Obwohl immer mehr Patienten der TAVI zugänglich gemacht werden können, ist die Datenlage bezüglich des Langzeitüberlebens aktuell nicht ausreichend. Besonders rar sind Daten zur Langzeitauswertung bei den Patientengruppen mit mäßiggradig reduzierter Ejektionsfraktion (LVEF 40-49%) oder hochgradig reduzierter Ejektionsfraktion (LVEF < 40%). Daher hat sich diese Arbeit zum Ziel gesetzt, diese speziellen Patientengruppen auf das Langzeitüberleben hin zu untersuchen. Es wurden dazu die Daten von 142 Patienten ausgewertet, die von 2009 bis 2016 im Herzzentrum Dresden eine TAVI erhalten haben. Der Gruppe mit einer mäßiggradig reduzierten EF konnten 58 Patienten zugeordnet werden und der Gruppe mit hochgradig reduzierter EF 84 Patienten. Nach Erhebung der Basiswerte wurden beide Patientengruppen miteinander verglichen um Unterschiede zwischen präoperativen - und postoperativen Parametern sowie der Mortalität zu detektieren. Anschließend wurden die Patienten mit der stärker reduzierten EF gesondert in Bezug auf Hospitalmortalität und Gesamtmortalität hin untersucht. Weiterhin wurden die entsprechenden Prädiktoren isoliert und auf Relevanz untersucht. Das Langzeitüberleben wurde für jede Probandengruppe getrennt ermittelt und mittels Kaplan-Meier-Kurve graphisch dargestellt. In dieser Arbeit konnte bewiesen werden, dass die EF sich als Prädiktor für die Gesamtmortalität eignet, da diese statistisch signifikant höher ist, wenn der Basiswert der EF < 40 % beträgt (48,8 % für EF < 40 % vs. 24,1 % für EF ≥ 40 %; p = 0,003). Ebenfalls wies sie für den Prädiktor EF < 40 % eine statistisch signifikante Unabhängigkeit nach (p = 0,04989). Zudem konnte gezeigt werden, dass die Gesamtmortalität in der Gruppe der Patienten mit stärker reduzierter EF um 19 % statistisch signifikant höher ist als in der Gruppe der Patienten mit mäßiggradig reduzierter EF (28,9 vs. 9,9 %; p = 0,003). Auch Prädiktoren für die Hospitalmortalität bei stärker reduzierter EF konnten mit den Parametern postoperative PVL (p = 0,044), postoperative Vmax (p = 0,034), postoperativer dpmax (p = 0,023) und postoperativer dpmean (p = 0,044) ermittelt werden. Die Gesamtmortalität betrachtend konnte für diese Patientengruppe kein statistisch signifikanter Prädiktor gefunden werden. Der Unterschied zwischen den Überlebenswahrscheinlichkeiten beider Gruppen lag nach einem Jahr bei 6,9 % (77,8 ± 6,2 vs. 70,9 ± 5,4 %), nach zwei Jahren bei 17,6 % (75,5 ± 6,4 vs. 57,9 ± 5,9 %) und zum längsten vergleichbaren Zeitraum nach 4,5 Jahren bei 23,5 % (60,0 ± 10,4 % vs. 36,5 ± 7,0 %), jeweils zum Nachteil der Probanden mit EF < 40 %.:1 EINLEITUNG 1.1 MOTIVATION DER ARBEIT 1.2 KRANKHEITSBILDER DES HERZENS DIE TAVI INDIZIEREN 1.2.1 AORTENKLAPPENSTENOSE 1.3 KATHETERGESTÜTZTER AORTENKLAPPENERSATZ 1.3.1 ENTWICKLUNG DER INDIKATIONSSTELLUNG ZUR TAVI MIT HILFE FÜHRENDER STUDIEN 1.3.2 INDIKATIONSSTELLUNG ZUR TAVI 1.4 MORTALITÄT – EINSCHÄTZUNG UND VERRINGERUNG 1.4.1 VORUNTERSUCHUNGEN 1.4.2 KOMPLIKATIONEN NACH TAVI 1.5 ZIEL DER STUDIE 2 MATERIAL UND METHODEN 2.1 EINGESCHLOSSENE PATIENTEN 2.2 RETROSPEKTIVE DATENERHEBUNG MITTELS MCC UND SEPAVAS 2.2.1 ERHOBENE PARAMETER 2.3 POSTALISCHE PATIENTENANSPRACHE 2.4 DATENAUFBEREITUNG UND VERFEINERUNG 2.5 ETHIKVOTUM 3 ERGEBNISAUSWERTUNG 3.1 STATISTIK 3.1.1 DESKRIPTIVE STATISTIK 3.1.2 SCHLIEßENDE STATISTIK 3.2 ALLGEMEINE ANALYSE 3.2.1 PATIENTEN BASISPARAMETER 3.2.2 OP-DATEN 3.2.3 POSTOPERATIVE HÄMODYNAMIK 3.2.4 POSTOPERATIVE KOMPLIKATIONEN NACH TAVI 3.2.5 POSTOPERATIVES OUTCOME 3.3 MORTALITÄTSANALYSE 3.3.1 UNIVARIATE MORTALITÄTSANALYSE BEZOGEN AUF GESAMTMORTALITÄT 3.3.2 UNIVARIATE MORTALITÄTSANALYSE BEZOGEN AUF HOSPITALMORTALITÄT 3.4 SUBGRUPPENANALYSE 3.4.1 VERGLEICH DER GRUPPEN EF ≥ 40 % UND < 40 % 3.4.2 SUBGRUPPENANALYSE DER EF < 40 % FÜR DIE HOSPITALMORTALITÄT 3.4.3 SUBGRUPPENANALYSE DER EF < 40 % FÜR DIE GESAMTMORTALITÄT 3.5 WEITERE STATISTISCHE ANALYSE 3.5.1 MULTIVARIANZANALYSE 3.5.2 COX REGRESSION 2 3.5.3 ÜBERLEBENSANALYSE NACH KAPLAN-MEIER 4 DISKUSSION 4.1 BEDEUTUNG DER ERGEBNISSE UND VERGLEICH MIT ANDEREN STUDIEN 4.1.1 GEEIGNETE PRÄDIKTOREN FÜR DIE MORTALITÄT 4.1.2 DIE EJEKTIONSFRAKTION ALS PRÄDIKTOR FÜR DIE MORTALITÄT 4.1.3 LANGZEITÜBERLEBENSWAHRSCHEINLICHKEIT 4.2 LIMITIERUNGEN DER ARBEIT 5 FAZIT 6 ZUSAMMENFASSUNG 7 SUMMARY 8 LITERATURVERZEICHNIS 9 TABELLENVERZEICHNIS 10 ABBILDUNGSVERZEICHNIS 11 DANKSAGUNG 12 ANLAGE 1 13 ANLAGE 2

