Provider: - Institution: - Data provided by Europeana Collections- Risk stratification and decision making are particularly complex in
asymptomatic patients with moderate or severe aortic stenosis ...(AS). When to
intervene in these patients is still matter of controversy, and
misinterpreting the findings might lead to an unnecessary delay of aortic
valve replacement. The risk of sudden death without preceding symptoms
remains a concern, as well as the risk of irreversible myocardial damage due
to the high global afterload. These factors may also be responsible for an
impairment of coronary flow reserve (CFR) and microvascular coronary
dysfunction, which has been observed in patients with AS and without
obstructive epicardial coronary artery disease. Therefore, valve replacement
prior to the onset of symptoms and LV dysfunction may be recommended;
however, data in patients with purely asymptomatic AS are lacking. The most
frequently used parameters such as mean pressure gradient (Pmean) and maximal
jet velocity (Vmax) are necessary in determining the AS severity, but less
useful in predicting the outcome and when to intervene in asymptomatic
patients. The dobutamine testing (DT) in asymptomatic AS is promising having
in mind that most of the Doppler-echocardiographic indices used for
evaluation of AS is flow-dependent. The pharmacologic increase of flow could
help to correctly assess disease severity, discover the existence of latent
symptoms, assess the LV systolic function and, therefore, to guide clinical
decisions. The new hemodynamic measurements of severity such as valve
resistance (Zva) and the energy-loss index (ELI) have been proposed, however,
a common limitation of most of these new indices, as well of the usefulness
of DT, is that longitudinal follow-up data from prospective studies are
lacking. The aim of this study was to assess which echocardiographic
parameter(s) can identify subset of asymptomatic AS patients who are at high
risk of short to mid-term cardiac events and to analyze the value of LV
systolic and diastolic parameters change during low-dose DT in asymptomatic
patients with moderate or severe AS and preserved EF at rest. Moreover, we
analyzed different echocardiographic parameters to see which of these
contributes the most to impairment of CFR in subgroup of AS patients with
nonobstructive coronary arteries. Method: A total of 126 asymptomatic
patients with aortic valve area (AVA) _ 1.5cm2 and EF > 50% were enrolled in
this prospective study. The follow-up period was 14 months. Clinical data at
follow-up were obtained in all patients by direct patient examination or
telephone interview. The composite outcome endpoint (MACE) was defined as
cardiac death, aortic valve replacement and hospitalization caused by AS
symptoms. For patients that had adverse cardiovascular events the
documentation was asked. The decision for aortic valve replacement was made
by the referring physician. After the baseline study, a low-dose dobutamine
infusion protocol was begun at 5 μgr/kg/min up to 20 μgr/kg/min, titrated
upward at steps of 5 μgr/kg every 3 minutes. The dobutamine infusion was
ended when the maximal dose or 85% of the maximal theoretic heart rate was
achieved, or when the patients developed symptoms. All standard
echocardiographic measures were recorded during last minute of each level and
analyzed off-line. A subgroup of patients that had no obstructive coronary
disease (defined as having no stenosis greater than 50% in diameter) on the
coronary angiogram taken within 1 year, had undergone adenosine stress
transthoracic Doppler-echo for a CFR measurement. Results: The study
population included 52 women and 74 men (58.73% males), mean age was
66.47±10.53; with no difference (p > 0.05) among them (men 66.52 ± 8.86
years, women 66.43 ± 11.67 years). Mean pressure gradient (Pmean) was 41,94 ±
11,22mmHg, mean AVA 0,82 ± 0,22cm2, and mean Vmax was 4,20 ± 0,49m/s. No
patient experienced a serious adverse event during or after DT. Eleven out of
126 patients (8.73%) developed symptoms during test. In addition, patients
who had an increase in AVA during DT _ 0.2cm2 and/or final AVA _ 1cm2 after
DT had significantly more often aortic valve replacement during follow-up
chi-square=9.5311, df=1, p=0.00202; OR =4.604 (95%CI= 1.7826-11.8915).
