Relationship of left ventricular hypertrophy to risk of cardiovascular events, and its relevance to medical certification of aircrew

Transcription

1 Eurpean Heart Jurnal (1992) 13 (Supplement H) Relatinship f left ventricular hypertrphy t risk f cardivascular events, and its relevance t medical certificatin f aircrew J. T. STEWART* AND W. J. MCKENNA Department f Cardilgical Sciences, St Gerge's Hspital Medical Schl, Cranmer Terrace, Lndn S Wl 7 ORE, U.K.; * Department f Cardilgy, St Thmas' Hspital, Lambeth Palace Rad, Lndn SE1 7 EH, U.K. KEY WORDS: Aircrew licensing, left ventricular hypertrphy, hypertensin, hypertrphic cardimypathy, athlete's heart syndrme, mrtality, sudden cardiac death, left ventricular functin, arrhythmias. Intrductin This paper will deal with the detectin f left ventricular hypertrphy in asymptmatic individuals, the differentiatin f physilgical frm pathlgical hypertrphy, and the prgnstic implicatins f left ventricular hypertrphy in thse shwn t have primary mycardial abnrmalities. Thse in whm hypertrphy is secndary t hypertensin r ther disrders will als be reviewed. It is useful t think f left ventricular hypertrphy (LVH) as a marker f the cardiac respnse t an abnrmal lad which can have prgnstic implicatins. The functin f the hypertrphic respnse is t nrmalize left ventricular wall stress, and the particular pattern f hypertrphy depends upn the type f lad t which the heart is expsed. A predminant increase in the systlic lad, r afterlad, leads t increased wall thickness with little change in chamber size. This pattern, with increased wall thickness relative t chamber size, is seen in hypertensin r pure artic stensis' 1 '. With vlume verlad (increased prelad), which impses increased diastlic stress, there is increased wall thickness which is assciated with chamber dilatatin. Under these cnditins (pure artic r mitral regurgitatin), there may be little increase r a frank reductin in the rati f wall thickness t chamber size 1 ' 1. Left ventricular hypertrphy is characterized histlgically by increased mycyte vlume, and hyperplasia f the interstitial cells (manifest as increased interstitial fibrsis). The bichemical changes which cntrl the hypertrphic respnse can be detected within minutes f the applicatin f a stimulus f increased wall stress in experimental mdels' 21. The time curse f the develpment f LVH in human disease states is difficult t quantify, but an echcardigraphic study f the effect f endurance athletic training n left ventricular dimensins and mass demnstrated increased LV dimensins within 1 week, and increased wall thickness by 5 weeks' 3 '. The effects f pathlgical LVH n indices f systlic and diastlic LV functin have been extensively studied in animal mdels and in humans. The current understanding f the mechanical cnsequences f LVH has been well reviewed recently 14 '. In sme hypertensive mdels, indices Crrespndtnce: Dr W. J. McKenna, MD, Reader in Clinical Cardilgy, Si Gerge's Hspital Medical Schl, Cranmer Terrace, Lndn SW17 0RE, U.K. f cntractility have been increased, implying enhanced systlic functin, but this has nt been a cnsistent finding. Mycardial stiffness is increased by the increased interstitial fibrsis in hypertrphied mycardium which, cupled with increased wall thickness, acts t reduce left ventricular diastlic cmpliance. The time curse f relaxatin during diastle als appears t be prlnged. Overall, pathlgical LVH is assciated with impaired left ventricular diastlic functin. Physilgical LVH, a cnsequence f athletic training, has nt been shwn t have adverse cnsequences n left ventricular perfrmance. Detectin f left ventricular hypertrphy The detectin f left ventricular hypertrphy in asymptmatic aircrew at the time f medical examinatin will usually depend upn inspectin f the surface 12 lead electrcardigram. Since all individuals will have a baseline electrcardigram fr the purpses f aircrew licensing, there shuld be evidence f any deviatin frm nrmal frm examinatin f previus recrdings, unless the index ECG is the first fr that individual. The standard ECG manifestatins f LVH are well knwn. These include an increase in QRS vltage, shift f the mean QRS axis psterirly, superirly, and t the left, prlngatin f deplarizatin (manifest as delay in nset