Eur J Cardiothorac Surg 2005;27:994-999
© 2005 Elsevier Science NL
Impact of postoperative blood pressure control on regression of left ventricular mass following valve replacement for aortic stenosis
Kazuhito Imanakaa,*,
Osami Kohmotob,
Shigeyuki Nishimurab,
Yuji Yokotea,
Shunei Kyoa
a Department of Cardiovascular Surgery, Saitama Medical School, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan
b Department of Cardiology, Saitama Medical School, Saitama, Japan
Received 28 October 2004;
received in revised form 15 February 2005;
accepted 21 February 2005.
* Corresponding author. Tel.: +81 492 76 1562; fax: +81 492 76 2062. (E-mail: imanaka{at}saitama-med.ac.jp).
 |
Abstract
|
|---|
Objective: Considerable left ventricular (LV) hypertrophy sometimes remains after aortic valve replacement (AVR) for aortic stenosis. For this issue, most previous studies have focused solely on transprosthetic pressure gradient, although true problem is not the pressure gradient itself but an elevated LV pressure. This study investigated the impact of blood pressure on postoperative LV mass regression, which had been overlooked in previous studies. Methods: Seventy-nine adult patients with pure aortic stenosis who were treated with AVR using bileaflet mechanical valves underwent echocardiography before surgery, around 6 months later (‘early’), and 2–3 years later (31.7±14.7 months, ‘late’). Patients were divided into two groups whether postoperative systolic blood pressure was below (n=47; N group) or above 130mmHg (n=32; H group) following recommendation of WHO-ISH and JNC 7th report. Preoperative LV mass (g/m2) did not differ significantly (232±80 vs. 243±76, P=0.91). Results: LV mass became significantly smaller and regression was significantly more effective in N group than in H group both at ‘early’ (145±43 vs. 180±54, regression against preoperative value 34.6±19.1 vs. 19.9±26.6%, P=0.007) and ‘late’ (132±41 vs. 178±51, regression 41.1±16.0 vs. 21.0±27.0%, P<0.001) evaluations. Regression between ‘early’ and ‘late’ evaluations was significant only in N group (P=0.012). The LV mass index returned to the normal range at ‘late’ evaluation in 52.1% of N group and 12.5% of H group patients (P<0.001), and 25 out of 29 patients without residual LV hypertrophy were N group patients. Multivariate analyses revealed that preoperative LV mass index (P<0.001) and postoperative systolic blood pressure (P=0.007) showed significant influence on postoperative LV mass index, and postoperative systolic blood pressure alone significantly (P<0.001) influenced the regression ratio of the LV mass against the preoperative value. No prosthesis related variables (size, orifice area index, pressure gradient) had significant influence. Conclusions: For LV mass regression after AVR, postoperative blood pressure appeared to be more important than prosthesis selection. Controlling the systolic blood pressure below 130mmHg was beneficial, which coincided with recommendation of WHO-ISH and JNC 7th report despite the pressure drop due to prosthesis in the aortic position.
Key Words: Left ventricular hypertrophy • Blood pressure • Prosthesis • Aortic valve replacement • Aortic stenosis
|
1. Introduction
|
|---|
In patients with aortic valve stenosis (AS), left ventricular hypertrophy (LVH) develops as an adaptive process in response to elevated pressure in the left ventricle (LV). Aortic valve replacement (AVR) is effective for relief of excessive afterload, but significant LVH often remains following AVR. Because severe LVH is a well-known hazard of cardiac events [1,2], its regression is one of the most important concerns. Lund et al. [3] recently showed that the LV mass index or its regression following AVR is closely related with the long-term survival. To investigate the factors that influence postoperative LV mass regression, most previous studies have focused solely on pressure gradient through the prosthetic valve. Consequently, most authors have solely discussed over the type and the size of the prostheses and almost uniformly made confusing conclusions, namely, prosthetic valves were hemodynamically unacceptable and clinically acceptable. Trigger stimulus of LVH is not the pressure gradient itself but an elevated LV pressure, which can be reduced by lowering the systemic blood pressure. Blood pressure can usually be reduced much more easily and effectively than transprosthetic pressure gradient. Blood pressure may be more important for LV mass regression after AVR than prosthesis selection, although almost all previous studies had overlooked this aspect. The present retrospective case-series study was conducted to test this hypothesis.
