Anti-HMGCR myopathy presenting with acute systolic heart failure

Abstract

Necrotising autoimmune myopathy (NAM) is an immune-mediated myopathy that may be associated with statin use, malignancy or an autoimmune connective tissue disease, but it can also be idiopathic. Anti-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) myopathy is an extremely rare side effect of statin use, occurring in approximately 2–3 out of every 100 000 patients who use statins. Patients typically present with subacute proximal muscle weakness and creatine kinase levels >10 times the upper limit of normal. The diagnosis is suggested by muscle biopsy showing necrotic fibres with minimal inflammation along with positive anti-HMGCR antibodies. Treatment nearly always requires multiple immunosuppressive agents, the earlier use of which is associated with improved outcomes. Reports of statin-induced NAM leading to heart failure are limited. We present the case of a 69-year-old woman with statin-induced NAM who presented with acute systolic heart failure. Early initiation of high-dose corticosteroids and IVIG resulted in significant improvement in her symptoms.

Case Report: Immune Mediated Necrotizing Myopathy With IgG Antibodies to 3-Hydroxy-3-Methylglutaryl-Coenzyme a Reductase (HMGCR) May Present With Acute Systolic Heart Failure

“…The existing literature suggests that cardiomyopathy is not a typical feature of anti-HMGCR myopathy ( 2 ). Our findings, in addition to two previous case reports ( 12 , 13 ), indicate that acute systolic heart failure can occur in HMGCR myopathy, and since this is a serious, treatable complication, early diagnosis is critical.…”

The Pathogenetic Basis of the Action of Bempedoic Acid

“…1), с чем связаны гипофункция коэнзима Q, митохондриальная дисфункция, гистотоксическая гипоксия, аберрантное пренилирование белков, в том числе регуляторных (малых ГТФ-аз Ras, Rac1, RhoA, RhoB, CDC42), угнетение трансляции протеинов, индукция апоптоза, мальадаптивной аутофагии. Смежные с данными, прочие механизмы обусловлены также гиперактивацией убиквитин-зависимой деградации белков, нарушением контроля внутриклеточной концентрации кальция и кальций-зависимой трансдукции сигнала, индукцией аутоиммунного ответа, например, выработкой антител против ГМГ-КоА-редуктазы (2-3 случая на 100 000 пациентов) скелетных мышц и сердца (с развитием кардиомиопатии) [7,10,12,[41][42][43][44][45]. За пределами настоящего обзора находятся обсуждение эффекта ноцебо и значения некомпетентного информирования пациентов о негативных последствиях приема статинов [46][47][48].…”

<p>Immune-Mediated Necrotizing Myopathy Initially Presenting as Erythema Nodosum</p>

“…2 It may also involve muscles of the respiratory and cardiovascular systems, which can cause severe morbidity and mortality. 2,[5][6][7] The recognized risk factors for IMNM include drug exposure (statins, pembrolizumab, and nivolumab), 8 connective tissue diseases, cancer (commonly gastrointestinal adenocarcinomas, and lung cancer) 9,10 and rarely, human immunodeficiency virus infection. 4 The muscular histopathology of IMNM shows significant myofiber necrosis and minimal lymphocytic infiltrates without perifascicular atrophy.…”