Table Of ContentPregledni rad / Review article
Almanah 2011. godine: valvularne bolesti srca.
»asopisi nacionalnih druπtava predstavljaju odabrana
istraæivanja koja predstavljaju napredak u kliniËkoj kardiologiji
Almanac 2011: valvular heart disease.
The national society journals present selected research that has
driven recent advances in clinical cardiology.
Raphael Rosenhek*
Vienna General Hospital, BeË, Austrija
Vienna General Hospital, Vienna, Austria
Uvod Introduction
Starenjem populacije i poboljπanim dijagnostiËke metodama With an ageing population and improved diagnostic modali-
ties, the number of patients with valvular heart disease (VHD)
registriran je dramatiËan porast broj pacijenata s bolestima
is dramatically increasing. Considering projected changes in
srËanih zalistaka. UzimajuÊi u obzir predviene promjene u
the age distribution, a further accentuation of this trend can
dobnoj distribuciji, moæemo oËekivati porast ovog trenda te
be expected and this may indeed be considered “the next
stoga ove bolesti mogu se doista smatrati “sljedeÊom kardi-
cardiac epidemic”.1Obviously, we are faced with more com-
oloπkom epidemijom”.1 Nema sumnje da se suoËavamo sa
plex decisions in patients with advanced age and increasing
sloæenijim odlukama kod pacijenata uznapredovale dobi i
comorbidities. Advances in percutaneous valve interventio-
prisutnog komorbiditeta. U rutinsku primjenu ulaze napred-
nal techniques have entered into routine practice. At the sa-
ne tehnike perkutane intervencije na valvulama. Istovreme-
me time, new data on the natural history of disease and the
no, novi podaci o prirodnom tijeku bolesti i identifikaciji pre-
identification of predictors of outcome permit improvement in
diktora ishoda omoguÊuju napredak u procesu donoπenja the decision-making process and management of patients
odluka i lijeËenju pacijenata s bolestima srËanih zalistaka. with VHD.
AORTNA STENOZA AORTIC STENOSIS
Disease progression
Progresija bolesti
In a population-based study which followed up 953 subjects
U populacijskoj studiji koja je pratila 953 ispitanika u trajanju
for ten years, a high prevalence of calcific aortic valve disea-
od deset godina, opisana je visoka uËestalost kalcificirane
se (28%) associated with longterm exposure to raised cho-
bolesti aortnih zalistaka (28%) povezane s dugotrajnim izla-
lesterol levels and active smoking was described.2 Intralea-
ganjem hiperkolesterolemiji i aktivnom puπenju.2 Krvarenje
flet haemorrhage (detected by immunohistochemistry at the
unutar listiÊa (koje se detektira pomoÊu imunohistokemije u
moment of aortic valve replacement surgery) was frequent-
trenutku operativnog zahvata zamjene aortnog zaliska) Ëe-
ly present in the valve leaflets of degenerative aortic steno-
sto je bilo prisutno u listiÊima zalistaka kod degenerativne
sis (AS) and was associated with rapid progression of AS.3
aortne stenoze (AS) te je povezano s brzom progresijom
bolesti.3 U maloj studiji na 164 pacijenta s reumatskom AS In a small study of 164 patients with rheumatic AS (of whom
(od kojih je 30 lijeËeno statinima), progresija AS je bila spori- 30 were treated with a statin), progression of AS was slower
ja kod pacijenata koji su primali statin nego kod nelijeËenih in patients receiving statins than in untreated patients (an-
(godiπnja promjena V . nad aortom: 0,056±0,07m/s/godiπ- nual change of peak aortic velocity: 0.05±0.07 m/s/year vs
max
nje nasuprot 0,126±0,11m/s/godiπnje, p=0,001).4 S druge 0.12±0.11 m/s/year, p=0.001).4 On the other hand in the
strane, u studiji ASTRONOMER, dvostrukoj slijepoj rando- ASTRONOMER trial, a randomised double-blind study, that
miziranoj studiji koja je 269 ispitanika lijeËila sa 40mg rosu- allocated 269 patients to rosuvastatin 40 mg daily or to pla-
vastatina dnevno ili placebom, terapija statinom nije smanji- cebo, statin treatment did not reduce progression of the dis-
la progresiju bolesti kod pacijenata s AS.5 ease in patients with AS.5
Prediktori ishoda Predictors of outcome
Na temelju brzine aortnog mlaza i razine natriuretskog pepti- Based on the aortic jet velocity and the B-type natriuretic
da tipa B (BNP), na nezavisnoj kohorti je izvedena i potvr- peptide (BNP) level, a risk score predicting outcome in
2012;7(3-4):65. KardioLIST
ena ljestvica rizika koja predvia ishod kod pacijenata s patients with moderate-to-severe asymptomatic AS was de-
umjerenom do teπkom asimptomatskom AS: ljestvica = (V rived and validated in an independent cohort: score=(peak
max
(m/s) 2) + (ln od vrijednosti BNP 1,5) +1,5 (ako se radi o velocity (m/s) x 2)+(ln of BNP x 1.5) +1.5 (if female sex).
æenskom spolu). Preæivljenje bez dogaaja nakon 20 mje- Event-free survival after 20 months was particularly poor
seci bilo je izrazito loπe (7%) za pacijente u Ëetvrtoj kvartili.6 (7%) for patients in the fourth quartile.6
U zasebnoj studiji pacijenata s teπkom asimptomatskom AS, In a separate study of patients with severe asymptomatic
AS, event-free survival rates at 3 years were 49%, 33% and
stopa preæivljenja bez dogaaja nakon tri godine je iznosila
11% for patients with peak aortic jet velocities between 4.0
49%, 33% odnosno 11% za pacijente s V nad aortom
max
and 5.0 m/s, 5.0 and 5.5 m/s or >5.5 m/s, respectively. In ad-
izmeu 4,0 i 5,0 m/s, 5,0 i 5,5m/s te >5,5 m/s. Uz vaæne im-
dition to the important implications for risk stratification,
plikacije za stratifikaciju rizika, ovi podaci nas uvode u temu
these data introduce us to the entity of “very severe aortic
“izrazito teπke aortne stenoze” na temelju V nad aortom
max stenosis” based on a peak aortic jet velocity >5.0m/s.7 In
≥5,0 m/s.7U drugoj studiji, analiza ROC krivulje identificirala
another study, receiver-operator curve analysis identified a
je V nad aortom ≥4,4 m/s, longitudinalnu deformaciju mio-
max peak aortic jet velocity ≥4.4m/s, a left ventricular (LV) longi-
karda lijeve klijetke (LV) ≤5,9%, valvularnu arterijsku impe-
tudinal myocardial deformation ≤5.9%, a valvular-arterial im-
danciju ≥4,9 mmHg/ml/m2i indeksiranu povrπina lijevog atri- pedance ≥4.9 mmHg/ml/m2 and an indexed left atrial area
ja ≥12,2 cm2/m2 kao Ëimbenike povezane s nepovoljnim ≥12.2 cm2/m2 as factors associated with adverse outcomes
ishodima kod 163 pacijenata s umjerenom do teπkom AS.8 in 163 patients with moderate to severe AS.8
Rane elektivne operacije su obavljene kod 102 pacijenta s Early elective surgery was performed on 102 patients with
teπkom AS (povrπina zaliska ≤0,75 cm2, Vmax nad aortom severe AS (valve area ≤0.75cm2, AV-velocity ≥4.5m/s), and
≥4,5 m/s), a konvencionalno je bilo lijeËeno 95 pacijenata. U conventional treatment was used for 95 patients. Compared
usporedbi s konvencionalnim lijeËenjem, pacijenti s teπkom with conventional treatment, early surgery in patients with
AS lijeËeni ranim operativnim zahvatom imali su bolje du- very severe AS was associated with improved long-term
goroËno preæivljavanje zbog smanjenja kardioloπkog morta- survival by decreasing cardiac mortality.9However, this was
liteta.9Meutim, ovo nije bila randomizirana studija i pristra- not a randomised study and selection bias might have af-
nost pri odabiru je mogla utjecati na rezultate. fected the results.
Kod asimptomatskih pacijenata s AS (n=135) i normalnim In asymptomatic patients with AS (n=135) and a normal
odgovorom na optereÊenje, porast srednjeg transvalvular- exercise response, an exercise-induced increase in mean
nog gradijenta za >20 mmHg u optereÊenju predstaljalo je transvalvular gradient >20mmHg was described as an inde-
neovisan prediktor rizika. Ovi rezultati stoga ukazuju da pendent risk predictor. These results thus suggest that exer-
stres ehokardiografija optereÊenjem moæe donijeti dodatne cise stress echocardiography may provide prognostic infor-
prognostiËke podatke uz one koji se dobivaju standardnim mation additional to that obtained by standard exercise test-
testovima optereÊenjem te ehokardiografijom u mirovanju.10 ing and resting echocardiography.10 Symptoms on treadmill
Prilikom testiranja optereÊenjem na pokretnoj traci 38 asim- exercise testing in 38 apparently asymptomatic patients with
ptomatskih pacijenata s umjerenom AS nastali simptomi bili at least moderate AS were associated with a lower peak
su povezani s niæom vrπnom VO2 miokarda, niæim vrπnim myocardial VO2, a lower peak stroke index during exercise
stroke indeksom u optereÊenju i niæim razinama BNP.11 and BNP levels.11 Increased valvuloarterial impedance
PoveÊana valvuloarterijalna impedancija (Z(va)) (procijenje- (Z(va)) (which is calculated by dividing the estimated LV sy-
ni sistoliËki tlak u LV (sistoliËki arterijski tlak + srednji trans- stolic pressure (systolic arterial pressure + mean transvalvu-
valvularni gradijent) podijeli se s udarnim volumenom ovis- lar gradient) by the stroke volume indexed for the body sur-
no o povrπini tijela) predstavlja marker prekomjernog hemo- face area) is a marker of excessive LV haemodynamic load,
dinamskog optereÊenja LV i vrijednost >3,5 uspjeπno identi- and a value >3.5 successfully identifies patients with AS with
ficira pacijente s AS i loπim ishodom.12 Meutim, i dalje je a poor outcome.12 However, the clinical value of this meas-
potrebno u potpunosti odrediti kliniËku vrijednost ove mjere. ure remains to be fully determined.
