Downloaded from heart.bmj.com on February 14, 2011 - Published by group.bmj.com Editorial LVH response. Particularly striking has Left ventricular hypertrophy in been the observation that outcome is improved in animals undergoing aortic binding by blocking the hypertrophic aortic valve stenosis: friend or response to pressure overload.10 Although genetically modified animals have higher foe? left ventricular systolic stress than their wild-type counter mates, this has no consequence on long-term myocardial Raquel Yotti, Javier Bermejo performance. In fact, knock-out animals lived longer. The conventional conception ‘How wonderful that we have found (LVM) was found in 59% of patients from of physiological adaptation to pressure a paradox. Now we have some hope of an unselected cohort with asymptomatic overload as a teleological mechanism ’ making progress. AS. Multivariate analysis showed the to reduce wall stress thus calls for e Neils Böhr (1885 1962) independent predictive value of and inap- revision.11 12 Concentric remodelling (reduction of the propriate LVM, in addition to well estab- There are several mechanisms by which fl diameter/thickness ratio) and hyper- lished indices that in uence outcome in excessive LVH may be related to the 34 trophy (increase of massdleft ventricular AS such as baseline disease severity or outcome of patients with AS. It has been fi 5 hypertrophy; LVH) have been classically the degree of valve calci cation. Although shown that left ventricular systolic func- interpreted as the physiological mecha- a potentially maladaptive effect of hyper- tion declines as hypertrophy develops, 6 6 nisms used by the left ventricle to trophy in AS had already been reported, increasing the risk of heart failure. Due fi compensate for chronic pressure over- this is the rst study demonstrating its to afterload dependence, systolic chamber fi load.1 At the cellular level, increasing the detrimental impact on patient outcome in function may be dif cult to quantify in number of contractile elements improves a longitudinal design. the presence of AS. As left ventricular contractile force. At the organ level, In hypertensive heart disease, the dele- volumes become smaller due to concentric a thicker myocardial wall reduces left terious consequences of left ventricular remodelling, stroke volume is reduced, ‘ ventricular radial, circumferential and remodelling have been unequivocally sometimes leading to the paradoxical fl ’ 13 meridional systolic stresses. Concentric proved. Best evidence comes from phar- low- ow AS phenomenon. Despite remodelling and hypertrophy thus take macological interventions showing normal ejection fraction, patients with advantage of Laplace’s law to benefit a reduction of cardiovascular events this condition show higher values of systolic function. Even under extreme parallel to the regression of LVH, inde- concentric remodelling and smaller 7 fl values of intraventricular pressure, overall pendent of their effect on blood pressure. ventricles than their normal- ow coun- fl systolic performance is maintained and A relatively large number of patients with terparts. In paradoxical low- ow AS, pump function remains normal in terms hypertension also develop inappropriate reduced output is believed to result in of cardiac output and filling pressures. In hypertrophy for the degree of load and, as the combination of systolic and diastolic the long term, if the systolic load is not in AS, the correlation of LVM with dysfunction. Under stress situations, the relieved, this compensatory mechanism outcome may not be linear. In fact, heart may fail to provide adequate output, fl fails, hypertrophy switches towards adverse inappropriate hypertrophy and patients with paradoxical low- ow eccentric remodelling, filling pressures rise beyond a given threshold had previously AS show an adverse prognosis, particu- and overt heart failure develops (a phase been described in hypertensive heart larly if they do not undergo valve 14 classically designated ‘afterload disease, and excessive LVM correlates with replacement. mismatch’). This has been the classic cardiovascular outcome, independently of Hypertension and AS frequently 8 conception of the favourable ‘adaptive’ conventional risk factors. coexist, and both conditions share effects of left ventricular remodelling A number of genetic, molecular, and a number of common mechanisms. They under increased systolic stress.1 cellular mechanisms related to secondary also multiply their effect on the systolic In their article published in this issue of LVH have been well characterised in the burden of the left ventricle. In fact, AS Heart, Cioffi et al2 (see page 301) analyse past few years. Interestingly, separate patients with hypertension show more the prognostic