In developing countries, rheumatic heart disease prevails as the main cause of valvular heart disease (VHD)  . Over the last decade, patients undergoing heart valve surgeries are more likely to be at higher surgical risk   compared to previous data. The most common factor influencing outcomes after heart valve surgery is coronary artery disease (CAD)   . Isolated valvular surgery seems to have a negative impact on the operative mortality when coronary artery stenosis was neglected  . Conversely, a significant reduction in mortality is seen in such patients who undergo concomitant coronary revascularization procedures   . In some previous reports, combined procedure was associated with elevated short- and long-term mortality  . More recently, improvement in surgical techniques, myocardial protection and post-operative care could explain better short-term outcomes. The purpose of the present study is to analyze the influence of coronary artery bypass grafting (CABG) on hospital mortality and morbidity in patients undergoing heart valve surgery in our institutions.
2. Patients and Methods
A retrospective review of the cardiac surgical data base from two institutions between January 2000 and December 2018 was performed to evaluate and compare the immediate outcome for patients undergoing isolated heart valve surgery (IVS) compared to patients undergoing a combined procedure including heart valve surgery and coronary artery bypass grafting (VS + CABG). During the study period, all consecutive patients with a valvular heart disease undergoing heart valve surgery were included. A total of 1667 patients were included and divided into two groups: Group A isolated heart valve surgery (IVS, n = 1608) and Group B with heart valve surgery and coronary artery bypass grafting (VS + CABG, n = 59). Although these two groups are expected to be very different in terms of cardiovascular risk, morbidity and mortality, we found very useful to make the comparison. Valve dysfunction and pathology was investigated by echocardiography and color Doppler while coronary artery disease (CAD) was defined as more than 50% stenosis of at least one major epicardial coronary artery  . Anesthetic, surgery and per operative management were practiced per divisional protocols. All surgical procedures were performed by cardiac surgeons of our medical centers. All procedures were performed through a median sternotomy with cardiopulmonary bypass (CPB) and under mild systemic hypothermia (32˚C - 34˚C). Myocardial protection was achieved with cold blood cardioplegia.
For patients undergoing combined surgery, distal anastomoses were performed before valve surgery. Proximal vein graft anastomoses were performed after valve surgery and aortic cross clamp was removed. Both bioprostheses and bileaflet mechanical heart valve were used for heart valve replacement. Heart valve repair was performed using a rigid ring. CABG was performed using the left internal mammary artery (LIMA), right internal mammary artery (RIMA) and/or venous grafting. To conclude the surgical indication, patients were discussed in a multidisciplinary heart team meeting.
30 days mortality was defined as death within 30 days of operation. Major cardio vascular events included: post operative acute myocardial infarction (AMl), stroke, cardiac death. Operative morbidity was defined as all postoperative complications: acute renal failure (ARF), stroke, prolonged ventilation, AMI, wound infection, re exploration for bleeding, Low cardiac output syndrome (LOS) causing longer Intensive Care Unit (lCU) stay, Multiple Organ Dysfunction Syndrome (MODS).
The local ethical committees of each participating institution approved aims and methods of this study.
Statistical analysis: Database management and statistical analysis were performed using SPSS version 19.0 (SPSS, lnc. Chicago, USA).
All continuous variables were expressed as mean ± SD. For asymetric variables, the median with the range interquartile were displayed. Normal and ordinal variables were expressed as effectif and percentages. For nominal variables, the chi-square tester Fisher’s exact test were used to compare the groups. Continuous variables were analyzed using student’s t test for normal distributions and Mann-Whitney’s test for non-normal distributions. P value < 0.05 was considered to be statistically significant. Missing data were handled by multiple imputations, extreme outliers were kept during post-test analysis and there was no need to indeterminate results management.
A total of 1667 adult consecutive patients who underwent heart valve surgery were included in the study. Among them 59 patients (3.5%) underwent combined procedure: valvular surgery + coronary artery bypass graft surgery (VS + CABG). Demographic and preoperative characteristics of the two groups are shown in Table 1.
Aortic Valve Replacement was more common in the VS + CABG goup 74.5% versus 51.6% in the Isolated Valve Surgery group while Aortic and Mitral Valve Replacement was less common 6.7% versus 24.7% in the IVS group (see Table 2).
Analysis shows a significant difference in gender (p = 0.0001). Patients with combined procedure were older than patients who underwent isolated valvular surgery (64.9 ± 9.2 years vs 44.4 ± 13.1 years; p = 0.0001) and there was a higher proportion of diabetics (40.7% vs 6.6%; p = 0.0001).
