Stabilization of Cardiac Function With Diflunisal in Transthyretin (ATTR) Cardiac Amyloidosis

Graham Lohrmann, Alexandra Pipilas, Roberta Mussinelli, Deepa M. Gopal, John L. Berk, Lawreen H. Connors, Nirupama Vellanki, Jennifer Hellawell, Omar K. Siddiqi, Jonathan Fox, Mathew S. Maurer, Frederick L. Ruberg

Research output: Contribution to journalArticle

Abstract

Background: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an underappreciated cause of heart failure that results from misfolded TTR (prealbumin) protein. Diflunisal is an approved non-steroidal anti-inflammatory drug that stabilizes TTR, with limited data available regarding effects on cardiac structure and function. Methods and Results: ATTR-CM patients (n=81, 41% treated with 250 mg twice-daily diflunisal by clinical practice) were retrospectively identified with baseline and follow-up (median interval 1 year) serum biomarker and echocardiographic data compared, including global longitudinal strain (GLS). Chi-squared and Wilcoxon tests assessed differences between subjects, divided by treatment group, and univariable and multivariable linear regression was performed. At baseline, patients treated with diflunisal were younger (68 vs 77 years, P = .0001), with lower B-type natriuretic peptide (BNP; 249 vs 545 pg/mL, P = .009) and serum creatinine (1.1 vs 1.2 mg/dL, P = .04), but similar TTR concentration (P = .31), cardiac troponin I (P = .06), and GLS (P = .67). At follow-up, diflunisal untreated versus treated patients showed differences in TTR concentration (19 vs 33 mg/dL, P = .01) and favorable differences in left atrial volume index (+4.6 vs −1.4 mL/m2, P = .002) and cardiac troponin I (+0.03 vs −0.01 ng/mL, P = .01) for the entire cohort. Among the subset with wild-type ATTR (n=53), diflunisal treatment was associated with differences in GLS (+1.2% untreated vs +0.1% treated, P = .03). Changes in wall thickness (P = .2), left ventricular ejection fraction (P = .71), and BNP (P = .42) were similar between groups. Conclusions: In ATTR-CM, diflunisal treatment resulted in measurable differences in some parameters of cardiac structure and function after only 1 year of administration. Further longer-term analysis is warranted.

Original languageEnglish
JournalJournal of Cardiac Failure
DOIs
Publication statusAccepted/In press - Jan 1 2020
Externally publishedYes

Fingerprint

Diflunisal
Prealbumin
Amyloidosis
Troponin I
Brain Natriuretic Peptide
Serum
Cardiomyopathies
Stroke Volume
Linear Models
Creatinine
Anti-Inflammatory Agents
Therapeutics
Heart Failure
Biomarkers
Pharmaceutical Preparations

Keywords

  • cardiac amyloidosis
  • diflunisal
  • transthyretin
  • Ventricular strain

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Lohrmann, G., Pipilas, A., Mussinelli, R., Gopal, D. M., Berk, J. L., Connors, L. H., ... Ruberg, F. L. (Accepted/In press). Stabilization of Cardiac Function With Diflunisal in Transthyretin (ATTR) Cardiac Amyloidosis. Journal of Cardiac Failure. https://doi.org/10.1016/j.cardfail.2019.11.024

Stabilization of Cardiac Function With Diflunisal in Transthyretin (ATTR) Cardiac Amyloidosis. / Lohrmann, Graham; Pipilas, Alexandra; Mussinelli, Roberta; Gopal, Deepa M.; Berk, John L.; Connors, Lawreen H.; Vellanki, Nirupama; Hellawell, Jennifer; Siddiqi, Omar K.; Fox, Jonathan; Maurer, Mathew S.; Ruberg, Frederick L.

In: Journal of Cardiac Failure, 01.01.2020.

