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.

Clinical and Pharmacological Implications of Time to Treatment with Interleukin-1 Blockade in ST-Segment Elevation Myocardial Infarction.

Interleukin-1 (IL-1) blockade with anakinra given within 12 hours from reperfusion has been shown to reduce the inflammatory response as well as prevent heart failure (HF) events in patients with STEMI. We sought to determine whether time-to-treatment influences the efficacy of anakinra on systemic inflammation and incidence of HF events in patients with STEMI. We divided the cohort in two groups base6d on the median time from percutaneous coronary intervention (PCI) to investigational drug, and analyzed the effects of anakinra on the area-under-the-curve for C reactive protein (AUC-CRP) and on incidence of the composite endpoint of death or new onset HF. We analyzed data from 139 patients: 84 (60%) treated with anakinra and 55 (40%) with placebo. The median time from PCI to investigational treatment was 271 (182-391) minutes. The AUC-CRP was significantly higher in patients receiving placebo versus anakinra both in those with time from PCI to treatment <271 minutes (222.6 [103.9-325.2] vs. 78.4 [44.3-131.2], P < 0.001) and those with time from PCI to treatment ≥271 minute (235.2 [131.4-603.4] vs. 75.5 [38.9-171.9], P < 0.001) (P > 0.05 for interaction). Anakinra significantly reduced the combined endpoint of death or new onset HF in patients with time from PCI to treatment <271 minutes (5 [11%] vs. 9n[36%], log-rank χ 2 5.985, P = 0.014) as well as in patients with time from PCI to drug ≥271 minutes (2n[5%] vs. 7 [23%], log-rank χ 2 3.995, P = 0.046) (P > 0.05 for interaction). IL-1 blockade with anakinra blunts the acute systemic inflammatory response and prevents HF events independent of time-to-treatment. SIGNIFICANCE STATEMENT: In patients with ST segment elevation presenting within 12 hours of pain onset and treated within 12 hours of reperfusion, interleukin-1 blockade with anakinra blunts the acute systemic inflammatory response, a surrogate of interleukin-1 activity, and prevents heart failure events independent of time-to-treatment.

Contribution of hemoglobin concentration to cardiorespiratory fitness in black African American patients with recently decompensated heart failure and reduced ejection fraction.

BACKGROUND: Previous studies have shown that patients with heart failure with reduced ejection fraction (HFrEF) and anemia have reduced peak oxygen consumption (VO2). Black or African American (B-AA) patients have a higher prevalence of anemia and are underrepresented in clinical studies of HFrEF. The aim of this study was to determine the contribution of hemoglobin to peak VO2 in B-AA patients recently hospitalized for acute decompensated HFrEF. METHODS: We analyzed cardiopulmonary exercise testing (CPX) data measured within two weeks of discharge for acute decompensated HF in B-AA patients with HFrEF (left ventricular ejection fraction [LVEF] ≤40%) without severe anemia (Hb<8 g/dL). Blood samples were collected prior to CPX. Data are reported as median [interquartile range] and compared between groups with the Mann-Whitney, Chi-Square, and Spearman's rank tests. RESULTS: We included 81 patients; 27 (33%) women, 57 [27-79] years of age, Body Mass Index of 33 [15-55] kg/m2 and LVEF of 30 [23-36] %. Hemoglobin ranged between 9.1 to 18.1 g/dL (median= 13.3 [11.9-14.5] g/dL); 26 (32%) were considered to have anemia based on a Hb concentration of males <13 g/dL and females <12 g/dL. Peak VO2 was lower in patients with anemia (11.8 [10.0-14.2] vs. 14.1 [10.6-17.0] mL·kg-1·min-1; P=0.010) with a significant correlation between peak VO2 and hemoglobin concentration (R=+0.455; P<0.001). CONCLUSIONS: Anemia is prevalent among B-AA patients with recently decompensated HFrEF and appears to be a significant contributor to reductions 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.

