M St John Sutton and T Plappert. Division of ... Correspondence: M St John Sutton, John W Bryfogle, Professor of. Cardiac .... 8 Vitale DF et al. Myocardial ...
Journal of Human Hypertension (2000) 14, 7–8 2000 Macmillan Publishers Ltd. All rights reserved 0950-9240/00 $15.00 www.nature.com/jhh
COMMENTARY
Myocardial texture in hypertrophic remodelling: new insight into ventricular load and function? M St John Sutton and T Plappert Division of Cardiology, Department of Medicine, University of Pennsylvania Medical Center, Philadelphia PA, USA
Keywords: hypertrophic remodelling; left ventricular myocardium
Arterial hypertension exposes the left ventricular myocardium to increased loading conditions and is a powerful stimulus for hypertrophy and ventricular remodelling. During normal human cardiac growth from the neonatum to adulthood, the relationship between left ventricular cavity size and wall thickness is tightly modulated so that in spite of the agerelated increases in systolic blood pressure and heart size, ventricular load—wall stress—remains within a narrow normal range. The interaction between left ventricular mass and volume in maintaining normal loading conditions is important, because failure to normalise increased wall stress is associated with deterioration in contractile function, since contractile function varies inversely with wall stress. Recent in vitro studies of cardiomyocytes have demonstrated that increased load is sensed and transduced via cell surface mechanoreceptors which activate intracellular biochemical signalling pathways that turn on production of contractile proteins and assembly of contractile units.1 Cardiomyocytes are terminally differentiated cells that are unable to replicate, so that when their capacity to elaborate contractile protein is exhausted, wall stress can no longer be normalised by hypertrophy, and ventricular decompensation occurs with dilatation and deterioration in contractile function. Left ventricular hypertrophy has been divided arbitrarily into three phases,2 an adaptive phase and a compensatory phase, in both of which relief of increased load is associated with reversal of contractile dysfunction; and a pathologic phase, in which contractile function is abnormal and removal of excessive load is not accompanied by return to normal contractile function. Thus, a method for reliably
Correspondence: M St John Sutton, John W Bryfogle, Professor of Cardiac Imaging, University of Pennsylvania Medical Center, 9th Floor Gates Building, 3400 Spruce Street, Philadelphia, PA 19104, USA Received and accepted 10 September 1999
detecting the onset of contractile dysfunction in patients with arterial hypertension before transition to irreversible damage would be important. Accurate assessment of the impact of hypertrophy on left ventricular function in patients with arterial hypertension is complicated by a number of factors. Hypertrophic remodelling alters ventricular architecture which compromises long axis systolic shortening and may impair diastolic filling. Left ventricular hypertrophy is associated with development of interstitial myocardial fibrosis which changes the material properties of the myocardium and may culminate in systolic or diastolic left ventricular dysfunction and heart failure depending on the severity and chronicity of the hypertension. Arterial hypertension is a risk factor for coronary heart disease which may contribute additionally to decline in left ventricular function. Previous attempts have been made to discriminate between the effects of increased wall thickness and increased collagen in the extracellular matrix on left ventricular function using ultrasound techniques in patients with left ventricular hypertrophy, including analysis of integrated backscatter and Doppler tissue imaging. In this issue of the Journal of Human Hypertension, Di Bello and collaborators3 examine the relationship between left ventricular load (endsystolic meridional and circumferential wall stress) and midwall shortening in a cohort of patients with left ventricular hypertrophy due to arterial hypertension. Their findings essentially confirm other studies in showing that midwall shortening may be decreased in concentric hypertrophy, but do not necessarily indicate impaired contractile function.4 Previous studies have extended these observations and demonstrated the importance of midwall shortening in patients with left ventricular hypertrophy from hypertension in predicting adverse cardiovascular events.5 More interestingly, the authors explore the interaction between end-systolic wall stress and myocardial textural analysis in untreated
Myocardial texture in hypertrophic remodelling M St John Sutton and T Plappert
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hypertensive patients with varying degrees of hypertrophy. Textural analysis of the myocardium is based upon backscatter of transmitted ultrasound which is influenced by the size, shape and distribution of scatterers and the acoustical properties of the individual scatterers within the myocardium. The principal scatterer of propagated ultrasound from myocardium is collagen located in the extracellular matrix. Collagen comprises the visco-elastic structural framework of interfibrillar struts and perimysial weave that aligns the myofilaments enabling optimal force development and it is this network that primarily determines the acoustical properties of normal myocardium. The authors used ultrasound to measure the cyclical variation index (CVI) of grey level amplitude to assess myocardial texture, which they defined as the difference in echodensity from end-diastole to endsystole, expressed as a percentage of end-diastolic signal intensity. Myocardial texture analysis was confined to two regions of interest, the interventricular septum and the posterior left ventricular wall. Thus far, myocardial textural analysis has only proved useful in patients following myocardial infarction6 and in cardiomyopathies.7,8 In this study, although echodensity of the septum and posterior left ventricular wall at end-diastole did not differ from normal, it was significantly greater than normal at end-systole, and for this reason CVI among hypertensive patients was less than normal. That CVI was unrelated to wall thickness per se was important, concordant with that demonstrated in athletes with left ventricular hypertrophy from isometric exercise. Interestingly, Di Bello et al3 found correlations in hypertensive patients between CVI in the septum and left ventricular posterior wall and midwall fractional shortening, and novel inverse correlations between CVI, systolic blood pressure, left ventricular mass and end-systolic wall stress. The correlations between CVI, blood pressure and myocardial mass were weak, but their directions were consistent with the logic that the higher the arterial blood pressure the greater the left ventricular mass, the more chronic and severe the hypertension, the greater likelihood of interstitial fibrosis and the more intense the backscatter. The linear relationship between CVI and load is less intuitive since in patients with compensated hypertrophy load is normal, and only when hypertrophy can no longer increase does load increase dramatically with deterioration in contractile function. Maybe change in CVI is triggered by the insidious development of interstitial myocardial fibrosis and as such provides a signal for decompensated hypertrophy and
Journal of Human Hypertension
decreasing contractile function. The authors would have been more convincing using CVI if they had segregated patients by increasing severity and chronicity of hypertrophy. All patients in the study were naive to treatment, and it is important to establish whether treatment of hypertension and demonstration that regression of hypertrophy was associated with restitution of CVI towards normal values. For example, treatment with angiotensin-converting enzyme inhibitor (ACE) therapy partially blocks production of angiotensin which is a key regulatory factor in collagen synthesis in the extracellular matrix. Does treatment with ACE reverse the CVI to a greater extent than an equipotent effect on regression of hypertrophy with another class of agent? Different pharmacologic treatments of hypertension might have dissimilar effects on CVI and ventricular function. If CVI is changing in relation to myocardial collagen volume, can it be regarded as a fiducial measure of intrinsic myocardial function in hypertrophic remodelling? Pursuit of detailed studies with CVI in hypertrophy is to be encouraged but caution is warranted in ascribing CVI as an index of myocardial function until more definitive studies are available.
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