BACKGROUND: Treatment of left-sided Infective Endocarditis (IE) is challenging due to the presence of both surgical and medical interventions. The choice typically depends on the patient’s surgical risk and severity of infection. Our aim is to compare outcomes of IE patients who undergo valve replacement surgery with patients who are treated with solely antibiotics. METHODS: Patients undergoing valve surgery at our institution from 1995 to 2014 (n=196) and patients who were treated medically for IE from 2001 to 2014 (n=120) were included in this study. In total, 316 patients were included and clinical data was retrospectively collected from chart review. Society of Thoracic Surgeons (STS) Scores were calculated to assess for surgical risk and data for preoperative fever, angina, and abscess was collected to assess for severity of infection. The primary outcome of interest was mortality at 30 days and 1 year post-treatment and secondary outcomes included post-treatment development of septic shock, MI, embolic events, recurrence of infection, stroke, and renal dysfunction. Cox regression analyses were performed to assess the likelihood of mortality based on the patient’s pre-intervention comorbidities and characteristics. A Kaplan-Meier Analysis was also conducted to assess for survival at both 30 days and 1 year. RESULTS: Pre-operative fever (68.88% surgical vs 52.50% medical, p=0.002), angina (13.78% surgical vs 2.50% medical, p<0.05), and presence of abscess (33.37% surgical vs 6.67% medical, p<0.05) were significantly higher in the surgical population. Mortality at both 30-days (7.65% surgical vs 29.17% medical, p<0.05) and 1 year (17.35% surgical vs 46.67% medical, p<0.05) was significantly higher in the medical cohort. Mortality in patients presenting with valvular abscess was significantly higher in the surgical population at 30 days (4.5% surgical vs 62.5% medical, p<0.05) and 1 year (15.15% surgical vs. 75.00% medical, p<0.05). Surgical risk was significantly higher in medical patients overall (p<0.05), but not significantly higher in the pathogen specific subgroups. By individual pathogen, medical mortality was significantly higher at both 30 days and 1 year in the MRSA (p=0.0004 and p=0.0002) and Staphylococcus population (p=0.001 and p=0.0005) but only significantly higher in the Streptococcus population at 1 year (p=0.032). CONCLUSION: Valve Replacement Surgery in patients with left-sided MRSA and non-MRSA Staphylococcus IE leads to significantly better mortality outcomes at 30 days and 1 year than medical management. Specifically, we suggest that patients with preoperative valvular abscess undergo valve replacement surgery, regardless of pathogen, and that patients with MRSA and non-MRSA Staphylococcus IE be strongly considered for surgical intervention.

Aortic valve replacement (AVR) is the only life-saving treatment for patients with severe symptomatic aortic stenosis. Bioprosthetic valves are used in 90% of AVRs because they do not require lifelong anticoagulation. The major limitation of bioprosthetic valves is their limited durability compared to mechanical valves. In addition, bioprosthetic valves still carry a 2-3% risk of symptomatic valve thrombosis, stroke, and thromboembolism in the first 30 days after implantation, and a 1% annual risk thereafter. The risk of subclinical valve thrombosis is around 10% at 30 days and 25% at 1 year, and prevention of subclinical valve thrombosis is hypothesized to reduce the risk of clinical thrombotic events and perhaps even improve valve durability, although high-quality evidence is lacking. This doctoral thesis comprises 7 chapters of varied methodology that summarize the evidence behind current recommendations for antithrombotic therapy after bioprosthetic AVR, identify evidence gaps, and present the design a randomized trial that aims to address some of these evidence gaps. Chapter 1 introduces each included study with a brief summary. Chapter 2 is a narrative review summarizing guideline recommendation for antithrombotic therapy after bioprosthetic AVR and the evidence upon which they are based. Chapter 3 is an observational study describing antithrombotic prescribing practices in the VISION Cardiac Surgery cohort study. Chapter 4 is a systematic review and network meta-analysis of randomized studies of antithrombotic therapy after transcatheter aortic valve replacement. Chapter 5 is a systematic review and meta-analysis of randomized and observational studies of subclinical valve thrombosis. Chapter 6 presents the design and rationale of a feasibility trial of direct oral anticoagulants versus vitamin K antagonists in patients with a new surgical bioprosthetic AVR and atrial fibrillation. Chapter 7 discusses the implications, limitations, and future avenues of the research presented in this doctoral thesis. / Thesis / Doctor of Philosophy (PhD) / More than 10,000 Canadians require aortic valve replacement each year. Bioprosthetic valves (made out of cow or pig tissue) are often preferred over mechanical valves (made out of metal) because the risk of blood clots forming on the valve or causing a stroke is lower. The disadvantage of bioprosthetic valves is that they can wear out and require re-replacement. The reason why bioprosthetic valves wear out is uncertain, but it may be related to small blood clots on the valve that are only detectable on a CT scan. This doctoral thesis explores the use of blood thinners for patients with bioprosthetic aortic valve replacement. Ideally, blood thinners would be able to prevent blood clots and stroke, and to improve the durability of bioprosthetic valves, without causing too much bleeding. The thesis reviews the available evidence, identifies unanswered questions, and ends with a proposal for a study to generate new data.

