Revealing of Initial Factors Defining Results of Operation in Patients with Aortic Valve Replacement and Coronary Artery Disease

Moderate aortic valve stenosis is a common condition in patients with coronary heart disease (Gullinov and Garsia, 2005). Recent studies have shown that progression of aortic valve stenosis depends on the degree of valvular leaflets calcification; that aortic valve replacement does not increase mortality after coronary artery bypass grafting (CABG); moreover,valve replacement performed after CABG leads to decreased mortality, it was especially confirmed in patients with severe aortic valve stenosis. However, review of the literature concerning integration of the mathematical approaches in medicine has demonstrated that, the simple prognosis is more significant than an evaluation based on organ and system modeling for choice of treatment method and options for patients with such combined pathology. Repeated intervention is one of the most significant prognostic factors. Thus, after analyzing of 13,346 CABG cases Yap et al (2007) have shown that mortality of repeated interventions is approximately 3 times higher than that of primary interventions (4.8% and 1.8%, respectively). Patient’s age is another such a factor. Urso et al. (2007) have established that one-year survival after aortic valve replacement in patients aged over 80 years (86,1%) is significantly less than that in the younger group. Analyzing of 1567 patients after valve replacement combined with CABG, Doenst et al.(2006) have demonstrated patients’ gender influence on surgery outcomes, postoperatively women had higher stroke possibility (risk index was 1.52). We believe that various influences of parameters characterizing patient’s baseline status on surgery outcome require more complex multivariate statistical analysis to be used. It allows defining rational number of the most significant factors determining the surgery prognosis related both to baseline status of patients with heart defects and immediate postoperative complications caused by interventional injury and heart hemodynamic changes (1, 2, 3, 4, 5, 6). Moreover, one of the authors of the article (Wann and Balkhy, 2009) considers that application of the most modern diagnostics tests (i.e. computed tomography coronary angiography) allows predicting an outcome of the scheduled surgery more accurately.


Introduction
Moderate aortic valve stenosis is a common condition in patients with coronary heart disease (Gullinov and Garsia, 2005). Recent studies have shown that progression of aortic valve stenosis depends on the degree of valvular leaflets calcification; that aortic valve replacement does not increase mortality after coronary artery bypass grafting (CABG); moreover,valve replacement performed after CABG leads to decreased mortality, it was especially confirmed in patients with severe aortic valve stenosis. However, review of the literature concerning integration of the mathematical approaches in medicine has demonstrated that, the simple prognosis is more significant than an evaluation based on organ and system modeling for choice of treatment method and options for patients with such combined pathology. Repeated intervention is one of the most significant prognostic factors. Thus, after analyzing of 13,346 CABG cases Yap et al (2007) have shown that mortality of repeated interventions is approximately 3 times higher than that of primary interventions (4.8% and 1.8%, respectively). Patient's age is another such a factor. Urso et al. (2007) have established that one-year survival after aortic valve replacement in patients aged over 80 years (86,1%) is significantly less than that in the younger group. Analyzing of 1567 patients after valve replacement combined with CABG, Doenst et al.(2006) have demonstrated patients' gender influence on surgery outcomes, postoperatively women had higher stroke possibility (risk index was 1.52). We believe that various influences of parameters characterizing patient's baseline status on surgery outcome require more complex multivariate statistical analysis to be used. It allows defining rational number of the most significant factors determining the surgery prognosis related both to baseline status of patients with heart defects and immediate postoperative complications caused by interventional injury and heart hemodynamic changes (1,2,3,4,5,6). Moreover, one of the authors of the article (Wann and Balkhy, 2009) considers that application of the most modern diagnostics tests (i.e. computed tomography coronary angiography) allows predicting an outcome of the scheduled surgery more accurately.

www.intechopen.com
Aortic Valve Surgery 20 The objective of this study was to investigate factors affecting the outcomes of combined interventions performed in patients with aortic valve defects and coronary artery lesions and to evaluate anatomical and hemodynamic parameters influencing the prognosis.

