Στην υπό μελέτη διατριβή διερευνήθηκε μια σειρά υποθέσεων που οδήγησαν: 1) Στη ανεύρεση μαθηματικών μοντέλων που δύνανται να υπολογίζουν το μήκος σημαντικών ανατομικών μεγεθών στη κατιούσα αορτή και κατ επέκταση να προσφέρουν βοήθεια στη επιλογή του ιδανικού μεγέθους ασκού ανά μεμονωμένο ασθενή. Δείξαμε ότι αυτά τα μοντέλα έχουν αυξημένο βαθμό προβλεπτικής αξίας. Περαιτέρω τα συγκρίναμε με τον κλασικό τρόπο επιλογής του ιδανικού μεγέθους και ευρέθησαν ανώτερα. 2)Στη δημιουργία και εξέταση των συνθηκών όπου συμβαίνει η τραυματική διαταραχή του έσω χιτώνα της κατιούσης αορτής κατά την διάρκεια της λειτουργίας του ενδοαορτικου ασκού. Η κίνηση του ασκού εντός του αορτικού αυλού είναι πολύπλοκη. Είναι σημαντική η παρατηρούμενη επαναλαμβανόμενη «επίδραση κρούσης δικην μαστιγίου» (whipping effect) του καθετήρα του ασκού στο οπίσθιο- πλάγιο αορτικό τοίχωμα. Αυτή η κίνηση φάνηκε να ενισχύεται κατά την παρατεταμένη φάση της σύμπτυξης του ασκού όταν ο ρυθμός λειτουργίας του IABP είναι 1:3. Κάτω από τέτοιες συνθήκες σημειώθηκε επιδείνωση του «score αορτικού τραύματος» που συνηγορεί υπέρ της αποφυγής του απογαλακτισμού με σταδιακή ελάττωση του ρυθμού λειτουργίας του ασκού (mode). Η επαναλαμβανόμενη κυκλική κίνηση του ενδοαορτικου ασκού επιβεβαιώθηκε κατά την διάρκεια της λειτουργίας του σε πτωματικές αθηρωματικες αορτές. Καταγραφή διαταραχών και αποκόλλησης ( fissuring) πλακών αποδόθηκε στο κύμα πίεσης που δημιουργήθηκε από την κίνηση του ασκού και λιγότερο σε άμεσο τραυματισμό. 3) Στη κλινική εξέταση των επιπλοκών καρδιοχειρουργικών ασθενών που χρειάσθηκαν θεραπεία με ενδοαορτικο ασκό, όπου βρέθηκαν συγκεκριμένα γκρουπ αυξημένου ρίσκου. Ασθενείς όπου η χρήση του ασκού χρησιμοποιηθηκε μετεγχειρητικά καθώς και ασθενείς όπου χρειάστηκαν θεραπεία με IABP μετά από αντικατάσταση βαλβίδας (ιδιαίτερα μιτροειδούς βαλβίδας) παρουσίασαν υψηλή μετεγχειρητική θνητότητα. Οι ακόλουθες μεταβλητές εμφανίσθηκαν ως παράγοντες κινδύνου αυξημένης θνησιμότητας: Θηλυκό γένος, κάπνισμα, αυξημένη προ-εγχειρητική κρεατινινη, ισχαιμικός χρόνος>80min και εισαγωγή του ασκού την μετεγχειρητική περίοδο. Με χρήση παλίνδρομης ανάλυσης, βρέθηκε ότι ιστορικό περιφερικής αγγειοπαθειας, και κλάσμα εξώθησης κάτω από 30% αποτελούν παράγοντας κινδύνου για την ανάπτυξη αγγειακών επιπλοκών. Επιπρόσθετα με την χρήση προδρομικής τυχαιοποιημένης μελέτης φάνηκε ότι απογαλακτισμός μέσω μείωσης του όγκου πλήρωσης του ασκού απετέλεσε προφυλακτικό παράγοντα για την ανάπτυξη αγγειακών επιπλοκών. Συμπερασματικά από αυτή την εργασία απορρέουν προτάσεις που πιθανώς θα επηρεάσουν την κλινική πράξη. Συγκεκριμένα προτίθεται ένας τρόπος επιλογής του ιδανικού μεγέθους ασκού που δύναται να οδηγήσει σε αποφυγή χρησιμοποίησης μεγάλων ασκών σε μικρόσωμες γυναίκες με αθηρωματικες αορτές με αποτέλεσμα περαιτέρω ελάττωση των αγγειακών επιπλοκών. Επιπρόσθετα έχοντας μελετήσει τον τρόπο κίνησης του ασκού κάτω από διαφορετικά αιμοδυναμικα σενάρια οδηγούμεθα στο συμπέρασμα ότι ο «απογαλακτισμός» πρέπει να γίνεται με ελάττωση του όγκου του ασκού (augmentation). Δείξαμε ότι αυτός ο τρόπος «απογαλακτισμού» έχει τη τάση να οδηγεί σε λιγότερες εμβολικες επιπλοκές. Τέλος έγινε ταυτοποίηση συγκεκριμένων γκρουπ ασθενών όπου αλλαγή πρακτικής όσο αναφορά την πιο πρώιμη χρησιμοποίηση του ασκού η την αλλαγή στον τρόπο απογαλακτισμού από αυτό μπορεί δυνητικά να οδηγήσει σε μείωση της θνητότητας και νοσηρότητας. / IAB size selection is based on patients height with the known risks of under or over sizing, although size selection should rely on individual hemodynamics & measurements of the length & diameter of the aorta from the left subclavian artery to the celiac axis. The first part of this project is a pilot study whereby an attempt was made, in order to predict thoracic aortic dimensions from easily obtainable external anatomical landmarks. That would potentially lead to an optimal selection of balloon sizes for an individual patient and thus reducing adverse effects of its use. The second part of the project is an