Identifying and Managing Hibernating Myocardium: What’s New and What Remains Unknown?

Ryan, M. J.; Perera, Divaka

doi:10.1007/s11897-018-0396-6

Cited by 24 publications

(13 citation statements)

References 64 publications

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“…Although obstruction of the epicardial coronary arteries has drawn much attention in its pathophysiology, the importance of the microcirculation in dictating IHD symptoms and prognosis is emerging. Indeed, CMD can coexist with macrovascular atherosclerosis, worsening the clinical scenario [1], as suggested in the context of chronic ischemia, leading to myocardial hibernation [33]. Indeed, hibernated, reperfused hearts that are unable to recover contractile function following reperfusion are characterized by: reduced capillary density associated with metabolic features of energy depletion, inflammation and ongoing cardiomyocyte de-differentiation and cell death [33,34].…”

Section: Discussionmentioning

confidence: 99%

Heart failure impairs the mechanotransduction properties of human cardiac pericytes

Rolle

Crivellari

Zanello

et al. 2021

Journal of Molecular and Cellular Cardiology

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The prominent impact that coronary microcirculation disease (CMD) exerts on heart failure symptoms and prognosis, even in the presence of macrovascular atherosclerosis, has been recently acknowledged. Experimental delivery of pericytes in non-revascularized myocardial infarction improves cardiac function by stimulating angiogenesis and myocardial perfusion.Aim of this work is to verify if pericytes (Pc) residing in ischemic failing human hearts display altered mechano-transduction properties and to assess which alterations of the mechano-sensing machinery are associated with the observed impaired response to mechanical cues. Results: Microvascular rarefaction and defects of YAP/TAZ activation characterize failing human hearts. Although both donor (D-) and explanted (E-) heart derived cardiac Pc support angiogenesis, D-Pc exert this effect significantly better than E-Pc. The latter are characterized by reduced focal adhesion density, decreased activation of the focal adhesion kinase (FAK)/ Crk-associated substrate (CAS) pathway, low expression of caveolin-1, and defective transduction of extracellular stiffness into cytoskeletal stiffening, together with an impaired response to both fibronectin and lysophosphatidic acid. Importantly, Mitogen-activated protein kinase kinase inhibition restores YAP/TAZ nuclear translocation. Conclusion: Heart failure impairs Pc mechano-transduction properties, but this defect could be reversed pharmacologically.

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Section: Discussionmentioning

confidence: 99%

Heart failure impairs the mechanotransduction properties of human cardiac pericytes

Rolle

Crivellari

Zanello

et al. 2021

Journal of Molecular and Cellular Cardiology

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“…Although this myocardial tissue has reduced contractility, it remains viable and may be recoverable with revascularization therapy. 3 …”

Section: Main Textmentioning

confidence: 99%

Synthetic mRNA Encoding VEGF-A in Patients Undergoing Coronary Artery Bypass Grafting: Design of a Phase 2a Clinical Trial

Anttila

Saraste

Knuuti

et al. 2020

Molecular Therapy - Methods & Clinical Development

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Therapeutic angiogenesis may improve outcomes in patients with coronary artery disease undergoing surgical revascularization. Angiogenic factors may promote blood vessel growth and regenerate regions of ischemic but viable myocardium. Previous clinical trials of vascular endothelial growth factor A (VEGF-A) gene therapy with DNA or viral vectors demonstrated safety but not efficacy. AZD8601 is VEGF-A 165 mRNA formulated in biocompatible citrate-buffered saline and optimized for high-efficiency VEGF-A expression with minimal innate immune response. EPICCURE is an ongoing randomized, double-blind, placebo-controlled study of the safety of AZD8601 in patients with moderately decreased left ventricular function (ejection fraction 30%–50%) undergoing elective coronary artery bypass surgery. AZD8601 3 mg, 30 mg, or placebo is administered as 30 epicardial injections in a 10-min extension of cardioplegia. Injections are targeted to ischemic but viable myocardial regions in each patient using quantitative 15 O-water positron emission tomography (PET) imaging (stress myocardial blood flow < 2.3 mL/g/min; resting myocardial blood flow > 0.6 mL/g/min). Improvement in regional and global myocardial blood flow quantified with 15 O-water PET is an exploratory efficacy outcome, together with echocardiographic, clinical, functional, and biomarker measures. EPICCURE combines high-efficiency delivery with quantitative targeting and follow-up for robust assessment of the safety and exploratory efficacy of VEGF-A mRNA angiogenesis (ClinicalTrials.gov: NCT03370887 ).

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“…It is presumed that the myocardium hibernates due to repeated coronary artery contraction. 11 – 14 In such cases, nitrates may be effective in improving myocardial hibernation. 15 – 18 This is because cardiac function can be expected to improve by supplying sufficient blood during long-term or repeated ischemic attacks.…”

Section: Double Left Ventriculography (Lvg) Before and After Intracoronary Administration Of Nitratesmentioning

confidence: 99%

A Pilot Evaluation Study of Diffuse Coronary Arterial Contraction Causing Ischemia by Double Measurement of Left Ventriculography Before and After Intracoronary Administration of Nitrates

et al. 2021

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Background: Abnormal diffuse coronary artery contraction is not easily diagnosed. In order to evaluate its true risk, we performed double left ventriculography (LVG) before and after intracoronary administration of isosorbide dinitrate (ISDN). We also investigated the relationship between changes in coronary lumen area and changes in left ventricular ejection fraction (LVEF) after ISDN. Methods and Results: The study included 53 patients who underwent an acetylcholine (ACh) provocation test after coronary angiogram and LVG. The second LVG was performed after intracoronary ISDN administration. Coronary lumen area was measured by quantitative coronary arteriography (QCA). Simple and multiple regression analyses showed a significant correlation between changes in total QCA area before and after ISDN administration (pre-and post-total QCA area, respectively) and changes in LVEF. Using structural equation modeling, we observed a negative effect of pre-total QCA area and a positive effect of post-total QCA area on LVEF improvement. Importantly, LVEF improvement was similar between the ACh-positive and -negative groups on the coronary artery spasm test. Receiver operating characteristic curves indicated that the cut-off value at which changes in total QCA area affected changes in LVEF was 5%. Conclusions: Performing double LVG tests before and after ISDN administration may detect myocardial ischemia caused by diffuse coronary artery contraction. The addition of this method to the conventional ACh provocation test may detect the presence of local and/or global myocardial ischemia.

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Identifying and Managing Hibernating Myocardium: What’s New and What Remains Unknown?

Cited by 24 publications

References 64 publications

Heart failure impairs the mechanotransduction properties of human cardiac pericytes

Heart failure impairs the mechanotransduction properties of human cardiac pericytes

Synthetic mRNA Encoding VEGF-A in Patients Undergoing Coronary Artery Bypass Grafting: Design of a Phase 2a Clinical Trial

A Pilot Evaluation Study of Diffuse Coronary Arterial Contraction Causing Ischemia by Double Measurement of Left Ventriculography Before and After Intracoronary Administration of Nitrates

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