Atherosclerosis in systemic autoimmune diseases : early markers and risk factors

Systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and granulomatosis with polyangiitis, are associated with an increased prevalence of cardiovascular disease (CVD), due to accelerated atherosclerosis. We studied early markers and potential risk factors for atherosclerosis in systemic autoimmune diseases. Pulse wave analysis (PWA) measures small artery elasticity (SAE) and was used as marker for EC function. SAE was decreased in patients with systemic autoimmune disease without overt atherosclerosis. Accumulation of advanced glycation end products (AGEs) was increased in patients with systemic autoimmune diseases and was related to SAE and intima media thickness, as marker for early atherosclerosis. Polymorphisms in the gene for the receptor for advanced glycation end products (RAGE) were associated with disease susceptibility for SLE and RA and were associated with cardiovascular disease and disease severity in RA. PWA is a sensitive method to detect early vascular changes in patients with systemic autoimmune diseases. AGEs and their receptor RAGE contribute to accelerated atherosclerosis in systemic autoimmune diseases. Prospective studies are necessary to establish whether decreased SAE is indeed an early marker for atherosclerosis and whether interventions to reduce accumulation of AGEs can suppress the development of atherosclerosis in patients with systemic autoimmune diseases.

A real-life cohort study of immunoglobulin light-chain (AL) amyloidosis patients ineligible for autologous stem cell transplantation due to severe cardiac involvement or advanced disease

Objective: To study the outcome of patients with AL amyloidosis who were ineligible for high dose melphalan (HDM) and autologous stem cell transplantation (ASCT).Methods: A real-life retrospective observational cohort study of Dutch patients with AL amyloidosis ineligible for HDM and ASCT was performed at the University Medical Center Groningen from January 2001 until April 2017. Primary outcome measure was overall survival (OS). Secondary outcome measures were hematological response (HR), organ responses, and treatment toxicity.Results: Eighty-four patients were included. Ineligibility was due to NYHA class III/IV (n = 58), otherwise advanced disease (n = 11), advanced age (n = 14), or treatment refusal (n = 1). Early death (<3 months) rate was high (44%). Median OS improved from 4 months in period 2001-2009 (n = 36) to 8 months in period 2009-2017 (n = 48, p = .02). HR was seen in 29%, and 42% of the patients, respectively. Median OS was 36 months after induction treatment with bortezomib (n = 32) and 18 months with immunomodulatory imide drug (IMID) (n = 16), both higher than median OS (7 months) with other regimens (n = 27). Incidence of toxicity was high (51%).Conclusion: OS improved in this high-risk group over the years, especially after introduction of new treatment modalities. However, early death rate remains high, illustrating the need for more effective treatment

Frequency of and Prognostic Significance of Cardiac Involvement at Presentation in Hereditary Transthyretin-Derived Amyloidosis and the Value of N-Terminal Pro-B-Type Natriuretic Peptide

The aim of this study is to assess the prevalence of cardiac involvement in hereditary transthyretin-derived (ATTRm) amyloidosis at the time of diagnosis and to determine the diagnostic and clinical value of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The University Medical Center Groningen is the national center of expertise for amyloidosis. All consecutive patients between 1994 and 2016 with ATTRm amyloidosis were followed prospectively. Baseline was set at the time of the first positive biopsy. All patients underwent a standard cardiac and neurologic work-up. Cardiac involvement was defined by otherwise unexplained left and/or right ventricular wall hypertrophy on cardiac ultrasound and/or advanced conduction disturbances. Seventy-seven patients had ATTRm amyloidosis and were included in the study. The TTR V30M mutation was present in 30 patients (39%). In both the V30M and the non-V30M groups, the neurologic presentation dominated (77% vs 51%), whereas cardiac presentation was infrequent (7% vs 15%). Clinical work-up showed that cardiac involvement was present at baseline in 51% of all patients irrespective of genotype and was associated with increased overall mortality (hazard ratio 5.95, 95% confidence interval 2.12 to 16.7), independent from clinical confounders. At a cutoff level of 125 ng/L, NT-proBNP had a sensitivity of 92% for establishing cardiac involvement. In conclusion, irrespective of the frequent noncardiac presentation of ATTRm amyloidosis, cardiac involvement is already present at diagnosis in half of the patients and is associated with increased mortality. NT-proBNP is a useful marker to determine cardiac involvement in this disease

Cardiac Transthyretin-derived Amyloidosis:An Emerging Target in Heart Failure with Preserved Ejection Fraction?

Heart failure with preserved ejection fraction (HFpEF) comprises half of the heart failure population. A specific, but underdiagnosed, cause for HFpEF is transthyretin-derived (ATTR) amyloidosis. This article reviews the clinical characteristics of cardiac ATTR amyloidosis. The clinical suspicion of cardiac ATTR amyloidosis is strong if pronounced left ventricular hypertrophy is present in the absence of hypertension. Scintigraphy with a diphosphonate tracer is a diagnostic tool for the early detection of cardiac ATTR amyloidosis with high sensitivity and specificity. First treatment options for ATTR amyloidosis recently emerged, and showed a reduction in morbidity and mortality, especially if treatment was started in the early stages of disease. In light of these results, screening for ATTR amyloidosis in the general HFpEF population with left ventricular hypertrophy might be useful