f the intrinsicid deflectin), and, ultimately, shift f the ST segment and T wave in a directin ppsite t that f the QRS cmplex. In additin t the mass f left ventricular muscle, ther factrs, such as lcatin f the heart within the thrax and its prximity t the chest wall, may play a rle in determining the size f the QRS vltages. (It will be assumed that such abnrmalities f the ECG as ventricular pre-excitatin via an accessry AV cnnectin, and bundle branch blck, which can increase left ventricular vltages, d nt require further discussin). Sme aspects f these changes are nt well understd. The superir and psterir rientatin f the mean QRS vectr is prbably related t disprprtinate hypertrphy f the basal prtin f the left ventricle, with delayed activatin relative t the rest f the ventricle. The increased QRS duratin (delay in deplarizatin) prbably results frm a cmbinatin f increased muscle mass, increased Purkinje fibre activatin, and lcalized X 92/0H0O $ The Eurpean Sciety f Cardilgy

2 L VH and risk f cardivascular events 97 intraventricular delays related t areas f fibrsis. These changes in mycardial activatin bring abut altered replarizatin which prceeds frm endcardium t epicardium, changing T wave plarity, but the mechanism f this change is nt clear. ST segment depressin may be due t the nset f replarizatin prir t the cmpletin f deplarizatin. Tw systems fr the detectin f LVH by electrical criteria have cme int cmmn use; that f Sklw and Lyn' 51, and the pint system f Rmhilt and Estes' 61. In the first, several cmbinatins f QRS vltages assciated with LVH were described, but the mst cmmnly used f these is the sum f the R wave vltage in V 3 r V 6 and f the S wave in V,, where R in V 5 r V 6 + S in V, > 3-5 mv" 1. The pint system is mre cmplex: amplitude f R r S wave in limb leads ;>20mV, rs, in V, r V 2^3-0mV,r R wave in V 5 r V 6^30mV = 3 pints. ST segment changes with r withut digitalis glycsides = 1 r 2 pints respectively. Left atrial enlargement = 3 pints. Left axis deviatin f 30 r mre = 2 pints. QRS duratin^ 90 ms and intrisicid deflectin in V 5 and V 6^ 50 ms= 1 pint each. Left ventricular hypertrphy is cnsidered likely if the number f pints = 4, and t be present if the ttal is 5 r mre pints' 6 '. Althugh bth systems may be useful, the sensitivity f ECG criteria fr the detectin f LVH is lw. Anatmical studies suggested that the sensitivity f the vltage criteria f Sklw and Lyn was abut 56%, but that the false psitive rate was up t 15% [7], while the Rmhilt-Estes pint system had abut a 50-60% sensitivity with a false psitive rate f 3-4%' 6J1. Mre recent echcardigraphic data suggest that the ECG is even less sensitive than was riginally thught; data frm the Framingham Heart Study suggested that the verall sensitivity was 6-9% (5-6% in wmen and 90% in men) 181. The specificity f electrcardigraphic diagnsis f LVH cmpared t anatmical r echcardigraphic data, hwever, is high (95-98%) The sensitivity f ECG criteria fr the detectin f LVH als varies with the underlying cardiac pathlgy, and is lwest in crnary artery disease 1 ' 01. The implicatin f these findings is that the surface ECG, when used as a screening tl in an asymptmatic ppulatin, will underdiagnse LVH, but all aircrew underg rutine echcardigraphy and thus underdiagnsis is inevitable. Echcardigraphy will almst always cnfirm the presence f LVH in thse aviatrs in whm the surface ECG shws the abve abnrmalities. The prgnstic implicatins f LVH vary with the respnsible underlying prcess and will be discussed under the headings f 'physilgical left ventricular hypertrphy' the athletic heart syndrme, primary hypertrphy hypertrphic cardimypathy, and secndary hypertrphy particularly with respect t systemic hypertensin. Physilgical left ventricular hypertrphy the athletic heart syndrme It wuld be unusual t find significant alteratins frm nrmal in the cardivascular systems f recreatinal athletes, althugh the cmbinatin f mild LVH and limited bdy fat in individuals wh undertake endurance events may give rise t increased QRS vltages n the ECG. In the highly trained cmpetitive athlete, hwever, significant adaptive changes, reflecting a nrmal physilgical respnse t repetitive exercise, may ccur. These can mimic pathlgical changes and, f curse, athletes