experimental Angioscopic and Pathological study that set off to investigate in a mock pig circulation model, whether weaning by mode or by augmentation produces more aortic intimal trauma. The third part of this work, studied the interaction between the intraaortic balloon catheter and the human atherosclerotic aorta. With the use of an artificial circulation we obtained direct visualisation of the dynamic action of the balloon catheter within the cadaveric human aorta. Sequelae of traumatic atherosclerotic plaque rapture due to the balloon action was observed. The last study was a clinical outcome analysis with an interest in complications in a cohort of patients requiring treatment with IABP in a single Cardiothoracic Unit over a five year period. During the initial part of the project, measurements were carried out from a series of 40 cadavers during autopsy. Internal Aortic dimensions and also external somatometric distances of the thoracic cage were obtained. Using multiple regression analysis a model was devised in order to predict aortic lengths. Being able to calculate internal aortic lengths, one could be lead to a better intraaortic balloon sizing. During the second part of the study an artificial pulsatile pump was used and an intact porcine aorta was incorporated into the circuit with the inflow at the aortic valve and the outflow at the right common iliac artery. Direct angioscopic images of the interior of the aorta were obtained. Keeping steady hemodynamic conditions, an “aortic impact score” was calculated taking into account angioscopic observational variables and biopsies of the aorta at 30min, 6hours and 12 hours following counterpulsation at 1:1, 1:2 ,1:3 Versus 1:1 and 75%, 50% and 25% augmentation. The previous model was extrapolated in to the third study whereby an artificial circulation was constructed using of PVC tubing, a filter and a roller pump. A series of 5 intact cadaveric human aortas were then individually studied by placing each in series within the circuit. A balloon catheter was advanced via the left common iliac artery into the descending aorta under direct angioscopic vision. Balloon pumping was then commenced. The circuit was perfused with Normal saline at a flow rate of 3L/minute. Pump actions of 1:1 and 1:2 were simulated. A microporous filter was incorporated into the system in order to collect embolic material during balloon action. Each aorta at the end of the experiment was subjected to histological examination. During the last study data were prospectively collected within a 5 year period from a single Cardiothoracic Unit. 2697 adult patients underwent cardiac surgery, out of which 136patients (5%) required IABP. Those patients were studied in terms of balloon associated complications. We create a model of optimal balloon sizing with a high prediction value. The performance of the model was tested against the current quidelines in a cross validation way and was found to be superior. Together with height, somatometric measurements of thoracic cage could lead to more optimal IAB size selection. During the angioscopic observational studies with porcine and also cadaveric aortas the movement of the balloon catheter in relation to the aorta was observed. The balloon catheter moves relative to the wall of the aorta during inflation and deflation. Contact between the balloon and the aorta only occurs during deflation. Side branches of the aorta are not occluded by the catheter. Plaque disruption and embolus formation appear to result from pressure wave action rather than direct contact with the balloon. By calculating the aortic impact score it appears that weaning by mode produces more aortic intimal trauma. 1:3 mode produces marked intimal disruption that worsens with time. Lastly during the clinical study of patients requiring treatment with an IABP we detected significant early mortality and morbidity associated with IABP, however intermediate follow up reveals favourable outcome.

