The demographic and clinical features of TA patients with and without cardiac involvement
In our study, a total of 127 patients with TA were analyzed retrospectively, with a male/female ratio of 1:17.1 (7/120). According to the comprehensive evaluation, 68 patients with evidence of TA-related cardiac involvement were included in group 1, and the other 59 patients without cardiac involvement were treated as group 2. The demographic and clinical features of patients were listed in Table 1. In terms of demographic characteristics, there were no significant differences in age, sex, disease duration, and body mass index (BMI) among the two groups (p>0.05). Besides, no significant differences were observed between the two groups in the history of hypertension, hyperlipidemia, cardiovascular disease (CVD), renal dysfunction, type 2 diabetes mellitus (T2DM) and smoking (P>0.05). Regarding baseline clinical manifestations, the proportion of neck pain in group 1 was significantly lower than that in group 2 (p<0.05). There were no statistical differences in the incidence of dizziness, headache, pulseless, bilateral blood pressure asymmetry, claudication, fever, palpitation, chest distress, chest pain, erythema nodular, and body weight reduction between the two groups (p>0.05).
Table 1 The demographic and clinical features of TA patients with and without cardiac involvement
|
the cardiac involvement group (n=68)
|
the non-cardiac involvement group (n=59)
|
P value
|
Age at onset, years
|
33.18±12.11
|
30.98±12.70
|
0.331
|
Male, n (%)
|
5(7.35)
|
2(3.39)
|
0.329
|
Disease duration, months
|
121.36±99.74
|
106.68±111.50
|
0.446
|
BMI, kg/m2
|
22.91±3.72
|
22.59±3.40
|
0.630
|
History
|
|
|
|
Hypertension, n (%)
|
32(47.06)
|
22(37.29)
|
0.179
|
Hyperlipidimia, n (%)
|
22(32.35)
|
20(33.90)
|
0.973
|
CVD, n (%)
|
5(7.35)
|
4(6.78)
|
1.000
|
Renal dysfunction, n (%)
|
12(17.65)
|
10(16.95)
|
0.838
|
T2DM, n (%)
|
4(5.88)
|
5(8.47)
|
0.734
|
Smoking, n (%)
|
5(7.35)
|
2(3.39)
|
0.443
|
Clinical symptoms
|
|
|
|
Dizzy, n (%)
|
24(35.29)
|
29(49.15)
|
0.149
|
Headache, n (%)
|
13(19.12)
|
10(16.95)
|
0.673
|
Pulseless, n (%)
|
11(16.18)
|
16(27.12)
|
0.159
|
Bilateral blood pressure asymmetry, n (%)
|
21(30.88)
|
19(32.20)
|
0.989
|
Claudication, n (%)
|
3(4.41)
|
3(5.08)
|
1.000
|
Fever, n (%)
|
4(5.88)
|
6(10.17)
|
0.513
|
Palpitation, n (%)
|
15(22.06)
|
6(10.17)
|
0.062
|
Chest distress, n (%)
|
22(32.35)
|
12(20.34)
|
0.104
|
Chest pain, n (%)
|
12(17.65)
|
6(10.17)
|
0.206
|
Neck pain, n (%)
|
2(2.94)
|
11(18.64)
|
0.006
|
Erythema nodosa, n (%)
|
2(2.94)
|
4(6.78)
|
0.418
|
Weight loss, n (%)
|
4(5.88)
|
3(5.08)
|
1.000
|
Abbreviations: BMI, body mass index; CVD, cardiovascular disease; T2DM, type 2 diabetes mellitus.
Comparison of laboratory parameters and disease activity in TA patients with and without cardiac involvement
In comparing the blood routine test between the two groups, neutrophil-to-lymphocyte ratio (NLR), homocysteine (HCY) and brain natriuretic peptide (BNP) in group 1 were higher than that of group 2 (p<0.05). There was no difference in liver and kidney function between the two groups (p>0.05). Immunity and inflammation markers such as serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, immunoglobulin (Ig) A, IgG, IgM, IgE, complement 3, complement 4, and positive antinuclear antibodies were not significantly different between the two groups (p>0.05). The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), as the activity indicators of TA, had been compared between the two groups. There was no difference in the level of CRP between the two groups (p>0.05), whereas the ESR in group 1 were significantly higher than those in group 2 (p<0.05) (Table 2).
