第一部分 心脏磁共振多心腔延迟强化评估在轻链型淀粉样变中的预后价值

目的：轻链型心脏淀粉样变（AL-CA）是一种造成进行性器官功能障碍的致死性疾病。既往研究表明左心室延迟强化（LGE）是AL-CA患者预后不良的预测因子。目前尚不清楚对全心不同心腔淀粉样蛋白浸润的评估是否具有更高的预后价值。本研究的目的是探索AL-CA患者的多心腔LGE特征及其预后价值。

方法：连续纳入2014年9月至2022年9月于我院接受心脏磁共振检查的AL-CA患者373例。纳入标准为活检组织学证明的轻链型淀粉样变。基于心脏磁共振LGE成像评估各心腔心肌的淀粉样蛋白浸润，左心室LGE模式评分为：0=无LGE，1=心内膜下LGE，2=透壁LGE；右心室游离壁、室间隔右室侧、左心房和右心房的LGE模式评分为：0=无LGE，1=阳性LGE。随访的终点为全因死亡。

结果：研究共纳入373例AL-CA患者（61.7%为男性；中位数[四分位数间距]：58 [51 – 64]岁）。在随访期间（中位随访时长39.1个月），115例（31%）患者达到终点。LGE成像提示的左、右心室及左、右心房四个心腔内的淀粉样蛋白浸润均与患者预后相关（均P < 0.05）。在多因素校正模型中，左心室弥漫LGE（HR: 2.533 [95% CI: 1.403, 4.573]，P = 0.002）、右心室游离壁LGE（HR: 2.457 [95% CI: 1.450, 4.165]，P = 0.001）和室间隔右室侧LGE（HR: 2.576 [95% CI: 1.471, 4.512]，P = 0.001）与全因死亡存在独立相关性。在左心室不同LGE模式的三个亚组中，右心室游离壁LGE均为患者结局的预测因子（均P < 0.05）。与左心室LGE评分相比，多心腔LGE评分的受试者工作特征曲线下面积（0.595 vs. 0.703）、C统计量（0.597 vs. 0.710）和特异性（45.3% vs. 67.8%）均明显提高。

结论：本研究发现基于全心LGE评分的多心腔受累评估与AL-CA患者全因死亡相关，为传统左心室LGE评分提供了增量预后价值。全心多心腔LGE模式评估不仅进一步细化了患者的风险分层，而且可以避免对不典型LGE模式患者不良预后风险的低估。

关键词：心脏磁共振；延迟强化；淀粉样变；生存分析

第二部分 心脏磁共振组织特征定量成像在轻链型淀粉样变中的预后价值

目的：轻链型心脏淀粉样变（AL-CA）是一种造成进行性器官功能障碍的致死性疾病，以心脏受累为重点的风险分层和动态监测至关重要。基于T1/T2 mapping技术的组织特征定量成像在AL-CA中是否具有在临床风险分层系统之上的预后价值尚未达成共识。本研究的目的是全面评估心脏磁共振（CMR）组织特征定量成像在AL-CA患者中的预后价值。

方法：连续纳入2014年9月至2022年9月于我院接受心脏磁共振检查的AL-CA患者345例。纳入标准为活检组织学证明的轻链型淀粉样变。应用心脏磁共振T1 mapping、T2 mapping成像定量评估心肌组织特征。随访时根据患者的实验室检查指标变化判断临床血液学疗效和心脏器官疗效，随访的终点为全因死亡。

结果：研究共纳入345例AL-CA患者（61.7%为男性；中位数[四分位数间距]：58 [51 – 64]岁）。在随访期间（中位随访时长39.2个月），101例（29.3%）患者达到终点。在多因素校正模型中，基于ECV测量的心肌淀粉样蛋白负荷与患者预后独立相关（HR: 1.067 [95% CI: 1.030, 1.106]，P < 0.001）。经NT-proBNP与肌钙蛋白I矫正后，只有ECV仍然保留独立预后价值（均P < 0.05），而心肌T1值与T2值不再与预后有显著关联（均P > 0.05）。在矫正血液学疗效后，心肌ECV（P < 0.001）及T1值（P = 0.008）与患者预后独立相关；而在矫正心脏器官疗效后，心肌ECV与患者预后独立相关（P = 0.008）。在Mayo II期和Mayo IIIa期患者中，ECV是全因死亡的独立预后因子（均P < 0.05）。与Mayo分期相比，融合多心腔LGE评分及ECV的CMR心肌组织特征模型的受试者工作特征曲线下面积（0.678 vs. 0.723）提高。在达到深度血液学缓解的患者中，ECV与全因死亡存在显著关联（HR: 1.095 [95% CI: 1.045, 1.148]，P < 0.001），并且在矫正心脏器官疗效（P = 0.018）及其他预后因子后（均P < 0.001）仍为患者结局的独立预测因子。

结论：本研究发现ECV作为评估心肌淀粉样蛋白负荷的CMR心肌组织特征定量指标，为AL-CA患者提供了独立预后信息，可以在Mayo预后分期的基础上进一步对患者进行风险分层，并可识别虽已达到血液学缓解但仍然具有预后风险的患者。

