Percutaneous Coronary Intervention is a common treatment for obstructive coronary artery disease, in both planned and emergency settings. Its use in the United Kingdom and elsewhere has increased dramatically in recent years due to its efficacy in the management of Acute Coronary Syndromes, increased access to PCI services, and more permissive patient selection practices. Further, a patient undergoing PCI now is likely to be treated quite differently than the same patient ten years ago, with the emergence of new interventional techniques, devices, stent types, and drugs. The widespread adoption of transradial access in favour of transfemoral access in particular has marked a new era in the delivery of PCI in the UK. Due to the rapid changes in patient and treatment characteristics, evidence generated in settings that no longer reflect the radial era is increasingly irrelevant. This thesis addresses this evidence deficit using data from the British Cardiovascular Intervention Society national PCI registry to describe contemporary trends in PCI practice and investigate the potential implications of these trends on the quality of PCI delivery. It focuses on the relationship between procedural volume, arterial access site, and short-term mortality which has not been explored in radial-era UK practice. Broadly, three research questions were posed: (1) What are the qualities and limitations of the British Cardiovascular Intervention Society PCI Registry in answering questions about routine clinical practice in the United Kingdom? (2) What is the impact on PCI outcomes of changes to the underlying patient population, changes to the selection of these patients, and changes to the treatment of these selected patients? (3) What are the consequences of these changes on the relationship of procedural volume and access site on outcomes? This thesis has showed that those centres adopting radial access more readily did not experience a decline in femoral quality, and in the most recent period were associated with better outcomes overall, particularly amongst the highest volume centres. Operator volume itself however was not associated with improved outcomes, suggesting the organisation of PCI services is not leaving operators with too few, or too many, procedures to perform competently. The current trajectory in UK practice of increasing radial adoption should continue unabated, with radial access considered as the primary access route across all clinical settings wherever possible.

Original published work submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Medicine (Internal Medicine) 18 October, 2017. / The very first coronary artery balloon angioplasty is reported to have been performed by Gruntzig in 1977.1 Subsequently to this, over the past 40 years, there have been significant advances in coronary angiography and intervention. Coronary artery interventional techniques have evolved and improved significantly. There have been considerable device developments, new generation stents and novel antiplatelet therapy which have all proved to reduce the incidence of the primary periprocedural complications associated with percutaneous coronary intervention (PCI). [No abstract provided. Information taken from introduction] / LG2018

UA Open Access Publishing Fund / Background: The use of intra-aortic balloon pump (IABP) via the trans-femoral approach has been established for hemodynamic support in patients undergoing high-risk percutaneous coronary intervention (PCI). However, there are various challenges associated with its use, especially in patients with aortoiliac occlusive arterial disease. Case presentation: We describe a case of high-risk PCI with IABP support complicated by intra-procedural detection of severe abdominal aortic stenosis that was successfully overcome with angioplasty of the stenotic lesion. Conclusions: Our report highlights distal abdominal aortic stenosis as a potential barrier to successful PCI with IABP support, and angioplasty as an effective means to overcome it.

Coronary heart disease is a significant cause of mortality and morbidity in the United States; Healthy People 2020 set an objective to reduce the rate of the disease by 20% to the baseline rate of 126 deaths per 100,000 population per year. In the local healthcare setting, heart disease was responsible for a high percentage of mortality and morbidity. To address this, the local site developed a plan to improve outcomes for patients seeking care at the facility. Because the femoral approach to percutaneous coronary intervention (PCI) was used to treat coronary heart conditions at the site and complications were frequent, a quality improvement initiative was begun that included a shift to the use of radial artery PCI. The purpose of this project was to evaluate whether the new approach lowered the complication rates. The project focused question asked how the complication rate of transradial and transfemoral approach to PCI compared. Data from nonrandom aggregate PCI results for 158 adult patients, ages 40-80 years; data from the National Cardiovascular Data Registry; and summarized unit reports were used to compare the transfemoral and transradial outcomes. Two-samples t test results indicated the complications were clinically and significantly lower (p < .01) with patients who underwent the transradial approach (n = 82) compared to those who had the transfemoral approach (n = 76). Study results suggest the new initiative using the transradial approach for PCI reduced the complications for patients undergoing PCI at the site. Positive social change is possible as the morbidity and mortality rates were reduced and consumers who need the procedure may experience a lower burden of physical and fiscal cost.

