Balloon Surface Research Articles

Contemporary Use of Drug-Coated Balloons for Coronary Angioplasty: A Comprehensive Review.

The interventional treatment of coronary artery disease (CAD) has undergone significant improvements thanks to technological innovations. Nowadays, percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation is the standard of care for the treatment of CAD. Nevertheless, the non-negligible incidence of in-stent restenosis (ISR) and suboptimal results in various anatomical settings has led to the development of drug-coated balloons (DCBs). DCBs are catheter-based balloons whose surface is coated with an anti-proliferative drug (mainly Paclitaxel or Sirolimus) loaded onto the balloon surface with different technologies and dose concentrations. In the beginning, these devices were used for the treatment of ISR showing an excellent efficacy profile in the inhibition of intimal hyperplasia. Subsequently, several studies evaluated their use in other angiographical and clinical contexts such as de novo lesions, small vessel disease, diffuse coronary disease, bifurcation lesions, acute coronary syndromes, high-bleeding risk and diabetic patients. This comprehensive review aims to describe the main DCB platforms on the market, their fields of application with the main supporting studies and their future perspectives.

Fiber Laser Writing of Highly Sensitive Nickel Nanoparticle-Incorporated Graphene Strain Sensors.

Unlocking new dimensions in wearable sensor technology, this research highlights ultrasensitive stretchable strain sensors fabricated with the customized laser-induced graphene (LIG) decorated with uniformly distributed nickel nanoparticles with a fiber laser writing process. The nickel nanoparticle-incorporated LIG (Ni-NPs@LIG) strain sensors fabricated by a simple all-laser-based method utilize a commercial fiber laser. The Ni-NPs@LIG sensors showcase an impressive gauge factor, reaching up to 248 for strain values below 5%, demonstrating a sensitivity increase of up to 430% compared to the pure LIG sensors. Moreover, these sensors offer adjustable strain sensitivity based on laser fluence. The key advancement of this study lies in the direct laser writing of highly porous nickel-graphene nanostructures with adjustable properties, making them applicable across a broad range of applications. As an application demonstration, the strain sensors were employed to assess the small deformation of a pouch battery or track the large deformation of a balloon surface.

Hydrophilic Coating Microstructure Mediates Acute Drug Transfer in Drug-Coated Balloon Therapy.

Drug-coated balloon (DCB) therapy is a promising endovascular treatment for obstructive arterial disease. The goal of DCB therapy is restoration of lumen patency in a stenotic vessel, whereby balloon deployment both mechanically compresses the offending lesion and locally delivers an antiproliferative drug, most commonly paclitaxel (PTX) or derivative compounds, to the arterial wall. Favorable long-term outcomes of DCB therapy thus require predictable and adequate PTX delivery, a process facilitated by coating excipients that promotes rapid drug transfer during the inflation period. While a variety of excipients have been considered in DCB design, there is a lack of understanding about the coating-specific biophysical determinants of essential device function, namely, acute drug transfer. We consider two hydrophilic excipients for PTX delivery, urea (UR) and poly(ethylene glycol) (PEG), and examine how compositional and preparational variables in the balloon surface spray-coating process impact resultant coating microstructure and in turn acute PTX transfer to the arterial wall. Specifically, we use scanning electron image analyses to quantify how coating microstructure is altered by excipient solid content and balloon-to-nozzle spray distance during the coating procedure and correlate obtained microstructural descriptors of coating aggregation to the efficiency of acute PTX transfer in a one-dimensional ex vivo model of DCB deployment. Experimental results suggest that despite the qualitatively different coating surface microstructures and apparent PTX transfer mechanisms exhibited with these excipients, the drug delivery efficiency is generally enhanced by coating aggregation on the balloon surface. We illustrate this microstructure-function relation with a finite element-based computational model of DCB deployment, which along with our experimental findings suggests a general design principle to increase drug delivery efficiency across a broad range of DCB designs.