Aortic Stenosis (AS) is the most common valvular heart disease. Aortic valve replacement (AVR) is the only acceptable treatment for AS. Several replacement methods are available to treat AS including conventional surgical aortic valve replacement (SAVR), transcatheter aortic valve replacement (TAVR), and Sutureless aortic valve replacement (SuAVR). SAVR showed excellent long-term results. However, it is an invasive procedure and is denied in substantial number of patients. TAVR showed excellent results and outcomes when compared to SAVR. However, it is associated with increased rate of paravalvular leaks that may impact long term outcomes. SuAVR has developed to overcome the drawbacks of SAVR and TAVR. SuAVR is associated with favorable short and midterm outcomes when compared to SAVR and TAVR. In this thesis, we summarize the safety, the evidence and the perceptions of using SuAVR in Canada. In Chapter1, we evaluated the use of SuAVR Perceval bioprosthesis in retrospective single center study of 415 patients with AS. SuAVR showed excellent immediate post-operative and hemodynamics outcomes. In chapter 2, we sought to establish perceptions and patterns to SuAVR use among Canadian cardiac surgeons. Sixty-Six Canadian cardiac Surgeons responded to the survey. Surgeons reported influential factors, barriers to use SuAVR, and their interest in a trial comparing SuAVR versus TAVR. Surgeons were likely to use SuAVR in high risk patients with hostile aortic root, small aortic annulus and in patients undergoing concomitant procedures whereas cost was the main limiting factor to use SuAVR in Canada. Majority of surgeons reported their interest in participating in a trial comparing SuAVR with TAVR. In chapter 3, we systematically reviewed and meta-analyzed the international evidence of using SuAVR versus SAVR and TAVR. SuAVR showed favorable or comparable results to SAVR and TAVR. However, long term and randomized data are needed to confirm these results. / Thesis / Master of Science (MSc) / Aortic valve stenosis (AS) is considered the most common valvular heart disease, which caused by narrowing of the aortic valve. Aortic valve replacement (AVR) is the only acceptable treatment to relieve the stenosis. Several strategies are available including conventional surgical aortic valve replacement (SAVR), transcatheter aortic valve replacement (TAVR), and sutureless aortic valve replacement (SuAVR). SAVR is an invasive procedure and denied in a considerable number of patients with aortic stenosis due to aging and presence of multiple diseases leading to higher risk of complications. TAVR is less invasive option and showed excellent results when compared to SAVR. However, it was associated with complications. SuAVR has developed to overcome some of the drawbacks of SAVR and TAVR. SuAVR is associated with short operation time and less complications compared to SAVR and TAVR. This thesis summarizes the safety, perceptions and evidence surrounding the use of SuAVR.

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13421号 / 論医博第2229号 / 新制||医||1052(附属図書館) / (主査)教授 伊達 洋至, 教授 大鶴 繁, 教授 中山 健夫 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Objectives To compare incidence of aortic regurgitation (AR), paravalvular AR and valvular performance with Doppler hemodynamic parameters following transcatheter aortic valve replacement (TAVR) with Edwards valve (EV) versus CoreValve (CV). Currently, there are scarce data on post-TAVR echocardiographic outcomes comparing EV and CV. Methods PubMed and the Cochrane Center Register of Controlled Trials were searched through May 2015. Twenty studies (n = 11,244) comparing TAVR procedure that used EV (n = 6445) and CV (n = 4799) were included. End points were post-TAVR moderate to severe AR and paravalvular AR, effective orifice area (EOA), mean trans-aortic pressure gradient (MPG), peak trans-aortic pressure gradient (PPG) and left ventricular ejection fraction (LVEF). The mean difference (MD) or relative risk (RR) with 95% confidence interval (CI) was computed and p < 0.05 was considered as a level of significance. Results Moderate to severe AR and paravalvular AR were significantly lower in EV group (RR: 0.57, CI: 0.52–0.63, p < 0.00001 and RR: 0.40, CI: 0.25–0.63, p < 0.0001 respectively) compared to CV group. EOA and PPG were not significantly different between EV and CV groups. MPG was significantly lower among patients in CV group (MD: 1.08, CI: 0.05–2.10, p = 0.04). LVEF was significantly higher in patients in EV group (MD: 2.26, CI: 0.77–3.74, p = 0.03). Conclusions This study showed CV is associated with higher incidence of post-TAVR moderate to severe paravalvular AR. Echocardiographic valvular performance measures (MPG, LVEF) showed minimal but significant difference, which may not be clinically significant.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20231号 / 医博第4190号 / 新制||医||1019(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 湊谷 謙司, 教授 山下 潤, 教授 川村 孝 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21652号 / 医博第4458号 / 新制||医||1035(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 川村 孝, 教授 福原 俊一, 教授 佐藤 俊哉 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

Risk assessment models developed from administrative and clinical databases are used for clinical decision making. Since these models are derived from a database, they have an inherent limitation of being as good as the data they are derived from. Many of these models under or overestimate certain clinical outcomes particularly mortality in certain group of patients. Undeniably, there is significant variability in all these models on account of patient population studied, the statistical analysis used to develop the model and the period during which these models were developed. This review aims to shed light on development and application of risk assessment models for cardiac surgery with special emphasis on risk stratification in severe aortic stenosis to select patients for transcatheter aortic valve replacement.

Transcatheter aortic valve replacement is a well-established alternative to surgical aortic valve replacement in high-risk patients with severe symptomatic aortic stenosis. Currently, this technique is shifting towards younger patient groups with intermediate- and low-risk profile, which raises the question about long-term durability. Despite acceptable results up to 5 years, little is currently known about valve performance beyond 5 years. Since valve deterioration, thrombosis and endocarditis seem to be the main factors affecting valve durability, precise and widely accepted definitions of these parameters were stated by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) in 2017, followed by the Valve in Valve International Data (VIVID) group definitions in 2018 and the Valve Academic Research Consortium 3 (VARC-3) definitions in 2021. Until the introduction of these definitions, interstudy comparisons were difficult due to missing uniformity. Since the release of these recommendations, an increasing number of studies have reported their data on long-term durability using these new criteria. The aim of the present article is to discuss the current definitions on bioprosthetic valve durability, and to summarize the available data on long-term durability of transcatheter aortic valves.