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Table 1 Patient characteristics of the training set

From: Development and validation of an early prediction model for cardiac death risk in patients with light chain amyloidosis: a multicenter study

Variables

Total (n = 124)

Cardiac death (n = 49)

Non-cardiac death (n = 75)

p value

Demographic and Clinical Characteristics

    

 Age at diagnosis (years), Mean ± SD

59.87 ± 9.24

59.82 ± 9.92

59.91 ± 8.84

0.958

 Age at symptom onset (years), Mean ± SD

59.08 ± 9.30

59.12 ± 9.65

59.05 ± 9.14

0.968

 Male sex, n (%)

80 (64.52)

32 (65.31)

48 (64.00)

0.882

 Height (cm), Median (IQR)

167.00 (160.00, 170.25)

165.00 (160.00, 171.00)

167.00 (160.00, 170.00)

0.632

 Weight (kg), Median (IQR)

64.00 (58.00, 71.25)

64.00 (57.50, 71.00)

64.00 (58.00, 72.00)

0.814

 Body mass index (kg/m²), Median (IQR)

23.19 (21.68, 25.38)

23.02 (21.88, 24.97)

23.34 (21.47, 26.08)

1.000

 Body surface area (m²), Median (IQR)

1.69 (1.56, 1.81)

1.67 (1.56, 1.82)

1.69 (1.59, 1.80)

0.671

 Mayo Clinic 2004 Staging System

   

< 0.001

  Stage 1, n (%)

15 (12.1)

0 (0.0)

15 (20.0)

 

  Stage 2, n (%)

60 (48.4)

20 (40.8)

40 (53.3)

 

  Stage 3, n (%)

49 (39.5)

29 (59.2)

20 (26.7)

 

 Mayo Clinic 2012 Staging System

   

< 0.001

  Stage 1, n (%)

33 (26.6)

3 (6.1)

30 (40.0)

 

  Stage 2, n (%)

34 (27.4)

14 (28.6)

20 (26.7)

 

  Stage 3, n (%)

49 (39.5)

27 (55.1)

22 (29.3)

 

  Stage 4, n (%)

8 (6.5)

5 (10.2)

3 (4.0)

 

 European Modification 2015 of Mayo Staging System

   

< 0.001

  Stage 1, n (%)

15 (12.1)

0 (0.0)

15 (20.0)

 

  Stage 2, n (%)

60 (48.4)

20 (40.8)

40 (53.3)

 

  Stage 3a, n (%)

32 (25.8)

19 (38.8)

13 (17.3)

 

  Stage 3b, n (%)

17 (13.7)

10 (20.4)

7 (9.3)

 

 NYHA functional class, Median (IQR)

2.00 (1.00, 2.25)

2.00 (2.00, 3.00)

1.00 (1.00, 2.00)

< 0.001

 Time from symptom onset to diagnosis (months), Median (IQR)

6.00 (2.00, 12.00)

6.00 (2.00, 12.00)

6.00 (2.50, 12.00)

0.841

 Cardiac manifestations as initial presentation, n (%)

34 (27.42)

23 (46.94)

11 (14.67)

< 0.001

 History of hypotension, n (%)

21 (16.94)

13 (26.53)

8 (10.67)

0.021

 Syncope/presyncope episodes, n (%)

10 (8.06)

9 (18.37)

1 (1.33)

0.002

 Initial admission MAP (mmHg), Mean ± SD

90.22 ± 12.12

87.91 ± 14.05

91.72 ± 10.51

0.108

 Initial admission SBP (mmHg), Median (IQR)

123.00 (110.00, 132.50)

120.00 (99.00, 135.00)

125.00 (114.00, 131.50)

0.181

 Initial admission DBP (mmHg), Median (IQR)

75.00 (68.00, 80.00)

70.00 (66.00, 80.00)

77.00 (70.00, 80.00)

0.069

 Lowest recorded MAP (mmHg), Median (IQR)

85.67 (72.92, 92.33)

76.67 (68.33, 86.67)

87.00 (82.00, 93.33)

0.001

 Lowest recorded SBP (mmHg), Median (IQR)

118.00 (97.00, 125.25)

100.00 (90.00, 120.00)

120.00 (110.00, 126.00)

0.005

 Lowest recorded MAP (mmHg), Median (IQR)

70.00 (60.00, 76.00)