Development of Kirigami‐Patterned Stretchable Tactile Sensor Array with Soft Hinges for Highly Sensitive Force Detection

AbstractFlexible and stretchable tactile sensors are attracted in the fields of soft robotics, wearable electronics, and healthcare monitoring. The sensing performance of tactile sensors is commonly affected by external deformations like stretching, bending, and twisting, thus they may fail to function on deformable object surfaces. This paper presents a stretchable tactile sensor array using kirigami‐patterned structural design and soft hinges to reduce the influences of deformation. The kirigami pattern of sensor array is parametrically studied to achieve the required expansion patterns. Laser engraving is employed to modify the micropillars on the force‐sensitive rubber surface to increase the sensitivity. Characterization tests show that the sensor array has high sensitivity (≈1.49 × 10−1 kPa−1) for force sensing, and the stretching and bending deformation have almost negligible effects on sensing performance. Under 40% stretching or 180° bending conditions, the measured resistance changes (ΔR/R0) is ≈0.03 and 0.06, respectively. To demonstrate the capability of developed sensor array, it is mounted on an expandable balloon surface for force detection. The recorded signals changed less than 1.5% during expanding process while rapidly rose under applied force, which indicated that the sensor array has the potential to effectively function on complex and deforming surfaces.

Evaluation of a Balloon Implant for Simultaneous Magnetic Nanoparticle Hyperthermia and High-Dose-Rate Brachytherapy of Brain Tumor Resection Cavities

Previous work has reported the design of a novel thermobrachytherapy (TBT) balloon implant to deliver magnetic nanoparticle (MNP) hyperthermia and high-dose-rate (HDR) brachytherapy simultaneously after brain tumor resection, thereby maximizing their synergistic effect. This paper presents an evaluation of the robustness of the balloon device, compatibility of its heat and radiation delivery components, as well as thermal and radiation dosimetry of the TBT balloon. TBT balloon devices with 1 and 3 cm diameter were evaluated when placed in an external magnetic field with a maximal strength of 8.1 kA/m at 133 kHz. The MNP solution (nanofluid) in the balloon absorbs energy, thereby generating heat, while an HDR source travels to the center of the balloon via a catheter to deliver the radiation dose. A 3D-printed human skull model was filled with brain-tissue-equivalent gel for in-phantom heating and radiation measurements around four 3 cm balloons. For the in vivo experiments, a 1 cm diameter balloon was surgically implanted in the brains of three living pigs (40–50 kg). The durability and robustness of TBT balloon implants, as well as the compatibility of their heat and radiation delivery components, were demonstrated in laboratory studies. The presence of the nanofluid, magnetic field, and heating up to 77 °C did not affect the radiation dose significantly. Thermal mapping and 2D infrared images demonstrated spherically symmetric heating in phantom as well as in brain tissue. In vivo pig experiments showed the ability to heat well-perfused brain tissue to hyperthermic levels (≥40 °C) at a 5 mm distance from the 60 °C balloon surface.

Feasibility Study of Numerical Calculation and Machine Learning Hybrid Approach for Renal Denervation Temperature Prediction

Transcatheter renal denervation (RDN) is a novel treatment to reduce blood pressure in patients with resistant hypertension using an energy-based catheter, mostly radio frequency (RF) current, by eliminating renal sympathetic nerve. However, several inconsistent RDN treatments were reported, mainly due to RF current narrow heating area, and the inability to confirm a successful nerve ablation in a deep area. We proposed microwave energy as an alternative for creating a wider ablation area. However, confirming a successful ablation is still a problem. In this paper, we designed a prediction method for deep renal nerve ablation sites using hybrid numerical calculation-driven machine learning (ML) in combination with a microwave catheter. This work is a first-step investigation to check the hybrid ML prediction capability in a real-world situation. A catheter with a single-slot coaxial antenna at 2.45 GHz with a balloon catheter, combined with a thin thermometer probe on the balloon surface, is proposed. Lumen temperature measured by the probe is used as an ML input to predict the temperature rise at the ablation site. Heating experiments using 6 and 8 mm hole phantom with a 41.3 W excited power, and 8 mm with 36.4 W excited power, were done eight times each to check the feasibility and accuracy of the ML algorithm. In addition, the temperature on the ablation site is measured for reference. Prediction by ML algorithm agrees well with the reference, with a maximum difference of 6 °C and 3 °C in 6 and 8 mm (both power), respectively. Overall, the proposed ML algorithm is capable of predicting the ablation site temperature rise with high accuracy.

