Cardiac function before and after treatment for various types of loading conditions and in myocardial restriction : A prospective study on pediatric patients with two- and three-dimensional echocardiography and measurement of serum natriuretic peptides

Background: The incidence of all forms of congenital heart defects is 0.75%. For patients with congenital heart defects, life-expectancy has improved with new treatment modalities. Structural heart defects may require surgical or catheter treatment which may be corrective or palliative. Even those with corrective therapy need regular follow-up due to residual lesions, late sequelae, and possible complications after interventions. Aims: The aim of this thesis was to evaluate cardiac function before and after treatment for volume overload of the right ventricle (RV) caused by atrial septal defect (ASD), volume overload of the left ventricle (LV) caused by patent ductus arteriosus (PDA), and pressure overload of the LV caused by coarctation of the aorta (CoA), and to evaluate cardiac function in patients with Mulibrey nanism. Methods: In Study I, of the 24 children with ASD, 7 underwent surgical correction and 17 percutaneous occlusion of ASD. Study II had 33 patients with PDA undergoing percutaneous occlusion. In Study III, 28 patients with CoA underwent either surgical correction or percutaneous balloon dilatation of CoA. Study IV comprised 26 children with Mulibrey nanism. A total of 76 healthy voluntary children were examined as a control group. In each study, controls were matched to patients. All patients and controls underwent clinical cardiovascular examinations, two-dimensional (2D) and three-dimensional (3D) echocardiographic examinations, and blood sampling for measurement of natriuretic peptides prior to the intervention and twice or three times thereafter. Control children were examined once by 2D and 3D echocardiography. M-mode echocardiography was performed from the parasternal long axis view directed by 2D echocardiography. The left atrium-to-aorta (LA/Ao) ratio was calculated as an index of LA size. The end-diastolic and end-systolic dimensions of LV as well as the end-diastolic thicknesses of the interventricular septum and LV posterior wall were measured. LV volumes, and the fractional shortening (FS) and ejection fraction (EF) as indices of contractility were then calculated, and the z scores of LV dimensions determined. Diastolic function of LV was estimated from the mitral inflow signal obtained by Doppler echocardiography. In three-dimensional echocardiography, time-volume curves were used to determine end-diastolic and end-systolic volumes, stroke volume, and EF. Diastolic and systolic function of LV was estimated from the calculated first derivatives of these curves. Results: (I): In all children with ASD, during the one-year follow-up, the z score of the RV end-diastolic diameter decreased and that of LV increased. However, dilatation of RV did not resolve entirely during the follow-up in either treatment group. In addition, the size of LV increased more slowly in the surgical subgroup but reached control levels in both groups. Concentrations of natriuretic peptides in patients treated percutaneously increased during the first month after ASD closure and normalized thereafter, but in patients treated surgically, they remained higher than in controls. (II): In the PDA group, at baseline, the end-diastolic diameter of LV measured over 2SD in 5 of 33 patients. The median N-terminal pro-brain natriuretic peptide (proBNP) concentration before closure measured 72 ng/l in the control group and 141 ng/l in the PDA group (P = 0.001) and 6 months after closure measured 78.5 ng/l (P = NS). Patients differed from control subjects in indices of LV diastolic and systolic function at baseline, but by the end of follow-up, all these differences had disappeared. Even in the subgroup of patients with normal-sized LV at baseline, the LV end-diastolic volume decreased significantly during follow-up. (III): Before repair, the size and wall thickness of LV were higher in patients with CoA than in controls. Systolic blood pressure measured a median 123 mm Hg in patients before repair (P < 0.001) and 103 mm Hg one year thereafter, and 101 mm Hg in controls. The diameter of the coarctation segment measured a median 3.0 mm at baseline, and 7.9 at the 12-month (P = 0.006) follow-up. Thicknesses of the interventricular septum and posterior wall of the LV decreased after repair but increased to the initial level one year thereafter. The velocity time integrals of mitral inflow increased, but no changes were evident in LV dimensions or contractility. During follow-up, serum levels of natriuretic peptides decreased correlating with diastolic and systolic indices of LV function in 2D and 3D echocardiography. (IV): In 2D echocardiography, the interventricular septum and LV posterior wall were thicker, and velocity time integrals of mitral inflow shorter in patients with Mulibrey nanism than in controls. In 3D echocardiography, LV end-diastolic volume measured a median 51.9 (range 33.3 to 73.4) ml/m² in patients and 59.7 (range 37.6 to 87.6) ml/m² in controls (P = 0.040), and serum levels of ANPN and proBNP a median 0.54 (range 0.04 to 4.7) nmol/l and 289 (range 18 to 9170) ng/l, in patients and 0.28 (range 0.09 to 0.72) nmol/l (P < 0.001) and 54 (range 26 to 139) ng/l (P < 0.001) in controls. They correlated with several indices of diastolic LV function. Conclusions (I): During the one-year follow-up after the ASD closure, RV size decreased but did not normalize in all patients. The size of the LV normalized after ASD closure but the increase in LV size was slower in patients treated surgically than in those treated with the percutaneous technique. Serum levels of ANPN and proBNP were elevated prior to ASD closure but decreased thereafter to control levels in patients treated with the percutaneous technique but not in those treated surgically. (II): Changes in LV volume and function caused by PDA disappeared by 6 months after percutaneous closure. Even the children with normal-sized LV benefited from the procedure. (III): After repair of CoA, the RV size and the velocity time integrals of mitral inflow increased, and serum levels of natriuretic peptides decreased. Patients need close follow-up, despite cessation of LV pressure overload, since LV hypertrophy persisted even in normotensive patients with normal growth of the coarctation segment. (IV): In children with Mulibrey nanism, the LV wall was hypertrophied, with myocardial restriction and impairment of LV function. Significant correlations appeared between indices of LV function, size of the left atrium, and levels of natriuretic peptides, indicating that measurement of serum levels of natriuretic peptides can be used in the clinical follow-up of this patient group despite its dependence on loading conditions.

