Trends in Conventional Heart Failure Therapy in a Real-World Multinational ATTR-CA Cohort
Abstract
1. Introduction
2. Materials and Methods
3. Results
3.1. Prescription Patterns
3.1.1. Beta-Blockers
3.1.2. Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers
3.2. Trends in Prescription Patterns
3.2.1. Beta-Blocker and ACEi/ARB Prescription
3.2.2. Combination Heart Failure Therapy
3.3. Heart Failure Medication and Survival
4. Discussion
Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Overall Population (n = 794) | LVEF < 50% (n = 249, 38.5%) | LVEF ≥ 50% (n = 397, 61.5%) | p-Value | |
---|---|---|---|---|
Sex (male) | 581 (73.2%) | 200 (80.3%) | 290 (73.0%) | 0.036 |
Age | 78 (66–83) | 80 (73–84) | 78 (64–83) | 0.001 |
AF/flutter in history | 329 (46.7%) | 142 (62.8%) | 137 (40.5%) | <0.001 |
CAD | 178 (22.4%) | 68 (27.3%) | 87 (22.0%) | 0.122 |
DM | 121 (15.3%) | 49 (19.8%) | 52 (13.2%) | 0.025 |
Hypertension | 417 (52.8%) | 128 (51.8%) | 224 (56.7%) | 0.206 |
Stroke/TIA | 87 (13.4%) | 35 (17.7%) | 41 (13.1%) | 0.157 |
NYHA class | <0.001 | |||
I | 217 (30.6%) | 36 (14.9%) | 120 (33.6%) | |
II | 336 (47.4%) | 132 (54.8%) | 174 (48.7%) | |
III | 138 (19.5%) | 66 (27.4%) | 53 (14.8%) | |
IV | 18 (2.5) | 7 (2.9%) | 10 (2.8%) | |
NAC stage | <0.001 | |||
I | 319 (59.6%) | 55 (34.8%) | 189 (65.9%) | |
II | 124 (23.2%) | 54 (34.2%) | 60 (20.9%) | |
III | 92 (17.2%) | 49 (31.0%) | 38 (13.2%) | |
NT-proBNP (ng/L) | 1508 (347–4009) | 1782 (3650–6918) | 1212 (312–3265) | <0.001 |
HS Troponin (ng/L) | 48 (28–82) | 57 (41–100) | 40 (21–68) | <0.001 |
eGFR (mL/min/1.73 m2) | 65.0 ± 25.1 | 55.6 ± 20.8 | 67.9 ± 24.0 | <0.001 |
CKD stage 3–5 | 319 (43.3%) | 135 (57.7%) | 147 (38.5%) | <0.001 |
Systolic blood pressure (mmHg) | 127.5 ± 21.4 | 124.6 ± 21.8 | 129.2 ± 21.0 | 0.012 |
Diastolic blood pressure (mmHg) | 73.8 ± 13.2 | 74.0 ± 14.3 | 73.5 ± 12.6 | 0.640 |
Electrocardiography | ||||
Rhythm at baseline | 0.003 | |||
Sinus rhythm | 470 (59.9%) | 124 (50.2%) | 253 (64.9%) | |
AF/flutter | 248 (31.6%) | 100 (40.5%) | 114 (29.2%) | |
Paced rhythm | 62 (7.9%) | 22 (8.9%) | 21 (5.4%) | |
Heart rate (bpm) | 74.7 ± 15.9 | 76.1 ± 18.3 | 73.1 ± 13.9 | 0.028 |
Conduction abnormalities | <0.001 | |||
LBBB | 125 (18.0%) | 56 (26.0%) | 59 (16.6%) | |
RBBB | 94 (13.5%) | 32 (14.9%) | 49 (13.8%) | |
Aspecific IV conduction delay | 46 (6.6%) | 25 (11.6%) | 16 (13.8%) | |
Low voltages | 156 (21.2%) | 63 (28.3%) | 70 (18.8%) | 0.007 |
Signs of LVH | 68 (9.3%) | 31 (14.1%) | 24 (6.5%) | 0.002 |
Echocardiography | ||||