62.00 (56.00, 70.00)

71.00 (67.00, 78.00)

0.001

 Hypertension, n (%)

52 (41.94)

23 (46.94)

29 (38.67)

0.361

 Coronary artery disease, n (%)

23 (18.55)

11 (22.45)

12 (16.00)

0.366

 Myocardial infarction history, n (%)

6 (4.84)

3 (6.12)

3 (4.00)

0.912

 Chronic kidney disease, n (%)

54 (43.55)

27 (55.10)

27 (36.00)

0.036

 Hepatic dysfunction, n (%)

21 (16.94)

13 (26.53)

8 (10.67)

0.021

 Hyperlipidemia, n (%)

45 (36.29)

16 (32.65)

29 (38.67)

0.496

 Multiple myeloma, n (%)

81 (65.32)

33 (67.35)

48 (64.00)

0.702

 Chemotherapy, n (%)

98 (79.03)

34 (69.39)

64 (85.33)

0.033

 Autologous stem cell transplantation, n (%)

14 (11.29)

1 (2.04)

13 (17.33)

0.009

Organs with amyloid deposition

    

 Renal involvement, n (%)

102 (82.26)

43 (87.76)

59 (78.67)

0.195

 Soft tissue involvement, n (%)

30 (24.19)

10 (20.41)

20 (26.67)

0.426

 Neurological involvement, n (%)

38 (30.65)

10 (20.41)

28 (37.33)

0.046

 Gastrointestinal involvement, n (%)

6 (4.84)

4 (8.16)

2 (2.67)

0.334

 Pulmonary involvement, n (%)

3 (2.42)

1 (2.04)

2 (2.67)

1.000

 Hepatic involvement, n (%)

25 (20.16)

16 (32.65)

9 (12.00)

0.005

 Total number of involved organs, Median (IQR)

2.00 (2.00, 3.00)

3.00 (2.00, 3.00)

2.00 (2.00, 3.00)

0.131

ECG features

    

 Heart rate (bpm), Mean ± SD

85.38 ± 14.05

84.82 ± 11.92

85.75 ± 15.35

0.720

 PR interval (ms), Mean ± SD

159.79 ± 26.32

165.59 ± 25.89

156.00 ± 26.08

0.047

 P-wave duration (ms), Median (IQR)

90.00 (84.00, 96.00)

90.00 (86.00, 96.00)

90.00 (82.00, 98.00)

0.840

 QRS duration (ms), Median (IQR)

88.50 (82.00, 94.00)

92.00 (84.00, 98.00)

86.00 (82.00, 92.00)

0.003

 Corrected QT interval (ms), Median (IQR)

428.00 (404.00, 450.50)

435.00 (414.00, 471.00)

425.00 (403.00, 443.50)

0.079

 QRS axis (degrees), Median (IQR)

30.50 (-39.00, 58.00)

4.00 (-54.00, 50.00)

35.00 (-5.00, 59.00)

0.094

 R-wave amplitude in lead V5 (mV), Median (IQR)

0.96 (0.58, 1.38)

0.80 (0.34, 1.08)

1.12 (0.68, 1.52)

0.006

 S-wave amplitude in lead V1 (mV), Median (IQR)

0.65 (0.45, 0.93)

0.65 (0.49, 0.92)

0.63 (0.41, 0.94)

0.838

 Sokolow-Lyon index (mV), Median (IQR)

1.46 (0.79, 2.52)

1.23 (0.55, 2.48)

1.56 (1.07, 2.54)

0.073

 R-wave in V5/S-wave in V1 ratio, Median (IQR)

1.63 (1.13, 2.21)

1.45 (0.98, 1.92)

1.74 (1.21, 2.35)

0.024

 Minimum limb lead voltage (mV), Median (IQR)

0.20 (0.15, 0.30)

0.20 (0.10, 0.30)

0.25 (0.20, 0.30)

0.127

 Maximum limb lead voltage (mV), Median (IQR)

0.65 (0.45, 0.85)

0.55 (0.45, 0.80)

0.70 (0.50, 0.88)

0.092

 Mean limb lead voltage (mV), Median (IQR)

0.45 (0.33, 0.59)

0.42 (0.29, 0.56)

0.47 (0.36, 0.60)

0.149

 QRS axis deviation (degrees), Median (IQR)

