TEE evaluation of function during diastole was inconsistent but increased over the course of the study, approaching 90% of eligible patients by the end of the study. Relative frequency of reasons for incomplete evaluation (eg. poor image alignment, excessive nonechocardiographic demands) could not be determined. Data were captured on one hundred seventy-six eligible subjects (mean age 65.2 +/- 9.2 years, 73% male, 76% white). Baseline characteristics of study participants, with normal (N = 105) vs abnormal (N = 71) baseline performance during diastole, are shown in Table 1. Those with diastolic dysfunction: 1) were older; 2) were more likely to be female, and/or have a history of congestive heart failure, valvular disease, and/or renal dysfunction; 3) trended toward a higher prevalence of prior myocardial infarction and history of chronic lung disease; 4) less likely to have hypertension; 5) trended towards a shorter duration of CPB. Overall, baseline characteristics suggested a greater burden of comorbidity at baseline for those with diastolic dysfunction, supported by significantly higher baseline ASA class, a composite comorbidity score well recognized to be associated with postoperative morbidity and mortality [18–20]. Based on the log-likelihood test and BIC, LCA classified subjects into 2 groups (high and low severity) based on baseline characteristics, and the burden of comorbid illness appeared to be greater in latent class 2 than 1 (Suppl Table 1). Subjects with diastolic dysfunction were more likely to be classified in latent class 2 than 1 (Table 1).
Table 1
Characteristics of study sample for subjects with abnormal and normal pre-surgical performance during diastole.
|
Abnormal
N = 105
|
Normal
N = 71
|
P-value
|
Age, yrs (SD)
|
67.5 ± 9.02
|
61.6 ± 8.5
|
< 0.001***
|
Gender Female, N (%)
|
36(34.2%)
|
11(15.4%)
|
0.009**
|
Race, N (%) White/Balck/Asian/others
|
80(76%)/12(11.5%)/
9(8.6%)/4(3.8%)
|
54(76%)/9(12.8%)/
4(5.7%)/4(5.7%)
|
0.86
|
Congestive Heart Failure, N (%)
|
21(20%)
|
4(5.6%)
|
0.01*
|
Valvular Disease, N (%)
|
28(26.6%)
|
8(11.2%)
|
0.02*
|
PERIVASC
|
15(14.2%)
|
5(7.0%)
|
0.21
|
Hypertension, N (%)
|
49(46.6%)
|
52(73.2%)
|
< 0.001***
|
Diabetes mellitus, N (%)
|
40(38%)
|
30(42%)
|
0.69
|
Chronic lung disease
|
25(23.8%)
|
8(11%)
|
0.06*
|
Chronic kidney disease
|
27(25.7%)
|
7(9.8%)
|
0.01*
|
Obesity, N (%)
|
33(31.4%)
|
22(31%)
|
0.99
|
Myocardial infarction, N (%)
|
29(27.6%)
|
10(14.0%)
|
0.052*
|
Stroke/TIA, N (%)
|
7(6.6%)
|
4(5.6%)
|
0.99
|
Arrhythmia, N (%)
|
26(24.7%)
|
11(15.4%)
|
0.16
|
ASA class = 4, N (%)
|
55(52.3%)
|
23(32.3%)
|
0.01*
|
Duration of CPB CPB
|
96.33 ± 37.5
|
108.0 ± 49.09
|
0.09*
|
Latent Class 2- High severity of illness
|
48(45.7%)
|
12(17%)
|
< 0.001***
|
Median time to hospital discharge was significantly longer for subjects with abnormal vs normal performance during diastole (abnormal: 9.1/IQR 6.6–13.5 days; normal: 6.5/IQR 5.3–9.7 days) (P < 0.001 by Kruskal-Wallace test). Probability of hospital discharge on any given postoperative day (hereafter referred to as “daily probability of discharge”) was significantly lower for those with diastolic dysfunction (Fig. 1).There was a dose-response relation between severity of diastolic dysfunction and daily probability of discharge - those having the most severely abnormal performance had the lowest daily probability of discharge (Fig. 2).
