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CLINICAL RESEARCH: VALVULAR HEART DISEASE

Usefulness of the Valvuloarterial Impedance to Predict Adverse Outcome in Asymptomatic Aortic Stenosis

Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Department of Medicine, Laval University, Québec City, Québec, Canada

Manuscript received December 2, 2008; revised manuscript received March 20, 2009, accepted April 21, 2009.

^_* Reprint requests and correspondence: Dr. Jean G. Dumesnil or Dr. Philippe Pibarot, Québec Heart and Lung Institute, 2725 Chemin Sainte-Foy, Québec City, Québec G1V 4G5, Canada (Email: jean.dumesnil{at}med.ulaval.ca).

	Abstract

Top Abstract Methods Results Discussion Conclusions References

 
Objectives: This study was designed to examine the prognostic value of valvuloarterial impedance (Z_va) in patients with aortic stenosis (AS).

Background: We previously showed that the Z_va is superior to standard indexes of AS severity in estimating the global hemodynamic load faced by the left ventricle (LV) and predicting the occurrence of LV dysfunction. This index is calculated by dividing the estimated LV systolic pressure (systolic arterial pressure + mean transvalvular gradient) by the stroke volume indexed for the body surface area.

Methods: We retrospectively analyzed the clinical and echocardiographic data of 544 consecutive patients having at least moderate AS (aortic jet velocity 2.5 m·s^–1) and no symptoms at baseline. The primary end point for this study was the overall mortality regardless of the realization of aortic valve replacement (AVR).

Results: Four-year survival was significantly (p < 0.001) lower in the patients with a baseline Z_va 4.5 mm Hg·ml^–1·m² (65 ± 5%) compared with those with Z_va between 3.5 and 4.5 mm Hg·ml^–1·m² (78 ± 4%) and those with Z_va 3.5 mm Hg·ml^–1·m² (88 ± 3%). The risk of mortality was increased by 2.76-fold in patients with Z_va 4.5 mm Hg·ml^–1·m² and by 2.30-fold in those with a Z_va between 3.5 and 4.5 mm Hg·ml^–1·m² after adjusting for other risk factors and type of treatment (surgical vs. medical).

Conclusions: Increased Z_va is a marker of excessive LV hemodynamic load, and a value >3.5 successfully identifies patients with a poor outcome. These findings suggest that beyond standard indexes of stenosis severity, the consideration of Z_va may be useful to improve risk stratification and clinical decision making in patients with AS.

Key Words: aortic valve • aortic stenosis • hypertension • arterial compliance • mortality

Abbreviations and Acronyms   AS = aortic stenosis   AVA = aortic valve area   AVR = aortic valve replacement   CABG = coronary artery bypass graft   CI = confidence interval   ELI = energy loss index   LV = left ventricle/ventricular   LVEF = left ventricular ejection fraction   PP = pulse pressure   SV = stroke volume   SVI = stroke volume index   Zva = valvuloarterial impedance

	Methods

Top Abstract Methods Results Discussion Conclusions References

 
Patient population.   We retrospectively reviewed the clinical and echocardiographic data that were prospectively collected in 544 asymptomatic patients (320 men and 224 women; mean age 70 ± 14 years; range 21 to 98 years) with at least a moderate AS, defined as peak aortic jet velocity 2.5 m·s^–1. The exclusion criteria were concomitant moderate or severe aortic insufficiency or mitral valve disease, left ventricular ejection fraction (LVEF) <50%, and the presence of symptoms at baseline.

Clinical data.   Clinical data included age, sex, history of smoking, documented diagnosis of hypertension, hypercholesterolemia, diabetes, obesity (body mass index 30 kg/m²), and coronary heart disease (5).

Systemic arterial hemodynamics.   Systemic arterial pressure was measured with the use of an arm cuff sphygmomanometer at the same time as the Doppler measurement of stroke volume (SV) was measured in the left ventricular outflow tract. The ratio of SVI to brachial pulse pressure (PP) was used as an indirect measure of total systemic arterial compliance: SAC = SVI/PP (1). The systemic vascular resistance was estimated by the formula: SVR = (80 x MAP)/CO, where MAP is the mean arterial pressure defined as diastolic pressure plus one-third of PP and CO is the cardiac output.

