Patient Population and Demographics
According to the established diagnostic criteria, a refined cohort of 415 patients was identified from the initial pool of 491 individuals. Among these patients, 316 (76.1%) received a diagnosis of left ventricular noncompaction cardiomyopathy (LVNC), 33 (8%) were diagnosed with right ventricular noncompaction cardiomyopathy (RVNC), and 66 (15.9%) exhibited biventricular noncompaction cardiomyopathy (BVNC). Of the 415 patients, 229 (44.1%) were female, and 232 (55.9%) were male. Stratification based on age resulted in three distinct groups: the 0–1 years old group, comprising 169 patients, with 94 (55.6%) males and 75 (44.4%) females; the 1–18 years old group, totaling 149 patients, including 68 (45.6%) males and 81 (54.4%) females; and the > 18 years old group, consisting of 97 patients, with 70 (72.7%) males and 27 (27.8%) females (Table 1, Fig. 1, Figure S6).
Table 1
|
Overall
(n = 415)
|
0–1 years old
(n = 169)
|
1–18 years old
(n = 149)
|
> 18 years old
(n = 97)
|
p
|
Demography
|
|
|
|
|
|
Male, n (%)
|
232 (55.9)
|
94 (55.6)
|
68 (45.6)
|
70 (72.2)
|
< 0.001
|
Heigh (mean (SD))
|
87.00 [60.00, 155.50]
|
58.00 [52.00, 64.00]
|
101.00 [85.00, 133.00]
|
165.00 [161.00, 172.00]
|
< 0.001
|
Weight, (kg)
|
11.50 [5.40, 44.00]
|
5.00 [3.58, 6.00]
|
15.00 [11.00, 28.00]
|
56.50 [53.00, 64.00]
|
< 0.001
|
Hospital stays, (days)
|
9.00 [5.00, 15.50]
|
12.00 [7.00, 19.00]
|
8.00 [5.00, 13.00]
|
8.00 [5.00, 12.00]
|
0.001
|
NYHA, n (%)
|
|
|
|
|
< 0.001
|
I
|
28 (6.7)
|
6 (3.6)
|
19 (12.8)
|
3 (3.1)
|
|
II
|
223 (53.7)
|
96 (56.8)
|
84 (56.4)
|
43 (44.3)
|
|
III
|
112 (27.0)
|
36 (21.3)
|
35 (23.5)
|
41 (42.3)
|
|
Ⅳ
|
52 (12.5)
|
31 (18.3)
|
11 (7.4)
|
10 (10.3)
|
|
SaO2, (%)
|
97.29 (5.13)
|
96.99 (4.61)
|
97.33 (5.76)
|
97.73 (4.97)
|
0.525
|
Combined with valvular regurgitation, n (%)
|
|
|
|
|
|
No valvular regurgitation
|
105 (25.3)
|
47 (27.8)
|
45 (30.2)
|
13 (13.4)
|
< 0.001
|
MR
|
75 (18.1)
|
36 (21.3)
|
22 (14.8)
|
17 (17.5)
|
|
TR
|
60 (14.5)
|
34 (20.1)
|
22 (14.8)
|
4 (4.1)
|
|
AR
|
10 (2.4)
|
4 (2.4)
|
4 (2.7)
|
2 (2.1)
|
|
PR
|
3 (0.7)
|
2 (1.2)
|
1 (0.7)
|
0 (0.0)
|
|
Multiple valve regurgitation
|
162 (39.0)
|
46 (27.2)
|
55 (36.9)
|
61 (62.9)
|
|
Combined with CHD, n (%)
|
|
|
|
|
< 0.001
|
Isolated NCM
|
169 (40.7)
|
26 (15.4)
|
54 (36.2)
|
89 (91.8)
|
|
PDA/PFO
|
91 (21.9)
|
51 (30.2)
|
35 (23.5)
|
5 (5.2)
|
|
ASD
|
29 (7.0)
|
7 (4.1)
|
20 (13.4)
|
2 (2.1)
|
|
VSD
|
37 (8.9)
|
22 (13.0)
|
15 (10.1)
|
0 (0.0)
|
|
Multiple CHD
|
76 (18.3)
|
58 (34.3)
|
18 (12.1)