|
2. Patients and methods
|
|---|
Between February 1991 and June 2000, 113 consecutive adult patients with pure AS (preoperative pressure gradient across the aortic valve greater than 50mmHg) underwent AVR using bileaflet mechanical valves (SJM Heart Valve (St. Jude Medical Inc., Minneapolis, MN) or CarboMedics Heart Valve (CarboMedics Inc., Austin, TX)). Surgery was carried out with a standard hypothermic cardiopulmonary bypass and cold crystalloid cardioplegia. During the study period, either type of valve was used in all patients undergoing AVR and valve type was determined according to the surgeons' preference. In this study, patients with coexistent disease that causes LV volume overload such as significant aortic regurgitation, significant mitral valve disease, or patent ductus arteriosus, were excluded. Therefore, aortic regurgitation was equal to or less than Sellers' first degree on aortography [4] in all patients, and concomitant cardiac procedures were coronary artery bypass grafting in 15 and tailoring of the ascending aorta in 3. No enlargement of the aortic annulus was attempted. There were six hospital deaths (hospital mortality 5.3%). Of the 107 survivors of the operation, 79 (73.8%) were nearby residents, and had been followed-up at our outpatient clinic. All these 79 patients underwent echocardiographic evaluation before AVR, around 6 months later (‘early’) and 2 or 3 years later (31.7±14.7 months, ‘late’) using an Aloka SSD-2200 or SSD-5500 ultrasound scanner (Aloka Inc., Tokyo, Japan). Echo images were independently reviewed by two or more sonographers.
The wall thickness and internal dimensions of the LV were determined with a routine M-mode scan. Transvalvular flow was measured by the continuous wave Doppler method from right parasternal portion or from apical portion. Peak pressure gradients were calculated using the Bernoulli's equation [5]: 
P=4V2.
The LV mass index was calculated with the following formula [6]
where BSA is body surface area; LVDd and LVDs are the end-diastolic and end-systolic dimensions of the LV; and IVSthd and Pwthd are the end-diastolic thicknesses of the interventricular septum and posterior wall of the LV, respectively.
The upper limit of the LV mass index was 134g/m2 in men and 110g/m2 in women [6]. LV mass index equal to or below these values was judged as normal.
The regression ratio of the LV mass index was defined as follows:
Table 1 shows the demographics of the study subjects. Systemic blood pressure just prior to AVR was normal in the vast majority. Seventeen patients had history of hypertension, but anti-hypertensive treatment had been discontinued in 11 and six patients were taking oral calcium blockers. Postoperatively, patients usually visited our outpatient clinic every month. Appropriately measured seated blood pressures at three or more visits around the day of echocardiography evaluation were averaged, and was used as postoperative blood pressure. According to the recommendation of WHO-ISH [7] and JNC 7th report [8], 79 patients were divided into two groups whether postoperative systolic blood pressure was below (n=47; N group) or above 130mmHg (n=32; H group) in comparative analyses. Calcium blockers, beta blockers, angiotensin converting enzyme inhibitors were administered in 15, 10, 18 of N group patients and in 15, 3, 11 of H group patients, respectively. Five patients of each group were free from these medicines.