Metallic implants called stents are an important part of the treatment of coronary heart disease. While clinical trials are excellent indicators of outcomes, microscopic evaluation of the host tissue response to the implant is required to assess their safety and efficacy. However, the evaluation of human autopsy tissue containing metal implants presents unique challenges in order to obtain the best results. We used integrated microscopy techniques incorporating microCT and novel plastic histology techniques to demonstrate its effectiveness on human stented vessels obtained at autopsy. A total of seven cases are demonstrated where our analysis techniques were able to elucidate the pathogenesis of the host response and identify the specific cause of the complications with the stented vessel seen clinically. These techniques are more cost effective and efficient than other techniques currently in use, which could enable them to be used as part of routine autopsy evaluation. The expansion of the pool of stented vessels able to be analyzed to include the often overlooked large population of autopsy cases could provide an enormous amount of data to guide future clinical trials and improve patient care.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22353号 / 医博第4594号 / 新制||医||1042(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 佐藤 俊哉, 教授 湊谷 謙司, 教授 福原 俊一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Background: The recent literature has shown that triple antiplatelet therapy with cilostazol in addition to the standard dual antiplatelet therapy with aspirin and clopidogrel may reduce platelet reactivity and improve clinical outcomes following percutaneous coronary intervention. The purpose of this meta-analysis is to compare the efficacy of triple antiplatelet therapy and dual antiplatelet therapy in regard to on-treatment platelet reactivity. Methods: Nine studies (n = 2179) comparing on-treatment platelet reactivity between dual antiplatelet therapy (n = 1193) and triple antiplatelet therapy (n = 986) in patients undergoing percutaneous coronary intervention were included. Primary end points were P2Y12 reaction unit (PRU) and platelet reactivity index (PRI). Secondary end points were platelet aggregation with adenosine diphosphate (ADP) 5 and 20 μmol/L and P2Y12% inhibition. Mean difference (MD) and 95% confidence intervals (CI) were computed and 2-sided α error <.05 was considered as a level of significance. Results: Compared to dual antiplatelet therapy, triple antiplatelet therapy had significantly lower maximum platelet aggregation with ADP 5 μmol/L (MD: -14.4, CI: -21.6 to -7.2, P < .001) and 20 mmol/L (MD: -14.9, CI: -22.9 to -6.8, P < .001), significantly lower PRUs (MD: -45, CI: -59.4 to -30.6, P < .001) and PRI (MD: -26, CI: -36.8 to -15.2, P < .001), and significantly higher P2Y12% inhibition (MD: 18.5, CI: 2.3 to 34.6, P = .025). Conclusion: Addition of cilostazol to conventional dual antiplatelet therapy significantly lowers platelet reactivity and may explain a decrease in thromboembolic events following coronary intervention; however, additional studies evaluating clinical outcomes will be helpful to determine the benefit of triple antiplatelet therapy.

Background: The recent literature has shown that triple antiplatelet therapy with cilostazol in addition to the standard dual antiplatelet therapy with aspirin and clopidogrel may reduce platelet reactivity and improve clinical outcomes following percutaneous coronary intervention. The purpose of this meta-analysis is to compare the efficacy of triple antiplatelet therapy and dual antiplatelet therapy in regard to on-treatment platelet reactivity. Methods: Nine studies (n = 2179) comparing on-treatment platelet reactivity between dual antiplatelet therapy (n = 1193) and triple antiplatelet therapy (n = 986) in patients undergoing percutaneous coronary intervention were included. Primary end points were P2Y12 reaction unit (PRU) and platelet reactivity index (PRI). Secondary end points were platelet aggregation with adenosine diphosphate (ADP) 5 and 20 μmol/L and P2Y12% inhibition. Mean difference (MD) and 95% confidence intervals (CI) were computed and 2-sided α error <.05 was considered as a level of significance. Results: Compared to dual antiplatelet therapy, triple antiplatelet therapy had significantly lower maximum platelet aggregation with ADP 5 μmol/L (MD: -14.4, CI: -21.6 to -7.2, P < .001) and 20 mmol/L (MD: -14.9, CI: -22.9 to -6.8, P < .001), significantly lower PRUs (MD: -45, CI: -59.4 to -30.6, P < .001) and PRI (MD: -26, CI: -36.8 to -15.2, P < .001), and significantly higher P2Y12% inhibition (MD: 18.5, CI: 2.3 to 34.6, P = .025). Conclusion: Addition of cilostazol to conventional dual antiplatelet therapy significantly lowers platelet reactivity and may explain a decrease in thromboembolic events following coronary intervention; however, additional studies evaluating clinical outcomes will be helpful to determine the benefit of triple antiplatelet therapy.

There are limited data on the outcomes of chronic liver disease (CLD) patients admitted for percutaneous coronary intervention (PCI). All PCI hospitalizations from the Nationwide Inpatient Sample (2004 to 2015) were analyzed and stratified by the presence, cause and severity of CLD, as well as the indication for PCI. Multivariable logistic regression analysis was performed to determine the adjusted odds ratios (aOR) of in-hospital adverse outcomes in patients with CLD compared with those without CLD. Among 7,296,679 PCI admissions, 54,368 (0.7%) had a CLD diagnosis. Among patients with CLD, 36,853 (67.8%) had severe CLD. Patients with CLD had higher likelihood of adverse outcomes including major adverse cardiovascular and cerebrovascular events (MACCE) (aOR 1.25, 95%CI 1.20 to 1.30), mortality (aOR 1.43, 95%CI 1.35 to 1.51), major bleeding (aOR 2.22, 95%CI 2.12 to 2.32). When accounting for severity, only severe CLD subgroup was more likely to have MACCE and all-cause mortality compared to no-CLD patients (p <0.001). Among CLD etiologic subgroups, those with ‘alcohol-related liver disease’ and ‘other CLD’ were consistently more likely to develop MACCE, all-cause mortality and major bleeding in comparison to no-CLD patients, while ‘chronic viral hepatitis’ subgroup had only increased odds of major bleeding (p <0.001). In conclusion, CLD patients admitted for PCI are more likely to have worse in-hospital outcomes, particularly in the severe CLD subgroup and ‘alcohol-related liver disease’ and ‘other CLD’ etiologic subgroups.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18162号 / 医博第3882号 / 新制||医||1003(附属図書館) / 31020 / 京都大学大学院医学研究科医学専攻 / (主査)教授 福原 俊一, 教授 佐藤 俊哉, 教授 坂田 隆造 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM