VPLIV TRANSENDOKARDNE TRANSPLANTACIJE CD34+ CELIC NA PARAMETRE DIASTOLIČNE FUNKCIJE LEVEGA PREKATA PRI BOLNIKIH Z DILATATIVNO KARDIOMIOPATIJO

Bervar, Mojca (author), Vrtovec, Bojan (mentor)

IZVLEČEK Izhodišča in hipoteze. Diastolična disfunkcija levega prekata je napovednik naravnega poteka srčnega popuščanja z ohranjenim ali zmanjšanim iztisnim deležem levega prekata. Učinek transplantacije matičnih celic, ki se uporablja za zdravljenje napredovalega srčnega popuščanja, na diastolično funkcijo levega prekata ni jasen. Zato smo z doktor¬skim delom ocenili, ali i) so ehokardiografski parametri diastolične disfunkcije povezani s parametri, ki jih pridobimo z elektroanatomsko kartografijo pred transplantacijo matičnih celic, ter ii) ali presaditev CD34+ matičnih celic izboljša diastolično funkcijo bolnikov s srčnim popuščanjem. Metode dela. V raziskavo smo vključili zaporedne bolnike z neishemično in ishemično dilatacijsko kardiomiopatijo, ki so bili predvideni za zdravljenje s CD34+ matičnimi celicami. Bolniki so imeli iztisni delež levega prekata manj kot 40 %, bili so v sinusnem ritmu, v klinično stabilnem stanju (funkcijski razred III po klasifikaciji newyorškega kardiološkega združenja) vsaj tri mesece pred vključitvijo. Bolnike smo razdelili v skupine glede na etiologijo kardiomiopatije in izhodiščno vrednost ehokardiografskega znaka povišanega polnitvenega tlaka levega prekata (E/e' ? 15) v podskupine. Pri vseh bolnikih smo iz periferne krvi mobilizirali CD34+ celice s pomočjo stimulacije kostnega mozga s filgrastimom in jih izolirali z aferezo. Z elektroanatomsko kartografijo smo določili glede na velikost unipolarnega endokardnega potenciala in linearno skraj¬šanje srčne mišice (LLS) predele zdrave (povprečen unipolarni potencial ? 8,27 mV in LLS ? 6 %) in hibernirane (povprečen unipolarni potencial ? 8,27 mV in LLS < 6 %) srčne mišice in predele brazgotine (povprečen unipolarni potencial < 8,27 mV in LLS < 6 %). Pri bolnikih z neishemično kardiomiopatijo smo izmerili tudi globalni čas relaksacije levega prekata in ga primerjali z ehokardiografskimi parametri diastolične disfunkcije. Matične celice smo vbrizgali transendokardno v predele hibernirane srčne mišice. Ob vključitvi v študijo in nato 3, 6 in 12 mesecev po transplantaciji CD34+ celic smo opravili ehokardiografsko preiskavo z oceno diastolične disfunkcije in spremljali klinične (klinični pregled in 6MWT) in laboratorijski pokazatelj srčnega popuščanja (nivo NT-proBNP v krvi). Diastolično disfunkcijo smo ocenjevali z ehokardiografskimi parametri E/A, DT, TR in E/e' in skladno s priporočili ASE/EACVI opredelili stopnjo diastolične disfunkcije. Rezultati. Vključili smo 58 bolnikov (povprečna starost vseh bolnikov je bila 54 ± 8,4 let; 20,8 % je bilo žensk). Neishemično kardiomiopatijo je imelo 38 bolnikov – 18 s povišanim polnilnim tlakom (skupina DKMP+), 20 z normalnim polnilnim tlakom (skupina DKMP?). Ishemično kardiomiopatijo je imelo 20 bolnikov; vsi so imeli povišan polnilni tlak (skupina IKMP+). Z endomiokardnim beleženjem unipolarnih potencialov smo v skupini DKMP+ ugotovili večji obseg hiberniranega miokarda kot v skupini DKMP? (4,9 ± 2,7 mV in 2,7 ± 2,9 mV; p = 0,03) in večji obseg brazgotin (2,2 ± 1,6 mV in 0,9 ± 1,1 mV; p = 0,02). Globalni čas relaksacije pri elektroanatomski meritvi ni koreliral s parametri diastolične funkcije (E/A, DT in stopnjo diastolične disfunkcije po ASE/EACVI), je pa koreliral s parametrom polnilnega tlaka E/e'. Transplantacija CD34+ ni bila povezana z značilno spremembo parametrov diastolične disfunkcije ali koncentracijo NT-proBNP v nobeni izmed skupin, bila pa je povezana z izboljšanjem 6MWT (DKMP+: 48 ± 58 m; p = 0,026; DKMP?: 52 ± 63 m, p = 0,05; IKMP+: 96 ± 62 m; p < 0,001). Transplantacija CD34+ celic je bila povezana z značilnim upadom v parametru polnilnega tlaka levega prekata E/e' le v skupini DKMP+ (?8,0 ± 10,3 mmHg; p = 0,008), ne pa v skupinah DKMP– in IKMP+. Zaključki. Podaljšan globalni čas relaksacije miokarda, izmerjen s pomočjo elektro¬ana-tomske mape, korelira s parametrom zvišanega polnilnega tlaka E/e', ne pa z ostalimi parametri diastolične disfunkcije. Zdravljenje s CD34+ matičnimi celicami zniža polnilni tlak levega prekata (E/e') le pri bolnikih z DKMP+ (ki imajo že zvišan izhodiščni polnilni tlak), ne pa pri bolnikih z DKMP? (kjer je parameter E/e' izhodiščno normalen) in z IKMP+ (kjer je obseg brazgotin večji). Izsledki raziskave nakazujejo novo možnost ocene zvišanega polnilnega tlaka levega prekata s pomočjo elektroanatomske mape in naka¬zujejo možnost ustreznejšega izbora kandidatov za zdravljenje s CD34+ matičnimi celicami. Ključne besede. Kardiomiopatija, CD34+ celice, diastolična, ehokardiografija, elektro-anatomska mapa

