Risk Scores Do Not Predict High Mortality After Coronary Artery Bypass Surgery in the Presence of Diastolic Dysfunction

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1 Risk Scores Do Not Predict High Mortality After Coronary Artery Byass Surgery in the Presence of Diastolic Dysfunction Lorenzo Merello, MD, Erick Riesle, MD, Javier Alburquerque, MD, Humberto Torres, MD, Ernesto Aránguiz-Santander, MD, FACC, Oneglio Pedemonte, MD, and Bernhard Westerberg, MD School of Medicine, University of Valaraíso, Valaraíso, and Cardiovascular Surgery Service, Hosital Dr. Gustavo Fricke, Viña del Mar, Chile Background. Although global ostoerative mortality an alteration of relaxation, mortality was 5 of atients 129 after on-um coronary artery byass grafting is aroximately 3%, in some grous it can be considerablyatients (12.5%); and in the restrictive grou it was 6 of (3.8%); in the seudonormal grou it was 2 of 16 higher. Many conditions are known to increase mortality 13 atients (46.1%; < 0.01). Parsonnet and EuroSCORE and have been included in well-known scoring systems; redicted a mortality of 1.5% to 1.6%, 1.5% to 2.0%, 1.5% however, left ventricular diastolic dysfunction has not to 2.2%, and 3.9% to 4.1% for each grou, resectively. been sufficiently evaluated to identify its redictive Mortality in the grou with E deceleration time of 150 ms value for mortality after coronary artery byass grafting, or greater was 2.8% and in the grou with E deceleration nor is it integrated in currently used risk scores. time less than 150 ms was 17.3% < ( 0.01). Postoerative Methods. Left ventricular filling attern was rosectively evaluated in 191 atients scheduled for on-um advanced dysfunction. comlications were also more frequent in the grou with coronary artery byass grafting. A follow-u of survival Conclusions. Severe diastolic dysfunction is a strong and comlications was made for 30 days ostoeratively. redictor of adverse outcome and mortality after onum coronary artery byass grafting, and this high risk Observed mortality was comared with the mortality redicted by the scores of EuroSCORE and Parsonnet. is not adequately redicted by EuroSCORE and Parsonnet score. Measures of diastolic function should be Results. A correlation was found between diastolic function, the resence of comorbidities, and ostoera- included in routine reoerative risk assessment. tive survival. There was no mortality in the grou with normal filling attern (0 of 33 atients). In the resence of (Ann Thorac Surg 2008;85: ) 2008 by The Society of Thoracic Surgeons Atherosclerotic coronary heart disease is the greatest cause of cardiovascular death in the world, and its incidence is rising worldwide, articularly in develoing countries as a result of demograhic and lifestyle changes [1]. The global erioerative mortality reorted by The Society of Thoracic Surgeons for coronary artery byass grafting (CABG) surgery is aroximately 3% [2], but unfortunately many factors have been identified to adversely affect the outcome, which can raise mortality in certain grous of atients. Different redictive factors have been groued in a number of reoerative risk evaluation scores to hel estimate the risk of death after surgery [3 13]. Among these factors, systolic dysfunction has been one of the most studied and is widely validated as a redictor of bad outcome and so is routinely evaluated and reorted reoeratively before CABG surgery. Nonetheless, through the echocardiograhic study, it is ossible to also Acceted for ublication Dec 26, Address corresondence to Dr Merello, University of Valaraiso, Anesthesiology, Servicio Cirugía Cardiovascular, Viña del Mar, Alvares 1532, Chile; lorenzomerello@gmail.com. acquire adequate information about the diastolic function of the left ventricle and its caacity of relaxation and suction. Thus, several indexes of diastolic filling attern have been validated. Most authors classify diastolic filling attern according to the relationshi between early filling deceleration time (EDT) and measurements of the ratio between early diastolic filling (E wave) and atrial contraction (A wave; the E/A relation), ulmonary venous flow, and isovolumetric relaxation time [14]. Among the multile variables described, the measurement of EDT has been considered a simle and useful variable to quantify the stiffness of the left ventricle [15]. This reort rosectively assesses the correlation between left ventricular diastolic filling atterns, measured by echocardiograhy, with ostoerative mortality and comlications in atients who underwent on-um CABG. The scarce evidence available suggests that in atients with severe systolic dysfunction, there is a correlation between the magnitude of the associated left ventricular diastolic dysfunction and erioerative mortality [16, 17]. It is also clear that usually the rogression 2008 by The Society of Thoracic Surgeons /08/$34.00 Published by Elsevier Inc doi: /j.athoracsur

2 1248 MERELLO ET AL Ann Thorac Surg DIASTOLIC DYSFUNCTION PREDICTS HIGH MORTALITY 2008;85: Table 1. Clinical Characteristics and Preoerative Risk Factors a,b Normal Filling Pattern (n 33) Alteration of Relaxation (n 129) Pseudonormal (n 16) Restrictive (n 13) Female sex 7 (21.2%) 42 (32.5%) 2 (12.5%) 2 (15.3%) 0.21 Age (y) Weight (kg) Height (cm) CCS class III or IV 17 (51.5%) 66 (51.1%) 11 (73.3%) 11 (91.6%) 0.02 Hyertension 23 (69.7%) 109 (84.5%) 11 (68.7%) 8 (61.5%) 0.04 Diabetes mellitus 11 (33.3%) 42 (32.5%) 3 (18.7%) 7 (53.8%) 0.27 Age y 5 (15.1%) 35 (27.1%) 3 (18.7%) 2 (15.3%) 0.46 Age y 0 (0%) 6 (4.6%) 0 (0%) 1 (7.7%) 0.37 Age 80 or more 1 (3.3%) 0 (0%) 1 (6.2%) 1 (7.7%) 0.03 LVEF (9.9%) 26 (20.1%) 6 (37.5%) 9 (69.2%) Renal failure 3 (9.9%) 1 (0.8%) 2 (12.5%) 5 (38.4%) Dialysis deendency 2 (6.6%) 0 (0%) 0 (0%) 2 (15.4%) Severe eriheral vascular disease 0 (0%) 6 (4.6%) 2 (12.5%) 0 (0%) 0.19 Obesity 4 (12.1%) 20 (15.5%) 2 (12.5%) 0 (0%) 0.57 Left main disease 3 (9.0%) 16 (12.4%) 3 (18.7%) 1 (7.9%) 0.75 Neurologic disorder 0 (0%) 4 (3.1%) 0 (0%) 0 (0%) 0.78 COPD 0 (0%) 2 (1.5%) 0 (0%) 0 (0%) 1.00 CPB time (min) Clam time (min) vessel disease 24 (72.7%) 87 (67.4%) 11 (68.7%) 10 (76.9%) 0.71 Number of grafts a Summary of clinical characteristics of atients groued by diastolic filling attern. The restrictive grou was older and had a significantly higher incidence of LVEF , renal failure, dialysis deendency, hyertension, and CCS class III or IV. They also had significantly higher CPB and cross-clam times. b s exressed in number and ercentage or mean and standard deviation. CCS Canadian Cardiovascular Society functional classification of angina; COPD chronic obstructive ulmonary disease; CPB cardioulmonary byass; EDT E wave deceleration time; LVEF left ventricular ejection fraction. in heart disease is accomanied by a worsening in other comorbidities, and the overall risk should be calculated considering the comlete clinical condition. However, there are no ublished studies designed to show the imortance of diastolic dysfunction as an indeendent redictor to recommend its incororation in the reoerative risk scores available. On the basis of this background this study sought to determine the imact of diastolic dysfunction on erioerative mortality and comlications and to comare these results with the redicted mortality calculated by the Euroean System for Cardiac Oerative Risk Evaluation (EuroSCORE) [9] and the Bernstein-Parsonnet risk stratification model [10]. We also tested the redictive value Table 2. Echocardiograhic s According to Diastolic Filling Pattern a Normal Filling Pattern (n 33) Alteration of Relaxation (n 129) Pseudonormal (n 16) Restrictive Pattern (n 13) E wave (m/s) A wave (m/s) E/A ratio LVEF EDT (ms) Left atrial size (mm) LVDd (mm) LVSd (mm) Setum (mm) Posterior wall (mm) a Summary of echocardiograhic measurements in atients groued by diastolic filling attern. EDT E wave deceleration time; LVDd left ventricle telediastolic diameter; LVSd left ventricle telesystolic diameter; LVEF left ventricular ejection fraction.

