Number 20, 2003
Hibernation preconditioning

Editorial

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Michael S. Marber
Department of Cardiology, KCL, St Thomas’ Hospital, London, UK
Correspondence: Professor Michael S. Marber, Department of Cardiology, KCL, St Thomas’ Hospital, Lambeth Place Road, London SE1 7EH, UK. e-mail: mike.marber@kcl.ac.uk

Cardiology trainee (just out of research): “I know he has had a big anterior infarct and LV function is poor, but, despite the area being akinetic at rest and only a little better on stress, PET shows hypoperfusion with normal FDG uptake in the septum and apex. I think this is a typical case of deep structural hibernation and his LAD should be angioplastied.”
Interventional cardiologist (in a nationalized health care system): “I wouldn’t go as far as that. I think he has a remodeled and old scar, since we all know flow has to be near normal, and some inotropic response present, for there to be good recovery. I think he has a chronically underperfused scarred anterior wall with a few islands of viable but probably mummified, stunned, or perhaps dedifferentiating preconditioned myocytes in a sea of fibrosis.”
Cardiology trainee: “You’re right, the dedifferentiation is worrying and may even be accompanied by apoptosis. He still needs urgent revascularization to prevent further embryonal regression and restore function.”
The “new” ischemic syndromes of stunning, hibernation, and ischemic preconditioning are confused by the inter-relationship of complex physiologies variously described in patients and animals. Despite the pure historical pedigree of these terms, as illustrated above, they are now used commonly, loosely, and often inappropriately in clinical parlance [1]. This issue of Heart and Metabolism is devoted to the assessment and treatment of patients with ischemic heart disease and potentially reversible chronic left ventricular dysfunction.
Jean-Louis Vanoverschelde and Jacques Melin provide a clear account of the spectrum of pathologies that may underlie myocardial segments with reversible contractile dysfunction. By combining information from clinical and large, long-term animal studies we are provided with a concise overview of how severe reductions in coronary flow reserve with little reduction in basal flow can lead to repetitive stunning with little histological abnormality. This process can then progress to reductions in basal coronary flow with consequent abnormalities in myocardial cellular and interstitial structure. Defining whether the physiological severity of an epicardial stenosis is sufficient to contribute to such processes within the subtended myocardium is addressed by Koen Marques.
In a lucid introduction Dr Marques discusses the fluid mechanics of a coronary stenosis and demonstrates that both flow and pressure really need to be measured simultaneously to determine whether flow is disordered and, if it is, whether the abnormal resistance lies epicardially or within the diseased distal vasculature. Obviously only the former will respond to revascularization. The synchronous measurement of intracoronary flow and pressure is still a research technique with real-time data analysis only available in a rudimentary form. What is really needed are further refinements in noninvasive imaging.
Anna John and Dudley Pennell provide an upbeat account of the capabilities of cardiac magnetic resonance imaging (cMR). Late enhancement with gadolinium provides high-resolution images of areas of myocardial necrosis and/or scarring. With the high spatial resolution offered by cMR, even small and nontransmural areas of nonviable myocardium can be delineated. It is known from biopsies harvested during surgical revascularization that scar indices provide a very good prediction of regional contractile recovery. It is likely that cMR will provide similar information noninvasively. In addition, analysis of gadolinium “wash in” can also provide measures of regional myocardial perfusion. Furthermore cMR allows imaging of myocardial translational movement as well as deformation during dobutamine stress. In essence Drs John and Pennell give the impression that cMR will be the noninvasive “one-stop shop” to the diagnosis of reversible contractile dysfunction. They may well be right if Professor Marwick’s view of the future becomes a reality!
Thomas Marwick provides an analytical and refreshing insight to a future where therapy is tailored to the physiological process underlying the contractile deficit. For example, those with severe structural hibernation could get a combination of revascularization to preserve and recover those myocytes that are salvageable, together with stem cells to replace those that are not. Similarly, in some patients, allowing the myocytes to make the most of their restricted blood flow could be sufficient and achievable with metabolic therapies and/or
b-adrenoceptor blockers.
A. Berger and W. Wijns allow us to get our feet firmly back on the ground by providing a sobering reminder of the high prevalence of heart failure and, in patients with systolic dysfunction, the high prevalence of segments with features of reversible left ventricular dysfunction. If these patients have both angina and proximal coronary artery disease, the arguments in support of revascularization are strong. However, in the absence of angina, the decision-making process is complicated by the lack of randomized controlled trial data showing that revascularization carries a prognostic benefit. In contrast there are overwhelming data to support the use of ACE inhibitors, b-blockers, and statins, and strong and growing evidence in support of aldosterone antagonists, internal cardioverter defibrilators and biventricular pacing. Drs Berger and Wijns summarize observational data to support the use of revascularization in the patient with heart failure but no angina. A reasonable alternative view is that such patients should only be offered revascularization if that is the group to which they are randomized in a trial. Ultimately, until such definitive data are forthcoming, decisions will continue to be made locally, based on the strengths of the evidence for reversibility balanced against the risks of revascularization.
Although this exciting issue provides a thorough overview of the current and the future investigation and treatment of the “new” ischemic syndromes, the conversation between the trainee and cardiologist suggests we still have a long way to go before conjecture is replaced by fact.

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