can have cardivascular diseases. As discussed earlier, there are tw main types f cardiac adaptatin, related t pressure verlad and t vlume verlad, bth f which represent remdelling f the heart t nrmalize wall stress. In respnse t chrnic pressure verlad, there is increased, usually cncentric, wall thickness with little r n change in chamber size. When there is chrnic vlume verlad, hwever, bth left ventricular end-diastlic vlume and septal and free wall thickness increase. The increased ventricular vlume and wall thickness seen in athletes wh require sustained increases in cardiac utput during cmpetitin (endurance events), can thus be cnsidered apprpriate cmpensatin fr this type f predminantly istnic stress'"' 121. By cntrast, pwer athletes, such as weight lifters, require shrt-lived increases f cardiac utput against cnsiderable artic pressure (up t 300 mmhg). In these individuals, whse sprt requires ismetric perfrmance, there may be a large increase in LV wall thickness, with relatively little crrespnding increase in LV vlume 1 ' 31. In the majrity f sprts, bth frms f exercise ccur, and the cardiac changes represent a mixture f adaptive respnses. These physilgical types f hypertrphy are nt assciated with any knwn adverse cnsequences, and left ventricular functin, bth systlic and diastlic, remains nrmal" In additin t LVH, cardivascular adaptatin invlves alteratins f the heart rhythm, the mst cmmn f which is resting sinus bradycardia, and smetimes varying degrees f atriventricular ndal blck. Such bradycardias are nrmally ascribed t increased vagal tne, but there is als sme experimental evidence t suggest an intrinsic cardiac cmpnent' 161. Restratin f sinus rhythm with nrmal atriventricular ndal cnductin is almst always seen during exercise. Tachyarrhythmias are nt a feature f the cardivascular respnse adaptatin t physical exertin, and bth supraventricular and ventricular premature beats ccur with the same frequency as in the nrmal ppulatin' Difficulties arise ver the questin f whether exercise, and the cardivascular respnses t it, are related t sudden cardiac death in athletes. The available evidence suggests that there is almst always underlying structural heart disease. Marn and his clleagues frm the Natinal Institutes f Health in the U.S. have prduced the mst cmprehensive summary f the causes f sudden death in athletes, frm their wn experience, and frm a review f the literature 1 ' 91. They cncluded that sudden death in yung athletes (age < 35 years) was usually due t previusly unsuspected cngenital heart disease, mst cmmnly (48%) hypertrphic cardimypathy. An additinal 18% f the hearts f yung athletes

3 98 J. T. Stewart and W. J. McKenna examined were hypertrphied, but did nt satisfy all f the expected diagnstic criteria f hypertrphic cardimypathy. The authrs cnceded, hwever, that they prbably did represent a variant f this cnditin. Other, less cmmn, causes f death were ruptured arta and crnary artery anmalies. Death in the lder athletes was almst always athermatus crnary artery disease" 91. These findings raise the issue f hw t differentiate physilgical hypertrphy frm pathlgical hypertrphy in a highly trained individual. In practice, in asymptmatic individuals with n family histry f hypertrphic cardimypathy, the magnitude f left ventricular wall thickness and left ventricular cavity dimensins n crss-sectinal echcardigraphy can prbably be used t discriminate 'nrmal' hypertrphy frm 'abnrmal' hypertrphy. The mst recent wrk f this srt, and the largest series in the literature, reprted the maximum echcardigraphic left ventricular wall thicknesses in 947 elite Italian athletes aged 13 t 49 (mean 22) years, frm a variety f sprting disciplines' 201. Only 16 athletes (1-7%) were shwn t have maximum left ventricular wall thickness within the range cmpatible with hypertrphic cardimypathy (;>13mm), 15 f whm were rwers r caneists (the 16th was a cyclist). All 16 als had enlarged left ventricular end-diastlic dimensins (increased left ventricular vlume). N athlete had maximal wall thickness > 16 mm. Nne f the 209 female athletes included in this study had maximal left ventricular wall thickness greater than 11 mm. The authrs cncluded that an athlete in whm the wall thickness was greater than 16 mm, and the cavity was nn-dilated was likely t have a primary frm f LVH, such as hypertrphic cardimypathy. Other smaller studies f LVH, such as that by Shapir et a/. 