Comparison of Drug-Coated Balloon and Drug-Eluting Stent for the Treatment of Small Vessel Disease (from the Dissolve SVD Randomized Trial)

The Dissolve drug-coated balloons (DCBs) is a new-generation DCB coated with paclitaxel of balloon surface, with midchain triglyceride excipient. Although the use of DCBs is a promising technique, little is known about the the clinical efficacy of the novel Dissolve DCB in coronary small vessel disease. This study was a prospective, randomized, multicenter, noninferiority trial comparing the Dissolve DCB with the Resolute drug-eluting stent (DES) in patients with a reference vessel diameter ≥2.25 and ≤2.75mm. Patients with a reference vessel diameter ≥2.00 and <2.25mm were enrolled in the very small vessel registry. The angiographic and clinical follow-up were planned at 9months and 1year in all patients, respectively. The primary end point was 9-month in-segment percentage diameter stenosis. A total of 247 patients with small vessel disease from 10 Chinese sites were included (Dissolve DCB, n=118; Resolute DES, n=129); 30 patients were treated with the DCB in the very small vessel cohort. The 9-month in-segment percentage diameter stenosis was 31.2 ± 2.0% with Dissolve DCB versus 26.1 ± 2.1% with Resolute DES; the 1-sided 97.5% upper confidence limit of the difference was 10.3% (p for noninferiority=0.0002). At 12months, the DCB and DES groups were associated with similar rates of target lesion failure (8.5% vs 6.1%, p=0.28) and major adverse cardiac and cerebrovascular events (20.9% vs 13.6%, p=0.12). In conclusion, the Dissolve DCB was noninferior to the Resolute DES for the primary end point of 9-month in-segment percentage diameter stenosis in this multicenter, head-to-head, randomized trial (a safety and efficacy study of Dissolve In Treatment Of Coronary Small Vessel Disease; NCT03376646).

Balloon surface temperature-controlled ablation using a second-generation radiofrequency HotBalloon: an in vivo feasibility study.

The first-generation radiofrequency HotBalloon (RHB) is a size-adjustable single-shot device used in atrial fibrillation. The energy output is determined by its central temperature and not by its balloon surface temperature (BST), thus limiting its efficacy and safety. Therefore, a second-generation RHB was developed to monitor BST and enable BST-controlled ablation. This animal study aims to evaluate the accuracy of a newly developed BST-monitoring system and validate the optimal BST for ablation. In Protocol 1, thermocapsules were attached to the superior vena cava (SVC) epicardium. The accuracy of BST monitoring was examined during SVC isolation. In Protocol 2, the efficacy and safety of different BST-controlled ablations were examined. In the acute model, electrophysiological and pathological findings were assessed after energy applications with BST at 51, 54, 57, and 60°C. In the chronic model, the lesion durability and pathological findings were assessed 8 weeks after BST-controlled ablation (57 and 60°C). A significant positive correlation was found between the epicardial temperature and the BST-monitoring value (r = 0.98). In the acute model, all target veins were electrically isolated with BST-controlled ablation at ≥57°C (18/18, 100%). In the chronic model, durable lesions were observed in all veins at 60°C, while 44% of the veins showed reconnection at 57°C. In both pathological analyses, significantly greater lesions were observed at 60°C than at 57°C. There were no significant differences in adverse events between the two groups. Balloon surface temperature-controlled ablation at 60°C using the second-generation RHB may be optimal for creating durable lesions without compromising safety.

Safety and Efficacy of an Innovative Everolimus-Coated Balloon in a Swine Coronary Artery Model.

