| Abstract | In contemporary clinical cardiology practice, echocardiography plays a leading role in the
diagnosis and management guidance of various forms of myocardial remodelling.
Furthermore, it is the most commonly used diagnostic technique in the elucidation of the
underlying substrates and pathophysiologic mechanisms of heart failure as a consequence
of ventricular remodelling. Due to its widespread availability, non-invasiveness, userfriendliness
and relatively low cost, echocardiography is still irreplaceable by other cardiac
imaging methods which should rather be seen as complementary diagnostic tools.
This thesis sought to study several types of ventricular remodelling and their
consequences on regional and global myocardial function, employing different
echocardiographic tools and dedicated signal and image analysis algorithms in the detection
of ventricular dysfunction.
Recent echocardiographic techniques based on Myocardial Velocity Imaging have
provided the possibility of a more detailed and integrated insight to cardiac (dys-) function.
Based on novel understandings, we first gave an original integrated overview on ‘cardiac
function’, distinguishing intrinsic myocyte function (often referred to as contractility) and
ventricular pump function as well as the main components of function, namely force
development and deformation. Additionally, the boundary conditions in which the heart
functions, which determine the interactions between these components were defined as: a)
wall properties such as tissue composition/elasticity, fibre structure and global geometry, and
b) interaction between the heart and peripheral circulation, mostly described as (pressure &
volume) loading conditions.
Furthermore, Doppler echocardiography data were analyzed in a study addressing flow
remodelling as a consequence of cellular and force remodelling in ischaemically remodelled
hearts. A dedicated automated quantification of the CW outflow Doppler traces was used to
define specific trace parameters indicative of myocardial dysfunction. It was shown that
decreased overall contractility results in a more symmetrical outflow velocity profile, which
would suggest that the global development of contractile force has been remodelled to cope
with the decreased output resulting from decreased contractility.
Similar automatic quantification of the aortic instantaneous peak velocities was further
employed in patients with hypertrophic remodelling due to aortic stenosis. This study has
shown that the values of trace asymmetry before surgery are predictive of the change in EF
112
pre- and postoperatively: all of the patients with markedly symmetric preoperative
instantaneous peak velocities showed stagnation or deterioration of EF postoperatively.
Furthermore, the study has proven that the symmetry of the shape of the instantaneous peak
velocities is a more reliable predictor of functional improvement after the valve replacement
procedure as compared to mean aortic gradient and aortic valve area which are widely used
in preoperative assessment of patients with aortic stenosis.
An intraoperative Doppler myocardial imaging study was performed along with standard
echocardiography in an analysis of electrical remodelling in patients with LBBB during the
CRT implantation procedure. In addition to confirming the septal flash as a mechanical
consequence of the underlying electrical problem and a valid marker of intraventricular
dyssynchrony, an acute contractility recruitment, resolution of the septal flash as well as
reverse remodelling immediately following CRT device activation was shown in these
patients.
As opposed to remodelling induced by changes in loading conditions, evidence of
hypertrophy and hypercontractility without an additional change in afterload resulting in
increased cardiac output and inducing additional signs of vascular remodelling was
demonstrated in patients with early stage acromegaly.
Finally, a comprehensive view on the changing role of echocardiography in the diagnosis
of hypertrophic myopathies is presented. Previous knowledge as well as regional
deformation data (including deformation pattern analysis) are combined to provide an
indicator toward the disease underlying hypertrophic ventricular remodelling: in hypertensive
heart disease LVH is predominantly localized in the basal septal region showing reduced
systolic strain values with post-systolic shortening; systemic diseases such as Fabry’s
disease often affect a specific region - the basal (infero)lateral segment in which post-systolic
deformation is often present. Hypertrophic cardiomyopathy is associated with regions of local
fibre disarray, in which no myocardial deformation is present at all, while in the surrounding
segments (often showing similar thickness) deformation is reduced, but almost normal as
compared to undiseased hearts. The absence of deformation is mostly associated with the
thickest segments. Amyloidosis seems to provide an exception in which the impairment of
systolic function affects the myocardium globally – it is presented with global LVH and
diffuse, severe reduction of longitudinal strain, while the radial strain is still preserved, but of
low values. |
| Abstract (croatian) | U suvremenoj kardiologiji ehokardiografija ima vodeću ulogu u dijagnostici i odabiru
postupaka u raznim oblicima remodeliranja miokarda. Nadalje, to je najčešće primjenjivana
metoda u rasvjetljavanju temeljnih supstrata i patofizioloških mehanizama zatajenja srca kao
posljedice remodeliranja klijetki. Zahvaljujući širokoj dostupnosti, neinvazivnosti, lakoći
primjene i relativno malenoj cijeni, ehokardiografija je i dalje nezamjenjiva u odnosu na druge
metode oslikavanja u kardiologiji, koje bi valjalo prihvatiti kao komplementarne dijagnostičke
metode.
Cilj je ove disertacije istražiti nekoliko oblika remodeliranja klijetki i njihovih posljedica na
regionalnu i globalnu funkciju miokarda, primjenom različitih ehokardiografskih metoda i
specifičnih algoritama analize signala i slike u otkrivanju disfunkcije srca.
