Randomized placebo controlled trial evaluating the safety and efficacy of single low-dose intracoronary insulin-like growth factor following percutaneous coronary intervention in acute myocardial infarction (RESUS-AMI)

Caplice, Noel M.; DeVoe, Mary C.; Choi, Jacqueline J.; Dahly, Darren; Murphy, Terry; Spitzer, Ernest; Geuns, Robert van; Maher, Michael M.; Tuite, David; Kerins, David M.; Ali, Mohammed T.; Kalyar, Imtiaz; Fahy, Eoin; Khider, Wisam; Kelly, Peter; Kearney, Peter; Curtin, Ronan J.; O’Shea, Catherine; Vaughan, Carl J.; Eustace, Joseph A.; McFadden, Eugène

doi:10.1016/j.ahj.2018.03.018

Cited by 16 publications

(14 citation statements)

References 24 publications

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“…In clinical studies, substitution with IGF1 was often followed by resolution of hypertension and improvement of the intima-media thickness of the arterial vessel wall [41–43]. Importantly, IGF1 has an immediate effect on repairing tissue damage after acute ischemic cerebral and myocardial injury [39, 44, 45]. In RA, the factors enhancing IGF1 levels attracted less attention.…”

Section: Discussionmentioning

confidence: 99%

Low serum IGF1 is associated with hypertension and predicts early cardiovascular events in women with rheumatoid arthritis

Erlandsson

Lyngfelt

Åberg

et al. 2019

BMC Med

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Objectives Since low insulin-like growth factor (IGF) 1 is often linked to inflammation, we analyze whether serum levels of IGF1 are associated with cardiovascular disease (CVD) in rheumatoid arthritis (RA) in a longitudinal observational study. Methods A CVD risk was estimated (eCVR) in 184 female RA patients (mean age 52 years) and in 132 female patients after ischemic stroke (mean age 56 years) with no rheumatic disease, using the Framingham algorithm. The median level of IGF1 divided the cohorts in IGF1 high and IGF1 low groups. A 5-year prospective follow-up for new CVD events was completed in all RA patients. The Mantel-Cox analysis and event-free survival curves were prepared. Unsupervised clustering of proteins within the IGF1 signaling pathway was employed to identify their association with eCVR. Results Low IGF1 resulted in a higher eCVR in RA patients (7.2% and 3.3%, p = 0.0063) and in stroke (9.3% and 7.1%, p = 0.033). RA had higher rate for new CVD events at prospective follow-up (OR 4.96, p = 0.028). Hypertension was the major risk factor associated with low IGF1 in RA and stroke. In hypertension, IGF1 was no longer responsible for intracellular activation and lost its correlation to IRS1/2 adaptor proteins. The clustering analysis confirmed that combination of low IGF1 and IRS1/2 with high IL6, insulin, and glucose predisposed to high eCVR and emphasized the functional role of serum IGF1. Conclusions Low serum IGF1 precedes and predicts development of early CVD events in female RA patients. Hypertension and aberrant IGF1 receptor signaling are highlighted as the important contributors to IGF1-related CVD events.

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Section: Discussionmentioning

confidence: 99%

Low serum IGF1 is associated with hypertension and predicts early cardiovascular events in women with rheumatoid arthritis

Erlandsson

Lyngfelt

Åberg

et al. 2019

BMC Med

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“…The pathophysiological process of cardiac remodelling starts immediately after an acute MI and, if not attenuated or reversed through effective interventions, results in poor clinical prognosis, including ventricular arrhythmias, heart failure and subsequent cardiovascular mortality 2,3 . Moreover, once cardiac remodelling manifests with clinical heart failure symptoms, standard pharmacotherapies including angiotensin receptor‐neprilysin inhibitor, natriuretic peptides, angiotensin‐converting enzyme inhibitors, or β‐blockers have limited effect on reversing the remodelling and/or improving the clinical symptoms 4 …”

Section: Introductionmentioning

confidence: 99%

In‐depth proteomics approach reveals novel biomarkers of cardiac remodelling after myocardial infarction: An exploratory analysis