Table 1. Pre-operative patient characteristics.
Table 2. Valve surgery procedures between groups.
The VS + CABG group had worse cardiac risk profiles, with significantly more diabetes mellitus (p = 0.0001), arterial hypertension (35.6% vs 9.2%; p < 0.001), dyslipidemia (30.5% vs 6.4%; p < 0.001), smoking (49.1% vs 25%; p < 0.001).
The mean number of cardiovascular risk factors was 1.73 ± 1.11 (VS + CABG) versus 0.60 ± 0.83 (IVS) (p = 0.0001). At the time of surgery, VS + CABG group had a worse clinical status with high NYHA class (NYHA functional class III-IV; 59.7% vs 38.9% (p = 0.002)). No significant differences were noted between groups in regard to previous stroke, chronic pulmonary obstructive disease (CPOD) and renal dysfunction.
A significant difference was found between the groups in terms of left ventricular ejection fraction (LVEF) 52.8% ± 13.7% (VS + CABG) vs 58.0% ± 11.2% (IVS) (p = 0.001). Patients with combined procedure had a higher proportion of left ventricular dysfunction (LVEF < 40%) 30.5% (VS + CABG) vs 9.5% (IVS) (p = 0.0001). The distribution of coronary artery disease in combined procedure group was: left main coronary stenosis (10.1%), left anterior descending artery LAD (77.9%), circumflex artery stenosis (30.5%), right coronary artery stenosis (20.3%). The prevalence of coronary artery disease (CAD) was higher in patients with aortic stenosis (AS) when compared to mitral valve disease. (AS + CAD = 39 cases). Aortic regurgitation + CAD = 1 case, mitral regurgitation + CAD = 6 cases, mitral + aortic disease + CAD = 5 cases. Coronary revascularization was performed in combined surgical procedure with a mean of 1.66 ± 0.76 (range = 1 - 4) distal grafts per patient.
Operative and post operative data were listed in Table 3 and Table 4. In VS + CABG group, CPB time, aortic cross clamp time, mechanical respiratory support time, and ICU stay were longer when compared to patients who underwent IVS.
The 30 days mortality rate in the combined procedure group was 18.6% versus 6.2% in isolated valve surgery (p = 0.001). The relative risk of overall 30 days mortality increases by 3 times between VS + CABG and IVS group. The main cause of early death was low cardiac output syndrome (LOS).
The main post operative complications included LOS, Acute Renal Failure, Myocardial Infarction, infection, re-exploration for bleeding and Multiple Organ Dysfunction Syndrome. All of these complications were more frequent in the VS + CABG group. This group also required Red Blood Cells transfusion more than IVS group (p < 0.001).
Table 3. Operative data.
Table 4. Results and outcomes:
The principal findings of this study are that combined surgery had a higher hospital mortality rate and more post operative complications than isolated valve surgery. Indeed, undergoing CABG procedure increases 3 times the overall 30 days mortality when compared to IVS group. This is not only related to the CABG procedure itself but also to more risk factors (age, Diabetes, Hypertension, higher Euroscore, high CVS risk factors, poor LVEF (40%)) and higher cardiopulmonary bypass and aortic cross clamp time.
The worse immediate results of combined procedure (VS + CABG) were associated with the effect of pre existing co morbidities.
This study compares IVS group and VS + CABG group in 1667 consecutive patients so that means the real heart valve surgery practice in our institutions. Although these two groups are very different in terms of cardiovascular risk, morbidity and mortality, we have compared them for many reasons: 1) to measure how important is the impact of cardiovascular risk factors between groups; 2) to evaluate the mortality in the combined group and assess prognosis for such patients in our daily surgical practice; 3) to compare the overall 30 days mortality between groups (to our knowledge no such comparisons have been done previously); 4) to define the relative risk of mortality for CABG in patients undergoing heart valve surgery; 5) to contribute to a very limited literature in developing countries in this topic.
Patients with VS + CABG were older and more symptomatic, and had more coronary risk factors than patients with isolated valve surgery. Some previous reports observed similar characteristics in patients candidates for combined surgery    . Patients with severe left ventricular dysfunction found to have worse early outcomes. Our results noted that more proportion of patients with valvular disease and CAD had impaired LV function compared to those with isolated valve disease, and it is well known that it contribute to early mortality  .