• Language: Slovenian
• Keywords: kardiomiopatija, CD34+ celice, diastolična, ehokardiografija, elektro-anatomska mapa
• Work type: Doctoral dissertation
• Organization: MF - Faculty of Medicine
• Year: 2020
• PID: 20.500.12556/RUL-115934
• Publication date in RUL: 30.04.2020

Secondary language

• Language: English
• Title: Influence of CD34+ cells transenocardial transplantation on diastolic function of the left ventricle in patients with dilative cardiomyopathy

Abstract

ABSTRACT Background and hypotheses. Left ventricular diastolic dysfunction is a predictor of the natural course of heart failure with a preserved or reduced left ventricular ejection fraction. The effect of stem cell transplantation used to treat advanced heart failure due to left ventricular diastolic dysfunction is unclear. The doctoral thesis evaluated whether i) echocardiographic parameters of diastolic dysfunction are related to parameters obtained by electroanatomical mapping prior to stem cell transplantation, and ii) whether CD34+ stem cell transplantation improves the left ventricular diastolic function of patients with advanced heart failure. Methods. We included consecutive patients with non-ischemic and ischemic dilated cardiomyopathy who were enrolled for a treatment with CD34+ stem cells. Patients had less than 40 % left ventricular ejection (LVEF), were in sinus rhythm, clinically stable (NYHA class III according to the New York Cardiac Association) for at least three months prior to enrollment. Patients were divided into groups according to the etiology of cardiomyopathy and baseline echocardiographic sign of elevated filling pressure (E/e' ⡥ 15) into subgroups. In all patients, CD34+ cells were mobilized from peripheral blood by bone marrow stimu-lation with filgrastim and isolated with apheresis. Electroanatomical mapping determined, according to the size of the unipolar endocardial potential and linear shortening of the heart muscle (LLS), areas of healthy (average unipolar potential ⡥ 8.27 mV and LLS ⡥ 6 %) and hibernated (average unipolar potential ⡥ 8.27 mV and LLS < 6 %) myo¬cardi-um, and scars (average unipolar potential < 8.27 mV and LLS < 6 %). We also measured global left ventricular relaxation time in patients with non-ischemic cardiomyopathy and compared it with echocardiographic parameters of diastolic dysfunction. Stem cells were injected transendocardially into areas of hibernated cardiac muscle. When enrolled in the study and 3, 6 and 12 months after CD34+ cell transplantation, an echocardiographic examination was performed to assess diastolic dysfunction and to monitor clinical (clinical examination and 6MWT) and laboratory parameters of heart failure (NT-proBNP blood level). Diastolic dysfunction was assessed by echo¬cardio-graphic parameters E/A, DT, TR and E/e', and the degree of diastolic dysfunction was determined in accordance with the ASE/EACVI recommendations. Results. We included 58 patients (mean age of all patients was 54 ± 8.4 years, 20.8 % were women). Non-ischemic cardiomyopathy had 38 patients ⠒ 18 with elevated filling pressure (DKMP+ group), 20 with normal filling pressure (DKMP⠒ group). Twenty patients had ischemic cardiomyopathy; all had elevated filling pressure (IKMP+ group). Endomyocardial recording of unipolar potentials resulted in a greater area of hibernated myocardium in the DKMP+ group than in the DKMP⠒ group (4.9 ± 2.7 mV and 2.7 ± 2.9 mV; p = 0.03) and a greater area of scars (2.2 ± 1.6 mV and 0.9 ± 1.1 mV; p = 0.02). Global relaxation time in electroanatomical measurement did not correlate with diastolic function indicators (E/A, DT and ASE/EACVI diastolic dysfunction rate), but correlated with E/e'. CD34+ transplantation was not associated with a significant change in diastolic dysfunction indicators or NT-proBNP concentration in any of the groups, but was associ-ated with improvement in 6MWT (DKMP+: 48 ± 58 m; p = 0.026: DKMP⠒: 52 ± 63 m; p = 0.05: ICMP+: 96 ± 62 m; p <0.001). CD34+ cell transplantation was associated with a significant decrease in the left ventricular E/e' pressure indicator only in the DKMP+ group (⠒8.0 ± 10.3; p = 0.008) and not in the DKMP– and IKMP+ groups. Conclusions. Prolonged global myocardial relaxation time, measured using an electro-anatomical map, correlates with the E/e' elevated filling pressure indicator but not with other indicators of diastolic dysfunction. Treatment with CD34+ stem cells lowers left ventricular filling pressure (E/e') only in DKMP+ patients (who have baseline elevated filling pressure), but not in DKMP– patients (where the E/e' indicator is baseline) or IKMP+ (where the extent of the scars is larger). The results of the study indicate a new possibility of assessment of elevated left ventricular filling pressure using an electro-anatomical map and indicate the possibility of a more appropriate selection of candidates for treatment with CD34+ stem cells.

• Keywords: cardiomyopathy, CD34+ cells, diastolic, echocardiography, electroana-tomical mapping.