We examined the independent relation of baseline diastolic dysfunction to daily probability of discharge in a series of unadjusted and adjusted Cox-Proportional Hazards models (Table 2) Daily probability of discharge was 46% lower (RR 0.54/95% CI 0.40–0.75) for those with diastolic dysfunction compared to those with normal performance during diastole in unadjusted analysis. Adjusting for age, sex (Table 2, Model 1), duration of CPB (Table 2, Models 1, 2), severity of illness latent class (Table 2, Models 2, 3) history of heart failure and myocardial infarction (Table 2, Model 3), the daily probability of discharge remained significantly lower for those with diastolic dysfunction. A Sensitivity Analysis excluding 5 subjects with more than mild valvular disease (eg. MAC, Aortic disease, Mitral disease) did not affect these results (RR 0.63/95% CI 0.45–0.90). Our propensity analysis successfully matched 42 subjects with and without diastolic dysfunction, and showed that daily probability of discharge was 37% lower (RR 0.63/95% CI 0.40-1.00) for those with diastolic dysfunction. Our LCA showed the daily probability of discharge: 1) was significantly lower for the group with both diastolic dysfunction and high severity of illness latent class (RR 0.39/95% CI 0.26–0.58; P < 0.001); 2) tended to be lower in the group with diastolic dysfunction and low severity of illness (RR 0.72/95% CI 0.50–1.05; P = 0.09); 3) had not pattern of relation for the two strata with normal performance during diastole (Fig. 3). Finally, in additional models that included LV performance during diastole E and the E/e’ ratio as covariates in the regression model, the association between abnormal e’ and discharge was unchanged (RR 0.61/ 95% CI 0.42–0.88). Abnormal E was also independently associated with discharge (RR 0.61/ 95%CI0.39-0.94), but E/e’ was not (RR 0.85/95% CI 0.48–1.52).
Table 2
Adjusted and un-adjusted rate ratios for discharge from the hospital using cox proportional hazard model
|
Un-adjusted Rate Ratios
|
P Value
|
Adjusted Rate Ratios Model 1
|
P Value
|
Adjusted Rate Ratios Model 2
|
P Value
|
Adjusted Rate Ratios Model 3
|
P Value
|
Abnormal pre-surgical performance during diastole
|
0.54*** (0.40,0.74)
|
< 0.001
|
0.52*** (0.36,0.75)
|
< 0.0001
|
0.56**
(0.39,0.79)
|
0.001
|
0.61** (0.42,0.88)
|
0.009
|
E; ref = normal
|
0.62* (0.41,0.94)
|
0.023
|
0.57* (0.37,0.88)
|
0.01
|
0.58* (0.38,0.88)
|
0.01
|
0.61* (0.39,0.94)
|
0.02
|
E-e prime ratio; ref = normal
|
0.57* (0.33,0.97)
|
0.04
|
0.78 (0.43,1.42)
|
0.42
|
0.82 (0.46,1.44)
|
0.49
|
0.85 (0.48,1.52)
|
0.60
|
Duration of CPB
|
0.99 (0.99,1.00)
|
0.61
|
0.997 (0.993,1.00)
|
0.17
|
0.997
(0.993,1.00)
|
0.12
|
0.996*(0.992,0.999)
|
0.044
|
Age
|
0.98 (0.97,1.00)
|
0.08
|
0.993 (0.97,1.01)
|
0.46
|
|
|
|
|
Female gender
|
1.46* (1.03,2.07)
|
0.03
|
1.05 (0.70,1.57)
|
0.80
|
|
|
|
|
CHF
|
0.43*** (0.26,0.71)
|
0.001
|
|
|
|
|
0.50* (0.25,0.99)
|
0.047
|
Valvular disease
|
0.70 (0.47,1.03)
|
0.07
|
|
|
|
|
|
|
Hypertension
|
1.67*** (1.22,2.29)
|
0.001
|
|
|
|
|
1.14 (0.67,1.92)
|
0.62
|
Chronic Lung disease
|
0.97 (0.66,1.42)
|
0.88
|
|
|
|
|
|
|
Renal
|
0.58*** (0.40,0.85)
|
0.006
|
|
|
|
|
0.55* (0.30,0.99)
|
0.049
|
Myocardial infarction
|
0.55*** (0.38,0.79)
|
0.001
|
|
|
|
|
0.51*** (0.35,0.75)
|
< 0.001
|
ASA = 4 (ASA = 3 as Ref)
|
0.75 (0.55,1.02)
|
0.06
|
|
|
|
|
|
|
Latent class 2- high severity of illness
|
0.56*** (0.40,0.78)
|
< 0.001
|
|
|
0.65*
(0.45,0.93)
|
0.02
|
1.20 (0.56,2.55)
|
0.63
|
There were no significant differences in intravenous fluid administration (6169 ± 2958 ml vs. 6229 ± 3542 ml, P = 0.99) or transfusion of packed red blood cells (229 ± 404 ml vs. 187 ± 377 ml; P = 0.48) between subjects with and without diastolic dysfunction. Secondary intermediate outcomes are shown in Table 3. Subjects with diastolic dysfunction were more likely to be extubated > 6 hours after surgery, to require supplemental oxygen longer, and to be diagnosed with the composite outcome of heart failure, respiratory insufficiency/failure, or pulmonary edema. We found no significant differences by performance during diastole in the incidences of postoperative atrial fibrillation, AKI, stroke, or infection. A higher proportion of subjects with diastolic dysfunction were readmitted to the ICU; however, this difference was not statistically significant (Table 3).