关键词：心脏磁共振；T1 mapping成像；T2 mapping成像；淀粉样变；生存分析

第三部分 基于心脏磁共振组织特征定量成像的轻链型淀粉样变疗效监测研究

目的：心脏磁共振（cardiac magnetic resonance，CMR）是一项重要的影像学检查，可准确评估心脏结构、功能和组织特征，并且可重复性高，可能有助于轻链型心脏淀粉样变（AL-CA）患者的化疗疗效监测。本研究的目的是探索CMR成像用于监测AL-CA患者化疗疗效的可行性。

方法：这项前瞻性研究纳入了111例AL-CA患者（50.5%为男性；中位数[四分位数间距]：54 [49 – 63]岁。对患者在化疗前后进行包括实验室检查和CMR检查在内的纵向监测。在化疗后的随访时，根据患者的实验室检查指标变化判断临床血液学疗效和心脏器官疗效，将患者按临床疗效分为明显缓解组和无明显缓解组。进而分析化疗过程中CMR参数的变化趋势以及各疗效组之间CMR参数变化幅度的差异。

结果：在接受化疗后（化疗前基线vs.化疗后），患者的心肌T2值显著升高（43.6 ± 3.5 vs. 44.6 ± 4.1 ms，P = 0.008）。同时，患者的右心室（right ventricular，RV）纵向应变好转（-9.6% [-13.5% – -7.0%] vs. -11.7% [-14.1% – -8.8%]，P = 0.031），伴有RV细胞外容积（extracellular volume，ECV）减低（53.9% [46.4% – 62.4%] vs. 51.6% [47.2% – 58.7%]，P = 0.048），这种变化趋势在明显缓解组患者中尤为明显。心脏明显缓解组患者与心脏无明显缓解组患者相比，其RV ECV（-2.9% [-8.7% – 1.1%] vs. 1.7% [-5.5% – 7.1%]，P = 0.017）和左心室ECV（-2.0% [-6.0% – 1.3%] vs. 2.0% [-3.0% – 5.0%]，P = 0.01）的减低更为显著。

结论：AL-CA患者在接受化疗后，心肌内沉积的淀粉样蛋白可逐渐消退，其中RV心肌的淀粉样蛋白消退与功能恢复发生得更早且更显著；同时伴有与化疗药物心肌毒性相关的心肌水肿。CMR是监测AL-CA患者化疗相关组织特征变化和心室功能恢复的有力工具，可应用于AL-CA患者的化疗疗效评估。

关键词：心脏磁共振；T1 mapping成像；T2 mapping成像；淀粉样变；化疗

PART I Multi-Chamber Late Gadolinium Enhancement Pattern and Associated Prognosis in Light-Chain Amyloidosis

Objective: Light-chain cardiac amyloidosis (AL-CA) is a progressive and ultimately fatal condition. Left ventricle (LV) late gadolinium enhancement (LGE) pattern is known to be highly predictive of the outcome. However, it remains unknown whether amyloid infiltration in different chambers of the heart could provide increased prognostic value. The aim of this study is to characterize the multi-chamber cardiac involvement using LGE imaging and assess the prognostic value of multi-chamber LGE pattern in patients with AL amyloidosis.

Methods: In this prospective study, patients with histologically proven AL amyloidosis who underwent cardiac magnetic resonance imaging were included. Amyloid infiltration in cardiac chambers were characterized with LGE imaging. The left ventricular LGE pattern was described as: 0, no LGE; 1, subendocardial LGE; and 2, transmural LGE. The LGE in the right ventricular free wall, right ventricular septal surface, left atrial, and right atrial was scored as: 0, absent; or 1, present. The endpoint was death from any cause.

Results: Overall, 373 patients were included in the study (61.7% male; median age: 58 [IQR, 51-64] years). During a median follow-up of 39.1 months, 115 (31%) patients reached the endpoint. All four cardiac chambers’ involvement shown on LGE imaging were associated with the outcome (all, P < 0.05). In the multivariable-adjusted model, greater extent of LV LGE (HR: 2.533 [95% CI: 1.403, 4.573]; P = 0.002) and presence of LGE in right ventricle free wall (HR: 2.457 [95% CI: 1.450, 4.165]; P = 0.001) and right ventricle septal surface (HR: 2.576 [95% CI: 1.471, 4.512]; P = 0.001) remained independent predictors of all-cause mortality. Right ventricular LGE was related to outcome in three subgroups of different LV LGE extent (all, P < 0.05). Compared with LV LGE scoring, multi-chamber LGE scoring showed notably increased area under the curve (0.595 vs. 0.703), C-statistics (0.597 vs. 0.710), and specificity (45.3% vs. 67.8%).

Conclusion: Multi-chamber LGE pattern is associated with all-cause mortality and provides incremental prognostic information over LV LGE pattern in patients with AL amyloidosis. Whole-heart multi-chamber LGE pattern assessment not only further refines the risk stratification of AL-CA patients, but also avoids underestimation of the risk of poor prognosis in patients with atypical LGE patterns.

