Clinical and imaging characteristics of patients with cardiac amyloidosis- a single center observational study

Figures & data

Figure 1. Study flow chart demonstrating selection of patients to the study.

Figure 2. CMR images of an 83-year-old male diagnosed with AL amyloidosis. The left image (Panel A – 4-chamber view) displays the typical distribution of Late Gadolinium Enhancement (LGE), with a prominent subendocardial involvement in the left ventricle and encompassing the walls of all cardiac chambers, including the interatrial septum. In the right image (Panel B), native T1 mapping acquisition (transverse plane) reveals an elevated measurement within the interventricular septum, registering at 1448 milliseconds. This value exceeds the recommended threshold, which should ideally be below 1371 milliseconds, their upper normal value is defined as mean + 2 standard deviations (SD).

Figure 3. Electrocardiographic and echocardiography (apical 4-chamber view) images showing low voltage QRS (A) and huge left ventricular hypertrophy (B), arrow pointing towards interventricular septum) in a study participant with amyloidosis.

Figure 4. Correlations between NT-proBNP and myocardial mass on CMR (g), p = 0.003.

Figure 5. Correlation matrix. The figure give the correlation between the different parameters investigated, the values are given as Pearson correlation coefficient (PCC) and corresponding p-values. Negative PCC indicates a negative correlation, and positive PCC indicates positive correlation. Abbreviations: EF: LV ejection fraction (%) on CMR. GLS: global longitudinal strain on echocardiography.

Table 1. Baseline characteristics and laboratory data.

Characteristic	AL (n = 69)	ATTR (n = 25)	p
Age (year)	64.4 ± 13.1	79.4 ± 5.3	<0.001
Male, n (%)	44 (64)	21 (84)	0.061
BMI (kg/m^2)	25.5 ± 3.9	24.9 ± 3.6	0.529
Diabetes, n (%)	7 (10.1)	5 (20)	0.292
Hypertension, n (%)	40 (58)	16 (64)	0.599
Heart rate (bpm ± SD)	81 ± 15	78 ± 20	0.497
Systolic blood pressure (mmHg ± SD)	122 ± 21	138 ± 20	0.001
Diastolic blood pressure (mmHg ± SD)	74 ± 13	80 ± 14	0.046
Coronary artery disease, n (%)	15 (22)	10 (40)	0.077
Cardiac involvement, n (%)	47 (68)	25 (100)	0.001
Atrial fibrillation, n (%)	26 (38)	17 (68)	0.009
Low-voltage ECG, n (%)	32 (47)	8 (32)	0.838
Pacemaker, n (%)	5 (7.4)	2 (8)	0.871
History of smoking, n (%)	35 (51)	12 (48)	0.815
Hb (g/dl) ± SD	12.8 ± 2.1	13.3 ± 1.9	0.289
Lpk ×10^9/L	7.7 (6.2–10.5)	6.9 (5.5–7.5)	0.069
Platelets × 10^9/L	257 (188–365)	195.5 (164–245)	0.008
CRP (mg/L)	3 (1–9)	4 (2–13)	0.732
SR (mm)	34 (14–65)	22 (10–45)	0.174
Troponin T (ng/L)	54 (26–143)	59 (47–134)	0.201
NT-pro-BNP (ng/L)	2662 (687–8539)	1958 (828–6105)	0.871
Albumin (g/L) ±SD	33 ± 9	40 ± 5	<0.001
Protein-total (g/L)	59 (49–68)	67 (64–72)	<0.001
IgA (g/L)	1.4 (0.6–3.1)	2.5 (1.5–3.9)	0.018
IgG (g/L)	5.6 (2.7–10.1)	11.5 (7.6–12.7)	<0.001
IgM (g/L)	0.5 (0.2–1.0)	0.8 (0.5–1.0)	0.059
Lambda light chains (mg/L)	54.5 (28.6–177.0)	31.4 (23.9–53.6)	0.025
Kappa light chains (mg/L)	19.3 (9.8–165.0)	26.4 (17.2–32.9)	0.473
Ratio kappa/lambda	0.24 (0.09–5.07)	0.87 (0.71–0.99)	0.078
Beta-2 microglobulin (mg/L)	3.7 (2.4–6.2)	2.9 (2.2–3.8)	0.213
Creatinine (µmol/L)	93 (67–152)	103 (86–154)	0.117

Variables are expressed as mean ± standard deviation, median with IQR or n (%). Variables are presented as mean ± SD if it is normally distributed, or as median with IQR if not. All variables and lab values are results from the hospital stay when the diagnosis of amyloidosis was confirmed, or in the closest possible date to diagnosis. Age (year) is set to age at diagnosis. BMI: body mass index; NT-pro-BNP: N-terminal brain natriuretic peptide; Hb: hemoglobin; Lpk: leukocyte particle count; CRP: C-reactive protein; SR: sedimentation rate; Ig: immunoglobulin.

Table 2. Echocardiographic and cardiac magnetic resonance (CMR) imaging characteristics.