LVEF (%) | 52.1 ± 12.2 | 39.5 ± 7.9 | 60.0 ± 6.5 | <0.001 |
IVSd (mm) | 15.6 ± 4.3 | 17.1 ± 3.6 | 15.4 ± 4.2 | <0.001 |
PWT (mm) | 14.1 ± 4.0 | 15.3 ± 3.5 | 14.1 ± 4.0 | <0.001 |
LAVI (mL/m2) | 49.3 ± 24.3 | 55.9 ± 29.1 | 46.6 ± 20.0 | <0.001 |
Indexed stroke volume (mL/m2) | 31.6 ± 11.0 | 26.8 ± 8.8 | 34.9 ± 11.2 | <0.001 |
LV GLS (%) | −13.3 ± 4.7 | −9.7 ± 2.9 | −14.6 ± 4.2 | <0.001 |
RELAS | 2.0 ± 0.9 | 2.0 ± 1.0 | 2.1 ± 0.8 | 0.898 |
TAPSE | 18.2 ± 5.2 | 15.6 ± 4.3 | 19.6 ± 10.9 | <0.001 |
RA area (cm2) | 20.8 ± 6.6 | 23.0 ± 6.6 | 19.7 ± 6.2 | <0.001 |
E/e’ | 17.5 ± 10.2 | 19.8 ± 10.9 | 16.5 ± 9.6 | <0.001 |
Medication | ||||
Beta-blocker | 346 (43.7%) | 139 (56.0%) | 161 (40.8%) | <0.001 |
ACEi/ARB | 326 (41.2%) | 109 (44.0%) | 157 (39.7%) | 0.292 |
Diuretics | 418 (52.8%) | 180 (72.9%) | 175 (44.2%) | <0.001 |
MRA | 204 (25.8%) | 88 (35.5%) | 87 (22.0%) | <0.001 |
Disease-modifying treatment | 315 (44.9%) | 95 (43.4%) | 169 (47.6%) | 0.324 |
Patients Treated with Beta-Blockers (n = 346, 43.7%) | Patients Not Treated with Beta-Blockers (n = 445, 56.3%) | p-Value | Patients Treated with ACEi/ARBs (n = 326, 41.2%) | Patients Not Treated with ACEi/ARBs (n = 465, 58.8%) | p-Value | |
---|---|---|---|---|---|---|
Sex (male) | 262 (75.5%) | 316 (71.0%) | 0.138 | 254 (77.9%) | 324 (69.7%) | 0.010 |
Age | 81 (76–86) | 80 (72–84) | <0.001 | 81 (77–84) | 80 (72–85) | <0.001 |
AF/flutter | 179 (60.3%) | 149 (36.8%) | <0.001 | 157 (54.0%) | 171 (41.6%) | 0.001 |
CAD | 98 (28.3%) | 80 (18.0%) | <0.001 | 90 (27.6%) | 88 (18.9%) | 0.004 |
DM | 66 (19.2%) | 55 (12.4%) | <0.001 | 58 (17.8%) | 63 (13.6%) | 0.104 |
Hypertension | 212 (61.4%) | 203 (45.8%) | <0.001 | 233 (71.7%) | 182 (39.3%) | <0.001 |
Stroke/TIA | 47 (17.7%) | 40 (10.4%) | 0.008 | 43 (16.6%) | 44 (11.3%) | 0.051 |
NYHA class | <0.001 | 0.108 | ||||
I | 69 (21.4%) | 148 (38.5%) | 81 (26.7%) | 136 (33.7%) | ||
II | 170 (52.8%) | 163 (42.4%) | 147 (48.5%) | 186 (46.2%) | ||
III | 73 (22.7%) | 65 (16.9%) | 64 (21.1%) | 74 (18.4%) | ||
IV | 10 (3.1%) | 8 (2.1%) | 11 (3.1%) | 7 (1.7%) | ||
NAC stage | <0.001 | 0.048 | ||||
I | 109 (48.0%) | 207 (67.9) | 116 (53.5%) | 200 (63.5%) | ||
II | 54 (23.8%) | 70 (23.0%) | 61 (28.1%) | 63 (20.0%) | ||
III | 64 (28.2%) | 28 (9.2%) | 40 (18.4%) | 52 (16.5%) | ||
NT-proBNP (ng/L) | 3195 (1207–6932) | 1882 (768–3892) | <0.001 | 2796 (1074–5917) | 2285 (901–5106) | <0.001 |
HS Troponin (ng/L) | 49 (31–92) | 42 (22–67) | <0.001 | 49 (34–88) | 46 (24–82) | 0.062 |
eGFR (mL/min/1.73 m2) | 57.8 ± 22.6 | 71.5 ± 25.3 | <0.001 | 60.8 ± 22.1 | 68.6 ± 26.6 | <0.001 |