3 Ann Thorac Surg MERELLO ET AL 2008;85: DIASTOLIC DYSFUNCTION PREDICTS HIGH MORTALITY 1249 Table 3. Clinical Characteristics of Patients According to E Wave Deceleration Time a,b of EDT as one single echocardiograhic variable in the stratification of risk. Material and Methods (n 139) (n 52) Female sex 36 (25.9%) 17 (32.6%) 0.36 Age (y) Weight (kg) Height (cm) CCS class III ó IV 73 (52.9%) 32 (62.7%) 0.25 Hyertension 110 (79.1%) 41 (78.8%) 1.00 Diabetes mellitus 43 (30.9%) 20 (38.4%) 0.38 Age y 29 (20.8%) 16 (30.7%) 0.18 Age y 4 (2.8%) 3 (5.7%) 0.39 Age 80 or more 2 (1.4%) 1 (1.9%) 1.00 LVEF (15.8%) 22 (42.3%) Renal failure 3 (2.1%) 8 (15.3%) Dialysis deendency 2 (1.4%) 2 (3.8%) 0.29 Severe eriheral 6 (4.3%) 2 (3.8%) 1.00 vascular disease Obesity 23 (16.5%) 3 (5.7%) 0.06 Left main disease 18 (12.9%) 5 (9.6%) 0.62 Neurologic disorder 3 (2.1%) 1 (1.9%) 1.00 COPD 2 (1.4%) 0 (0%) 1.00 CPB time (min) Clam time (min) vessel disease 94 (67.6%) 38 (73.1%) 0.47 Number of grafts a Summary of clinical characteristics of atients stratified by E wave deceleration time. The grou with EDT less than 150 ms was older, had lower body weight, and had a higher incidence of low ejection fraction and renal failure. b s exressed in number and ercentage or mean and standard deviation. CCS Canadian Cardiovascular Society functional classification of angina; COPD chronic obstructive ulmonary disease; EDT E wave deceleration time; LVEF left ventricular ejection fraction. After the aroval by the institutional review board, 191 atients scheduled for on-um CABG surgery were recruited between March 2004 and May Because no secial care interventions were mandated by the rotocol, signed atient consent was waived. Exclusion criteria included off-um CABG, CABG associated with valve surgery, severe mitral or aortic valvuloathy, atrial fibrillation, and imlanted acemaker. Preoerative risk scores according to 2,000 Bernstein- Parsonnet and EuroSCORE algorithms were alied to all atients in this study. Then a comlete reoerative echocardiograhic evaluation was undertaken, including measurement of the diastolic filling attern of the left ventricle. Echocardiograhic Studies The echocardiograhic assessment was done with a General Electric model Vivid 7 (GE Healthcare, Milwaukee, WI) and the echocardiograhic studies were erformed by a single oerator. All studies were recorded on videotae and on hotograhic aer for further evaluation if necessary. A second oerator evaluated all cases that were difficult to interret. For the evaluation of diastolic function, ulsed Doler mitral filling flow was measured at the level of the oen mitral leaflets in the aical four-chamber view. The echocardiograhic exloration was obtained in a lateral decubitus osition, and measurements were made in M mode, two-dimensional, ulsed Doler, and colored Doler. The measurements included left ventricular end-diastolic diameter, left ventricular end-systolic diameter, setal wall, osterior wall, left atrium, and left ventricular ejection fraction. In all cases eak velocities of blood flow during early diastolic filling (E wave) and atrial contraction (A wave) are measured, and the E/A ratio was calculated. Measurements also included ulmonary venous flow, E wave deceleration time (EDT), and the resonse to the Valsalva maneuver in atients with normal or seudonormal filling attern. Classification of Patients According to the transmitral flow attern, atients were subdivided in four grous: grou 0 normal filling attern, with an E/A ratio less than 1.5 and EDT of 150 ms or greater; grou 1 alteration of relaxation, with an E/A ratio less than 1 and EDT of 150 to 250 ms; grou 2 seudonormal, with an E/A ratio less than 1.5 and EDT of 150 ms or greater, and a resonse to Valsalva ( ); and grou 3 restrictive, with an E/A ratio greater than 1.5 and EDT less than 150 ms. The relationshi between EDT and outcome was also evaluated; therefore, atients were subsequently divided into two grous according to the criteria ublished by Yong and colleagues [18]: grou A, EDT equal or greater than 150 ms, and grou B, less than 150 ms. Table 4. Echocardiograhic s According to E Wave Deceleration Time a (n 139) (n 52) E wave (m/s) A wave (m/s) E/A ratio LVEF EDT (ms) Left atrial size (mm) LVDd (mm) LVSd (mm) Setum (mm) Posterior wall (mm) a Summary of echocardiograhic measurements in atients groued by EDT. EDT E wave deceleration time; LVDd left ventricular telediastolic diameter; LVSd left ventricular telesystolic diameter; LVEF left ventricular ejection fraction.

