Elsevier

The Lancet

Volume 383, Issue 9932, 31 May–6 June 2014, Pages 1933-1943
The Lancet

Review
Cardiovascular remodelling in coronary artery disease and heart failure

https://doi.org/10.1016/S0140-6736(14)60107-0Get rights and content

Summary

Remodelling is a response of the myocardium and vasculature to a range of potentially noxious haemodynamic, metabolic, and inflammatory stimuli. Remodelling is initially functional, compensatory, and adaptive but, when sustained, progresses to structural changes that become self-perpetuating and pathogenic. Remodelling involves responses not only of the cardiomyocytes, endothelium, and vascular smooth muscle cells, but also of interstitial cells and matrix. In this Review we characterise the remodelling processes in atherosclerosis, vascular and myocardial ischaemia–reperfusion injury, and heart failure, and we draw attention to potential avenues for innovative therapeutic approaches, including conditioning and metabolic strategies.

Introduction

“The heart is the beginning of life, for it is by the heart the blood is moved…the source of all action”, wrote William Harvey in 1673. The concept that such action could vary and the heart undergo remodelling in disease stretches back to the classic writings of Corvisart in 1806, when he described “two types of dilatation, active with thick walls and increased force of contraction, and passive with thinning of the walls and a decreased force of contraction”. These notions correspond to current concepts of left ventricular hypertrophy and dilatation as two contrasting types of cardiac remodelling. Yet we have to wait till 1984 before the then novel term remodelling more precisely described the early and later structural changes that occurred in infarcted and non-infarcted ventricular myocardium after coronary artery ligation.1 The next conceptual advance was that disproportionate thinning and dilatation occurred in the infarct region, accompanied by remote remodelling of non-infarcted myocardium, correlated with the extent of expansion. By 2000 the topic was sufficiently prominent to merit a consensus review document from the International Forum on Cardiac Remodelling. Patients with major remodelling underwent progressive worsening of cardiac function, and slowing or reversal of remodelling became a new goal of heart failure therapy.2

Originally, the term remodelling was proposed to characterise the response of remote myocardium to regional infarction and the progression from acute myocardial infarction to chronic heart failure.1, 3 Independently and at about the same time, the term remodelling was also used to characterise the progression of atherosclerotic vascular lesions.4, 5 In our Review, we advocate the concept of remodelling in a broader and more general sense to characterise the responses of myocardium and vasculature to potentially noxious haemodynamic, metabolic, and inflammatory stimuli, a process that is initially functional, compensatory, and adaptive in nature but, when sustained, progresses to structural changes that become self-perpetuating and pathogenic. Remodelling involves not only responses of the specific cardiovascular cells—cardiomyocytes, endothelium, smooth muscle cells—but also the interstitial cells and matrix.

Section snippets

Endothelial remodelling

The endothelial cell, positioned at the interface between the blood vessels and tissues, stands poised to sense the environment and signal modulations of vascular function to maintain homoeostasis and host defences against microbial invaders and injury.6 Inappropriate signalling from vascular endothelial cells can also contribute to common diseases characterised by arterial remodelling, notably atherosclerosis and hypertension. Endothelial cells sense the environment in two major ways: local

Coronary microvascular dysfunction and remodelling in ischaemic and reperfused myocardium

Remodelling of the epicardial coronary arteries has preoccupied clinical cardiologists because constrictive remodelling often yields stenotic plaques that cause chronic myocardial ischaemia, whereas expansive remodelling characterises plaques that rupture and provoke acute thromboses. The reperfusion era brought substantial changes in the management of acute myocardial infarction. The relief of symptoms in stable coronary artery disease and the prognosis of acute coronary syndromes have

Remodelling after myocardial reperfusion injury

Acute myocardial infarction is a major cause of death and disability worldwide. Much of this morbidity and mortality relates to the remodelling that occurs post infarction. Although cardiac remodelling is often associated with events that occur in the weeks and months after an acute myocardial infarction, its consequences invariably relate to the initial size of the associated infarction. Therefore optimum positive remodelling after a severe acute ischaemia–reperfusion event can improve patient

Myocardial remodelling in heart failure

Factors such as loading conditions, neurohormonal activation patterns, genetic background, and comorbid conditions affect the size, shape, and ultrastructure of the heart. In conditions such as pregnancy or endurance exercise terms such as physiological, adaptive, beneficial, or compensated remodelling are used, whereas during pathological stimulation by pressure or volume overload, the condition is described as maladaptive or decompensated remodelling.74 The phenotype, including ventricular

Impaired mitochondrial oxidative metabolism and adverse energetic remodelling of the failing heart

In addition to structural remodelling, remodelling of cardiac energy metabolism can contribute to the severity of heart failure.111 In particular, both a decrease in energy production and a switch in energy substrate use that occur with remodelling can worsen heart failure.111, 112

The progression of heart failure is associated with compromised myocardial energy production indicated by decreased concentrations of both ATP and phosphocreatine.113, 114 This depletion seems to result primarily from

Summary

Remodelling of the heart and vessels characterises coronary artery disease, hypertension, and heart failure. Remodelling of the coronary arteries starts in the endothelium and progressively advances towards the atherosclerotic plaque that when causing ischaemia and infarction provokes myocardial remodelling. The arteriolar microvascular response to hypertension, luminal narrowing, smooth muscle hyperplasia, and medial thickening perpetuates raised blood pressure that predisposes to myocardial

Search strategy and selection criteria

For this Review, each contributing author selected references that he viewed as most relevant for his particular topic.

References (130)

  • HE Bøtker et al.

    Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial

    Lancet

    (2010)
  • F Thuny et al.