35.00 (14.00, 84.00)

68.00 (26.00, 99.00)

32.00 (11.50, 61.50)

0.009

 Low Sokolow-Lyon index (< 1.5), n (%)

56 (45.16)

28 (57.14)

28 (37.33)

0.030

 Low limb lead voltage, n (%)

56 (45.16)

30 (61.22)

26 (34.67)

0.004

 Low precordial lead voltage, n (%)

29 (23.39)

17 (34.69)

12 (16.00)

0.016

 Pseudo-infarct pattern, n (%)

39 (31.45)

21 (42.86)

18 (24.00)

0.027

 Impaired R-wave progression, n (%)

39 (31.45)

21 (42.86)

18 (24.00)

0.027

 Arrhythmias, n (%)

31 (25.00)

22 (44.90)

9 (12.00)

< 0.001

 Bradycardia and conduction abnormalities, n (%)

33 (26.61)

23 (46.94)

10 (13.33)

< 0.001

 T-wave abnormality, n (%)

51 (41.13)

28 (57.14)

23 (30.67)

0.003

 ST-segment abnormalities, n (%)

19 (15.32)

8 (16.33)

11 (14.67)

0.802

 Fragmented QRS complexes, n (%)

12 (9.68)

7 (14.29)

5 (6.67)

0.275

 Atrial arrhythmias, n (%)

20 (16.13)

11 (22.45)

9 (12.00)

0.122

 Ventricular arrhythmias, n (%)

16 (12.90)

14 (28.57)

2 (2.67)

< 0.001

 Left axis deviation, n (%)

44 (35.48)

23 (46.94)

21 (28.00)

0.031

Echocardiographic features

    

 LV end-diastolic diameter (mm), Mean ± SD

45.79 ± 5.36

45.71 ± 6.22

45.85 ± 4.75

0.901

 LV end-systolic diameter (mm), Median (IQR)

29.00 (26.75, 32.25)

31.00 (29.00, 36.00)

28.00 (26.00, 30.50)

< 0.001

 LVEF (%), Median (IQR)

64.00 (56.75, 69.00)

56.00 (47.00, 65.00)

66.00 (62.00, 71.00)

< 0.001

 Left atrial anteroposterior diameter (mm), Mean ± SD

38.86 ± 5.51

41.22 ± 4.57

37.32 ± 5.56

< 0.001

 Left atrial transverse diameter (mm), Mean ± SD

40.74 ± 5.80

42.60 ± 4.51

39.53 ± 6.24

0.002

 Left atrial longitudinal diameter (mm), Median (IQR)

53.00 (49.00, 56.00)

54.00 (53.00, 57.00)

50.00 (46.00, 53.00)

< 0.001

 Left atrial diameter index, Mean ± SD

23.00 ± 3.58

24.59 ± 3.60

21.96 ± 3.18

< 0.001

 Right atrial transverse diameter (mm), Median (IQR)

36.00 (33.00, 39.00)

38.00 (36.00, 42.00)

35.00 (32.50, 37.00)

< 0.001

 Right atrial anteroposterior diameter (mm), Median (IQR)

47.00 (44.00, 51.00)

50.00 (47.00, 54.00)

46.00 (42.85, 50.00)

< 0.001

 Right ventricular diameter (mm), Median (IQR)

33.00 (30.00, 37.00)

35.00 (32.00, 38.00)

31.00 (29.00, 36.00)

0.002

 LV mass (g), Median (IQR)

201.33 (164.45, 257.14)

216.55 (188.02, 262.62)

189.19 (147.83, 243.88)

0.007

 LV mass index (g/m²), Median (IQR)

118.96 (95.40, 150.37)

130.87 (108.14, 158.08)

106.72 (87.73, 143.43)

0.005

 Interventricular septal thickness (mm), Median (IQR)

12.30 (10.00, 14.00)

13.00 (11.30, 15.00)

12.00 (10.00, 13.65)

0.008

 LV posterior wall thickness (mm), Median (IQR)

11.40 (10.00, 13.00)

12.00 (11.00, 15.00)

11.00 (10.00, 12.40)

0.002

 LV relative wall thickness, Median (IQR)

0.49 (0.42, 0.58)

0.54 (0.43, 0.64)

0.48 (0.40, 0.56)

0.011

 LV hypertrophy, n (%)