4 1250 MERELLO ET AL Ann Thorac Surg DIASTOLIC DYSFUNCTION PREDICTS HIGH MORTALITY 2008;85: Table 5. Exected and Observed Mortality According to Filling Pattern a,e Normal Filling Pattern (n 33) Alteration of Relaxation (n 129) Pseudonormal (n 16) Restrictive (n 13) Parsonnet 1.5% ( ) 1.5% ( ) 1.5% ( ) 3.9% ( ) b EuroSCORE 1.6% ( ) 2.0% ( ) c 2.2% ( ) c 4.1% ( ) b Observed mortality 0.0% d 3.8% ( ) d 12.5% ( ) d 46.2% ( ) d a Observed mortality after coronary artery byass grafting surgery in atients with different diastolic filling atterns. Mortality was significantly higher in the restrictive grou (odds ratio, 20.9; 95% confidence interval, 5.5 to 78.9). This result is comared with the redicted mortality calculated by the scores of Parsonnet and EuroSCORE. b The redicted mortality was significantly higher for restrictive attern atients comared with other grous ( 0.01). c EuroSCORE redicted a higher mortality than Parsonnet in atients with alteration of relaxation and seudonormal attern ( 0.01). d Significant difference ( 0.001) for observed versus redicted mortality in all grous. Note that there was no mortality in atients with normal filling attern. e s exressed in mean and 95% confidence interval. Surgery Coronary artery byass grafting was erformed under cardioulmonary byass in mild hyothermia (34 C) and with alha-stat regulation of H. Myocardial rotection was achieved with crystalloid cardiolegia followed by intermittent cold blood antegrade or retrograde cardiolegia. Follow-U Data During the ostoerative eriod, data of survival and comlications were recorded u to 30 days after surgery. Tabulated comlications included erioerative myocardial infarction (new Q waves or creatine kinase MB elevation 50 U), atrial fibrillation, ventricular tachycardia or other arrhythmias requiring theray, heart failure or low cardiac outut (cardiac index less than 2 L min 1 m 2 lus inotroic agent use), cerebrovascular accident (focal deficit documented by clinical or scanner examination), rolonged mechanical ventilation (more than 24 hours ostoeratively), acute renal failure (urinary outut less than 400 ml/24 hours, creatinine levels twice the reoerative values, or increase in uremia by more than 50 mg%), reoeration of any cause, and intraoerative mortality and mortality u to 30 days. The follow-u after discharge was made by telehone. Statistical Analysis In-hosital and 30-day ostoerative mortality was considered the binary resonse variable. For each atient several covariates were registered that allowed the calculation of both EuroSCORE and Parsonnet as a measure of risk of death. In addition, diastolic dysfunction severity (0, 1, 2, and 3, where 0 means no diastolic dysfunction and 3 means the most severe dysfunction) was registered. The binary mortality through logistic models for each of three covariates (EuroSCORE, Parsonnet, and diastolic filling attern) searately and together was evaluated. A binary diastolic dysfunction was defined as equal to zero if there was no dysfunction or it was tye 1 or 2, and equal to one if there was a tye 3 dysfunction, because it was susected that the restrictive attern is a better redictor of ostoerative mortality. This logistic model will allow the acquisition of the odds ratio of death among the atients who have tye 3 dysfunction with resect to those atients who have no dysfunction or tye 1 or 2 diastolic dysfunction. Fig 1. Relationshi between redicted mortality (Parsonnet, light gray bars, and EuroSCORE, darker gray bars) and observed mortality (black bars), according to left ventricular diastolic filling attern. The grous with seudonormal and restrictive attern had a mortality significantly higher than redicted. (Alt altered.)