Thirty six patients (28.57%) had low (or no) contractile reserve LV, defined
as a decrease in SVi or EF during DT. A total of 70 patients had composite
MACE (55,55%), of which 9 patients (7,14%) have died during follow-up. Out of
70 patients, 56 patients (80%) had an aortic valve replacement during
follow-up period. Univariate analysis showed that resting mean values of
Vmax, Pmean, AVA, Zva, ELI, AVR (aortic valve resistance) and S’ were
associated (p<0.05) with MACE. Although 28.57% patients had a decrease in SVi
and EF during DT, this was not significant in terms of predicting MACE
(p>0.05). The multivariate analysis revealed that AVR (p=0.007; HR=1,004;
CI=1.001-1.006) was independently associated with MACE. The cut-off value of
172.27 dynes•s•cm-5 had a sensitivity of 99% and specificity of 30% to
predict MACE. However, regarding death only, Zva was independent predictor
according to multivariate analysis (p=0.017; HR=3.244; CI=1.669-6.309), with
Zva value of 5,5 mmHg•ml/m2 having sensitivity and specificity (67% and 72%,
respectively). Patients who have experienced symptoms during DT had more
often MACE comparing to patients who were asymptomatic during DT (hi =
6,7408; p < 0,001; df = 1), while AVR, SWL and Pmean had higher prognostic
significance in predicting MACE than echocardiographic parameters analyzed at
rest (p < 0.05). Results of univariate regression analysis showed AVA, Vmax,
Pmean, Pmax, ELI, AVR and SWL were associated (p<0.05) with impaired CFR.
Multivariate analysis showed that AVR was the best predictor of impaired CFVR
(RR 0.900, CI: 0.983-0.997, p=0.007). Using ROC analysis, the AVR value of
211.22 dynes•s•cm-5 had the highest accuracy in predicting the impaired CFVR
(area under the curve 0.681, p=0.007, sensitivity 72%, specificity 52%, CI:
0,561-0.800). Discussion: To the best of the author’s knowledge, this
doctoral thesis is the first to compare clinical efficacy of different
indices of AS, including new-mathematically derived parameters, at rest and
after low-dose DT. The results of this study point out the high risk of MACE,
including death, in even relatively short follow-up period. In addition, our
results show that ’wait and follow’ strategy could be risky in these patients
and that there are parameters who can with high certainity establish the risk
of future MACE in asymptomatic patients with hemodinamically significant AS.
In other words, for accurate estimation of AS severity and patients’s
prognosis, it is crucial to analyze not only aortic valve, but peripheral
system and its physiological consequences to LV function. This doctoral
thesis is showing, for the first time, that asymptomatic patients with
hemodinamically significant AS and preserved EF can actually have a decrease
in systolic function during DT. This clearly shows that these patients have
structural myocardial changes and that for them LV EF is not the best
parameter for assessing systolic function. Low-dose DT is safe to perform in
asymptomatic patients with moderate or severe AS and preserved EF. Together
with the fact that measuring AVA during DT can be helpful in suggesting when
to intervene in this group of patients, the results of this study suggest
that DT has a place in assessment of asymptomatic patients with moderate and
severe AS and preserved EF, as better management decisions can be made on the
result of a dobutamine echocardiogram. In addition, patients with
moderate/severe AS can have an impaired coronary microvascular function. The
hemodynamic indexes of AS severity are main determinants of CFR. Among all
parameters, AVR is the strongest predictor of CFR in patients with moderate
or severe AS and nonobstructive coronary arteries. Conclusion: The present
doctoral dissertation demonstrates that AVR and Zva, as well as flow-mediated
changes in AVA during dobutamine infusion, can provide new, clinically
relevant information in terms of outcome and timing of valve replacement in
asymptomatic patients with moderate and severe AS and preserved EF. Thus,
these indices, as well as low-dose DT, should be incorporated in clinical
assessment of AS and used to aid patient management in unclear situations.- Procena rizika i donošenje odluka su posebno teški u grupi asimptomatskih
pacijenata sa umerenom i tesnom aortnom stenozom (AS). Kada izvršiti hiruršku
intervenciju kod ovih pacijenata još uvek je nejasno, iako kasna hirurška
intervencija i zamena aortnog zaliska može dovesti do suboptimalnog rezultata
operacije. Opasnost od nagle srčane smrti kod asimptomatskih AS pacijenata
postoji, kao i rizik od ireverzibilnog oštećenja miokarda zbog visokog
naknadnog opterećenja leve komore (LK). Takođe, pokazano je da visoko
naknadno opterećenje LK uzrokuje i disfunkciju koronarne mikrocirkulacije, to
jest smanjenje rezerve koronarnog protoka (CFR) kod asimptomatskih pacijenata
sa AS i neopstruktivnim koronarnim angiogramom. Zbog toga, za očekivati je da
bi zamena aortnog zaliska pre pojave simptoma i disfunkcije LK bila od
koristi, ali još uvek nema dovoljno urađenih prospektivnih studija koje bi
ovu pretpostavku i potvrdile. Najčešće korišćeni Doppler-ehokardiografski
parametri, poput srednjeg gradijenta pritiska (Psrednje) i maksimalne brzine
protoka (Vmax) su neophodni u određivanju težine AS, ali su manje korisni u
predikciji ishoda, pojave simptoma i određivanju optimalnog vremena za zamenu
zaliska kod asimptomatskih pacijenata. Novi ehokardiografski parametri, poput
valvulo-arterijalne impedance (Zva), i indeksa gubitka energije (ELI) su
predloženi kao alternativa, ali još uvek nema dovoljno
longitudinalnih-prospektivnih studija koje bi potvrdile njihovu korisnost.