Ukrainan vuosien 1932-33 nälänhädän historiapolitiikka

Ukrainan presidentiksi nousi ns. oranssin vallankumouksen nosteessa Viktor Justsenko. Hänen presidenttikaudellaan (2005-2010) vuosien 1932-33 nälänhätä (holodomor) nousi keskeiseksi sekä sisä-, että ulkopolitiikan teemaksi. Holodomor, joka viittaa nälällä aiheutettuun tuhoon, pyrittiin tuomaan osaksi ukrainalaista kollektiivista muistia. Justsenkon aloitteesta säädettiin laki, jonka mukaan holodomor oli ukrainalaisten kansanmurha. Vuosina 1932-33 ympäri Neuvostoliittoa vallitsi nälänhätä. Ukrainalainen maaseutu kärsi pahoin nälänhädän seurauksista, sillä eri arvioiden mukaan 3,5-10 miljoonaa ukrainalaista menehtyi joko suoranaisesti tai välillisesti nälänhädän seurauksena. Ukrainan itsenäistyttyä nälänhätä, jota oli diasporassa alettu kutsua holodomoriksi (nälkätuho), nousi kansallisen historian keskeiseksi teemaksi. Ukrainalainen historioitsija Georgi Kasjanov on nimittänyt tätä uutta vaihetta historian kansallistamiseksi. Tässä työssä pohditaan sitä, miksi holodomor nostettiin keskeiseen asemaan presidentti Viktor Justsenkon valtakaudella. Keskeinen vastakkainasettelun lähtökohta on ollut itsenäisen Ukrainan ja Neuvostoliiton seuraajavaltion Venäjän suhtautuminen nälänhätään 1932-33. Ukrainalaisissa näkökulmissa on painottunut stalinistisen järjestelmän kritiikki, mikä toisaalta on saatettu tulkita myös koko kommunistisen aikakauden tuomitsemiseksi. Venäjällä taas nälänhätä on tulkittu useimmiten yleisneuvostoliittolaiseksi tragediaksi, joka ei kohdistunut erityisesti mitään tiettyä kansallisuutta vastaan. Tutkimuksen keskeinen lähtökohta on tarkastella ukrainalaisten ja venäläisten tulkintojen eroja ja sitä, millä tavoin holodomorilla on tehty politiikkaa. Tutkimusaineistona on käytetty ukrainalaisten osalta presidentti Justsenkon puheita, lakialoitteita ja muita julkilausumia, sekä eräiden yhteiskunnallisten toimijoiden ja historioitsijoiden kannanottoja. Venäläisen osapuolen tulkintoja on pyritty luomaan muutamien tutkimusten ja yhteiskunnallisten toimijoiden, sekä poliitikkojen lausumien pohjalta. Suurin osa aineistosta on kerätty venäjänkielisistä verkkolehdistä. Presidentti Justsenkolle vuosien 1932-1933 historiasta muodostui ase, jolla hän kävi omaa poliittista taisteluaan lännen puolesta itää vastaan. Välit Venäjään olivat viileät koko hänen presidenttikautensa ajan. Lähimmäksi presidentin kantaa holodomor-kysymyksessä tulivat diasporaukrainalaiset. Venäjällä kritisoitiin ankarasti Justsenkon tanssia haudoilla eli hänen tapaansa käyttää nälänhädän uhreja oman politiikkansa välineenä. Venäläiset korostivat nälänhädän tragediaa kaikkien Neuvostoliiton kansojen tragediana. Holodomor oli osa kansallisen historian uudelleenkirjoitusta ja kansakunnan rakentamisen prosessia. Justsenkon päämääränä oli lähentää Ukrainaa länteen, jolloin ukrainalaisen kansakunnan uhriasema antoi oikeutuksen sanoutua irti neuvostoajasta. Tietyssä mielessä holodomor-projekti oli venäläisvastainen, sillä se implisiittisesti tuki käsitystä venäläisistä rikollisina, kansanmurhan toimeenpanijoina.