of survival and functional results after aortic valve replacement for chronic aortic regurgitation? J Am Coll Cardiol 1987;10:713-716.[ISI][Medline]
  12. Bonow RO, Doss JT, Maron BJ, et al. Long-term serial changes in left ventricular function and reversal of ventricular dilatation after valve replacement for chronic aortic regurgitation Circulation 1988;78:1108-1120.[Abstract/Free Full Text]
  13. Henry WL, Bonow RO, Borer RJ, et al. Observations on the optimum time for operative intervention for aortic regurgitationI: Evaluation of the results of aortic valve replacement in asymptomatic patients. Circulation 1980;61:471-483.[Abstract/Free Full Text]
  14. Bonow RO, Carabello B, de Leon AC, et al. The ACC/AHA guidelines for the management of patients with valvular heart disease J Am Coll Cardiol 1998;32:1486-1588.[Free Full Text]
  15. Iung B, Gohlke-Barwolf C, Tornos P, et al. Recommendations on the management of the asymptomatic patient with valvular heart disease Eur Heart J 2002;23:1253-1266.[Free Full Text]
  16. Scognamiglio R, Rahimtoola SH, Fasoli G, Nistri S, Dalla-Volta S. Nifedipine in asymptomatic patients with severe aortic regurgitation and normal left ventricular function N Engl J Med 1994;331:689-694.[Abstract/Free Full Text]
  17. Perry GJ, Helmcke F, Nanda NC, Byard C, Soto B. Evaluation of aortic insufficiency by Doppler color flow mapping J Am Coll Cardiol 1987;9:952-959.[Abstract]
  18. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies J Chronic Dis 1987;40:373-383.[CrossRef][ISI][Medline]
  19. Hela JW, Reichek N. Quantitation of human left ventricular mass and volume by two-dimensional echocardiography: in vitro anatomic validation Circulation 1981;63:1398-1407.[Free Full Text]
  20. Gault JH, Covell JW, Braunwald E, Ross Jr J. Left ventricular performance following correction of free aortic regurgitation Circulation 1970;42:773-780.[Abstract/Free Full Text]
  21. Clark DG, McAnulty JH, Rahimtoola SH. Valve replacement in aortic insufficiency with left ventricular dysfunction Circulation 1980;61:411-421.[Free Full Text]
  22. Greves J, Rahimtoola SH, McAnulty SH. Preoperative criteria predictive of late survival following valve replacement for severe aortic regurgitation Am Heart J 1981;101:300-308.[CrossRef][ISI][Medline]
  23. Bonow RO, Picone AI, McIntosh CL, et al. Survival and functional results after valve replacement for aortic regurgitation from 1976 to 1983: impact of preoperative left ventricular function Circulation 1985;72:1244-1256.[Abstract/Free Full Text]
  24. Gaasch WH, Carroll JD, Levine HJ, Criscitiello MG. Chronic aortic regurgitation: prognostic value of left ventricular end-systolic dimension and end-diastolic radius/thickness ratio J Am Coll Cardiol 1983;1:775-782.[Abstract]
  25. Starling MR, Kirsh MM, Montgomery DG, Gross MD. Mechanisms for left ventricular systolic dysfunction in aortic regurgitation: importance for predicting the functional response to aortic valve replacement J Am Coll Cardiol 1991;17:887-897.[Abstract]
  26. Borer JS, Hochreiter C, Herrold EM, et al. Prediction of indications for valve replacement among asymptomatic or minimally symptomatic patients with chronic aortic regurgitation and normal left ventricular function Circulation 1998;97:525-534.[Abstract/Free Full Text]
  27. Chaliki HP, Mohty D, Avierinos JF, et al. Outcomes after aortic valve replacement in patients with severe aortic regurgitation and markedly reduced left ventricular function Circulation 2002;106:2687-2693.[Abstract/Free Full Text]
  28. Spagnuolo M, Kloth H, Taranta A, Doyle E, Pasternack B. Natural history of rheumatic aortic regurgitation: criteria predictive of death, congestive heart failure, and angina in young patients Circulation 1971;44:368-380.[Abstract/Free Full Text]



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