Doppler echocardiographic data.   Aortic Valve Stenosis Severity
The Doppler echocardiographic indexes of AS severity included: the mean transvalvular pressure gradient obtained with the use of the modified Bernoulli equation, the AVA obtained with the use of the standard continuity equation, and the energy loss index (ELI) as previously described in Garcia et al. (6). Severe AS was defined as an AVA 1.0 cm².

LV Geometry
Two-dimensionally directed LV M-mode dimensions were measured in the left parasternal long-axis view following the recommendations of the American Society of Echocardiography. Left ventricular minor axis internal dimension (LVID), posterior wall thickness (PWT), and interventricular septal thickness (IVST) were measured at end-diastole (d). The LV mass was calculated using the corrected formula of the American Society of Echocardiography and was indexed for body surface area. Significant LV hypertrophy was defined as LV mass index >134 g/m² in men and >110 g/m² in women. The relative wall thickness (RWT) was calculated with the formula: RWT = (PWTd + IVSTd)/LVIDd.

LV Systolic Function
Diastolic function was assessed as previously described (7). The LVEF was determined in all patients using the Quinones method, the Dumesnil method (8), and visual estimate. In the case of a disagreement among these methods, the reviewing cardiologist selected the value that seemed the most representative.

Global LV Hemodynamic Load
As a measure of global LV load, we calculated the valvuloarterial impedance: Z_va = (SAP + MG)/SVI, where SAP is the systolic arterial pressure and MG is the mean transvalvular pressure gradient (1). Hence, Z_va represents the valvular and arterial factors that oppose ventricular ejection by absorbing the mechanical energy developed by the LV.

Clinical outcomes.   The primary end point for this study was overall death regardless of whether or not there was aortic valve replacement (AVR). Hence, this includes the deaths occurring in patients who did not undergo AVR as well as those occurring after operation in patients who underwent AVR. The outcome data were retrospectively obtained from patients' charts or death certificates.

Statistical analysis.   We subdivided the patients into 3 groups according to the level of Z_va: 1) Z_va 3.5 mm Hg·ml^–1·m² (low Z_va group, n = 172; 32%); 2) 3.5 < Z_va <4.5 mm Hg·ml^–1·m² (medium Z_va group, n = 192; 35%); and 3) Z_va 4.5 mm Hg·ml^–1·m² (high Z_va group, n = 180, 33%). These 3 groups correspond approximately to the tertiles of Z_va.

Continuous data were expressed as mean ± SD and compared among the 3 Z_va groups using a 1-way analysis of variance followed by a Tukey test. Categorical data were given as a percentage and compared with a chi-square test. Cumulative probability of survival was estimated with the Kaplan-Meier method and compared between groups using a log-rank test. The survival observed in these groups was also compared with that of the general population in the Québec province matched for age and sex. The survival data of this control population were derived from the 2002 life tables of Canada Statistics. The effect of the clinical and Doppler echocardiographic variables on survival was assessed with the use of a Cox proportional hazards model. All of the variables presented in Tables 1, 2, and 3 as well as the type of treatment (medical vs. surgical, i.e., AVR) were tested in univariate analysis, and those with a p value <0.20 on univariate analysis were incorporated into the multivariate models. Age was forced into the model. To avoid colinearity among a subset of several variables measuring the same phenomenon (e.g., AVA, peak gradient, mean gradient, ELI), we entered in the multivariate models the variable that had the strongest association with mortality on univariate analysis. We constructed a first series of multivariate models with independent variables entered in continuous format and then a second series with these variables entered in dichotomous formats.

	Results

Top Abstract Methods Results Discussion Conclusions References

Table 2 shows the data of the Doppler echocardiographic and systemic arterial indexes reflecting the valvular load (i.e., AS severity) and the arterial load. As expected, patients with high Z_va had a higher valvular load, that is, more severe valvular stenosis, as reflected by smaller AVA and ELI and higher transvalvular gradients compared with patients with medium or low Z_va (Fig. 1). Patients with medium Z_va also had significantly smaller AVA but similar gradients compared with patients with low Z_va. Patients with higher levels of Z_va also had a higher vascular load as reflected by reduced systemic arterial compliance, increased systemic vascular resistance, and higher systolic and diastolic arterial pressures.