value of LVH in a prospec- intracellular pathways have been identi- unfavourable remodelling than normo- fi 15 tive cohort of patients with aortic valve ed to modulate adaptive and maladaptive tensive individuals. This has led some 9 stenosis (AS). The major finding of their hypertrophy. Signalling molecules that authors to propose combined indices of e study is related to adverse outcome if involve the phosphoinositide-3-kinase systolic load such as the valvular vascular values are 110% higher than the values cascade exert a protective role in progres- impedance, which may allow prognosis fi expected for wall stress, body size and sion towards heart failure, whereas path- to be strati ed in given subsets of patients 16 gender. Importantly, such an inappro- ways involving G-protein signalling with AS. However, even these more priate increase in left ventricular mass enhance apoptosis and extracellular sophisticated measurements of systolic fibrosis. Further understanding of these load only consider singular measurements molecular mechanisms will help drug at a given time point. Indices accounting development to prevent the transition for the degree of left ventricular Department of Cardiology, Hospital General Universitario from left ventricular concentric remodel- remodelling and LVM may have the Gregorio Maran˜o´n, Madrid, Spain ling to heart failure. In addition, clarifica- advantage of reflecting the effects of an Dr Javier Bermejo, Department of Correspondence to tion of the signal pathways of LVH has abnormal load during a long period of Cardiology, Hospital General Universitario Gregorio ‘ Maran˜o´n, Dr Esquerdo 46, 28007 Madrid, Spain; allowed investigators to develop geneti- time, acting as a cumulative systolic load [email protected] cally modified murine models of blunted dose’ indicators. Heart February 2011 Vol 97 No 4 269 Downloaded from heart.bmj.com on February 14, 2011 - Published by group.bmj.com Editorial Localised LVH at the basal septum is surgery.29 Patients are also sometimes overload hypertrophy prevent cardiac dysfunction particularly prevalent in hypertensive operated on when myocardial damage is despite increased wall stress. Circulation 17 2002;105:85e92. patients with AS, and may occasionally already irreversible. Current European 11. Buermans HP, Paulus WJ. Iconoclasts topple cause associated subvalvular outflow practice guidelines accept severe LVH (in adaptive myocardial hypertrophy in aortic stenosis. obstruction (‘double outflow stenosis’), the absence of hypertension) as a IIb Eur Heart J 2005;26:1697e9. thus accelerating patient symptom devel- (level of evidence C) class recommendation 12. Sano M, Schneider MD. Still stressed out but doing opment. Even milder and non-obstructive for valve replacement in asymptomatic fine: normalization of wall stress is superfluous to maintaining cardiac function in chronic pressure 30 fi degrees of basal septal hypertrophy may patients. However, the study by Ciof overload. Circulation 2002;105:8e10. 18e20 2 be detrimental. Significant reductions et al suggests that efforts should be made 13. Dumesnil JG, Pibarot P, Carabello B. Paradoxical low of annular size (most frequently found in to explore further the role of more refined flow and/or low gradient severe aortic stenosis female patients with an advanced measurements of ventricular remodelling despite preserved left ventricular ejection fraction: implications for diagnosis and treatment. Eur Heart J concentric remodelling pattern) may in prospective clinical trials. The prog- 2010;31:281e9. complicate therapeutic interventions, nostic value of ventricular variables beyond 14. Hachicha Z, Dumesnil JG, Bogaty P, et al. increasing the risk of patienteprosthesis ejection fraction need to be analysed, and Paradoxical low-flow, low-gradient severe aortic mismatch,18 or precluding transcatheter surrogate indices such as systolic pulmo- stenosis despite preserved ejection fraction is 31 associated with higher afterload and reduced survival. valve implantation. Importantly, LVH and nary artery pressure or natriuretic e 32 Circulation 2007;115:2856 64. concentric remodelling are associated with peptides are particularly promising. 15. Rieck AE, Cramariuc D, Staal EM, et al. Impact of increased perioperative and mid-term Although the level of evidence is currently hypertension on left ventricular structure in patients mortality.19 20 too weak to recommend anticipating with asymptomatic aortic valve stenosis (a SEAS e The worse prognosis associated with surgery in the asymptomatic patient based substudy). J Hypertens 2010;28:377 83. 16. Hachicha Z, Dumesnil JG, Pibarot P. Usefulness of inappropriately high LVM in AS may also only on the degree of hypertrophy, the left the valvuloarterial impedance to predict adverse