Table 2 The laboratory parameters of TA patients with and without cardiac involvement
|
the cardiac involvement group (n=68)
|
the non-cardiac involvement group (n=59)
|
P value
|
WBC (109/L)
|
6.8(5.2,10.4)
|
6.4(5.0,8.8)
|
0.392
|
NE (109/L)
|
4.8(3.3,7.2)
|
3.7(2.9,6.1)
|
0.114
|
LY (109/L)
|
1.6(1.2,2.1)
|
1.8(1.5,2.4)
|
0.201
|
PLT (109/L)
|
241.5(186.3,301.8)
|
228.0(225.0,321.0)
|
0.210
|
PLR
|
145.2(110.1,203.3)
|
142.5(105.6,192.6)
|
0.793
|
NLR
|
2.9(1.9,4.2)
|
2.2(1.6,3.2)
|
0.027
|
RBC (1012/L)
|
4.1(3.7,4.5)
|
4.2(4.0,4.6)
|
0.107
|
Hb (g/L)
|
122.0(107.8,135.0)
|
121.0(107.5,130.5)
|
0.846
|
ALT (U/L)
|
13.0(8.0,18.0)
|
11.5(9.0,14.0)
|
0.712
|
Cr (μmol/l)
|
60.5(53.5,68.3)
|
56.2(47.4,63.0)
|
0.076
|
Fasting glucose (mmol/l)
|
4.6(4.2,5.0)
|
4.5(4.2,5.2)
|
0.798
|
HCY (μmol/l)
|
12.1(9.8,13.6)
|
9.2(8.0,11.0)
|
<0.001
|
BNP (pg/ml)
|
119.0(54.0,320.0)
|
21.0(9.8,48.5)
|
<0.001
|
TG (mmol/l)
|
1.0(0.8,1.4)
|
0.9(0.7,1.2)
|
0.100
|
TCHO (mmol/l)
|
4.2(3.2,4.8)
|
4.1(3.3,4.5)
|
0.685
|
LDL-C(ng/ml)
|
2.2(1.7,2.9)
|
2.2(1.7,2.8)
|
0.648
|
IL-6 (pg/ml)
|
9.9(4.8,19.3)
|
6.2(3.8,13.7)
|
0.081
|
TNF-α (pg/ml)
|
11.5(5.3,41.3)
|
7.0(3.5,29.3)
|
0.499
|
IgA (g/l)
|
2.1(1.6,2.7)
|
2.1(1.7,2.6)
|
0.709
|
IgG (g/l)
|
11.7(9.0,14.8)
|
10.4(8.3,13.7)
|
0.470
|
IgM (g/l)
|
1.2(0.7,1.5)
|
1.2(0.8,1.7)
|
0.453
|
IgE (g/l)
|
8.2(3.3,40.3)
|
16.3(6.0,31.6)
|
0.355
|
C3 (g/l)
|
1.2(0.9,1.3)
|
1.1(1.0,1.3)
|
0.923
|
C4 (g/l)
|
0.24(0.19,0.31)
|
0.21(0.16,0.26)
|
0.088
|
ESR (mm/1 h)
|
18.0(9.0,30.0)
|
11.0(7.0,18.0)
|
0.025
|
CRP (mg/l)
|
5.5(1.0,14.1)
|
1.5(0.5,5.3)
|
0.061
|
Abbreviations: WBC, white blood cell; NE, neutrophil; LY, lymphocyte; PLT, platelet; PLR, platelet-to-lymphocyte ratio; NLR, neutrophil-to-lymphocyte ratio; RBC, red blood cell; Hb, hemoglobin; ALT, alanine aminotransferase; Cr, creatinine; HCY, homocysteine; BNP, brain natriuretic peptide; TG, triglyceride; TCHO, total cholesterol; LDL-C, low-density lipoprotein cholesterol; IL, interleukin; TNF, tumor necrosis factor; Ig, immunoglobulin; C3, complement 3; C4, complement 4; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein.
