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Ann Thorac Surg 2003;76:1107-1113
© 2003 The Society of Thoracic Surgeons

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Original article: cardiovascular

Mass regression in aortic stenosis after valve replacement with small size pericardial bioprosthesis

^a Department of Cardiac Surgery, Hospital Poliambulanza, Brescia, Italy

Accepted for publication April 8, 2003.

^* Address reprint requests to Dr Tasca, UF di Cardiochirurgia, Casa di Cura, Poliambulanza, Via L. Bissolati 57, 25125 Brescia, Italy
e-mail: cch-segreteria.poli{at}poliambulanza.it

	Abstract

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
BACKGROUND: The aim of the study was to determine whether left ventricular mass regression is influenced by valve size after the implantation of a Carpentier-Edwards Perimount (CEP) pericardial bioprosthesis for pure aortic stenosis.

METHODS: Patients receiving 19-mm, 21-mm, and 23-mm CEP aortic valves underwent echocardiography preoperatively and at least 1 year after surgery (mean, 2.3 ± 1 years) and the echocardiograms were compared within and between groups.

RESULTS: The study involved a total of 88 patients: 34 receiving 19-mm CEPs, 29 receiving 21-mm CEPs, and 25 receiving 23-mm CEPs. The mean postoperative prosthetic gradients were respectively 20.6 ± 6.6 mm Hg, 17.9 ± 5.8 mm Hg, and 13.2 ± 4.1 mm Hg (p = 0.0001); the mean postoperative valve areas were respectively 1.24 ± 0.16 cm², 1.45 ± 0.2 cm², and 1.63 ± 0.21 cm² (p = 0.0001). In comparison with the preoperative echocardiographic measurements absolute left ventricular mass significantly decreased by -54.1 ± 48.8 g, -54.1 ± 55.1 g, and -74.4 ± 57.4 g respectively with no statistically significant between-group difference (analysis of variance) but ventricular septum and posterior wall thickness significantly decreased in each group (p < 0.05).

CONCLUSIONS: The implantation of 19-mm, 21-mm, and 23-mm CEP aortic prostheses significantly reduces left ventricular mass without any size-related differences.

	Introduction

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Left ventricular (LV) hypertrophy is an independent predictor of mortality and morbidity in hypertensive patients or otherwise healthy adults [1]. The primary purpose of aortic valve replacement surgery is to relieve the high pressure gradient and allow the ventricular hypertrophy to regress. However the effects of surgery may be diminished by the residual postoperative gradients that often remain after aortic valve replacement and increase with decreasing prosthetic valve size and a greater body surface area. Barner and associates [2] found that LV mass regression is better for patients given a 21-mm or larger prosthesis than for patients whose prostheses are less than 21 mm. The in vitro effective orifice area is the major determinant of postoperative gradients [3] and as the indexed effective orifice area (effective orifice area divided by body surface area) is closely related to the extent of LV mass regression [4], a larger prosthesis size would seem to be preferable.

Carpentier-Edwards Perimount (CEP [Edwards Lifesciences, Irvine, CA]) pericardial valves are stented tissue valves made of bovine pericardium that are widely used in patients with small aortic roots. The purpose of this study was to ascertain whether patients with pure aortic stenosis receiving a 19-mm, 21-mm, or 23-mm CEP aortic valve show significant and size-related LV mass regression.

	Material and methods

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Patient population
The study population consisted of 88 patients with pure aortic stenosis (no patient had more than trace or mild aortic regurgitation) and no other heart disease (apart from coronary artery disease) who underwent aortic valve replacement with CEP valves at the Poliambulanza Hospital in Brescia, Italy, between September 1997 and July 2001. Of the 100 patients discharged after aortic valve replacement during this period, 5 died late (see Table 1) and 7 refused to participate in the follow-up study (see Table 2).

Clinical, echocardiographic, operative, and outcome data were prospectively collected in our institutional database and the patients were divided into three groups (CEP-19, CEP-21, and CEP-23) on the basis of the size of the prosthesis.

Echocardiographic measurements
The preoperative and postoperative echocardiographic studies (see Appendix) were performed by four experienced echocardiographers using an Acuson 128 Computed Sonograph (Acuson, Mountain View, CA) equipped with 2.5 to 3.5 MHz transducers. The preoperative echocardiograms were recorded 0 to 7 days before surgery and the postoperative echocardiograms used for this study at least 1 year after the operation. The dimensions of the left ventricle were assessed using two-dimensionally guided M-mode tracings, with the measurements being made according to the recommendations of the American Society of Echocardiography (ASE); if the M-mode recordings were technically inadequate, two-dimensional measurements were used. Left ventricular mass was calculated by means of the ASE modified formula. Residual LV hypertrophy was defined as a LV mass index of more than 131 g/m² in males and more than 100 g/m² in females. The effect of aortic valve replacement was quantified on the basis of absolute and relative LV mass regression. Left ventricular performance was evaluated on the basis of the ejection fraction (EF) calculated using Simpson's rule. Blood flow velocity in the LV outflow tract and across the valve was respectively estimated by means of pulsed and continuous wave Doppler using an apical four-chamber view. Peak and mean valve gradients were calculated using the modified Bernoulli equation. Valve area was calculated using the continuity equation. A patient-prosthesis mismatch was defined as an indexed effective orifice area of less than 0.85 cm² [5].

