C-Reactive Protein Apheresis as Anti-inflammatory Therapy in Acute Myocardial Infarction: Results of the CAMI-1 Study

Abstract

Background: C-reactive protein (CRP) is a well-known marker of inflammation. It is less known that CRP mediates tissue damage in acute myocardial infarction (AMI) thus potentially worsening prognosis. A newly developed specific CRP adsorber allows efficient lowering of CRP levels and may improve survival.Objectives: Aim of this multi-center, controlled, non-randomized first-in-man CRP apheresis in Acute Myocardial Infarction study (CAMI-1) was to investigate the relationship between CRP levels (CRP gradient), myocardial infarct size and function as well as safety and efficacy of CRP apheresis in the setting of acute ST-segment Elevation Myocardial Infarction (STEMI) in humans.Methods: Eighty-three patients (45 apheresis, 38 controls) were recruited. CRP apheresis was performed 24 ± 12, 48 ± 12, and optionally 72 ± 12 h after onset of symptoms. First aphereses were performed at a median CRP concentration of 23.0 mg/L (range 9–279). In each apheresis session, 5,900 ± 400 mL plasma was processed via peripheral venous access. Primary study endpoint was a reduction in myocardial infarct size after STEMI as determined by cardiovascular magnetic resonance (CMR).Results: In controls, the CRP concentration significantly correlated with infarct size (p = 0.002) and decreased myocardial function (p ≤ 0.001). The CRP concentration in apheresis patients did not correlate with infarct size (p = 0.66) or left ventricular (LV) function (p = 0.79) and global strains and therefore significantly differed from controls (p = 0.03 and p = 0.002). Three major adverse cardiac events occurred in the control group after 12 months, none occurred in the apheresis group. Mean CRP depletion achieved over all apheresis procedures was 53.0 ± 15.1%. Apheresis sessions were well-tolerated. Reduced infarct size in the apheresis group compared to the control group (primary endpoint) was not achieved according to the original statistical analysis plan. Taking into account the individual CRP levels, however, revealed significant results. Modifications of the analysis plan were introduced in order to recruit a sufficient number of patients.Conclusions: This pilot study in humans reveals a correlation between CRP concentration and myocardial infarct size. CRP concentrations in STEMI can effectively be reduced by CRP apheresis without relevant side effects. CRP apheresis has the potential to interfere with deleterious aspects of STEMI. By lowering CRP levels, it resulted in the loss of correlation of CRP concentrations with myocardial infarct sizes as well as LV function. These results encourage a larger, randomized clinical trial.Clinical Trial Registration:https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00008988, DRKS00008988.

Case Report: C-Reactive Protein Apheresis in a Patient With COVID-19 and Fulminant CRP Increase

“…CRP concentration kinetics showed a rapid increase in plasma levels between 96 and 132 h after positive SARS-CoV-2 antigen test and 1 st apheresis was then initiated. Apheresis treatments were performed as described elsewhere in detail ( 27 ) and the blood was anticoagulated with ACD-A (1 st apheresis) or ACD-A and additional heparin (2 nd - 4 th apheresis). Treated plasma volume was dependent on patient condition and CRP concentration.…”

“…Selective, extracorporeal CRP apheresis with a CRP adsorber ( 25 ) lowers the CRP concentration drastically within a few hours, and the repeatable treatment is safe and efficient ( 26 , 27 ). Clear evidence has been shown in previous clinical studies, investigating CRP apheresis after myocardial infarction, that CRP depletion reduces systemic inflammation and cardiac tissue damage ( 27 ). We used this therapy in the early phase of incipient pulmonary fibrosis in a patient diagnosed with SARS-CoV-2 infection.…”

Past, Present, and Future of Blood Biomarkers for the Diagnosis of Acute Myocardial Infarction—Promises and Challenges

“…In animal studies, CRP removal was able to significantly reduce infarct size and improve outcomes [ 65 ]. Ries et al, in a pilot study in humans with AMI (CAMI-1 study), reported that CRP apheresis managed to reduce circulating CRP levels and a loss of correlation between CRP levels and infarct size, although CRP reduction was not associated with a significant reduction in infarct size [ 66 ]. However, because CRP increases in a wide variety of other settings, its levels are not sufficiently specific to qualify it as a reliable marker of AMI.…”

Association of C-Reactive Protein Velocity with Early Left Ventricular Dysfunction in Patients with First ST-Elevation Myocardial Infarction

“…According to Świątkiewicz et al, changes in CRP concentrations during STEMI might serve as a risk marker for post-infarct LV systolic dysfunction and heart failure [ 14 , 15 , 16 ], even years after the index event, as well as LV remodeling [ 17 ], underlining the clinical usefulness of CRP dynamics in this patient setting. In the CAMI-1 study, the CRP gradient was suggested to correlate with a greater extent of myocardial infarct size (IS) and reduced LVEF [ 18 ].…”