Introduction
Methods
Study population
Follow-up
Cell culture
Immunohistological staining
Cell size analysis
Statistical analysis
Results
Study population
ATTRv-CA (n = 36) | ATTRv-PN (n = 23) | ATTRwt (n = 30) | Control (n = 16) | p value | |
---|---|---|---|---|---|
Age (years) | 59.4 ± 1.6 | 57.5 ± 3.2 | 76.3 ± 1.2 | 50.6 ± 3.7 | < 0.001 |
Sex | 0.022 | ||||
Male | 26 (72.2%) | 17 (73.9%) | 26 (86.7%) | 7 (43.8%) | |
Female | 10 (27.8%) | 6 (24.0%) | 4 (13.3%) | 9 (56.3%) | |
BMI | 26.8 ± 5.7 | 25.0 ± 4.1 | 25.5 ± 2.9 | 26.7 ± 6.7 | 0.3 |
Medication | |||||
Tafamidis | 11 (30.6%) | 13 (56.5%) | 0 (0.0%) | 0 (0%) | 0.68§ |
Beta blocker | 10 (27.8%) | 7 (30.4%) | 25 (83.3%) | 3 (18.8%) | < 0.001 |
ACE inhibitors/AT1 antagonists | 13 (36.1%) | 4 (17.4%) | 21 (70.0%) | 3 (18.8%) | < 0.001 |
Diuretics | 16 (44.4%) | 7 (30.4%) | 29 (96.7%) | 2 (12.5%) | < 0.001 |
Other antihypertensive medication (amlodipine, doxazosin, nitrendipine) | 2 (5.6%) | 2 (8.7%) | 6 (20.0%) | 0 (0.0%) | 0.06 |
Functional impairment | |||||
Karnofsky performance index | 0.18 | ||||
≥ 80 | 33 (91.7%) | 16 (69.6%) | 17 (56.7%) | 16 (100%) | |
< 80 | 3 (8.3%) | 4 (17.4%) | 1 (3.3%) | 0 (0%) | |
NYHA class | < 0.001 | ||||
I | 17 (47.2%) | 11 (47.8%) | 1 (3.3%) | 14 (87.5%) | |
II | 11 (30.6%) | 6 (26.1%) | 13 (43.3%) | 2 (12.5%) | |
III | 5 (13.8%) | 0 (0%) | 15 (50%) | 0 (0) | |
IV | 1 (2.8%) | 0 (0%) | 1 (3.3%) | 0 (0) | |
Medical history | |||||
Pacemaker implantation | 4 (11.1%) | 3 (13.0%) | 6 (20.0%) | 0 (0.0%) | 0.12 |
Carpal tunnel syndrome | 18 (50.0%) | 12 (52.2%) | 16 (53.3%) | 0 (0.0%) | 0.54§ |
Diabetes | 3 (8.3%) | 0 (0.0%) | 6 (20.0%) | 0 (0.0%) | 0.01 |
Atrial fibrillation | 8 (22.2%) | 5 (21.7%) | 22 (73.3%) | 2 (12.5%) | < 0.001 |
ECG findings | |||||
Number of bundle branch | 0.7 ± 0.8 | 0.7 ± 0.9 | 1.2 ± 0.7 | 0.3 ± 0.6 | 0.03 |
Sinus rhythm | 30 (83.3%) | 17 (73.9%) | 14 (46.7%) | 15 (93.8%) | 0.03 |
Atrial fibrillation | 5 (13.9%) | 4 (17.4%) | 13 (43.3%) | 1 (6.3%) | 0.003 |
Pace maker rhythm | 1 (2.8%) | 1 (4.3%) | 3 (10.0%) | 0 (0.0%) | 0.28 |
Low voltage pattern | 6 (16.7%) | 3 (13.0%) | 8 (26.7%) | 0 (0.0%) | 0.03 |
Heart frequency (bpm) | 71.3 ± 13.7 | 70.5 ± 25.0 | 77.4 ± 13.4 | 68.4 ± 9.2 | 0.94 |