Kod 143 pacijenta s AS procijenjen je prognostiËki znaËaj The prognostic significance of mid-wall fibrosis and infarct
fibroze srednjeg dijela stijenke i infarktnih obrazaca detekti- patterns detected by late gadolinium enhancement was eva-
ranih pomoÊu oslikavanja odgoenim bojanjem gadolinije- luated in 143 patients with aortic stenosis. Mid-wall fibrosis
vim kontrastom. Fibroza srednjeg dijela stijenke (HR=5,35; (HR=5.35; p=0.03) and ejection fraction (HR=0.96; p=0.01)
p=0,03) i ejekcijska frakcija (HR=0,96; p=0,01) su bili neo- were independent predictors of all-cause mortality and may
visni prediktori ukupne smrtnosti te mogu dati korisnu meto- provide a useful method of risk stratification.13 There is evi-
du stratifikacije rizika.13 Postoje dokazi o subkliniËkoj dis- dence of subclinical myocardial dysfunction early in the di-
funkciji miokarda rano u tijeku bolesti unatoË normalnoj ejek- sease process despite normal left ventricular ejection frac-
cijskoj frakciji lijeve klijetke (LVEF). »ini se da disfunkcija tion (LVEF). The myocardial dysfunction appears to start in
miokarda poËinje u subendokardu i napreduje do transmu- the subendocardium and to progress to transmural dysfunc-
ralne disfunkcije s poveÊanjem teæine AS. Simptomatski pa- tion with increasing AS severity. Symptomatic patients with
cijenti s AS imaju jaËe oπteÊene multidirekcionalne funkcije AS have more impaired multidirectional myocardial func-
miokarda od asimptomatskih pacijenata.14 Kod pacijenata s tions than asymptomatic patients.14 In patients with severe
teπkom AS, naruπeno je multidirekcionalno naprezanje LV i AS, impaired multidirectional LV strain and strain rate are
stupanj naprezanja Ëak i uz oËuvanu LVEF, a znaËajno po- present even with preserved LVEF, but a significant impro-
boljπanje nastupa po zamjeni aortnog zaliska (AVR).15 Niæe vement occurs after aortic valve replacement (AVR).15Lower
prosjeËno longitudinalno naprezanje povezano je s viπom average longitudinal strain is related to higher LV mass,
LV masom, koncentriËnom geometrijom i teæom AS.16Nepri- concentric geometry and more severe AS.16 Inappropriately
mjereno velika masa LV je registrirana kod 58% asimpto- high LV mass was found in 58% of asymptomatic patients
matskih pacijenata s teπkom AS i bila je povezana s kardio- with severe AS and was related to cardiovascular events.
vaskularnim dogaajima. Preæivljenje bez dogaaja u paci- Event-free survival for patients with appropriate and inap-
jenata s primjerenom i neprimjerenom masom LV, bilo je propriate LV mass, respectively, was 78% vs 56% at 1 year,
KardioLIST 2012;7(3-4):66.
78% naspram 56% nakon godine dana, 68% naspram 29% 68% vs 29% at 3 years and 56% vs 10% at 5 years (all
nakon tri godine te 56% naspram 10% nakon pet godina p<0.01).17However, in patients with calcific AS and a normal
(sve p<0,01).17Meutim, kod pacijenata s kalcificiranom AS LVEF the severity of stenosis was the most important corre-
i normalnom LVEF teæina stenoze je bila najvaænija poveza- late of symptomatic deterioration. Tissue Doppler measures
nost s pogorπanjem simptoma. Mjerenja sistoliËke i dijasto- of LV systolic and diastolic function and LV mass provide
liËke funkcije i mase LV tkivnim doplerom donose ograni- limited predictive information after accounting for the sever-
Ëene prediktivne podatke nakon πto se uzme u obzir teæina ity of stenosis.18
stenoze.18
Outcome of symptomatic patients with aortic
Ishodi simptomatskih pacijenata s aortnom stenosis
stenozom
Severe aortic valve stenosis is a medical condition with lim-
Teπka AS predstavlja bolest s ograniËenim kratkoroËnim ited short-term survival for patients over the age of 75 years,
preæivljenjem kod pacijenata starijih od 75 godina, naroËito particularly those at high surgical risk. Patients with the high-
onih s visokim operativnim rizikom. Pacijenti s najviπim oper- est surgical risk have the worst prognosis if AS is not trea-
ativnim rizikom imaju najloπiju prognozu ako ne lijeËe AS.19 ted.19It has been confirmed, that patients screened but with-
Utvreno je da pacijenti kod kojih je probir obavljen bez kri- out the inclusion/exclusion criteria necessary to participate
terija ukljuËivanja/iskljuËivanja nuænih za sudjelovanje u stu- in a transcatheter aortic valve implantation trial do poorly
diji transkateterske implantacije aortnog zaliska imaju loπ and have extremely high mortality rates, especially in non-
ishod i iznimno visoku uËestalost smrtnosti, naroËito u skupi- surgical groups: 274 such patients were treated medically or
ni koja nije operativno lijeËena: 274 pacijenata lijeËeno je with balloon aortic valvuloplasty and had a mortality of
medikamentima ili balonskom aortnom valvulopastikom uz 37.2% as compared with a mortality of 21.5% for 88 patients
smrtnost od 37,2% u usporedbi sa 21,5% kod 88 pacijenata who underwent AVR (these latter patients were less symp-
podvrgnutih AVR (koji su bili manje simptoma i niæi EURO- tomatic and had a lower EUROscore) during a median fol-
score) tijekom prosjeËnog vremena praÊenja u trajanju od low-up of about 1 year.20 In an observational study of 25
oko 1 godine.20U opservacijskoj studiji s 25 pacijenta s teπ- patients with severe AS presenting in cardiogenic shock, the
kom AS koja se manifestirala kardiogenim πokom, uporaba use of an intra-aortic balloon pump improved the cardiac
intra-aortne balonske pumpe je poboljπala srËani indeks sa index from 1.77 to 2.18 and 2.36 l/min/m2 at 6 and 24 h,
1,77 na 2,18 l/min/m2nakon 6 h i na 2,36 l/min/m2nakon 24 respectively (p<0.001) and should thus be considered in this
h (p<0,001) te bi se stoga trebala uzeti u obzir kod ovih kri- critically ill population while being evaluated for further inter-
tiËno bolesnih pacijenata dok se obavljaju procjene za mo- ventions.21
guÊe daljnje intervencije.21
Low gradient aortic stenosis
Aortna stenoza niskog gradijenta
Five-year survival in patients with low-flow/low-gradient aor-
Petogodiπnje preæivljenje kod pacijenata s AS niskog proto- tic stenosis without contractile reserve was higher in patients
ka/niskog gradijenta bez kontraktilne rezerve bilo je viπe kod undergoing AVR than in medically managed patients
pacijenata koji su podvrgnuti AVR nego onih lijeËenih lije- (54±7% vs 13±7%, p=0.001) despite a high operative mor-
kovima (54±7% naspram 13±7%, p=0,001) unatoË visokom tality of 22%. Surgery should thus not be withheld in this
operativnom mortalitetu od 22%. Operacijsko lijeËenje stoga subset of patients solely on the basis of lack of contractile
ne bi trebalo biti uskraÊeno ovoj podskupini pacijenata is- reserve on dobutamine stress echocardiography.22
kljuËivo na temelju nedostatka kontraktilne rezerve na dobu- Measuring the degree of aortic valve calcification by multi-
taminskoj stres ehokardiografiji.22 slice CT in patients with mild-to-moderate AS and an EF≥
Mjerenje stupnja kalcifikacije aortnog zaliska pomoÊu viπe- 40%, showed that a threshold of 1651 arbitrary units provid-
slojnog CT kod pacijenata s blagim do umjerenim stupnjem ed 82% sensitivity, 80% specificity, 88% negative-predictive
AS i EF≥40%, pokazalo je da prag od 1.651 arbitrarne je- value and 70% positive-predictive value to diagnose severe
dinice daje 82% osjetljivost, 80% specifiËnost, 88% nega- AS. Performance was best in a subset of patients with low
tivnu prediktivnu vrijednost i 70% pozitivnu prediktivnu vri- EF when the threshold correctly differentiated between pa-
jednost za dijagnozu teπke AS. UËinak je bio najbolji u pod- tients with severe AS (the diagnosis was confirmed by mean
skupini pacijenata s niskom EF kada je graniËni prag u 46 gradient, natural history or dobutamine stress echocardiog-
od 49 sluËajeva toËno klasificirao pacijente s teπkom AS (di- raphy) and those with non-severe AS in 46 of 49 cases. This
jagnoza je potvrena srednjim gradijentom, tijekom bolesti ili method may be particularly useful for the evaluation of AS
dobutaminskom stres ehokardiografijom) i od onih s lakπim severity in difficult cases, such as patients with reduced EF
stupnjem AS. Ova je metoda naroËito korisna za procjenu and low or absent contractile reserve.23
teæine AS kod sluËajeva pacijenata s reduciranom EF te On echocardiography approximately one-third of patients
niskom ili odsutnom kontraktilnom rezervom.23 with severe aortic valve stenosis, based on aortic valve area
Na ehokardiografiji je otprilike treÊina pacijenata s teπkom <1.0 cm2, have a non-severe mean pressure gradient (≤40
AS, na temelju povrπine aortnog zaliska <1,0cm2, imala blaæi mmHg) despite apparently normal left ventricular function.