Keywords: Cardiac magnetic resonance; Late gadolinium enhancement; Amyloidosis; Survival analysis

PART II Comprehensive Prognosis Assessment of Cardiovascular Magnetic Resonance Parametric Mapping in Light-Chain Amyloidosis

Objective: Light-chain cardiac amyloidosis (AL-CA) is a fatal disease causing progressive organ dysfunction, necessitating focused risk stratification and dynamic monitoring of cardiac involvement. The prognostic value of tissue characterization via T1/T2 mapping techniques in AL-CA beyond established clinical risk stratification systems remains unclear. This study aims to comprehensively evaluate the prognostic value of cardiac magnetic resonance (CMR)-derived tissue characterization in AL-CA patients.

Methods: A total of 345 consecutive AL-CA patients who underwent CMR at our institution from September 2014 to September 2022 were enrolled. Inclusion criteria required histologically proven light-chain amyloidosis. Myocardial tissue characterization was quantitatively assessed using CMR T1 mapping and T2 mapping. The statistical analyses included native T1, extracellular volume (ECV), and T2 as variates under investigation, adjusted for well-established prognostic markers. The endpoint was death from any cause.

Results: The cohort comprised 345 AL-CA patients (61.7% male; median age: 58 [IQR, 51–64] years). During follow-up (median duration: 39.2 months), 101 patients (29.3%) reached the endpoint. In multivariable-adjusted models, myocardial amyloid burden measured by ECV was independently associated with prognosis (HR: 1.067 [95% CI: 1.030–1.106], P < 0.001). After adjustment for NT-proBNP and troponin I, only ECV retained independent prognostic significance (all P < 0.05), while native T1 and T2 values lost significance (all P > 0.05). After adjusting for hematologic response, both ECV (P < 0.001) and native T1 (P = 0.008) independently predicted outcomes. Post-adjustment for cardiac organ response, ECV remained independently prognostic (P = 0.008). ECV was an independent predictor of all-cause mortality in both Mayo II and Mayo IIIa stage patients (all P < 0.05). Compared with Mayo staging, CMR myocardial tissue characterization model integrating multi-chamber late gadolinium enhancement scoring and ECV showed increased area under the curve (0.678 vs. 0.723). Among patients achieving deep hematologic response, ECV significantly correlated with mortality (HR: 1.095 [95% CI: 1.045–1.148], P < 0.001), retaining independence after adjusting for cardiac organ response (P = 0.018) and other prognostic factors (all P < 0.001).

Conclusion: ECV, a CMR-derived quantitative marker of myocardial amyloid burden, provides independent prognostic information in AL-CA patients. It enhances risk stratification within the Mayo staging system. Moreover, myocardial amyloid burden assessment identified patients in need of adjunctive therapies, which is of particular prognostic significance in patients with deep therapeutic response.

Keywords: Cardiac magnetic resonance; T1 mapping; T2 mapping; Amyloidosis; Survival analysis

Part III Cardiac Magnetic Resonance Assessment of Response to Light-Chain Cardiac Amyloidosis Chemotherapy

Objective: Cardiac magnetic resonance (CMR) imaging is a diagnostic tool that provides precise and reproducible information about cardiac structure, function, and tissue characterization, which may assist in the monitoring of responses to chemotherapy for light-chain cardiac amyloidosis (AL-CA). The aim of this study is to evaluate the feasibility of CMR in monitoring responses to chemotherapy in patients with AL-CA.

Methods: In this prospective study, we enrolled 111 patients with AL-CA (50.5% male; median age, 54 [interquartile range, 49 – 63] years). The patients underwent longitudinal monitoring using biomarkers and CMR. At the follow-up after chemotherapy, patients were categorized into superior and inferior responses based on their hematologic and cardiac laboratory responses to chemotherapy. Changes in CMR findings across therapy and differences in CMR findings between the response groups were analyzed.

Results: Following chemotherapy (before vs. after), there were significant increase in myocardial T2 (43.6 ± 3.5 vs. 44.6 ± 4.1 ms, P = 0.008), recovery in right ventricular (RV) longitudinal strain (median of -9.6% vs. -11.7%, P = 0.031), and decrease in RV extracellular volume (ECV) fraction (median of 53.9% vs. 51.6%, P = 0.048). These changes were more pronounced in the superior response group. Patients with superior cardiac laboratory response compared with those with inferior response showed significantly greater reductions in RV ECV fraction (-2.9% [interquartile range, -8.7% – 1.1%] vs. 1.7% [-5.5% – 7.1%], P = 0.017) and left ventricular ECV fraction (-2.0% [-6.0% – 1.3%] vs. 2.0% [-3.0% – 5.0%], P = 0.01).

Conclusion: Cardiac amyloid deposition can regress following chemotherapy in AL-CA, more prominently and probably earlier in RV. CMR may be an effective tool for monitoring the associated tissue characteristics and ventricular functional recovery in patients with AL-CA undergoing chemotherapy, supporting its usefulness in the treatment response assessment.

Keywords: Cardiac magnetic resonance; T1 mapping; T2 mapping; Amyloidosis; Chemotherapy