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Hypertrophic cardiomyopathy (HCM) is regarded as one of the most common inherited cardiac diseases. In a number of population studies the prevalence of HCM is estimated in the general population to be at least 1 in 500. HCM is inherited with an autosomal dominant Mendelian pattern, variable expressivity, and age-related (and incomplete) penetrance. Clinical diagnosis of HCM requires confirmation of phenotypic expression, that is an unexplained increase in left ventricular (LV) wall thickness (≥15 mm in adults) associated with a nondilated LV chamber with cardiac imaging (usually echocardiography). Phenotype positive patients may show different patterns of LV hypertrophy: reverse septal curvature, sigmoidal and apical forms have been described. Relatives identified with pathogenic mutations (gene carriers) but without evidence of the disease phenotype comprise a new HCM subgroup, designated as genotype positive-phenotype negative individuals. The risk of eventually developing LV hypertrophy in this group is currently uncertain. In this thesis we investigated the value of speckle tracking echocardiographically (STE)-derived global and regional LV rotation and strain in HCM mutation gene carriers and patients, both in systole and diastole. In the first part of this thesis STE analysis of myocardial velocity, rotation and strain in systole and diastole is introduced. In Chapter 2 a literature review of LV twist mechanics in cardiomyopathies is presented. Analysis of LV twist mechanics may provide substantial pathophysiological understanding in a variety of cardiomyopathies. In the second part of this thesis the feasibility of STE is studied. In Chapter 3 it is shown with a moving phantom model that mitral annular velocities can be accurately determined by STE in an angle independent way. In Chapter 4 the feasibility, observer variability and test-retest variability of LV twist measurements by STE is described. The method appeared to be feasible in approximately

OBJECTIVES: Recent improvements in coronary stent design have focussed on thinner struts, different alloys and architecture, more biocompatible polymers, and shorter drug absorption times. This study evaluates safety and efficacy of a newer generation thin-strut cobalt chromium sirolimus-eluting coronary stent (SES, Ultimaster) in comparison with a second-generation thicker strut stainless steel biolimus-eluting stent (BES, Nobori) in percutaneous coronary intervention (PCI) practice. METHODS: A propensity score analysis was performed to adjust for differences in baseline characteristics of 8137 SES patients and 2738 BES patients of two PCI registries (e-Ultimaster and NOBORI 2). An independent clinical event committee adjudicated all endpoint-related adverse events. RESULTS: The use of SES, as compared with BES was associated with a significantly lower rate of myocardial infarction (MI) (1.2% vs 2.2%; P = 0.0006) and target vessel-related MI (1.1% vs 1.8%; P = 0.002) at 1 year. One-year composite endpoints of all predefined endpoints were lower in patients undergoing SES implantation (target lesion failure: 3.2% vs 4.1%; P = 0.03, target vessel failure: 3.7% vs 5.0%; P = 0.003, patient-oriented composite endpoint 5.7% vs 6.8%; P = 0.03). No significant differences between SES and BES were observed in all-cause death (2.0% vs 1.6%; P = 0.19), cardiac death (1.2% vs 1.2%; P = 0.76) or stent thrombosis (0.6% vs 0.8%; P = 0.43). CONCLUSIONS: These findings suggest an improved clinical safety and efficacy of a newer generation thin-strut SES as compared with a second-generation thicker strut BES., Funding Agency:Terumo Europe

Background Chronic kidney disease (CKD) is highly prevalent in patients with coronary artery disease (CAD). Objective The outcome following revascularization using contemporary technologies (new-generation abluminal sirolimus-eluting stents with thin struts) in patients with CKD (i.e., glomerular filtration rate of < 60 mL/min/1.73m2) and in patients with hemodialysis (HD) is unknown. Methods e-Ultimaster is a prospective, single-arm, multi-center registry with clinical follow-up at 3 months and 1 year. Results A total of 19,475 patients were enrolled, including 1466 patients with CKD, with 167 undergoing HD. Patients with CKD had a higher prevalence of overall comorbidities, multiple/small vessel disease (≤ 2.75 mm), bifurcation lesions, and more often left main artery treatments (all p < 0.0001) when compared with patients with normal renal function (reference). CKD patients had a higher risk of target lesion failure (unadjusted OR, 2.51 [95% CI 2.04–3.08]), target vessel failure (OR, 2.44 [95% CI 2.01–2.96]), patient-oriented composite end point (OR, 2.19 [95% CI 1.87–2.56]), and major adverse cardiovascular events (OR, 2.34 [95% CI 1.93–2.83, p for all < 0.0001]) as reference. The rates of target lesion revascularization (OR, 1.17 [95% CI 0.79–1.73], p = 0.44) were not different. Bleeding complications were more frequently observed in CKD than in the reference (all p < 0.0001). Conclusion In this worldwide registry, CKD patients presented with more comorbidities and more complex lesions when compared with the reference population. They experienced higher rate of adverse events at 1-year follow-up. Graphic abstract One-year summary outcomes of contemporary PCI in renal insufficiency. CKD chronic kidney disease, POCE patient oriented composite endpoint, MACE major adverse cardiovascular events, TLF target lesion failure, TLR target lesion revascularization, ST stent thrombosis

Background-As bioresorbable vascular scaffolds (BVSs) are being increasingly used in complex real-world lesions and populations, BVS thrombosis cases have been reported. We present angiographic and optical coherence tomography (OCT) findings in a series of patients treated in our center for definite bioresorbable scaffold thrombosis. Methods and Results-Up to June 2014, 14 patients presented with definite BVS thrombosis in our center. OCT was performed in 9 patients at the operator's discretion. Angiographic and OCT findings were compared with a control group comprising 15 patients with definite metallic stent thrombosis. In the BVS group, time interval from index procedure to scaffold thrombosis ranged from 0 to 675 days. Incomplete lesion coverage by angiography was identified in 4 of 14 cases, malapposition by OCT in 5 of 9 cases, strut discontinuity in 2 of 9 cases, and underexpansion in 2 of 9 cases. Five patients had discontinued dual antiplatelet therapy, and in 3 of them discontinued dual antiplatelet therapy discontinuation had occurred the week preceding the event. There were no significant differences in angiographic or OCT findings between BVS and metallic stent thrombosis. Conclusions-Suboptimal implantation with incomplete lesion coverage, underexpansion, and malapposition comprises the main pathomechanism for both early and late BVS thrombosis, similar to metallic stent thrombosis. Dual antiplatelet therapy discontinuation seems to also be a secondary contributor in several late events. Our observations suggest that several potential triggers for BVS thrombosis could be avoided.