srednji gradijent tlaka (≤40mmHg) uz normalnu funkciju LV. Three hundred and thirty-three consecutive patients under-
333 uzastopna pacijenta bilo je podvrgnuto kateterizaciji went cardiac catheterisation within 30 days after their index
srca unutar 30 dana nakon njihove poËetne ehokardiografi- echocardiography. On invasive testing, 85 patients (26%)
je. Na invazivnom testiranju, 85 pacijenata (26%) je pokaza- demonstrated inconsistent grading, with a significantly lower
lo nekonzistentno stupnjevanje, sa znaËajno niæim udarnim stroke volume and stroke volume index. However, 48% of
volumenom i indeksom udarnog volumena. Meutim, 48% inconsistently graded patients had a normal stroke volume
nekonzistentno stupnjevanih pacijenata imalo je normalan index >35 ml/m2. In the framework of current guidelines
2012;7(3-4):67. KardioLIST
indeks udarnog volumena >35 ml/m2. U okviru trenutnih inconsistent grading of aortic valve stenosis is common, ex-
smjernica nekonzistentno stupnjevanje AS je uobiËajeno, tends to cardiac catheterisation and is only partially ex-
obuhvaÊa kateterizaciju srca te je samo djelomiËno objaπ- plained by low stroke volume despite apparently normal left
njeno niskim udarnim volumenom unatoË normalnoj sisto- ventricular systolic function.24 In this SEAS substudy, aortic
liËkoj funkciji LV.24 U podstudiji SEAS, dogaaji povezani s valve-related events, major cardiovascular events and car-
aortnim zaliscima, veliki kardiovaskularni dogaaji i kardio- diovascular death in patients with low-gradient “severe” aor-
vaskularna smrt kod pacijenata s niskim gradijentom “teπke” tic stenosis (aortic valve area <1.0 cm2 and mean gradient
AS (povrπina aortnog zaliska <1,0 cm2i srednji gradijent ≤40 ≤40mmHg) were comparable to those of patients with mod-
mmHg) bili su usporedivi s onima kod pacijenata s um- erate stenosis (aortic valve area 1.0-1.5 cm2; mean gradient
jerenom stupnjem AS (povrπina aortnog zaliska 1,0-1,5 cm2; 25-40 mmHg).25 These results fuel the debate on the man-
srednji gradijent 5-40 mmHg).25Ovi rezultati potiËu debatu o agement of such patients. In severe AS, a low gradient is
lijeËenju takvih pacijenata. Kod teπke AS, niski gradijent je associated with a higher degree of interstitial fibrosis in bio-
povezan s viπim stupnjem intersticijalne fibroze u uzorcima psy samples and more late-enhancement MRI segments,
biopsije i viπe segmenata kod MRI s odgoenim bojanjem te decreased longitudinal function assessed by echocardiogra-
ehokardiografski smanjenom longitudinalnom funkcijom i lo- phy and poorer clinical outcome despite preserved EF.26
πijim kliniËkim ishodom unatoË oËuvane EF.26
Experimental studies in aortic stenosis
Eksperimentalne studije aortne stenoze
Higher serum phosphate levels within the normal range
Viπe serumske razine fosfata unutar normalnog raspona were associated with aortic valve sclerosis and mitral and
povezane su sa sklerozom aortnog zaliska te mitralnom i aortic annular calcification in a community-based cohort of
aortnom kalcifikacijom u starijih odraslih osoba. Suprotno older adults. In contrast, serum calcium, parathyroid hormo-
tome, serumske razine kalcija, koncentracije paratiroidnog ne and 25-hydroxyvitamin D concentrations were not asso-
hormona i 25-hidroksivitamina D nisu povezane s aortnom ili ciated with aortic or mitral calcification. Phosphate may be a
mitralnom kalcifikacijom. Fosfati bi mogli biti novi faktor ri- new risk factor for calcific aortic valve disease and warrants
zika za kalcificirajuÊu bolest aortnih zalistaka te zahtijevaju further study.27The upregulation of the leukotriene pathway
daljnje studije.27 PoveÊanje leukotrijenskog puta kod AS u in human aortic valve stenosis and its correlation with clini-
pacijenata i njegova veza s kliniËkom teæinom stenoze te po- cal stenosis severity, taken together with the potentially de-
vezanost s potencijalno πtetnim uËincima na valvularne mio- trimental leucotriene-induced effects on valvular myofibrob-
fibroblaste koji su inducirani leukotrijenom, ukazuje na mo- lasts, suggests one possible role of inflammation in the de-
guÊu ulogu upale u razvoju AS.28 Evaluirane su mehaniËke velopment of AS.28 Mechanical properties of porcine aortic
znaËajke aortnog zaliska svinje: serotonin je inducirao sma- valve leaflets were evaluated: serotonin induced a decrease
njenje povrπinske krutosti kuspisa, πto je poniπteno djelo- in the areal stiffness of the cusp, which was reversed by N-
vanjem N-nitro-L-arginin-metil estera ili endotelijalnom de- nitro-L-arginine-methyl ester or endothelial denudation. En-
nudacijom. Endotelin-1 je uzrokovao poveÊanje krutosti, ali dothelin-1 caused an increase in stiffness, but not in the pre-
ne u prisutnosti citokalazina B. Promjene u krutosti kuspisa sence of cytochalasin B. Changes in cusp stiffness were ac-
su popraÊene relaksacijom aortnih kuspisa uz 5-hidroksi- companied by aortic cusp relaxations to 5-hydroxytriptami-
triptamin, πto se poniπtava endotelijalnom denudacijom i N- ne, which were reversed by endothelial denudation and by
nitro-L-arginin-metil esterom. Ovi podaci naglaπavaju ulogu N-nitro-L-arginine-methyl ester. These data highlight the ro-
endotela u regulaciji mehaniËkih svojstava aortnih kuspisa le of the endothelium in regulating the mechanical properties
te istiËu vaænost staniËnog integriteta za optimalnu funkciju of aortic valve cusps and underline the importance of valve
zaliska.29 Smanjeni regenerativni kapacitet valvularnih en- cellular integrity for optimal valve function.29A reduced rege-
dotelnih stanica zbog starenja i smanjene razine endotelnih nerative capacity of valvular endothelial cells due to senes-
progenitorskih stanica mogao bi, bar djelomiËno, biti pato- cence and decreased levels of endothelial progenitor cells
loπka veza za uniπtenje valvularnih endotelnih stanica, πto might be, at least in part, a pathological link for the destruc-
rezultira progresijom degenerativne AS.30Podastrt je izravan tion of valvular endothelial cells, resulting in progression of
in vivo dokaz da katepsinom S inducirana elastoliza ubrza- degenerative AS.30Direct in vivo evidence was provided that
va kalcifikacije arterija i kalcifikacije aortnog zaliska kod kro- cathepsin S-induced elastolysis accelerates arterial and aor-
niËne bolesti bubrega, πto daje novi uvid u patofiziologiju tic valve calcification in chronic renal disease, providing new
kardiovaskularnih kalcifikacija.31Kod miπeva s nedostatkom insight into the pathophysiology of cardiovascular calcifica-
receptora za LDL, redovito vjeæbanje sprjeËava sklerozu tion.31 In the low-density lipoprotein-receptor-deficient mou-
aortnog zaliska pomoÊu nekoliko mehanizama ukljuËujuÊi se, regular exercise training prevents aortic valve sclerosis
oËuvanje endotelnog integriteta, smanjenja upale i oksida- by several mechanisms, including the preservation of endo-
tivnog stresa te inhibiciju osteogenog puta.32Terapija rekom- thelial integrity, a reduction in inflammation and oxidative
binantnim apolipoproteinom A-I Milano preokreÊe tijek AS stress, and inhibition of the osteogenic pathway.32 Recom-
na eksperimentalnom zeËjem modelu. »ini se da do korisnih binant apolipoprotein A-I Milano treatment reverses AS in an
uËinaka dolazi posredstvom poboljπanog uklanjanja koleste- experimental rabbit model. The beneficial effects seem to be
rola i smanjenjem upale i kalcifikacija.33Dodatni podaci upu- mediated by enhanced cholesterol removal and by reduced
Êuju na to da razina lipida u plazmi pomoÊu genetske inak- inflammation and calcification.33Additional data indicate that
tivacije MTTP gena kod hiperkolesterolemiËnih miπeva s reducing plasma lipid levels by genetic inactivation of the
ranom nastalom bolesti aortnog zaliska normalizira oksida- MTTP gene in hypercholesterolaemic mice with early aortic
tivni stres, smanjuje proosteogeno signaliziranje i zaustavlja valve disease normalises oxidative stress, reduces pro-
progresiju AS.34 Pacijenti s AS i dijabetesom imaju teæu di- osteogenic signalling and halts the progression of aortic
jastoliËku LV disfunkciju, koja je predispozicija za zatajivan- valve stenosis.34Patients with AS and diabetes have worse
je srca. »ini se da je to rezultat veÊe fibroze miokarda (doku- diastolic LV dysfunction, predisposing to heart failure. It ap-
mentirane perioperativnom biopsijom LV), viπeg intra- pears to result from greater myocardial fibrosis (documented
KardioLIST 2012;7(3-4):68.
