Left Ventricular Diastolic Dysfunction as Predictor of Unfavorable Prognosis After ESUS

Figures & data

Table 1 Basic Characteristics of Patients in Both Groups

Parameters	Patients with ESUS (N=64)	Control Group (N=36)	p
Gender (male) [%]	42	61	0.059
Median age [years]	54 (47–58)*	53 (47–58)*	0.89
BMI [kg/m^2]	26.1 (22.4–28.7)*	25 (21.8–28.1)*	0.49
SBP [mmHg]	136 ± 18.7	128 ± 19.7	0.05
DBP [mmHg]	82 ± 9.9	81.8 ± 9	0.72
CAD [%]	9	9	0.76
Hypertension [%]	52	43	0.36
DM [%]	8	0	0.23
Smoking [%]	38	13	0.02
Laboratory results
LDL cholesterol [mmol/l]	2.83 (2.07–4)*	3.02 (2.66–3.67)*	0.37
HDL cholesterol [mmol/l]	1.19 (0.95–1.46)*	1.37 (1.19–1.6)*	0.02
Triglycerides [mmol/l]	1.58 (1.11–2)*	1.33 (0.86–1.7)*	0.16
Adiponectin [µg/mL]	6.65 (3.99–10.03)	6.62 (4.47–8.80)	0.70
Selected echocardiographic parameters
LVEF [%]	60 (55–64)*	63 (60–66)*	0.009
E [cm/s]	69 ± 17	76 ± 17	0.09
A [cm/s]	79 ± 19	64 ± 17	0.001
Mean E’ [cm/s]	8.6 (7.1–10.3)*	12.5 (9.6–14)*	0.0008
S’ [cm/s]	7.0 ± 1.0	8.0 ± 1.0	0.03
E/E’ [cm/s]	7.6 (6.1–8.9)*	6.0 (5.3–6.9)*	0.0002
LVMI [g/m^2]	112 (90–125.5)*	89.5 (77–101)*	0.0004
LA [mm]	36 (33–41)*	35 (32–38)*	0.07
LAVI [mL/m^2]	27 ± 11	21 ± 5	0.01
IVRT [m/s]	113 ± 23	97 ± 30	0.001
Evaluation of hemodynamic parameters using SphygmoCor system
AP [mmHg]	11.0 (7–18)*	6.0 (3–13)*	0.0018
AIx [%]	27 ± 13	22 ± 13	0.03
AIx75 [%]	25 ± 11	18 ± 12	0.009
PWV [m/s]	7.2 (6.1–8.4)*	7.4 (6.2–9.4)*	0.24
HRV index	6.6 (4.7–9)*	8.7 (5.9–12.1)*	0.006
DP aortic [mmHg]	83.0 (78–90)*	81.0 (76–90)*	0.59
SP aortic [mmHg]	121.28 ± 17.72	124.64 ± 18.27	0.42
Selected biomarkers
ADMA [µmol/l]	0.44 (0.39–0.55)*	0.36 (0.32–0.4)*	0.0002
IL-6 [pg/mL]	2.6 (0.8–8.1)*	0.7 (0.4–1.2)*	0.002
NT-proBNP [pg/mL]	391 (107.9–1249.22)*	109 (46.22–236.9)*	0.0003

Notes: *Median; for parameters with nonnormal distribution median values, lower and higher values are given. For parameters with normal distribution mean values ± standard deviation (SD) are given.

Abbreviations: BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; CAD, coronary artery disease; DM, diabetes mellitus; LDL, low-density lipoprotein; HDL, high-density lipoprotein; LVEF, left ventricular ejection fraction; E, early diastolic filling velocity; A, late diastolic filling velocity; E’, early diastolic mitral annular velocity; S’, right ventricular systolic excursion velocity; A’, late mitral annular motion; E/E’, ratio of peak velocity of early diastolic transmitral flow to peak velocity of early diastolic mitral annular motion; LVMI, left ventricular mass index; LA, left atrium; LAVI, left atrial volume index; IVRT, isovolumetric relaxation time; AP, augmentation pressure; AIx-augmentation index; AIx75, adjusted augmentation index at heart rate 75 beats per minute; PWV, pulse wave velocity; HRV index, heart rate velocity; DP, diastolic pressure; SP, systolic pressure; ADMA, asymmetric dimethylarginine; IL-6, interleukin 6; NT-proBNP, N-terminal prohormone of brain natriuretic peptide.

Figure 1 Kaplan–Meier survival analysis.

