Netti Lucrezia, Ioannou Adam, Martinez-Naharro Ana, Razvi Yousuf, Porcari Aldostefano, Venneri Lucia, Maestrini Viviana, Knight Dan, Virsinskaite Ruta, Rauf Muhammad U, Kotecha Tushar, Patel Rishi K, Wechelakar Ashutosh, Lachmann Helen, Kellman Peter, Manisty Charlotte, Moon James, Hawkins Philip N, Gillmore Julian D, Fontana Marianna
Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.
National Amyloidosis Centre, University College London, Royal Free Campus, London, UK.
Eur J Heart Fail. 2024 Oct 18. doi: 10.1002/ejhf.3481.
Cardiac amyloidosis (CA) is characterized by deposition of amyloid fibrils within the extracellular space, causing disarray of the myocardial structure and capillary architecture. This study aims to characterize the prevalence of microvascular obstruction (MVO) in patients with CA and to assess the association between MVO and prognosis.
The study population comprised 800 patients, of which 400 had light-chain CA (AL-CA) and 400 had transthyretin CA (ATTR-CA). MVO was present in 221 (27.6%) patients, and more common in ATTR-CA than AL-CA (124 [56.1%] vs. 97 [43.9%], p = 0.033). Patients with MVO had a more severe cardiac phenotype evidenced by higher N-terminal pro-brain natriuretic peptide (3516 ng/L [1944-6247] vs. 2508 ng/L [1203-5752], p < 0.001), worse global longitudinal strain (-10.5% [-12.6; -7.9] vs. -12.0% [-16.0; -8.9], p < 0.001), and higher extracellular volume (56% [51-61] vs. 50% [45-57], p < 0.001). Patients with AL-CA and MVO had a higher serum troponin (86 ng/L [47-148] vs. 59 ng/L [44-78], p < 0.001), and higher T2 (53 ms [50-56] vs. 50 ms [48-52], p < 0.001), but lower extracellular volume (55% [50-60] vs. 58% [53-61], p = 0.008) and lower indexed myocyte cell volume (48.6 g/m [41.1-59.8] vs. 55.7 g/m [47.5-68.4], p < 0.001) than patients with ATTR-CA and MVO. MVO was associated with an increased risk of mortality in the overall population (hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.03-1.59, p = 0.025), and the subgroup with AL-CA (HR 1.59, 95% CI 1.17-2.17, p = 0.003) but not ATTR-CA (HR 1.04, 95% CI 0.77-1.40, p = 0.814).
Microvascular obstruction is common in CA and is related to markers of amyloid infiltration. MVO is associated with an increased risk of mortality in AL-CA, but not in ATTR-CA. This reflects the intrinsic differences in disease biology between these two forms of CA, with MVO likely related to multiple myocardial processes, amyloid infiltration, oedema and myocyte death.
心脏淀粉样变性（CA）的特征是淀粉样原纤维在细胞外间隙沉积，导致心肌结构和毛细血管结构紊乱。本研究旨在描述CA患者微血管阻塞（MVO）的患病率，并评估MVO与预后之间的关联。
研究人群包括800例患者，其中400例为轻链CA（AL-CA），400例为转甲状腺素蛋白CA（ATTR-CA）。221例（27.6%）患者存在MVO，在ATTR-CA中比AL-CA更常见（124例[56.1%]对97例[43.9%]，p = 0.033）。MVO患者具有更严重的心脏表型，表现为更高的N末端脑钠肽前体（3516 ng/L [1944 - 6247]对2508 ng/L [1203 - 5752]，p < 0.001）、更差的整体纵向应变（-10.5% [-12.6; -7.9]对-12.0% [-16.0; -8.9]，p < 0.001）以及更高的细胞外容积（56% [51 - 61]对50% [45 - 57]，p < 0.001）。与ATTR-CA合并MVO的患者相比，AL-CA合并MVO的患者血清肌钙蛋白更高（86 ng/L [47 - 148]对59 ng/L [44 - 78]，p < 0.001）、T2更高（53 ms [50 - 56]对50 ms [48 - 52]，p < 0.001），但细胞外容积更低（55% [50 - 60]对58% [53 - 61]，p = 0.008）以及心肌细胞指数容积更低（48.6 g/m [41.1 - 59.8]对55.7 g/m [47.5 - 68.4]，p < 0.001）。MVO与总体人群死亡率增加相关（风险比[HR] 1.28，95%置信区间[CI] 1.03 - 1.59，p = 0.025），在AL-CA亚组中相关（HR 1.59，95% CI 1.17 - 2.17，p = 0.003），但在ATTR-CA亚组中不相关（HR 1.04，95% CI 0.77 - 1.40，p = 0.814）。
微血管阻塞在CA中常见，且与淀粉样蛋白浸润标志物相关。MVO与AL-CA患者死亡率增加相关，但与ATTR-CA患者无关。这反映了这两种形式的CA在疾病生物学上的内在差异，MVO可能与多种心肌过程、淀粉样蛋白浸润、水肿和心肌细胞死亡有关。