5 Ann Thorac Surg MERELLO ET AL 2008;85: DIASTOLIC DYSFUNCTION PREDICTS HIGH MORTALITY 1251 Table 6. Exected and Observed Mortality According to E Wave Deceleration Time a,b Table 8. Multivariate Forward Stewise Logistic Analysis Results a (n 139) (n 52) Odds Ratio 95% Confidence Interval Parsonnet 1.4% ( ) 2.2% ( ) EuroSCORE 1.8% ( ) 2.8% ( ) Observed mortality 2.8% ( ) 17.3% ( ) a Observed mortality after coronary artery byass grafting surgery in atients with different diastolic filling atterns. Mortality was significantly higher in the grou with E wave deceleration time (EDT) less than 150 ms (odds ratio, 7.0; 95% confidence interval, 2.0 to 24.0). This result is comared with the redicted mortality calculated by the scores of Parsonnet and EuroSCORE. b s exressed in mean and 95% confidence interval. Renal failure Restrictive filling attern Age 70 y a Significant redictive conditions for ostoerative mortality after onum CABG. Results are resented as odds ratios with 95% confidence intervals. statistical comutations were erformed with Stata (StataCor, 2005, College Station, TX). A searate univariate logistic regression analysis was drawn from the clinical variables described in EuroSCORE and the score of Parsonnet. Then a forward stewise multile logistic regression analysis was erformed to evaluate the indeendent role of each significant variable identified by the univariate analysis, using robability values of 0.10 as the threshold for entering variables. s were included in the model if they reached a significance level of robability of less than 0.05 in univariate analysis. For other numerical variables, the unaired Student s t test was used to comare means between two grous. Analysis of variance and Bonferroni multile comarison tests were used for comarison among multile grous. The 2 test or Fisher s exact test was used for categorical variables. s are exressed as the mean standard deviation unless otherwise secified. The statistical analysis was erformed by the Center of Statistical Studies of the University of Valaraíso. All the Table 7. Univariate Analysis Results a Odds Ratio 95% Confidence Interval Age 70 y Female sex Left main disease Congestive heart failure Diabetes mellitus Ejection fraction Hyertension Obesity (BMI 30) Reoeration Renal failure Dialysis deendency Restrictive diastolic dysfunction CCS class III or IV ms a Univariate analysis assessing the individual associations of the risk factors with in-hosital or 30-day mortality. Results are resented as odds ratios with 95% confidence intervals. BMI body mass index; CCS Canadian Cardiovascular Society; EDT E wave deceleration time. Results Patients were divided into four grous according to reoerative left ventricular filling attern. Baseline clinical characteristics and reoerative risk factors are summarized in Table 1. According to the left ventricular filling attern, 33 of 191 atients (17.3%) had reserved diastolic function, 129 of 191 atients (67.5%) had a attern of alteration of relaxation or grade 1 dysfunction, 16 of 191 atients (8.4%) had a seudonormal attern or grade 2 dysfunction, and 13 of 191 atients (6.8%) had a restrictive filling attern or grade 3 dysfunction. Age, sex, incidence of diabetes mellitus, obesity (body mass index 30 kg/m 2 ), and left main disease did not differ significantly among grous. The grou with more advanced imairment of diastolic function had a higher incidence of renal failure, dialysis deendency, low ejection fraction, and a higher incidence of Canadian Cardiovascular Society (CSS) functional class III or IV. In agreement with the tyical echocardiograhic and Doler waveforms found in left ventricular diastolic dysfunction, the grous differed in E and A wave eak velocities, EDT, and ejection fraction ( 0.01). The echocardiograhic characteristics are listed in Table 2. The resence of EDT less than 150 ms as a marker of clinically significant diastolic filling abnormality was found in 52 of 191 atients (27.2%). The grou with EDT less than 150 ms was significantly older, had lower body weight, and a higher incidence of ejection fraction less than 0.50 and renal failure. This association could be exlained by the arallel rogression of other athologic conditions and the rogressive reduction of the amount of viable myocardium. Tables 3 and 4 list the clinical and echocardiograhic variables for each grou according to the EDT. Patients with higher grades of diastolic dysfunction showed reduced ejection fraction, shorter EDT, and increased systolic and diastolic ventricular dimensions. There was no difference in the number of diseased vessels, number of grafts, or cross-clam time. Preoerative Estimation of Risk The overall reoerative estimation of risk according to the criteria defined by Parsonnet resulted in a mean score