12 ' 1, have shwn greater verlap between athletes and patients with hypertrphic cardimypathy. Bth studies, hwever, cnfirm that in the athletes there is almst always increased cavity dimensins in assciatin with the increased wall thickness, whereas increased cavity dimensins are rarely seen in hypertrphic cardimypathy in the absence f impaired systlic perfrmance The imprtance f differentiating left ventricular hypertrphy due t athleticism frm hypertrphy which is secndary t pathlgical prcesses is that there is n relatinship between adverse utcme and physilgical hypertrphy. If dubt still exists abut the implicatin f LVH in an athletically trained individual, he r she shuld be asked t 'detrain'. Changes in LV wall thickness and cavity dimensins have been shwn t ccur quickly after the nset f a regular exercise prgramme; reversal f all r mst f these changes als ccurs quickly after the cessatin f training 13 '. Regressin f left ventricular hypertrphy in hypertrphic cardimypathy has been demnstrated as part f the natural histry in a minrity with reduced systlic functin, but des nt ccur within the time curse seen in the regressin f left ventricular hypertrphy assciated with athletic detraining. Primary left ventricular hypertrphy hypertrphic cardimypathy Hypertrphic cardimypathy is defined as a heart muscle disrder f unknwn rigin that is characterized by hypertrphy f a nn-dilated left ventricle. The initial descriptins f this disrder, in the 1960s, highlighted the features f hyperdynamic systlic functin, and the presence f left ventricular utflw tract gradients in patients with the classical symptms f chest pain, dyspnea, and syncpe. The literature frm that era suggested that hypertrphic cardimypathy was an uncmmn disease with a pr prgnsis. Mre recent data, particularly since the advent f crss-sectinal echcardigraphy, has shwn that it is mre cmmn than was riginally thught, and that the prgnsis may be quite benign Natural histry and family studies suggest that the prgnsis is prbably genetically determined Apprximately 50% f affected adults present with symptms. In such individuals there is usually slw prgressin f symptms ver many years, but there is als an annual disease-related mrtality f 2 t 3% frm sudden unexpected cardiac death 125 " 291. Analysis f utcme in large series f patients indicates that thse features which best predict the risk f sudden death are: diagnsis in childhd r adlescence, a family histry f hypertrphic cardimypathy and sudden death, and syncpal episdes 130 '. It is seldm pssible t be certain whether systlic r diastlic left ventricular dysfunctin, bth f which are cmmn in hypertrphic cardimypathy, is the mre imprtant cause f symptms in a particular individual. It is prbable that bth may be imprtant t varying degrees in different patients. It is clear that symptm status des nt relate well t the magnitude r distributin f hypertrphy 13 ' 1, and there is debate ver the relatinship between extent f LVH and prgnsis. Observatins in the U.K. and the U.S.A. had suggested that there was n particular relatinship between sudden death and LVH [2<a81, but a recent paper has cast dubt n this' 32 '. A descriptin f 78 patients with hypertrphic cardimypathy, selected because they died suddenly (66) r were successfully resuscitated frm cardiac arrest (12), was made by Marn et al. in 1982' 28 '. (Sixteen ther patients with hypertrphic cardimypathy wh died f nn-cardiac causes e.g. strke, pulmnary emblism, r wh had crnary artery disease, were excluded frm analysis.) The clinical prfile f the study patients was matched t that f a cntrl grup f 76 age- and sex-matched patients with hypertrphic cardimypathy withut cardiac arrest r sudden cardiac death. Septal thickness in the grup with sudden death was 25-2±0-9mm, and in survivrs was 23-6±0-8mm. The authrs stated categrically: 'Ventricular septal thickness als did nt differ substantially between patients wh died suddenly and the surviving cntrls. Therefre, abslute ventricular septal thickness cannt be used t predict sudden death in a ppulatin f patients with hypertrphic cardimypathy.'

