Effect of Diflunisal in Patients with Transthyretin Cardiomyopathy: A Pilot Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Trial Oversight
2.2. Patients
2.3. Trial Design
Basal and 12-Month Protocol Studies
2.4. Statistical Analysis
3. Results
3.1. Baseline Characteristics
3.2. Diflunisal Tolerance
3.3. Changes in Biomarkers
3.4. Changes in Transthoracic Echocardiogram Parameters
3.5. Changes in Cardiac Magnetic Resonance Parameters
3.6. Functional Assessment
4. Discussion
Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
Appendix A.1. Biomarker Determination
Appendix A.2. Image Acquisition Transthoracic Echocardiography
Appendix A.3. Cardiac Magnetic Resonance Protocol and Image Analysis
Appendix A.4. CMR Analysis
Appendix A.5. Functional Assessment. Six-Minute Walk Test (6MWT)
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VARIABLE | Patients Treated with Diflunisal n = 16 |
---|---|
Age (years, IQR) | 82.2 (78.5–87.0) |
Male/Female | 13/3 |
ATTRm/ATTRwt | 2/14 |
Comorbidities | |
Smoker (%) | 37.5 |
Hypertension (%) | 75.0 |
Diabetes mellitus (%) | 12.5 |
Dyslipidemia (%) | 75.0 |
Obesity (%) | 18.8 |
Coronary artery disease (%) | 11.1 |
Cerebrovascular disease (%) | 6.3 |
Previous heart failure (%) | 37.5 |
Atrial fibrillation (%) | 50 |
Chronic kidney disease (%) | 50.0 |
Carpal tunnel syndrome (%) | 18.8 |
Lumbar canal stenosis (%) | 18.8 |
Polyneuropathy (%) | 12.5 |
Previous Medical Treatment | |
Antiagregants (%) | 6.3 |
Anticoagulants (%) | 43.8 |
SLT2i (%) | 31.3 |
ACEi (%) | 18.8 |
ARB (%) | 18.8 |
MRA (%) | 31.3 |
Beta-blockers (%) | 31.3 |
Antiarrhythmic drugs (%) | 12.5 |
Digoxin (%) | 0 |
VARIABLE | Visit 0 | Visit 1 | p |
---|---|---|---|
Laboratory and Biomarker Determinations | |||
Hb (g/dL± SD) (n = 16) | 14.3 ± 1.7 | 14.0 ± 1.8 | 0.263 |
eGFR (mL/min/1.73 m2, ± SD) (n = 16) | 60.6 ± 14.6 | 52.5 ± 14.7 | 0.036 |
NT-proBNP (pg/mL, IQR) (n = 16) | 1815.0 (1132.5–3642.5) | 2020.0 (836.25–3997.5) | 0.272 |
HsTnI (pg/mL, ± SD) (n = 9) | 154.6 ± 114.9 | 153.1 ± 137.8 | 0.971 |
IL-6 (pg/mL, IQR) (n = 9) | 2.7 (2.4–36.2) | 3.0 (1.3–6.3) | 0.08 |
TIM-1 (pg/mL, ± SD) (n = 9) | 199.6 ± 104.2 | 232.8 ± 131.6 | 0.359 |
Gal3 (pg/mL, ± SD) (n = 9) | 7544.7 ± 2307.5 | 8945.4 ± 3926.3 | 0.303 |
hsCPR (mg/L, ± SD) (n = 9) | 2.4 ± 2.8 | 2.3 ± 1.7 | 0.952 |
CK-MB (ng/mL, ± SD) (n = 9) | 1.7 ± 0.7 | 2.6 ± 1.3 | 0.165 |
NT-ProANP (ng/mL, ± SD) (n = 9) | 65.2 ± 12.6 | 64.5 ± 12.2 | 0.790 |
PTH (pg/mL, ± SD) (n = 9) | 78.9 ± 32.0 | 90.0 ± 43.0 | 0.418 |
Klotho (pg/mL, ± SD) (n = 9) | 535.4 ± 124.6 | 564.5 ± 169.4 | 0.669 |
FGF-23 (RU/mL, IQR) (n = 9) | 257 (126.5–328.5) | 149 (131–207) | 0.499 |