PQ (ms) | 167.4 ± 38.3 | 166.2 ± 36.6 | 215.1 ± 35.1 | 159.7 ± 27.1 | 0.61 |
QRS (ms) | 107.0 ± 25.4 | 111.1 ± 30.1 | 128.2 ± 36.1 | 96.5 ± 11.0 | 0.69 |
QTc (ms) | 423.4 ± 34.7 | 388.3 ± 117.6 | 446.7 ± 34.1 | 402.6 ± 9.3 | 0.15 |
Echocardiography | |||||
IVS (mm) | 15.5 ± 4.9 | 13.9 ± 6.4 | 19.2 ± 4.7 | 11.4 ± 1.3 | 0.43 |
HW (mm) | 13.3 ± 4.0 | 11.1 ± 4.2 | 15.7 ± 3.4 | 9.6 ± 1.0 | 0.45 |
Ejection fraction(%) | 51.3 ± 10.0 | 53.0 ± 9.8 | 41.2 ± 10.5 | 56.4 ± 8.7 | 0.48 |
Diastolic dysfunction | 23 (63.9%) | 14 (60.9%) | 27 (90.0%) | 2 (12.5%) | |
Strain | 13.5 ± 6.4 | 14.2 ± 3.9 | 7.6 ± 5.8 | 21.0 ± 3.5 | 0.74 |
MAPSE (cm) | 1.2 ± 0.5 | 1.8 ± 2.8 | 0.8 ± 0.2 | 1.3 ± 0.4 | 0.81 |
TAPSE (cm) | 1.9 ± 0.6 | 2.4 ± 2.5 | 1.3 ± 0.5 | 2.0 ± 0.5 | 0.41 |
Pericardial effusion | 3 (8.3%) | 1 (4.3%) | 4 (13.3%) | 0 (0%) | 0.17 |
PA pressure (mmHg) | 30.7 ± 8.4 | 34.1 ± 11.3 | 41.0 ± 10.2 | 27.5 ± 3.5 | 0.57 |
Biomarkers | |||||
NTproBNP (pg/ml) | 1451.3 ± 328.9 | 1427.3 ± 457.4 | 4254.1 ± 561.9 | 117.3 ± 75.6 | 0.11 |
hsTnT (ng/l) | 51.9 ± 19.8 | 20.9 ± 11.0 | 67.1 ± 6.8 | 7.2 ± 2.7 | < 0.001 |
GFR | 78.5 ± 26.7 | 87.0 ± 25.4 | 52.6 ± 15.9 | 91.6 ± 24.3 | < 0.001 |
Follow up | 0.01 | ||||
Median FU (95% CI) | 14.8 (13.90–16.9) | 14.8 (13.67–16.9) | 21.2 (17.12–25.9) | 10.5 (4.79–14.2) |
Hypertrophic growth due to phenylephrine treatment is attenuated in ATTRv-CA- and ATTRwt-plasma treated NRCMs
Feature | HR (95% CI) | p value | n/events | |
---|---|---|---|---|
Combined endpoint | Cell size (dichotom), high vs low | 0.24 (0.11–0.55) | < 0.001 | 105/25 |
NTproBNP, log | 1.15 (0.92–1.45) | 0.23 | 89/20 | |
NTproBNP, GFR adjust, log | 2.02 (1.40–2.91) | < 0.001 | 95/25 | |
TnT, log | 3.01 (1.89–4.78) | < 0.001 | 98/25 | |
GFR | 0.96 (0.94–0.97) | < 0.001 | 102/25 | |
Age | 1.06 (1.02–1.10) | < 0.001 | 105/25 | |
Sex, male vs female | 4.32 (1.02–18.35) | 0.047 | 105/25 | |
Group, ATTRv-PN vs ATTRwt | 0.62 (0.20–1.93) | 0.41 | 105/25 | |
Group, ATTRv-CM vs ATTRwt | 0.87 (0.38–2.02) | 0.75 | ||
MAPSE, log | 0.38 (0.13–1.13) | 0.08 | 93/25 | |
EDD | 0.99 (0.92–1.07) | 0.83 | 94/25 | |
Posterior wall | 1.24 (1.12–1.37) | < 0.001 | 93/25 | |
Intraventricular septum | 1.14 (1.06–1.22) | < 0.001 | 94/25 | |