Novije ehokardiografske tehnike temeljene na oslikavanju miokardnih brzina gibanja
(Myocardial Velocity Imaging) omogućuju podrobniji i integrirani pogled u (dis)funkciju srca.
Na temelju novijih spoznaja, na početku disertacije prikazan je originalni, integrirani pregled
„srčane funkcije“, razlikujući intrinzičnu funkciju miocita (obično nazivanu kontraktilitetom) i
crpnu funkciju klijetki, kao i glavne sastojnice srčane funkcije, to jest razvoj sile i deformaciju.,
Uvjeti u kojima srce radi, koji određuju odnos između navedenih sastavnica, definirani su
kao: a) svojstva stijenke poput građe/elastičnosti tkiva, strukture vlakna i globalne geometrije,
te b) interakcija srca i periferne cirkulacije koja se većinom opisuje kao stanje punjenja
(tlačno i volumno opterećenje).
U ispitivanju remodeliranja protoka kao posljedici staničnog remodeliranja i remodeliranja
sile u ishemijski remodeliranom srcu, obrađivali smo podatke Dopplerske ehokardiografije.
Posebna automatska kvantifikacija Dopplerskih zapisa istiska lijeve klijetke primijenjena je u
definiranju specifičnih svojstava krivulje, koja ukazuju na disfunkciju miokarda. Dokazali smo
da smanjenje ukupne kontraktilnosti uzrokuje simetričniji oblik krivulje istiska lijeve klijetke,
što sugerira remodeliranje globalne kontraktilne sile, kako bi se prilagodila smanjenju istiska
zbog smanjene kontraktilnosti.
Slična automatska kvantifikacija trenutnih vršnih brzina protoka kroz aortni zalistak
primijenjena je i u bolesnika s hipertrofijskim remodeliranjem klijetki u aortnoj stenozi. Ovo
istraživanje pokazalo je da predoperativne vrijednosti asimetrije Dopplerskog zapisa
predskazuju poslijeoperacijsku promjenu ejekcijske frakcije: u svih bolesnika sa značajno
simetričnim predoperativnim vršnim brzinama kroz aortni zalistak dokazali smo pogoršanje ili
114
istovjetnu ejekcijsku frakciju nakon operacije. Nadalje, ovo je istraživanje dokazalo da je
simetričnost vršnih brzina pouzdaniji predskazatelj funkcijskog oporavka nakon zamjene
aortnog zalistka, u usporedbi sa srednjim transaortnim gradijentom i površinom aortnog ušća
koji se često koriste u predoperativnoj evaluaciji bolesnika s aortnom stenozom.
U analizi električnog remodeliranja u bolesnika s blokom lijeve grane, provedeno je, uz
standardnu ehokardiografiju, intraoperacijsko ispitivanje miokardnog Dopplera tijekom
postupka ugradnje resinkronizacijskog elektrostimulatora. Uz potvrdu flash - septuma kao
mehaničke posljedice temeljnog električnog problema te valjanog pokazatelja
intraventrikulske disinkronije, u ovoj skupini bolesnika dokazano je i akutno poboljšanje
kontraktilnosti, nestanak flash - septuma kao i povratno remodeliranje lijeve klijetke
neposredno nakon uključivanja resinkronizacijskog elektrostimulatora.
Za razliku od remodeliranja uzrokovanog promjenom uvjeta punjenja, u skupini bolesnika
s akromegalijom dokazali smo hipertrofiju i hiperkontraktilnost lijeve klijetke uz posljedično
povećanje minutnog volumena srca te razvoj znakova vaskularnog remodeliranja, bez
dodatnih promjena u tlačnom opterećenju srca.
Disertacija završava širim prikazom izmijenjene uloge ehokardiografije u dijagnozi
hipertrofijskih bolesti miokarda. Prethodna saznanja kao i podatci o regionalnoj deformaciji
(uključujući analizu uzoraka deformacije) povezani su u svrhu prepoznavanja bolesti koja je u
podlozi hipertrofijskom remodeliranju klijetki: u hipertenzivnoj bolesti srca hipertrofija je
većinom lokalizirana u bazalnom interventrikulskom septumu uz smanjenje vrijednosti
sistoličkog strain-a te nastanak post-sistoličkog izduljenja. Sistemske bolesti poput Fabryjeve
bolesti često zahvaćaju određenu regiju srca – bazalni (infero)lateralni segment u kojem je
često prisutno post-sistoličko zadebljanje. Hipertrofijska kardiomiopatija je povezana s
ograničenim područjima poremećene arhitekture srčanih vlakana, u kojima je deformacija u
potpunosti odsutna, dok je u okolnim segmentima (često slične debljine stijenke) deformacija
smanjena, no gotovo normalna. Odsutnost deformacije obično je povezana s
najzadebljanijim segmentima. Čini se da amiloidoza predstavlja iznimku u kojoj smanjenje
sistoličke funkcije globalno zahvaća miokard - nalazi se globalna hipertrofija lijeve klijetke te
difuzno, teško oštećenje logitudinalnog straina dok je radijalni strain još očuvan, ali malenih
vrijednosti. |
