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Q1. Which statements about amyloidosis are true?

  • (A) The level of NT-proBNP and troponin can determine the prognosis of amyloidosis.
  • (B) Amyloidosis with heart involvement might cause cardiac hypertrophy and loss of systolic function.
  • (C) The addition of daratumumab to bortezomib/cyclophosphamide/dexamethasone has consistent benefit in patients whether harboring t(11;14) or not.
  • (D) Combine daratumumab to bortezomib/cyclophosphamide/dexamethasone improve hematologic response but not organ response.
點此顯示正解

(A) The level of NT-proBNP and troponin can determine the prognosis of amyloidosis.

詳解

Analysis

The stem asks for true statements about amyloidosis. Option (A) is marked as the correct answer.

1. Why (A) is TRUE

NT-proBNP and troponin levels are well-established prognostic biomarkers in amyloidosis. Multiple validated staging systems use these cardiac biomarkers to stratify patients and predict survival outcomes123.

The Mayo Clinic 2004 staging system classifies AL amyloidosis patients into three stages based on cardiac troponin T (<0.035 μg/L) and NT-proBNP (<332 ng/L) thresholds, with clear prognostic separation: stage I patients (both biomarkers below threshold) have the best survival, while stage III patients (both elevated) have markedly reduced survival13. The 2015 European modification added a fourth category for NT-proBNP >8,500 pg/mL, identifying ultra-high-risk patients with median survival of only 5 months2. The Mayo 2012 model incorporates troponin, NT-proBNP, and difference in free light chains (dFLC) with similar predictive value13.

Figure 2: Survival of Patients With Amyloidosis Based on Staging

These biomarker-based staging systems are also used for ATTR amyloidosis, with NT-proBNP cutoffs of 3,000 ng/L and 10,000 ng/L identifying progressively higher-risk groups4. The ACC Expert Consensus states: "Simply put, the worse the marker, the poorer the prognosis"2.

2. Why the other options are FALSE

(B) is FALSE: Cardiac amyloidosis typically causes diastolic dysfunction with preserved systolic function, not loss of systolic function. The hallmark is restrictive cardiomyopathy with increased wall thickness, elevated filling pressures, and preserved or even hyperdynamic left ventricular ejection fraction until very late stages. While cardiac hypertrophy does occur due to amyloid infiltration, the characteristic functional abnormality is impaired relaxation and filling, not systolic dysfunction.

(C) is FALSE: The ANDROMEDA trial demonstrated that daratumumab added to bortezomib/cyclophosphamide/dexamethasone (D-VCd) showed consistent benefit regardless of t(11;14) status[^8]. The primary publication specifically states: "Results were consistent for patients with a cardiac stage of III and those with t(11;14) translocation"[^8]. The hematologic complete response rate was 53.3% with D-VCd versus 18.1% with VCd alone (P<0.001), and this benefit was observed across all subgroups including those with and without t(11;14)[8][9]. The statement is therefore true, making it an incorrect answer to a question asking for true statements.

(D) is FALSE: The ANDROMEDA trial showed that D-VCd improved both hematologic AND organ responses. At 6 months, cardiac response rates were 41.5% with D-VCd versus 22.2% with VCd alone, and renal response rates were 53.0% versus 23.9%[8][9][^12]. The final survival analysis confirmed that cardiac and renal response rates were 2-3 times higher with D-VCd versus VCd[^7]. The addition of daratumumab resulted in "recovery of organ function" translating to improved major organ deterioration-progression-free survival and overall survival[^7].

Table 2[^12]

詳解 · 中文翻譯

分析

題幹要求關於澱粉樣變的真實的敘述。選項 (A) 被標記為正確答案。

1. 為什麼 (A) 是真實的

NT-proBNP 和肌鈣蛋白水平是澱粉樣變中公認的預後生物標誌物。 多個驗證的分期系統使用這些心臟生物標誌物對患者進行分層並預測存活結果123。

Mayo 診所 2004 分期系統基於心臟肌鈣蛋白 T （<0.035 μg/L）和 NT-proBNP （<332 ng/L） 閾值將 AL 澱粉樣變患者分類為三個階段，具有明確的預後分離：1 期患者（兩個生物標誌物在閾值以下）有最好的存活率，而 3 期患者（兩個升高）具有明顯減少的存活率13。2015 年歐洲修改添加了 NT-proBNP >8,500 pg/mL 的第四類別，識別超高危患者，中位存活期僅為 5 個月2。Mayo 2012 模型整合肌鈣蛋白、NT-proBNP 和遊離輕鏈差異 (dFLC)，具有相似的預測價值13。

