The Short Physical Performance Battery Score Is Associated With Quality Of Life In Black And Hispanic Outpatients With Stable Congestive Heart Failure
HFSA ePoster Library. Valente C. 09/10/21; 343326; 105
Christopher Valente
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Abstract
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Introduction: Immune Check Point Inhibitors (ICIs) have revolutionized the immunotherapy improving the poor prognosis for patients with cancer ICIs are monoclonal antibodies which block the cytotoxic T-lymphocyte-associated antigen 4 (αCTLA-4) or programmed cell death protein 1 (αPD-1) principally, releasing the immune system activation against cancer cells Several immune-related adverse events (irAEs) have been described for ICIs, mainly when they are used as combination therapy (αCTLA-4 + αPD-1) Cardiac irAEs including mainly myocarditis can become life-threatening and the exact mechanism is unknow Here, we hypothesized that a previous damage or insult in the heart is necessary for autoantigens release, inducing myocarditis
Methods: An angiotensin II-induced heart failure (HF) model was used to generate a chronic injury in mice In parallel to the development of the HF model, combination therapy of ICIs (αCTLA-4 + αPD-1) was applied weekly for 4 weeks (HF + ICIs) Control groups included ICIs administrated to healthy mice (CTRL+ ICIs), HF mice, and healthy mice (CTRL) After 4 weeks, an analysis was carried out regarding mice survival and immune cells recruitment to the heart (myocarditis score) Additionally, heart tissue was analyzed for remodeling markers (collagen and TGF-β), inflammatory cytokines (ILF-1β, IL-6 and TNF-α), and immunohistochemical assays (IHQ) for infiltrate characterization
Results: The CTRL + ICIs group did not show statistically significant differences in survival, infiltrating cells (myocarditis score), and local inflammation compared to CTRL group Similar results were observed for the HF group However, when mice were subjected to the HF and ICIs therapy (HF + ICIs), the survival of mice was diminished to 50%, compared to 83% of the HF group; in the former it was observed lymphoid cells infiltration, characterized mainly by T CD8+ cells TNF-α and BNP were 2-fold upregulated in HF +ICIs group as compared with the other experimental groups The autoantibodies against heart proteins were determined by ELISA and a significant increase was observed only in the HF + ICIs group, we observed twice as autoantibodies compared with the control groups
Conclusion: We found that a chronic damage is necessary to induce damage associated with ICIs administration, leading to development of myocarditis for the animals that survived full therapy It is possible the existence of autoimmune reactions against heart with the increase of autoantibody-production after ICIs treatment
Methods: An angiotensin II-induced heart failure (HF) model was used to generate a chronic injury in mice In parallel to the development of the HF model, combination therapy of ICIs (αCTLA-4 + αPD-1) was applied weekly for 4 weeks (HF + ICIs) Control groups included ICIs administrated to healthy mice (CTRL+ ICIs), HF mice, and healthy mice (CTRL) After 4 weeks, an analysis was carried out regarding mice survival and immune cells recruitment to the heart (myocarditis score) Additionally, heart tissue was analyzed for remodeling markers (collagen and TGF-β), inflammatory cytokines (ILF-1β, IL-6 and TNF-α), and immunohistochemical assays (IHQ) for infiltrate characterization
Results: The CTRL + ICIs group did not show statistically significant differences in survival, infiltrating cells (myocarditis score), and local inflammation compared to CTRL group Similar results were observed for the HF group However, when mice were subjected to the HF and ICIs therapy (HF + ICIs), the survival of mice was diminished to 50%, compared to 83% of the HF group; in the former it was observed lymphoid cells infiltration, characterized mainly by T CD8+ cells TNF-α and BNP were 2-fold upregulated in HF +ICIs group as compared with the other experimental groups The autoantibodies against heart proteins were determined by ELISA and a significant increase was observed only in the HF + ICIs group, we observed twice as autoantibodies compared with the control groups
Conclusion: We found that a chronic damage is necessary to induce damage associated with ICIs administration, leading to development of myocarditis for the animals that survived full therapy It is possible the existence of autoimmune reactions against heart with the increase of autoantibody-production after ICIs treatment
