Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai, India.
Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai, India.
Eur J Pharmacol. 2023 Dec 5;960:176142. doi: 10.1016/j.ejphar.2023.176142. Epub 2023 Oct 20.
Cardiac Amyloidosis (CA) is a toxic infiltrative cardiomyopathy occurred by the deposition of the amyloid fibres in the extracellular matrix of the myocardium. This results in severe clinical complications such as increased left ventricular wall thickness and interventricular stiffness, a decrease in left ventricular stroke volume and cardiac output, diastolic dysfunction, arrhythmia, etc. In a prolonged period, this condition progresses into heart failure. The amyloid fibres affecting the heart include immunoglobulin light chain (AL - amyloidosis) and transthyretin protein (ATTR - amyloidosis) misfolded amyloid fibres. ATTRwt has the highest prevalence of 155 to 191 cases per million while ATTRv has an estimated prevalence of 5.2 cases per million. The pathological findings and therapeutic approaches developed recently have aided in the treatment regimen of cardiac amyloidosis patients. In recent years, understanding the pathophysiology of amyloid fibres formation and mechanistic pathways triggered in both types of cardiac amyloidosis has led to the development of new therapeutic approaches and agents. This review focuses on the current status of emerging therapeutic agents in clinical trials. Earlier, melphalan and bortezomib in combination with alkylating agents and immunomodulatory drugs were used as a standard therapy for AL amyloidosis. Tafamidis, approved recently by FDA is used as a standard for ATTR amyloidosis. However, the emerging therapeutic agents under development for the treatment of AL and ATTR cardiac amyloidosis have shown a potent and rapid effect with a safety profile.
心脏淀粉样变性（CA）是一种由心肌细胞外基质中淀粉样纤维沉积引起的毒性浸润性心肌病。这会导致严重的临床并发症，如左心室壁增厚和室间僵硬增加、左心室射血分数和心输出量减少、舒张功能障碍、心律失常等。在较长时间内，这种情况会进展为心力衰竭。影响心脏的淀粉样纤维包括免疫球蛋白轻链（AL-淀粉样变性）和转甲状腺素蛋白（ATTR-淀粉样变性）错误折叠的淀粉样纤维。ATTRwt 的患病率最高，为每百万 155 至 191 例，而 ATTRv 的患病率估计为每百万 5.2 例。最近的病理发现和治疗方法的发展有助于心脏淀粉样变性患者的治疗方案。近年来，对两种类型的心脏淀粉样变性中淀粉样纤维形成和触发的机制途径的病理生理学的理解，导致了新的治疗方法和药物的发展。这篇综述重点介绍了临床试验中新兴治疗药物的现状。早期，马法兰和硼替佐米联合烷化剂和免疫调节剂被用作 AL 淀粉样变性的标准治疗方法。最近被 FDA 批准的塔法米迪作为 ATTR 淀粉样变性的标准治疗药物。然而，正在开发用于治疗 AL 和 ATTR 心脏淀粉样变性的新兴治疗药物具有强大且快速的作用，且安全性良好。