6 1252 MERELLO ET AL Ann Thorac Surg DIASTOLIC DYSFUNCTION PREDICTS HIGH MORTALITY 2008;85: Table 9. Adverse Events a Tye of Comlication Normal Filling Pattern (n 33) Alteration of Relaxation (n 129) Pseudonormal (n 16) Restrictive (n 13) Low cardiac outut 0 (0%) 3 (2.3%) 1 (6.2%) 3 (23.1%) Acute renal failure 1 (3.0%) 2 (1.5%) 0 (0%) 6 (46.1%) Prolonged mechanical ventilation 0 (0%) 6 (4.6%) 0 (0%) 8 (61.5%) Perioerative infarction 1 (3.0%) 6 (4.6%) 0 (0%) 1 (7.7%) 0.75 Atrial fibrillation 5 (15.1%) 19 (14.7%) 1 (6.2%) 5 (38.4%) 0.14 Other arrhythmias 2 (6.6%) 9 (6.9%) 2 (12.5%) 1 (7.7%) 0.75 Any comlication 9 (27.2%) 42 (32.5%) 4 (25%) 10 (76.9%) 0.01 a Postoerative comlications after coronary artery byass grafting surgery according to the resence of left ventricular diastolic dysfunction. The restrictive grou had a higher incidence of low cardiac outut, acute renal failure, and rolonged mechanical ventilation. of 9.1 for the cohort studied (range, 0 to 35 oints). Patients with the most severely imaired diastolic function had a number of associated clinical conditions that increased their redicted mortality. The scores of Parsonnet and the EuroSCORE identified this increased risk, showing a statistically significant raise of estimated mortality in the grou with more severe dysfunction ( 0.01). There were no fatalities in the grou with normal filling attern (0 of 33 atients). In the resence of alteration of relaxation mortality was 5 of 129 atients (3.8%), in the seudonormal grou, 2 of 16 atients (12.5%), and in the restrictive grou, 6 of 13 atients (46.1%; 0.01). The odds ratio was 20.9 for the restrictive grou versus the nonrestrictive (95% confidence interval, 5.5 to 78.9). The mortality rate observed in the grous with seudonormal and restrictive filling attern largely exceeded the mortality redicted by the risk scores (Table 5). The relationshi between exected mortality derived from the alication of Parsonnet and EuroSCORE and observed mortality is shown in Figure 1. When data were analyzed according to EDT, the redicted mortality calculated by EuroSCORE risk scale was slightly higher than the redicted by Parsonnet (Table 6). The grou with EDT less than 150 ms had a much higher Fig 2. Frequency of ostoerative adverse events according to left ventricular diastolic filling attern. There is a statistically significant higher number of adverse events in the restrictive grou. (Alt altered.) mortality than the grou with EDT of 150 ms or greater (odds ratio, 7.0; 0.01). Although observed mortality was statistically higher than exected in both grous, it was not clinically significant in the low-risk grou. Conversely, the observed mortality in the grou with EDT less than 150 ms was much higher than exected. Risk scores were able to detect the slightly higher mortality exected with the associated extracardiac conditions, but were insufficiently accurate to redict the high mortality seen in the grous with seudonormal or restrictive filling atterns. Table 7 lists the results of the univariate logistic analysis for the evaluated risk factors. In the final multivariate regression model, the only variables found to indeendently redict mortality were renal failure, restrictive filling attern, and advanced age (Table 8). Adverse Events The incidence of clinically significant ostoerative comlications differed between normal and imaired diastolic function atients. Adverse events were observed in 9 of 33 atients (27.2%) with normal filling attern, in 42 of 129 atients (32.5%) with grade 1 dysfunction, in 4 of 16 atients (25%) with grade 2 dysfunction, and in 10 of 13 atients (76.9%) with grade 3 or restrictive filling attern. Postoerative low cardiac outut, acute renal failure, rolonged mechanical ventilation, and overall comlication rate was higher in the restrictive grou (Table 9). Mean length of stay in the hosital was 8 days for grous 0, 1, and 2 and 13 days for atients with grade 3 dysfunction as a result of a higher morbidity rate in atients with more severe ventricular dysfunction. The need of rolonged mechanical ventilation was also higher in the grou with EDT less than 150 ms; they also had a higher incidence of atrial fibrillation, erioerative infarction, other arrhythmias, and acute renal failure. The overall incidence of comlications was also significantly higher in atients with EDT less than 150 ms ( 0.01). Desite the incidence of articular comlications being higher in this grou, it did not reach statistical significance, excet for acute renal failure ( 0.01). The mean event rate er atient was also increased in the grou with restrictive filling attern as shown in Figure 2. These results show that the rogression of left ventricular filling abnormality is associated with more