Drug-coated balloons have been used as a non-stenting treatment in coronary and peripheral artery disease. Until recently, only sirolimus- and paclitaxel-coated balloons have been investigated in clinical trials. We evaluated the safety and efficacy of an innovative everolimus-coated balloon (ECB) in a swine coronary artery model. thirty-two swine coronary arteries were prepared through dilatation with a non-coated angioplasty balloon in a closed-chest model. During a period of 90 days, the following four groups (four animals per group, two coronary arteries per animal) were compared for safety and efficacy: A, Rontis ECB with 2.5 μg/mm2 of drug per balloon surface; B, Rontis ECB with 7.5 μg/mm2; C, Rontis Europa Ultra bare balloon; and D, Magic Touch, Concept Medical, sirolimus-coated balloon with a drug load of 1.3 μg/mm2. Differences in local biological effects (arterial reaction scores) and surface of intimal area (mm2) were not statistically significant between the treatment groups. Numerically, group A showed the lowest intimal area and intimal mean thickness, while group B showed the lowest stenosis among all groups. ECB was safe and effective in a porcine coronary artery model. The dose of everolimus may play a role in the biocompatibility of the balloon.

Clinical Characterization of a Novel Robotic IORT Unit

A novel mobile robotically-guided low-energy intra-operative radiation therapy device was characterized for clinical use. The compact system offers flexible positioning with treatment delivery up to 70 kV energy and 10 Gy/min dose rate with radially collimated emission, and underwent characterization for its dosimetric performance, positioning accuracy and overall clinical suitability. The Morpheus system (Empyrean Medical Systems) consists of a miniature electron esource and a partitioned partial-transmission tungsten target capable of producing 50, 60, and 70 kVp x-rays, mounted on a robotic arm and supported by a motorized mobile base. The radially collimated beam is partitioned in six segments with three radial positions per segment for selective emission, target irradiation and tissue sparing. The beam characteristics were assessed with ion chamber and film dosimetry, both in-air and in a water tank. Radiation levels were assessed for safety and shielding requirements. The absolute dose rate at the surface of a 2 cm radius sterilizable treatment balloon is 8 Gy/min for the 70 kV beam using the AAPM TG-61 formalism. The six treatments sectors emit radially in 60 degrees wedges to within +/- 15% of each other, which can be simply corrected for treatment delivery. The dose falls off to 50% of its initial value within 8 mm from the surface of a treatment balloon for a 70 kV beam. The robotic arm enables a free-hand positioning of the X-ray treatment head to within 1 mm. All interlocks and sterility requirements for operation within an operating room environment were found to be satisfactory. Radiation levels require mobile shielding or a shielded room to be within permissible public radiation levels. The clinical characterization shows the new unit provides a stable and flexible beam delivery platform suitable for IORT treatments. The simplified docking and collimated beam emission provides enhanced capabilities for patient treatment.

Analysis of stretch distribution of high compliant elastomers within folded lumen vessels

Abstract Elastomer based high compliant balloons containing strain sensing element(s) (SEs) is currently under development intended for in-vivo biomechanical diagnostics of vessels. It could potentially reveal local lumen features based on patterns derived from the sensing elements. A Finite Element based, simulation study in COMSOL® (v5.6) focusses on in-vivo inflation behavior of an elastomeric balloon being equipped with SE, whose compliance is ideally magnitudes higher than the surrounding tissue in an idealized 2D setup. We hypothesized the vessel’s inner wall as a closed convexconcave 4-fold structure correlated to surface structures found in urethrae and parameterized the fold depth. A set of SEs consisted of one SE over the inner surface of balloon while the other over the outer wall. Out of the three adjacent placed sets, The first set was closer to the tissue lumen while the third set the farthest. We assessed the stretch of balloon over its inner circumference through SEs. At conformal contact with the tissue wall, The first SE shows a higher value, while the third element undergoes the least stretch within the three sensing elements. The SE’s over the outer circumference show the exact opposite relation. The differences between the sensing elements over the inner and outer circumferences show a correlation with the curvature of the tissue it conforms to. With use of balloon that was 10x thicker (10μm vs 1μm), around 10x larger stretch differences were captured suggesting possibility to use less sensitive measuring system. For the ideal situations performed, the curvature and depth information may be comprehended by observing differences between inner and outer SEs while thicker balloons prove to be more useful to generate differences that are easier to capture in practical situations. This semiquantitative study suggests that simulation studies are powerful tools to obtain new analytical techniques for shape characterization.

