Vpliv vstavitve zmanjševalca pretoka skozi koronarni sinus na telesno zmogljivost, obseg miokardne ishemije in EKG kazalnike aritmogenosti srca pri bolnikih z odporno angino pektoris

Mrak, Miha (author), Bunc, Matjaž (mentor), Žižek, David (comentor)

Omejevalec pretoka skozi koronarni sinus (angl. coronary sinus reducer, CSR) je nova metoda zdravljenja odporne angine pektoris. Randomizirana raziskava je pokazala izboljšanje simptomov angine pektoris pri bolnikih z ishemijo v povirju leve koronarne arterije (angl. left coronary artery, LCA). Učinkovitosti zdravljenja s CSR pri bolnikih z kronično popolno zaporo (angl. chronic total occlusion, CTO) desne koronarne arterije (angl. right coronary artery, RCA) ne poznamo, prav tako nimamo randomiziranih podatkov o vplivu CSR na izboljšanje telesne zmogljivosti. Predklinične raziskave so nakazale na povezavo med zožitvijo koronarnega sinusa in antiaritmičnim učinkom. Kliničnih raziskav o vplivu CSR na pojavnosti aritmij ni. V prvem delu naloge smo primerjali vpliv zdravljenja s CSR na izboljšanje simptomov angine pektoris pri bolnikih s CTO RCA in pretežno ishemijo v področju spodnje stene in bolnikih z ishemijo v povirju LCA. Dvaindvajset bolnikov s CTO RCA smo primerjali s 24 bolniki z ishemijo v povirju LCA. Po posegu se je v skupini s CTO RCA povprečni funkcijski razred kanadskega združenja za srčno-žilno medicino (angl. Canadian cardiovascular society, CCS) izboljšal s 2,73±0,46 na 1,82±0,73 (p <0,001) in v LCA skupini s 2,67±0,57 na 1,92±0,72 (p <0,001). Stopnja izboljšanja v obeh skupinah je bila primerljiva (p= 0,350). V obeh skupina je prišlo do pomembnega in primerljivega izboljšanja vseh domen Seattleskega vprašalnika o angini pektoris (angl. Seattle angina questionnaire, SAQ). Obremenitveno magnetno-resonančno slikanje srca (angl. cardiac magnetic resonance imaging, CMR) v področju spodnje stene ni pokazalo spremembe v številu ishemičnih segmentov, pokazalo pa je izboljšanje transmuralnega indeksu (p = 0,03) in indeksa perfuzijske rezerve miokarda ishemičnih segmentov (p = 0,03). V drugem delu naloge smo opravili randomizirano raziskavo Crossroad v kateri smo vključili bolnike z odporno angino pektoris CCS razreda II-IV in dokazano reverzibilno ishemijo v povirju LCA. Izboljšanje objektivnih kazalnikov telesne zmogljivosti pri bolnikih z vstavljenim CSR (13 bolnikov) smo primerjali s spremembo teh kazalnikov pri bolnikih z opravljenim navideznim posegom (12 bolnikov). Ob vključitvi in po 6 mesecih sledenja smo pri obeh skupinah bolnikov opravili s simptomi omejeno kardio-pulmonalno obremenitveno testiranje s prilagojenim zveznim protokolom. V skupini z vstavljenim CSR smo beležili porast največje porabe kisika s 15,56 ± 4,05 na 18,4 ± 5.2 mL/kg/min (p = 0,03). V skupini z navideznim posegom do spremembe v porabi kisika ni prišlo (p = 0,53). Porast porabe kisika pri bolnikih z vstavljenim CSR je bila glede na bolnike v skupini z opravljenim navideznim posegom pomembno višja (p = 0,03). V nasprotju z izboljšanjem objektivnih kazalnikov telesne zmogljivosti, razlik pri izboljšanju funkcijskega razreda CCS in posameznih domen SAQ nismo ugotavljali. V tretjem delu naloge smo opravili podanalizo bolnikov vključenih v raziskavo Crossroad. Pred in po posegu smo v obeh skupinah bolnikov posneli 5-minutni posnetek visokoločljivostnega EKG (angl. high resolution ECG, hrECG). Po 6 mesecih sledenja smo primerjali spremembe trajanja intervala TpTe (angl. T-peak T-end interval), spremembo prostorskega kóta med osjo QRS in T valom (kót QRS-T) z uporabo največje (kót QRSTP) in srednje (kót QRSTM) amplitude vektorjev QRS in T, indeks QT variabilnosti (QTVi), razmerje QT variabilnosti, amplitudo prostorskega prekatnega gradienta (angl. spatial ventricular gradient, SVG) in variabilnost srčne frekvence z uporabo časovne in frekvenčne domene. Ob vključitvi so bili analizirani parametri medsebojno primerljivi, med sledenjem je ostala srčna frekvenca nespremenjena. Analiza znotraj posameznih skupin po 6 mesecih pri spremembi analiziranih parametrov ni pokazala statistično pomembnih razlik. Tudi primerjava med skupinama pomembnih razlik ni pokazala. Z delom v okviru te doktorske naloge smo pokazali, da se izboljšanje subjektivnih kazalnikov angine pektoris po vstavitvi CSR med bolniki z ishemijo v povirju LCA in bolniki s CTO RCA in pretežno ishemijo v področju spodnje stene ne razlikuje. Pri bolnikih z ishemijo v povirju LCA je vstavitev CSR povezana z izboljšanjem telesne zmogljivosti, ki presega učinkovitost proti-ishemičnega zdravljenja z zdravili. V nasprotju s predkliničnimi raziskavami, po vstavitvi CSR pomembnih sprememb v aritmogenosti srca nismo ugotavljali.