|
0 (0.0)
|
|
Others
|
13 (3.1)
|
5 (3.0)
|
7 (4.7)
|
1 (1.0)
|
|
Electrocardiograph
|
|
|
|
|
|
Rhythm, n (%)
SR
AT
VT
Heart block
Others
|
256 (61.7)
44 (10.7)
29 (7.0)
69 (16.7)
17 (4.1)
|
149 (88.2)
10 (5.9)
0 (0.0)
7 (4.1)
2 (1.8)
|
77 (51.7)
12 (8.2)
6 (4.1)
20 (27.4)
14 (9.4)
|
30 (30.9)
22 (22.7)
23 (23.7)
22 (22.7)
0 (0.0)
|
< 0.001
|
QRS duration, (ms)
|
81.00 [65.00, 100.00]
|
66.00 [60.00, 78.00]
|
84.00 [70.00, 100.00]
|
103.00 [94.00, 122.00]
|
< 0.001
|
PR duration, (ms)
|
128.00 [112.00, 154.00]
|
120.00 [102.00, 126.00]
|
130.00 [115.00, 156.00]
|
160.00 [142.00, 176.00]
|
< 0.001
|
QT, (ms)
|
314.00 [271.00, 377.00]
|
276.00 [244.00, 294.00]
|
336.00 [290.00, 376.00]
|
400.00 [367.00, 426.00]
|
< 0.001
|
QRS axis, (°)
|
62.00 [11.00, 89.50]
|
70.00 [23.00, 98.00]
|
68.00 [14.00, 92.00]
|
36.00 [-7.00, 75.00]
|
0.005
|
QTc, (ms)
|
431.00 [400.50, 461.50]
|
418.00 [396.00, 453.00]
|
431.00 [402.00, 463.00]
|
448.00 [422.00, 471.00]
|
0.009
|
Laboratory examination
|
|
|
|
|
|
TnT, (pg/ml)
|
44.60 [9.80, 114.00]
|
57.30 [10.80, 105.70]
|
61.80 [9.80, 565.00]
|
19.40 [9.10, 52.10]
|
0.002
|
NT-proBNP, (pg/ml)
|
1746.00 [116.10, 5034.50]
|
3584.00 [1200.00, 15466.00]
|
344.00 [33.50, 3485.00]
|
1062.00 [117.80, 3581.00]
|
< 0.001
|
CK, (U/L)
|
100.00 [68.50, 168.50]
|
123.00 [79.00, 241.00]
|
103.00 [71.00, 147.00]
|
77.00 [54.00, 103.00]
|
0.041
|
CKMB, (U/L)
|
18.60 [11.05, 27.75]
|
24.10 [18.10, 33.90]
|
18.20 [11.40, 26.10]
|
10.50 [8.90, 12.40]
|
0.001
|
LDH, (U/L)
|
276.00 [206.50, 347.00]
|
320.00 [275.00, 396.00]
|
267.00 [216.00, 345.00]
|
180.00 [153.00, 229.00]
|
0.003
|
INR
|
1.10 [1.02, 1.22]
|
1.11 [1.04, 1.26]
|
1.10 [1.02, 1.19]
|
1.07 [1.01, 1.18]
|
0.255
|
NCM location (%)
|
|
|
|
|
< 0.001
|
LVNCM
|
316 (76.1)
|
120 (71.0)
|
102 (68.5)
|
94 (96.9)
|
|
RVNCM
|
33 (8.0)
|
19 (11.2)
|
12 (8.1)
|
2 (2.1)
|
|
BVNCM
|
66 (15.9)
|
30 (17.8)
|
35 (23.5)
|
1 (1.0)
|
|
Echocardiograph
|
|
|
|
|
|
LA diameter, (mm)
|
26.00 [20.00, 35.00]
|
20.00 [16.00, 24.00]
|
29.00 [23.70, 34.00]
|
40.00 [32.00, 46.00]
|
< 0.001
|
RA diameter, (mm)
|
23.00 [17.00, 39.50]
|
17.00 [15.00, 20.00]
|
25.00 [22.00, 33.00]
|
48.00 [42.00, 55.00]
|
< 0.001
|
MR area, (cm2)
|
0.79 [0.00, 2.55]
|
0.20 [0.00, 1.00]
|
0.70 [0.00, 2.70]
|
3.00 [1.00, 9.60]
|
< 0.001
|
TR area, (cm2)
|
0.60 [0.00, 1.70]
|
0.20 [0.00, 0.90]
|
0.80 [0.00, 2.00]
|
1.50 [0.00, 4.00]
|
< 0.001
|
AR area, (cm2)
|
0.00 [0.00, 0.00]
|
0.00 [0.00, 0.00]
|
0.00 [0.00, 0.00]
|
0.00 [0.00, 1.30]
|
< 0.001
|
LVEF, (%)
|
64.00 [38.00, 71.00]