4 L VH and risk f cardivascular events 99 E 45-3O s " « k O * 4 Sudden death O OO 0 1 Survivrt Figure I Ventricular septal thickness in 62 patients with hypertrphic cardimypathy wh died suddenly r had cardiac arrest, cmpared with a cntrl grup f 62 age- and sex-matched surviving patients with hypertrphic cardimypathy. Mean values are indicated. =at necrpsy; = by ech, in diastle; A = survived cardiac arrest. By 1990 the same institutin had apparently cme t the ppsite cnclusin, stating: 'It is cncluded that mst asymptmatic r mildly symptmatic patients with hypertrphic cardimypathy wh die suddenly have marked and diffuse left ventricular hypertrphy, and that a relatin exists between the extent f hypertrphy and the ccurrence f sudden and unexpected death in this disease' In this study the maximum left ventricular wall thickness in the sudden death grup was 26 ±7 mm, cmpared with 21 ±5 mm in the survivrs. Unfrtunately clinical characterizatin f the patient grups was limited t age and symptm class in this study, and inspectin f the figure shwing the scatter f wall thicknesses suggests that remval f three utlying patients in the sudden death grup wuld remve the difference between the grups. The data frm the largest study, that f Marn el a/.' 28 ', still appear the mst dependable when examined clsely. It is clear frm that wrk that many f thse wh die suddenly may have nly minimal left ventricular hypertrphy (Fig. 1). The magnitude f hypertrphy is nt a useful predictr f the risk f adverse events. The single best marker f the high risk adults is the identificatin f nn-sustained ventricular tachycardia n ambulatry ECG mnitring, which is assciated with a seven-fld increase in the incidence f sudden death' '. In studies frm the Natinal Institutes f Health, Bethesda, and the Hammersmith Hspital, Lndn, the finding f nn-sustained ventricular tachycardia was a sensitive (69%) and specific (80%) marker f increased risk f sudden death. The negative predictive accuracy was high (97%), but the psitive predictive accuracy was relatively lw (23%), reflecting the fact that the majrity f patients with nn-sustained ventricular tachycardia d nt die during shrt term (3 year) fllw-up. The relatively lw sensitivity in these studies is due in part t the inclusin f an adlescent in the NIH series wh died suddenly withut nn-sustained ventricular tachycardia; it is nw knwn that spntaneus arrhythmias are rare in yung patients, and that ther clinical features are mre useful in them' 351. (The individual cncerned had had recurrent episdes f syncpe and presyncpe, and had shwn herself t be at high risk f sudden death.) In additin, all fur patients wh died suddenly withut nn-sustained ventricular tachycardia had nly 24 h f ambulatry ECG mnitring, thus a sampling errr may have ccurred. Taking these cnsideratins int accunt, the sensitivity f nn-sustained ventricular tachycardia as a marker f the high risk adult is prbably even greater than 69%, and perhaps mre imprtantly the negative predictive accuracy is between 95% and 100%. Thus an adult with hypertrphic cardimypathy wh des nt have nn-sustained ventricular tachycardia is at lw risk indeed. In additin t the identificatin f individuals with 'electrical instability' wh have nn-sustained ventricular tachycardia, recent bservatins suggest that abnrmalities in cntrl f the peripheral vasculature may als predispse t sudden cllapse. Apprximately ne third f a cnsecutive series f ver 100 patients demnstrated exertinal hyptensin despite an apprpriate increase in cardiac utput. These findings were independent f measurements f left ventricular wall thickness, systlic and diastlic functin, and left ventricular utflw tract gradients, but were strngly assciated with yung age and a family histry f sudden cardiac death' 3 * 1. Frearm plethysmgraphy during supine exercise shwed inapprpriate vasdilatatin f nn-exercising vascular beds in the patients with exertinal hyptensin. Fllwup is shrt but preliminary bservatins suggest that the patients with the mst marked vascular abnrmalities are at particular risk f sudden death' 371. At present, the unequivcal diagnsis f hypertrphic cardimypathy disqualifies the individual cncerned frm hlding any frm f medical certificatin t fly. As we have seen, this is prbably t rigrus and reflects an utdated view f the predictive pwer f hypertrphy in terms f utcme. Nevertheless, under the existing regulatins, the imprtant decisin is whether r nt a particular individual with LVH has hypertrphic cardimypathy. Fr the time being that decisin will prbably be made n the basis f the

