The bright and the dark sides of brachytherapy: mechanisms of stenosis reduction and findings of intracoronary β-radiation therapy revealed by IVUS-3D and QCA

Sincethe first percutaneous coronary intervention, 24 years ago, the field of interventional cardiology has continued to grow rapidly. Although PTCA has demonstrated superiority to medical therapy in alleviating angina, restenosis and acute closure of the treated vessel remained major limitations. Stent has improved both problems by preventing residual dissection, elastic recoil and negative remodeling. However, the occurrence of restenosis after stenting remains unresolved. Furthermore, in-stent restenosis has become a new enemy in the field of interventional cardiology, since the conventional treatment of in-stent restenosis is rather disappointing with high restenosis rates (around 30 - 70%). Therefore, the holy grail to overcome this immense enemy went unabated. Intracoronary brachytherapy is a powerful therapy to prevent restenosis after percutaneous transluminal coronary intervention. The purpose of this thesis is to explore the mechanism of action of intracoronary radiation and the problems related to this procedure. For this purpose, three-dimensional intravascular ultrasound (IVUS) and quantitative coronary angiography (QCA) were applied as investigational tools. This thesis consists of 2 parts; the first part deals with the positive aspect of intracoronary brachytherapy which explains its increasing application (Chapter 2) and its mechanistic interpretation (Chapters 3-7). The second part reports on the dark sides of intracoronary brachytherapy (Chapters 8-12)

Medium and long-term prognosis of transcatheter aortic valve implantation from the perspective of left ventricular diastolic function

Background: The effects of left ventricular (LV) diastolic function are well known in cardiac surgery, but unclear in transcatheter aortic valve implantation (TAVI). The objective of this study was to exam- ine the association of preoperative LV diastolic function with medium to long-term outcomes of TAVI. Methods: Eighty patients who underwent TAVI were classified into grades I, II and III based on pre- operative LV diastolic function. Findings related to cardiovascular outcomes after TAVI were extracted retrospectively from clinical and echocardiographic data and relationships with diastolic function were examined. Results: The average follow-up was 529 days (interquartile range {IQR] 358–741 days). Cardiovascu- lar events occurred in 17 cases, including 6 deaths, and were significantly associated with Euro II score (p = 0.043), albumin level (p = 0.026), coronary artery disease (CAD) (p = 0.017), and diastolic func- tion (p < 0.001). The 360-day event-free rates were 89.5%, 89.5% and 37.5% for grades I, II and III (p = 0.00013). Median event-free survival (EFS) in grade III cases was 180 days. In a Cox propor- tional hazard model, LV diastolic dysfunction (hazard ratio [HR] 3.99, 95% confidence interval [CI] 1.35–11.80, p = 0.012) and low albumin (HR 4.73, 95% CI 1.42–15.80, p = 0.012) were significant independent predictors of reduced EFS. Conclusions: Medium to long-term outcomes of TAVI were poorer in patients with deteriorated LV diastolic function, and outcomes in grade III cases were significantly worse than those in grade I and II cases. Preoperative LV diastolic function may be useful in prediction of outcomes after TAVI. 

Effect of olmesartan on the levels of circulating endothelial progenitor cell after drug-eluting stent implantation in patients receiving statin therapy

AbstractBackgroundThe endothelial progenitor cell (EPC) plays an important role in repairing vascular injury. Statins and angiotensin II receptor blockers increase the level of circulating EPCs. However, it is unknown whether the angiotensin II receptor blocker olmesartan synergistically acts with statins to increase the levels of circulating EPCs. Moreover, the association between the levels of circulating EPCs and endothelial dysfunction after implantation of drug-eluting stents (DESs) has not been evaluated.MethodsNine patients with stable coronary artery disease underwent percutaneous coronary intervention (PCI) and received DES implantation. All patients received olmesartan in addition to statin therapy after PCI. The dose of olmesartan was based on the physician's discretion as per the patients’ blood pressure. The levels of circulating EPCs were analyzed at baseline, post-PCI, and 1, 2, 3, and 8 months after PCI. Coronary angiography and the acetylcholine provocation test were performed on all patients at 8 months.ResultsAlthough the angiotensin II level significantly changed, the levels of circulating EPCs did not change during 8 months of olmesartan treatment (3.1±0.6cells/ml, 2.5±0.8cells/ml, 2.0±0.6cells/ml, 2.9±0.9cells/ml, 3.0±0.4cells/ml, 3.4±0.8cells/ml, p=0.64). The patients were subsequently divided into two groups based on whether the level of circulating EPCs was less or greater than 4cells/ml at 8 months. There were no significant differences in the mean vessel diameter of each segment (proximal, proximal edge, distal edge, and distal) after the acetylcholine provocation test between the two groups.ConclusionsLow-to-moderate doses of olmesartan might not increase the level of circulating EPCs in patients receiving statin therapy. There might be no association between the levels of circulating EPCs and the degree of coronary vasospasm in the acetylcholine provocation test 8 months after DES implantation

Ischemic and Bleeding Risk After Percutaneous Coronary Intervention in Patients With Prior Ischemic and Hemorrhagic Stroke

Background: Prior stroke is regarded as risk factor for bleeding after percutaneous coronary intervention (PCI). However, there is a paucity of data on detailed bleeding risk of patients with prior hemorrhagic and ischemic strokes after PCI. Methods and Results: In a pooled cohort of 19 475 patients from 3 Japanese PCI studies, we assessed the influence of prior hemorrhagic (n=285) or ischemic stroke (n=1773) relative to no-prior stroke (n=17 417) on ischemic and bleeding outcomes after PCI. Cumulative 3-year incidences of the co-primary bleeding end points of intracranial hemorrhage, non-intracranial global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries (GUSTO) moderate/severe bleeding, and the primary ischemic end point of ischemic stroke/myocardial infarction were higher in the prior hemorrhagic and ischemic stroke groups than in the no-prior stroke group (6.8%, 2.5%, and 1.3%, P<0.0001, 8.8%, 8.0%, and 6.0%, P=0.001, and 12.7%, 13.4%, and 7.5%, P<0.0001). After adjusting confounders, the excess risks of both prior hemorrhagic and ischemic strokes relative to no-prior stroke remained significant for intracranial hemorrhage (hazard ratio (HR) 4.44, 95% CI 2.64-7.01, P<0.0001, and HR 1.52, 95% CI 1.06-2.12, P=0.02), but not for non-intracranial bleeding (HR 1.18, 95% CI 0.76-1.73, P=0.44, and HR 0.94, 95% CI 0.78-1.13, P=0.53). The excess risks of both prior hemorrhagic and ischemic strokes relative to no-prior stroke remained significant for ischemic events mainly driven by the higher risk for ischemic stroke (HR 1.46, 95% CI 1.02-2.01, P=0.04, and HR 1.49, 95% CI 1.29-1.72, P<0.0001). Conclusions: Patients with prior hemorrhagic or ischemic stroke as compared with those with no-prior stroke had higher risk for intracranial hemorrhage and ischemic events, but not for non-intracranial bleeding after PCI