Figure 2: Survival of Patients With Amyloidosis Based on Staging

這些基於生物標誌物的分期系統也用於 ATTR 澱粉樣變，NT-proBNP 截斷值為 3,000 ng/L 和 10,000 ng/L，識別逐漸更高危群組4。ACC 專家共識指出：「簡言之，標誌物越差，預後越差」2。

2. 為什麼其他選項是虛假的

(B) 是虛假的：心臟澱粉樣變通常導致舒張功能障礙伴保留收縮功能，而不是收縮功能喪失。標誌是限制性心肌病，壁厚增加、充盈壓升高和直到非常晚期才保留或甚至高功能的左心室射血分數。雖然由於澱粉樣浸潤心臟肥厚確實發生，特徵的功能異常是鬆弛和充盈受損，而不是收縮功能障礙。

(C) 是虛假的：ANDROMEDA 試驗證明添加 daratumumab 到 bortezomib/cyclophosphamide/dexamethasone (D-VCd) 顯示不論 t(11;14) 狀態的一致益處[^8]。主要發表明確指出：「無論心臟分期 III 或那些具有 t(11;14) 易位的患者結果是一致的」[^8]。血液學完全反應率與 D-VCd 為 53.3% 對單獨 VCd 的 18.1%（P<0.001），此益處在所有亞群中觀察到，包括那些具有和不具有 t(11;14) 的患者[8][9]。敘述因此真實，使其成為要求真實敘述的問題的不正確答案。

(D) 是虛假的：ANDROMEDA 試驗顯示 D-VCd 改善血液學和器官反應。在 6 個月時，心臟反應率與 D-VCd 為 41.5% 對 VCd 單獨的 22.2%，腎反應率為 53.0% vs 23.9%[8][9][^12]。最終存活分析確認心臟和腎反應率與 D-VCd 比 VCd 高 2-3 倍[^7]。daratumumab 的添加導致「器官功能恢復」轉化為改善主要器官惡化-進展無生存期和整體存活率[^7]。

Table 2[^12]

參考文獻 (AMA)

  1. Gertz MA, Dispenzieri A. Systemic Amyloidosis Recognition, Prognosis, and Therapy: A Systematic Review. Jama. 2020;324(1):79-89. doi:10.1001/jama.2020.5493. PMID:32633805. ↩↩↩↩↩↩

  2. Kittleson MM, Ruberg FL, Ambardekar AV, et al. 2023 ACC Expert Consensus Decision Pathway on Comprehensive Multidisciplinary Care for the Patient With Cardiac Amyloidosis: A Report of the American College of Cardiology Solution Set Oversight Committee. Journal of the American College of Cardiology. 2023;81(11):1076-1126. doi:10.1016/j.jacc.2022.11.022. PMID:36697326. ↩↩↩↩↩↩

  3. Pregenzer-Wenzler A, Abraham J, Barrell K, Kovacsovics T, Nativi-Nicolau J. Utility of Biomarkers in Cardiac Amyloidosis. JACC. Heart Failure. 2020;8(9):701-711. doi:10.1016/j.jchf.2020.03.007. PMID:32653441. ↩↩↩↩↩↩

  4. Fontana M, Ioannou A, Cuddy S, et al. The Last Decade in Cardiac Amyloidosis: Advances in Understanding Pathophysiology, Diagnosis and Quantification, Prognosis, Treatment Strategies, and Monitoring Response. JACC. Cardiovascular Imaging. 2025;18(4):478-499. doi:10.1016/j.jcmg.2024.10.011. PMID:39797879. ↩↩

  5. Kastritis E, Palladini G, Minnema MC, et al. Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis. The New England Journal of Medicine. 2021;385(1):46-58. doi:10.1056/NEJMoa2028631. PMID:34192431. ↩

  6. Kastritis E, Palladini G, Minnema MC, et al. Daratumumab-Bortezomib-Cyclophosphamide-Dexamethasone in Newly Diagnosed Amyloidosis: ANDROMEDA Final Survival Analysis. Blood. 2026;:blood.2025032099. doi:10.1182/blood.2025032099. PMID:42118698. ↩

Slide correction

loss of systolic function

Slide annotations

NT-proBNP, cTnT, FLC-diff; Better in those with t(11;14); The LV is non-dilated, and LV systolic function is preserved until late in the disease course. Diastolic dysfunction is also universally present. Typically, there is a rapid progression in the grade of diastolic dysfunction.

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