5 100 J. T. Stewart and W. J. McKenna extent and severity f LVH seen n the echcardigram, taking int accunt family histry. Finally, symptms r ptential fr symptms as well as risk f sudden cardiac death have t be taken int accunt when making an assessment. Althugh utside the scpe f the current discussin, nte shuld be taken f new develpments in the area f diagnsis. Tw families were reprted recently in whm there were the characteristic histlgical abnrmalities f hypertrphic cardimypathy mycyte disarray and an excess f lse cnnective tissue in the absence f cardiac hypertrphy 138 ' 391. Ultimately, accurate diagnsis f the cnditin may require identificatin f the gene respnsible r f a genetic marker which is linked t the gene lcus. A recent publicatin reprted the finding f a DNA lcus n chrmsme 14 which was cinherited with familial hypertrphic cardimypathy in a large kindred' 401. Subsequent wrk demnstrated that there was a single base pair substitutin in the DNA encding beta heavy chain mysin' 41 "' 31. This advance in the understanding f the genetics f hypertrphic cardimypathy means that a mlecular diagnsis, using a gene prbe, may ultimately replace crss-sectinal echcardigraphy as the diagnstic test f chice. Current recmmendatins fr the licensing f individuals with mild LVH in the absence f cnditins such as hypertensin r valvular heart disease, but wh d nt have definite hypertrphic cardimypathy, are pragmatic. Such individuals may be entitled t unrestricted certificatin prvided that they have a satisfactry exercise perfrmance n the treadmill, have n significant rhythm disturbance n Hlter mnitring, are nt taking cardiactive medicatin, have n ther echcardigraphic abnrmality (including Dppler flw studies), and underg annual cardilgical assessment. If a mlecular diagnsis f hypertrphic cardimypathy becmes available, licensing f such peple will be placed n a mre secure scientific basis. An algrithm fr the licensing f individuals with hypertrphic cardimypathy based n the infrmatin which is currently available is given belw: Diagnsis f hypertrphic cardimypathy RISK STRATIFICATION FOR SUDDEN DEATH Risk < 1%/year N VT n 48 h Hlter Nrmal bld pressure respnse n exercise N syncpe Restricted Class I licence Secndary left ventricular hypertrphy Risk > 1%/year Nn-sustained VT n Hlter Hyptensin n exercise Syncpe Disqualify The paradigm fr the secndary develpment f 'pathlgical LVH' is the systlic verlad resulting frm systemic arterial hypertensin. The management f hypertensin was discussed at the 2nd U.K. Wrkshp in Aviatin Cardilgy in 1987* 441 ; this sectin will cncentrate n the influence f LVH n the risk f cardivascular events rather than n the cause f the LVH. The age range f the patients frm whm the data n the prgnstic imprtance f LVH has been derived verlaps the age range f aircrew, but the data are prbably weighted by lder patients. In much f the literature it is difficult t ascertain the age at which events ccur in relatin t the age f detectin f LVH. The left ventricular hypertrphy which develps in respnse t pathlgical stresses n the heart is assciated with adverse sequelae, unlike the physilgical hypertrphy which develps in respnse t physical training. Data frm 30 years f fllw-up in the Framingham study have demnstrated that electrcardigraphic evidence f LVH, particularly when assciated with abnrmalities f replarizatin, are indicative f an increased risk f cardivascular pathlgy Individuals f bth sexes with ECG changes f LVH had a much greater incidence f crnary artery disease, cngestive cardiac failure, strke, and peripheral arterial disease than age-matched individuals withut such ECG abnrmalities. Electrcardigraphic LVH preceded 30% f all deaths and 45% f cardivascular deaths in this study, and was assciated with a 3-fld increase in the risk f death attributable t hypertensin alne. Once vert crnary artery disease had develped, the appearance f LVH n the ECG increased the risk f death 4-fld ver thse patients withut LVH. Unfrtunately the Framingham data presents nly age-adjusted relative risk, and des nt prvide infrmatin in terms f abslute numbers f events per annum fr thse with electrcardigraphic evidence f LVH cmpared t nrmal cntrls. As we have already seen the ECG is an insensitive indicatr f LVH, s the likelihd is that the patients in the Framingham study with this abnrmality had advanced mycardial hypertrphy, as well as interstitial fibrsis and cellular ischaemia. Lesser degrees f LVH, hwever, als appear t be predictive f an adverse utcme. Casale et al. perfrmed echcardigraphy in 140 men with uncmplicated hypertensin, and fllwed events fr almst 5 years' 4 * 1. Twenty-nine patients (mean age 48 years) had LVH by echcardigraphic criteria, in seven f whm mrbid events (death, mycardial infarctin, strke, CABG) ccurred during fllw-up (4-6 events per 100 patient years). Seven f the 111 withut LVH n the echcardigram (mean age 44 years) als had mrbid events (1-4 per 100 patient years). Thus, the risk f an adverse utcme was greater in thse with LVH, and was independent f age, and the level f bth systlic and diastlic bld pressures. When ther risk factrs were taken int accunt in multivariate analysis, the left ventricular mass index was the highest independent risk factr fr future events; age, systlic and diastlic bld pressure, and resting LV functin were relatively weak predictrs f utcme. T few patients in this study had ECG evidence f LVH fr the ECG t be f predictive value, cnfirming the limitatin f the ECG as a screening tl.

