EFFECTS OF CD34+ STEM CELL TRANSPLANTATION ON RIGHT VENTRICULAR FUNCTION IN PATIENTS WITH NONISCHEMIC DILATED CARDIOMYOPATHY

Frljak, Sabina (author), Vrtovec, Bojan (mentor)

ABSTRACT Aims. Contraction of interventricular septum (IVS) represents an important component of right ventricular (RV) function. We investigated the effects of transendocardial delivery of CD34+ cells into IVS on RV function in patients with non-ischemic dilated cardiomyopathy (DCM). Methods. We enrolled 80 patients with non-ischemic DCM, NYHA functional class 3 and LVEF<40%. At baseline, patients received granulocyte-colony stimulating factor; cells were collected by apheresis and immunomagnetic selection to yield a total dose of 80 million CD34+ cells. With the guidance of electroanatomical mapping cell suspension was injected transendocardialy in the areas of myocardial hibernation, defined as unipolar voltage &#8805;8.27 mV and linear shortening <6%. Each patient received 20 injections of 0.3 mL. Patients who received cell at least 1 cell injection in the IVS area were included in Group A (N=40), and patients without IVS cell injections were assigned to Group B (N=40). Patients from both groups were followed for 6 months and changes in RV function were assessed by tricuspid annular plane systolic excursion (TAPSE), peak systolic velocity of tricuspid annulus (St), and fractional area change (FAC). Results. At baseline, the groups did not differ in age (57±9 years in Group A vs. 55±10 years in Group B, P=0.48), gender (male: 87% vs. 80%, P=0.54), LVEF (30.3±8.2% vs. 31.7±6.8%, P=0.32), or NTproBNP (1219±1338 pg/ml vs. 1298±1359 pg/ml, P=0.79). Similarly, we found no inter-group difference in RV function (TAPSE: 1.82±0.40 cm vs. 1.86±0.52 cm, P=0.69; St: 10.3±2.2 cm/s vs. 10.6±3.2 cm/s, P=0.70; FAC: 30±6% vs. 31±9%, P=0.66). At 6 months, we found an overall improvement in all parameters of RV function (TAPSE: +0.31±0.12 cm, P=0.001; St: +1.0±1.2 cm/s; P=0.002; FAC: +8.9±2.9%, P=0.01). RV function improvement was more prominent in Group A (TAPSE: +0.43±0.64 cm, P=0.001; St: +1.5±2.4 cm/s; P=0.01; FAC: +9.9±2.1%, P=0.01) than in Group B (TAPSE: +0.18±0.14 cm, P=0.24; St: +0.4±1.1 cm/s; P=0.30; FAC: +8.7±3.1%, P=0.01). In both groups we found a significant correlation between TAPSE and IVS viability as measured by unipolar voltage (Pearson r=0.58, P<0.001). Conclusions. In non-ischemic DCM, RV function correlates with the viability of IVS. In these patients, cell therapy targeting IVS area appears to be associated with improvement of RV function.

• Language: English
• Keywords: CD 34+ Cells, Right Ventricular Function, Dilated Cardiomyopathy, Heart Failure
• Work type: Doctoral dissertation
• Organization: MF - Faculty of Medicine
• Year: 2018
• PID: 20.500.12556/RUL-100916
• COBISS.SI-ID: 4758700
• Publication date in RUL: 21.04.2018

Secondary language

• Language: Slovenian
• Title: VPLIV PRESADITVE CD34+ MATIČNIH CELIC NA DELOVANJE DESNEGA PREKATA PRI BOLNIKIH Z NEISHEMIČNO DILATATIVNO KARDIOMIOPATIJO

Abstract

IZVLEČEK Namen. Krčenje prekatnega pretina pomembno prispeva k funkciji desnega prekata. V raziskavi smo preučili vpliv presaditve CD34+ matičnih celic v področje prekatnega pretina na delovanje desnega prekata pri bolnikih z neishemično dilatativno kardiomiopatijo. Zasnova raziskave, opis metod, preiskovancev. V raziskavo smo vključili 80 bolnikov z dilatativno kardiomiopatijo in napredovalim srčnim popuščanjem v funkcijskem razredu III po klasifikaciji Newyorškega združenje za srce (NYHA) in iztisnim deležem levega prekata (LVEF) manj kot 40%. Pri vseh bolnikih smo opravili mobilizacijo matičnih celic z rastnim dejavnikom celic granulocitne vrste, matične celice smo zbrali s postopkom afereze; z imunomagnetno osamitvijo izdelali pripravek matičnih celic, ki je vseboval 80 milijonov CD34+ matičnih celic. S pomočjo elektroanatomske kartografije levega prekata smo določili območja hiberniranega miokarda, ki so določena kot točke z unipolarnimi potenciali &#8805;8.3 mV in linearnim krčenjem <6%. V ta področja smo transenokardialno vbrizgali po 0.3 ml raztopine matičnih celic. Vsak bolnik je prejel 20 injekcij. Bolnike, ki so prejeli vsaj eno aplikacijo matičnih celic v področje prekatnega pretina, smo razvrstili v skupino A (N=40), in bolnike, ki v predel prekatnega pretina niso prejeli matičnih celic, v skupino B (N=40). Obe skupini bolnikov smo opazovali 6 mesecev. Spremembe funkcije desnega prekata smo ocenili z: spremembo longitudinalnega sistoličnega gibanja prostega roba trikuspidalne zaklopke (TAPSE), spremembo največje sistolične hitrosti trikuspidalnega obroča (St), ter s spremembo površine desnega prekata (FAC). Rezultati. Ob vključitvi se skupini nista pomembno razlikovali glede na starost (57±9 let vs. 55±10 let, P=0.48), spol (moški: 87% vs. 80%, P=0.54), LVEF (30.3±8.2% vs. 31.7±6.8%, P=0.32), ali NTproBNP (1219±1338 pg/ml vs. 1298±1359 pg/ml, P=0.79), in glede na funkcijo desnega prekata (TAPSE: 1.82±0.40 cm vs. 1.86±0.52 cm, P=0.69; St: 10.3±2.2 cm/s vs. 10.6±3.2 cm/s, P=0.70; FAC: 30±6% vs. 31±9%, P=0.66). 6 mesecev po transplantaciji matičnih celic je prišlo do statistično pomembnega izboljšanja vseh kazalcev sistolične funkcije desnega prekata (TAPSE: +0.31±0.12 cm, P=0.001; St: +1.0±1.2 cm/s; P=0.002; FAC: +8.9±2.9%, P=0.01). Sistolična funkcija desnega prekata se je statistično pomembneje izboljšala v skupini A (TAPSE: +0.43±0.64 cm, P=0.001; St: +1.5±2.4 cm/s; P=0.01; FAC: +9.9±2.1%, P=0.01) v primerjavi s skupino B (TAPSE: +0.18±0.14 cm, P=0.24; St: +0.4±1.1 cm/s; P=0.30; FAC: +8.7±3.1%, P=0.01). V obeh skupinah je vrednost TAPSE pomembno korelirala z unipolarnimi potenciali izmerjeno viabilnostjo prekatnega pretina (Pearson r=0.58, P<0.001). Zaključki. Pri bolnikih z neishemično dilatativno kardiomiopatijo funkcija desnega prekata pomembno korelira z viabilnostjo prekatnega pretina. Presaditev matičnih celic v področje prekatnega pretina je povezano z izboljšanjem funkcije desnega prekata.

• Keywords: CD 34+ matične celice, funkcija desnega prekata, dilatativna kardiomiopatija, srčno popuščanje