Drug-coated balloons are a new tool for the treatment of de novo or in-stent stenosis; as yet little is known about the principle by which these devices apply their therapeutic agents during intervention. Concerns remain regarding clinical safety and efficacy of different coatings, mainly influenced by the amount of drug transferred into the arterial tissue and lost into the bloodstream. To assess whether the chemical or mechanical set-up influences drug migration and wash-off, we compared four paclitaxel-coated balloon platforms differing in surface structure (folded versus non-folded) and coating compounds (pure paclitaxel versus paclitaxel plus excipient) in a porcine coronary model. The study revealed high wash-off rates for all devices, exceeding 54.4% of the initial coating contents. In terms of tissue concentration significant differences could be observed between the coating compounds independently from the device platform. For the paclitaxel versus paclitaxel plus excipient balloons tissue concentrations of 0.02 and 0.33μg/mm2, respectively (p<0.01), were detected; for the paclitaxel versus paclitaxel plus excipient-wrapped balloons tissue concentrations were 0.13 and 0.53μg/mm2, respectively (p=0.04). The main driver of drug migration from drug-coated balloon surfaces into arterial tissue is the chemical set-up of the coating. Hydrophilic excipients allow higher tissue concentrations of paclitaxel independent from the mechanical platform. The wash-off from the surface coating remains an unsolved safety issue and may be solved by mechanical modifications of these devices.

Treatment of ventricular tachyarrhythmias in the setting of chronic myocardial infarction requires accurate characterization of the arrhythmia substrate. New mapping technologies have been developed that facilitate identification and ablation of critical areas even in rapid, hemodynamically unstable ventricular tachycardia. A noncontact mapping system was used to analyze induced ventricular tachycardia in a closed-chest sheep model of chronic myocardial infarction. Twelve sheep were studied 96 +/- 10 days after experimental myocardial infarction. During programmed stimulation, 15 different ventricular tachycardias were induced in nine animals. Induced ventricular tachycardia had a mean cycle length of 190 +/- 30 ms. In 12 ventricular tachycardias, earliest endocardial activity was recorded from virtual electrodes, preceding the surface QRS onset by 30 +/- 7 ms. Noncontact mapping identified diastolic activity in ten ventricular tachycardias. Diastolic potentials were recorded over a variable zone, spanning more than 30 mm. Timing of diastolic potentials varied from early to late diastole and could be traced back to the endocardial exit site. Entrainment with overdrive pacing was attempted in nine ventricular tachycardias, with concealed entrainment observed in seven. Abnormal endocardium in the area of chronic myocardial infarction identified by unipolar peak voltage mapping was confirmed by magnetic resonance imaging. These data suggest that induced ventricular tachycardia in the late phase of myocardial infarction in the sheep model is due to macroreentry involving the infarct borderzone. The combination of this animal model with noncontact mapping technology will allow testing of new strategies to cure and prevent ventricular tachycardia in the setting of chronic myocardial infarction.

Background: The diameter of balloons or stents is selected according to the estimated reference vessel diameter and do not adapt to the vessel anatomy. The aim of the present preclinical studies was to investigate a novel, vessel anatomy adjusting hypercompliant drug-coated balloon catheter (HCDCB). Methods: Hypercompliant balloon membranes were coated in a constricted state with high drug density. Drug adherence was investigated in vitro, transfer to the porcine peripheral arteries and longitudinal distribution in vivo. In young domestic swine, neointimal proliferation was induced by vessel overstretch and continuous irritation by permanent stents. Uncoated hypercompliant balloons (HCB), and standard uncoated balloons and drug-coated balloons (DCB) served as controls. Efficacy was assessed by angiography, optical coherence tomography (OCT), and histomorphometry.Results: HCDCB lost 18.0 ± 3.9% of dose during in vitro simulated delivery to the lesion. Drug transfer to the vessel wall was 13.9 ± 6.4% and drug concentration was 1,044 ± 529 ng/mg tissue. Four weeks after treatment, the histomorphometric neointimal area was smaller with HCDCB versus uncoated HCB (2.39 ± 0.55 mm 2 vs. 3.26 ± 0.72 mm 2 , p = .038) and area stenosis (OCT) was less (11.6 ± 6.9% vs. 24.7 ± 9.7%, p = .022). No premature death occurred and no in-life clinical symptoms or treatment-associated thrombi were observed.Conclusions: HCDCB were found to inhibit excessive neointimal proliferation. Balloon adaption to different vessel diameters and shapes may provide drug-delivery in irregular lumen and facilitate balloon selection. K E Y W O R D S drug transfer, inhibition of neointimal proliferation, vessel anatomy adjusting drug-coated balloon 1 | INTRODUCTION Restenosis after percutaneous transluminal procedures occurs due to the vessel wall trauma induced by balloon dilatation or stent Abbreviations: DCB, drug-coated balloon (=standard drug-coated PTA balloon); FU, followup; HCB, hypercompliant balloon; HCDCB, hypercompliant drug-coated balloon; MLD, minimal lumen diameter; OCT, optical coherence tomography; PTA, percutaneous transluminal angioplasty; QA, quantitative angiography; RFD, reference diameter; SLD, stent struts-to-lumen distance.

In an animal model of healthy adult sheep, implantation of CMCS with a transvenous LV lead already in place was feasible and without major problems with either the CMCS or the LV lead. Electrical performance of the LV leads was excellent. All LV leads could be extracted without migration of the CMCS.

Pace prevention of atrial tachyarrhythmias is based in part on the reduction of intra-atrial (IAA) and/or inter-atrial (IEA) conduction. We previously introduced a novel pacing mode using floating atrial ring electrodes on a VDD-lead (BIdirectional MO nophasic impulSe: BIMOS). The effects of BIMOS pacing on IAA and IEA conduction times has not been studied. In nine Merino sheep electrode catheters were placed at the His-Bundle (HBE), high right atrium (HRA), coronary sinus ostium (Cs-Os), and left lateral atrium (LLA). A VDD-lead was introduced with floating electrodes in the high and mid right atrium (Floating). IAA (S/P-HRA, S/P-Cs-Os, S/P-HBE, S/P-Floating), IEA conduction times (S/P-LLA), and P-wave duration (PD) were measured during sinus rhythm (S), during bipolar cathodal pacing (P) in the HRA, in the Cs-Os position, as well as during BIMOS floating pacing. The mean PD during S was significantly shorter than during HRA- (66. 6+/-12.8ms; vs. 116.2+/-11.1ms; p<0.05) and Cs-Os-P (66.6+/-12.8ms vs. 94.4+/-9.0ms; p<0.05). In comparison to HRA-P, BIMOS configuration lead to a significant reduction of the P-wave duration (116.2+/-11.1ms vs. 85. 4+/-8.8ms; p<0.05). During BIMOS pacing, the global atrial conduction time was significantly shorter than during pacing in the HRA and Cs-Os position. The results of this study demonstrate a clear reduction of IAA and IEA conduction times using BIMOS configurations compared to conventional HRA-P. Furthermore, BIMOS pacing produced a more homogeneous atrial activation when compared with conventional HRA- and Cs-Os-P.