Orifice area (cm2) provided by manufacturers was indexed by body surface area of the patients (m2), and was also used for analysis.
|
3. Statistical analysis
|
|---|
Statistical analysis was carried out with Statview ver. 5.0 (SAS Institute, Cary, NC). Continuous data are shown as mean±SD. The analysis of variance (ANOVA) and the Chi-square test were used for intergroup comparison, and paired t-test for intragroup analysis. Univariate (simple linear regression) and multivariate (stepwise logistic regression) analysis was used to assess the influence of variables on the LV mass index and its regression. Differences were regarded as statistically significant at P<0.05.
|
4. Results
|
|---|
In entire group of patients (n=79), the LV mass index both at ‘early’ (157±51) and at ‘late’ (150±50) evaluation was significantly smaller (P<0.001) than that before AVR (237±78), and the difference between ‘early’ and ‘late’ evaluation was not significant (P=0.10). When postoperative blood pressure was taken into consideration, however, there was a clear contrast. Except for age and frequency of calcific valve disease, N group had almost the same variables with H group including preoperative LV mass index (232±80 vs. 243±76, P=0.91). However, the postoperative LV mass index of N group was significantly smaller than that of H group both at ‘early’ (145±43 vs. 180±54, P=0.019) and ‘late’ (132±41 vs. 178±51, P<0.001) evaluations. In N group, moreover, the LV mass index was significantly reduced (P=0.012) during the postoperative study interval, but it remained almost the same in H group (P=0.93) (Fig. 1). The LV mass regression ratio of N group was significantly greater than that of H group both at ‘early’ (34.6±19.1 vs. 19.9±26.6%, P=0.007) and ‘late’ (41.1±16.0 vs. 21.0±27.0%, P<0.001) evaluations.
View larger version (19K):
[in this window]
[in a new window]
|
Fig. 1. Regression of the left ventricular mass and postoperative systolic blood pressure. Patients were divided into 2 groups according to whether postoperative systolic blood pressure was maintained below 130mmHg or not. The left ventricular mass index was almost the same in both groups before surgery, but it was significantly smaller in patients with lower blood pressure both at 6 months and 2–3 years later (P<0.001). In patients with blood pressure below 130mmHg, the left ventricular mass regressed significantly (P=0.012) beyond 6 months postoperatively, whereas it remained almost the same (P=0.93) in their counterparts.
|
|
In entire group of patients, the LV mass index returned to the normal range [5] in 29 patients (36.7%), whereas 50 patients showed residual LVH at ‘late’ postoperative evaluation. In this regard also, there was a clear contrast according to the postoperative blood pressure. The LV mass index had returned to the normal range in 52.1% of N group patients and only in 12.5% of H group patients (P<0.001). That is, blood pressure was below 130mmHg in 25 (85.6%) of 29 patients whose LV mass index had normalized, and four were H group patients. Among 50 patients with residual LVH, on the other hand, 22 were N group and 28 were H group patients. Patients without residual LVH showed significantly smaller preoperative LV mass index (194±60 vs. 261±78, P<0.001), significantly larger regression ratio (42±17 vs. 27±25%, P=0.004), significantly lower postoperative blood pressure (122±14 vs. 135±20, P=0.008), and significantly younger age (59.5±12.9 vs. 64.9±8.9, P=0.03) than patients with residual LVH. However, prosthesis related variables (valve size, orifice area index, and transprosthetic pressure gradient) were similar in both groups (Table 2).
Factors that may have affected regression of the LV mass were evaluated. The etiology of AS, preoperative NYHA classes, presence of diabetes, history of hypertension, and concomitant coronary artery bypass grafting did not lead to statistically significant differences either in the absolute value or in the regression ratio of the LV mass index. Male patients had significantly larger LV masses than the women both before and after AVR, but the regression ratio was almost the same (34.4±21.3 vs. 30.0±25.6%). Tables 3 and 4 show the results of univariate analysis and multivariate stepwise regression analysis. Variables that had significant influence on the late postoperative LV mass index were the preoperative LV mass index and the postoperative systolic blood pressure, but neither of prosthesis related variables had significant influence (Table 3). Postoperative systolic blood pressure (P<0.001), transprosthetic pressure gradient (P=0.02), and the orifice area index (P=0.04) were shown to be associated with the regression ratio of the LV mass index by univariate analysis. However, multivariate analysis revealed that postoperative systolic blood pressure was the only variable that significantly (P<0.001) influenced the regression ratio of the LV mass index (Table 4).