miokardijalnog vaskularnog taloæenja unaprijeenog glikaci- with perioperative LV biopsies), more intra-myocardial vas-
jskog zavrπnog proizvoda i viπeg kardiomiocitnog Fpasiva, cular advanced glycation end-product deposition and higher
πto je povezano s hipofosforilacijom N2B tinin izoforma.35 cardiomyocyte Fpassive, which is related to hypophospho-
rylation of the N2B titin isoform.35
AORTNA REGURGITACIJA
AORTIC REGURGITATION
U opservacijskoj studiji sa 756 pacijenata s teπkom aortnom
regurgitacijom (AR), skupina koja je lijeËena beta-bloka- In an observational study of 756 patients with severe aortic
torom (n=355) imala je znaËajno bolju stopu preæivljenja na- regurgitation (AR), those taking a beta-blocker (n=355) had
kon prve i pete godine (90%, odnosno 70%) od pacijenata significantly better survival rates of 90% and 70% at 1- and
koji nisu primali tu terapiju (75% i 55%, p=0,0009), πto uka- 5-years than patients not receiving treatment (75% and
zuje da pacijenti s teπkom AR mogu imati koristi od terapije 55%, respectively; p=0.0009), suggesting that beta-blocker
beta-blokatorima.36 Oko Ëetvrtine pacijenata (191 od 756) s treatment may confer a survival benefit in patients with se-
teπkom AR imaju bar umjerenu mitralnu regurgitaciju (MR) vere AR.36 About one-quarter (191 of 756) of patients with
te je u retrospektivnoj kohortnoj studiji MR bila neovisni pre- severe AR have at least moderate mitral regurgitation (MR),
diktor loπijeg preæivljenja. DapaÊe, AVR zajedno sa istodob- and in a retrospective cohort study MR was an independent
nom rekonstrukcijom mitralnog zaliska (MV) povezani su s predictor of reduced survival. Moreover, performing AVR
poboljπanim preæivljenjem. Ovi podaci ukazuju da razvoj MR plus concomitant mitral valve repair was associated with
moæe dati korisne informacije o izboru vremena operacije improved survival. These data suggest that the development
kod pacijenata s AR.37 of MR might provide useful information about the timing of
LijeËnici Ëesto nerado preporuËaju AVR pacijentima s surgery in patients with AR.37 Doctors are often reluctant to
teπkom AR i povezanom teπkom disfunkcijom LV (EF≤35%), offer AVR to patients with severe
no nedavna studija je ipak pokazala da lijeËenje primjenom AR and associated severe LV dysfunction (EF≤35%), yet a
AVR rezultira znaËajno boljim stopama preæivljenja nakon 5 recent study has shown that it results in significantly impro-
godina od 70% u usporedbi s 37% za pacijente na kojima ved 5-year survival rates of 70% as compared with 37% for
nije uËinjen operativni zahvat. Meutim, znaËajno je napo- patients not receiving surgery. Significantly, however, sur-
menuti da su operativni zahvati obavljeni na samo 53 od 166 gery was only performed in 53 of 166 patients.38In patients
pacijenata.38Kod pacijenata s AR, makroskopska hipertrofi- with AR macroscopic LV hypertrophy normalises late after
ja LV se normalizira kasno nakon AVR, iako hipertrofija AVR, although fibre hypertrophy persists. These changes in
vlakana ostaje. Ove promjene u strukturi miokarda LV kasno LV myocardial structure late after AVR are accompanied by
nakon AVR popraÊene su promjenom pasivnih elastiËnih a change in passive elastic properties with persistent dias-
svojstava uz perzistentnu dijastoliËku disfunkciju.39 tolic dysfunction.39
Postoji sve veÊi interes za postupke kirurπke rekonstrukcije There is increasing interest in surgical reconstruction proce-
te postoje izvjeπÊa o dobrim ranim rezultatima u iskusnim dures and in experienced hands, good early results have
rukama. Stoga je kod 316 pacijenata koji su podvrgnuti re- been reported. Thus, in 316 patients who underwent recon-
konstrukciji regurgitantnog bikuspidnih aortnih zalistaka bol- struction of regurgitant bicuspid aortic valves hospital mor-
niËki mortalitet iznosio 0,63%, a preæivljenje nakon 10 godi- tality was 0.63% and survival was 92% at 10 years. Free-
na bilo je 92%. Izostanak potrebe za reoperacijom nakon 5 dom from reoperation at 5 and 10 years was 88% and 81%,
godina je iznosio 88%, a nakon 10 godina 81%. Prediktori respectively. Predictors of reoperation were age, aortoven-
reoperacije su bili starost, aortoventrikularni promjer, efek- tricular diameter, effective height, commissural orientation
tivna visina, komisuralna orijentacija i uporaba perikardijalne and the use of a pericardial patch.40 In another study, an
zakrpe.40U drugoj studiji registriran je pozitivan srednjoroËni acceptable mid-term outcome was reported for aortic valve-
ishod za poπtedan operativni zahvat aortnog zaliska. Repa- sparing surgery. Root repair was performed with either a
racija korijena je obavljena ili s reimplantacijom (74%) ili teh- reimplantation (74%) or a remodelling (26%) technique.
nikom remodeliranja (26%). Reparacija kuspisa je bila po- Cusp repair was required more often in bicuspid valves than
trebna ËeπÊe kod bikuspidnih zalistaka nego kod trikuspid- in tricuspid valves (91% vs 38%, p<0.001).
nih zalistaka (91% naspram 38%, p<0,001). At 8 years, freedom from reoperation was 90±7% and over-
Nakon osam godina, izostanak potrebe za reoperacijom je all survival was 88±8%. Predictors of recurrent moderate or
iznosio 90±7%, a ukupno preæivljenje je bilo 88±8%. Pre- severe AR were preoperative left ventricular end-diastolic
diktori rekurentnog umjerenog ili teπkog AR bili su predope- diameter and more than mild AR on discharge echocardiog-
rativni zavrπni dijastoliËki promjer LV i teæi stupanj od blage raphy.41
AR ehokardiografijom kod otpusta.41
BICUSPID AORTIC VALVE DISEASE
BIKUSPIDNI AORTNI ZALISTAK
Cardiovascular magnetic resonance allows characterisation
Kardiovaskularna magnetska rezonancija omoguÊava ka- of valve phenotype in patients with bicuspid aortic valves
rakterizaciju fenotipa zaliska kod pacijenata s bikuspidnim (BAVs). A raphe was identified in the majority of patients
aortnom valvulom (BAV). Greben (raphe) je identificiran kod (n=90; 86%). Among patients with raphe, 76 patients had
veÊine pacijenata (n=90; 86%) od kojih je njih 76 imalo fuzi- fusion between the right and left cusps and 14 patients had
ju desnog i lijevog kuspisa, a kod 14 pacijenata registrirano fusion between the right and the non-coronary cusps.42The
je spajanje desnog i nekoronarnog kuspisa.42 Spojeni desni fused right and non-coronary leaflet BAVs are the product of
i nekoronarni listiÊi kod BAV nastaju morfogenetskim defek- a morphogenetic defect that occurs before cardiac outflow
tom koji se pojavljuje prije septacije izlaznog trakta u srcu te tract septation and probably relies on an exacerbated nitric
vjerojatno ovisi o pogorπanju o duπikovom oksidu ovisne oxide-dependent epithelial-to-mesenchymal transformation.
