Effect of Timely Availability of TTR-Stabilizing Therapy on Diagnosis, Therapy, and Clinical Outcomes in ATTR-CM

Dobner, Stephan; Zarro, Sara; Wieser, Fabian; Kassar, Mohammad; Alaour, Bashir; Wiedemann, Sebastian; Bakula, Adam; Caobelli, Federico; Stortecky, Stefan; Gräni, Christoph; Hunziker, Lukas; Bernhard, Benedikt

doi:10.3390/jcm13175291

Open AccessArticle

Effect of Timely Availability of TTR-Stabilizing Therapy on Diagnosis, Therapy, and Clinical Outcomes in ATTR-CM

by

Stephan Dobner

^1,2,*

,

Sara Zarro

^1,†,

Fabian Wieser

^1,†,

Mohammad Kassar

¹

,

Bashir Alaour

^1,3,

Sebastian Wiedemann

¹,

Adam Bakula

¹

,

Federico Caobelli

⁴,

Stefan Stortecky

¹,

Christoph Gräni

¹

,

Lukas Hunziker

¹ and

Benedikt Bernhard

¹

Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland

²

3rd Medical Department of Cardiology and Intensive Care Medicine, Clinic Ottakring (Former Wilhelminenhospital), 1160 Vienna, Austria

³

British Heart Foundation Centre for Research Excellence, King’s College London, London SE1 9NH, UK

⁴

Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

J. Clin. Med. 2024, 13(17), 5291; https://doi.org/10.3390/jcm13175291

Submission received: 15 August 2024 / Revised: 27 August 2024 / Accepted: 4 September 2024 / Published: 6 September 2024

(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Amyloidosis)

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Abstract

Background: Tafamidis reduces cardiovascular morbidity and mortality in transthyretin amyloid cardiomyopathy (ATTR-CM), yet availability and access to therapy vary. Objective: To determine how availability and access to tafamidis impact time-to-diagnosis, time-to-therapy, and cardiovascular outcomes in ATTR-CM. Methods: Ninety-one consecutive ATTR-CM (~97% wt-TTR) patients diagnosed between June 2019 and June 2021 were evaluated for tafamidis. Access to therapy was regulated by compassionate use [n(CU) = 42] prior to, and insurance [n(IA) = 49] after regulatory approval. Results: Tafamidis was started in 37/42 (88.1%), and 39/49 (79.6%) patients, respectively. At diagnosis, ATTR-CM disease stage (≤stage 2: 88.2% vs. 90.9%, p = 0.92) was similar between groups. Timely access (after tafamidis approval) reduced the median time from first presentation to diagnosis from 6.2 (IQR: 1.3–28.9) to 2.4 (0.7–21.7) months, and from first presentation to therapy from 24.4 (10.7–46.8) to 11.8 (6.4–32.4) months. While RV function significantly worsened between diagnosis and therapy initiation in CU patients diagnosed before tafamidis approval (S’-velocity 10.0 ± 2.2 to 9.2 ± 2.2 cm/s; p = 0.018; TAPSE 17.3 ± 4.7 to 15.7 ± 3.9 mm, p = 0.008), it remained unchanged in IA patients (S’-velocity 9.6 ± 2.6 to 9.4 ± 2.3 cm/s; p = 0.83; TAPSE 15.6 ± 4.2 to 16.3 ± 3.1 mm, p = 0.45). After a median follow-up of 42.3 and 24.9 months in CU and IA patients, respectively, timely availability was associated with a reduction in annual heart failure hospitalizations (0.40 vs. 0.16 per patient, p < 0.001) and improved MACE-free survival (HR = 0.51; 95%CI: 0.26–1.00; p = 0.051). Timely diagnosis (<12-months) prolonged MACE-free survival (HR = 0.424; 95%CI: 0.22–0.81; p = 0.004), and reduced HFH (HR = 0.40; 95%CI: 0.19–0.81); p = 0.011) and all-cause mortality (HR = 0.29; 95%CI: 0.11–0.74); p = 0.009). Conclusions: Availability of tafamidis improves diagnostic efficacy in ATTR-CM patients. Timely diagnosis and initiation of therapy reduces adverse cardiovascular events.

Keywords: cardiac amyloidosis; transthyretin; tafamidis

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MDPI and ACS Style

Dobner, S.; Zarro, S.; Wieser, F.; Kassar, M.; Alaour, B.; Wiedemann, S.; Bakula, A.; Caobelli, F.; Stortecky, S.; Gräni, C.; et al. Effect of Timely Availability of TTR-Stabilizing Therapy on Diagnosis, Therapy, and Clinical Outcomes in ATTR-CM. J. Clin. Med. 2024, 13, 5291. https://doi.org/10.3390/jcm13175291

AMA Style

Dobner S, Zarro S, Wieser F, Kassar M, Alaour B, Wiedemann S, Bakula A, Caobelli F, Stortecky S, Gräni C, et al. Effect of Timely Availability of TTR-Stabilizing Therapy on Diagnosis, Therapy, and Clinical Outcomes in ATTR-CM. Journal of Clinical Medicine. 2024; 13(17):5291. https://doi.org/10.3390/jcm13175291

Chicago/Turabian Style

Dobner, Stephan, Sara Zarro, Fabian Wieser, Mohammad Kassar, Bashir Alaour, Sebastian Wiedemann, Adam Bakula, Federico Caobelli, Stefan Stortecky, Christoph Gräni, and et al. 2024. "Effect of Timely Availability of TTR-Stabilizing Therapy on Diagnosis, Therapy, and Clinical Outcomes in ATTR-CM" Journal of Clinical Medicine 13, no. 17: 5291. https://doi.org/10.3390/jcm13175291

APA Style

Dobner, S., Zarro, S., Wieser, F., Kassar, M., Alaour, B., Wiedemann, S., Bakula, A., Caobelli, F., Stortecky, S., Gräni, C., Hunziker, L., & Bernhard, B. (2024). Effect of Timely Availability of TTR-Stabilizing Therapy on Diagnosis, Therapy, and Clinical Outcomes in ATTR-CM. Journal of Clinical Medicine, 13(17), 5291. https://doi.org/10.3390/jcm13175291

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Effect of Timely Availability of TTR-Stabilizing Therapy on Diagnosis, Therapy, and Clinical Outcomes in ATTR-CM

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