65 (52.42)

34 (69.39)

31 (41.33)

0.002

 Aortic diameter (mm), Median (IQR)

31.00 (29.00, 33.00)

31.00 (29.00, 33.00)

31.00 (29.50, 33.00)

0.937

 Ascending aorta diameter (mm), Mean ± SD

33.45 ± 3.81

33.53 ± 3.86

33.40 ± 3.79

0.856

 Pulmonary artery diameter (mm), Median (IQR)

25.00 (24.00, 27.00)

26.00 (24.00, 28.00)

25.00 (23.00, 26.50)

0.006

 E-wave (m/s), Median (IQR)

89.50 (73.00, 105.25)

97.00 (84.00, 115.00)

85.00 (66.50, 95.50)

< 0.001

 A-wave (m/s), Mean ± SD

81.94 ± 26.86

74.80 ± 29.10

86.60 ± 24.37

0.016

 E/A ratio, Median (IQR)

1.15 (0.76, 1.46)

1.29 (1.14, 1.92)

0.86 (0.73, 1.21)

< 0.001

 Pericardial effusion (grade), Median (IQR)

0.00 (0.00, 2.00)

1.00 (0.00, 2.00)

0.00 (0.00, 1.00)

< 0.001

 Valvular regurgitation (grade), Median (IQR)

2.00 (1.00, 2.00)

2.00 (2.00, 3.00)

2.00 (1.00, 2.00)

< 0.001

 Valvular thickening, n (%)

17 (13.71)

6 (12.24)

11 (14.67)

0.701

 Wall motion abnormality, n (%)

25 (20.16)

19 (38.78)

6 (8.00)

< 0.001

 LV systolic dysfunction, n (%)

25 (20.16)

21 (42.86)

4 (5.33)

< 0.001

 LV diastolic dysfunction, n (%)

94 (75.81)

39 (79.59)

55 (73.33)

0.426

 Right ventricular systolic dysfunction, n (%)

12 (9.68)

8 (16.33)

4 (5.33)

0.087

 Pulmonary arterial hypertension, n (%)

34 (27.42)

21 (42.86)

13 (17.33)

0.002

Combined ECG and echocardiographic parameters

   

 Limb leads QRS score to LV wall thickness ratio, Median (IQR)

0.23 (0.16, 0.33)

0.20 (0.12, 0.30)

0.24 (0.17, 0.34)

0.011

 Sokolow-Lyon index / LV posterior wall thickness, Median (IQR)

1.50 (0.92, 2.05)

1.23 (0.72, 1.68)

1.73 (1.00, 2.22)

0.004

 Sokolow-Lyon index / LV relative wall thickness, Median (IQR)

32.13 (20.68, 49.79)

28.75 (15.05, 40.00)

39.75 (23.04, 53.41)

0.010

 Sokolow-Lyon index / LV mass, Median (IQR)

0.08 (0.05, 0.12)

0.07 (0.04, 0.10)

0.11 (0.06, 0.13)

0.001

 Voltage-to-mass ratio, Median (IQR)

0.14 (0.09, 0.21)

0.11 (0.07, 0.15)

0.17 (0.10, 0.23)

0.001

Laboratory examination

    

 Cardiac troponin I (ng/mL), Median (IQR)

0.06 (0.02, 0.21)

0.12 (0.05, 0.25)

0.03 (0.01, 0.11)

0.002

 BNP (pg/mL), Median (IQR)

403.92 (133.52, 1339.66)

1202.24 (407.20, 2986.00)

202.00 (72.98, 724.00)

< 0.001

 NT-proBNP (pg/mL), Median (IQR)

3149.00 (849.83, 7746.75)

6204.00 (3846.00, 13306.25)

1537.50 (456.10, 4525.00)

< 0.001

 Serum albumin (g/L), Median (IQR)

32.90 (26.65, 36.52)

33.60 (29.40, 36.50)

32.30 (24.65, 36.60)

0.297

 Serum globulin (g/L), Median (IQR)

25.50 (20.17, 32.85)

27.50 (21.20, 32.40)

24.00 (19.70, 32.90)

0.252

 Serum total protein (g/L), Median (IQR)

59.80 (50.43, 69.60)

62.30 (55.30, 68.80)

59.00 (48.55, 70.10)