    Post-conditioning reduces infarct size and edema in patients with ST-segment elevation myocardial infarction

    J Am Coll Cardiol

    (2012)
  • M Thielmann et al.

    Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial

    Lancet

    (2013)
  • LH Opie et al.

    Controversies in ventricular remodelling

    Lancet

    (2006)
  • P Boström et al.

    C/EBPβ controls exercise-induced cardiac growth and protects against pathological cardiac remodeling

    Cell

    (2010)
  • A Elsässer et al.

    Human hibernating myocardium is jeopardized by apoptotic and autophagic cell death

    J Am Coll Cardiol

    (2004)
  • BM Patel et al.

    Aldosterone and angiotensin: role in diabetes and cardiovascular diseases

    Eur J Pharmacol

    (2012)
  • BC Jensen et al.

    Alpha-1-adrenergic receptors: targets for agonist drugs to treat heart failure

    J Mol Cell Cardiol

    (2011)
  • JM Pfeffer et al.

    Influence of chronic captopril therapy on the infarcted left ventricle of the rat

    Circ Res

    (1985)
  • CK Zarins et al.

    Arterial disruption and remodeling following balloon dilatation

    Surgery

    (1982)
  • P Libby et al.

    Progress and challenges in translating the biology of atherosclerosis

    Nature

    (2011)
  • EL Schiffrin

    Vascular remodeling in hypertension: mechanisms and treatment

    Hypertension

    (2012)
  • KJ Williams et al.

    Lipoprotein retention—and clues for atheroma regression

    Arterioscler Thromb Vasc Biol

    (2005)
  • JP Sluijter et al.

    Vascular remodeling and protease inhibition—bench to bedside

    Cardiovasc Res

    (2006)
  • P Libby

    Mechanisms of acute coronary syndromes and their implications for therapy

    N Engl J Med

    (2013)
  • P Libby

    Collagenases and cracks in the plaque

    J Clin Invest

    (2013)
  • E Falk et al.

    Update on acute coronary syndromes: the pathologists' view

    Eur Heart J

    (2013)
  • SE New et al.

    Macrophage-derived matrix vesicles: an alternative novel mechanism for microcalcification in atherosclerotic plaques

    Circ Res

    (2013)
  • SJ Nicholls et al.

    Effect of two intensive statin regimens on progression of coronary disease

    N Engl J Med

    (2011)
  • A Lerman et al.

    Microcirculatory dysfunction in ST-elevation myocardial infarction: cause, consequence, or both?

    Eur Heart J

    (2007)
  • A Prasad et al.

    Reperfusion injury, microvascular dysfunction, and cardioprotection: the “dark side” of reperfusion

    Circulation

    (2009)
  • C Zhang et al.

    Regulation of coronary microvascular resistance in health and disease

  • JM Canty et al.

    Reduced regional myocardial perfusion in the presence of pharmacologic vasodilator reserve

    Circulation

    (1985)
  • G Heusch et al.

    alpha-adrenergic coronary vasoconstriction and myocardial ischemia in humans

    Circulation

    (2000)
  • G Heusch et al.

    Attenuation of exercise-induced myocardial ischemia in dogs with recruitment of coronary vasodilator reserve by nifedipine

    Circulation

    (1987)
  • G Heusch et al.

    Myocardial hibernation: a delicate balance

    Am J Physiol Heart Circ Physiol

    (2005)
  • O Sorop et al.

    Functional and structural adaptations of coronary microvessels distal to a chronic coronary artery stenosis

    Circ Res

    (2008)
  • I Mills et al.

    Adaptive responses of coronary circulation and myocardium to chronic reduction in perfusion pressure and flow

    Am J Physiol

    (1994)
  • G Heusch et al.

    Coronary microembolization: from bedside to bench and back to bedside

    Circulation

    (2009)
  • RA Kloner et al.

    The “no-reflow” phenomenon after temporary coronary occlusion in the dog

    J Clin Invest

    (1974)
  • H Dörge et al.

    Perfusion-contraction mismatch with coronary microvascular obstruction: role of inflammation

    Am J Physiol Heart Circ Physiol

    (2000)
  • E Falk

    Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death. Autopsy evidence of recurrent mural thrombosis with peripheral embolization culminating in total vascular occlusion

    Circulation

    (1985)
  • A Skyschally et al.

    Bidirectional role of tumor necrosis factor-alpha in coronary microembolization: progressive contractile dysfunction versus delayed protection against infarction

    Circ Res

    (2007)
  • G Heusch

    Nitroglycerin and delayed preconditioning in humans: yet another new mechanism for an old drug?

    Circulation

    (2001)
  • SH Rezkalla et al.

    Ischemic preconditioning and preinfarction angina in the clinical arena

    Nat Clin Pract Cardiovasc Med

    (2004)
  • A Skyschally et al.

    Coronary microembolization during early reperfusion: infarct extension, but protection by ischaemic postconditioning

    Eur Heart J

    (2013)
  • P Kleinbongard et al.

    Vasoconstrictor potential of coronary aspirate from patients undergoing stenting of saphenous vein aortocoronary bypass grafts and its pharmacological attenuation

    Circ Res

    (2011)
  • P Kleinbongard et al.

    Aspirate from human stented native coronary arteries vs. saphenous vein grafts: more endothelin but less particulate debris

    Am J Physiol Heart Circ Physiol

    (2013)
  • W Desmet et al.

    High-dose intracoronary adenosine for myocardial salvage in patients with acute ST-segment elevation myocardial infarction

    Eur Heart J

    (2011)
  • LF Robbers et al.

    Magnetic resonance imaging-defined areas of microvascular obstruction after acute myocardial infarction represent microvascular destruction and haemorrhage

    Eur Heart J

    (2013)
  • Cited by (583)

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