View larger version (41K): [in this window] [in a new window] [Download PPT slide]   Figure 1 Distribution of Stenosis Severity and Paradoxical Low-Flow Pattern Versus Zva Percentage of patients with moderate versus severe aortic stenosis (AS) (A) and with normal flow (NF) versus paradoxical low flow (PLF) (B) according to the level of valvuloarterial impedance (Zva) (low Zva 3.5, moderate 3.5 <Zva <4.5, high Zva 4.5). The numbers in the bars are percentages.

Moreover, as shown in Figure 1, the proportion of patients with a paradoxical low flow pattern, defined as stoke volume index 35 ml·m^{– 2} in the setting of LVEF 50%, was much higher (p < 0.001) in the high Z_va group (n = 90, 50%) than that in the medium Z_va group (n = 28, 15%) or in the low Z_va group (n = 7, 4%), which is consistent with our previous study showing that patients with paradoxical low flow are characterized by a markedly increased Z_va (5). Hence, among the 125 patients with paradoxical low flow, 90 (72%) had a high Z_va, and of these patients 74 (82%) had a severe AS.

Type of treatment.   Aortic valve replacement was performed during follow-up in 54 (31%) patients in the low Z_va group, 58 (30%) in the medium Z_va group, and 64 (36%) in the high Z_va group. Coronary artery bypass grafting (CABG) was performed concomitantly in 75 of 176 (43%) patients. Among the 176 patients undergoing AVR, 166 (94%) had severe AS at the time of operation (67 of these patients underwent CABG) and 10 (6%) had moderate AS (8 underwent CABG).

Clinical outcome.   The mean follow-up time in the total cohort was 2.5 ± 1.8 years (median 2.1 years). The follow-up was complete in all patients, and there was no significant difference between groups with regard to the duration of follow-up.

Overall, there were 91 deaths: 15 (9%) in the low Z_va group, 36 (19%) in the medium Z_va group, and 40 (22%) in high Z_va group. Among them 51 (56%) were from a cardiovascular cause: 7 (4%) in low Z_va group, 19 (10%) in the medium Z_va group, and 25 (14%) in the high Z_va group. Seventy-eight of the 91 deaths occurred in patients treated medically, whereas 13 occurred after AVR. Six of these post-operative deaths occurred in the early post-operative period (<30 days).

Four-year survival was significantly (p < 0.001) lower in the high Z_va group (65 ± 5%) than in the medium (78 ± 4%) and low (88 ± 3%) Z_va groups. Survival was also significantly (p = 0.007) lower in the patients with medium Z_va compared with those with low Z_va (Fig. 2). Patients with low Z_va had similar survival compared with that of the general population in Quebec, whereas patients in the medium and high Z_va groups had lower (p < 0.05) survival than in this control population.

View larger version (14K): [in this window] [in a new window] [Download PPT slide]   Figure 2 Overall Survival Versus Zva Overall survival as a function of the level of valvuloarterial impedance (Zva) (low Zva 3.5 [green line], moderate 3.5 < Zva <4.5 [blue line], high Zva 4.5 [red line]). Survival was compared with that in the general population in Quebec matched for age and sex (control group; black line).

View larger version (20K): [in this window] [in a new window] [Download PPT slide]   Figure 3 Overall Survival Versus Zva and Type of Treatment Overall survival as a function of the level of valvuloarterial impedance (Zva) (low Zva 3.5 [green lines], moderate 3.5 < Zva <4.5 [blue lines], high Zva 4.5 [red lines]) and the type of treatment: medical (solid lines) versus surgical (dashed lines). Survival was compared with that in the general population in Quebec matched for age and sex (control group; black line).

	Discussion

Top Abstract Methods Results Discussion Conclusions References

The valvuloarterial impedance provides an estimate of the global LV hemodynamic load that results from the summation of the valvular and vascular loads, and the concept is very useful because it incorporates stenosis severity, volume flow rate, body size, and systemic vascular resistance. Moreover, Z_va can easily be calculated using Doppler echocardiography from 3 simple measurements, that is, the SVI in the LV outflow tract, the transvalvular mean gradient, and systolic arterial pressure, and as previously shown (1), it is superior to the standard indexes of AS severity in predicting LV dysfunction. These results have been independently corroborated by a substudy of the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) trial (9), in which increased Z_va was a powerful independent predictor of myocardial systolic dysfunction in asymptomatic patients with mild to severe AS. Moreover, in a recent study (5) including only patients with severe AS, a value of Z_va >5.5 mm Hg·ml^–1·m² was associated with a 2.5-fold increase in the risk of overall mortality, regardless of the type of treatment (AVR or medical). An important limitation of that study, however, is that many patients were already symptomatic at baseline.