0.342

 Albumin-to-globulin ratio, Mean ± SD

1.24 ± 0.54

1.22 ± 0.50

1.26 ± 0.57

0.690

 Serum creatinine (µmol/L), Median (IQR)

85.00 (65.40, 150.53)

96.50 (71.90, 216.80)

81.60 (63.90, 123.65)

0.070

 Creatinine clearance (mL/min), Median (IQR)

71.10 (39.38, 93.36)

68.92 (26.50, 79.18)

74.42 (50.85, 96.12)

0.068

 β2-Microglobulin (mg/L), Median (IQR)

4.83 (2.94, 7.35)

5.30 (3.10, 9.86)

4.14 (2.90, 6.29)

0.037

 ALT (U/L), Median (IQR)

18.00 (13.00, 26.00)

18.00 (12.00, 29.00)

18.00 (13.50, 23.50)

0.446

 AST (U/L), Median (IQR)

22.50 (17.00, 29.00)

24.00 (19.00, 36.00)

22.00 (16.00, 25.00)

0.024

 AST-to-ALT ratio, Median (IQR)

1.27 (0.95, 1.55)

1.33 (1.00, 1.57)

1.21 (0.95, 1.52)

0.421

 Serum calcium (mmol/L), Median (IQR)

2.16 (2.01, 2.29)

2.16 (2.01, 2.28)

2.17 (2.01, 2.31)

0.988

 Hemoglobin (g/L), Median (IQR)

107.50 (83.50, 126.50)

106.00 (82.00, 118.00)

113.00 (84.50, 132.00)

0.147

 White blood cell count (×10⁹/L), Median (IQR)

6.01 (5.00, 7.62)

5.71 (4.98, 7.70)

6.09 (5.08, 7.50)

0.609

 Platelet count (×10⁹/L), Median (IQR)

198.50 (138.00, 272.00)

168.00 (117.00, 236.00)

213.00 (164.00, 283.50)

0.014

 Immunoglobulin G (mg/dL), Median (IQR)

666.50 (414.25, 1072.50)

769.00 (451.00, 1320.00)

643.00 (378.50, 889.00)

0.149

 Immunoglobulin A (mg/dL), Median (IQR)

62.90 (31.15, 132.25)

53.30 (31.00, 93.40)

68.40 (32.55, 202.50)

0.138

 Immunoglobulin M (mg/dL), Median (IQR)

31.65 (20.12, 48.82)

31.80 (19.20, 45.00)

31.50 (22.25, 50.85)

0.590

 Immunoglobulin E (IU/mL), Median (IQR)

18.50 (17.70, 40.10)

18.50 (17.70, 42.80)

19.40 (17.70, 39.00)

0.739

 Serum free light chain-λ (mg/dL), Median (IQR)

318.50 (195.50, 588.25)

413.00 (240.00, 715.00)

269.00 (182.00, 440.00)

0.002

 Serum free light chain-κ (mg/dL), Median (IQR)

450.00 (295.25, 617.50)

402.00 (266.00, 526.00)

492.00 (322.00, 653.00)

0.022

 Urine free light chain-λ (mg/dL), Median (IQR)

5.44 (5.00, 27.63)

16.50 (5.00, 48.40)

5.00 (5.00, 14.50)

0.005

 Urine free light chain-κ (mg/dL), Median (IQR)

3.98 (1.85, 16.83)

4.20 (1.85, 16.90)

3.51 (1.85, 15.75)

0.985

 Difference of free light chains (mg/dL), Median (IQR)

248.50 (102.50, 536.75)

244.00 (64.00, 542.00)

249.00 (116.00, 504.00)

0.354

 Free light chain ratio, Median (IQR)

1.92 (1.34, 3.13)

1.72 (1.17, 3.79)

2.01 (1.39, 3.07)

0.200

  1. t: t-test; Z: Mann-Whitney test; χ²: Chi-square test; SD: Standard deviation; IQR: Interquartile range
  2. Creatinine clearance is calculated by the Cockcroft-Gault formula
  3. NYHA: New York Heart Association; MAP: mean arterial pressure; SBP: systolic blood pressure; DBP: diastolic blood pressure; LVEF: left ventricular ejection fraction; E-wave: Early diastolic mitral inflow velocity; A-wave: Late diastolic mitral inflow velocity; ALT: alanine aminotransferase; AST: aspartate aminotransferase