7 Ann Thorac Surg MERELLO ET AL 2008;85: DIASTOLIC DYSFUNCTION PREDICTS HIGH MORTALITY 1253 atients with comlicated ostoerative course and also accomanied by an increase in the number of comlications er atient. Comment In recent years increasing evidence has been gathered to show that imairment in diastolic function is associated with a oor rognosis in atients with ischemic cardioathy [19], congestive heart failure [20], or dilated myocardioathy [21]. On the other hand, there has been growing interest in making risk-adjusted analysis of outcome after heart surgery. Nevertheless, the role of diastolic dysfunction in ostoerative mortality after CABG is still not well established. In fact, there are only a few reorts that suggest that left ventricular diastolic dysfunction is a redictor of oor ostoerative outcome, and to the resent day it has not been incororated in any cardiac surgery risk score. In this study, we comared our results with two well-validated risk models [22]. Early investigations showed that atients with elevated end-diastolic ressures exerienced more comlications and greater erioerative mortality than atients with normal telediastolic ressures [23]. With the advance of noninvasive exloration with echocardiograhy and cardiac Doler, diastolic function can be easily and recisely evaluated, in a raid and simle way, ositioning this method as the gold standard for the assessment of diastolic function [24]. Desite the knowledge gained in recent years, the relationshi between diastolic dysfunction and erioerative mortality after CABG surgery is not well known. Also there is no universal consensus about the best way of defining diastolic dysfunction. A study ublished in 2001 by Vaskelyte and associates [16] analyzed atients with severely imaired systolic function (left ventricular ejection fraction less than 0.35) undergoing CABG and who also had a restrictive diastolic filling attern. Their erioerative mortality was high (33%) comared with atients with less severely altered filling attern, who had a mortality of 13.6%. The 56 atients included in this study had left ventricular diastolic dysfunction, and there were no atients with normal filling attern. The study concluded that grade 3 diastolic dysfunction drastically affects erioerative mortality and that systolic function did not imrove after surgery in this grou, contrasting with the imrovement seen in atients with less severe dysfunction. This observation has led the authors to question the benefit of CABG surgery in atients with restrictive filling attern [16]. The above-mentioned study was the first to oint out the redictive value of the assessment of left ventricular diastolic function by echocardiograhy before CABG surgery, but did not include a control grou with normal filling attern, or normal or less severe alteration of systolic function. It also excluded atients with diabetes mellitus, nehroathy, or other morbidity osing some unanswered questions. The study did not stratify atients according to the estimated reoerative risk by any validated risk score index to hel evaluate the results with reference to an established risk. A more recent study erformed in the University of Yamaguchi in Ube, Jaan, by Liu and coworkers [17] comares longtime survival in 102 atients who underwent CABG surgery according to the ostoerative filling attern. After a 60-month follow-u, the authors conclude that atients with normal or grade 1 diastolic dysfunction have a better long-term survival comared with atients with seudonormal or restrictive attern, in which survival declined at 50 months to 40% and 20%, resectively. These results agree with the results by Vaskelyte and coworkers [16] in a oulation that excludes chronic renal failure. Owing to the long-term design, in this reort there is no conclusion about erioerative mortality and there is no evaluation of erioerative comlications. A third study correlates EDT with myocardial viability. This study by Yong and colleagues [18] shows that atients with EDT less than 150 ms undergoing CABG have less viable segments measured by echocardiograhic dobutamine stress test and by single-hoton emission comuted tomograhic myocardial scintigrahy. This grou had a lower recueration of systolic function after surgery and worse rognosis after 3 months follow-u. Our study corroborates the high incidence of abnormal diastolic function in atients undergoing CABG. Some degree of dysfunction was found in 156 of 191 atients (81.7%) entering this study. The observed mortality in the grous with normal or nonrestrictive filling attern was 5 of 162 atients (3,08%) as comared with the restrictive grou, which was 6 of 13 atients (46.2%; odds ratio, 20.9). These results agree with the conclusions by other reorts suggesting that advanced diastolic dysfunction is a strong redictor of ostoerative morbidity and mortality after on-um CABG. It is known that left ventricular diastolic dysfunction is associated with a variety of conditions that increase ostoerative risk, such as aging, history of myocardial infarction, diabetes, low ejection fraction, renal function imairment, and others [25]. We also found that the grou with more severe dysfunction had a higher incidence of reoerative low ejection fraction and renal failure, with a tendency to be older and to have lower body weight. Even considering the higher incidence of associated comorbidity in atients with more severe imairment of diastolic function, the mortality redicted by the scores of Parsonnet and EuroSCORE was only around 4% in the restrictive attern grou. This study shows the low redictive value of these otherwise wellvalidated scores in the rediction of mortality in atients with advanced diastolic dysfunction. Consistent with the results of the logistic regression analysis, the incororation of diastolic dysfunction as a risk factor would add a owerful redictor of ostoerative adverse outcome. The analysis of ostoerative comlications also showed a significant increase of adverse events in the restrictive grou. This condition was associated with a higher incidence of low cardiac outut, rolonged me-