6 L VH and risk f cardivascular events 101 Subsequent studies have shwn cnsistent results. Cper et al., in a study f patients underging cardiac catheterizatin fr presumed crnary artery disease, shwed that echcardigraphic LVH was predictive f mrtality independently f left ventricular functin and severity f crnary artery stenses' 471. Using stepwise regressin analysis f a number f variables they shwed that echcardigraphic measures f LVH were the mst imprtant predictrs f survival. The relative risk assciated with a 100 g mass increase was 21, while a 0-1 cm increase in psterir LV wall thickness was assciated with almst a 7-fld increase in the risk f death; abslute risk data and cmparisns with a nrmal cntrl ppulatin were nt presented. In an epidemilgical study f asymptmatic middle-aged men frm Italy, electrcardigraphic indices f LVH were assciated with an increased risk f sudden and nn-sudden cardiac death' 48 '. Many studies have shwn mre frequent and mre cmplex ventricular ectpic activity, and an increased incidence f nn-sustained ventricular tachycardia, in patients with LVH than in similar patients withut LVH' 49 " 5 ". The clear assciatin f LVH with cmplex ventricular arrhythmias raises the pssibility f a cause and effect relatinship between arrhythmias and cardiac death, particularly sudden death, in patients with LVH. Since there is reduced crnary flw reserve in LVH' 52^3', mycardial ischaemia may als have an imprtant rle in the cardiac mrtality seen in LVH. The exact relatinship between LVH, cmplex ventricular arrhythmias, ischaemia, and sudden death, hwever, is nt yet knwn. Cnclusin In cnclusin, the imprtance f LVH must be seen in relatin t the underlying cnditin. In the highly trained, cmpetitive athlete LVH represents the physilgical adaptatin f the left ventricle t sustained high levels f exercise, and shuld nt be seen as pathlgical. Hypertrphic cardimypathy is assciated with a risk f sudden incapacity and sudden death. That risk in adults, hwever, is unrelated t the extent and magnitude f LVH and at present can best be quantified by the presence r absence f nn-sustained ventricular tachycardia n ambulatry ECG mnitring. Subjects wh have hypertrphic cardimypathy withut adverse features such as syncpe, and wh d nt have nn-sustained ventricular tachycardia r an abnrmal bld pressure respnse t exercise culd be cnsidered fr restricted Class I certificatin, subject t annual cardilgical review. Where LVH is secndary t hypertensin, the situatin is nt s clear. There des appear t be an increased risk f adverse cardivascular utcme (strke, mycardial infarctin and death) in individuals with hypertensin and LVH, cmpared t age-matched individuals with the same levels f bld pressure wh d nt have LVH. The wrk f Casale et a/. 14 * 1 suggests a risk f adverse events f 4-6 per patient years in patients with cntrlled hypertensin, increased LV mass, and a nrmal ECG, but a frmal cmparisn with a nrmal cntrl ppulatin has nt been made. The present denial f certificatin t persnnel with electrcardigraphic evidence f hypertensive left ventricular hypertrphy and strain shuld be allwed t stand. Other subjects with established hypertensin but withut electrcardigraphic changes shuld underg crss-sectinal echcardigraphy, particularly if unrestricted certificatin is under cnsideratin. An increased left ventricular muscle mass in the presence f hypertensin shuld at least deny unrestricted certificatin t fly. References [1] Grssman W, Jnes D, McLaurin LP. Wall stress and patterns f hypertrphy in the human left ventricle. J Clin Invest 1975; 56: [2] Wikman-Cffelt J, Parmly W, Masn DT. The cardiac hypertrphy prcess: analysis f factrs determining pathlgical versus physilgical hypertrphy. 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