The echocardiographic findings of TA patients with and without cardiac involvement
As shown in Table 3, there were significant differences in LAD, interventricular septum thickness (IVST), LV posterior wall thickness (LVPWT), LV end-diastolic dimension (LVEDD), LV end-systolic dimension (LVESD), LV ejection fraction (LVEF), LV mass, LV mass/body surface area (BSA), main pulmonary artery diameter (MPAD), E peak of mitral valve pulse by doppler spectrum (E peak) and A peak of mitral valve pulse by doppler spectrum (A peak) between the two groups (p<0.05). Besides, the maximal diameter of the sinuses of Valsalva and the proximal ascending aorta in group 1 were greater than that of group 2 (p<0.05). However, the diameter of right ventricular outflow tract (RVOT) in parasternal long-axis view (PLAX) had no statistical significance between the two groups (p>0.05).
Table 3 The echocardiographic parameters of TA patients with and without cardiac involvement
|
the cardiac involvement
group (n=68)
|
the non-cardiac involvement group
(n=59)
|
P value
|
LAD, mm
|
36.19±5.01
|
31.49±3.28
|
<0.001
|
IVST, mm
|
10.69±2.12
|
8.66±0.99
|
<0.001
|
LVPWT, mm
|
10.32±1.94
|
8.75±0.93
|
<0.001
|
LVEDD, mm
|
49.97±7.16
|
44.19±2.93
|
<0.001
|
LVESD, mm
|
32.72±7.31
|
28.17±2.53
|
<0.001
|
LVEF, %
|
61.60±8.63
|
65.61±4.31
|
0.002
|
LV mass, g
|
200.49±74.46
|
124.44±22.97
|
<0.001
|
LV mass/BSA, g/m2
|
124.81±47.16
|
77.13±13.51
|
<0.001
|
RVOT PLAX diameter, mm
|
25.59±3.76
|
26.03±7.27
|
0.659
|
the maximal diameter of the sinuses of Valsalva, mm
|
32.77±5.52
|
30.00±3.36
|
0.001
|
the maximal diameter of the proximal ascending aorta, mm
|
35.59±6.83
|
31.70±5.64
|
0.001
|
MPAD, mm
|
24.63±4.01
|
21.57±2.09
|
<0.001
|
E peak, cm/s
|
93.40±25.92
|
84.59±17.34
|
0.009
|
A peak, cm/s
|
80.69±22.22
|
76.17±15.05
|
0.03
|
Abbreviations: LAD: left atrial diameter; IVST: interventricular septum thickness; LVPWT: left ventricular posterior wall thickness; LVEDD: left ventricular end-diastolic dimension; LVESD: left ventricular end-systolic dimension; LVEF: left ventricular ejection fraction; LV mass: left ventricular mass; BSA: body surface area; RVOT: right ventricular outflow tract; PLAX: parasternal long-axis view; MPAD: main pulmonary artery diameter; E peak: E peak of mitral valve pulse by doppler spectrum; A peak: A peak of mitral valve pulse by doppler spectrum.
The main classification manifestations of echocardiography in TA patient with cardiac involvement were as follows: hypertensive heart disease, coronary heart disease, myocardial abnormalities, valvular abnormalities and PH. Echocardiographic findings in group 1 were shown in Table 4.
Echocardiographic features of the hypertensive heart disease in TA patients included left atrial dilation, LV enlargement and ventricular wall thickening. In group 1, left atrial dilation were found in 40 patients (40/68, 58.82%) and 32 patients (32/68, 47.06%) demonstrated LV enlargement. Six patients (6/68, 8.82%) presented isolated ventricular septal thickening. Twenty-four patients (24/68, 35.29%) were diagnosed LV concentric hypertrophy which manifested the thickening of interventricular septum and posterior LV wall. Hypertension was observed in 22 of the 30 patients accompanied ventricular wall thickening (73.33%).
Coronary artery abnormalities could be manifested with wall motion abnormalities. In our study, echocardiography indicated that wall motion abnormalities were found in 11 patients. Four patients (4/68, 5.88%) were diagnosed with diffuse decrease of wall motion and all of them had been confirmed to have coronary involvement. The regional wall motion abnormalities had been indicated in 7 patients (7/68, 10.29%). Of the 7 cases, 1 case had been considered that the abnormal wall motion of middle inferior-posterior left ventricle wall was associated with the impact of severe AR. The results of coronary arteries angiographic examinations had proved that the other 6 cases had coronary involvement.