Objective: Aortic valve (AV) leaflets rely on a precise extracellular matrix (ECM) microarchitecture for appropriate biomechanical performance. The ECM structure is maintained by valvular interstitial cells (VICs), which reside within the leaflets. The presence of pigment produced by a melanocytic population of VICs in mice with dark coats has been generally regarded as a nuisance, as it interferes with histological analysis of the AV leaflets. However, our previous studies have shown that the presence of pigment correlates with increased mechanical stiffness within the leaflets as measured by nanoindentation analyses. In the current study, we seek to better characterize the phenotype of understudied melanocytic VICs, explore the role of these VICs in ECM patterning, and assess the presence of these VICs in human aortic valve tissues. Approach and Results: Immunofluorescence and immunohistochemistry revealed that melanocytes within murine AV leaflets express phenotypic markers of either neuronal or glial cells. These VIC subpopulations exhibited regional patterns that corresponded to the distribution of elastin and glycosaminoglycan ECM proteins, respectively. VICs with neuronal and glial phenotypes were also found in human AV leaflets and showed ECM associations similar to those observed in murine leaflets. A subset of VICs within human AV leaflets also expressed dopachrome tautomerase, a common melanocyte marker. A spontaneous mouse mutant with no aortic valve pigmentation lacked elastic fibers and had reduced elastin gene expression within AV leaflets. A hyperpigmented transgenic mouse exhibited increased AV leaflet elastic fibers and elastin gene expression. Conclusions: Melanocytic VIC subpopulations appear critical for appropriate elastogenesis in mouse AVs, providing new insight into the regulation of AV ECM homeostasis. The identification of a similar VIC population in human AVs suggests conservation across species.

No description available.

Ischemia caused by particles becoming dislodged during transcatheter aortic valve replacement (TAVR) is a possible complication of TAVR. The particles that become dislodged can travel out of the aortic valve, into the aortic arch, and then into either the brachiocephalic artery, the left common carotid artery, the left subclavian artery or continue into the descending aorta. If the particles continue into the descending aorta it poses no risk of causing ischemia however if it travels into the other arteries then it increases the possibility of the particle causing an ischemic event. The goal of this study is to determine what parameters cause the particle to enter one artery over another. The parameters analyzed are the particle diameter, the particle density, the blood pressure, and the diameter of the catheter used in the surgery. This was done by creating a finite element model in COMSOL Multiphysics® to track the particles flowing through a scan of an actual aortic arch. It was determined that the particle diameter, particle density, and the blood pressure affect which artery the particles take to exit the aortic arch. However the diameter of the surgical catheter used in a transaortic approach is not statistically significant when determining which artery the particles will exit. The study shows that larger diameter particle would lead to a higher transmissions probability into the brachiocephalic artery, the left common carotid artery, and the left subclavian artery while a smaller diameter particle would have a higher transmission probability for the descending aorta. Averaging all particle diameters, densities and blood pressure found that 54.95 ± 13.66% of the particles released will travel into the cerebral circulatory system.