CKD stage 3–5 | 182 (55.8%) | 235 (33.1%) | <0.001 | 153 (50.7%) | 164 (38.0%) | <0.001 |
Systolic blood pressure (mmHg) | 128.9 ± 23.1 | 126.3 ± 19.9 | 0.139 | 129.2 ± 21.7 | 126.3 ± 21.2 | 0.095 |
Diastolic blood pressure (mmHg) | 73.9 ± 14.1 | 73.8 ± 16.9 | 0.819 | 74.3 ± 12.3 | 73.4 ± 13.8 | 0.399 |
Electrocardiographic parameters | ||||||
Rhythm at baseline | 0.097 | 0.116 | ||||
Sinus rhythm | 189 (55.6%) | 278 (63.0%) | 183 (56.7%) | 284 (62.0%) | ||
AF/flutter | 124 (36.5%) | 124 (28.1%) | 114 (35.3%) | 134 (29.3%) | ||
Paced rhythm | 25 (7.4%) | 37 (8.4%) | 26 (8.0%) | 36 (7.9%) | ||
Heart rate (bpm) | 73.8 ± 16.9 | 75.4 ± 15.0 | 0.152 | 73.5 ± 15.3 | 75.6 ± 16.2 | 0.077 |
Conduction abnormalities | 0.012 | 0.565 | ||||
LBBB | 55 (18.4%) | 69 (17.5%) | 52 (18.7%) | 72 (17.3%) | ||
RBBB | 53 (17.7%) | 41 (10.4%) | 42 (15.1%) | 52 (12.5%) | ||
Aspecific IV conduction delay | 23 (7.7%) | 22 (5.6%) | 20 (7.2%) | 25 (6.0%) | ||
Low voltages | 75 (23.1%) | 81 (19.9%) | 0.280 | 65 (21.6%) | 91 (21.1%) | 0.876 |
Signs of LVH | 28 (8.7%) | 40 (9.9%) | 0.585 | 31 (10.3%) | 37 (8.6%) | 0.435 |
Echocardiographic parameters | ||||||
LVEF (%) | 50.0 ± 11.8 | 53.8 ± 12.2 | <0.001 | 51.2 ± 11.8 | 52.2 ± 12.4 | 0.164 |
IVSd (mm) | 16.5 ± 3.8 | 15.0 ± 4.6 | <0.001 | 16.4 ± 3.8 | 15.1 ± 4.5 | <0.001 |
PWT (mm) | 14.8 ± 4.0 | 13.6 ± 3.9 | <0.001 | 14.6 ± 4.1 | 13.8 ±3.9 | 0.008 |
LAVI (mL/m2) | 53.3 ± 27.9 | 46.2 ± 20.6 | 0.001 | 52.5 ± 28.3 | 46.9 ± 20.6 | 0.011 |
Indexed stroke volume (mL/m2) | 30.7 ± 11.4 | 32.3 ± 10.4 | 0.123 | 31.9 ± 11.4 | 31.2 ± 10.5 | 0.541 |
LV GLS (%) | −12.2 ± 4.5 | −14.0 ± 4.7 | <0.001 | −12.4 ± 4.2 | −13.8 ± 4.9 | <0.001 |
RELAS | 2.03 ± 0.97 | 2.02 ± 0.79 | 0.900 | 2.09 ± 0.94 | 1.98 ± 0.82 | 0.191 |
TAPSE | 17.5 ± 5.0 | 18.8 ± 5.3 | 0.003 | 18.1 ± 5.1 | 18.3 ± 5.3 | 0.554 |
RA area (cm2) | 21.7 ± 7.1 | 20.1 ± 6.1 | 0.008 | 21.7 ± 6.4 | 20.1 ± 6.6 | 0.010 |
E/e’ | 18.6 ± 5.3 | 16.6 ± 9.0 | 0.022 | 17.9 ± 10.2 | 17.2 ± 10.3 | 0.448 |
Medication | ||||||
Diuretics | 234 (68.0%) | 183 (41.1%) | <0.001 | 218 (67.3%) | 199 (42.8%) | <0.001 |
MRA | 108 (31.2%) | 96 (21.6%) | 0.002 | 102 (31.3%) | 102 (21.9%) | 0.003 |
Disease-modifying treatment | 115 (38.3%) | 199 (49.9%) | 0.002 | 117 (41.6%) | 197 (47.1%) | 0.152 |
Overall Population (n = 791) | Before 2016 (n = 136) | 2016–2021 (n = 493) | After 2021 (n = 107) | p-Value | |
---|---|---|---|---|---|
BB and ACE | 115 (14.5%) | 11 (8.1%) | 84 (17.0%) | 19 (17.8%) | 0.030 |
BB and MRA | 40 (5.1%) | 5 (3.7%) | 28 (5.7%) | 7 (6.5%) | 0.568 |