VitD (ng/mL, ± SD) (n = 9) | 33.1 ± 13.2 | 34.7 ± 9.6 | 0.776 |
RBP4 (µg/mL, ± SD) (n = 9) | 28.0 ± 10.5 | 33.6 ± 13.0 | 0.020 |
TIMP-1 (ng/mL, ± SD) (n = 9) | 183.5 ± 31.3 | 201.8 ± 33.1 | 0.069 |
TIMP-2 (ng/mL, ± SD) (n = 9) | 116.9 ± 12.6 | 124.0 ± 22.9 | 0.371 |
MMP-2 (ng/mL, ± SD) (n = 9) | 330.2 ± 47.0 | 339.1 ± 54.9 | 0.619 |
MMP-9 (ng/mL, IQR) (n = 9) | 365 (228–571) | 497.5 (227.8–966.0) | 0.515 |
Prealbumin (mg/dL, IQR) (n = 9) | 26.5 (19.6–28.7) | 32.3 (27.3–33.6) | 0.008 |
VARIABLE | Visit 0 | Visit 1 | p |
---|---|---|---|
Transthoracic Echocardiogram | |||
TAPSE (mm, IQR) (n = 16) | 16.5 (15.3–21.0) | 18.0 (13.5–27.5) | 0.285 |
LVEF Simpson biplane (%, ± SD) (n = 16) | 49.8 ± 11.0 | 51.9 ± 9.6 | 0.303 |
E/E’ (n = 16) | 16.2 ± 4.6 | 16.3 ± 4.7 | 0.947 |
Vein cava diameters (mm) (n = 16) | 16.0 (15.0–18.0) | 15.5 (14.3–17.0) | 0.752 |
GLS LV (%, ± SD) (n = 9) | −11.2 ± 3.9 | −10.6 ± 5.3 | 0.728 |
GLS RV (%, ± SD) (n = 9) | −10.3 ± 4.5 | −9.7 ± 3.5 | 0.523 |
GLS LA (%, ± SD) (n = 9) | 9.1 ± 5.6 | 6.4 ± 6.8 | 0.181 |
Cardiac Magnetic Resonance | |||
LVEF (%, ± SD) (n = 9) | 56 ± 7.2 | 59 ± 8.3 | 0.376 |
LVMi (g/m2, ± SD) (n = 9) | 53.2 ± 32.3 | 71.3 ± 36.0 | 0.139 |
Native T1 (ms, ± SD) (n = 9) | 1424.9 ± 51.9 | 1446.9 ± 54.8 | 0.004 |
Post-contrast T1 (ms, ± SD) (n = 9) | 524.8 ± 68.1 | 499.7 ± 52.9 | 0.130 |
ECV (%, ± SD) (n = 9) | 40.7 ± 8.3 | 42.7 ± 9.4 | 0.415 |
T2 (ms, IQR) (n = 9) | 55.3 (52.7–58.7) | 58.8 (54.6–60.2) | 0.401 |
6-min Walk Test (6MWT) | |||
Distance (m, ± SD) (n = 9) | 238.5 ± 66.7 | 223.8 ± 64.1 | 0.626 |
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Camblor Blasco, A.; Devesa, A.; Nieto Roca, L.; Gómez-Talavera, S.; Lumpuy-Castillo, J.; Pello Lázaro, A.M.; Llanos Jiménez, L.; Sánchez González, J.; Lorenzo, Ó.; Tuñón, J.; et al. Effect of Diflunisal in Patients with Transthyretin Cardiomyopathy: A Pilot Study. J. Clin. Med. 2024, 13, 5032. https://doi.org/10.3390/jcm13175032
Camblor Blasco A, Devesa A, Nieto Roca L, Gómez-Talavera S, Lumpuy-Castillo J, Pello Lázaro AM, Llanos Jiménez L, Sánchez González J, Lorenzo Ó, Tuñón J, et al. Effect of Diflunisal in Patients with Transthyretin Cardiomyopathy: A Pilot Study. Journal of Clinical Medicine. 2024; 13(17):5032. https://doi.org/10.3390/jcm13175032
Chicago/Turabian StyleCamblor Blasco, Andrea, Ana Devesa, Luis Nieto Roca, Sandra Gómez-Talavera, Jairo Lumpuy-Castillo, Ana María Pello Lázaro, Lucía Llanos Jiménez, Javier Sánchez González, Óscar Lorenzo, Jose Tuñón, and et al. 2024. "Effect of Diflunisal in Patients with Transthyretin Cardiomyopathy: A Pilot Study" Journal of Clinical Medicine 13, no. 17: 5032. https://doi.org/10.3390/jcm13175032