epitelijalno-mezenhimalne transformacije. Fuzirani desni i Fused right and left leaflet BAVs result from anomalous sep-
2012;7(3-4):69. KardioLIST
lijevi listiÊi kod BAV rezultat su anomalne septacije proksi- tation of the proximal portion of the cardiac outflow tract,
malnog dijela izlaznog trakta, πto je najvjerojatnije uzroko- probably caused by the distorted behaviour of neural crest
vano neispravnim ponaπanjem stanica neuralnog grebena. cells. The two phenotypes are different aetiological entities
Dva fenotipa rezultat su razliËitih etioloπkih subjekata i mogu and may rely on different genotypes.43 The prevalence of
ovisiti o razliËitim genotipima.43UËestalost dilatacije korijena aortic root dilation in BAV patients is 32% and 53% in their
aorte kod pacijenata s BAV je 32% te 53% kod njihovih ro- first-degree relatives (even with tricuspid aortic valves). Like
aka u prvom koljenu (Ëak i s trikuspidnom aortnom valvu- patients with BAV, their first-degree relatives have a signifi-
lom). Kao i pacijenti s BAV, njihovi roaci u prvom koljenu cantly lower aortic distensibility and greater aortic stiffness
imaju znaËajno niæi indeks aortne rastezljivosti i veÊi indeks index than control subjects. Screening of first-degree rela-
aortne krutosti od kontrolne skupine. Kod pacijenata s BAV tives of patients with a bicuspid aortic valve by echocardio-
probir roaka iz prvog koljena ehokardiografijom treba raz- graphy should be considered for detection of aortic valve
motriti da bi se otkrile malformacije aortnog zaliska i dilataci- malformation and dilated ascending aorta.44 Careful clinical
ja uzlazne aorte.44 Potrebno je paæljivo kliniËko praÊenje follow-up of patients after successful resection of subaortic
pacijenata nakon uspjeπne resekcije subaortne stenoze. Od stenosis is required. Of 121 adults with subaortic stenosis,
121 odrasle osobe s subaortnom stenozom, 23% je imalo 23% had bicuspid valves and 21% had coarctation of the
bikuspidne zaliske, a 21% je imalo koarktaciju aorte. Kirur- aorta. Seventy-nine per cent of the patients had a surgical
πku resekciju subaortog tkiva trebalo je 79% pacijenata. resection of subaortic tissue. Valve surgery for AS was re-
Operacija zaliska za AS bila je potrebna kod 26%, a bila je quired in 26% and was more common in patients with con-
uËestalija kod pacijenata s pridruæenom BAV, koarktacijom comitant BAV disease, coarctation of the aorta and supra-
aorte i supravalvularnom stenozom. Umjerena do teπka AR valvular stenosis. Moderate to severe AR was present in
bila je prisutna kod 16% pacijenata.45 16% of patients.45
AORTNA BOLEST AORTIC DISEASE
©atorasto povlaËenje aortnih kuspisa u dijastoli znaËajno je Diastolic tenting of aortic leaflets is strongly related to the
povezano s teæinom funkcijske AR kod pacijenata s aneur- severity of functional AR in patients with ascending thoracic
izmom uzlazne torakalne aorte. Neusklaenost sinotubular- aortic aneurysms. A sinotubular junction/annulus mismatch
nog spoja/anulusa je znaËajno povezana s πatorastim po- is significantly associated with diastolic leaflet tenting and
vlaËenjem aortnih kuspisa u dijastoli i regurgitacijom zaliska, valve regurgitation, independently of the aneurysm dimen-
neovisno od veliËine aneurizme.46 sion.46
Dilatacija aortnog korijena i smanjena elastiËnost aorte Ëesti Aortic root dilatation and reduced aortic elasticity are com-
su kod pacijenata s tetralogijom Fallot, uz blaæe stupnjeve mon in patients with tetralogy of Fallot, in addition to minor
AR i reduciranu sistoliËku funkciju LV. Patologija zida aorte degrees of AR and reduced left ventricular systolic function.
kod pacijenata s repariranom tetralogijom Fallot moæe neo- Aortic wall pathology in patients with repaired tetralogy of
visno doprinositi disfunkciji LV, kao dio procesa uzroko- Fallot may therefore represent an independent contributor to
vanom viπestrukim Ëimbenicima.47Kod pacijenata s aneuriz- left ventricular dysfunction, as part of a multifactorial pro-
mom uzlazne aorte (bez pridruæenog aortitisa ili akutne dis- cess.47In patients with ascending aortic aneurysm (unasso-
ekcije), aortni zalistak je kongenitalno malformiran (unikusp- ciated with aortitis or acute dissection), the aortic valve is
idan ili bikuspidan) kod 98% pacijenata s AS te kod 60% congenitally malformed (unicuspid or bicuspid) in 98% of
pacijenata s AR. Meu pacijentima s kongenitalno malformi- patients with AS, and in 60% of patients with AR. Among the
ranim zaliscima, oni s AR imaju znaËajno veÊu πansu od patients with congenitally malformed valves, those with AR
znaËajnog gubitka medijalnih elastiËnih vlakana aorte u have a significantly greater likelihood of significant aortic
odnosu na one s AS. Razlika izmeu AS i AR je od velike medial elastic fibre loss than those with AS. Distinction
pomoÊi u predvianju gubitka medijalnih elastiËnih vlakana between AS and AR is helpful in predicting loss of aortic
aorte kod pacijenata s aneurizmom uzlazne aorte i bolesti medial elastic fibres in patients with ascending aortic aneu-
aortnog zaliska.48 Ukupno 93 pacijenta s teπkom izoliranom rysms and aortic valve disease.48 Ninety-three patients with
kalcificirajuÊom AS s trikuspidnim aortnim zaliskom i umje- severe isolated calcific AS with a tricuspid aortic valve who
renom dilatacijom uzlazne aorte (promjer 50-59mm) bilo je also had moderate dilatation of the ascending aorta (diame-
podvrgnuto iskljuËivo AVR. Tijekom praÊenja u trajanju od ter 50e59 mm) underwent AVR only. During a follow-up of
15 godina, nije bilo akutnih aortnih dogaaja (ruptura, disek- 15 years, no acute aortic events (rupture, dissection, pseu-
cija, pseudoaneurizma), ili potrebe za reoperacijom. Osim doaneurysm), or need for reoperation occurred. Furthermo-
toga, nije bilo znaËajnog poveÊanja dimenzije aorte, πto re, there was no substantial increase in aortic dimensions,
ukazuje da se indikacije za pridruæenu operaciju aorte kod suggesting that indications for concomitant aortic surgery in
pacijenata s umjernom poststenotiËnom dilatacijom uzlazne patients with moderate post-stenotic dilatation of the as-
aorte i trikuspidnog aortnog zaliska mogu razmatrati popu- cending aorta anda tricuspid aortic valve, may be viewed
stljivije, naroËito u odsutnosti poremeÊaja vezivnog tkiva.49 U more leniently, particularly in the absence of connective tis-
studiji s ukljuËenih 416 uzastopnih pacijenata s definitivnom sue disorders.49 In a community cohort that included 416
ehokardiografskom dijagnozom BAV koji su bili praÊeni consecutive patients with definite BAV diagnosed by echo-
16±7 godina, incidencija aortne disekcije je bila niska (2 od cardiography, followed up for 16±7 years, the incidence of
416 pacijenata), no viπa u odnosu na opÊu populaciju. Od aortic dissection was low (2 out of 416 patients) but higher
384 pacijenata bez poËetne aneurizme, njih 49 je razvilo than in the general population. Of 384 patients without base-
aneurizmu tijekom praÊenja, a 25-godiπnja stopa operacija line aneurysms, 49 developed aneurysms at follow-up and
aorte iznosila je 25%.50 the 25-year rate of aortic surgery was 25%.50
Brza dijagnoza akutne aortne disekcije spaπava æivote. Eho- Prompt diagnosis of acute aortic dissection saves lives.
kardiografija dugo ima znaËajnu ulogu, a nedavni radovi Echocardiography has a time-honoured role, and recent
KardioLIST 2012;7(3-4):70.
