Eur J Echocardiography (2001) 2, doi: /euje , available online at on

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1 Eur J Echocardiography (2001) 2, doi: /euje , available online at on Coronary Artery Bypass Grafting in Patients with Severe Left Ventricular Dysfunction: Predictive Significance of Left Ventricular Diastolic Filling Pattern J. Vaskelyte*, N. Stoskute, S. Kinduris and E. Ereminiene Cardiosurgery Clinic and Biomedical Research Institute of the Kaunas University of Medicine, Kaunas, Lithuania Aims: The aim of our study was to evaluate the influence of left ventricular (LV) diastolic filling impairment on postoperative results in patients (pts) with low LV ejection fraction (EF) (<35%) undergoing coronary artery bypass grafting (CABG). Methods: The study covered 56 patients (mean age years). Two dimensional Doppler echocardiographic investigations were performed pre- and days post-cabg. Patients were divided into three s according to the LV diastolic filling. Results: Early postoperative mortality rate (including perioperative period and 2 weeks after surgery) was highest in the restriction (33%) vs. pseudonormalization (12 5%) vs. impaired relaxation (13 6%). Postoperative cardiovascular complications rate was highest also in the restriction, 55 5%, and did not differ between pseudonormalization (25%) and impaired relaxation (27 2%). Logistic regression analysis showed that restrictive LV filling pattern, early diastolic filling deceleration time and LV end-diastolic diameter independently influence perioperative mortality. In the early postoperative period mean LV wall motion score (WMS) did not improve in 8/19 (42%), 6/14 (43%) and 8/12 (67%) patients, respectively, in the impaired relaxation, pseudonormalization and restriction. Conclusions: In patients with severe LV dysfunction undergoing CABG, impaired relaxation and pseudonormal pattern of LV diastolic filling correlated with postoperative improvement in LV regional contraction, while restrictive pattern correlated with high early postoperative mortality, morbidity and minimal improvement in LV systolic function. Restrictive LV filling pattern, early diastolic filling deceleration time and LV end-diastolic diameter were found to be independent predictors of perioperative mortality. (Eur J Echocardiography 2001; 2: 62 67) 2001 The European Society of Cardiology Key Words: coronary artery disease; low left ventricular ejection fraction; left ventricular diastolic filling. Introduction Coronary artery bypass grafting (CABG) is an alternative to cardiac transplantation for patients (pts) with coronary artery disease (CAD) and severe left ventricular (LV) dysfunction [1]. Cohort studies evaluating the efficacy of CABG have shown that these patients benefit most from revascularization, especially if symptoms of angina are present [2,3]. Myocardial revascularization in *Address for correspondence: Jolanta Vaskelyte, Cardiosurgery Clinic, Kaunas University of Medicine, Eiveniu 2, 3007 Kaunas, Lithuania. patients with severe LV dysfunction prevents further myocardial damage, preserves the remaining myocardium and induces the recovery of systolic function of hypoperfused and hypocontractile LV myocardium segments. However, postoperative mortality rate in this patient ranges from 1 6 to 40 [4]. Multivariate predictors of significant functional improvement after CABG include concomitant angina [5] and preoperative extent of viable myocardium [6]. Risk factors for operative death from CABG are defined in general population and include age, LV ejection fraction (EF), urgency of operation, previous CABG, female sex, left main coronary artery stenosis, presence and severity /01/ $35.00/ The European Society of Cardiology

2 Coronary Artery Bypass Grafting and Left Ventricular Dysfunction 63 of comorbid conditions [7]. LVEF is commonly used for risk stratification of patients undergoing CABG, but alone is not always accurate predictor of survival [8]. Several studies have also proved that increased LV end-systolic and end-diastolic volumes in conjunction with low LVEF are a definitive risk for CABG [8 10]. The majority of the studies dealing with CABG efficacy and its prediction in patients with ischaemic LV dysfunction usually analyse only the parameters of LV systolic function [1 5]. Thus, the aim of our study was to evaluate the influence of LV diastolic filling impairment on postoperative results in patients with low LV EF undergoing CABG. Methods From September 1996 to September 1998, 126 patients with LVEF <35% underwent CABG. Clinical exclusion criteria were: valvular heart disease (including > moderate mitral regurgitation), acute myocardial infarction (MI), severe arrhythmia, comorbid conditions such as diabetes mellitus, renal dysfunction, previous CABG, resection of ventricular aneurysm, valve replacement and other surgical procedures. Therefore, 56 patients (49 male and seven female) (mean age years) constituted the final study population. Three-vessel CAD and MI in history was noted in 50/56 (93) patients. III IV CHA angina class was noted in 43/56 (78%) patients. III IV NYHA functional class was noted in 46/56 (82%) patients. In the preoperative period the medication therapy was optimized and consisted of: (1) nitrates in 56 (100%) patients; (2) ACE inhibitors 55/ 56 (96%) patients (including 22 (100%) patients with impaired relaxation filling pattern, 16 (100%) patients pseudonormal and 17/18 (94%) patients restrictive filling); (3) loop diuretics 32/56 (57%) patients (including 8/22 (36%) patients with impaired relaxation, 7/16 (43%) patients pseudonormal and 17/18 (94%) patients restrictive filling); and (4) B blockers 40/56 (71%) patients (including 16/22 (73%) patients with impaired relaxation, 11/16 (69%) patients pseudonormal and 13/18 (72%) patients restrictive filling). CABG was performed using conventional techniques with crystalloid cardioplegia. Venous saphena grafts and internal mammary artery were used in all cases, with revascularization index graft/patient. Two-dimensional Doppler echocardiography was performed preoperatively and days after CABG using Sigma 44 system (Kontron Intruments, France) equipped with 3 5 MHz transducer. Images were recorded on videotape and independently assessed by two experienced observers. Two dimensional echocardiographic investigations included measurements of LV end-diastolic diameter (EDD), LV wall thickness, LV mass index and LV EF, which were made according to American Society Echocardiography guidelines [11].LV segmental wall motion was analysed according to the 16-segments model grading (normal motion as 1, hypokinesis 2, akinesis 3, dyskinesis 4) and wall motion score (WMS) index was calculated. LV diastolic filling was analysed from the fourchamber view with PW Doppler sample volume positioned at the leaflet tips of the opened mitral valve. The greatest velocity of diastolic flow was obtained by visual guidance, making efforts to reach the smallest possible angle between the blood flow direction on colour Doppler and the cursor at the sampling region. Peak flow velocities were measured at the darkest point of the spectral waveform. Measurements included transmitral early (E) and late (A) peak filling velocities, their ratio (E/A), E-velocity deceleration time (DT E ), A- velocity deceleration time (DT A ) and isovolumic relaxation time (IVRT). Three to five cardiac cycles were analysed. Mean heart rate did not differ significantly during pre ( bpm) and postoperative ( bpm) studies. The impaired relaxation filling pattern was defined as E/A ratio <1 and deceleration time >220 ms. The pseudonormal filling pattern was defined as an E/A ratio between 1 and 2 with deceleration time between 150 and 220 ms. The restrictive filling pattern was defined as an E/A 2 or by the combination of an E/A ratio between 1 and 2 with a deceleration time <150 ms [12]. Statistical Analysis All values in the text and tables are given as mean standard deviation. Clinical data was compared by the Mann Whitney U test, a two-tailed t-test or Kruskal Wallis one-way Anova when appropriate. Frequency of events was compared by the Chi-squared test. Difference between two percentages was evaluated by two-sided test. A P<0 05 was considered statistically significant. A number of variables which might affect perioperative events were entered into a stepwise logistic regression model. Variables were entered into or removed from the model on the basis of a computed significance probability. The P-values to enter or remove variables were 0 05 and 0 1, respectively. The demographic variables selected for examination were age (continued values), gender (female yes/no); clinical variables: left main coronary artery stenosis (yes/no), perioperative death (yes/no); echocardiographic variables: LV EF, LVE DD, LV mass index, LV WMS (continued values for all); Doppler variables: E/A ratio, deceleration time (DT E ) (continued values) and the presence of a restrictive filling pattern (yes/no). Results All patients under the study were divided into three s according to the LV diastolic filling pattern:

3 64 J. Vaskelyte et al. Table 1. Clinical data. Impaired relaxation n=22 Pseudonormalization n=16 Restriction n=18 Mean age (years) CAD Two-vessel 2/22 (9%) 0 3/18 (16 7%) Three-vessel 20/22 (91%) 16 (100%) 15/18 (83 3%) Angina III IV CHA class 17/22 (77%) 14/16 (87%) 13/18 (72%) Previous MI Anterior 14/22 (63%) 10/16 (62 5%) 11/18 (61%) Posterior 9/22 (40%) 8/16 (50%) 9/18 (50%) >1 MI 6/22 (27%) 5/16 (31 3%) 6/18 (33%) NYHA functional class III IV 17/22 (77 3%) 13/16 (81%) 15/18 (83 3%) CAD, coronary artery disease; CHA, Canadian Heart Association; MI, myocardial infarction. Table 2. Two-dimensional Echocardiographic data. Impaired relaxation n=22 Pseudonormalization n=16 Restriction n=18 LV EDD (mm) LV WTh (mm) LV MMI (g/m 2 ) * * LV EF (%) * * LV WMS * * *Differences between the s P<0 05. EDD, end diastolic diameter; EF, ejection fraction; LV, left ventricle; MMI, myocardial mass index; WMS, wall motion score; WTh, wall thickness. Table 3. Early postoperative clinical data (complications). Impaired relaxation n=22 Pseudonormalization n=16 Restriction n=18 Postoperative mortality rate (perioperative+2 weeks after operation) Postoperative cardiovascular complications (perioperative MI, low cardiac output, arrhythmias) rate 3/22 (13 6%)* 2/16 (12 5%) 6/18 (33%)* 6/22 (27 2%)* 4/16 (25%) 10/18 (55 5%)* *Differences between the s, P< , impaired relaxation, 22 patients; 2, pseudonormalization, 16 patients; 3, restriction, 18 patients. Patients clinical data are presented in Table 1. Mean age, severity of involvement of coronary arteries, rate of angina, previous MI, multiple MI and III IV NYHA functional class did not differ significantly between the s. Echocardiographic data are presented in Table 2. Mean LV EDD, LV mass index and LV WMS was highest and LV EF lowest in the restriction. The three latter indices significantly differed between the pseudonormalization and restriction s. Postoperative complications are shown in Table 3. Mortality rate, including perioperative period and 2 weeks after surgery, was highest in the restriction and lowest in the impaired relaxation. Cardiovascular complications (perioperative MI, low cardiac output or/and arrhythmias including atrial fibrillation flutter, ventricular tachycardia) rate was highest in

4 Coronary Artery Bypass Grafting and Left Ventricular Dysfunction 65 Table 4. Logistic regression for perioperative events (mortality). Variable β-coefficient Wald 95% Confidence interval for Exp (β) P value DT E Restrictive filling pattern LV EDD Constant LV EF LV MMI LV WMS E/A ratio Left main coronary artery stenosis Age Female gender DT E, early diastolic filling velocity deceleration time; E/A, ratio of early to late filling velocity; EDD, end diastolic diameter; EF, ejection fraction; LV, left ventricle; MMI, myocardial mass index; WMS, wall motion score. Table 5. Preoperative LV diastolic filling indices related to postoperative changes of LV WMS. Impaired relaxation Postoperative WMS Decreased (n=11) Unchanged (n=8) Pseudonormalization Postoperative WMS Decreased (n=8) Unchanged (n=6) Decreased (n=4) Restriction Postoperative WMS Unchanged (n=8) E (cm/s) A (cm/s) ** ** E/A DT E (s) ** ** DT A (s) IVRT (s) **Differences between subs, P<0 05. A, late diastolic filling velocity; DT E, early diastolic filling velocity deceleration time; DT A, late diastolic filling velocity deceleration time; E, early diastolic filling velocity; E/A, ratio of early to late filling velocity; IVRT, isovolumic relaxation time; LV, left ventricular; WMS, wall motion score. the restriction. Perioperative event rate differed between the restriction and impaired relaxation. Variables including demographic (age, gender), clinical (left main coronary artery stenosis), echocardiographic (LV EF, LV EDD, LV mass index, LV WMS) and Doppler (restrictive filling pattern, DT E, E/A ratio) which might influence perioperative events (mortality) were entered for logistic regression analysis. Among the variables evaluated, only LV EDD, restrictive filling pattern and DT E were found to be independent predictors of perioperative mortality (Table 4). The influence of diastolic filling indices on postoperative dynamics of LV function was analysed in the survivors. After CABG, mean LV WMS had a tendency to decrease in all s: in the impaired relaxation from to ; pseudonormalization from to ; and restriction from to However, LV WMS did not improve in 8/19 (42%), 6/14 (43%) and 8/12 (67%) patients, respectively, in the impaired relaxation, pseudonormalization and restriction s. Distribution of patients according to the postoperative changes in LV WMS permitted the retrospective comparison of the values of LV diastolic filling indices in patients with postoperative improvement in regional LV contraction vs. no improvement (Table 5). In the impaired relaxation and pseudonormalization s preoperative values of LV diastolic filling indices did not differ between subs with and without improvement in regional LV contraction. In restriction A velocity was significantly lower and DT E shorter in the patients sub without postoperative improvement in regional LV contraction. Analysis of absolute values of A-velocity and DT E in two subs of patients with the restrictive pattern of LV filling showed that, in the case of unimproved LV WMS after CABG in all patients A-velocity was 30 cm/s and DT E 0 11 s, while in the case of improved LV regional contraction, A-velocity lower than 30 cm/s was noted only in one patient, and all DT E values were 0 12 s. Discussion Impairment of LV diastolic filling is a common consequence of myocardial ischaemia or infarction in patients