Comparison with previous studies.   Previous studies of patients with asymptomatic AS have identified older age, hemodynamic severity of AS, severe aortic valve calcification, physical inactivity, coronary artery disease, and renal failure as independent predictors of adverse events generally defined as AVR (or onset of symptoms) and death (10–12). In the present study, we identified some of these factors, such as age and baseline AVA, as predictors of mortality. It should also be emphasized that Z_va was not determined in previous studies. Moreover, we selected overall mortality as the end point for the present study rather than a combined end point of AVR or death as used in some previous studies.

AS: a disease not only limited to the valve.   There is now a strong body of evidence suggesting that degenerative AS is an active disease akin to atherosclerosis (13,14), and in this context, it is not surprising that many patients with degenerative AS also have manifestations of atherosclerosis in other target organs. Many patients with degenerative AS thus also may present with concomitant systolic hypertension, and indeed, a markedly reduced arterial compliance was previously found to be present in up to 40% of patients with at least moderate AS (1). As well, such patients also may have alterations of LV function that might not only be caused by AS as such but also by hypertension and/or associated coronary artery disease and in varying proportions depending on the severity of each entity. Thus, degenerative AS cannot be viewed as an isolated disease strictly limited to the valve, but rather as part of a continuum that may also include a reduction in systemic arterial compliance and/or alterations of LV function. From the results of the present study, it would indeed seem that the pathophysiology of adverse outcomes in AS is primarily related to an imbalance between the global increase in LV overload, independent of whether it be of valvular and/or vascular origin, and LV reserve both at rest and during exercise; as well, it becomes evident that Z_va is the best-suited and most relevant parameter to clinically quantify this "global or total" increase in LV hemodynamic load.

The chronic exposure to a high level of afterload may eventually lead to a reduction in the coronary vasodilatory reserve, an intrinsic impairment of myocardial contractile function, and a decrease in cardiac output (1,5,9,15). To this effect, previous studies from our laboratory (1,5) and from the SEAS investigators (9) have reported that patients with a markedly increased Z_va often have decreases in LVEF, mid-wall fractional shortening, and cardiac output. The consequences of a reduction in cardiac output are a reduction of transvalvular gradients and a pseudo-normalization of peripheral blood pressure, which may occur in up to 30% of patients (1,5). Clinically, this situation is highly insidious because both AS and hypertension may appear less severe on the basis of the transvalvular gradients and blood pressure, whereas, in fact, these patients are at a more advanced stage of their disease. In this regard, the calculation of Z_va may be useful for identifying the patients in whom disease severity is masked by this pseudo-normalization phenomenon.

Clinical implications.   These results strengthen the need for a more comprehensive evaluation of AS that should include indexes such as: 1) AVA and ELI (in patients with a small aorta) for the assessment of valvular load; 2) systemic arterial compliance and vascular resistance for the assessment of arterial load; and finally, 3) Z_va to quantify global LV load. The consideration of these indexes easily measurable by Doppler echocardiography allows the clinician to better quantify the severity of the disease and could be particularly helpful in the 3 following clinical situations.

Asymptomatic Patients with Severe AS
Management of these patients remains a source of debate (16,17), and recent studies have suggested that those treated surgically may have better survival than those treated medically (18–20). This difference may be related to underestimation of symptoms and/or stenosis severity in some patients, especially in the elderly sedentary patients (5,19,20). Moreover, it has been argued that a "wait for symptoms" strategy may result in some patients undergoing surgery too late (i.e., at a stage of the disease when myocardial impairment has become, at least in part, irreversible) (21). On the other hand, AVR is not without risk (22), and the decision to operate on such patients therefore requires careful weighing of benefits against risks. To this effect, Z_va may be useful for identifying patients who are at higher risk and may be an indication for closer follow-up and further investigation. In this context, exercise stress testing may be particularly useful to corroborate symptomatic status in patients with a Z_va >4.5 mm Hg·ml^–1·m² who claim to be asymptomatic. If the exercise test is abnormal (exercise-limiting symptoms, decrease in blood pressure), AVR can be contemplated (16), whereas in the case of a normal test, the patient can be followed up more closely with a clinical brain natriuretic peptide level and/or echocardiographic evaluation every 6 to 12 months (23).

