Response to interleukin-1 blockade with anakinra in women and men with ST-segment elevation myocardial infarction.

BACKGROUND: Interleukin-1 blockade with anakinra reduces high-sensitivity C-reactive protein (hsCRP) levels and prevents heart failure (HF) events after ST-segment myocardial infarction (STEMI). Sex-based differences in STEMI patients have been reported, but no data are available regarding response to anakinra. METHODS: We analyzed the systemic inflammation and composite end-point of new-onset HF or death in women and men with STEMI treated with anakinra from three different Virginia Commonwealth University Anakinra Response Trial (VCUART) randomized clinical trials. RESULTS: We analyzed 139 patients, 29 (21%) were women while 110 (79%) were men. Baseline hsCRP was higher in women compared to men (8.9 [5.2-13.5] vs. 4.2 [2.1-7.7] mg/L, P<0.001). Eighty-four patients were treated with anakinra (22 [75%] women and 62 [56%] men). The area under the curve of hsCRP (hsCRP-AUC) after 14 days was numerically lower in patients receiving anakinra versus placebo both in men (86 [37-130] vs. 223 [119-374] mg day/L) and in women (73 [46-313] vs. 242 [102-988] mg day/L) (P<0.001 for multiple groups, P for interaction 0.22). The incidence of the composite endpoint was also numerically lower in the anakinra group compared to placebo, both in men (4 [6.4%] vs. 14 [29.1%]) and in women (3 [13.6%] vs. 2 [28.5%]) (P=0.019 for multiple groups, P for interaction 0.44). There were no statistically significant differences between women and men in hsCRP-AUC and death or HF events when comparing separately the anakinra and placebo groups (all P>0.05). CONCLUSIONS: Women were underrepresented in the VCUART trials, they appeared to have higher hsCRP levels at time of presentation, yet to benefit similar to men by treatment with anakinra in STEMI.

Change in Eosinophil Count in Patients with Heart Failure Treated with Anakinra.

BACKGROUND: Interleukin-1 blockade with anakinra leads to a transient increase in eosinophil blood count (eosinophils) in patients with acute myocardial infarction. We aimed to investigate the effect of anakinra on changes in eosinophils in patients with heart failure (HF) and their correlation with cardiorespiratory fitness (CRF). METHODS: We measured eosinophils in 64 patients with HF (50% females), 55 (51-63) years of age, before and after treatment, and, in a subset of 41 patients, also after treatment cessation. We also evaluated CRF, measuring peak oxygen consumption (VO2) with a treadmill test. RESULTS: Treatment with anakinra significantly and transiently increased eosinophils, from 0.2 [0.1-0.3] to 0.3 [0.1-0.4] × 103 cells/µL (p < 0.001) and from 0.3 [0.2-0.5] to 0.2 [0.1-0.3] × 103 cells/µL, with suspension (p < 0.001). Changes in eosinophils correlated with the changes in peak VO2 (Spearman's Rho = +0.228, p = 0.020). Eosinophils were higher in patients with injection site reactions (ISR) (n = 8, 13%; 0.5 [0.4-0.6] vs. 0.2 [0.1-0.4] × 103 cells/µL, p = 0.023), who also showed a greater increase in peak VO2 (3.0 [0.9-4.3] vs. 0.3 [-0.6-1.8] mLO2·kg-1·min-1, p = 0.015). CONCLUSION: Patients with HF treated with anakinra experience a transient increase in eosinophils, which is associated with ISR and a greater improvement in peak VO2.

