A third-generation coronary drug-eluting resorbable magnesium scaffold (DREAMS 3G) was developed to enhance the performance of previous scaffold generations and achieve angiographic outcomes comparable to those of contemporary drug-eluting stents. This prospective, multicenter, non-randomized, first-in-human study was conducted at 14 centers in Europe. Eligible patients had stable or unstable angina, documented silent ischemia, or non-ST-elevation myocardial infarction, and a maximum of two single de novo lesions in two separate coronary arteries with a reference vessel diameter between 2.5 mm and 4.2 mm. Clinical follow-up was scheduled at one, six and 12 months and annually thereafter until five years. Invasive imaging assessments were scheduled six and 12 months postoperatively. The primary endpoint was angiographic in-scaffold late lumen loss at six months. This trial was registered at ClinicalTrials.gov (NCT04157153). Between April 2020 and February 2022, 116 patients with 117 coronary artery lesions were enrolled. At six months, in-scaffold late lumen loss was 0.21 mm (SD 0.31). Intravascular ultrasound assessment showed preservation of the scaffold area (mean 7.59 mm² [SD 2.21] post-procedure vs 6.96 mm² [SD 2.48]) at six months) with a low mean neointimal area (0.02 mm² [SD 0.10]). Optical coherence tomography revealed that struts were embedded in the vessel wall and were already hardly discernible at six months. Target lesion failure occurred in one (0.9%) patient; a clinically driven target lesion revascularization was performed on post-procedure day 166. No definite or probable scaffold thrombosis or myocardial infarction was observed. These findings show that the implantation of DREAMS 3G in de novo coronary lesions is associated with favorable safety and performance outcomes, comparable to contemporary drug-eluting stents. This study was funded by BIOTRONIK AG.

C-reactive protein (CRP), the prototype human acute phase protein, may be causally involved in various human diseases. As CRP has appeared much earlier in evolution than antibodies and nonetheless partly utilizes the same biological structures, it is likely that CRP has been the first antibody-like molecule in the evolution of the immune system. Like antibodies, CRP may cause autoimmune reactions in a variety of human pathologies. Consequently, therapeutic targeting of CRP may be of utmost interest in human medicine. Over the past two decades, however, pharmacological targeting of CRP has turned out to be extremely difficult. Currently, the easiest, most effective and clinically safest method to target CRP in humans may be the specific extracorporeal removal of CRP by selective apheresis. The latter has recently shown promising therapeutic effects, especially in acute myocardial infarction and COVID-19 pneumonia. This review summarizes the pros and cons of applying this novel technology to patients suffering from various diseases, with a focus on its use in cardiovascular medicine.

C-reactive protein (CRP) may be causative in cardiovascular disease. As yet, no specific CRP inhibitor for human application has been described. A 69-year-old male was referred with ST segment elevation myocardial infarction (STEMI). Typical symptoms of chest pain started at 10.00 p.m. The patient was admitted to the hospital at 1.30 a.m. the next day. As ECG showed anterior wall myocardial infarction, the patient was immediately transferred to successful emergency angioplasty/drug-eluting- (DE-) stenting of the subtotally occluded left anterior descending artery. Consecutively, the hemodynamically stable patient was monitored at the chest pain unit. C-reactive protein (CRP) apheresis using the CRP adsorber (PentraSorb® CRP) within CAMI-1 trial was performed 34 h and 58 h after the onset of symptoms. In each apheresis session, 6000 ml plasma was treated via peripheral venous access. Plasma CRP levels decreased from 28.77 mg/l to 12.58 mg/l during the first apheresis session and from 24.17 mg/l to 11.55 mg/l during the second session, respectively. No side effects were observed. This is the first report of selective CRP apheresis in a man. The technology offers multiple opportunities to clarify the immunological/pathogenic role of CRP in health and disease.