|
5. Discussion
|
|---|
Aortic annuli of patients with AS are often disproportionately small, which can cause what is called a ‘patient–prosthesis mismatch’ [9]. A small sized valve causes a large pressure gradient and considerable residual LVH and result in poor outcome, and selection of an appropriate prosthesis for each patient to bring the pressure gradient within an acceptable range may contribute to better outcome. This is the ‘classic’ aspect of residual LVH after AVR, and may have tended to be overemphasized [9,10]. Although some have been aware that prosthesis itself might not have been very important [3,11], most physicians, especially surgeons, have concerned about the pressure gradient across the prosthetic valve after AVR, and have eagerly but solely discussed over the size and type of the prostheses. To discuss residual LVH, poor functional status, or late survival after AVR for AS, some had focused mainly on the valve size [12,13], others on echocardiographic data at rest [14,15], or on data under stress [16]. All investigators found that small size prosthesis caused high pressure gradient and small effective orifice area, but most of them failed to show close relationship between data on examination and clinical results. Fairly satisfactory clinical results were obtained with hemodynamically suboptimal prostheses, which led to aforementioned confusing conclusion. This might have been partly because pressure gradient is highly dependent on transprosthetic flow and has an inherent limitation as an assessment measure [17]. However, overemphasis of pressure gradient might have been the major flaw. The true obstacle for regression of the LV mass is not the transprosthetic pressure gradient itself but the elevated LV pressure. Pressure gradient is merely one of the factors of the LV pressure elevation.
Another key to lower the LV pressure is the systemic blood pressure which can be reduced much more easily and effectively than transprosthetic pressure gradient but had been overlooked in previous studies with very few exceptions. The present study focused on this aspect according to the recommendation of WHO-ISH [7] and JNC 7th report [8], and revealed that blood pressure was very important for LV mass regression after AVR and that those recommendations were applicable even to patients with a prosthetic valve in the aortic position, although transprosthetic pressure gradient was not negligible in most of our patients.
In patients with systolic blood pressure below 130mmHg after AVR, postoperative LV mass regression (both absolute value and percentage) was significantly more effective both at ‘early’ and at ‘late’ evaluations. Moreover, although LV mass regression following AVR have been believed to be almost completed by 6 months postoperatively [18], this study demonstrated further significant LV mass regression beyond 6 months later in patients whose systolic blood pressure was below 130mmHg.
The LV mass index was found 2–3 years later to be within the normal range in 36.7% of all our patients, and blood pressure was below 130mmHg in the vast majority of them. Excellent performance of modern bileaflet prosthetic valves may have been a prerequisite of the result of this study. However, this analysis strongly suggested that very effective LV mass regression could eliminate LVH and that blood pressure control, not prosthesis related variables, could be important. Enormous LVH before surgery was certainly a major hindrance for ‘normalization’ of the absolute value. During evaluation of the LV mass regression, however, relative regression ratio is much more important than the absolute value. For example, regression of the LV mass index from 250 to 150 (40% decrease) is more effective than regression from 160 to 128 (20%), although the absolute value does not become within normal range in the former case.
Multivariate analyses revealed that, as far as bileaflet valves were concerned, the systolic blood pressure following AVR was the single variable that had significant influence on regression of the LV mass (both the absolute value and the regression ratio) and that blood pressure control appeared to have a greater impact on the regression of the LV mass than prosthetic valve related variables. As well as transprosthetic pressure gradient, blood pressure is also one of the factors of the LV pressure elevation. We do not believe that LV mass regression depends solely on it. However, physicians should be more aware of its implication. Especially in patients with large residual pressure gradients, maintaining a lower systemic blood pressure can be beneficial to decrease the LV pressure and, as a result, to prevent severe residual LVH. Patients of this study were given various types and doses of vasodepressants. Their purely pharmacological effects on myocardium seemed unlikely to have largely affected our results but could not be ruled out. Moreover, an experimental study [19] showed that such effect was not strong enough in the presence of significant afterload, although wide evidence on this aspect is lacking so far.