Safety, Tolerability, and Effects of a Single Subcutaneous Administration of SP16 - a SERPIN-like, Small Peptide Agonist of the Low-Density Lipoprotein-like Receptor 1- on the Acute Inflammatory Response in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Modulation of the inflammatory response is a promising therapeutic strategy in acute myocardial infarction. The novel approach is based on the anti-inflammatory and cytoprotective properties mediated by the engagement of the low-density lipoprotein‒related protein 1 (LRP1) receptor. SERPIN peptide 16 (SP16) is a synthetic, selective LRP1 agonist. We herein present the results of a study with a single subcutaneous administration of SP16 in 10 patients with STEMI, to appraise its safety and tolerability and explore the effects on the acute inflammatory response, infarct size, and cardiac function. METHODS: Ten patients with ST-segment elevation myocardial infarction (STEMI) were enrolled within 12 hours of symptoms onset and 6 hours of percutaneous coronary intervention in a single-center, single-arm, open-label study of a single subcutaneous administration of SP16 (0.2 mg/kg). Serial clinical biomarkers and echocardiography data were collected up to 12 months. The data are presented separately for the treatment group and compared with historical controls from a placebo-treated arm in a recently completed clinical trial (N = 28) with similar enrollment criteria. RESULTS: All ten patients with STEMI received subcutaneous administration of SP16, 381 [272-478] minutes after percutaneous coronary intervention, without any treatment-related adverse events. The area under the curve for C-reactive protein was 133 [46-528] mg·d/L in the SP16-treated group versus 286 [141-581] mg·d/L in the historical placebo-treated group ( P = 0.161). The area under the curve for creatine kinase-myocardial band was 1432 [675-3089] ng·d/mL in the SP16-treated group versus 2367 [830-4750] ng·d/mL in the historical placebo-treated patients ( P = 0.428). Left ventricular ejection fraction was 46% [39-54] at baseline and 51% [46-58] at 1 year follow-up in SP16-treated patients (interval change 5% [-0.3% to +9%] P = 0.05) and 44% [38%-56%] at baseline and 53% [43%-59%] at 1 year follow-up in historical placebo-treated patients (interval change 3% [-5% to 10%], P = 0.305). CONCLUSION: A single subcutaneous administration of SP16, a synthetic targeted LRP1 agonist, was safe and well-tolerated in patients with STEMI. A trend toward reduction in the inflammatory response and infarct size with SP16 was noted; however, the sample size for this study was not based on formal statistical criteria. More extensive studies are planned to determine the clinical efficacy of SP16 in STEMI.NCT: NCT04225533.

Rationale and design of interleukin-1 blockade in recently decompensated heart failure (REDHART2): a randomized, double blind, placebo controlled, single center, phase 2 study.

BACKGROUND: Heart failure (HF) is a global leading cause of mortality despite implementation of guideline directed therapy which warrants a need for novel treatment strategies. Proof-of-concept clinical trials of anakinra, a recombinant human Interleukin-1 (IL-1) receptor antagonist, have shown promising results in patients with HF. METHOD: We designed a single center, randomized, placebo controlled, double-blind phase II randomized clinical trial. One hundred and two adult patients hospitalized within 2 weeks of discharge due to acute decompensated HF with reduced ejection fraction (HFrEF) and systemic inflammation (high sensitivity of C-reactive protein > 2 mg/L) will be randomized in 2:1 ratio to receive anakinra or placebo for 24 weeks. The primary objective is to determine the effect of anakinra on peak oxygen consumption (VO2) measured at cardiopulmonary exercise testing (CPX) after 24 weeks of treatment, with placebo-corrected changes in peak VO2 at CPX after 24 weeks (or longest available follow up). Secondary exploratory endpoints will assess the effects of anakinra on additional CPX parameters, structural and functional echocardiographic data, noninvasive hemodynamic, quality of life questionnaires, biomarkers, and HF outcomes. DISCUSSION: The current trial will assess the effects of IL-1 blockade with anakinra for 24 weeks on cardiorespiratory fitness in patients with recent hospitalization due to acute decompensated HFrEF. TRIAL REGISTRATION: The trial was registered prospectively with ClinicalTrials.gov on Jan 8, 2019, identifier NCT03797001.