Symptomatic Patients with Moderate AS
Patients with moderate AS may become symptomatic because of concomitant hypertension. The calculation of Z_va may thus help to reconcile the apparent discrepancy between stenosis severity and symptomatic status. If the Z_va is <3.5 mm Hg·ml^–1·m², the symptoms could be related to a concomitant disease such as coronary artery disease, whereas if it is >3.5 mm Hg·ml^–1·m², the symptoms could be caused by the additive effects of the moderate AS and reduced arterial compliance and/or increased vascular resistance.

In such patients, the logical first step would be to treat their hypertension and then to re-evaluate symptomatic status and Z_va under treatment. Traditionally, vasodilator therapy has been considered relatively contraindicated in patients with AS because of its hypotensive effects, but recent studies, however, suggest that except in patients with very severe disease, it can be applied both safely and beneficially (23,24). Nonetheless, therapy should be introduced cautiously, particularly in patients with severe AS. Further studies will, however, be necessary to determine whether symptomatic status and outcome can be significantly improved in this fashion. Indeed, because AS patients often have reduced arterial compliance (1), blood pressure levels may not be completely normalized by treatment.

Paradoxical Low-flow, Low-gradient, Severe AS
We recently reported that an important proportion of the patients with severe AS on the basis of AVA paradoxically have a low transvalvular flow rate (SVI <35 ml/m²) and thus a low gradient (<40 mm Hg) despite the presence of a preserved LVEF (50%) (5). When compared with patients with severe AS, normal LV output and thus high gradient, these patients with paradoxical low flow were characterized by a higher degree of LV concentric remodeling, a lower LVEF (although still within the normal range), a reduced mid-wall shortening, a markedly higher level of LV global load reflected by a higher Z_va, and a worse prognosis if treated medically. Hence, it can be conceived that a greater and more longstanding increase in afterload may result in more pronounced LV concentric remodeling, a smaller LV cavity size, and a decrease in intrinsic myocardial function. This paradoxical low-flow, low-gradient AS pattern may bring some uncertainty about the actual severity of AS and may lead clinicians to erroneously conclude that the stenosis is not severe and that surgery is not indicated. Hence, the consideration of Z_va may be helpful in these patients to determine the actual level of global LV hemodynamic load that is often underestimated because of a reduction of transvalvular gradients and a pseudo-normalization of arterial pressures inherent to the low-flow state. If the Z_va is high, it is likely that the excessive hemodynamic load imposed by AS and/or hypertension contributed to the alteration of LV geometry and function that, in turn, led to the paradoxical low-flow state. In the present series, the vast majority (72%) of patients with paradoxical low flow had high Z_va, and among these patients >80% had a severe AS. In the subset of patients with moderate AS, the severe augmentation of Z_va is most likely caused by the coexistence of hypertension. On the other hand, if Z_va is low, the alteration of the LV geometry and function leading to a paradoxical low-flow state may be caused by concomitant risk factors or diseases such as diabetes, metabolic syndrome, or hypertrophic cardiomyopathy.

Study limitations.   One limitation of this study is its retrospective design. The baseline data were prospectively collected in consecutive patients with asymptomatic AS referred to the echocardiographic laboratory. However, the outcome data were retrospectively obtained from patients' charts or death certificates. Consequently, we did not have the information on: 1) the exact timing of symptom onset during follow-up; 2) the proportion of patients in whom severe symptomatic AS developed and who were not referred to AVR because of advanced age, comorbidities, or inappropriate management; and 3) the primary reason that motivated AVR. These limitations were, at least in part, compensated by the fact that we used overall survival (and not AVR) as the primary end point for this study and that we adjusted for the type of treatment in the multivariate analyses.