Material and methods of the study
One hundred twenty eight (128) patients who underwent one-step aortic valve replacement and CABG were enrolled in the study (104 men and 24 women aged from 40 to 73, mean age was 56.4±1.5 years). Aortic valve stenosis was predominant in 82.8% (106) cases; aortic insufficiency was predominant in 17.2% (22) cases. Aortic valve lesions were caused by rheumatic process (65.6%), atherosclerotic degeneration and calcification (15.6%), and infective endocarditis (18.8%). All patients underwent examination including chest X-ray, ECG, EchoCG. Increase in cardiothoracic index and change in pulmonary circulation were observed on X-ray scans. Enlargement of ascending aorta was revealed in all patients. Left ventricle hypertrophy and intraventricular conduction disturbance were observed on ECG. Aortic valve defect was complicated by valvular and extravalvular calcification in 87.1% patients: 3.2% -Grade I, 22.6% -Grade II, 32.3% -Grade III, 29% -Grade IV, absolutely, it was a complicating factor for surgery. Table 1   Consistency of numerical data with normal distribution law was assessed with Kolmogorov test. If the numerical data did not correspond to normal distribution law, non-parametric statistical methods were used -Wilcoxon rank test. Power and direction of correlation between the signs were determined by Pearson correlation coefficient (r) and Spearman rank correlation, if distribution of the baseline data was not normal. The values of these tests range from -1 to +1. The extreme values are observed in signs associated with linear functional relation. The significance of selected correlation coefficient is assessed by statistics value r* 2 n − / 12 r − = ta,f (1). Expression (1) permits to determine a, i.e. possibility of correlation coefficient difference from zero depending on r and sample size n. This, in turn, allows comparing the correlation of the same signs in the different sample sizes by possibility. Correlation power was assessed by a value of the correlation coefficient: strong, if r ≥0.7, moderate, if r = 0.3-0.7, weak, if r<0.3. The differences between compared values were significant if р<0.5, it is consistent with criteria accepted in medical and biological researches. Prognosis model is based on the regression analysis. Regression analysis was directed to the test of significance of one (dependent) variable Y from set of other ones, so called independent variables Xj = {X1, X2, … Xp}. The values of the prognostic parameter are defined as a result of determination of the risk factors based on analysis of the clinical materials. The purpose of linear regression analysis in this study was to predict the values of the resulted variable Y using the known values of physical parameters, EchoCG parameters and various additional features related to surgery specificity. Parameter of favorable surgery outcome was calculated as an arithmetic mean of risk factors. As a result of these calculations, the model was developed. Based on this model the program was created in "Excel-2000»: «Program for outcome prognosis of aortic valve replacement combined with coronary heart disease» (CERTIFICATE SPD RUz № DGU 01380») allowing to calculate a percentage of favorable surgery outcome and dynamics of LV ejection fraction after a surgery with prognostic significance 75-90%.