Occlusion balloon during transvenous lead extraction-Lessons learned from a case series

Abstract Funding Acknowledgements Type of funding sources: None. Background Lead-extraction for infected or dysfunctional electrodes are these days often performed with a high success rate of complete lead removal. The risk for major complications ranges between 1-5 %. The most catastrophic complication is a tear of the superior vena cava with a high mortality despite urgent cardiothoracic surgical intervention. The use of a transvenously placed occlusion balloon has been shown to be associated with a reduced mortality risk in cases where an SVC tear occurred (reference 1). However, there have been reports showing a risk of clot formation on the surface of the occlusion balloon. Purpose To investigate the feasibility and safety of an occlusion balloon during lead extraction. Methods Prospective case series of 10 patients where the occlusion-balloon during transvenous lead extraction was used prophylactically. Occurrence of clots on the device, complications as a result of the inflated balloon as well as the handling were recorded and documented. Results In this prospective analysis, the occlusion-balloon was staged prophylactically in 10 patients undergoing transvenous lead extraction. The device could be placed successfully in all patients without any complications. After correct positioning (figure 1), the balloon was deflated and staged either at the level of the SVC (30 %), within the sheath (40 %) or within the IVC (30%) during lead extraction procedure. The total dwell time was 18.3 10.3 min. After successful extraction of the leads, the balloon could be readvanced over the wire without using fluoroscopy in all cases (final acceptable position was then reconfirmed via fluoroscopy). No clot formation was observed either on TEE during the procedure nor after removal of the balloon as well as no injury to cardiac or venous structures have been found. However, in one patient suffering from severe heart failure, occlusion of the SVC during balloon inflation resulted in a relevant decrease of the cardiac preload and a drop in blood pressure of which the hemodynamic values recovered completely after deflation. Conclusions Transvenously positioning of an occlusion balloon is a safe procedure according to this case series. Importantly, no clot formation could have been observed which is most likely due to the much shorter dwelling time compared to previous reports. Furthermore, repositioning of the balloon without fluoroscopy at the same level within the SVC is safe and feasible. In patients with severly impaired cardiac function however, the potential decrease in preload due to the inflated balloon can result in a transient decrease of the cardiac function.

Advances in Design and Development of Lumi-Solve: A Novel Drug-Eluting Photo-Angioplasty Device.

The Lumi-Solve photo-angioplasty drug eluting balloon catheter (DEBc) may afford safety advantages over current DEBc. Lumi-Solve utilises the guidewire (GW) port and lumen to deliver fibre-optic UV365nm light to the angioplasty balloon which may be problematic. We explore and evaluate alternative Lumi-Solve design options to circumvent fibre-optic use of the GW port and lumen which may enhance efficacy and clinical utility. Effects of guidewire shadowing (GWS) on visible and UV365nm light transmission were evaluated and modelled in-silico. To evaluate the effect of a dedicated intra-balloon fibre-optic port, modified angioplasty balloons and sections of translucent polyethylene terephthalate (PET) GW port tubing were utilised. Investigation of the effect of GWS on chemical and biological photo-activation of balloon surface drug was performed utilising LCMS analysis and inhibition of histone deacetylase activity (HDACi) was measured in human umbilical vein endothelial cells (HUVEC). Parallel fibre-optic and GW port configurations generated a GWS of approximately 18.0% of the evaluable balloon surface area and attenuated both visible and UV light intensity by 20.0-25.0% and reduced chemical photo-activation of balloon surface drug and HDACi by at least 40-45%. Alternative fibre-optic port configurations including a spiral design significantly mitigated GWS effects on UV light transmission. To avoid use of the GW port and its associated complications a dedicated third port and lumen for the Lumi-Solve fibre-optic may be required. To maximize balloon surface chemical and biological photo-activation, non-parallel, intra-balloon, fibre-optic lumen trajectories, including a spiral design may be useful.