Patients with more than mild aortic insufficiency were excluded from the study. In the presence of significant aortic insufficiency, both the numerator (transvalvular gradient) and the denominator (SVI measured in the LV outflow tract) of Z_va may increase, which may reduce the ability of this index to correctly quantify the severity of the hemodynamic load in patients with mixed valvular dysfunction, and further studies are thus needed to examine the applicability and utility of Z_va in patients with mixed dysfunction.

	Conclusions

Top Abstract Methods Results Discussion Conclusions References

 
Increased Z_va is a marker of excessive LV hemodynamic load and identifies patients with a poor outcome. These findings suggest that beyond standard indexes of stenosis severity, LV geometry, and function, the consideration of Z_va may be useful to improve risk stratification and clinical decision making in patients with AS.

	Acknowledgments

 
The authors thank Dominique Labrèche, PhD, Isabelle Laforest, MS, Isabelle Fortin, and Marie-Annick Clavel, DVM, for data collection and validation, and Claudia Blais, PhD, Valérie Jomphe, MS, and Nicolas Girerd, MS, for their assistance in the statistical analyses.

	Footnotes

 
This work was supported by a grant from the Canadian Institutes of Health Research (MOP-82873), Ottawa, Canada.

Dr. Pibarot holds the Canada Research Chair in Valvular Heart Diseases, Canadian Institutes of Health Research, Ottawa, Ontario, Canada.

	References

Top Abstract Methods Results Discussion Conclusions References

 
1. Briand M, Dumesnil JG, Kadem L, et al. Reduced systemic arterial compliance impacts significantly on left ventricular afterload and function in aortic stenosis: implications for diagnosis and treatment J Am Coll Cardiol 2005;46:291-298.[Abstract/Free Full Text]

2. Nemes A, Forster T, Csanady M. Decreased aortic distensibility and coronary flow velocity reserve in patients with significant aortic valve stenosis with normal epicardial coronary arteries J Heart Valve Dis 2004;13:567-573.[Web of Science][Medline]

3. Yap SC, Nemes A, Meijboom FJ, et al. Abnormal aortic elastic properties in adults with congenital valvular aortic stenosis Int J Cardiol 2007;128:336-341.[CrossRef][Web of Science][Medline]

4. Nistri S, Grande-Allen J, Noale M, et al. Aortic elasticity and size in bicuspid aortic valve syndrome Eur Heart J 2008;29:472-479.[Abstract/Free Full Text]

5. Hachicha Z, Dumesnil JG, Bogaty P, Pibarot P. Paradoxical low flow, low gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival Circulation 2007;115:2856-2864.[Abstract/Free Full Text]

6. Garcia D, Pibarot P, Dumesnil JG, Sakr F, Durand LG. Assessment of aortic valve stenosis severity: a new index based on the energy loss concept Circulation 2000;101:765-771.[Abstract/Free Full Text]

7. Dumesnil JG, Paulin C, Pibarot P, Arsenault M, Coulombe D. Mitral annulus velocities by tissue Doppler imaging: practical implications with regards to preload alterations, sample position, and normal values J Am Soc Echocardiogr 2002;15:1226-1231.[CrossRef][Web of Science][Medline]

8. Dumesnil JG, Dion D, Yvorchuk K, Davies RA, Chan K. A new, simple and accurate method for determining ejection fraction by Doppler echocardiography Can J Cardiol 1995;11:1007-1014.[Web of Science][Medline]

9. Cramariuc D, Cioffi G, Rieck AE, et al. Low-flow aortic stenosis in asymptomatic patients: valvular arterial impedance and systolic function from the SEAS substudy J Am Coll Cardiol Img 2009;2:390-399.[Abstract/Free Full Text]

10. Otto CM, Burwash IG, Legget ME, et al. Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome. Circulation 1997;95:2262-2270.[Abstract/Free Full Text]

11. Rosenhek R, Binder T, Porenta G, et al. Predictors of outcome in severe, asymptomatic aortic stenosis N Engl J Med 2000;343:611-617.[CrossRef][Web of Science][Medline]

12. Pellikka PA, Sarano ME, Nishimura RA, et al. Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosis during prolonged follow-up Circulation 2005;111:3290-3295.[Abstract/Free Full Text]

13. Freeman RV, Otto CM. Spectrum of calcific aortic valve disease: pathogenesis, disease progression, and treatment strategies Circulation 2005;111:3316-3326.[Free Full Text]