ukazuju da primjena kontrasta u usporedbi s konvencional- work suggests that contrast-enhanced as compared with
nim transtorakalnim snimanjem poboljπava dijagnostiËku conventional transthoracic imaging improves diagnostic
osjetljivost s 73,7% na 86,8% (p<0,005) i specifiËnost za sensitivity and specificity for ortic dissection from 73.7% to
aortnu disekciju s 71,2% na 90,4% (p<0,05). DijagnostiËka 86.8% (p<0.005) and from 71.2% to 90.4% (p<0.05), res-
osjetljivost i specifiËnost kontrastnog transtorakalnog sni- pectively. Indeed, the diagnostic sensitivity and specificity of
manja bila je sliËna klasiËnoj transezofagusnoj ehokardio- contrast-enhanced transthoracic imaging was similar to that
grafiji uzlazne aorte (93,3% naspram 95,6% te 97,6% na- of conventional transoesophageal echocardiography in the
spram 96,4%) i luka aorte (88,4% naspram 93.0% te 95,0% ascending aorta (93.3% vs 95.6% and 97.6% vs 96.4%,
naspram 98,82%) te bi se trebalo razmotriti kao inicijalni respectively) and in the arch (88.4% vs 93.0% and 95.% vs
98.82%, respectively) and should be considered as an initial
naËin snimanja u hitnim sluæbama.51
imaging modality in an emergency.51
MITRALNA REGURGITACIJA
MITRAL REGURGITATION
Degenerativna mitralna regurgitacija (MR) Ëesto je dinamiË-
Degenerative mitral regurgitation (MR) is often dynamic,
na, a pojaËanje teæine MR inducirano vjeæbom moæe se reg-
and exercise-induced increases of MR severity are seen in
istrirati zapaziti kod treÊine pacijenata, πto je povezano s
one-third of patients, associated with changes in systolic
promjenama sistoliËkog tlaka u pulmonalnoj arteriji (PA) i
pulmonary artery pressure and reduced symptom-free sur-
kraÊim preæivljenjem bez simptoma.52 Kad je stupanj MR
vival.52When MR is severe it may be associated with unilat-
teæak moæe se povezati s unilateralnim edemom pluÊa.53
eral pulmonary oedema.53
Pronalaæanje optimalnog vremana za operativni zahvat de-
Improving the timing of surgery for degenerative MR based
generativne MR na temelju prediktora ishoda predstavlja
on predictors of outcome is an important topic. The left atri-
vaænu temu. Pokazalo se da indeks lijevog atrija predvia
al index was shown to predict outcome in 492 patients in
ishod kod 492 pacijenata u sinusnom ritmu s organskom
sinus rhythm with organic MR and should thus be incorpo-
MR pa bi stoga trebao biti ukljuËen u rutinsku kliniËku prak-
rated into routine clinical practice for risk stratification and
su za stratifikaciju rizika i donoπenje kliniËkih odluka.54 Ne- clinical decision-making.54 A recent study showed that in
davna studija je dokazala da se kod MR zbog flail leaflets MR, owing to flail leaflets, a left ventricular end-systolic dia-
(kuspisi invertirani u sistoli s gubitkom koaptacije) promjer meter ≥40mm is independently associated with increased-
LV na kraju sistole ≥40 mm neovisno povezan s poveÊanom mortality for medically and surgically managed patients. Ne-
smrtnosti kod pacijenata lijeËenih farmakoloπki i kirurπki. vertheless, the left ventricular end-systolic dimension may
Iako, promjer LV na kraju sistole moæe dati korisnu smjer- provide a useful guide for the timing of surgery in these pa-
nicu za optimalno vrijeme operativnog zahvata zbog uklju- tients but because both asymptomatic and symptomatic
Ëenih asimptomatskih i simptomatskih pacijenata, potrebna patients were included, the findings need confirmation in
je potvrda nalaza kod serije pacijenata sa simptomima.55 U symptomatically homogeneous cohorts.55 In another study
drugoj studiji s ukljuËenih 256 pacijenata s organskom MR of 256 patients with organic MR referred for mitral valve sur-
upuÊenih na operaciju MV, poËetni sistoliËki tlak u PA pred- gery, baseline pulmonary artery systolic pressure predicted
viao je dugoroËno postoperativno preæivljenje — uz long-term postoperative survival with 8-year survival rates of
osmogodiπnje stope preæivljenja od 58,6% za pacijente Ëiji 58.6% and 86.6% for patients whose PA pressures were
je tlak u PA bio >50 mmHg te 86,6% kod onih s tlakom <50 greater or less than 50 mm Hg, respectively (p<0.0001).56
mmHg (p<0,0001).56 As with other valvular pathologies, oxidative stress may be
aetiologically important in MR. Thus, LV biopsy specimens
Kao i sve ostale valvularne patologije, oksidativni stres mo-
taken during mitral valve repair surgery for isolated MR de-
æe biti etioloπki vaæan kod MR. Stoga su uzorci biopsije LV
monstrated that increased oxidative stress could cause lipo-
uzeti tijekom reparacije MV zbog izolirane MR pokazali da bi
fuscin deposition and cardiomyocyte myofibrillar degenera-
poveÊani oksidativni stres mogao uzrokovati depoziciju lipo-
tion.57
fuscina i miofibrilarnu degeneraciju kardiomiocita.57
The severity of MR seems to be an important determinant of
»ini se da je teæina MR vaæna determinanta reverznog re-
left ventricular reverse remodelling after cardiac resynchro-
modeliranja LV nakon terapije kardioloπkom resinkronizaci-
nisation therapy when gains in LVEF and forward stroke vol-
jom gdje je poboljπanje LVEF i udarnog volumena bilo najz- ume are greatest for patients with improvement in total MR,
naËajnije kod pacijenata s nepostojanjem MR, osrednje za intermediate for those with mild or no MR at baseline and
one s blagim stupnjem ili bez poËetne MR te najmanje kod least in those whose MR shows no improvement.58
onih kod kojih nije bilo registrirano poboljπanje stupnja MR.58
Guideline indications for surgical intervention in patients
Kardiolozi Ëesto zanemaruju indikacije za kirurπku interven- with MR are often ignored by cardiologists and in a recent
ciju prema smjernicama kod pacijenata s MR te je u nedav- assessment of current practice, surgery was performed in
nim procjenama trenutne prakse kirurπki zahvat obavljen only about 50% of cases despite the fact that guideline indi-
kod svega 50% pacijenata unatoË Ëinjenici da je indikacija cations for intervention were present in many of the patients
za intervenciju bila prisutna kod mnogih pacijenata koji nisu not receiving surgery.59 Among patients with guideline indi-
operirani.59Kod pacijenata s indikacijama prema smjernica- cations any delay in carrying out surgery may have impor-
ma bilo kakva odgoda operativnog zahvata moæe imati tant adverse consequences as reflected in a recent report
ozbiljne neæeljene posljedice kao πto je vidljivo iz nedavnog where surgery at a median time of 0.42 months after listing
izvjeπÊa u kojem je kirurπki zahvat u srednjem vremenu od was associated a lower hazard for death than for those who
0,42 mjeseca nakon uvrπtenja povezan s niæim rizikom od underwent later surgery at a median time of 8.75 months
smrtnog ishoda nego kod onih podvrgnutih kasnijim kirur- (HR=0.54, p=0.039).60
πkim zahvatima u srednjem vremenu od 8,75 mjeseci In the study of Samad et al, mitral valve repair was inde-
(HR=0,54, p=0,039).60 pendently associated with mproved survival (HR=0.45,
2012;7(3-4):71. KardioLIST
U studiji Samad i sur., reparacija MV bio je neovisno pove- p=0.01).60 This has been shown in many other recent stud-
zan s poboljπanim preæivljenjem (HR=0,45, p=0,01).60 Ovo ies but an assessment of ‘real-world’ clinical practice based
navode i mnoge druge nedavne studije, no procjena “stvar- on 12,255 mitral valve operations performed in the UK
ne” kliniËke prakse na temelju 12.255 operacija MV u Ujedi- between 2004 and 2008 showed a national rate of only 51%,
njenom Kraljevstvu izmeu 2004. i 2008. je pokazala nacio- and variability of 20% to 90% among different hospitals,
nalnu stopu od svega 51% te varijabilnost od 20% do 90% which the authors likened to a “lottery of mitral valve repair
meu razliËitim bolnicama, πto autor navodi kao “lutrija surgery.”61 This was emphasised further in a more recent
reparacije MV”.61 Ovo je naglaπeno i u novijoj analizi STS analysis of the STS Adult Cardiac Surgery Database, which
Adult Cardiac Surgery Database, koja je pokazala znaËajnu showed substantial variability in rates of mitral valve repair
varijabilnost u stopama reparacije MV meu pojedinim ki- among individual surgeons, ranging from 0% to 100%
rurzima, u rasponu od 0% do 100% (srednja vrijednost (mean 41%). The greatest variability in repair rates was
41%). NajveÊa varijabilnost u stopama reparacije je uoËena seen among surgeons carrying out a low volume of proce-
kod kirurga koji su obavljali mali broj operacija, a poveÊani dures, with increased surgeon-level mitral volume being
broj operacija neovisno je povezan s poveÊanom vjerojatno- independently associated with an increased probability of
sti reparacije MV.62 mitral repair.62
EKSPERIMENTALNE STUDIJE MEHANIZMA EXPERIMENTAL STUDIES ON THE
MITRALNE REGURGITACIJE MECHANISM OF MITRAL REGURGITATION
Razumijevanje mehanizma adaptacije zaliska omoguÊuje Understanding the mechanism of valve adaptation provides
identifikaciju novih bioloπkih i kirurπkih terapijskih ciljeva. An- a potential means of identifying new biological and surgical
teroapikalni infarkt miokarda (IM) s inferoapikalnom eksten- therapeutic targets. Anteroapical myocardial infarction (MI)
zijom moæe mehaniËki pomaknuti papilarne miπiÊe i uzroko- with inferoapical extension can mechanically displace papil-
vati MR, unatoË nedostatku abnormalnosti gibanja bazalne i lary muscles, causing MR despite the absence of basal and