|
69.00 [50.00, 77.00]
|
66.00 [52.00, 71.00]
|
37.00 [29.00, 51.00]
|
< 0.001
|
FS, (%)
|
33.00 [19.00, 39.00]
|
37.00 [25.00, 43.00]
|
36.00 [27.00, 39.00]
|
19.00 [13.00, 25.00]
|
< 0.001
|
LVED diameter, (mm)
|
36.00 [27.00, 50.00]
|
27.00 [21.00, 32.00]
|
37.00 [32.00, 45.00]
|
61.00 [53.00, 69.00]
|
< 0.001
|
LVES diameter, (mm)
|
23.90 [17.00, 36.00]
|
17.00 [13.00, 22.00]
|
24.00 [20.00, 32.00]
|
50.00 [39.00, 57.00]
|
< 0.001
|
RV diameter, (mm)
|
23.00 [17.00, 44.00]
|
16.00 [14.00, 19.00]
|
25.00 [21.00, 33.00]
|
57.00 [49.00, 62.00]
|
< 0.001
|
Data are count (%), mean (SD), or median [25th–75th percentiles]; NYHA, New York Heart Association functional classification; SaO2, arterial oxygen saturation; MR, mitral regurgitation; TR, tricuspid regurgitation; AR, aortic regurgitation; PR, Pulmonary regurgitation; NCM, noncompaction cardiomyopathy; CHD, congenital heart disease; PFO, patent foramen oval; PDA, patent ductus arteriosus; ASD, atrial septal defect; VSD, ventricular septal defect; SR, sinus rhythm; AT, atrial tachycardia; VT, ventricular tachycardia; TnT, troponin T; CK, creatine kinase; CKMB, creatine kinase isoenzyme; LDH, lactic dehydrogenase; N-BNP, N-terminal pro-B-type natriuretic peptide; INR, international normalized ratio; LVNCM, left ventricular noncompaction cardiomyopathy; RVNCM, right ventricular noncompaction cardiomyopathy; BVNCM, biventricular noncompaction cardiomyopathy; LA, left atrial; RA, right atrium; LVEF, left ventricular ejection fraction; FS, left ventricular fractional shortening; LVED, left ventricular end-diastolic; LVES, left ventricular end-systolic; RV, right ventricular. |
Table 2. The main clinical presentation of NCM patients
Clinical Presentation, n (%)
|
Overall (n=415)
|
0~1 years old
(n=169)
|
1~18 years old (n=149)
|
>18 years old (n=97)
|
Asymptomatic
|
43 (10.4)
|
22 (13.0)
|
17 (11.4)
|
4 (4.1)
|
Newborn with severe malformation
|
21 (5.1)
|
21 (12.4)
|
0 (0.0)
|
0 (0.0)
|
Heart failure
|
112 (27.0)
|
33 (19.5)
|
26 (17.4)
|
53 (54.6)
|
Palpitation/Abnormal ECG
|
29 (7.0)
|
2 (1.2)
|
14 (9.4)
|
13 (13.4)
|
Murmur
|
102 (24.6)
|
42 (24.9)
|
57 (38.3)
|
3 (3.1)
|
Cardiomegaly on chest radiograph
|
10 (2.4)
|
3 (1.8)
|
7 (4.7)
|
0 (0.0)
|
Dizziness/Syncope
|
18 (4.3)
|
0 (0.0)
|
10 (6.7)
|
8 (8.2)
|
Pulmonary infection
|
56 (13.5)
|
38 (22.5)
|
13 (8.7)
|
5 (5.2)
|
Chest pain
|
11 (2.7)
|
0 (0.0)
|
2 (1.3)
|
9 (9.3)
|
Failure to thrive
|
5 (1.2)
|
5 (3.0)
|
0 (0.0)
|
0 (0.0)
|
Others
|
8 (1.9)
|
3 (1.8)
|
3 (2.0)
|
2 (2.1)
|
ECG. Electrocardiogram.