Left ventricular hypertrophy index | 12.39 (3.18–48.3) | < 0.001 | 93/25 | |
Decompensation only | Cell size (dichotom), high vs low | 0.26 (0.11–0.62) | 0.003 | 105/21 |
NTproBNP, log | 1.17 (0.90–1.52) | 0.24 | 89/16 | |
NTproBNP, GFR adjust, log | 2.17 (1.43–3.28) | < 0.001 | 95/21 | |
TnT, log | 2.85 (1.76–4.61) | < 0.001 | 99/21 | |
GFR | 0.96 (0.94–0.98) | < 0.001 | 102/21 | |
Age | 1.06 (1.02–1.11) | < 0.001 | 105/21 | |
Sex, M vs F | 7.72 (1.04–57.58) | 0.046 | 105/21 | |
Group, ATTRv-PN vs ATTRwt | 0.60 (0.18–1.97) | 0.4 | 105/21 | |
Group, ATTRv-CM vs ATTRwt | 0.61 (0.23–1.63) | 0.33 | ||
MAPSE, log | 0.46 (0.14–1.45) | 0.18 | 93/21 | |
EDD | 0.97 (0.90–1.05) | 0.46 | 94/21 | |
HW | 1.26 (1.14–1.41) | < 0.001 | 93/21 | |
Septum | 1.16 (1.07–1.25) | < 0.001 | 94/21 | |
Left ventricular hypertrophy index | 16.71 (4.2–66.3) | < 0.001 | 93/21 | |
Death/HTX | Cell size (dichotom), high vs low | 0.12 (0.02–0.58) | 0.009 | 105/9 |
NTproBNP, log | 0.85 (0.57–1.27) | 0.43 | 88/6 | |
NTproBNP, GFR adjust, log | 1.66 (0.96–2.88) | 0.07 | 95/9 | |
TnT, log | 3.34 (1.31–8.52) | 0.01 | 98/9 | |
GFR | 0.93 (0.89–0.97) | 0.002 | 102/9 | |
Age | 1.04 (0.98–1.11) | 0.21 | 105/9 | |
Sex, male vs female | 2.41 (0.30–19.31) | 0.1 | 105/9 | |
Group, ATTRv-PN vs ATTRwt | 0.96 (0.17–5.48) | 0.96 | 105/9 | |
Group, ATTRv-CM vs ATTRwt | 0.75 (0.17–3.4) | 0.71 | ||
MAPSE, log | 2.30 (0.62–8.51) | 0.21 | 93/9 | |
End diastolic diameter | 0.99 (0.89–1.11) | 0.93 | 94/9 | |
Posterior wall | 1.10 (0.92–1.32) | 0.31 | 93/9 | |
Intraventricular septum | 1.13 (1.00–1.27) | 0.054 | 94/9 | |
Left ventricular hypertrophy index | 4.86 (0.38–62.5) | 0.23 | 93/9 |
Feature | HR (95% CI) | p value |
---|---|---|
Cell size (dichotom), high vs low | 0.31 (0.12–0.82) | 0.02 |
NTproBNP, GFR adj, log | 0.79 (0.98–3.27) | 0.06 |
TnT, log | 1.55 (0.8–2.99) | 0.19 |
GFR | 0.99 (0.96–1.01) | 0.26 |
Age | 0.96 (0.9–1.02) | 0.17 |
Sex, male vs female | 1.36 (0.25–7.5) | 0.73 |
Posterior wall | 1.04 (0.81–1.33) | 0.77 |
Septum | 0.98 (0.8–1.21) | 0.84 |
LVHI | 0.85 (0.01–80.37) | 0.94 |
NYHA class | ||
II | 0.74 (0.3–1.85) | 0.52 |
III | 0.89 (0.34–2.31) | 0.81 |
IV | 1.56 (0.2–12.35) | 0.67 |