Follow-up
After a clinical follow-up at 3 months the patients were interviewed by telephone annually in order to assess their clinical status and collect survival data. Follow-up was 100% complete. The survivors were invited to undergo an echocardiographic control examination at our hospital between April and August 2002.

Statistical analysis
The data were statistically analyzed using SPSS 9.0 (SPSS, Chicago, IL). The continuous variables were expressed as mean values ± SD with 95% confidence intervals (CI) and compared using a two-tailed t test (paired or unpaired when appropriate). One-way analysis of variance (ANOVA) was used to evaluate the significance of the differences among the valve size groups. If the F value was significant and variance was homogeneous, Tukey's multiple comparison test was used to assess the differences between the individual groups; otherwise, Tamhane's T2 test was used. The Kruskal-Wallis test was used to compare the three groups in terms of one dichotomous variable. A p value of less than 0.05 was considered significant. The relationships between the Doppler echocardiographic variables and prosthesis size and effective orifice area were evaluated by means of simple linear regression analysis to calculate r (Pearson's correlation coefficient) and R² (the coefficient of determination).

	Results

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
There were 34 patients in the CEP-19 group, 29 in the CEP-21 group, and 25 in the CEP-23 group. Their clinical characteristics are shown in Table 3. Concomitant coronary artery bypass graft procedures were performed in 54.5% of the patients (48 of 88).

View larger version (15K): [in this window] [in a new window]   Fig 1. (A) Simple linear regression analysis between mean prosthesis gradient and prosthesis size: r = 0.46; R2 = 0.21; p = 0.00001. Solid squares = observed; solid line = linear regression line. (B) Simple linear regression analysis between the effective orifice area and size of the prosthesis: r = 0.62; R2 = 0.38; p = 0.00001. Solid squares = observed; solid line = linear regression line.

	Comment

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

The implantation of a small aortic valve prosthesis, with a possible patient-prosthesis mismatch or residual gradient, may negatively affect LV mass regression [2]. In order to reduce this negative effect many different annulus-enlarging procedures have been recommended to allow the implantation of larger prostheses but these can increase operative mortality [7]. Despite these potential drawbacks small CEP valves are widely used (particularly in elderly patients) and have led to good early and long-term clinical results [8, 9]. The hemodynamic performance of CEP valves seems to be better than that of other stented tissue valves at all of the sizes tested in vitro [10] although no difference was observed under resting conditions in one clinical study [11]. Even a 19-mm CEP can increase effective orifice area at an anticipated rate pari passu with increasing cardiac output during stress testing [12] although as expected the larger valve sizes led to larger effective orifice areas and lower postoperative mean and peak gradients. Our results are consistent with those reported by Takamura and associates [11] and McDonald and associates [12].

Left ventricular morphologic changes
All of our patient groups showed a significant regression in LV mass and LV mass index irrespective of the prosthesis size. Although the patients in the CEP-23 group showed a better absolute regression in LV mass and a higher indexed effective orifice area in comparison with the other two groups, no statistical difference was found. Our results confirm those of other studies showing that prosthesis size, indexed effective orifice area, prosthesis type, and Doppler gradient do not negatively affect LV mass regression [13–16].

Some of the differences in LV mass regression between our observations and those of Khan [13] seem to be due to differences in patients selected for the study (associated mitral disease), in the methods used to calculate LV mass, and in the distribution of preoperative LV mass index in the prosthesis-size groups. In our study the CEP-23 group had the highest preoperative LV mass index, a slightly less concentric LV radius-to-wall ratio, and a lower EF than the other two groups. The regression in LV mass index in this group was due more to the normalization of LVDD than to the reduction in wall thickness. The hypothesis of this mechanism is supported by the lack of statistically significant reduction in the postoperative LV radius-to-wall ratio in the CEP-23 group. In the CEP-19 and CEP-21 groups the regression in LV mass was mainly due to the reduction in ventricular wall thickness: the LV radius-to-wall ratio, IVS, and PW significantly decreased only in these groups whereas there was no statistically significant reduction in LVDD.

These results may been influenced by the different sex distribution in the three groups: all of the CEP-23 patients were male and almost all of the CEP-19 patients were female. It is well known that there is a sex-related difference in the behavior of pressure overload-induced LVH, with males developing a greater mass, less concentric hypertrophy, more systolic stress, and a lower EF.