Clinical Presentation
Among the cohort of 415 patients diagnosed with NCM, 169 individuals were identified within the first year of birth. Key clinical manifestations of NCM patients are summarized in Table S1, where the predominant symptomatology included chest tightness and shortness of breath, indicative of heart failure, observed in 112 patients (27%). Additionally, heart murmur was reported in 102 patients (24.6%). Less frequent manifestations encompassed cyanosis, syncope, chest pain, and growth retardation. Notably, 43 patients (10.4%) were asymptomatic, and 56 patients (13.5%) exhibited symptoms such as cough, phlegm, and fever secondary to pulmonary infection. Palpitations or abnormal electrocardiograms were present in 29 patients (7%). In patients aged > 18 years, heart failure emerged as the predominant clinical presentation, whereas murmur was more prevalent in the other two age groups (Table S1). Of the total cohort, 164 patients (39.5%) were categorized as New York Heart Association (NYHA) III-IV, with the majority belonging to the > 18 years old age group, accounting for 51 patients (52.6%). Tragically, 8 patients succumbed during hospitalization. Causes of mortality included severe heart failure (4 patients), septic shock (1 patient), disseminated intravascular coagulation (1 patient), and acute rejection after heart transplantation (2 patients) (Table 2).
NCM with valvular regurgitation
Patients with noncompaction cardiomyopathy (NCM) exhibited a heightened incidence of valvular regurgitation, with 310 patients (74.7%) manifesting this cardiac anomaly. Evaluation of mitral, tricuspid, aortic, and pulmonary valve function revealed that 105 patients (25.3%) showed no valvular regurgitation. The prevailing condition among NCM patients was multiple valve regurgitation, observed in 162 patients (39%), with more than two valve regurgitations. Multivalvular regurgitation was most prevalent in patients aged > 18 years, accounting for 61 patients (62.9%), followed by patients aged 1–18 years, with 55 patients (36.9%). The lowest proportion was observed in patients aged 0–1 years, constituting only 46 patients (27.3%) (Table 1 and Fig. 2). These findings underscore the notable association between NCM and valvular regurgitation, with a notable prevalence of multivalvular involvement, particularly in older patient populations.
The next most common were NCM patients with isolated MR (75 patients, 18.1%). Comparing NCM patients with MR alone and those without valvular regurgitation, we found that patients with MR alone had significantly worse left heart function and significantly dilated left heart across all age groups. In 0–1 years old patients combined with MR alone, LVEF (70.00 [65.00, 77.00] % vs 63.50 [40.00, 71.00] %, p = 0.012) and FS (37.00 [33.00, 44.00] %vs 33.00 [18.50, 39.50] %, p = 0.018) significantly decreased; left atrium (LA) diameter (18.60 [15.50, 21.00]mm vs 22.50 [19.00, 27.00]mm, p < 0.001), LVES diameter(16.00 [12.50, 18.50]mm vs 21.00 [17.00, 27.10]mm, p < 0.001), and LVED diameter(24.00 [20.10, 30.00]mm vs 32.50 [26.00, 36.00]mm, p < 0.001) significantly dilated (Table S1, Fig. 3, Fig. 4). In 1–18 years old patients combined with MR alone, a noteworthy decline in left ventricular ejection fraction (LVEF) (70.00 [65.00, 77.00] % vs 63.50 [40.00, 71.00] %, p = 0.012) and fractional shortening (FS) (37.00 [33.00, 44.00] % vs 33.00 [18.50, 39.50] %, p = 0.018) was observed. Additionally, there was a significant dilation in left atrium (LA) diameter (18.60 [15.50, 21.00]mm vs 22.50 [19.00, 27.00]mm, p < 0.001), left ventricular end-systolic (LVES) diameter (16.00 [12.50, 18.50]mm vs 21.00 [17.00, 27.10]mm, p < 0.001), and left ventricular end-diastolic (LVED) diameter (24.00 [20.10, 30.00]mm vs 32.50 [26.00, 36.00]mm, p < 0.001) (Table S1, Fig. 3, Fig. 4). In > 18 years old patients combined with MR alone, LVEF (55.69 (16.50) % vs 37.59 (13.34) %, p = 0.008) and FS (29.85 (10.79) % vs 17.82 (7.75) %, p = 0.016) significantly decreased; LVES diameter (30.00 [27.00, 40.00]mm vs 50.00 [43.00, 57.00]mm, p = 0.003), LVED diameter (50.00 [45.00, 52.00]mm vs 61.00 [57.00, 68.00]mm, p = 0.002) significantly dilated(Table S3, Fig. 3, Fig. 4).