Effect of IL-1 Blockade With Anakinra on Heart Failure Outcomes in Patients With Anterior Versus Nonanterior ST Elevation Myocardial Infarction.

ABSTRACT: Patients with ST elevation myocardial infarction (STEMI) are at risk of future heart failure (HF), particularly those with anterior STEMI. Interleukin-1 (IL-1) is a key mediator of the inflammatory response, and its blockade has emerged as a potential therapeutic strategy to prevent HF events. The aim of this analysis was to explore the effects of anakinra, an IL-1 receptor antagonist, on HF outcomes based on anterior versus nonanterior location STEMI and to explore whether this effect is mediated through the amelioration of left ventricular systolic function and cardiac remodeling. We pooled data from 3 early phase randomized clinical trials. The primary end point was a composite of all-cause death and new-onset HF at 1-year follow-up. The left anterior descending coronary artery as culprit vessel was used to identify anterior STEMI. We included 139 patients, 47 (34%) with anterior STEMI and 92 (66%) with nonanterior STEMI. Anakinra significantly reduced the combined end point of death or new-onset HF in patients with anterior STEMI [4 (13%) vs. 7 (42%), log-rank P value = 0.049] and in patients with nonanterior STEMI [3 (6%) vs. 9 (24%), log-rank P value = 0.014]. We found no significant differences comparing anakinra versus placebo in interval changes in left ventricular ejection fraction and volumes in anterior and nonanterior STEMI. In conclusion, anakinra is associated with a reduction of HF events in patients with STEMI, irrespective of anterior or nonanterior location, or of changes in left ventricular ejection fraction or cardiac remodeling.

Effect of interleukin-1 blockade with anakinra on leukocyte count in patients with ST-segment elevation acute myocardial infarction.

Leukocytosis is a common finding in patients with ST elevation myocardial infarction (STEMI) and portends a poor prognosis. Interleukin 1-ß regulates leukopoiesis and pre-clinical studies suggest that anakinra (recombinant human interleukin-1 [IL-1] receptor antagonist) suppresses leukocytosis in myocardial infarction. However, the effect of IL-1 blockade with anakinra on leukocyte count in patients with STEMI is unknown. We reviewed the white blood cell (WBC) and differential count of 99 patients enrolled in a clinical trial of anakinra (n = 64) versus placebo (n = 35) for 14 days after STEMI. A complete blood cell count with differential count were obtained at admission, and after 72 h, 14 days and 3 months. After 72 h from treatment, anakinra compared to placebo led to a statistically significant greater percent reduction in total WBC count (- 35% [- 48 to - 24] vs. - 21% [- 34 to - 10], P = 0.008), absolute neutrophil count (- 48% [- 60 to - 22] vs. - 27% [- 46 to - 5], P = 0.004) and to an increase in absolute eosinophil count (+ 50% [0 to + 100] vs. 0% [- 50 to + 62], P = 0.022). These changes persisted while on treatment at 14 days and were no longer apparent at 3 months after treatment discontinuation. We found that in patients with STEMI IL-1 blockade with anakinra accelerates resolution of leukocytosis and neutrophilia. This modulation may represent one of the mechanisms by which IL-1 blockade improves clinical outcomes.

Early changes in N-terminal pro-brain natriuretic peptide levels predict new-onset heart failure in patients with STEMI.