ACEi/ARB and MRA | 34 (4.3%) | 5 (3.7%) | 19 (3.9%) | 10 (9.3%) | 0.042 |
BB, ACEi/ARB, and MRA | 68 (8.6%) | 11 (8.1%) | 45 (9.1%) | 12 (11.2%) | 0.698 |
No use of BB, ACEi/ARB, or MRA | 240 (30.3%) | 61 (44.9%) | 117 (23.7%) | 20 (18.7%) | <0.001 |
Beta-Blocker | ACEi/ARB | |||
---|---|---|---|---|
HR (95% CI) | p-Value | HR (95% CI) | p-Value | |
Age at diagnosis | 1.073 (1.028–1.120) | <0.001 | 1.074 (1.028–1.121) | 0.001 |
AF | 1.977 (0.884–4.419) | 0.097 | 1.887 (0.851–4.184) | 0.118 |
CAD | 1.131 (0.592–2.163) | 0.709 | 1.102 (0.580–2.096) | 0.767 |
DM | 0.528 (0.203–1.374) | 0.191 | 0.526 (0.201–1.375) | 0.190 |
Wild-type | 0.678 (0.678–0.193) | 0.544 | 0.669 (0.193–2.321) | 0.669 |
NAC stage | ||||
I vs. II | 1.009 (0.395–2.580) | 0.985 | 1.115 (0.447–2.782) | 0.816 |
I vs. III | 4.702 (2.022–910.937) | <0.001 | 4.302 (1.873–9.882) | <0.001 |
LV GLS | 00.928 (0.851–1.013) | 0.095 | 0.933 (0.857–1.016) | 0.111 |
Beta-blocker | 0.666 (0.352–1.262) | 0.213 | - | - |
ACEi/ARB | - | - | 0.878 (0.490–1.575) | 0.663 |
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van der Geest, E.H.; Ajmone Marsan, N.; Laenens, D.; Debonnaire, P.J.M.R.; Claeys, M.; Pinto, F.; Brito, D.; Donal, E.; Droogmans, S.; Van de Veire, N.; et al. Trends in Conventional Heart Failure Therapy in a Real-World Multinational ATTR-CA Cohort. J. Cardiovasc. Dev. Dis. 2025, 12, 403. https://doi.org/10.3390/jcdd12100403
van der Geest EH, Ajmone Marsan N, Laenens D, Debonnaire PJMR, Claeys M, Pinto F, Brito D, Donal E, Droogmans S, Van de Veire N, et al. Trends in Conventional Heart Failure Therapy in a Real-World Multinational ATTR-CA Cohort. Journal of Cardiovascular Development and Disease. 2025; 12(10):403. https://doi.org/10.3390/jcdd12100403
Chicago/Turabian Stylevan der Geest, Eva H., Nina Ajmone Marsan, Dorien Laenens, Philippe J. M. R. Debonnaire, Mathias Claeys, Fauto Pinto, Dulce Brito, Erwan Donal, Steven Droogmans, Nico Van de Veire, and et al. 2025. "Trends in Conventional Heart Failure Therapy in a Real-World Multinational ATTR-CA Cohort" Journal of Cardiovascular Development and Disease 12, no. 10: 403. https://doi.org/10.3390/jcdd12100403
APA Stylevan der Geest, E. H., Ajmone Marsan, N., Laenens, D., Debonnaire, P. J. M. R., Claeys, M., Pinto, F., Brito, D., Donal, E., Droogmans, S., Van de Veire, N., Bertrand, P., Nabeta, T., Graziani, F., & Regeer, M. V. (2025). Trends in Conventional Heart Failure Therapy in a Real-World Multinational ATTR-CA Cohort. Journal of Cardiovascular Development and Disease, 12(10), 403. https://doi.org/10.3390/jcdd12100403