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

Trankle, Cory R.; Canada, Justin M.; Cei, Laura; Abouzaki, Nayef; Oddi‐Erdle, Claudia; Kadariya, Dinesh; Christopher, Sanah; Viscusi, Michele Mattia; Buono, Marco Giuseppe Del; Kontos, Michael C.; Arena, Ross; Tassell, Benjamin Van; Abbate, Antonio

doi:10.1016/j.amjcard.2018.07.002

Cited by 59 publications

(31 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The link between inflammation and heart failure is discussed for more than 2 decades [26,27]. In accordance to our findings, a recent subgroup analysis of the CANTOS trial described improved outcomes in patients with CHD and heart failure after anti-inflammatory-therapy with Canakinumab [28]. In the meantime, there is numerous evidences suggesting that activation of the innate and adaptive immune system plays a critical role in pathogenesis and maintenance of heart failure, various cytokines and chemokines were described as supportive evidence in this content [29,30].…”

Section: Discussionsupporting

confidence: 89%

Residual inflammatory risk in coronary heart disease: incidence of elevated high-sensitive CRP in a real-world cohort

et al. 2019

View full text Add to dashboard Cite

Background Inflammation drives atherosclerosis and its complications. Anti-inflammatory therapy with interleukin 1 beta (IL-1β) antibody reduces cardiovascular events in patients with elevated high-sensitive C-reactive protein (hsCRP). This study aims to identify the share of patients with coronary heart disease (CHD) and residual inflammation who may benefit from anti-inflammatory therapy. Methods hsCRP and low-density lipoprotein (LDL) levels were determined in 2741 all-comers admitted to the cardiological ward of our tertiary referral hospital between June 2016 and June 2018. Patients without CHD, with acute coronary syndrome, chronic or recurrent systemic infection, use of immunosuppressant or anti-inflammatory agents, chronic inflammatory diseases, chemotherapy, terminal organ failure, traumatic injury and pregnancy were excluded. Results 856 patients with stable CHD were included. 42.7% of those had elevated hsCRP ≥ 2 mg/l. Within the group of patients with LDL-cholesterol < 70 mg/dl, 30.9% shared increased hsCRP indicating residual inflammation. After multivariate adjusted backward selection elevated Lipoprotein (a) (OR 1.61, p = 0.048), elevated proBNP (OR 2.57, p < 0.0001), smoking (OR 1.70, p = 0.022), and obesity (OR 2.28, p = 0.007) were associated with elevated hsCRP. In contrast, the use of ezetimibe was associated with normal hsCRP (OR 0.51, p = 0.014). In the subgroup of patients with on-target LDLcholesterol < 70 mg/dl, backward selection identified elevated proBNP (OR 3.49, p = 0.007) as independent predictor of elevated hsCRP in patients with LDL-cholesterol < 70 mg/dl. Conclusion One-third of all-comers patients with CHD showed increased levels of hsCRP despite a LDL-cholesterol < 70 mg/ dl potentially qualifying for an anti-inflammatory therapy. Elevated proBNP is an independent risk factor for hsCRP elevation.

show abstract

Section: Discussionsupporting

confidence: 89%

Residual inflammatory risk in coronary heart disease: incidence of elevated high-sensitive CRP in a real-world cohort

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Recent results from the CANTOS study showed that anti-inflammatory therapy with canakinumab, a therapeutic monoclonal antibody targeting IL-1β, resulted in reduced rate of recurrent atherosclerotic cardiovascular events in post-infarct patients with CRP ≥ 2 mg/L, especially in patients with greater CRP reduction, even in the absence of lipid lowering [39,40]. The findings of small prespecified secondary analysis of CANTOS may also indicate a positive impact of canakinumab on long-term LVEF in patients with post-infarct systolic HF [41]. CANTOS also provided proof of concept evidence in humans that modulation of the IL-6 signaling pathway-at least with canakinumab-is associated with reduced cardiovascular event rates [42].…”

Section: Discussionmentioning

confidence: 97%

Enhanced Inflammation is a Marker for Risk of Post-Infarct Ventricular Dysfunction and Heart Failure