Mao

Liang

Chen

et al. 2020

J Cellular Molecular Medi

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Cardiac remodelling following myocardial infarction (MI) is a maladaptive change associated with progressive heart failure and compromises long‐term clinical outcome. A substantial proportion of patients afflicted by MI still develop adverse outcomes associated with cardiac remodelling. Therefore, it is crucial to identify biomarkers for the early prediction of cardiac remodelling. An in‐depth proteomics approach, including both semi‐quantitative and quantitative antibody arrays, was used to identify circulating biomarkers that may be associated with detrimental cardiac remodelling. Furthermore, statistical correlation analysis was performed between the candidate biomarkers and clinical cardiac remodelling data to demonstrate their clinical utility. A systematic proteomics approach revealed that sclerostin (SOST), growth differentiation factor‐15 (GDF‐15), urokinase‐type plasminogen activator (uPA), and midkine (MK) were increased, while monocyte chemotactic protein‐3 (MCP‐3) was uniquely decreased in MI patients who developed cardiac remodelling, compared to MI patients who did not develop cardiac remodelling and healthy humen. Moreover, correlation analyses between serum proteomes and cardiac remodelling echocardiographic parameters demonstrated a moderate positive association between left ventricular end‐diastolic volume index (LVEDVi) and the three serum proteins, uPA, MK and GDF‐15 (P < .05, respectively), and a moderate negative correlation between LV ejection fraction (LVEF) and these serum proteins (P < .05, respectively). Importantly, uPA and MK were firstly identified to be associated with the development of cardiac remodelling. The present study contributes to a better understanding of the various cytokines expressed during adverse cardiac remodelling. The identified biomarkers may facilitate early identification of patients at high risk of ischaemic heart failure pending further confirmation through larger clinical trials.

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“…No safety concerns were raised during or after intracoronary administration. Two months post-MI, remodeling-indices were improved after high-dosage IGF-1, as shown by smaller LV dimensions and mass, as well as higher stroke volume; there was also evidence of decreased fibrosis examined by late gadolinium enhancement in magnetic resonance imaging [45]. We feel that these very encouraging results call for larger scale clinical trials in acute MI.…”

Section: Gh In Post-mi Remodelingmentioning

confidence: 72%

“…This concept was subsequently confirmed in a similar large animal model [19] after a single dosage of IGF-1 [44]. The intracoronary approach surfaced later into a small-scale clinical trial performed by the same investigators in patients with acute MI undergoing PCI [45]. The study randomized 47 such patients with depressed LV function after successful PCI into three groups, namely high-dose IGF-1, low-dose IGF-1, and saline, in addition to optimal medical therapy.…”

Section: Gh In Post-mi Remodelingmentioning

confidence: 91%

Electrophysiologic Effects of Growth Hormone Post-Myocardial Infarction

Stamatis

Kontonika²,

Daskalopoulos

et al. 2020

IJMS

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Myocardial infarction remains a major health-related problem with significant acute and long-term consequences. Acute coronary occlusion results in marked electrophysiologic alterations that can induce ventricular tachyarrhythmias such as ventricular tachycardia or ventricular fibrillation, often heralding sudden cardiac death. During the infarct-healing stage, hemodynamic and structural changes can lead to left ventricular dilatation and dysfunction, whereas the accompanying fibrosis forms the substrate for re-entrant circuits that can sustain ventricular tachyarrhythmias. A substantial proportion of such patients present clinically with overt heart failure, a common disease-entity associated with high morbidity and mortality. Several lines of evidence point toward a key role of the growth hormone/insulin-like growth factor-1 axis in the pathophysiology of post-infarction structural and electrophysiologic remodeling. Based on this rationale, experimental studies in animal models have demonstrated attenuated dilatation and improved systolic function after growth hormone administration. In addition to ameliorating wall-stress and preserving the peri-infarct myocardium, antiarrhythmic actions were also evident after such treatment, but the precise underlying mechanisms remain poorly understood. The present article summarizes the acute and chronic actions of systemic and local growth hormone administration in the post-infarction setting, placing emphasis on the electrophysiologic effects. Experimental and clinical data are reviewed, and hypotheses on potential mechanisms of action are discussed. Such information may prove useful in formulating new research questions and designing new studies that are expected to increase the translational value of growth hormone therapy after acute myocardial infarction.

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Randomized placebo controlled trial evaluating the safety and efficacy of single low-dose intracoronary insulin-like growth factor following percutaneous coronary intervention in acute myocardial infarction (RESUS-AMI)

Cited by 16 publications

References 24 publications

Low serum IGF1 is associated with hypertension and predicts early cardiovascular events in women with rheumatoid arthritis

Low serum IGF1 is associated with hypertension and predicts early cardiovascular events in women with rheumatoid arthritis

In‐depth proteomics approach reveals novel biomarkers of cardiac remodelling after myocardial infarction: An exploratory analysis

Electrophysiologic Effects of Growth Hormone Post-Myocardial Infarction

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