8 1254 MERELLO ET AL Ann Thorac Surg DIASTOLIC DYSFUNCTION PREDICTS HIGH MORTALITY 2008;85: chanical ventilation, arrhythmias, and ostoerative acute renal failure. Most of the ublished aers do not reort the incidence of comlications, which are associated with higher hosital workload and economic costs associated with treatment. All the comorbidities found in the higher risk atients can exlain in art the higher mortality in this grou. Otherwise, the risk scores even considering these comorbid conditions in the estimation of ostoerative outcome were unable to accurately redict the high mortality associated with diastolic dysfunction. It is necessary to elucidate whether some of the comorbid conditions incororated in these risk scores, such as advanced renal failure, increase mortality through an imact on diastolic function. Prognostic Significance of E Wave Deceleration Time In search of a simle and readily available measurement of diastolic function, we evaluated the redictive value of a simle way to analyze and stratify left ventricular filling attern. The first stratification was according to a commonly used graduation in severity, and the other was based on the measurement of one single variable (EDT) as a marker of clinically significant left ventricular diastolic filling abnormality, with a cutoff oint of 150 ms. Although the second is simle because it considered only one measure, the first allowed identifying the subgrou with the highest risk, reresented by the restrictive attern. It is robable, however, that if the cutoff oint for EDT to define significant diastolic dysfunction is set at a lower level, eg, 130 ms, it could ossibly identify a grou with higher risk of morbidity and mortality. Diastolic dysfunction seems to be a rogressive disease, with a worse rognosis and increased mortality in advanced stages, as occurs in diabetes, renal disease, aging, and other conditions. Because of the comlexity of diastolic function, it aears reasonable that no single variable or Doler attern should be used in isolation, and conversely, all comrehensive Doler and two-dimensional features should be considered to accurately assess diastolic function. It is of interest to note the high revalence (64%) of alteration of relaxation (grade 1 dysfunction) in our study oulation. Desite its aarent benign condition, a discrete higher morbidity and mortality was observed in this grou comared with atients with normal filling attern. Further studies in a larger oulation should be undertaken to confirm this finding. Study Limitations Our study included only atients who were oerated on using on-um techniques, so a difference in results with off-um CABG could exist. However, there is evidence in a reort by Ng and associates [26] that shows there is no difference in the filling attern after on-um versus off-um CABG, suggesting that robably there is no difference in resulting morbidity or mortality between the two techniques. It is also necessary to consider that the evaluation of diastolic function could be limited in the resence of tachycardia, atrial fibrillation, and other situations that could render its measurement difficult. Another limitation in this study is the difference in the number of atients in each grou, which was conditioned by the design in which we included all atients scheduled for on-um CABG who met the inclusion criteria. Desite this limitation, it allowed us to observe how these variables are seen in the usual oulation scheduled for CABG. In conclusion, our findings suggest that diastolic dysfunction is a strong indeendent redictor of adverse outcome and that it should be considered as a clinical variable to be evaluated routinely in the risk stratification systems. Considering that Doler echocardiograhy screening is routinely erformed reoeratively before cardiac surgery, information about diastolic function should be regularly obtained. Larger studies are needed to identify the best way to accurately define the resence and severity of diastolic dysfunction and also to calculate its secific redictive ower comared with other conditions already incororated in the commonly used risk scores. Studies should be designed additionally to identify better strategies to lower the morbidity and mortality in these high-risk atients. We are grateful to Carlos Henríquez-Roldan, PhD, Centro de Estudios Estadísticos, Universidad de Valaraíso, Valaraíso, Chile, for his exert statistical advice and assistance. 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