. Correlation between prognosis and functional class
Physical parameters (F2) suggested that PSG on AV had a trend to increase with age (r=0.264), i.e. compensated processes are progressing depending on age, although general biological and physiological processes are decreasing. However, age had no significant influence on surgery prognosis (r=-0.162). Moderate correlation between prognosis (r>0.31) and peak SPG (r>0,206) was observed when hemodynamic parameters were analyzed (F3). The correlation was direct for prognosis and reverse for SPG: e.g. in patients with CO more than 4.0 l/min surgery prognosis was higher. This parameter increased not due to HR, but due to minute volume (r=-0.215). Such pattern was observed between parameters of LV stroke work (Asw): surgery prognosis was higher if LV Asw was higher (r=0.468). But if SPG was increased, decrease in LV Asw was observed (r=-0.295). It may be concluded that increase in afterload leads to decrease in LV work efficacy (Figure 3). If peak SPG is more than 60 mmHg, LV Asw becomes less than 100 U, and favorable surgery prognosis does not exceed 80%. If stroke work was more than 100 U, positive surgery prognosis was 80-100%. It means that in patients with coronary artery lesions in combination with aortic defect SPG ≥ 60 mmHg is one of indications for aortic valve replacement. Heart parameters (F4) had the greatest influence on surgery prognosis. Thus, www.intechopen.com LV parameters had direct correlation with prognosis (r>0.224) and LV EF dynamics (r> 0.598) and reverse correlation with SPG (r<-0.343). LV end-diastolic dimension (EDD) and end-diastolic volume (EDV) had a greater influence on prognosis (r=0.349 and r=0.429, respectively), than LV end-systolic dimension (ESD) and end-systolic volume (ESV) (r=0.303 and r=0.352, respectively). Even in cases when increase in LV EDD (EDV) was observed after surgery and LV ESD (ESV) was constant (or decreased), possibility of favorable surgery prognosis was increased. This relationship between EDV and ESV contributes to increase in stroke volume (SV) and suggests preservation of LV myocardial contraction. The analysis showed that increased SV (r=0.458) and stroke index (SI) (r=0.385) was associated with increased percentage of favorable prognosis. We have found that if SI was >40 ml/m2 (SV=80 ml), positive surgery prognosis was more than 80% ( Figure 4). Analysis of influence of baseline EDV and ESV on postoperative LV EF has shown that this value was greater in patients with preserved LV parameters ( Figure 5), and in patients with significant reduction of LV EDV and ESV ( Figure 6). The performed analysis revealed that in patients with normal LV myocardial contractility at baseline we had good prognosis and increased LV EF after surgery. It was determined that if LV EF is higher than 50% at baseline, the positive surgery prognosis exceeds 80%. Such pattern of baseline EDV and ESV influence on LV EF dynamics was observed, if LV EF parameters obtained from calculation using the program for prognosis were analyzed. (Figure 7). Assessment of correlation between postoperative LV EF parameters and calculated ones using the program for surgery prognosis revealed a common pattern (trend lines had similar direction of dynamics and were approximately at the same level) (Figure 9). Decrease in postoperative LV EF is caused by cardiopulmonary bypass, aortic occlusion, and cardioplegia through unfavorable influence on myocardial contractility in spite of coronary artery bypass grafting, procedure improving coronary blood supply, activation of hibernated myocyte. Analysis of myocardial function parameters (F5) showed that surgery prognosis is highly affected by posterior left ventricular wall thickness (PLVWT) (r=-0.306) and to lesser extent by interventricular septum thickness (IVST) (r=-0.072). Increase in IVST leads to greater increase in peak SPG rather than PLVWT (r=0.679 and r=0.526, respectively). It can be possibly explained by appearance of additional component of LV outflow tract obstruction as a hypertrophied IVS. When thickness of IVC and PLVW ranges from 1.5 to 2.0 cm, SPG is equal to 80-120 mmHg, and positive surgery prognosis is 80-100%. However, increased dimensions of IVS and PLVW lead to decrease in percentage of favorable prognosis. Degree of ejection fraction increase was mostly related to PLVWT (r=0.433) than to IVST (r=0.265), had no relation with LV myocardial mass (r=-0.113), although increase in myocardial mass improved surgery prognosis. Thus, optimal left ventricle myocardial mass (LVMM) value was 350-600 g (200-400 g/m2) in the presence of corresponding linear parameters of LV and IVS. In these cases, positive surgery prognosis was more than 80%. Increase in ejection fraction more than 50% was postoperatively observed especially in patients with such characteristics. Analysis of valve morphology parameters (F6) revealed that significance of aortic valve calcification increases in peak SPG (r=0.448), but not affecting surgery prognosis (r=0.172). Baseline AV regurgitation also does not influence on surgery outcome (r=0.263).
We can see the possible explanation of this fact is that AV calcification in the patients was mostly caused by age-related sclerosis and rheumatoid degeneration with no elements of myocardial inflammation (myocarditis) and inflammation of conduction system.

Conclusion
Patients with aortic valve lesion combined with coronary artery lesion are a severe group for surgical treatment and require intervention at early stages of the disease. NYHA FC IV is a high-risk predictor for combined surgeries CHD + CABG. We believe that systolic gradient ≥60 mmHg in patients assigned to CABG is an indication for combined aortic valve surgery.
Analysis of LV linear and volume parameters revealed that LV diastolic dimension and diastolic volume had the greatest influence on prognosis in this patient group. iEDV/iESV ratio with SI>40 ml/ m2 (SV=80 ml) is a good prognostic sign allowing to predict a prognosis of more than 80%. The optimal LVMM value was 350-600 g (200-400 g/m2) in the presence of corresponding linear parameters of LV and IVS, when a surgery prognosis was higher than 80%, and baseline LVEF was more than 50%. Appearance of functional changes in MV (regurgitation grade >1) and TV (regurgitation grade >1) is a poor prognostic factor. LAD grafting in these patients is a required intervention, even is a lesion degree is less than 70%. It allows increasing the favorable surgery percentage. www.intechopen.com