To further explore the relationship between MR and left heart function and structure of NCM patients, we conducted correlation analysis of MR area and cardiac function parameters in NCM patients with MR alone. The results showed, in 0–1 years old patients, that the MR area was significantly correlated with LVED diameter (r = 0.434, p = 0.008), LVES diameter (r = 0.404, p = 0.015) and LA diameter (r = 0.522, p = 0.001), but no correlation between LVEF (p = 0.448) and FS (p = 0.365). In 1–18 years old patients, the MR area demonstrate a significant correlation with LVED diameter (r = 0.691, p < 0.001), LVES diameter (r = 0.784, p < 0.001), LA diameter (r = 0.894, < 0.001), FS (r = 0.584, p = 0.004) and LVEF (r = 0.546, p < 0.001). In > 18 years old patients, the MR area was significantly correlated with LVED diameter (r = 0.512, p = 0.035), LVES diameter (r = 0.508, p = 0.037) and LA diameter (r = 0.748, p < 0.001), but not with LVEF (p = 0.448) (Table 3 and Figure S2-S4). It is worth noting that there was a significant correlation between MR area and NC ratio (r=-0.441, p < 0.04) in 1–18 years old patients, which was not found in other age groups (Fig. 5).
Table 3
Correlation analysis of left ventricular echocardiography parameters and mitral regurgitation area in NCM patients with mitral regurgitation alone
|
MR area, (cm2)
|
|
0–1 years old (n = 36)
|
|
1–18 years old (n = 22)
|
|
> 18 years old (n = 17)
|
|
r
|
p
|
|
r
|
p
|
|
r
|
p
|
LVEF, (%)
|
-0.130
|
0.448
|
|
-0.546
|
0.009
|
|
-0.479
|
0.052
|
FS, (%)
|
-0.156
|
0.365
|
|
-0.584
|
0.004
|
|
-0.498
|
0.042
|
LVED diameter, (mm)
|
0.434
|
0.008
|
|
0.691
|
< 0.001
|
|
0.512
|
0.035
|
LVES diameter, (mm)
|
0.404
|
0.013
|
|
0.784
|
< 0.001
|
|
0.508
|
0.037
|
LA diameter, (mm)
|
0.522
|
0.001
|
|
0.894
|
< 0.001
|
|
0.748
|
< 0.001
|
NC/C
|
-0.004
|
0.980
|
|
-0.441
|
0.040
|
|
-0.047
|
0.856
|
MR, mitral regurgitation; LVEF, left ventricular ejection fraction; FS, left ventricular fractional shortening; LVED, left ventricular end-diastolic; LVES, left ventricular end-systolic; LA, left atrial; NC/C, Noncompaction myocardium thickness/compaction myocardium thickness. |
A total of 60 (14.5%) NCM patients presented with TR alone. In comparing NCM patients with TR alone to those without regurgitation, distinctive findings emerged, particularly in the 0–1 years old group. The right ventricular (RV) diameter (16.00 [13.00, 18.00]mm vs 18.00 [16.00, 16.00, 21.75]mm, p = 0.005) and right atrial (RA) diameter (16.00 [14.00, 19.00]mm vs 19.00 [16.00, 22.00]mm, p = 0.005) were significantly dilated in this age group. However, no significant differences were observed in other age groups (Table S1 and Figure S5).