Interleukin-1 Blockade Inhibits the Acute Inflammatory Response in Patients With ST-Segment-Elevation Myocardial Infarction.

Background ST-segment-elevation myocardial infarction is associated with an intense acute inflammatory response and risk of heart failure. We tested whether interleukin-1 blockade with anakinra significantly reduced the area under the curve for hsCRP (high sensitivity C-reactive protein) levels during the first 14 days in patients with ST-segment-elevation myocardial infarction (VCUART3 [Virginia Commonwealth University Anakinra Remodeling Trial 3]). Methods and Results We conducted a randomized, placebo-controlled, double-blind, clinical trial in 99 patients with ST-segment-elevation myocardial infarction in which patients were assigned to 2 weeks treatment with anakinra once daily (N=33), anakinra twice daily (N=31), or placebo (N=35).

Usefulness of Canakinumab to Improve Exercise Capacity in Patients With Long-Term Systolic Heart Failure and Elevated C-Reactive Protein.

Interleukin-1β (IL-1β) is a cytokine involved in atherothrombosis and is known to depress cardiac function. We hypothesized that blocking IL-1β in patients with symptomatic systolic heart failure (HF) would improve their cardiorespiratory fitness. The purpose of the study was to measure changes in peak oxygen consumption (VO) in 30 patients with prior myocardial infarction, high-sensitivity C-reactive protein ≥ 2 mg/l and HF with left ventricular ejection fraction (LVEF) < 50% enrolled in the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) in an independent single center substudy.

Administration of Rotaglide™ solution for treating refractory severe radial artery spasm: A case report.

Severe radial artery spasm is a complication of transradial cardiac catheterization. We describe a case of severe radial artery spasm causing catheter entrapment. The spasm was refractory and resistant to intra-arterial vasodilators, systemic vasodilators, and moderate sedation.

Inhibiting the Inflammatory Injury After Myocardial Ischemia Reperfusion With Plasma-Derived Alpha-1 Antitrypsin: A Post Hoc Analysis of the VCU-α1RT Study.

Background: Despite the benefits of reperfusion in limiting myocardial injury, the infarct size continues to expand after reperfusion because of secondary inflammatory injury. Plasma-derived alpha-1 antitrypsin (AAT) inhibits the inflammatory injury in myocardial ischemia and reperfusion. To explore the effects of plasma-derived AAT on the inflammatory response to ischemia-reperfusion injury, we analyzed time-to-reperfusion and enzymatic infarct size estimates in a post hoc analysis of the VCU-α1RT clinical trial (clinicaltrials.

Effects of empagliflozin on cardiorespiratory fitness and significant interaction of loop diuretics.

The effects of empagliflozin on cardiorespiratory fitness in patients with type 2 diabetes mellitus (T2DM) and heart failure with reduced ejection fraction (HFrEF) are unknown. In this pilot study we determined the effects of empagliflozin 10 mg/d for 4 weeks on peak oxygen consumption (VO ) in 15 patients with T2DM and HFrEF. As an exploratory analysis, we assessed whether there was an interaction of the effects of empagliflozin on peak VO of loop diuretics.

Interleukin-1 Blockade in Recently Decompensated Systolic Heart Failure: Results From REDHART (Recently Decompensated Heart Failure Anakinra Response Trial).

Background: An enhanced inflammatory response predicts worse outcomes in heart failure (HF). We hypothesized that administration of IL-1 (interleukin-1) receptor antagonist (anakinra) could inhibit the inflammatory response and improve peak aerobic exercise capacity in patients with recently decompensated systolic HF.

Methods And Results: We randomly assigned 60 patients with reduced left ventricular ejection fraction (<50%) and elevated C-reactive protein levels (>2 mg/L), within 14 days of hospital discharge, to daily subcutaneous injections with anakinra 100 mg for 2 weeks, 12 weeks, or placebo.

Interleukin-1 Blockade in Acute Decompensated Heart Failure: A Randomized, Double-Blinded, Placebo-Controlled Pilot Study.

Background: Heart failure is an inflammatory disease. Patients with acute decompensated heart failure (ADHF) exhibit significant inflammatory activity on admission. We hypothesized that Interleukin-1 blockade, with anakinra (Kineret, Swedish Orphan Biovitrum), would quench the acute inflammatory response in patients with ADHF.

Usefulness of C-Reactive Protein Plasma Levels to Predict Exercise Intolerance in Patients With Chronic Systolic Heart Failure.

Patients with heart failure (HF) have evidence of chronic systemic inflammation. Whether inflammation contributes to the exercise intolerance in patients with HF is, however, not well established. We hypothesized that the levels of C-reactive protein (CRP), an established inflammatory biomarker, predict impaired cardiopulmonary exercise performance, in patients with chronic systolic HF.

Comparative safety of interleukin-1 blockade with anakinra in patients with ST-segment elevation acute myocardial infarction (from the VCU-ART and VCU-ART2 pilot studies).

Two pilot studies of interleukin-1 (IL-1) blockade in ST-segment elevation myocardial infarction (STEMI) showed blunted acute inflammatory response and overall favorable outcomes at 3 months follow-up. We hereby present a patient-level pooled analysis with extended follow-up of 40 patients with clinically stable STEMI randomized to anakinra, a recombinant IL-1 receptor antagonist, 100 mg/day for 14 days or placebo in a double-blinded fashion. End points included death, cardiac death, recurrent acute myocardial infarction (AMI), stroke, unstable angina, and symptomatic heart failure.

Effects of Prolastin C (Plasma-Derived Alpha-1 Antitrypsin) on the acute inflammatory response in patients with ST-segment elevation myocardial infarction (from the VCU-alpha 1-RT pilot study).

Alpha-1 antitrypsin (AAT) has broad anti-inflammatory and immunomodulating properties in addition to inhibiting serine proteases. Administration of human plasma-derived AAT is protective in models of acute myocardial infarction in mice. The objective of this study was to determine the safety and tolerability of human plasma-derived AAT and its effects on the acute inflammatory response in non-AAT deficient patients with ST-segment elevation myocardial infarction (STEMI).

Leukocyte activity in patients with ST-segment elevation acute myocardial infarction treated with anakinra.

Anakinra, the recombinant form of the human interleukin (IL)-1 receptor antagonist, blunts the acute systemic inflammatory response in patients with ST-segment elevation myocardial infarction (STEMI), by determining a fall in peripheral blood leukocyte and plasma C-reactive protein levels. The aim of the present study was to determine the effects of anakinra on the activity of leukocytes measured ex vivo. Blood was collected 72 h after admission in 17 patients enrolled in the Virginia Commonwealth University-Anakirna Remodeling Trial (2) (VCU-ART2) and randomly treated with anakinra (N=7) or placebo (N=10).