BACKGROUND: Previous studies suggested that N-terminal pro-brain natriuretic peptide (NT-proBNP) level is a powerful independent predictor of death or heart failure (HF) when measured at admission in patients with chest pain or acute coronary syndrome. Little is known about the role of NT-proBNP level measured during a hospitalization for ST segment elevation myocardial infarction (STEMI) in predicting clinical outcomes. We evaluated the optimal NT-proBNP timing (admission, 72 hours, or delta [Δ] NT-proBNP [72 hours minus admission]) to predict 1-year new-onset HF in STEMI patients. METHODS: We measured NT-proBNP levels at admission and 72 hours in 72 patients with STEMI. HF events were adjudicated and defined as hospitalization for HF or need for new initiation of a loop diuretic at 1-year follow-up. Values are presented as medians and interquartile range or frequencies (%) as appropriate. Cox regression analysis was used to determine predictors of adverse events. A receiver-operative-curve was constructed to identify the discriminative value and optimal cut-off points for NT-proBNP. RESULTS: Patients (age 56 [49-64] years, males 59 [82%]) were followed for a median duration of 365 [180-365] days. HF events were recorded in 9 (12.5%) patients. NT-proBNP values at admission, 72 hours, and ΔNT-proBNP were 89 (26-268) pg/mL, 452 (223-1064) pg/mL, and 283 (68-686) pg/mL, respectively. NT-proBNP at 72 hours and ΔNT-proBNP, but not admission NT-proBNP predicted new-onset HF events at follow-up (P=0.03, P=0.002 and P=0.89, respectively). The optimal area under the curve of 0.771 (95%, CI [0.630-0.912], P= 0.009) and cut-off value of 830 pg/mL (sensitivity 79%; specificity 76%) were found for NT-proBNP at 72 hours. The Kaplan-Meier survival curves for NT-proBNP at 72 hours dichotomized above and below this cut-off value, confirmed NT-proBNP at 72 hours >830 pg/mL as predictive of HF events (log-rank statistic = 8.688, P=0.003). CONCLUSIONS: NT-proBNP level at 72 hours and ΔNT-proBNP (72 hours minus admission), but not at time of admission, predicted HF events in patients following STEMI.

Interleukin-1 blockade with anakinra and heart failure following ST-segment elevation myocardial infarction: results from a pooled analysis of the VCUART clinical trials.

AIMS: ST-segment elevation myocardial infarction (STEMI) is associated with an intense acute inflammatory response and an increased risk of death and heart failure (HF). In this study, we sought to evaluate the effect of anakinra, a recombinant interleukin-1 receptor antagonist, on the incidence of HF. METHODS AND RESULTS: We performed a pooled analysis of three early phase randomized clinical trials. The endpoints included the composite of all-cause death and new-onset HF, and the composite of all-cause death and hospitalization for HF at 1-year follow-up. Safety events, including injection site reaction and serious infections, were also recorded. We analysed 139 patients with STEMI from three separate trials: VCUART (N = 10), VCUART2 (N = 30), and VCUART3 (N = 99). Of these, 84 (60%) patients were randomized to anakinra and 55 (40%) to placebo. Treatment with anakinra significantly reduced the incidence of all-cause death or new-onset HF (7 [8.2%] vs. 16 [29.1%], log-rank P = 0.002) and of all-cause death or HF hospitalization (0 [0] vs. 5 [9.1%], log-rank P = 0.007). Patients treated with anakinra had significantly higher injection site reactions (19 [22.6%] vs. 3 [5.5%], P = 0.016) without a significant difference in the incidence of serious infections (11 [13.1%] vs. 7 [12.7%], P = 0.435). Treatment with anakinra significantly reduced the area under the curve for high-sensitivity C-reactive protein between baseline and 14 days (75.48 [41.7-147.47] vs. 222.82 [117.22-399.28] mg day/L, P < 0.001). CONCLUSION: IL-1 blockade with anakinra for 14 days in patients with STEMI reduces the incidence of new-onset HF or hospitalization for HF at 1 year following STEMI.

Preservation of Cardiac Reserve and Cardiorespiratory Fitness in Patients With Acute De Novo Versus Acute on Chronic Heart Failure With Reduced Ejection Fraction.