Introduction: Immune Check Point Inhibitors (ICIs) have revolutionized the immunotherapy improving the poor prognosis for patients with cancer ICIs are monoclonal antibodies which block the cytotoxic T-lymphocyte-associated antigen 4 (αCTLA-4) or programmed cell death protein 1 (αPD-1) principally, releasing the immune system activation against cancer cells Several immune-related adverse events (irAEs) have been described for ICIs, mainly when they are used as combination therapy (αCTLA-4 + αPD-1) Cardiac irAEs including mainly myocarditis can become life-threatening and the exact mechanism is unknow Here, we hypothesized that a previous damage or insult in the heart is necessary for autoantigens release, inducing myocarditis
Methods: An angiotensin II-induced heart failure (HF) model was used to generate a chronic injury in mice In parallel to the development of the HF model, combination therapy of ICIs (αCTLA-4 + αPD-1) was applied weekly for 4 weeks (HF + ICIs) Control groups included ICIs administrated to healthy mice (CTRL+ ICIs), HF mice, and healthy mice (CTRL) After 4 weeks, an analysis was carried out regarding mice survival and immune cells recruitment to the heart (myocarditis score) Additionally, heart tissue was analyzed for remodeling markers (collagen and TGF-β), inflammatory cytokines (ILF-1β, IL-6 and TNF-α), and immunohistochemical assays (IHQ) for infiltrate characterization
Results: The CTRL + ICIs group did not show statistically significant differences in survival, infiltrating cells (myocarditis score), and local inflammation compared to CTRL group Similar results were observed for the HF group However, when mice were subjected to the HF and ICIs therapy (HF + ICIs), the survival of mice was diminished to 50%, compared to 83% of the HF group; in the former it was observed lymphoid cells infiltration, characterized mainly by T CD8+ cells TNF-α and BNP were 2-fold upregulated in HF +ICIs group as compared with the other experimental groups The autoantibodies against heart proteins were determined by ELISA and a significant increase was observed only in the HF + ICIs group, we observed twice as autoantibodies compared with the control groups
Conclusion: We found that a chronic damage is necessary to induce damage associated with ICIs administration, leading to development of myocarditis for the animals that survived full therapy It is possible the existence of autoimmune reactions against heart with the increase of autoantibody-production after ICIs treatment
Methods: An angiotensin II-induced heart failure (HF) model was used to generate a chronic injury in mice In parallel to the development of the HF model, combination therapy of ICIs (αCTLA-4 + αPD-1) was applied weekly for 4 weeks (HF + ICIs) Control groups included ICIs administrated to healthy mice (CTRL+ ICIs), HF mice, and healthy mice (CTRL) After 4 weeks, an analysis was carried out regarding mice survival and immune cells recruitment to the heart (myocarditis score) Additionally, heart tissue was analyzed for remodeling markers (collagen and TGF-β), inflammatory cytokines (ILF-1β, IL-6 and TNF-α), and immunohistochemical assays (IHQ) for infiltrate characterization
Results: The CTRL + ICIs group did not show statistically significant differences in survival, infiltrating cells (myocarditis score), and local inflammation compared to CTRL group Similar results were observed for the HF group However, when mice were subjected to the HF and ICIs therapy (HF + ICIs), the survival of mice was diminished to 50%, compared to 83% of the HF group; in the former it was observed lymphoid cells infiltration, characterized mainly by T CD8+ cells TNF-α and BNP were 2-fold upregulated in HF +ICIs group as compared with the other experimental groups The autoantibodies against heart proteins were determined by ELISA and a significant increase was observed only in the HF + ICIs group, we observed twice as autoantibodies compared with the control groups
Conclusion: We found that a chronic damage is necessary to induce damage associated with ICIs administration, leading to development of myocarditis for the animals that survived full therapy It is possible the existence of autoimmune reactions against heart with the increase of autoantibody-production after ICIs treatment
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