J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 11, Number 1, January 2019, pages 49-55

Renoprotective Benefit of Tolvaptan in Acute Decompensated Heart Failure Patients With Loop Diuretic-Resistant Status

Figure 1. Comparison of (a) days to heart failure improvement, (b) BW reduction , and (c) CTR reducing between TLV and non-TLV. BW: body weight. CTR: cardiac thoracic ratio; LVEF: left ventricular ejection fraction.

Figure 2. (a) Averaged loop diuretic dose before hospitalization. (b) Total loop diuretic used dose for 1 week from the start of treatment. (c) Blood pressure changes during 1 week compared TLV and non-TLV. (c-1) Systolic blood pressure. (c-2) Diastolic blood pressure. (c-3) Heart rate. Day: number of days since start TLV treatment; LVEF: left ventricular ejection fraction.

Figure 3. Changes in parameters of renal function prior to the treatment and 1 week after the treatment ((a): ΔBUN, (b): ΔCr, (c): ΔeGFR). (d) WRF appearance rate (%) during hospitalization. WRF is defined as increase in serum creatinine levels at 0.3mg/dL and more. ΔBUN: delta blood urea nitrogen; ΔCr: delta creatinine; ΔeGFR: delta estimated glomerular filtration rate; WRF: worsening renal function.

**Table 1.** Patients Characteristics in the TLV and Non-TLV Groups
	All (n = 99)	TLV (n = 39)	non-TLV (n = 60)	P value
Data are shown as the mean ± standard deviation (SD) or n (%) or as the median (interquartile range). UCG-LVEF: ultrasonic cardiogram-left ventricular ejection fraction; CTR: cardiac thoracic ratio; NYHA: New York Heart Association; SBP: systolic blood pressure; DBP: diastolic blood pressure; HR: heart rate; ACE-I/ARB: angiotensin converting enzyme inhibitor/angiotensin receptor blocker; CCB: calcium channel blocker; BUN: blood urea nitrogen; Cr: creatinine; eGFR: estimated glomerular filtration rate; Na: sodium; K: potassium; Cl: chloride ion; NT-proBNP: n-terminal pro b-type natriuretic peptide.
Age, yrs	81 (73 - 87)	79 (74.5 - 86)	83 (72 - 88)	0.85
Male, n (%)	53 (54)	23 (59)	30 (50)	0.43
Body weight, kg	55.9 (49.6 - 65.4)	57.8 (52.9 - 69.5)	52.9 (46.9 - 60.7)	0.09
UCG-LVEF, %	46.1 (31.5 - 60.9)	48.8 (38.4 - 60.4)	45.7 (30 - 60.8)	0.45
Chest X-ray CTR, %	61 (58 - 65)	61 (58 - 66)	61 (58 - 64.5)	0.32
NYHA classification
Class III, n (%)	39 (39)	18 (46)	21 (35)	0.29
Class IV, n (%)	18 (18)	4 (10)	14 (23)	0.09
Etiology
Ischemia, n (%)	28 (28)	6 (15)	15 (25)	0.24
Hypertension, n (%)	66 (67)	7 (18)	14 (23)	0.49
Arrhythmia, n (%)	12 (12)	3 (8)	9 (15)	0.26
Valvular, n (%)	11 (11)	4 (10)	7 (12)	0.81
Cardiomyopathy, n (%)	7 (7)	4 (10)	3 (5)	0.33
Others, n (%)	26 (26)	15 (38)	11 (18)	0.03
Hemodynamics
SBP, mm Hg	128 (110.5 - 149.8)	116 (102 - 131)	141 (122 - 157.5)	< 0.0001
DBP, mm Hg	74.5 (64.3 - 89.8)	65 (60.5 - 74.5)	81 (68 - 98.5)	< 0.0001
HR, bpm	82.5 (65.5 - 105)	73 (62.5 - 90)	90 (70 - 108)	0.02
Drugs
ACE-I/ARB, n (%)	57 (58)	23 (59)	21 (35)	0.89
CCB, n (%)	31 (31)	15 (38)	13 (33)	0.24
Β-blocker, n (%)	67 (68)	29 (74)	22 (56)	0.29
Laboratory data
BUN, mg/dL	23 (18 - 31)	24 (20.5 - 35)	23 (15.5 - 29)	0.08
Cr, mg/dL	1.1 (0.9 - 1.5)	1.3 (1.1 - 1.7)	0.9 (0.8 - 1.3)	0.01
eGFR, mL/min/1.73m²	40.6 (32.0 - 56.4)	35.3 (27.1 - 43.5)	48.2 (36.4 - 59.2)	0.003
Na, mEq/L	140 (138 - 142)	139 (136 - 141)	141 (139 - 142.5)	0.21
K, mEq/L	4.1 (3.8 - 4.4)	4.2 (4 - 4.5)	4.0 (3.7 - 4.5)	0.10
Cl, mEq/L	105 (103 - 108)	104.5 (101 - 107)	106 (104 - 108)	0.33
Albumin, g/dL	3.5 (3.1 - 3.7)	3.6 (3.2 - 3.8)	3.4 (3.1 - 3.7)	0.88
Hemoglobin, g/dL	11.9 (10.2 - 12.8)	11.7 (10.2 - 12.5)	12.1 (9.8 - 13.3)	0.51
NT-proBNP	6,430 (2,596 - 13,541)	5,503 (3,152 - 15,244)	6,490 (2,619 - 13,478)	0.34
Type of used diuretics
Carperitide, n (%)	45 (45)	17 (44)	28 (47)	0.71
Carperitide, γ	0.009 ± 0.012	0.009 ± 0.012	0.009 ± 0.012	0.96
Frosemide, mg	21.7 ± 15.3	24.4 ± 18.2	20.0 ± 12.9	0.21
Spironolactone, mg	17.9 ± 13.0	14.7 ± 13.7	20.1 ± 12.2	0.05
Catecholamine, n(%)	14 (14)	7 (18)	7 (12)	0.39

