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ONLINE APPENDIX
Online Table 1. Relation Between Estimated and Directly Measured Right Atrial
Pressure (RAP)
Directly measured RAP, mm Hg
Estimated, mm Hg
0–5
6–10
>10
Sum
0–5
32
18
0
50
13
13
4
30
>10
0
0
23
23
Sum
45
32
26
103
6–10
The agreements of both methods were moderate because the kappa coefficient was 0.48.
However, in the patients with directly measured RAP ≤10 mm Hg, the agreements were poor
(kappa coefficient = 0.15). If patients were classified in a binary manner, i.e., RAP ≤10 mm
Hg and >10 mm Hg, the agreements were excellent (kappa coefficient = 0.92). Therefore, the
binary classification by echocardiography was used to estimate RAP.
Online Table 2.Clinical Characteristics of Controls and Patients with Heart Failure
Control
Total
Event (+)
Event (-)
p Value
Characteristic
(n = 38)
(n = 217)
(n = 59)
(n = 158)
Event + vs.
-
Age, yrs
46 ± 15
60 ± 16*
61.7 ±
58. 4 ± 15.8
0.28
15.3
Male
15
126 (58)
34 (57.6)
92 (58.2)
0.93
22 ± 2.7
23 ± 4.7*
21.5 ± 4.3
22.8 ± 4.1
0.07
118 ± 15
113 ± 21
109.6 ±
114.4 ± 20.4
0.04
(39)
Body mass index
Systolic blood pressure, mm Hg
21.7
Heart rate, beats/min
71 ± 13
74 ± 15
74.9 ± 13.2
73.9 ± 16.2
0.78
Hypertension
-
93 (43)
28 (47.5)
65 (41.1)
0.40
Diabetes
-
63 (29)
18 (30.5)
45 (28.5)
0.77
NYHA class III or IV
-
94 (43.4)
42 (71.2)
52 (32.9)
<0.001
Cardiac diseases
0.47
Coronary artery diseases
-
22 (15)
10 (17)
12 (8)
0.04
Nonischemic
-
91 (42)
25 (43)
66 (42)
0.94
-
36 (17)
9 (15)
27 (17)
0.74
cardiomyopathy
Valvular disease
Mitral regurgitation
13 (36)
2 (22)
11 (41)
Mitral stenosis
5 (19)
0 (0.0)
5 (23)
Aortic regurgitation
8 (22)
3 (23)
5 (19)
Aortic stenosis
10 (28)
4 (44)
6 (22)
VSD/ASD
-
9 (4)
1 (2)
8 (5)
0.27
Pulmonary artery
-
20 (9)
4 (7)
16 (10)
-
64 (30)
16 (27)
48 (30)
Hemoglobin, g/dL
14 ± 1.9
13 ± 2.3†
12 ± 2.1
13 ± 2.2
<0.001
BUN, mg/dL
14 ± 2.5
22 ± 14*
27 ± 19
20 ± 12
0.003
89 ± 21
64 ± 26*
57 ± 23
67 ± 27
0.01
142 ± 1.8
140 ± 3.4*
138 ± 4.0
140 ± 3.0
0.45
hypertension
HFpEF
0.64
Laboratory data
eGFR, mL/min per 1.73 m2
Sodium, mEq/L
<0.001
BNP, pg/mL
-
481 ± 753
WRF, n (available cases, %)
39 (151,
860 ± 940
13 (40, 33)
26)
339 ± 616
<0.001
26 (111,
0.26
23)
Medications, n (%)
ACE-I/ARB
-
158 (73)
45 (77)
113 (72)
0.48
β-blocker
-
150 (69)
40 (68)
110 (69)
0.72
Loop diuretics
-
136 (63)
47 (80)
89 (56)
0.001
Spironolactone
-
110 (51)
32 (54)
78 (49)
0.37
Values are means ± SD or numbers (%). ACE-I = angiotensin-converting enzyme inhibitors; ARB =
angiotensin II receptor blocker; BNP = brain natriuretic peptide; BUN = blood urea nitrogen; eGFR =
estimated glomerular filtration rate; HFpEF = heart failure with preserved ejection fraction; VSD/ASD =
ventricular septal defect/atrial septal defect; WRF = worsening renal function.
* p<0.001, † p<0.05 vs. Control.