In the present study, patients with valvular heart disease and coexisting coronary artery disease undergoing Heart Valve Surgery and Coronary Artery Bypass Grafting had substantially higher 30 days mortality than those having valve surgery procedure alone (18.6% vs 6.2%, p = 0.001). This result was consistent with some previous reports   . As the most valvular heart disease was aortic stenosis (AS) in our series, the increase in mortality could be related to subendocardial ischemia related to coronary artery disease with left ventricular hypertrophy; it is also known that hypertrophied heart is more susceptible to inflammatory response and ischemia-reperfusion injury during cardiopulmonary bypass  . Left ventricle hypertrophy and its effects were certainly increased by the Arterial Hypertension history among the VS + CABG group (35.6% versus 9.2% in the IVS group). The increased mortality observed could also be related to the prevalence of diabetes mellitus in the VS + CABG (40.7% versus 6.6% in the IVS group) as it is well known that this cardiovascular risk factor can increase mortality 2 to 4 times and may be more in patients with severe atherosclerotic coronary artery disease. Gunay et al.  reported an overall operative mortality of concomitant AS + CABG as 10% with aortic stenosis having a higher mortality 11.2% than aortic regurgitation 5%. However, the early surgical results have been improving during the last decade as result of improvement of surgical technique, better understanding of myocardial protection, and post-operative management  . Sakakura et al.  found no significant difference in 30-day mortality between Group A (Aortic Valve Replacement for aortic stenosis) and Group AC (Aortic Valve Replacement for aortic stenosis associated to CABG): 1.5% vs. 0.8%, p = 1.000.
The present study demonstrates that patients undergoing this major surgical procedure experienced also adverse postoperative events. This is particularly true in previous Vasques et al.  reports concerning patients of 80 years and older undergoing Aortic Valve Replacement and CABG.
The classic incidence of CAD in patients’ candidates for valvular surgery varies widely from 37% to 20%  . In previous reports, the overall prevalence of CAD in patients undergoing valve replacement has been shown to vary widely from 9% to 41%   . In western countries, the majority of those patients are elderly, have degenerative valve disease and multiple coronary risk factors. Aortic valve stenosis is the most frequent valve disease requiring intervention in the advanced age, and coronary artery disease affects 40% to 60% of them   , however, in developing countries heart valve disease is rheumatic and the prevalence of concomitant CAD is lower  . In the present study, the prevalence of CAD in patients submitted to valve surgery was 3.5% which is much consistent with reports published by other developing countries  .
Oliveira  observed that presence of more than one coronary lesion, determined risk of hospital death 4.99 times higher than in patients without this association. In our study, 66.1% of patients had more than one coronary artery disease lesion. The Fractional Flow Reverve (FFR)-Guided revascularization in patients with aortic stenosis in patients treated with CABG impacts the management with less venous grafts and anastomoses without increasing adverse event rates up to 5 years  . More recently, Shah et al.  suggested that the validity of FFR to guide surgical treatment in concomitant valvular disease is controversial and was “downgrading” coronary lesions. These findings could be related to left ventricular hypertrophy, and elevated left ventricle end-diastolic pressure (LVEDP) leading to increased microvascular resistance.
The prevalence of CAD according to valvular dysfunctions was reported by Emren  : mitral stenosis (26.4%), mitral regurgitation (41.9%), aortic stenosis (57.7%) and aortic regurgitation (44.4%). As it is known the incidence of CAD is more common in patients with aortic stenosis as compared to other groups 66.1% in the VS + CABG group in our series. This phenomenon most likely reflects similar pathogenic mechanisms related to calcify aortic stenosis and atherosclerotic coronary artery disease  . Age related calcification of the aortic valve is the most common cause of AS in adult population  . Therefore, there is a growing consensus that degenerative calcifies AS shares common pathophysiological features and metabolic pathways with atherosclerosis that can be targeted of disease   .
6. Study Limitation
The findings from this study suffer from the limitations due to its retrospective design. Also, the results showed comparable hospital mortality morbidity with some previous reports, but the comparison of the results in terms of risk factors for mortality seems to be difficult because of small sample and heterogeneous valve pathology.
We conclude that coexistent coronary artery has a negative influence on the early results in patients submitted to combined surgery. Early mortality in VS + CABG group is very high, and three times higher than IVS group. It is related to the risk factors, the coronary artery disease, the heart valve disease (and its consequences), the CABG procedure and the perioperative management. Indeed more careful patient management contributes to improve results and reduce hospital mortality.