Table 1. Patients Characteristics in the TLV and Non-TLV Groups

All (n = 99)

TLV (n = 39)

non-TLV (n = 60)

P value

Data are shown as the mean ± standard deviation (SD) or n (%) or as the median (interquartile range). UCG-LVEF: ultrasonic cardiogram-left ventricular ejection fraction; CTR: cardiac thoracic ratio; NYHA: New York Heart Association; SBP: systolic blood pressure; DBP: diastolic blood pressure; HR: heart rate; ACE-I/ARB: angiotensin converting enzyme inhibitor/angiotensin receptor blocker; CCB: calcium channel blocker; BUN: blood urea nitrogen; Cr: creatinine; eGFR: estimated glomerular filtration rate; Na: sodium; K: potassium; Cl: chloride ion; NT-proBNP: n-terminal pro b-type natriuretic peptide.

Age, yrs

81 (73 - 87)

79 (74.5 - 86)

83 (72 - 88)

0.85

Male, n (%)

53 (54)

23 (59)

30 (50)

0.43

Body weight, kg

55.9 (49.6 - 65.4)

57.8 (52.9 - 69.5)

52.9 (46.9 - 60.7)

0.09

UCG-LVEF, %

46.1 (31.5 - 60.9)

48.8 (38.4 - 60.4)

45.7 (30 - 60.8)

0.45

Chest X-ray CTR, %

61 (58 - 65)

61 (58 - 66)

61 (58 - 64.5)

0.32

NYHA classification

Class III, n (%)

39 (39)

18 (46)

21 (35)

0.29

Class IV, n (%)

18 (18)

4 (10)

14 (23)

0.09

Etiology

Ischemia, n (%)

28 (28)

6 (15)

15 (25)

0.24

Hypertension, n (%)

66 (67)

7 (18)

14 (23)

0.49

Arrhythmia, n (%)

12 (12)

3 (8)

9 (15)

0.26

Valvular, n (%)

11 (11)

4 (10)

7 (12)

0.81

Cardiomyopathy, n (%)

7 (7)

4 (10)

3 (5)

0.33

Others, n (%)

26 (26)

15 (38)

11 (18)

0.03

Hemodynamics

SBP, mm Hg

128 (110.5 - 149.8)

116 (102 - 131)

141 (122 - 157.5)

< 0.0001

DBP, mm Hg

74.5 (64.3 - 89.8)

65 (60.5 - 74.5)

81 (68 - 98.5)

< 0.0001

HR, bpm

82.5 (65.5 - 105)

73 (62.5 - 90)

90 (70 - 108)

0.02

Drugs

ACE-I/ARB, n (%)

57 (58)

23 (59)

21 (35)

0.89

CCB, n (%)

31 (31)

15 (38)

13 (33)

0.24

Β-blocker, n (%)

67 (68)

29 (74)

22 (56)

0.29

Laboratory data

BUN, mg/dL

23 (18 - 31)

24 (20.5 - 35)

23 (15.5 - 29)

0.08

Cr, mg/dL

1.1 (0.9 - 1.5)

1.3 (1.1 - 1.7)

0.9 (0.8 - 1.3)

0.01

eGFR, mL/min/1.73m²

40.6 (32.0 - 56.4)

35.3 (27.1 - 43.5)

48.2 (36.4 - 59.2)

0.003

Na, mEq/L

140 (138 - 142)

139 (136 - 141)

141 (139 - 142.5)

0.21

K, mEq/L

4.1 (3.8 - 4.4)

4.2 (4 - 4.5)

4.0 (3.7 - 4.5)

0.10

Cl, mEq/L

105 (103 - 108)

104.5 (101 - 107)

106 (104 - 108)

0.33

Albumin, g/dL

3.5 (3.1 - 3.7)

3.6 (3.2 - 3.8)

3.4 (3.1 - 3.7)

0.88

Hemoglobin, g/dL

11.9 (10.2 - 12.8)

11.7 (10.2 - 12.5)

12.1 (9.8 - 13.3)

0.51

NT-proBNP

6,430 (2,596 - 13,541)

5,503 (3,152 - 15,244)

6,490 (2,619 - 13,478)

0.34

Type of used diuretics

Carperitide, n (%)

45 (45)

17 (44)

28 (47)

0.71

Carperitide, γ

0.009 ± 0.012

0.96

Frosemide, mg

21.7 ± 15.3

24.4 ± 18.2

20.0 ± 12.9

0.21

Spironolactone, mg

17.9 ± 13.0

14.7 ± 13.7

20.1 ± 12.2

0.05

Catecholamine, n(%)

14 (14)

7 (18)

7 (12)

0.39

**Table 2.** Independent Predictors of Worsening Renal Function
	Odds ratio	95% CI	P value
CI: confidence interval; HT: hyper tension; eGFR: estimated glomerular filtration rate.
HT	2.07	0.49 - 8.72	0.32
eGFR	1.36	0.26 - 7.25	0.72
Tolvaptan	0.14	0.02 - 0.98	0.04

Table 2. Independent Predictors of Worsening Renal Function

Odds ratio

95% CI

P value

CI: confidence interval; HT: hyper tension; eGFR: estimated glomerular filtration rate.

2.07

0.49 - 8.72

0.32

eGFR

1.36

0.26 - 7.25

0.72

Tolvaptan

0.14

0.02 - 0.98

0.04