Table 3
Secondary outcomes for subjects with abnormal and normal pre-surgical performance during diastole.
|
Abnormal
N = 105
|
Normal
N = 71
|
P-value
|
Interval to extubation > 6 hrs, N (%)
|
45 (42.8%)
|
17 (23.9%)
|
0.01*
|
Interval to breathing from room air, days, median (IQR)
|
1.63 (0.68,3.04)
|
0.89 (0.55,2.82)
|
0.05 (Kruskal- Wallace)
|
Composite cardiopulmonary morbidity
|
21 (20%)
|
6 (8.4%)
|
0.037
|
Atrial fibrillation, N (%)
|
30 (28.5%)
|
14 (19.7%)
|
0.26
|
Hypotension, N (%)
|
47 (44%)
|
23 (32%)
|
0.13
|
Hypervolemia, N (%)
|
48 (46%)
|
34 (49%)
|
0.89
|
Maximum increase in creatinine, %, SD
|
18 ± 27
|
14 ± 15
|
0.21
|
KDIGO AKI, N (%)
|
26 (24.7%)
|
18 (25.3%)
|
0.99
|
Ischemic stroke, N (%)
|
0 (0%)
|
2 (2.8%)
|
0.16
|
Composite Infectious morbidity
|
6 (5.7%))
|
1 (1.4%)
|
0.23
|
ICU readmission, N (%)
|
8 (7.6%)
|
1 (1.4%)
|
0.08
|
Composite infectious morbidity = SSI, pneumonia, sepsis; Composite cardiopulmonary morbidity = heart failure, resp failure, resp insufficiency, pulm edema
|
The relation of diastolic dysfunction and secondary intermediate outcomes to daily probability of discharge is shown in Table 4. Similar to baseline diastolic dysfunction, each of the secondary outcomes was associated with a lower daily probability of discharge in unadjusted analysis. In multivariable cox regression, secondary outcomes had modest effect on the relation between baseline diastolic dysfunction and daily probability of discharge, which remained 37% less likely for those with diastolic dysfunction (Table 4).
Table 4
Relation of baseline abnormal nonsystolic function and secondary outcomes to time to hospital discharge
|
Un-adjusted Rate Ratios
|
P Value
|
Adjusted Rate Ratios Model1
|
P Value
|
Dysfunction before surgery
|
0.54*** (0.40,0.75)
|
< 0.001
|
0.63* (0.45,0.89)
|
0.01
|
Latent class 2- high severity of illness
|
0.53*** (0.38,0.74)
|
< 0.001
|
0.73 (0.50,1.07)
|
0.11
|
Duration of CPB
|
0.99 (0.99,1.00)
|
0.70
|
0.997 (0.992,1.001)
|
0.16
|
Interval to extubation > 6
|
0.60** (0.44,0.83)
|
0.002
|
0.81 (0.57,1.15)
|
0.25
|
Time to room air
|
0.88*** (0.81,0.94)
|
< 0.001
|
0.93 (0.86,1.00)
|
0.08
|
Composite cardiopulmonary morbidity
|
0.47*** (0.31,0.73)
|
< 0.001
|
0.78 (0.47,1.30)
|
0.34
|
Atrial fibrillation
|
0.70* (0.49,0.99)
|
0.04
|
0.87 (0.60,1.26)
|
0.49
|
Hypotension
|
0.61** (0.44,0.83)
|
0.001
|
0.73 (0.52,1.01)
|
0.06
|
Composite Infectious morbidity
|
0.30** (0.13,0.70)
|
0.005
|
0.30* (0.12,0.77)
|
0.01
|
ICU Readmission
|
0.46* (0.23,0.90)
|
0.02
|
0.60 (0.29,1.26)
|
0.18
|
Composite infectious morbidity = SSI, pneumonia, sepsis; Composite cardiopulmonary morbidity = heart failure, resp failure, resp insufficiency, pulm edema
|