Online Table 3. Echocardiographic and Intrarenal Doppler Ultrasound Data in Controls and Patients
with Heart Failure
Characteristic
LVEDV, ml
Control
Total
Event (+)
Event (-)
p Value
(n = 38)
(n = 217)
(n = 59)
(n = 158)
Event +
vs. -
±
151 ± 80*
172.4 ± 95.6
143.6 ± 72.7
0.01
35.7 ± 34.2
89 ± 74*
94.3
17.0*
LVESV, ml
115.8 ±
79.6 ± 66.9
0.002
50.4 ± 17.8
0.006
86.9
LVEF, %
E/A (available cases)
68.0 ± 3.5*
1.3 ± 0.9
(172)
(39)
(133)
14 ± 8.0*
18.3 ± 9.6
12.7 ± 7.4
<0.001
55 ± 46*
68.6 ± 61.1
50.3 ± 39.1
0.04
TR grade
Less than mild, n (%)
175 (81)
27 (12)
41 (70)
11 (19)
134 (85)
16 (10)
Moderate
Severe
TR-PG, mm Hg (available
cases)
RV-FAC, %
15 (7)
7 (12)
36 ± 18
(203)
36.1 ± 13.5*
41 ± 16
(54)
30 ± 13
38 ± 13
<0.001
61 (28.1)
32 (54)
29 (18)
<0.001
1.1 ± 0.8 *
0.8 ± 0.9
1.1 ± 0.8
0.04
RI
1.6 ± 0.5
(36)
0.6 ± 0.1
0.7 ± 0.1*
0.8 ± 0.1
0.7 ± 0.1
0.001
VII
0.3 ± 0.1
0.6 ± 0.4*
0.9 ± 0.2
0.6 ± 0.3
<0.001
LAVI, ml/m2
1.5 ± 1.0
42.1 ± 19.6
2.1 ± 1.3
E/E’
1.3 ± 0.3
49 ± 19*
6.8 ± 2.3*
19.5
±
<0.001
5.3*
Estimated RAP > 10 mm
Hg
HV-S/D
49.5 ± 7.8
-
8 (5)
34 ± 19
(149)
IRVF pattern
Continuous
Biphasic
Monophasic
0.03
0.01
<0.001
38
(100)
-
117 (54)
51 (24)
49 (23)
7 (12)
19 (32)
33 (56)
110 (70)
32 (20)
16 (10)
Values are means ± SD or numbers (%). E/A = ratio of early diastolic peak velocity of Doppler transmitral
flow to peak velocity at atrial contraction; E/E’ = ratio of early diastolic peak velocity of Doppler
transmitral flow to early diastolic mitral annular velocity; HV-S/D = hepatic systolic and diastolic flow
velocity ratio; IRVF = intrarenal venous flow; LAVI = left atrial volume index; LVEDV = left ventricular
end-diastolic volume; LVEF = left ventricular ejection fraction; LVESV = left ventricular end-systolic
volume; RAP = right atrial pressure; RI = resistance index; RV-FAC = right ventricular fractional area
change ratio; TR = tricuspid regurgitation; TR-PG = tricuspid regurgitation/pressure gradient; VII = venous
impedance index. * p<0.001 vs. Control.
In patients with cardiac events, the systolic blood pressure was lower, New York Heart
Association (NYHA) class was higher, Hb, sodium, and eGFR values were lower, and BUN
and BNP values were higher compared to patients without events (Table 2). In addition, left
ventricular (LV) systolic and diastolic dysfunction was more advanced in patients with events
compared to patients without events (Table 3). RV-FAC also was lower in patients with
events. Estimated RAP ≥10 mm Hg was more prevalent in patients with events; however,
significant differences were not observed in the HV-S/D ratio. In the IRD studies, RI and VII
were significantly higher in patients with events compared to those without events. In
addition, significant differences in IRVF patterns were observed between patients with and
without events. In patients with cardiac events, a discontinuous flow pattern was more
prevalent than in patients without events. In particular, the monophasic pattern was observed
in more than half of these patients.
Online Table 4. Simple Logistic Regression Analysis for IRD Profile
RI ≥0.70
Characteristic
Biphasic pattern
OR (95%
CI)
1.03 (1.01–
1.05)
P
value
0.01
Hemoglobin (per 1g/dL
0.81 (0.71–
0.001
increase)
BUN (per 10mg/dL
increase)
0.92)
Age (per 1year increase)
OR (95%
CI)
P
value
SBP (per 10mm Hg
increase)
NYHA class III or IV
eGFR (per 10mL/min /1.73
m2
Increase)
Sodium (per 1 mEq/L
increase)
BNP (per 100 pg/mL
increase)
0.81 (0.71–
0.92)
1.05 (1.01–
0.002
0.02
1.10)
1.93 (1.10–
3.39)
1.05 (1.01–
0.01
1
.
0
9
)
0.02
LAVI (per 10 mL increase)
RV-FAC (per 10%
increase)
Moderate or severe TR
Estimated RAP > 10 mm
Hg
3.35 (1.78–
6.29)
OR (95%
P
CI)
value
1.03 (1.004– 0.02
1.05)
0.84 (0.74– 0.01
0.96)
3.62 (1.84– <0.00
7.10)
1
0.77 (0.66– 0.001
0.89)
1.41 (1.14–
1.75)
Loop diuretics
E/E’>15
Monophasic pattern
<0.0
01
2.67 (1.41– 0.003
5
.
0.002
0.80 (0.68–
0.94)
0.006
0.82 (0.75–
0.91)
1.04 (1.01–
<0.00
1
0.03
1.08)
3.43 (1.70–
6.94)
2.59 (1.35–
4.97)
1.36 (1.20–
0.001
<0.00
1.54)
0.57 (0.45–
0.74)
9.25 (4.36–
19.6)
25.9 (11.3–
59.2)
1
<0.00
1
<0.00
1
<0.00
1
0.004
1
2
)
HV-S/D <0.55 (lower
quartile)
PCWP (per 1 mm Hg
increase)
3.09 (1.67–
5.71)
1.09 (1.03–
1.16)
<0.00
1
0.004
Mean RAP (per 1 mm Hg
increase)
1.10 (1.01–
1
.
0.03
2
0
)
12.6 (2.52– 0.002
63.2)
1.14 (1.05– 0.001
1
.
2
3
)
1.12 (1.01–
1.25)
0.03
1.40 (1.21– <0.00
1 1
.
6
3
)
Values are means ± SD. BNP = brain natriuretic peptide; BUN = blood urea nitrogen; CI = confidence
interval; eGFR = estimated glomerular filtration rate; E/E’ = ratio of early diastolic peak velocity of
Doppler transmitral flow to early diastolic mitral annular velocity; HV-S/D = hepatic systolic and diastolic
flow velocity ratio; LAVI = left atrial volume index; OR = odds ratio; PCWP = pulmonary capillary
wedge pressure; RAP = right atrial pressure; RV-FAC = right ventricular fractional area change ratio; SBP
= systolic blood pressure.