Common Genetic Variants and Risk of Ischemic Heart Failure: An Evaluation of a Negative Genetic Study

Cardiology ◽  
2015 ◽  
Vol 130 (3) ◽  
pp. 167-168
Author(s):  
Reza Jabbari ◽  
Stig Haunsø ◽  
Jacob Tfelt-Hansen
Keyword(s):  
Heart Failure ◽  
Genetic Study ◽  
Genetic Variants ◽  
Ischemic Heart ◽  
Ischemic Heart Failure ◽  
Common Genetic Variants

scholarly journals Genetic Variants Are Not Associated with Outcome in Patients with Coronary Artery Disease and Left Ventricular Dysfunction: Results of the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) Trials

Cardiology ◽  
2015 ◽  
Vol 130 (2) ◽  
pp. 69-81 ◽  
Author(s):  
Arthur M. Feldman ◽  
Lilin She ◽  
Dennis M. McNamara ◽  
Douglas L. Mann ◽  
Michael R. Bristow ◽  
...  
Keyword(s):  
Heart Failure ◽  
Coronary Artery ◽  
Surgical Treatment ◽  
Genetic Variants ◽  
Receptor Gene ◽  
Left Ventricular ◽  
Ischemic Heart ◽  
Ischemic Heart Failure ◽  
Increased Risk ◽  
Left Ventricular Reconstruction

Objectives and Background: We evaluated the ability of 23 genetic variants to provide prognostic information in patients enrolled in the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Methods: Patients assigned to STICH Hypothesis 1 were randomized to medical therapy with or without coronary artery bypass grafting (CABG). Those assigned to STICH Hypothesis 2 were randomized to CABG or CABG with left ventricular reconstruction. Results: In patients assigned to STICH Hypothesis 2 (n = 714), no genetic variant met the prespecified Bonferroni-adjusted threshold for statistical significance (p < 0.002); however, several variants met nominal prognostic significance: variants in the β2-adrenergic receptor gene (β2-AR Gln27Glu) and in the A1-adenosine receptor gene (A1-717 T/G) were associated with an increased risk of a subject dying or being hospitalized for a cardiac problem (p = 0.027 and 0.031, respectively). These relationships remained nominally significant even after multivariable adjustment for prognostic clinical variables. However, none of the 23 genetic variants influenced all-cause mortality or the combination of death or cardiovascular hospitalization in the STICH Hypothesis 1 population (n = 532) by either univariate or multivariable analysis. Conclusion: We were unable to identify the predictive genotypes in optimally treated patients in these two ischemic heart failure populations.

scholarly journals ACE Inhibition Modulates Myeloid Hematopoiesis after Acute Myocardial Infarction and Reduces Cardiac and Vascular Inflammation in Ischemic Heart Failure

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 396
Author(s):  
Wolf-Stephan Rudi ◽  
Michael Molitor ◽  
Venkata Garlapati ◽  
Stefanie Finger ◽  
Johannes Wild ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Bone Marrow ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Vascular Inflammation ◽  
Ace Inhibition ◽  
Left Ventricular ◽  
Ischemic Heart ◽  
Ischemic Heart Failure

Aims: Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a cornerstone of drug therapy after myocardial infarction (MI) and improve left ventricular function and survival. We aimed to elucidate the impact of early treatment with the ACE inhibitor ramipril on the hematopoietic response after MI, as well as on the chronic systemic and vascular inflammation. Methods and Results: In a mouse model of MI, induced by permanent ligation of the left anterior descending artery, immediate initiation of treatment with ramipril (10 mg/k/d via drinking water) reduced cardiac inflammation and the number of circulating inflammatory monocytes, whereas left ventricular function was not altered significantly, respectively. This effect was accompanied by enhanced retention of hematopoietic stem cells, Lin−Sca1−c-Kit+CD34+CD16/32+ granulocyte–macrophage progenitors (GMP) and Lin−Sca1−c-Kit+CD150−CD48− multipotent progenitors (MPP) in the bone marrow, with an upregulation of the niche factors Angiopoetin 1 and Kitl at 7 d post MI. Long-term ACE inhibition for 28 d limited vascular inflammation, particularly the infiltration of Ly6Chigh monocytes/macrophages, and reduced superoxide formation, resulting in improved endothelial function in mice with ischemic heart failure. Conclusion: ACE inhibition modulates the myeloid inflammatory response after MI due to the retention of myeloid precursor cells in their bone marrow reservoir. This results in a reduction in cardiac and vascular inflammation with improvement in survival after MI.

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