Some investigators have reported a negligible pressure drop and nearly perfect relief of LVH after stentless xenograft valve implantation [20,21]. However, investigations on blood pressure were omitted in those papers and no wide consensus exists on this matter at present [22]. It may not show an entirely appropriate attitude to use stentless xenografts for all patients undergoing AVR, because, in addition to problems that are related to more complicated and more technically demanding surgery, future degeneration is probably inevitable. From the standpoint of LVH in AS patients, use of stentless xenograft appears to obtain a marked but only transient success at the expense of complicated procedure. Keeping systolic blood pressure below 130mmHg and prescribing vasodepressants if necessary can be a management of choice.
|
6. Limitations of the study
|
|---|
As blood pressure is labile in nature, we used the average blood pressure at 3 or more visits, although some errors may still exist. Especially in patients with asymmetrical septal hypertrophy, calculation of the LV mass according to the formula based on M-mode echocardiography could be inaccurate. This is a retrospective observational study and is not free from all limitations of the study design. The relatively small number of our patients may have precluded the identification of some factors (advanced NYHA class for example) that had influenced LV mass regression. Moreover, vasodepressants were prescribed in non-randomized manner, which might have caused bias. Randomized studies with large patient numbers would be necessary to obtain conclusive evidences.
|
7. Conclusions
|
|---|
To achieve effective regression of LVH following AVR for AS, postoperative blood pressure appeared to be more important than the prosthesis related variables. Keeping systolic blood pressure below 130mmHg was highly beneficial, which coincided with the recommendation of WHO-ISH and JNC 7th report.
|
References
|
|---|
- Mathew J, Sleight P, Lonn E, Johnstone D, Pogue J, Yi Q, Bosch J, Sussex B, Probstfield J, Yusuf S, Heart Outcomes Prevention Evaluation (HOPE) Investigators. Reduction of cardiovascular risk by regression of electrocardiographic markers of left ventricular hypertrophy by the angiotensin-converting enzyme inhibitor Ramipril. Circulation 2001;104:1615-1621.[Abstract/Free Full Text]
- Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, Fyhrquist F, Ibsen H, Kristiansson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H, LIFE Study Group. Cardiovascular morbidity and mortality in the Losartan intervention for endpoint reduction in hypertensionstudy (LIFE): a randomized trial against atenolol. Lancet 2002;359:995-1003.[CrossRef][Medline]
- Lund O, Emmertsen K, Dorup I, Jensen FT, Flo C. Regression of left ventricular hypertrophy during 10 years after valve replacement for aortic stenosis is related to the preoperative risk profile. Eur Heart J 2003;24:1437-1446.[Abstract/Free Full Text]
- Davidson CJ, Bonow RO. Cardiac catheterization. In: Braunwald E, Zipes DP, Libby P, editors. Heart diseases. 6th ed. PA: Saunders; 2001. pp. 379.
- Hatle L, Angelsen BA, Tromsdal A. Non-invasive assessment of aortic stenosis by Doppler ultrasound. Br Heart J 1980;43:284-292.[Abstract/Free Full Text]
- Devereux RB. Detection of left ventricular hypertrophy by M-mode echocardiography: anatomic validation, standarization and comparison to other methods. Hypertension 1987;9(Suppl. II):19-24.
- Guidlines subcommittee 1999 World Health Organization-International Society of Hypertension guidelines for the management of hypertension. J Hypertens 1999;17:151–183..
- Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ, National Heart. Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure; The JNC 7 report. J Am Med Assoc 2003;289:2560–2572..
