Background

Heart Transplantation (HT) is a rational therapy for advanced transthyretin cardiac amyloidosis (ATTR-CA), but the impact of ongoing amyloid deposition is not well defined. We evaluated a cohort of patients who underwent HT for ATTR-CA to determine the incidence of de novo or progression of post-HT ATTR deposition.

Methods

All patients who were followed post-HT for ATTR-CA at our center were included. Baseline demographics and post-HT manifestations of TTR deposition were collected. All patients completed the Composite Autonomic Symptom Score (COMPASS-31 quantifies autonomic symptoms, with a higher score [0-100] indicating more severe autonomic dysfunction) and Polyneuropathy Disability Score (PND, range from 0 [asymptomatic] to IV [confined to wheelchair/bed]) questionnaires.

Results

Twelve patients (5 wild-type, 7 variant [6 p.Val142Ile, 1 p.Thr80Ala]) were included. Mean age at HT was 64.6 (SD: 4.8) years, 83.3% male, and 50% Black. At a median of 4.0 years (IQR 2.4, 5.9) post-HT, 8 patients had symptoms of ATTR deposition (5 with gastrointestinal involvement, 4 orthopedic and 4 neurologic), with 4 patients having ≥2 body systems involved. There were no patients with recurrent cardiac involvement. Median COMPASS-31 score was 17.3 (IQR 11.3, 23.5) at 3.9 years (IQR 2.4, 5.9) post-HT. Four patients had a PND score of stage 1 (sensory disturbance), 1 patient was stage 2 (impaired walking) and 1 patient stage 3b (required a walking aid).

Conclusions

More than 50% of patients had evidence of progressive or de novo ATTR deposition post-HT, impairing quality of life despite a well-functioning cardiac allograft. These observations highlight an unmet need to establish the role of formal surveillance and treatment of TTR using TTR disease-modifying therapies, which may maintain or improve quality of life post-HT for ATTR-CA.

中文翻译：

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新型疾病修饰疗法时代心脏移植后转甲状腺素蛋白淀粉样变疾病进展的监测

背景

心脏移植(HT) 是晚期转甲状腺素蛋白心脏淀粉样变性 (ATTR-CA)的合理疗法，但持续性淀粉样蛋白沉积的影响尚不明确。我们评估了一组接受 HT 治疗 ATTR-CA 的患者，以确定从头发生或 HT 后 ATTR 沉积进展的发生率。

方法

所有在我们中心接受 ATTR-CA HT 后随访的患者都包括在内。收集了 TTR 沉积的基线人口统计数据和 HT 后表现。所有患者均完成了综合自主神经症状评分（COMPASS-31 量化自主神经症状，评分越高 [0-100] 表明自主神经功能障碍更严重）和多发性神经病残疾评分（PND，范围从 0 [无症状] 到 IV [仅限轮椅） /bed]) 问卷。

结果

包括 12 名患者（5 名野生型，7 名变异 [6 p.Val142Ile，1 p.Thr80Ala]）。HT 的平均年龄为 64.6 (SD: 4.8) 岁，83.3% 为男性，50% 为黑人。在 HT 后 4.0 年（IQR 2.4, 5.9）的中位时间，8 名患者出现 ATTR 沉积症状（5 名胃肠道受累，4 名骨科和 4 名神经系统受累），其中 4 名患者有 ≥2 个身体系统受累。没有复发性心脏受累的患者。在 HT 后 3.9 年（IQR 2.4, 5.9）时，COMPASS-31 得分中位数为 17.3（IQR 11.3, 23.5）。4 名患者的 PND 评分为 1 期（感觉障碍），1 名患者为 2 期（行走障碍）和 1 名患者为 3b 期（需要助行器）。

结论

超过 50% 的患者在 HT 后有进行性或新发 ATTR 沉积的证据，尽管心脏同种异体移植物功能良好，但仍会损害生活质量。这些观察结果强调了一个未满足的需求，即使用 TTR 疾病修饰疗法确定正式监测和治疗 TTR 的作用，这可能维持或改善 ATTR-CA HT 后的生活质量。