Unusual clinical course Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced pneumonia is a disease with high mortality and, still, no effective treatment. Excessively elevated C-reactive protein (CRP) plasma levels inversely correlate with prognosis. As CRP, via complement and macrophage activation, can cause organ damage in COVID-19, we have recently introduced selective CRP apheresis as a potentially effective treatment. Now, we report on the first patients with severe SARS-CoV-2-induced pneumonia treated within the “C-reactive protein Apheresis in COVID” (CACOV) registry. Seven sequential hospitalized patients with documented COVID-19, strongly elevated CRP plasma levels, and respiratory failure were treated by selective CRP apheresis in addition to standard therapy after having given their informed consent for inclusion in the CACOV registry. We performed 2-8 CRP apheresis sessions via either peripheral or central venous access depending on clinical course and CRP plasma levels. CRP apheresis, in COVID-19, reduced CRP plasma levels by approximately 50–90%, and it was thus highly effective, feasible, and safe. Despite severe radiological lung involvement in all our patients, only 2 patients finally required intubation, and none required extracorporeal membrane oxygenation (ECMO). All 7 patients were discharged from our 2 hospitals in good clinical condition. Selective CRP apheresis, starting early after patient admission, may be an effective treatment of SARS-CoV-2-induced pneumonia. SARS-COV-2 can cause organ damage and multiple organ failure predominantly by an excessive CRP-mediated autoimmune response of the ancient innate immune system. Further registry data and randomized trials are needed.

BACKGROUND:High C-reactive protein (CRP) plasma levels in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are associated with poor prognosis. CRP, by activating the classical complement pathway and interacting with macrophages via Fc gamma receptors, can cause pulmonary inflammation with subsequent fibrosis. Recently, we have reported first-in-man CRP apheresis in a “high-risk” COVID-19 patient. Treatment was unfortunately clinically unsuccessful. Here, we report on successful CRP apheresis treatment in a “lower-risk” COVID-19 patient with respiratory failure. CASE REPORT:A 39-year-old male patient suffering from fatigue, dyspnea, and fever for 4 days was referred to us. The patient had to be intubated. Polymerase chain reaction (PCR) analysis of a throat smear revealed SARS-CoV-2 infection. Mutation analysis revealed the VOC B. 1.1.7 variant. CRP levels were 79.2 mg/L and increased to 161.63 mg/L. Procalcitonin (PCT) levels were continuously normal (<0.5 ng/ml). Antibiotic therapy was started to avoid bacterial superinfection. CRP apheresis was performed once via central venous access. CRP levels declined from a maximum of 161.63 mg/L to 32.58 mg/L. No apheresis-associated adverse effects were observed. Subsequently, CRP plasma levels declined day by day and normalized on day 5. The patient was extubated on day 5 and discharged from the Intensive Care Unit (ICU) on day 6. A second low CRP peak (maximum 22.41 mg/L) on day 7 remained clinically inapparent. The patient was discharged in good clinical condition with a CRP level of 6.94 mg/L on day 8. CONCLUSIONS:SARS-CoV-2 infection can induce an uncontrolled CRP-mediated autoimmune response of ancient immunity. In this patient, the autoimmune response was potently and successfully suppressed by early selective CRP apheresis.

In the multicenter, non-randomized, exploratory C-reactive protein (CRP) Apheresis in Myocardial Infarction (CAMI-1) study, CRP apheresis after ST-Elevation Myocardial Infarction (STEMI) significantly decreased blood CRP concentrations in humans. Cardiac damage was assessed by Cardiac Magnetic Resonance (CMR1) 3–9 d after onset of STEMI symptoms and quantified by myocardial infarct size (IS; %), left ventricular ejection fraction (LVEF; %), circumferential strain (CS) and longitudinal strain (LS). Compared with the control group (n = 34), cardiac damage was significantly lower in the apheresis group (n = 32). These findings suggested improved wound healing due to CRP apheresis already within few days after the STEMI event. In the current supplementary data analysis of CAMI-1, we have tested by a follow-up CMR (CMR2) after an average of 88 (65–177) d whether the effect of CRP apheresis is clinically maintained. After this time period, wound healing in STEMI is considered complete. Whereas patients with low CRP production and a CRP gradient cut off of 0.6 mg/L/h (23 of 32 patients in the CRP apheresis group) showed significant treatment benefit. In the latter patients, CMR2 revealed a lower IS (−5.4%; p = 0.05), a better LVEF (+6.4%; p = 0.03), and an improved CS (−6.1%; p = 0.005). No significant improvement, however, was observed for LS (−2.9%; p = 0.1). These data suggest a sustained positive effect of CRP apheresis on heart physiology in STEMI patients with high CRP production well beyond the period of its application. The data demonstrate the sustainability of the CRP removal from plasma which is associated with less scar tissue.