Abbreviation: ESUS, embolic strokes of undetermined etiology.

Table 2 Characteristics of Patients Who Survived and Those Who Died

Parameters	Patients Who Died (N=6)	Patients Who Survived (N=94)	p
Basic parameters
Gender (male) [%]	83%	49%	0.23
Median age [years]	54.5 (48–57)*	54 (47–59)*	0.98
BMI [kg/m^2]	27.3 (25.8–29.8)*	25.5 (21.8–28.6)*	0.14
SBP [mmHg]	126 ± 15.22	134 ± 19.42	0.3
DBP [mmHg]	75 ± 10.53	83 ± 9.41	0.047
CAD [%]	16.67	8.7	0.94
Hypertension [%]	50	48.39	0.73
Smoking [%]	50	28.89	0.53
Laboratory results
LDL cholesterol [mmol/l]	2.25 (1.53–2.77)*	3.01 (2.41–3.78)*	0.015
HDL cholesterol [mmol/l]	0.9 (0.84–1.05)*	1.3 (1.07–1.52)*	0.014
Triglycerides [mmol/l]	2.11 (1.81–2.42)*	1.39 (1.02–1.86)*	0.023
Adiponectin [µg/mL]	3.3 (3.02–4.7)*	6.71 (4.31–10.17)*	0.016
Selected echocardiographic parameters
LVEF [%]	55 (55–60)*	60 (55–65)*	0.21
E [cm/s]	64.4 ± 16.13	72.71 ± 18.05	0.32
A [cm/s]	78.6 ± 11.99	74.57 ± 20.6	0.67
Mean E’ [cm/s]	7.95 (7.85–8.15)*	9.95 (8–13)*	0.04
S’ [cm/s]	13.6 (11–14)*	13 (11–15.6)*	0.7
E/E’ [cm/s]	8.8 (6.29–9.57)*	6.89 (5.71–8.21)*	0.22
LVMI [g/m^2]	107.5 (96.5–115)*	101 (82–120)*	0.65
LA [mm]	36 (33–37)*	36 (32–39)*	0.88
LAVI [mL/m^2]	19.92 ± 15.99	25.69 ± 9.79	0.33
IVRT [m/s]	107.2 ± 15.01	101.91 ± 28.47	0.68
Selected biomarkers
ADMA [µmol/l]	0.48 (0.39–0.69)*	0.42 (0.35–0.48)*	0.33
IL-6 [pg/mL]	9.94 (1.93–104.39)*	2.16 (0.63–4.2)*	0.17
NT-proBNP [pg/mL]	410.76 (147.17–1639)*	225.68 (71.45–693.99)*	0.31

Notes: *Median; for parameters with nonnormal distribution median values, lower and higher values are given. For parameters with normal distribution mean values ± standard deviation (SD) are given.

Abbreviations: BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; CAD, coronary artery disease; DM, diabetes mellitus; LDL, low-density lipoprotein; HDL, high-density lipoprotein; LVEF, left ventricular ejection fraction; E, early diastolic filling velocity; A, late diastolic filling velocity; E’, early diastolic mitral annular velocity; S’, right ventricular systolic excursion velocity; A’, late mitral annular motion; E/E’, ratio of peak velocity of early diastolic transmitral flow to peak velocity of early diastolic mitral annular motion; LVMI, left ventricular mass index; LA, left atrium; LAVI, left atrial volume index; IVRT, isovolumetric relaxation time; ADMA, asymmetric dimethylarginine; IL-6, interleukin 6; NT-proBNP, N-terminal prohormone of brain natriuretic peptide.

Figure 2 Occurrence of atrial fibrillation – Kaplan–Meier curves.

Abbreviation: ESUS, embolic strokes of undetermined etiology.

Table 3 Multivariate Analysis

Parameters	Odds Ratio (OR)	95% Confidence Interval	p
Cardiovascular hospitalizations assessed at 12-month follow-up
E’	0.76	0.61–0.95	0.02
AF occurrence in the 12-month follow-up
S’	0.65	0.46–0.93	0.02
Recurrent stroke at 12-month follow-up
E/E’	7.44	1.16–47.6	0.03
Composite endpoint consisting of hospitalization and recurrent stroke at 12-month follow-up
E/E’	1.96	1.18–3.25	0.01

Abbreviations: E’, early diastolic mitral annular velocity; S’, right ventricular systolic excursion velocity; E/E’, ratio of peak velocity of early diastolic transmitral flow to peak velocity of early diastolic mitral annular motion.