Habilitacijos procedūrai teikiamoje mokslo darbų apžvalgoje apibendrinama Vilniaus universiteto Širdies ir kraujagyslių ligų klinikoje taikyto sunkaus širdies nepakankamumo gydymo patirtis. Įrodytas intraaortinės kontrapulsacijos balionėliu taikymo tikslingumas pacientams su dekompensuota dilatacine kardiomiopatija. Įvertintas dirbtinių skilvelių, kaip tilto į transplantaciją ar likimo terapiją efektyvumas. Nustatyta, kaip techniniai dirbtinių skilvelių pakeitimai gali daryti įtaką gydymo rezultatams. Ištirtas dirbtinių skilvelių poveikis recipiento imuninei sistemai prieš ir po transplantacijos. Apžvelgti alternatyvūs širdies transplantacijai chirurginiai gydymo metodai. Pasiūlyta originali modifikuotos labirinto operacijos technika, įvertintas jos saugumas, efektyvumas ir galimybė derinti su kitomis širdies operacijomis. Prognozuojamos ateities tendencijos labai sunkiam širdies nepakankamumui gydyti. Šiame darbe remiamasi kartu su bendraautoriais atliktų tyrimų 2001-2009 m. rezultatais. Autorius visuose apžvelgiamuose tyrimuose dalyvavo tiesiogiai, kaip padalinio, kuriame gydomi pacientai su labai sunkiu širdies nepakankamumu, vadovas ir kaip chirurgas. Remiantis publikuota medžiaga buvo daryti pranešimai ir Lietuvoje, ir užsienyje. / The experience of treatment of end-stage heart failure cumulated at Vilnius University Cardiovascular Surgery Clinic is provided for habilitation procedure. The experience of intraaortic balloon counterpulsation for the patients suffering from decompensated dilatative cardiomyopathy has been proven. The efficacy of artificial ventricular assist devices as a bridge to transplantation or destination therapy has been evaluated. The role of technical modifications of ventricular assist devices for the outcomes of treatment has been assessed. The impact of assist devices on the immune status of the patient pre- and post-transplantation has also been evaluated. The alternative methods of treatment instead of heart transplantation are reviewed. The original technique of modified maze procedure is proposed; the safety, efficacy and possibilities of combining this technique with other heart operations are assessed. The future trends for treatment of end-stage heart failure are predicted. This study is based on the investigations performed with co-authors during the period since 2001 to 2009. The author has participated directly in all reviewed investigations as the head of the department where patients suffering from end-stage heart failure are being treated and as well as a surgeon. The reports based on the published material have been presented in Lithuania and abroad.

Intraaortic balloon counterpulsation (IABP) is the most widely used mechanical support in the assistance of a failing heart.1 Despite extensive research in this field no experimental or clinical studies have been undertaken to evaluate the most effective manner to wean IABP.2 The research reported in this thesis examines early recognition of cardiac decompensation and the management of IABP weaning. Conducted in three phases, the aim of this research programme was to determine the best manner by which to wean IABP. Phase 1 utilised a comparative descriptive design to examine IABP practice at a single cardiothoracic tertiary referral hospital. The majority of data collection was prospective, however, the required sample size saw inclusion of some retrospective data. This single centre data were than compared with an international registry to contrast IABP management and outcome. Phase 2 utilised a questionnaire survey to audit all Australasian intensive care units. Survey results were combined and statistically analysed to describe Australasian IABP management, weaning and outcome. Phase 3 utilised a quasi-experimental, one-group, posttest-only design to clinically validate a tool designed to monitor a patient's cardiac function - the 'cardiac decompensation tool'. Phase 1 saw data collected for 669 IABP insertions over an 11 year period at a single Australian hospital. This cohort was compared against the 38,606 patient dataset of The Benchmark Counterpulsation Outcomes Registry. Australian IABP practice saw later application of the device in a higher acuity patient. Australian practice demonstrated a prejudice toward intraoperative use (34.2% versus 16.6%; p=< 0.0001) and an aversion to catheter laboratory support (10.6% versus 19%; p=< 0.0001). Australian mortality while slightly higher, remained comparable (22% versus 20.8%; p=ns). Phase 2 response rate was 60%. The most common Australasian method of IABP support withdrawal was ratio reduction only (61%). Units with a documented weaning policy were less likely to require balloon reinsertion or pharmacologic escalation following IABP removal (p=0.06). Indicators most likely to demonstrate a patient's readiness for IABP weaning were blood pressure (92%), heart rate (76%) and wedge pressure (59%). Phase 3 revealed cardiac decompensation tool scores to increase immediately prior to a treatment escalation (p=0.022) and decrease immediately following this escalation in therapy (p=0.0096). There was also some indication of decreasing scores prior to treatment minimisation (p=0.005). Tool scores demonstrated a corresponding treatment fluctuation up to three hours prior to the treatment intervention. With Phase 1 and 2 revealing many aspects of IABP practice to vary, the need for some direction regarding weaning is evident. Timely recognition of cardiac decompensation during IABP weaning allows an opportunity for the earlier escalation of treatment and consequent provision of increased cardiac support. Application of the Phase 3 cardiac decompensation tool can only assist in ensuring the best manner by which to support IABP weaning.