Willixhofer Robin, Contini Mauro, Emdin Michele, Magrì Damiano, Bonomi Alice, Salvioni Elisabetta, Celeste Fabrizio, Del Torto Alberico, Passino Claudio, Capelle Christophe D J, Arzilli Chiara, Fiori Emiliano, Capra Nicolò, Kronberger Christina, Ermolaev Nikita, Kammerlander Andreas, Musumeci Beatrice, Vergaro Giuseppe, Castiglione Vincenzo, Rettl René, Tini Giacomo, Baggiano Andrea, Fabiani Iacopo, Sciomer Susanna, Badr Eslam Roza, Agostoni Piergiuseppe
Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
Centro Cardiologico Monzino, IRCCS, Milan, Italy.
ESC Heart Fail. 2025 Apr;12(2):1326-1335. doi: 10.1002/ehf2.15147. Epub 2024 Nov 14.
Amyloid cardiomyopathy is caused by the deposition of light chain (AL) or transthyretin amyloid (ATTR) fibrils, that leads to a restrictive cardiomyopathy, often resulting in heart failure (HF) with preserved or reduced ejection fraction. This study aimed to determine whether cardiac output reduction or ventilation inefficiency plays a predominant role in limiting exercise in patients with amyloid cardiomyopathy.
We conducted a multicentre prospective study in patients with AL or ATTR cardiomyopathy who underwent cardiopulmonary exercise testing across four centres. Patients were compared with a propensity-score matched HF cohort based on age, gender, left ventricular ejection fraction (LVEF), and peak oxygen consumption (VO).
Data from 267 amyloid patients aged 77 (72, 81) years, 86% male, with a median N-terminal pro B-type natriuretic peptide (NT-proBNP) of 2187 (1140, 4383) ng/L, exercise parameters of peak VO of 14.1 (11.6;16.9) mL/min/kg, a minute ventilation to carbon dioxide production (VE/VCO) slope of 37.4 (32.5, 42.6) and a LVEF of 50% (44%, 59%) were analysed. We identified 251 amyloid cardiomyopathy-HF matches. Amyloid patients had a signifnicantly higher VE/VCO slope [37.4, inter quartile range (IQR): 32.7, 43.1 vs. 32.1, IQR: 28.7, 37.0, P < 0.0001], NT-proBNP (2249, IQR: 1187, 4420 vs. 718, IQR: 405, 2161 ng/L, P < 0.001), peak heart rate (121 ± 28 vs. 115 ± 27 beats/min, P = 0.007) and peak ventilation (51, IQR: 42, 62 vs. 43, IQR: 33, 53 L/min, P < 0.0001) with earlier anaerobic threshold (VO at AT: 8.9, IQR: 6.8, 10.8 vs. 10.8, IQR: 8.9, 12.7 mL/min/kg, P < 0.0001) compared with HF. Between amyloid patients, AL patients (n = 27) were younger (63, IQR: 58, 70 vs. 78, IQR: 72, 81 years, P < 0.0001), had lower VE/VCO slope (35.0, IQR: 30.0, 38.7 vs. 38.0, IQR: 32.8, 43.1, P = 0.019), higher end-tidal carbon dioxide partial pressure both at AT (35.1 ± 4.8 vs. 31.4 ± 4.7 mmHg, P < 0.001) and peak exercise (32, IQR: 28, 35 vs. 30, IQR: 26, 33 mmHg, P = 0.039) as compared with ATTR (n = 233).
A higher VE/VCO slope and an earlier AT, determining functional capacity impairment, was assessed in patients with amyloid cardiomyopathy compared with the matched HF cohort. Additionally, patients with ATTR might display more severe exercise limitations as compared with AL.
淀粉样心肌病由轻链（AL）或转甲状腺素蛋白淀粉样变（ATTR）纤维沉积引起，导致限制性心肌病，常导致射血分数保留或降低的心力衰竭（HF）。本研究旨在确定心输出量减少或通气效率低下在限制淀粉样心肌病患者运动中是否起主要作用。
我们对四个中心接受心肺运动试验的AL或ATTR心肌病患者进行了一项多中心前瞻性研究。根据年龄、性别、左心室射血分数（LVEF）和峰值耗氧量（VO），将患者与倾向评分匹配的HF队列进行比较。
分析了267例淀粉样变患者的数据，这些患者年龄为77（72，81）岁，男性占86%，N末端B型利钠肽原（NT-proBNP）中位数为2187（1140，4383）ng/L，峰值VO运动参数为14.1（11.6；16.9）mL/min/kg，分钟通气量与二氧化碳产生量（VE/VCO）斜率为37.4（32.5，42.6），LVEF为50%（44%，59%）。我们确定了251例淀粉样心肌病-HF匹配患者。与HF相比，淀粉样变患者的VE/VCO斜率显著更高[37.4，四分位间距（IQR）：32.7，43.1对32.1，IQR：28.7，37.0，P<0.0001]，NT-proBNP（2249，IQR：1187，4420对718，IQR：405，2161 ng/L，P<0.001），峰值心率（121±28对115±27次/分钟，P=0.007）和峰值通气量（51，IQR：42，62对43，IQR：33，53 L/min，P<0.0001），无氧阈值更早（AT时的VO：8.9，IQR：6.8，10.8对10.8，IQR：8.9，12.7 mL/min/kg，P<0.0001）。在淀粉样变患者中，与ATTR（n=233）相比，AL患者（n=27）更年轻（63，IQR：58，70对78，IQR：72，81岁，P<0.0001），VE/VCO斜率更低（35.0，IQR：30.0，38.7对38.0，IQR：32.8，43.1，P=0.019），AT时和峰值运动时的呼气末二氧化碳分压更高（分别为35.1±4.8对31.4±4.7 mmHg，P<0.001和32，IQR：28，35对30，IQR：26，33 mmHg，P=0.039）。
与匹配的HF队列相比，淀粉样心肌病患者的VE/VCO斜率更高且AT更早，这决定了功能能力受损。此外，与AL患者相比，ATTR患者可能表现出更严重的运动限制。