Sarcopenic Obesity Is Associated With Reduced Cardiorespiratory Fitness Compared With Nonsarcopenic Obesity in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Sarcopenia impairs cardiorespiratory fitness (CRF) in patients with heart failure with reduced ejection fraction (HFrEF). Obesity has also been shown to impair CRF; however, the effects of sarcopenia on CRF in patients with obesity and HFrEF are unknown. The aim of this analysis was to examine differences in CRF between patients with sarcopenic obesity (SO) and non-SO (NSO) with HFrEF. We also assessed associations between skeletal muscle mass index (SMMI) and CRF. METHODS: Forty patients with HFrEF and obesity underwent cardiopulmonary exercise testing to collect measures of CRF including peak oxygen consumption (VO2), circulatory power, oxygen uptake efficiency slope, O2 pulse, and exercise time. Body composition was performed in all patients using bioelectrical impedance analysis to quantify fat mass index and divide patients into SO and NSO based on SMMI cutoffs. Results are presented as mean (SD) or median [interquartile range] as appropriate. RESULTS: Nearly half (43% [n=17]) of patients had SO. Patients with SO had a lower SMMI than those with NSO, and no differences in fat mass index were observed between groups. Those with SO achieved a lower absolute peak VO2 (NSO, 1.62±0.53 L·min-1 versus SO, 1.27±0.44 L·min-1, P=0.035), oxygen uptake efficiency slope (NSO, 1.92±0.59 versus SO, 1.54±0.48, P=0.036), and exercise time (NSO, 549±198 seconds versus SO, 413±140 seconds, P=0.021) compared to those with NSO. On multivariate analysis, SMMI remained a significant predictor of absolute peak VO2 when adjusted for age, sex, adiposity, and HF severity. CONCLUSIONS: In patients with HFrEF and obesity, sarcopenia, defined as low SMMI, is associated with a clinically significant reduction in CRF, independent of adiposity.

Arrhythmic Recurrence and Outcomes in Patients Hospitalized With First Episode of Electrical Storm.

Electrical storm (ES) is a life-threatening condition that may lead to recurrent arrhythmias, need for ventricular mechanical support, and death. The study aimed to assess the burden of arrhythmia recurrence and in-hospital outcomes of patients admitted for ES in a large urban hospital. We performed a retrospective analysis of patients admitted with ventricular arrhythmias from January 2018 to June 2021 and identified 61 patients with ES, defined as 3 or more episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF) within 24 hours. We reviewed the in-hospital outcomes and compared outcomes between patients who had no recurrence of VT/VF after the first 24 hours (34 [56%]), those with recurrence of 1 or 2 episodes of VT/VF within a 24-hour period (15 [24%]), and patients with 3 or more recurrent VT/VF events consistent with recurrent ES after the first 24 hours (12 [20%]). Patients with recurrent ES had significantly higher in-hospital mortality as compared with those with recurrent VT/VF not meeting criteria for ES or no recurrences of VT/VF (3 [25%] vs 0 [0%] vs 0 [0%]; p = 0.002). Moreover, patients with recurrent ES also had higher rates of the combined end points of ventricular mechanical support and death (7 [58%] vs 1 [6%] vs 1 [3%], p <0.001), invasive mechanical ventilation and death (10 [83%] vs 2 [13%] vs 2 [6%], p <0.001), catheter ablation or death (12 [100%] vs 7 [47%] vs 12 [35%], p <0.001) and heart transplantation and death (3 [25%] vs 2 [13%] vs 0 [0%], p = 0.018). In conclusion, patients admitted with ES have a high risk of in-hospital recurrence, associated with extremely poor outcomes.

Recurrent pericarditis: an update on diagnosis and management.

Acute pericarditis is a disease of the pericardium characterized by inflammation. Around 16-38% of patients develop recurrent events after the first episode. Recurrent pericarditis (RP) seems to be caused by a pathological immune response. An inadequate treatment in terms of drug choice, dose, duration of therapy or tapering, has been shown to increase the risk of recurrences. Symptoms, physical and electrocardiographic signs are usually less severe during a recurrent event as compared to the first episode, thus favoring imaging as a tool to confirm the diagnosis of RP. Cardiac magnetic resonance is becoming the technique of choice because of its ability to detect active pericardial inflammation. Inflammatory biomarkers can be used to assess the risk of recurrences and to guide the tapering of treatments. First-line treatment is based on non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine. NSAIDs are useful for pain control, and colchicine has shown to reduce the risk of further recurrences. Glucocorticoids are often used as second-line drugs, but they are associated with a high rate of recurrent events. Interleukin-1 inhibitors, such as anakinra and rilonacept, significantly reduce the risk of recurrences in patients with RP while on treatment.