Myocardial abnormalities were found in 18 patients (18/68, 26.47%), in which 2 patients were clinically confirmed with dilated cardiomyopathy. Among the patients with myocardial involvement, left atrial dilation were found in 17 patients (17/18, 94.44%), LV enlargement in 15 patients (15/18, 83.33%), LV systolic dysfunction in 9 patients (9/18, 50.00%). In terms of myocardial echo, 1 patient presented inhomogeneous myocardial echoes with high-echo dots.
Pathological valvular abnormalities were found in 55 TA patients (55/68, 80.88%). The most common valvular finding was AR (45/55, 81.82%) (Fig. 1), in which the percentage of severe AR was up to 44.44% (20/45). Six patients with severe AR went to surgery for aortic replacement. 31.11% (14/45) of patients with AR were combined with aortic root dilatation. Aortic stenosis was found in 3 patients (3/55, 5.45%). Thirty-eight cases (38/55, 69.09%) had mitral valve involvement and all of them suffered from insufficiency. Among them, one patient (1/55, 2.63%) was combined with mitral stenosis. Mitral valve leaflet prolapse were observed in 5 patients (5/55, 9.09%), one of whom might undergo changes similar to valvular myxomatous degeneration according to results of echocardiography (Fig. 2). Three of the patients with severe mitral regurgitation went to mitral replacement. The rate of tricuspid valve involved was 54.55% (30/55). There were 4 patients (4/55,7.27%) who had pulmonary insufficiency. Valve calcification was found in 3 cases (3/55, 5.45%). Ten patients (10/55, 18.18%) presented with valve thickening (9 case in the aortic valve, 1 case in the mitral valve).
PH was detected in 11 patients (11/68, 16.18%). Among the patients with PH, pulmonary arterial involvement was present in 5 patients confirmed by CTPA. The left 6 patients with PH were caused by simple left-sided heart diseases. Severe PH was found in 3 patients and all of them were accompanied by moderate or severe tricuspid regurgitation. Of the 3 patients, right ventricular enlargement and dysfunction were found in 2 patients and were not associated with left-sided heart diseases.
In the present study, 1 (1/68, 1.47%) case was diagnosed with aortic dissection. There was pericardial effusion in 11 cases (11/68, 16.18%).
Table 4 Echocardiographic findings of TA patients with cardiac involvement
Echocardiographic characteristics
|
|
n (%)
|
Enlargement of left atrium
|
|
40(58.82)
|
Enlargement of right atrium
|
|
10(14.71)
|
Enlargement of left ventricular
|
|
32(47.06)
|
Isolated ventricular septal thickening
|
|
6(8.82)
|
Left ventricular hypertrophy
|
|
24(35.29)
|
Ventricular systolic dysfunction
|
|
10(14,71)
|
Ejection fraction
|
<30
|
0(.0)
|
|
31–40
|
2(2.94)
|
|
41–50
|
8(11.76)
|
|
51–60
|
14(20.59)
|
|
>60
|
44(64.71)
|
Diffuse decrease of wall motion
|
|
4(5.88)
|
Regional wall motion abnormalities
|
|
7(10.29)
|
pathological valvular abnormalities
|
|
55(80.88)
|
Aortic valve abnormalities
|
|
|
Aortic valve stenosis
|
|
3(5.45)
|
Aortic valve regurgitation
|
Total
|
45(81.82)
|
|
Mild
|
12(21.82)
|
|
Moderate
|
13(23.64)
|
|
Severe
|
20(35.36)
|
Aortic valve calcification
|
|
2(3.64)
|
Aortic valve thickening
|
|
9(16.36)
|
Mitral valve abnormalities
|
|
|
Mitral valve stenosis
|
|
1(1.82)
|
Mitral valve regurgitation
|
Total
|
38(69.09)
|
|
Mild
|
20(36.36)
|
|
Moderate
|
13(23.64)
|
|
Severe
|
5(9.09)
|
Mitral valve leaflet prolapse
|
|
5(9.09)
|
Mitral valve calcification
|
|
1(1.82)
|
Mitral valve thickening
|
|
1(1.82)
|
Tricuspid valve abnormalities
|
|
|
Tricuspid valve stenosis
|
|
0(.0)
|
Tricuspid valve regurgitation
|
Total
|
30(54.55)
|
|
Mild
|
21(38.18)
|
|
Moderate
|
8(14.55)
|
|
Severe
|
1(1.82)
|
Pulmonary insufficiency
|
|
4(7.27)
|
SPAP
|
|
11(16.18)
|
SPAP (mmHg)
|
40–54
|
3(4.41)
|
|
55–64
|
5(7.35)
|
|
>65
|
3(4.41)
|
Pulmonary trunk dilation
|
|
12(17.65)
|
Aortic dissection
|
|
1(1.47)
|
Pericardial effusion
|
|
11(16.18)
|
Abbreviations: SPAP: systolic pulmonary arterial pressure.