14. Rajamannan NM, Bonow RO, Rahimtoola SH. Calcific aortic stenosis: an update Nat Clin Pract Cardiovasc Med 2007;4:254-262.[CrossRef][Web of Science][Medline]

15. Rajappan K, Rimoldi OE, Camici PG, Bellenger NG, Pennell DJ, Sheridan DJ. Functional changes in coronary microcirculation after valve replacement in patients with aortic stenosis Circulation 2003;107:3170-3175.[Abstract/Free Full Text]

16. Bonow RO, Carabello BA, Kanu C, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Valvular Heart Disease) J Am Coll Cardiol 2006;48:e1-e148.[Free Full Text]

17. Vahanian A, Baumgartner H, Bax J, et al. Guidelines on the management of valvular heart disease: The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology Eur Heart J 2007;28:230-268.[Free Full Text]

18. Brown ML, Pellikka PA, Schaff HV, et al. The benefits of early valve replacement in asymptomatic patients with severe aortic stenosis J Thorac Cardiovasc Surg 2008;135:308-315.[Abstract/Free Full Text]

19. Pai RG, Kapoor N, Bansal RC, Varadarajan P. Malignant natural history of asymptomatic severe aortic stenosis: benefit of aortic valve replacement Ann Thorac Surg 2006;82:2116-2122.[Abstract/Free Full Text]

20. Mihaljevic T, Nowicki ER, Rajeswaran J, et al. Survival after valve replacement for aortic stenosis: implications for decision making J Thorac Cardiovasc Surg 2008;135:1270-1278.[Abstract/Free Full Text]

21. Lund O. Preoperative risk evaluation and stratification of long-term survival after valve replacement for aortic stenosis. Reasons for earlier operative intervention. Circulation 1990;82:124-139.[Abstract/Free Full Text]

22. Pibarot P, Dumesnil JG. Prosthetic heart valves: Selection of the optimal prosthesis and long-term management Circulation 2009;119:1034-1048.[Free Full Text]

23. Otto CM. Valvular aortic stenosis: disease severity and timing of intervention J Am Coll Cardiol 2006;47:2141-2151.[Abstract/Free Full Text]

24. O'Brien KD, Zhao XQ, Shavelle DM, et al. Hemodynamic effects of the angiotensin-converting enzyme inhibitor, ramipril, in patients with mild to moderate aortic stenosis and preserved left ventricular function J Investig Med 2004;52:185-191.[Web of Science][Medline]

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				P. Lancellotti, E. Donal, J. Magne, K. O'Connor, M. L. Moonen, B. Cosyns, and L. A. Pierard Impact of global left ventricular afterload on left ventricular function in asymptomatic severe aortic stenosis: a two-dimensional speckle-tracking study Eur Heart J Cardiovasc Imaging, July 1, 2010; 11(6): 537 - 543. [Abstract] [Full Text] [PDF]

				T. Z. Naqvi Diastolic Dysfunction in Aortic Stenosis and Arterial Stiffness J. Am. Coll. Cardiol., March 16, 2010; 55(11): 1164 - 1164. [Full Text] [PDF]

				J. G. Dumesnil and P. Pibarot Reply. J. Am. Coll. Cardiol., March 16, 2010; 55(11): 1165 - 1166. [Full Text] [PDF]

				P. Samarendra Usefulness of Valvuloarterial Impedance to Predict Adverse Outcomes in Patients With Asymptomatic Aortic Stenosis J. Am. Coll. Cardiol., March 16, 2010; 55(11): 1164 - 1165. [Full Text] [PDF]

				A. N. DeMaria, J. J. Bax, O. Ben-Yehuda, G. K. Feld, B. H. Greenberg, J. Hall, M. Hlatky, W. Y.W. Lew, J. A.C. Lima, A. S. Maisel, et al. Highlights of the Year in JACC 2009 J. Am. Coll. Cardiol., January 26, 2010; 55(4): 380 - 407. [Full Text] [PDF]

				H. Baumgartner and C. M. Otto Aortic Stenosis Severity: Do We Need a New Concept? J. Am. Coll. Cardiol., September 8, 2009; 54(11): 1012 - 1013. [Full Text] [PDF]

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