Objectives: As surgical experience with infective endocarditis following transcatheter aortic valve replacement is scarce, this study compared the perioperative and short-term outcomes of patients suffering from endocarditis following surgical aortic valve replacement and transcatheter aortic valve replacement. Methods: Between January 2013 and December 2020, 468 consecutive patients were admitted to our center for surgery for IE. Among them, 98 were operated on for endocarditis following surgical aortic valve replacement and 22 for endocarditis following transcatheter aortic valve replacement. Results: The median EuroSCORE II (52.1 (40.6–62.0) v/s 45.4 (32.6–58.1), p = 0.207) and STS-PROM (1.8 (1.6–2.1) v/s 1.9 (1.4–2.2), p = 0.622) were comparable. Endocarditis following transcatheter aortic valve replacement accounted for 13.7% of the aortic prosthetic valve endocarditis between 2013 and 2015; this increased to 26.9% in the years 2019 and 2020.Concomitant procedures were performed in 35 patients (29.2%). The operative mortality was 26.5% in the endocarditis following surgical aortic valve replacement group and 9.1% in the endocarditis following transcatheter aortic valve replacement group (p = 0.098). Upon follow-up, survival at 6 months was found to be 98% in the group with endocarditis following surgical aortic valve replacement and 89% in the group with endocarditis following transcatheter aortic valve replacement (p = 0.081). Conclusions: Patients suffering from endocarditis following surgical aortic valve replacement and transcatheter aortic valve replacement present with comparable risk profiles and can be surgically treated with comparable results. Surgery as a curative option should not be rejected even in this intermediate-risk cohort

No description available.

No description available.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23767号 / 医博第4813号 / 新制||医||1056(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 大鶴 繁, 教授 小西 靖彦, 教授 森田 智視 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Continuous-wave (CW) Doppler recordings of ascending aortic maximal blood flow acceleration (PkA), maximal velocity (PkV) and systolic velocity integral (SVI) were taken at each stage of a graded exercise treadmill test on two separate days with 30 physically active adult males. Signals were measured (Quinton Exerdop) for all cardiac cycles in the 3rd minute of each stage using a hand-held probe positioned at the suprasternal notch. A dedicated microcomputer, programmed to select "valid" beats on the basis of value consistency in the sample set, determined the acceptability of signals. No significant differences were found between the three trial means within each stage on either day for PkA, PkV or SVI. Significant (p <.01) intraclass reliability estimates ranged from r = 0.89 to 0.97 (Pk.A), r = 0.90 to 0.98 (PkV) and r = 0.85 to 0.95 (SVI) . Coefficients of variation were calculated at each stage to estimate the relative consistency of each measure. A gradual reduction of the coefficient of variation was observed for each blood flow measure between stages one and four. The test-retest (between days) reliability coefficients for PkA, PkV and SVI for stages one to four ranged between r = 0.51 to 0.78 (P <.004), but correlations for the pre-exercise baseline and stages five and six were lower. These results indicate that (1) PkA, PkV and SVI demonstrate greater measurement stability within each stage of a graded exercise test than is the case between separate days of measurement at the same stage; and (2) there is modest day-to-day response stability for clinical testing with the Doppler parameter of PkV. Reliability/stability was best in exercise stages which encompass the speed and grade range of 45.0 m•min⁻¹/10%. - 111.7 m•min⁻¹/14%, i.e., those in which all subjects can walk. / Master of Science

Yes / Objectives: This study aimed to determine the impact on radiation dose and image quality of a new cardiac interventional X-ray system for trans-catheter aortic valve implantation (TAVI) patients compared to the previously-used cardiac X-ray system. Methods: Patient dose and image data were retrospectively collected from a Philips AlluraClarity (new) and Siemens Axion Artis (reference) X-ray system. Patient dose area product (DAP) and fluoroscopy duration of 41 patient cases from each X-ray system were compared using a Wilcoxon test. Ten patient aortograms from each X-ray system were scored by 32 observers on a continuous scale to assess the clinical image quality at the given phase of the TAVI procedure. Scores were dichotomised by acceptability and analysed using a Chi-squared test. Results: Significant reductions in patient dose (p<<0.001) were found for the new system with no significant change in fluoroscopy duration (p=0.052); procedure DAP reduced by 55%, fluoroscopy DAP by 48% and “cine” acquisition DAP by 61%. There was no significant difference between image quality scores of the two X-ray systems (p=0.06). Conclusions: The new cardiac X-ray system demonstrated a very significant reduction in patient dose with no loss of clinical image quality. Advances in Knowledge: The huge growth of TAVI may impact on the radiation exposure of cardiac patients and particularly on operators including anaesthetists; cumulative exposure of interventional cardiologists performing high volume TAVI over 30-40 years may be harmful. The Phillips Clarity upgrade including improved image enhancement and optimised X-ray settings significantly reduced radiation without reducing clinically acceptable image quality.