Although the reduction in LV mass was significant in each group it is worth noting that the average postoperative LV mass index for the entire series remained above normal in 59% of the patients (Table 4). Similar observations have been made in other studies of mechanical and tissue, stented and stentless valves [13, 17]. The lack of LV mass normalization seems to be mainly due to incomplete IVS regression [13, 15]. The reasons for incomplete hypertrophy regression include a residual aortic gradient due to a patient-prosthesis mismatch, suboptimal hypertension treatment (68% of our patients had a history of hypertension), or physical activity. Furthermore nonhemodynamic factors such as genotype (angiotensin phenotype expression) [18] and the environment can affect the degree of mass regression [19].

It should be noted that preoperative LV mass in patients affected by aortic stenosis is markedly high and that the magnitude of absolute LV mass regression is closely related to preoperative LV mass [4]. In our population this correlation was r = 0.57, R² = 0.33, p = 0.0001. The long-standing high degree of LV mass in aortic stenosis can eventually lead to irreversible myocardial changes and may be another cause of incomplete LV mass regression. Lund and associates [20] found that LV mass index 18 months after surgery significantly correlated with myocyte cell diameter, nucleus volume, the muscle cell mass index, and the fibrous tissue mass index, all of which were identified as signs of irreversible hypertrophy. The degree of hypertrophy regression after the removal of the hypertrophic trigger therefore seems to be caused by presumably irreversible changes in the hypertrophic myocytes of many patients. It has been demonstrated that residual hypertrophy is related to significant ventricular fibrosis and the consequent end-stage disease characterizing surgical patients with aortic stenosis [21].

There are no published data concerning the prognostic importance of hypertrophy regression in large groups of patients undergoing surgery for pure aortic stenosis although in a small group of patients Lund and associates [20] found an association between a high myocyte nucleus volume (an indirect index of LVH) and 6-year postoperative survival.

Study limitations
The study has a number of limitations. First, it was retrospective. The nonhomogeneous sex distribution in the groups may have influenced the results. In our series the preoperative LV radius-to-wall ratio in males and females was 0.51 ± 0.09 versus 0.57 ± 0.12 (p = 0.009) and the LV mass index was 168.8 ± 36.3 g/m² versus 150.1 ± 35.6 g/m² (p = 0.019). The mean age of our patient population was 75 years and so any inferences derived from our results may only apply to elderly patients. The echocardiographic examinations were performed by four echocardiographers but interobserver variability was not quantified. The analysis involved 92.6% of the survivors. The difference in follow-up intervals (longer in the CEP-19) may have altered the results. It is assumed that mass regression is a continuing process and further reductions in LV mass may occur 1 to 5 years postoperatively [22]. Finally the small number of patients in each group may have been responsible for the absence of statistical significance in the ANOVA of the difference between the absolute LV mass and LV mass index reductions.

Clinical implications
As reported by others [13–16] the magnitude of LV mass regression was not influenced by the size of the prostheses. The CEP has a good early performance and has been recently reported as being stable over time [23]. Moreover in elderly patients 19-mm CEP valves are associated with good event-free survival [8]. Together with these positive characteristics of CEP our results justify its wide use in elderly patients with small and calcified aortic roots. Our data clearly show the absence of any proof of a patient-prosthesis mismatch effect although it must be admitted that there is still no universal agreement about the definition of a mismatch or its importance in influencing clinical results.

This study shows that the effect of aortic valve replacement on LV mass regression must be analyzed using homogeneous criteria in terms of population (valve lesion, preoperative clinical characteristics) and methods. Furthermore comparisons of prostheses of different sizes or types and the validation of expected better performances of new prostheses (new-generation mechanical valves, stentless tissue valves, stented tissue valves with a better size/effective orifice area ratio) should be made using similar standards of evaluation.

	Acknowledgments

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
We would like to thank Dr Pier Virgilio Parrella for his assistance with the statistical analysis.

	Appendix

 
Echocardiographic data
Structural LV Measurements

The left ventricular variables measured from M-mode tracings: ,

Relative left ventricular wall thickness (RLVWT) was calculated as EDD/(PW + PW).

Left ventricular mass (LVM) was calculated in grams using an ASE-corrected formula.

Absolute LVM regression = postop. LVM - preop. LVM expressed in grams.

Relative LVM regression % = (preop. LVM - postop. LVM)/preop. LVM.

Doppler measurements
Modified Bernoulli equation for mean and peak pressure drop p = 4*(V²₁ - V²₂).

The effective orifice area (EOA) of the prosthesis was calculated using the modified continuity equation:

	References

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 

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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 Author home page(s): Federico Brunelli Marco Cirillo Zen Mhagna Giovanni Troise Eugenio Quaini Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tasca, G. Articles by Quaini, E. Search for Related Content PubMed PubMed Citation Articles by Tasca, G. Articles by Quaini, E. Related Collections Valve disease