- Rahimtoola SH. The problem of valve prosthesis-patient mismatch. Circulation 1978;58:20-24.[Abstract/Free Full Text]
- Pibarot P, Dumensil JG. Patient-prosthesis mismatch is not negligible. Ann Thorac Surg 2000;69:1983-1984.[Free Full Text]
- Hanayama N, Christakis GT, Mallidi HR, Joyner CD, Fremes SE, Morgan CD, Mitoff PR, Goldman BS. Patient prosthesis mismatch is rare after aortic valve replacement: valve size may be irrelevant. Ann Thorac Surg 2002;73:1822-1829.[Abstract/Free Full Text]
- Medalion B, Blackstone EH, Lytle BW, White J, Arnold JH, Cosgrove DM. Aortic valve replacement: is valve size important?. J Thorac Cardiovasc Surg 2000;119:963-974.[Abstract/Free Full Text]
- De Paulis R, Sommariva L, De Matteis GM, Caprara E, Tomai F, Penta de Peppo A, Polisca P, Bassano C, Chiariello L. Extent and pattern of regression of left ventricular hypertrophy in patients with small size CarboMedics aortic valves. J Thorac Cardiovasc Surg 1997;113:901-909.[Abstract/Free Full Text]
- Milano AD, De Carlo M, Mecozzi G, D'Alfonso A, Scioti G, Nardi C, Bortolotti U. Clinical outcome in patients with 19-mm and 21-mm St. Jude aortic prostheses: comparison at long-term follow-up. Ann Thorac Surg 2002;73:37-43.[Abstract/Free Full Text]
- Yamasaki M, Sasaguri S, Hosoda Y, Takazawa K, Yamamoto T, Hariya A. Long-term results for aortic valve replacement with small aortic annulus. Artif Organs 2002;26:474-478.[CrossRef][Medline]
- Izzat MB, Kadir I, Reeves B, Wilde P, Bryan AJ, Angelini GD. Patient-prosthesis mismatch is negligible with modern small-size aortic valve prostheses. Ann Thorac Surg 1999;68:1657-1660.[Abstract/Free Full Text]
- Okura H, Yoshikawa J, Yoshida K, Akasaka T, Shakudo M, Hozumi T, Takagi T, Honda Y, Yamamuro A. Value and limitations of valve resistance in assessing prosthetic aortic valve function: clinical study using dobutamine stress doppler echocardiography. J Cardiol 1996;27:9-13.[Medline]
- Sharma UC, Barenbrug P, Pokharel S, Dassen WR, Pinto YM, Maessen JG. Systematic review of the outcome of aortic valve replacement in patients with aortic stenosis. Ann Thorac Surg 2004;78:90-95.[Abstract/Free Full Text]
- Weinberg EO, Lee MA, Weigner M, Lindpaintner K, Bishop SP, Benedict CR, Ho KK, Douglas PS, Chafizadeh E, Lorell BH. Angiotensin AT1 receptor inhibition. Effects on hypertrophic remodeling and ACE expression in rats with pressure-overload hypertrophy due to ascending aortic stenosis. Circulation 1997;95:1592-1600.[Abstract/Free Full Text]
- Jin XY, Westaby S, Gibson DG, Pillai R, Taggart D. Left ventricular remodeling and improvement in freestyle stentless valve haemodynamics. Eur J Cardiothorac Surg 1997;12:63-69.[Abstract]
- Walther T, Falk V, Langebartels G, Kruger M, Bernhardt U, Diegeler A, Gummert J, Autschbach R, Mohr FW. Prospectively randomized evaluation of stentless versus conventional biological aortic valves-impacts on early regression of left ventricular hypertrophy. Circulation 1999;100(Suppl. II):II6-II10.
- Doss M, Martens S, Wood JP, Aybek T, Kleine P, Greinecker GW, Moritz A. Performance of stentless versus stented aortic bioprostheses in the elderly patients: a prospective randomized trial. Eur J Cardiothorac Surg 2003;23:299-304.[Abstract/Free Full Text]
Top
Abstract
1. Introduction