There is limited understanding on the potential differences in the pathophysiology between de novo heart failure with reduced ejection fraction (HFrEF) and acute on chronic HFrEF. The aim of this study was to assess differences in cardiorespiratory fitness (CRF) parameters between de novo heart failure and acute on chronic HFrEF using cardiopulmonary exercise testing (CPX). We retrospectively analyzed CPX data measured within 2 weeks of discharge following acute hospitalization for HFrEF. Data are reported as median and interquartile range or frequency and percentage (%). We included 102 patients: 32 (31%) women, 81 (79%) black, 57 (51 to 64) years of age, BMI of 34 (29 to 39) Kg/m2. Of these, 26 (25%) had de novo HFrEF and 76 (75%) had acute on chronic HFrEF. When compared with acute on chronic, patients with de novo HFrEF had a significantly higher peak oxygen consumption (VO2) (16.5 [12.2 to 19.4] vs 12.8 [10.1 to 15.3] ml·kg-1·min-1, p <0.001), %-predicted peak VO2 (58% [51 to 75] vs 49% [42 to 59]) p = 0.012), peak heart rate (134 [117 to 147] vs 117 [104 to 136] beats/min, p = 0.004), peak oxygen pulse (12.2 [10.5 to 15.5] vs 9.9 [8.0 to 13.1] ml/beat, p = 0.022) and circulatory power (2,823 [1,973 to 3,299] vs 1,902 [1,372 to 2,512] mm Hg·ml·kg-1·min-1, p = 0.002). No significant difference in resting left ventricular ejection fraction was found between groups. In conclusion, patients with de novo HFrEF have better CRF parameters than those with acute on chronic HFrEF. These differences are not explained by resting left ventricular systolic function but may be related to greater preservation in cardiac reserve during exercise in de novo HFrEF patients.

Phase 1B, Randomized, Double-Blinded, Dose Escalation, Single-Center, Repeat Dose Safety and Pharmacodynamics Study of the Oral NLRP3 Inhibitor Dapansutrile in Subjects With NYHA II-III Systolic Heart Failure.

ABSTRACT: The NLRP3 inflammasome has been implicated in the development and progression of heart failure. The aim of this study was to determine the safety of an oral inhibitor of the NLRP3 inflammasome, dapansutrile (OLT1177), in patients with heart failure and reduced ejection fraction (HFrEF). This was a phase 1B, randomized, double-blind, dose escalation, single-center, repeat dose safety and pharmacodynamics study of dapansutrile in stable patients with HFrEF (New York Heart Association Class II-III). Subjects were randomized to treatment with dapansutrile for up to 14 days at a ratio of 4:1 into 1 of 3 sequential ascending dose cohorts (500, 1000, or 2000 mg) each including 10 patients. Subjects underwent clinical assessment, biomarker determination, transthoracic echocardiogram, and maximal cardiopulmonary exercise testing at baseline, day 14, and day 28 to ascertain changes in clinical status. Placebo cases (N = 2 per cohort) were used as a decoy to reduce bias and not for statistical comparisons. Thirty participants (20 men) were treated for 13 (12-14) days. No serious adverse events during the study were recorded. All clinical or laboratory parameters at day 14 compared with baseline suggested clinical stability without significant within-group differences in the dapansutrile-pooled group or the 3 dapansutrile cohorts. Improvements in left ventricular EF [from 31.5% (27.5-39) to 36.5% (27.5-45), P = 0.039] and in exercise time [from 570 (399.5-627) to 616 (446.5-688) seconds, P = 0.039] were seen in the dapansutrile 2000 mg cohort. Treatment with dapansutrile for 14 days was safe and well tolerated in patients with stable HFrEF.

Sepsis-Induced Cardiomyopathy: a Comprehensive Review.

PURPOSE OF REVIEW: To briefly review epidemiology and pathophysiology of SICM and provide a more extensive review of the data on diagnostic and management strategies. RECENT FINDINGS: SICM is likely underdiagnosed and that has mortality implications. Current evidence supports speckle tracking echocardiography to identify decreased contractility irrespective of left ventricular ejection fraction for the diagnosis of SICM. There continues to be a dearth of large clinical trials evaluating the treatment of SICM and current consensus focuses on supportive measures such as vasopressors and inotropes. Sepsis is a significant cause of mortality, and sepsis-induced cardiomyopathy has both prognostic and management implications for these patients. Individualized work-up and management of these patients is crucial to improving outcomes.