inferiorne stijenke.63 Na modelu ovce kod IM inferiorne sti- midinferior wall motion abnormalities.63In a sheep model of
jenke, epikardijalna zakrpa koja ograniËava dilataciju i MR inferior MI an epicardial patch to limit ventricular dilatation
nakon 3 mjeseca rezultirala je povrπinom listiÊa koja nije bila and MR resulted in a leaflet area at 3 months that was not
znaËajno razliËita od poËetnih vrijednosti. Kod nelijeËenih significantly different from baseline values. In untreated
modela, povrπina MV se poveÊala tijekom vremena kako se sheep, mitral valve area increased over time as the left ven-
LV remodelirao nakon IM inferiorno, neovisno od sistoliËkog tricular remodelled after inferior MI, independently of systolic
rastezanja no nije adekvatno kompenzirala istezanje kako bi stretch but failed to compensate adequately for tethering to
to sprijeËio MR.64LijeËenje teπkog stupnja ishemijske MR je prevent MR.64 Management of severe ischaemic MR re-
i dalje teπko s razoËaravajuÊim ranim i srednjeroËnim kirur- mains difficult with disappointing early and intermediate-
πkim rezultatima reparacije zaliska. Predlaæe se produljenje term surgical results of valve repair. Posterior leaflet exten-
posteriornog listiÊa anuloplastikom MV kod teπkih IIIb oblika sion with annuloplasty of the mitral valve for severe type IIIb
ishemijske regurgitacije kako bi se dobila dobra rana i sred- ischaemic regurgitation has been suggested to provide good
njeroËna sposobnost MV i funkcionalan status.65Na eksperi- early and intermediate-term competence of the mitral valve
mentalnom modelu, vrπci papilarnih miπiÊa kod πest odraslih and functional status.65In an experimental model, the papil-
ovaca su se uvukli u apeks, gotovo proizvevπi MR te su tako lary muscle tips in six adult sheep were retracted apically,
replicirali uËinke istezanja bez pridruæenog IM ili turbulenci- short of producing MRdthus replicating the effects of tether-
je. Nakon 60 dana, ukupna povrπina mitralnih listiÊa u dijas- ing without confounding MI or turbulence. At 60 days, total
toli se poveÊala za 17% te su rastegnuti mitralni kuspisi bili diastolic mitral leaflet area increased by 17% and stretched
2,8 puta deblji od normalnih s poveÊanim spongioznim slo- mitral valves were 2.8 times thicker than normal with an
jem. StaniËne promjene sugeriraju reaktivaciju puteva iz increased spongiosa layer. Cellular changes suggest a re-
embrionalnog razvoja.66 Ustanovljeno je da tenting MV koji activation of embryonic developmental pathways.66 It has
dovodi do funkcijske MR veÊinom odreen silama istezanja been shown that mitral tenting leading to functional MR is
(pomicanje papilarnih miπiÊa) i stezanja (poveÊani tlak lije- mainly determined by tethering (displacement of papillary
vog atrija), neovisno od funkcije klijetke, a ti nalazi nagla- muscles) and pushing forces (increased left atrial pressure),
πavaju srediπnju ulogu predoptereÊenja LV kao kljuËne de- independently of ventricular function, findings that empha-
terminante funkcijske MR.67 sise the central role of left ventricular preload as a key deter-
Kod pacijenata s idiopatskom dilatativnom kardiomiopatijom minant of functional MR.67
koji su bili podvrgnuti anuloplastici zbog funkcijske MR, post- In patients with idiopathic dilated cardiomyopathy who un-
operativni distalni kut prednjeg mitralnog kuspisa (PMK) bio derwent annuloplasty for functional MR, the postoperative
je glavna determinanta povratne funkcijske MR. Preope- distal mitral anterior leaflet angle was the major determinant
rativni distalni kut PMK bio je najbolji prediktor ponavljanja of recurrent functional MR. The preoperative distal mitral
MR. Kako je istezanje straænjeg mitralnog kuspisa neprom- anterior leaflet angle was the best predictor of MR recur-
jenjivo nakon mitralne anuloplastike, postoperativna funkci- rence. Since posterior leaflet tethering is invariable after mi-
ja MV uvelike ovisi o mobilnosti PMK.68 Opisana je snaæna tral annuloplasty, postoperative mitral competence is highly
povezanost izmeu postojeÊe arterijske hipertenzije i ruptu- dependent on distal anterior leaflet mobility.68A strong asso-
re idiopatske mitralne korde tendinee, no ostaje nejasno da ciation between preexisting hypertension and idiopathic
li se to moæe prevenirati kontrolom arterijske hipertenzije.69 mitral chordae tendineae rupture was described. However, it
remains unclear whether prevention by hypertension control
is feasible.69
KardioLIST 2012;7(3-4):72.
TRIKUSPIDNA REGURGITACIJA TRICUSPID REGURGITATION
Trikuspidni zalistak se Ëesto naziva zaboravljeni zalistak, The tricuspid valve is often called the forgotten valve, partly
djelomiËno zato πto su ograniËeni podaci vezani za optimal- because data concerning the optimal timing of surgery in tri-
no vrijeme operativnog zahvata kod trikuspidne regurgitaci- cuspid regurgitation (TR) are limited.
je (TR). During inspiration, a large increase in effective regurgitant
Tijekom inspirija, veliko poveÊanje efektivne povrπine regur- orifice causes a notable increase in tricuspid regurgitant vol-
gitirajuÊeg otvora uzrokuje zamjetno poveÊanje trikuspidnog ume, despite a decline in regurgitant gradient. Effective re-
regurgitirajuÊeg volumena, unatoË smanjenju regurgitiraju- gurgitant orifice changes are independently linked to inspi-
Êeg gradijenta. Promjene efektivnog regurgitirajuÊeg otvora ratory annular enlargement (decreased valvular coverage)
su neovisno povezane s inspiracijskim poveÊanjem anulusa and to inspiratory right ventricular (RV) shape widening with
(smanjena valvularna pokrivenost) te s proπirenjem inspi- increased valvular tenting.
racijskog oblika desne klijetke (RV) s poveÊanim tentingom These physiological insights are important for clinical evalu-
valvule. ation of the severity of TR.70 Severe TR, constrictive peri-
Ove fizioloπke spoznaje su vaæne za kliniËku procjenu teæi- carditis and restrictive cardiomyopathy can all present with
ne TR.70Teπki stupanj TR, konstriktivni perikarditis i restrik- signs and symptoms of right heart failure and similar hae-
tivna kardiomiopatija se mogu prezentirati sa znacima i modynamic findings of elevation and equalisation of dias-
simptomima zatajivanja desnog srca i sliËnim hemodinam- tolic pressures at catheterisation. The haemodynamic find-
skim nalazima porasta i izjednaËavanja dijastoliËkog tlaka ings at cardiac catheterisation in patients with severe, symp-
kod kateterizacije. Hemodinamski nalazi kod kateterizacije tomatic TR are similar to those of constrictive pericarditis.
srca kod pacijenata s teπkom, simptomatskom TR sliËni su Careful analysis of the relationship of the LV and RV dias-
onima s konstriktivnim perikarditisom. Paæljiva analiza tolic pressures during respiration can help differentiate bet-
odnosa dijastoliËkih tlakova LV i RV tijekom respiracije mo- ween the two entities. During inspiration, the difference bet-
æe pomoÊi kod diferenciranja izmeu ta dva entiteta. Ti- ween the LV and RV diastolic pressures widens in patients
jekom inspiracije, razlika izmeu LV i RV dijastoliËkih tlako- with TR but narrows in those with constrictive pericarditis.71
va se poveÊava kod pacijenata s TR, no smanjuje kod onih Of 69 consecutive patients undergoing surgery for isolated
s konstriktivnim perikarditisom.71Od 69 uzastopnih pacijena- severe TR, seven (10.1%) died before discharge. Of the
ta koji su podvrgnuti operativnom zahvatu zbog izolirane te- remaining 62 patients, three died during follow-up and eight
πke TR, njih sedam (10,1%) je umrlo prije otpusta. Od pre- were readmitted owing to cardiovascular problems. RV end-
ostalih 62, troje je umrlo tijekom praÊenja, a osam je ponov- systolic area (p=0.006) and haemoglobin level (p<0.001)
no primljeno zbog kardiovaskularnih problema. Povrπina RV were independent predictors of event-free survival. When
na kraju sistole (p=0,006) i razina hemoglobina (p<0,001) su early postoperative echocardiography variables were
bili neovisni prediktori preæivljenja bez dogaaja. UkljuËe- included, early postoperative RV fractional area change pro-
njem ranih postoperativnih ehokardiografskih varijabli, pro- vided additional information for predicting long-term clinical
mjena rane postoperativne RV frakcijskog povrπine, dobi- events following corrective TR surgery.72 The overall inci-
vene su dodatne informacije za predvianje dugoroËnih kli- dence of late significant TR after successful left-sided valve
niËkih dogaaja nakon korektivnog operativnog zahvata surgery was 7.7% (49/638). Age, female gender, rheumatic
TR.72Ukupna incidencija kasne znaËajne TR nakon uspjeπ- aetiology, atrial fibrillation and peak pressure gradient of TR
ne lijevostrane operacije zaliska iznosila je 7,7% (49/638). at follow-up were independent factors associated with de-
Dob, æenski spol, reumatska etiologija, fibrilacija atrija i mak- velopment of late significant TR. Patients who developed
simalno gradijent TR tijekom praÊenja predstavljali su neza- late significant TR showed a significantly lower 8-year clini-
visne Ëimbenike povezane s razvojem kasnije znaËajne TR. cal event-free survival rate (76% vs 91%, p<0.001).73 After
Pacijenti koji su razvili kasniju znaËajnu TR imali su znaËa- tricuspid annuloplasty, tenting angles of the three leaflets
jno niæu osmogodiπnju stopu preæivljenja bez komplikacija increase, whereas the annulus diameter decreases. Pre-