Echocardiography	AL (n = 68)	ATTR (n = 25)	p
Typical echocardiographic features of amyloidosis, n (%)	40 (62)	21 (84)	0.041
Left atrial dilatation, n (%)	38 (59)	20 (80)	0.056
Pleural effusion on echo, n (%)	13 (19)	2 (8)	0.340
Pericardial effusion on echo	28 (41)	7 (28)	0.187
Left ventricular end-diastolic dimension (mm)	44 (38–50)	44 (38–47)	0.661
Interventricular septum thickness (mm)	15.6 ± 3.3	19.1 ± 2.9	<0.001
Posterior wall thickness (mm)	13.0 (11.0–15.0)	15.0 (12.5–18.0)	0.014
Left ventricular relative wall thickness	0.64 ± 0.23	0.86 ± 0.75	0.037
Systolic function
LV ejection fraction (%)	56 ± 10	51 ± 10	0.085
Global longitudinal strain (%)	12.1 ± 4.9	9.9 ± 2.7	0.153
CMR	AL (n = 38)	ATTR (n = 24)	p-Value
Typical LGE	19 (50)	22 (92)	<0.001
Atypical LGE	4 (11)	0 (0)	0.287
End-diastolic dimension (mm)	47.0 ± 6.0	47.4 ± 3.7	0.784
End-systolic dimension (mm)	30.3 ± 6.4	33.5 ± 4.8	0.040
Septum (mm)	13.6 ± 3.2	18 ± 4.5	<0.001
Right ventricular free wall	10.4 ± 2.8	11.9 ± 3.4	0.061
LV mass (g)	169.7 ± 59.0	225.6 ± 63.1	<0.001
LV mass index (g/m^2)	87.8 ± 28.0	117.2 ± 31.3	<0.001
End-diastolic volume (mL)	144 ± 53	155 ± 30	0.345
End-systolic volume (mL)	55.0 (36.5–70.5)	84.5 (67.0–101.0)	0.001
Stroke-volume (mL)	81.5 ± 29.3	72.4 ± 19.2	0.185
LV ejection fraction (%)	57.9 ± 11.1	46.9 ± 10.1	<0.001

Echocardiographic and cardiac magnetic resonance (CMR) imaging characteristics. All variables are expressed as mean ± standard deviation, median with IQR or n (%). Variables are presented as mean ± SD if it is normally distributed, or as median with IQR if not. LGE: late gadolinium enhancement. Typical LGE for amyloidosis is considered a global subendocardial enhancement with different contrast kinetics. Left atrial dilatation (LAVi > 34 ml/m²), LAVi: left atrial volume index.

Figure 6. Kaplan–Meier curves of atrial fibrillations (upper) and atrial dilatation (lower), with log rank p values.

Table 3. Univariate and multivariate associations with all-cause mortality.

	Univariate		Multivariate
	HR (95% CI)	p	HR (95% CI)	p
Age at diagnosis	1.04 (1.01–1.06)	0.005	0.98 (0.94–1.02)	0.268
Gender	1.18 (0.64–2.17)	0.590
BMI	0.96 (0.89–1.04)	0.345
History of smoking	1.39 (0.78–2.50)	0.268
Hypertension	1.02 (0.57–1.85)	0.937
Diabetes	2.33 (1.06–5.11)	0.036
CAD	1.22 (0.63–2.37)	0.558
Pacemaker	1.56 (0.56–4.41)	0.394
AF	2.40 (1.33–4.34)	0.004	3.17 (1.19–8.45)	0.021
Systolic blood pressure	0.99 (0.97–1.00)	0.051
Diastolic blood pressure	0.98 (0.96–1.00)	0.076
Cardiac involvement	1.44 (0.72–2.84)	0.301
Serum creatinine	1.00 (1.00–1.00)	0.049
Ln NT-ProBNP	1.70 (1.35–2.15)	<0.001	1.38 (0.92–2.06)	0.110
Ln troponin T	1.57 (1.23–2.01)	<0.001	1.06 (0.66–1.71)	0.800
CMR
Typical LGE	1.62 (0.64–4.07)	0.306
Atypical LGE	1.88 (0.55–6.34)	0.312
RV free wall	1.09 (0.96–1.23)	0.208
Myocardial mass	1.00 (1.00–1.01)	0.597
Mass index	1.00 (0.99–1.02)	0.505
Ejection fraction	0.98 (0.95–1.01)	0.183
Echocardiography
Typical echocardiographic features of amyloidosis	1.37 (0.72–2.59)	0.336
Left atrial dilatation (LAVI > 34 ml/m^2)	3.60 (1.66–7.82)	0.001	4.34 (1.45–13.01)	0.009
Pericardial effusion on echo 1 = mild, 2 = moderate, 3= severe	1. 1.70 (0.90–3.18) 2. 6.47 (0.84–49.83) 3. 0.00 (0.00–.)	0.096 0.073 0.981
Pleural effusion on echo	7.49 (3.64–15.42)	<0.001	4.70 (1.78–12.37)	0.002
Global longitudinal strain	0.80 (0.66–0.98)	0.027
LV ejection fraction echo	0.98 (0.95–1.01)	0.125

Univariate and multivariate associations with all-cause mortality. All variables that reached significant values in univariate model was tested as multivariate. BMI: body mass index; CAD: coronary artery disease; AF: atrial fibrillation; NT-pro-BNP: N-terminal brain natriuretic peptide; LGE: late gadolinium enhancement.