High-Sensitivity Troponins in Cardiovascular Disease.

Each new troponin assay generation is more sensitive, with recent generation high-sensitivity troponin (hsTn) assays able to detect minimal myocardial injury, even in asymptomatic patients. PURPOSE OF THE REVIEW: We reviewed recent information on the use of hsTn assays for assessing acute and chronic cardiovascular disease. RECENT FINDINGS: hsTn is used for early emergency department diagnosis, accelerating early discharge with a low event rate comparable if not better than current strategies. Low levels of hsTn are detected in a variety of chronic cardiac and non-cardiac conditions, non-disease conditions including heart failure, chemotherapy, and others. These elevations identify a population at increased risk for long-term cardiovascular events. However, management strategies remain unclear. hsTn has substantial advantages in emergency department use. They hold promise for identifying subclinical cardiac disease, with the potential for earlier intervention with the possibility of decreasing disease progression. Additional studies, however, are needed to determine if this strategy will lead to improved outcomes.

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). hsCRP area under the curve was significantly lower in patients receiving anakinra versus placebo (median, 67 [interquartile range, 39-120] versus 214 [interquartile range, 131-394] mg·day/L; P<0.001), without significant differences between the anakinra arms. No significant differences were found between anakinra and placebo groups in the interval changes in left ventricular end-systolic volume (median, 1.4 [interquartile range, -9.8 to 9.8] versus -3.9 [interquartile range, -15.4 to 1.4] mL; P=0.21) or left ventricular ejection fraction (median, 3.9% [interquartile range, -1.6% to 10.2%] versus 2.7% [interquartile range, -1.8% to 9.3%]; P=0.61) at 12 months. The incidence of death or new-onset heart failure or of death and hospitalization for heart failure was significantly lower with anakinra versus placebo (9.4% versus 25.7% [P=0.046] and 0% versus 11.4% [P=0.011], respectively), without difference between the anakinra arms. The incidence of serious infection was not different between anakinra and placebo groups (14% versus 14%; P=0.98). Injection site reactions occurred more frequently in patients receiving anakinra (22%) versus placebo (3%; P=0.016). Conclusions In patients presenting with ST-segment-elevation myocardial infarction, interleukin-1 blockade with anakinra significantly reduces the systemic inflammatory response compared with placebo. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01950299.

Intravenous Fluid Therapy Is Associated with a Reduced Incidence of Contrast-Induced Nephropathy but not with a Reduced Long-Term Incidence of Renal Dysfunction After Cardiac Catheterization.

BACKGROUND: Intravenous fluid (IVF) administration for the prevention of contrast-induced nephropathy (CIN) is considered standard of care, but the effect of IVF therapy on longer-term outcomes after radiocontrast dye administration is not well known. METHODS AND RESULTS: We studied 4367 patients undergoing coronary and peripheral angiography and intervention at a veterans' administration medical center. 2653 patients (61%) received IVF prior to the procedure and 1714 (39%) did not. Of the 4367 subjects 1962 (45%) had repeat creatinine values at 72 h and 3100 (70%) had repeat creatinine values at 3 months. CIN at 72 h occurred in 68 (6.7%) patients in the IVF group and in 87 patients (9.8%) in the group receiving no IVF (odds ratio [OR] 0.97; 95% confidence interval [CI] 0.94-0.99; p = 0.004). At 3 months, renal dysfunction was seen in 224 (11.5%) patients of the IVF group versus 152 (13.1%) of the group receiving no IVF (OR 0.98, CI 0.96-1.01; p = 0.18). In adjusted analyses using a propensity score, IVF therapy was associated with a significant reduction in CIN occurrence at 72 h (OR = 0.97, (95% CI 0.94-0.99, p = 0.01) but was not associated with a change in the incidence of renal dysfunction at 3 months (OR 0.98, 95% CI 0.96-1.01. p = 0.18). CONCLUSION: In this cohort of US veterans, IVF administration was associated with a decreased incidence of CIN at 72 h but was not associated with a decreased incidence of renal dysfunction at 3 months.