Research output: Contribution to journalArticle

Lohrmann, G, Pipilas, A, Mussinelli, R, Gopal, DM, Berk, JL, Connors, LH, Vellanki, N, Hellawell, J, Siddiqi, OK, Fox, J, Maurer, MS & Ruberg, FL 2020, 'Stabilization of Cardiac Function With Diflunisal in Transthyretin (ATTR) Cardiac Amyloidosis', Journal of Cardiac Failure. https://doi.org/10.1016/j.cardfail.2019.11.024
Lohrmann, Graham ; Pipilas, Alexandra ; Mussinelli, Roberta ; Gopal, Deepa M. ; Berk, John L. ; Connors, Lawreen H. ; Vellanki, Nirupama ; Hellawell, Jennifer ; Siddiqi, Omar K. ; Fox, Jonathan ; Maurer, Mathew S. ; Ruberg, Frederick L. / Stabilization of Cardiac Function With Diflunisal in Transthyretin (ATTR) Cardiac Amyloidosis. In: Journal of Cardiac Failure. 2020.
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abstract = "Background: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an underappreciated cause of heart failure that results from misfolded TTR (prealbumin) protein. Diflunisal is an approved non-steroidal anti-inflammatory drug that stabilizes TTR, with limited data available regarding effects on cardiac structure and function. Methods and Results: ATTR-CM patients (n=81, 41{\%} treated with 250 mg twice-daily diflunisal by clinical practice) were retrospectively identified with baseline and follow-up (median interval 1 year) serum biomarker and echocardiographic data compared, including global longitudinal strain (GLS). Chi-squared and Wilcoxon tests assessed differences between subjects, divided by treatment group, and univariable and multivariable linear regression was performed. At baseline, patients treated with diflunisal were younger (68 vs 77 years, P = .0001), with lower B-type natriuretic peptide (BNP; 249 vs 545 pg/mL, P = .009) and serum creatinine (1.1 vs 1.2 mg/dL, P = .04), but similar TTR concentration (P = .31), cardiac troponin I (P = .06), and GLS (P = .67). At follow-up, diflunisal untreated versus treated patients showed differences in TTR concentration (19 vs 33 mg/dL, P = .01) and favorable differences in left atrial volume index (+4.6 vs −1.4 mL/m2, P = .002) and cardiac troponin I (+0.03 vs −0.01 ng/mL, P = .01) for the entire cohort. Among the subset with wild-type ATTR (n=53), diflunisal treatment was associated with differences in GLS (+1.2{\%} untreated vs +0.1{\%} treated, P = .03). Changes in wall thickness (P = .2), left ventricular ejection fraction (P = .71), and BNP (P = .42) were similar between groups. Conclusions: In ATTR-CM, diflunisal treatment resulted in measurable differences in some parameters of cardiac structure and function after only 1 year of administration. Further longer-term analysis is warranted.",
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AU - Mussinelli, Roberta

AU - Gopal, Deepa M.

AU - Berk, John L.

AU - Connors, Lawreen H.

AU - Vellanki, Nirupama

AU - Hellawell, Jennifer

AU - Siddiqi, Omar K.

AU - Fox, Jonathan

AU - Maurer, Mathew S.

AU - Ruberg, Frederick L.

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N2 - Background: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an underappreciated cause of heart failure that results from misfolded TTR (prealbumin) protein. Diflunisal is an approved non-steroidal anti-inflammatory drug that stabilizes TTR, with limited data available regarding effects on cardiac structure and function. Methods and Results: ATTR-CM patients (n=81, 41% treated with 250 mg twice-daily diflunisal by clinical practice) were retrospectively identified with baseline and follow-up (median interval 1 year) serum biomarker and echocardiographic data compared, including global longitudinal strain (GLS). Chi-squared and Wilcoxon tests assessed differences between subjects, divided by treatment group, and univariable and multivariable linear regression was performed. At baseline, patients treated with diflunisal were younger (68 vs 77 years, P = .0001), with lower B-type natriuretic peptide (BNP; 249 vs 545 pg/mL, P = .009) and serum creatinine (1.1 vs 1.2 mg/dL, P = .04), but similar TTR concentration (P = .31), cardiac troponin I (P = .06), and GLS (P = .67). At follow-up, diflunisal untreated versus treated patients showed differences in TTR concentration (19 vs 33 mg/dL, P = .01) and favorable differences in left atrial volume index (+4.6 vs −1.4 mL/m2, P = .002) and cardiac troponin I (+0.03 vs −0.01 ng/mL, P = .01) for the entire cohort. Among the subset with wild-type ATTR (n=53), diflunisal treatment was associated with differences in GLS (+1.2% untreated vs +0.1% treated, P = .03). Changes in wall thickness (P = .2), left ventricular ejection fraction (P = .71), and BNP (P = .42) were similar between groups. Conclusions: In ATTR-CM, diflunisal treatment resulted in measurable differences in some parameters of cardiac structure and function after only 1 year of administration. Further longer-term analysis is warranted.

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