(76% nasuprot 91%, p<0,001).73 Nakon trikuspidne anulo- surgical tenting volume and anteroposterior tricuspid annu-
plastike, kutovi tentinga tri listiÊa se poveÊavaju, dok se pro- lus diameter are independent predictors of residual TR se-
mjer anulusa smanjuje. Predkirurπki tenting volumen i ante- verity, and may help to identify patients at high risk for se-
roposteriorni trikuspidni promjer anulusa su nezavisni pre- vere residual TR for whom tricuspid valve replacement may
diktori teæine TR te mogu pomoÊi kod identifikacije pacijena- be considered.74 Tricuspid valve replacement for severe
ta s visokim rizikom od teπke rezidualne TR za koje se moæe TR can be performed with an acceptable operative mortali-
razmotriti zamjena trikuspidnog zaliska.74Zamjena trikuspid- ty if patients undergo surgery before the onset of advanced
nog zaliska kod teπke TR se moæe obaviti uz prihvatljivi heart failure symptoms. Late mortality is associated with a
operativni mortalitet ako se pacijenti podvrgnu operativnom high preoperative Charlson index, short right index of
zahvatu prije nastupanja simptoma uznapredovalog zataji- myocardial performance ratio and advanced New York
vanja srca. Kasni mortalitet se povezuje s visokim preope- Heart Association class.75
rativnim Charlson indeksom, kratkim desnim indeksom mio-
kardijalne uËinkovitosti i uznapredovalim stupnjem prema
RISK OF NON-CARDIAC SURGERY
New York Heart Association.75
In a prospective cohort of 2,054 patients undergoing elec-
RIZIK OD NEKARDIOLO©KE OPERACIJE tive major non-cardiac surgery, high preoperative NT-pro-
BNP or C reactive protein were strong, independent predic-
U prospektivnoj kohorti od 2.054 pacijenata koji su pod- tors of perioperative major cardiovascular events (MI, pul-
vrgnuti znaËajnijoj elektivnoj ne-kardioloπkoj operaciji, viso- monary oedema or cardiovascular death) in non-cardiac
ka preoperativna vrijednost NT-proBNP ili CRP su bili snaæ- surgery. The relative event-risk of highest versus lowest
ni, neovisni prediktori znaËajnih perioperativnih kardiova- quartile was 5.2 for NT-proBNP (p<0.001) and 3.7 for C
2012;7(3-4):73. KardioLIST
skularnih dogaaja (IM, edem pluÊa ili kardiovaskularna reactive protein (p<0.001). The predictive power of the cur-
smrt) kod nekardioloπke operacije. Relativni rizik od doga- rent clinical risk evaluation system might be strengthened by
aja za najviπu naspram najniæe kvartile iznosio je 5,2 za application of these biomarkers.76
NTproBNP (p<0,001) i 3,7 za CRP (p<0,001). Prediktivna
moÊ trenutnog sustava procjene kliniËkog rizika bi se mogla
ENDOCARDITIS
poboljπati primjenom ovih biomarkera.76
The high mortality of patients with endocarditis makes it an
ENDOKARDITIS important focus of continuing clinical research. Blood cul-
ture-negative early prosthetic valve endocarditis exhibits
Obzirom na visoku smrtnost endokarditis kontinuirano pred- specific aetiologies, and fungi are the most common patho-
stavlja vaæan predmet kliniËkih istraæivanja. Rani endokardi- gens identified. They should be investigated by molecular
tis umjetne valvule kojeg prate negativne hemokulture ima methods on surgical specimens and an antifungal drug
specifiËnu etiologiju od kojih su gljivice najËeπÊi identificirani might be added to the empirical treatment.77Almost 50% of
patogen. Trebalo bi ih ispitati pomoÊu molekularnih metoda cases of coagulase-negative staphylococcal prosthetic
na kirurπkim uzorcima te bi se empirijskom lijeËenju mogli valve endocarditis occur between 60 and 365 days after
dodati antifungalni lijekovi.77Gotovo 50% sluËajeva endokar- prosthetic valve implantation and are associated with a high
ditisa proteze srËanog zaliska zbog koagulaza negativnih rate of methicillin resistance and significant valvular compli-
stafilokoka se pojavljuje izmeu 60 i 365 dana nakon im- cations.78Increasing age is associated with less valvular im-
plantacije zaliska te su povezani s visokom stopom otpor- pairment (insufficiency and perforation) and a more fa-
nosti na meticilin i znaËajnim valvularnim komplikacijama.78 vourable microbiological profile in patients with left-sided
PoveÊana dob se povezuje s manjim valvularnim oπteÊe- infective endocarditis. However, the therapeutic approach
njem (insuficijencijom i perforacijom) i pogodnijim mikrobio- differs depending on patient age because of the growing
loπkim profilom kod pacijenata s lijevostranim infektivnim proportion of older patients who receive only medical treat-
endokarditisom. Meutim, terapijski pristup se razlikuje ovis- ment. Clinical course and hospital prognosis are worse in
no o dobi pacijenta zbog rastuÊeg udjela pacijenata starije older patients because of an increased surgical mortality.79
æivotne dobi koji se lijeËe iskljuËivo medikamentozno. Kli- Three independent risk factors obtained within 72 h of ad-
niËki tijek i bolniËka prognoza loπiji su kod starijih pacijenata mission for left-sided infective endocarditis (Staphylococcus
zbog poveÊanog kirurπkog mortaliteta.79 Tri neovisna Ëim- aureus, heart failure and periannular complications) predict
benika rizika dobivena unutar 72 sata od prijema kod lijevo- in-hospital mortality or the need for urgent surgery.80 Bicu-
stranog infekcijskog endokarditisa (Staphylococcus aureus, spid aortic valve infective endocarditis accounts for 16% of
zatajvanje srca i perianularne komplikacije) predviaju bol- cases of definite native aortic valve endocarditis and is
niËki mortalitet ili potrebu za hitnim kirurπkim zahvatom.80 associated with a perivalvular aortic abscess in half of the
Infekcijski endokarditis BAV obuhvaÊa 16% sluËajeva defin- cases. The presence of a bicuspid aortic valve (HR=3.79,
itivnog endokarditisa nativnog aortnog zaliska te je povezan p<0.001) is independently predictive of abscess formation,
s perivalvularnim aortnim apscesom u polovice sluËajeva. and early surgery is often required.81There is now evidence
that preoperative coronary angiography can be performed
Prisutnost BAV (HR=3,79, p<0,001) neovisno predvia for-
maciju apscesa te je Ëesto potreban rani operativni zahvat.81 with low risk in selected patients with aortic valve endocardi-
tis. A recent study reported no embolic events, no increase
Sada postoji dokaz da se preoperativna angiografija moæe
in in-hospital mortality (p=0.80) and no worsening of renal
obaviti uz nizak rizik kod odabranih pacijenata s endokardi-
function (p=0.93).82 By performing preoperative coronary
tisom aortnog zaliska. Nedavna studija je izvijestila da nije
angiography in patients with cardiovascular risk factors,
bilo embolijskih dogaaja, niti poveÊanja bolniËkog mortali-
those with significant coronary disease can be considered
teta (p=0,80), a niti pogorπanja bubreæne funkcije (p=0,93).82
for bypass at the time of valve surgery. In a multinational
Po uËinjenoj koronarografiji preoperativno kod pacijenata s
cohort of 1552 patients with native valve endocarditis, early
Ëimbenicima kardiovaskularnog rizika, moæe se razmotriti
surgery was associated with a significant reduction in mor-
indikacija za prijemosnicu kod onih sa znaËajni stupnje ko-
tality compared with medical treatment (12.1% vs 20.7%).83
ronarnom bolesti srca u trenutku operacije zaliska. U multi-
Strategies of early surgery within 7 days, at the discretion of
nacionalnoj studiji s ukljuÊËenih 1.552 pacijenata s endokar-
the attending doctor, and of conventional management in
ditisom nativnog zaliska, rani operativni zahvat bio je pove-
patients with left-sided native-valve were compared in
zan sa znaËajnim smanjenjem smrtnosti u usporedbi s me-
another study. During the initial hospitalisation, there were
dikamentoznim lijeËenjem (12,1% naspram 20,7%).83U dru-
no embolic events and two in-hospital deaths in the surgical
goj studiji je uËinjena usporedba strategija ranog opera-
group (n=64) and 14 embolic events and two in-hospital
tivnog zahvata unutar sedam dana, prema procjeni deæur-
deaths in the conventional group (n=68). The 5-year event-
nog lijeËnika i konvencionalnog lijeËenja pacijenata s lijevos-
free survival rate was significantly better in the surgical
tranim nativnim zaliskom. Tijekom inicijalne hospitalizacije,
group (93±3%) than in the conventional group (73±5%,
tijekom bolniËkog lijeËenja u operiranoj skupini nije bilo em-
p=0.0016).84 Although the timing of surgery was not ran-
bolijskih dogaaja, a registrirane su dva smrtna ishoda
domly allocated, the data suggest that early surgery, when
(n=64) dok je u konvencionalnoj skupini registrirano 14 em-
feasible, may offer important advantages to the patient.
bolijskih dogaaja i dva smrtna ishoda u bolnici (n=68). Pe-
togodiπnje preæivljenje bez dogaaja je bilo znaËajno bolje u
kirurπkoj (93±3%) nego konvencionalnoj skupini (73±5%, VALVE SURGERY
p=0,0016).84 Iako vrijeme operativnih zahvata nije odre- Ross procedure
ivano nasumiËno, podaci ukazuju da rani operativni zahvat
moæe ponuditi dobrobit pacijentima. The controversy surrounding the Ross procedure is high-
lighted by four studies. In a randomised study 216 patients
received either an autograft or a homograft aortic root re-
KardioLIST 2012;7(3-4):74.
Description:bolesti.3 U maloj studiji na 164 pacijenta s reumatskom AS. (od kojih je 30 tients undergoing renal transplantation requiring valve replacement