The echocardiographic parameters of TA patients with cardiac involvement associated with and without PH
Compared to group 2, both patients in group 1 with and without PH presented with significant differences of echocardiographic parameters regarding LAD, IVST, LVPWT, LVEDD, LVESD, LVEF, LV mass, LV mass/BSA and MPAD (P<0.05). We also compared the echocardiographic parameters between the patients with and without PH in group 1, the differences were of no statistical significance (p>0.05) (Table 5).
Table 5 The echocardiographic parameters in TA patients with cardiac involvement associated with and without PH
Variables
|
the cardiac involvement
group (n=68)
|
the non-cardiac involvement group
(n=59)
|
P value
|
Patients with PH (n=11)
|
Patients without PH (n=57)
|
Patients with PH vs without PH
|
Patients with PH vs the non-cardiac involvement group
|
Patients without PH vs the non-cardiac involvement group
|
LAD, mm
|
36.09±5.47
|
36.21±4.97
|
31.49±3.28
|
0.933
|
0.001
|
<0.001
|
IVST, mm
|
10.42±2.53
|
10.74±2.06
|
8.66±0.99
|
0.57
|
0.002
|
<0.001
|
LVPWT, mm
|
10.46±1.92
|
10.30±1.95
|
8.75±0.93
|
0.761
|
0.001
|
<0.001
|
LVEDD, mm
|
51.91±5.17
|
49.59±7.46
|
44.19±2.93
|
0.211
|
<0.001
|
<0.001
|
LVESD, mm
|
35.55±6.55
|
32.17±7.38
|
28.17±2.53
|
0.068
|
<0.001
|
<0.001
|
LVEF, %
|
58.73±10.24
|
62.16±8.28
|
65.61±4.31
|
0.136
|
0.003
|
0.008
|
LV mass, g
|
207.89±61.98
|
199.06±77.04
|
124.44±22.97
|
0.638
|
<0.001
|
<0.001
|
LV mass/BSA, g/m2
|
132.14±43.93
|
123.58±47.95
|
77.13±13.51
|
0.508
|
<0.001
|
<0.001
|
RVOT PLAX diameter, mm
|
27.64±3.83
|
25.19±3.65
|
26.03±7.27
|
0.191
|
0.389
|
0.424
|
the maximal diameter of the sinuses of Valsalva, mm
|
30.55±4.08
|
33.19±5.68
|
30.00±3.36
|
0.083
|
0.719
|
<0.001
|
the maximal diameter of the proximal ascending aorta, mm
|
33.64±7.19
|
35.97±6.76
|
31.70±5.64
|
0.262
|
0.349
|
<0.001
|
MPAD, mm
|
25.36±4.52
|
24.49±3.93
|
21.57±2.09
|
0.419
|
0.001
|
<0.001
|
E, cm/s
|
102.27±23.49
|
91.68±26.21
|
84.59±17.34
|
0.151
|
0.017
|
0.089
|
A, cm/s
|
75.00±20.61
|
81.68±22.52
|
76.17±15.05
|
0.312
|
0.859
|
0.125
|
Abbreviations: LAD: left atrial diameter; IVST: interventricular septum thickness; LVPWT: left ventricular posterior wall thickness; LVEDD: left ventricular end-diastolic dimension; LVESD: left ventricular end-systolic dimension; LVEF: left ventricular ejection fraction; LV mass: left ventricular mass; BSA: body surface area; RVOT: right ventricular outflow tract; PLAX: parasternal long-axis view; MPAD: main pulmonary artery diameter; E peak: E peak of mitral valve pulse by doppler spectrum; A peak: A peak of mitral valve pulse by doppler spectrum.