Department of Cardiology Aarhus University Hospital Aarhus Denmark.
The National Amyloidosis Centre, The Royal Free Hospital London UK.
J Am Heart Assoc. 2024 Jul 2;13(13):e034213. doi: 10.1161/JAHA.124.034213. Epub 2024 Jun 27.
Wild-type transthyretin amyloid (ATTRwt) cardiomyopathy is increasingly recognized in the development of heart failure. The link between cardiac performance, hemodynamics, and mitochondrial function in disease stages of ATTRwt has not previously been studied but may provide new insights into the pathophysiology and clinical performance of the patients.
The study investigated 47 patients diagnosed with ATTRwt at Aarhus University Hospital, Denmark. Patients were stratified according to the disease stages of the National Amyloidosis Centre (NAC) as NAC I with low levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) (NAC I-L, n=14), NAC I with high levels NT-proBNP (NAC I-H, n=20), and NAC II-III (n=13). Exercise testing with simultaneous right heart catheterization was performed in all patients. Endomyocardial biopsies were collected from the patients and the mitochondrial oxidative phosphorylation capacity was assessed. All NAC disease groups, even in the NAC I-L group, a significant abnormal increase in biventricular filling pressures were noted during exercise while the filling pressures was normal or near normal at rest. The inotropic response to exercise was reduced with diminished increase in cardiac output which was significantly more pronounced in the NAC I-H (Diff. -2.4, 95% CI (-4.2: -0.7), =0.00) and the NAC II-III group (Diff: -3.1 L/min, 95% CI (-5.2: -1.1), =0.00) compared with the NAC I-L group. The pulmonary artery wedge pressure to cardiac output ratio at peak exercise was significantly different between NAC I-L and NAC II-III (Diff: 1.6 mm Hg*min/L, 95% CI (0.01:3.3, =0.04)). Patients with ATTRwt had a reduced oxidative phosphorylation capacity which correlated to left ventricular mass but not to cardiac output capacity.
An abnormal restrictive left ventricle and right ventricle response to exercise was demonstrated, even present in patients with early-stage ATTRwt. In more advanced disease stages a progressive impairment of the pressure-flow relationship was noted. The myocyte energetics is deranged but not associated to the contractile reserve or restrictive filling characteristics in ATTRwt.
野生型转甲状腺素蛋白淀粉样变（ATTRwt）心肌病在心力衰竭的发展中日益受到关注。在 ATTRwt 的疾病阶段，心脏功能、血液动力学和线粒体功能之间的联系以前尚未研究过，但可能为患者的病理生理学和临床表现提供新的见解。
该研究调查了丹麦奥胡斯大学医院诊断为 ATTRwt 的 47 名患者。根据国家淀粉样变性中心（NAC）的疾病阶段，患者分为 NAC I 低 NT-proBNP（N 端脑利钠肽前体）水平（NAC I-L，n=14）、NAC I 高 NT-proBNP（NAC I-H，n=20）和 NAC II-III（n=13）。所有患者均进行运动试验并同时进行右心导管检查。从患者中采集心肌活检，并评估线粒体氧化磷酸化能力。所有 NAC 疾病组，甚至在 NAC I-L 组，在运动过程中均观察到左右心室充盈压显著异常增加，而在休息时充盈压正常或接近正常。运动时的变力反应降低，心输出量增加减少，在 NAC I-H（差异-2.4，95%CI（-4.2：-0.7），=0.00）和 NAC II-III 组（差异：-3.1 L/min，95%CI（-5.2：-1.1），=0.00）中更为明显与 NAC I-L 组相比。运动峰值时肺动脉楔压与心输出量比值在 NAC I-L 与 NAC II-III 之间有显著差异（差异：1.6mmHg*min/L，95%CI（0.01：3.3），=0.04）。ATTRwt 患者的氧化磷酸化能力降低，与左心室质量相关，但与心输出量能力无关。
即使在早期 ATTRwt 患者中，也发现了异常的限制性左心室和右心室对运动的反应。在更晚期的疾病阶段，压力-流量关系逐渐受损。ATTRwt 患者的肌细胞能量代谢紊乱，但与收缩储备或限制性充盈特征无关。
