Light chain cardiac amyloidosis

• Published in: Current problems in cancer Vol. 41; no. 2; pp. 144 - 156
• Main Authors: Mankad, Anit K., M.D., F.A.C.C, Sesay, Isata, M.D, Shah, Keyur B., M.D., F.A.C.C
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2017
• Subjects: Amyloid Neuropathies, Familial - complications; Amyloid Neuropathies, Familial - immunology; Amyloid Neuropathies, Familial - metabolism; Amyloid Neuropathies, Familial - pathology; autologous; bortezomib; Cardiac amyloidosis; Cardiomyopathies - complications; Cardiomyopathies - immunology; Cardiomyopathies - metabolism; Cardiomyopathies - pathology; heart transplantation; Hematology, Oncology and Palliative Medicine; Humans; Immunoglobulin Light Chains - metabolism; light chain amyloidosis; Prognosis; stem cell transplantation; TTE; BNP; ISHLT; LVAD; Wild-type transthyretin amyloidosis; NT-proBNP; Transthyretin amyloidosis; Hereditary amyloidosis (mutation in transthyretin sequence); Vincritine, adriamycin and dexamethasone; Left ventricular assist device; International Society of Heart and Lung Transplant; HMI; Light chain amyloidosis; ATTRm; Implantable cardioverter defibrillator; Transthyretin; Cyclophosphamide, vincristine, adriamycin and methylprednisolone; CMR; AL; ICD; C-VAMP; TnI; ATTR; Troponin T; B-type natriuretic peptide; Troponin I; Autologous stem cell transplant; VAD; High-dose melphalan; TnT; ATTRwt; ASCT; N-terminal B-type natriuretic peptide; Cardiac magnetic resonance imaging; light chain amyloidosis; Cardiac amyloidosis; bortezomib; heart transplantation; autologous; stem cell transplantation
• ISSN: 0147-0272; 1535-6345
• DOI: 10.1016/j.currproblcancer.2016.11.004

Abstract Cardiac amyloidosis is an under-recognized condition in which delays to diagnosis have great implications on management options, prognosis, and morbidity. Once cardiac tissue is infiltrated by amyloid fibrils, there is a cascade of pathological changes that can display an array of clinical manifestations, from impaired relaxation of the ventricular myocardium to severe restrictive disease or even progressive systolic heart failure. Management is guided not only by recognizing the subtype of amyloidosis (primary, hereditary, and wild-type transthyretin amyloidosis), but also the clinical stage of the disease. It is important for those managing such patients to understand and differentiate disease associated to fibrils composed of transthyretin versus light chains proteins. Kappa and lambda light chains of primary amyloidosis are particularly toxic to myocytes, leading to accelerated clinical illness in the face of intolerance to treatment and poor survival. Limitations to treatment of primary cardiac amyloidosis are related to multiorgan dysfunction and the inability to tolerate appropriate chemotherapy. Bortezomib, a selective protease inhibitor, has been shown to be and an effective and tolerable option for those with myocardial amyloid infiltration. Standard goal-directed optimal medical management for cardiomyopathy (such as beta blockers and ace inhibitors) does not offer a survival benefit with cardiac amyloidosis, and often is associated with adverse effects. Despite advances in treatment of advanced heart failure therapy, end stage cardiomyopathy in the setting of amyloidosis is not well stabilized by inotropes or mechanical circulatory support, and offers restricted candidacy for heart transplantation. We review the salient features of cardiac amyloidosis to help general practitioners and subspecialists manage this unique clinical condition.