5 66 J. Vaskelyte et al. with CAD [13]. Impaired LV relaxation is an early finding of the disease. With disease progression, LV compliance becomes reduced and filling pressures begin to increase making filling pattern pseudonormal. Patients with advanced heart disease stage present with restrictive filling pattern: very severe decrease in LV compliance and marked elevation in LA pressure [14,15]. In our study different patterns of LV diastolic filling were noted despite pronounced CAD (93% of patients had three-vessel CAD and previous MI) and severely depressed LV function. The degree of involvement of coronary arteries and rate of previous myocardial infarction did not differ between the s, and differences in the diastolic dysfunction degree may be related to the duration of CAD, to the timing of previous myocardial infarction, and to the presence or absence of collateral coronary arteries. Though severity of CAD did not differ between the s, LV systolic dysfunction was most marked in the restriction : echocardiographic investigation revealed the highest LV EDD, LV mass index and LV WMS and lowest LV EF. Significant differences were found between these indices in the restriction vs. pseudonormalization. These findings are in agreement with the experimental and clinical studies proving association between restrictive filling pattern and advanced stage of myocardial involvement [16 19]. In our study restrictive LV diastolic filling pattern was the marker of poor prognosis in patients with low LV EF undergoing CABG, as the postoperative complications and mortality rate was highest and the number of patients presenting with improved systolic function after CABG was lowest in the restriction. Moreover, the logistic regression analysis showed that restrictive filling pattern and DT E as well as LV EDD independently influenced perioperative mortality in this of patients. Prognostic value of the diastolic filling patterns has already been demonstrated in patients with dilated [19] and restrictive [20] cardiomyopathies as well as in patients with acute myocardial infarctions [21].Itwas also stated that mitral deceleration time is the most powerful predictor of LV dilation after reperfused acute myocardial infarction [22]. In some studies in patients with dilated cardiomyopathy and cardiac amyloid, restrictive diastolic filling pattern and the mitral deceleration time was the best predictor of reduced survival and was independent of LV systolic function [23]. Deceleration time of early filling was confirmed to be a powerful independent predictor of poor prognosis in patients with symptomatic or asymptomatic LV systolic dysfunction [24]. Predictors of reduced survival after CABG have been determined in general population [7] : however, the relation between mortality after CABG and LV diastolic filling indices has not been fully investigated. The relation between perioperative mortality and restrictive diastolic filling, determined in the present study, is in agreement with other studies which already have proved that elevated LV filling pressure is a strong predictor of perioperative mortality in this subs of patients [25]. Limitations of the study are the small number of patients in the subs, early postoperative follow-up (10 14 days after operations) and only conventional mitral inflow indices used for evaluation of LV diastolic function. This study will be continued in order to encounter more patients and evaluate changes in the late postoperative period. Conclusions In patients with severe LV dysfunction undergoing CABG, impaired relaxation and pseudonormal pattern of LV diastolic filling correlated with postoperative improvement in LV regional contraction, while restrictive pattern correlated with high early postoperative mortality, morbidity and minimal improvement in LV systolic function. Restrictive LV diastolic filling pattern, DT E and LV EDD were found independently to influence perioperative mortality in patients with low LV EF undergoing CABG. Despite the limitations (concerning the small number of patients and short follow-up), our data may be helpful in identifying patients with severely depressed LV function who will or will not benefit from CABG. References [1] Winkel E, Piccione W. Coronary artery bypass surgery in patients with left ventricular dysfunction: candidate selection and perioperative care. Heart Lung Transplant 1997; 16: S19 S24. [2] Elefteriades JA, Kron IL. CABG in advanced left ventricular dysfunction. In: Elefteriades JA, Lee FA, Letsou GV (eds). Cardiology clinics: Advanced treatment options for the failing left ventricle. Philadelphia: WS Saunders Company, 1995; [3] Bounous EP, Mark DB, Pollock BK et al. Surgical survival benefits for coronary disease patients with left ventricular dysfunction. 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