Świątkiewicz

Magielski

Kubica

et al. 2020

IJMS

View full text Add to dashboard Cite

Acute ST-segment elevation myocardial infarction (STEMI) activates inflammation that can contribute to left ventricular systolic dysfunction (LVSD) and heart failure (HF). The objective of this study was to examine whether high-sensitivity C-reactive protein (CRP) concentration is predictive of long-term post-infarct LVSD and HF. In 204 patients with a first STEMI, CRP was measured at hospital admission, 24 h (CRP24), discharge (CRPDC), and 1 month after discharge (CRP1M). LVSD at 6 months after discharge (LVSD6M) and hospitalization for HF in long-term multi-year follow-up were prospectively evaluated. LVSD6M occurred in 17.6% of patients. HF hospitalization within a median follow-up of 5.6 years occurred in 45.7% of patients with LVSD6M vs. 4.9% without LVSD6M (p < 0.0001). Compared to patients without LVSD6M, the patients with LVSD6M had higher CRP24 and CRPDC and persistent CRP1M ≥ 2 mg/L. CRP levels were also higher in patients in whom LVSD persisted at 6 months (51% of all patients who had LVSD at discharge upon index STEMI) vs. patients in whom LVSD resolved. In multivariable analysis, CRP24 ≥ 19.67 mg/L improved the prediction of LVSD6M with an increased odds ratio of 1.47 (p < 0.01). Patients with LVSD6M who developed HF had the highest CRP during index STEMI. Elevated CRP concentration during STEMI can serve as a synergistic marker for risk of long-term LVSD and HF.

show abstract

“…Gaining a better understanding of the relationship between CRP and cardiac function in patients who have undergone radiation therapy could potentially help to optimize treatment, and ideally, serve as therapeutic targets to minimize long-term unwanted cardiac side-effects. IL-1 blockers are being studied for the prevention and treatment of heart failure, showing a promising safety and efficacy profile [30][31][32][33][34][35] thus introducing the possibility of future clinical trials investigating IL-1 blockade to treat patients at risk for radiation-induced heart failure. Abbreviations Δ: Delta; E: Early transmitral velocity; e': Early diastolic mitral annular velocity; Gy: Gray; HF: Heart failure; hsCRP: High-sensitivity C-reactive protein; IL-1: Interleukin-1; IQR: Interquartile range; LVEF: Left-ventricular ejection fraction; LVOT VTI CO: Left-ventricular outflow tract velocity time integral cardiac output; MCRD: Mean cardiac radiation dose Fig.…”

Section: Discussionmentioning

confidence: 99%

Increased C-reactive protein is associated with the severity of thoracic radiotherapy-induced cardiomyopathy

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background: Irradiation of the heart during cancer radiotherapy is associated with a dose-dependent risk of heart failure. Animal studies have demonstrated that irradiation leads to an inflammatory response within the heart as well as a reduction in cardiac reserve. In the current study we aimed to evaluate whether inflammatory biomarkers correlated with changes in cardiac function and reserve after radiotherapy for breast or lung cancer. Methods and results: We studied 25 subjects with a history of breast or lung cancer without a prior diagnosis of cardiovascular disease or heart failure, 1.8 years [0.4-3.6] post-radiotherapy involving at least 5 Gray (Gy) to at least 10% of the heart. High-sensitivity C-reactive protein (CRP) was abnormal (≥2 mg/L) in 16 (64%) subjects. Cardiac function and reserve was measured with Doppler echocardiography before and after exercise and defined as leftventricular ejection fraction (LVEF), early diastolic mitral annulus velocity (e'), and increase in LV outflow tract velocity time integral cardiac output (cardiac reserve) with exercise. Subjects with abnormal CRP had significantly lower LVEF (51 [44-59] % vs 61 [52-64] %, P = 0.039), lower e' (7.4 [6.6-7.9] cm/sec vs 9.9 [8.3-12.0] cm/sec, P = 0.010), and smaller cardiac reserve (+ 1.5 [1.2-1.7] L/min vs + 1.9 [1.7-2.2] L/min, P = 0.024). Conclusion: Elevated systemic inflammation is associated with impaired left-ventricular systolic and diastolic function both at rest and during exercise in subjects who have received radiotherapy with significant incidental heart dose for the treatment of cancer.

show abstract

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

Cited by 59 publications

References 15 publications

Residual inflammatory risk in coronary heart disease: incidence of elevated high-sensitive CRP in a real-world cohort

Residual inflammatory risk in coronary heart disease: incidence of elevated high-sensitive CRP in a real-world cohort

Enhanced Inflammation is a Marker for Risk of Post-Infarct Ventricular Dysfunction and Heart Failure

Increased C-reactive protein is associated with the severity of thoracic radiotherapy-induced cardiomyopathy

Contact Info

Product

Resources

About