Bikuspidna aortna valvula najčešća je prirođena srčana bolest, ali se u užemu smislu ne smatra bolešću, nego predispozicijom za njezin razvoj. Dijapazon prezentacije i vrijeme pojave bolesti takvog ...aortnog zalistka vrlo je raznovrstan. U našoj praksi bolesnike koji se prezentiraju u ranoj dobi te osobito ako imaju pridružene anomalije (aneurizmu aorte, koarktaciju, membranu), razmatramo u okviru grupe za kongenitalne srčane bolesti, osobito stoga što, kako je ovdje prikazano, takvi bolesnici trebaju trajno praćenje i često višekratne intervencije. Prikazani je bolesnik i dobar primjer kombinacije prirođenog defekta i „stečene“ (koronarne) bolesti srca, što je jedna od karakteristika populacije s prirođenim srčanim bolestima, u dugotrajnom praćenju.
Aortalna stenoza najčešća je bolest zalistaka u zemljama zapadne hemisfere. Njezina se prevalencija povećava sa starošću populacije te iznosi 2 – 4% u osoba starijih od 65 godina. Usprkos ...kardiokirurškoj operaciji gotovo trećina bolesnika nije operirana zbog visokog operativnog rizika i komorbiditeta. Transkateterska implantacija aortalnog zalistka (TAVI) danas je općepriznata metoda za liječenje teške aortalne stenoze kod bolesnika čiji je kardiokirurški rizik neprihvatljivo visok ili koji su iz nekoga drugog razloga proglašeni neoperabilnima. Tom se metodom, na kucajućem srcu, s pomoću katetera postavlja umjetna biološka valvula na mjesto degenerirane nativne valvule. U KBC-u Zagreb program TAVI provodi se od 2012. godine, od kada su učinjena 44 zahvata. Svi zahvati, kao i prijeoperacijske obrade, izvođeni su prema svim vrijedećim preporukama i smjernicama Europskog i Američkoga kardiološkog društva, što je rezultiralo jednakom uspješnošću zahvata. U ovom članku istaknute su najbitnije činjenice o metodi TAVI, nakon čega su prikazani rezultati KBC-a Zagreb.