• Language: Slovenian
• Keywords: angina pektoris, koronarni sinus, omejevalec pretoka, CSR, ishemija, obremenitveno testiranje, CCS, SAQ, visokoločljivostni EKG, RCA
• Work type: Doctoral dissertation
• Organization: MF - Faculty of Medicine
• Year: 2024
• PID: 20.500.12556/RUL-155954
• Publication date in RUL: 25.04.2024

Secondary language

• Language: English
• Title: The influence of coronary flow reducer implantation on exertional capacity, extent of myocardial ischemia and ECG arrhythmogenic markers in patients with resistant angina pectoris

Abstract

Coronary sinus reducer (CSR) implantation is a new treatment option for patients with refractory angina. The previous randomized trial showed improvement of angina symptoms in patients with reversible ischemia in the territory of the left coronary artery (LCA). The efficiency of CSR treatment in patients with chronic total occlusion (CTO) of the right coronary artery (RCA) remains unknown. Furthermore, there is no randomized data, which would show the improvement of exercise capacity after the treatment. Preclinical studies have shown a link between coronary sinus narrowing and antiarrhythmic effect. There is no prospective clinical data on this effect in patients treated with CSR. In the first part of this thesis, we compared the efficacy of CSR implantation in patients with CTO RCA and predominant ischemia of the inferior wall and patients with ischemia in the territory of LCA. Twenty-two patients with CTO RCA were compared to 24 patients with LCA ischemia. After the procedure, the average functional class of the Canadian Cardiovascular Society (CCS) in the CTO RCA group improved from 2.73±0.46 to 1.82±0.73 (p <0.001) and in the LCA group from 2.67±0.57 to 1.92±0.72 (p <0.001). The improvement in both groups was comparable (p= 0.350). In both groups, there was a significant and comparable improvement in all domains of the Seattle Angina Questionnaire (SAQ). Cardiac stress magnetic resonance imaging (CMR) showed no change in the number of ischemic segments in the inferior and inferoseptal wall but showed an improvement of transmurality index (p = 0.03) and myocardial perfusion reserve index (p = 0.03) in segments with inducible ischemia. In the second part of the thesis, we conducted a randomized study (Crossroad) that included patients with refractory angina CCS class II-IV and inducible ischemia in the LCA territory. The improvement of exercise parameters in patients with implanted CSR (13 patients) was compared with the improvement in patients who underwent a sham procedure (12 patients). At baseline and after 6 months of follow-up a symptom-limited cardiopulmonary stress test was performed in both groups with the use of adjusted ramp protocol. In the CSR group, the maximum oxygen consumption increased from 15.56 ± 4.05 to 18.4 ± 5.2 mL/kg/min (p = 0.03). In the sham group, there was no significant change in oxygen consumption (p = 0.53). The improvement of oxygen consumption in the CSR group was significantly higher if compared to patients in the sham group (p = 0.03). In contrast to the improvement of exercise parameters, there was no difference in the improvement of CCS class or SAQ domains. In the third part of the thesis, we performed a sub-analysis of the Crossroad study. At baseline and after 6 months of follow-up, a 5-minute high-resolution ECG (hrECG) was recorded in both patient groups. We analyzed changes in the duration of the T-peak T-end interval, change of the spatial angle between the QRS axis and T wave (QRS-T angle) using the either maximum (QRSTP angle) or mean (QRSTM angle) QRS and T vector amplitudes, QT variability index (QTVi), QT variability ratio, spatial ventricular gradient (SVG) amplitude and heart rate variability using the time and frequency domains. At baseline, all analyzed parameters were comparable between both groups and heart rate remained constant. The intragroup analysis did not show any significant change in TpTe, QRSTP, QRSTM, SVG, QT, and heart rate variability at follow-up. Furthermore, intergroup comparison between CSR implantation and sham procedure also did not show any significant difference in the change of analyzed parameters. In this thesis, we have shown that the symptomatic improvement after CSR implantation in patients with CTO RCA and predominant ischemia of the inferior wall does not differ from the improvement in patients with LCA ischemia. In patients with LCA ischemia CSR implantation improves exercise capacity beyond that of anti-ischemic medical therapy. In contrast to preclinical studies, we did not find any significant impact of CSR implantation on hrECG indicators of arrhythmic properties of the heart.

• Keywords: angina pectoris, coronary sinus, coronary sinus reducer, CSR, ischemia, exercise test, CCS, SAQ, high-resolution ECG, RCA