Bikuspidalna aortalna valvula (BAV) epidemiološki se ne uvrštava u studije prirođenih srčanih grješaka (PSG) u djece iako se u odrasloj dobi smatra najčešćim PSG-om, s prevalencijom od 0,5 do 2%. ...Poremećaj aortalne valvulogeneze posljedica je genski uvjetovanih promjena u izlaznom dijelu lijeve klijetke (LVOT) u koje spadaju: sindrom hipoplastičnoga lijevog srca (HLHS), aortalna stenoza (AS) i insuficijencija (AI), dilatacija uzlazne aorte (DAA), koarktacija aorte (CoA), Shoneov sindrom (SS), a vjerojatno i neki drugi poremećaji. Mi smo zapazili da su uz BAV vezane znatne patomorfološke promjene već u dječjoj dobi. U retrospektivnu studiju dugu 11 godina (od 2002. do 2012.) uključeno je 229-ero djece s BAV-om, s predominacijom muških (1,7). Najčešća grješka pridružena BAV-u bila je CoA (75 bolesnika ili 32,6%). Od djece s BAV-om njih 62,4% (143 : 229) imalo je hemodinamske promjene na aortalnoj valvuli koje se očituju kao aortalna stenoza i/ili insuficijencija. AS je većinom progresivan i postaje već u dječjoj dobi hemodinamski važan u dijela bolesnika, a AI je većinom blag i rijetko hemodinamski važan.Velik broj bolesnika imao je izolirani AS uz DAA (21 ili 14,7%), a najveći broj imao je kombinaciju AS-a i AI (29 ili 20,3%). Zbog morfoloških promjena na samoj valvuli i pridruženim grješkama učinjeni su brojni intervencijski i kardiokirurški zahvati. Njihov broj rastao je s dobi, sukladno očekivanoj progresiji patoloških promjena na samoj valvuli (AS, AI) ili na aorti (DAA). Kod djece s BAV-om nalazimo DAA u 76 (33,2%) bolesnika, i to u raznim kombinacijama s drugim grješkama LVOT-a. Uz osnovnu dijagnozu BAV-a već u dječjoj dobi učinjene su ove operacije: resekcija CoA s T-T-anastomozom 56 bolesnika (24,5%), balonska dilatacija BAV-a 28 bolesnika (12,3%), komisurotomija 19 bolesnika (8,3%), balonska dilatacija CoA 15 bolesnika (6,5%), resekcija subaortalne membrane 11 bolesnika (4,8%), operacija prema Rossu 8 bolesnika (3,5%), resekcija CoA s rekonstrukcijom 8 bolesnika (3,5%), valvuloplastika 6 bolesnika (2,6%), plastika ascendentne aorte 5 bolesnika (2,2%), mehanička aortalna valvula 3 bolesnika (1,3%), potključni režanj (subclavian flap) 3 bolesnika (1,3%), biološka aortalna valvula 2 bolesnika (0,9%), operacija prema Bentallu 1 bolesnik (0,4%), operacija prema Davidu 1 bolesnik (0,4%). Doprinos studije: Nalaz BAV-a kod djece prediktivni je čimbenik (navješćivač) progresivnog razvoja morfoloških promjena u različitim dijelovima LVOT-a, s potrebom za uklanjanjem hemodinamskih reperkusija u dijela bolesnika već u dječjoj dobi. Zaključak: Pojam valvularna aortopatija, odnosno sindrom bikuspidalne aortalne valvule trebalo bi rabiti već u dječjoj dobi, a anomaliju valja uključiti u epidemiološka istraživanja PSG-a.
Prikazujemo obiteljski oblik balansirane translokacije t(7;14) koji je nađen u majke i dva njezina sina. Majka je imala samo šum nad aortnim ušćem bez hemodinamskog značenja, djeca su imala gotovo ...istovjetan klinički nalaz; značajnu supravalvularnu aortnu stenozu tipa pješćanog sata, intrakavitarnu stenozu u lijevoj klijetki i multiple periferne pulmonalne stenoze. Nisu imali niti jedan drugi klinički znak Williams-Beurenova sindroma, osim vjerojatno dubokog metaličnog glasa.
Konvencionalna kromosomska analiza neočekivano je pokazala da je riječ o balansiranoj translokaciji t(7;14), identična translokacija pronađena je u majke i brata. Fluorescentna in situ hibridizacija s WSCR probama pokazala je da je prijelomna točka uzdužno pocijepala elastinsku regiju u sve troje ispitanika. Kariotip ispitanika interpretiran je prema ISCN-u kao
46,XY,t(7;14)(q11.23;p12).ish t(7;14)(D7Z1+,ELNsp;D14Z1/D22Z1+,ELNsp+)mat. Drugim riječima, translokacija je pocijepala elastinsku regiju, što može biti razlogom nastanka razvojnih anomalija karakterističnih za Williams-Beurenov sindrom.
Pregledom kroz literaturu našli smo da ovakav nalaz nije dosad objavljen u genetičkoj obradi supravalvularne aortne stenoze, odnosno Williams-Beurenova sindroma ili stanja koja se ne mogu razvrstati u ove dvije krajnje kategorije zbog šarolikosti fenotipskih karakteristika.
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