Drug-loaded balloon with built-in NIR controlled tip-separable microneedles for long-effective arteriosclerosis treatment

Drug-eluting balloon (DEB) angioplasty has emerged as an effective treatment for cardiovascular and cerebrovascular diseases. However, distal embolism and late lumen restenosis could be caused by drug loss during DEB handling and rapid drug metabolization. Here, a drug-loaded balloon equipped with tip-separable microneedles on the balloon surface (MNDLB) was developed. Inbuilt near-infrared (NIR) ring laser inside the catheter inner shaft was introduced to activate the biodegradable microneedle tips for the first time. The drug-loaded tips thus could be embedded in the vasculature and then released antiproliferative drug - paclitaxel slowly via polymer degradation for more than half a year. A significant increase in drug delivery efficiency and superior therapeutic effectiveness compared with the standard DEB were demonstrated using an atherosclerosis rabbit model.

To what extent are anorectal function tests comparable? A study comparing digital rectal examination, anal electromyography, 3-dimensional high-resolution anal manometry, and transperineal ultrasound

BackgroundAnorectal function tests are helpful for objective investigation of anorectal (dys)function. A variety of tests are available, but there is no recommendation when to perform which test. Furthermore, which test is the most accurate is controversial and the correlation between these tests is not very clear. The aim of our study was to examine the correlation of anal pressures and the possibility to diagnose pelvic floor dyssynergia between digital rectal examination (DRE) and several anorectal function tests.MethodsBetween January 2020 and April 2022, all men and women aged 18 to 80 years, treated at the Proctos Clinic, who were referred for pelvic floor physical therapy (PFPT) by the surgeon and underwent anorectal function tests, were included. DRE was performed to establish the anal pressure at rest and during squeeze and straining. Anorectal function tests included 3D high-resolution anal manometry (3D-HRAM), balloon expulsion test (BET), transperineal ultrasound (TPUS), and surface electromyography (s-EMG).ResultsA total of 50 patients, 37 (74%) females, were included. Median age was 51 years. Twenty-three (62%) females had a history of two or more vaginal deliveries. The most frequent reason for referral for PFPT was fecal incontinence in 27 (54%) patients. The assessed pressures and pelvic floor function measured with DRE by the surgeon and the pelvic floor physical therapist during rest, squeeze, and straining correlated in 78%, 78%, and 84%, respectively. Correlation between DRE and 3D-HRAM or s-EMG was better for squeeze pressures than resting pressures. The correlation between s-EMG and 3D-HRAM was better during squeeze than at rest with an agreement of 59% and 37%, respectively.ConclusionDRE by an experienced investigator is of sufficient value for daily clinical practice to detect dyssynergia and to measure sphincter tone. Commonly performed anorectal function tests correlate poorly with DRE and with other anorectal function tests. When conservative treatment fails, further investigation is warranted; however, these results should be interpreted with caution.What does this paper add to the literature?Anorectal function tests such as the 3D high-resolution anorectal manometry, balloon expulsion test, surface electromyography, and transperineal ultrasound are all frequently performed in the diagnostic workup in patients with defecation disorders. No previous study has compared these tests regarding their outcomes, nor has the interrater agreement been measured regarding the digital rectal examination by two experienced observers. Furthermore, transperineal ultrasound is in all probability not frequently used and therefore underexposed in the diagnostic workup of patients with dyssynergic defecation.

Evaluation of the direction and extent of ice formation during cryoballoon ablation: an experimental study.

The distal hemisphere of a balloon is generally cooled during cryoapplication. However, a wide ablation area can be acquired after cryoballoon ablation. This study aimed to evaluate the extent of ice formation on two types of balloon surfaces through experimental and simulation studies. A standard cryoballoon (SCB; Arctic Front Advance Pro, Medtronic) and novel cryoballoon (NCB; POLARx, Boston Scientific) were frozen for 240s in 36°C normal saline solution to observe ice formation on the balloon surface. Pieces of porcine tissue were placed between the upper and lower sides of the balloon, and the balloon was frozen in the horizontal direction for 240s in 20 attempts (10 for SCB and NCB each). The measured areas of ice formation were evaluated and compared between the upper and lower sides of each balloon. Ice formation was greater on the lower side of the balloon than on the upper side. A larger area of ice formation in the tissue slab was observed on the lower side than on the upper side in both balloons, and the ice formation extended to the proximal hemisphere on the lower side of the balloon. The ice formation area in the NCB was significantly larger than that in SCB. Ice formation was significantly greater on the lower side of the cryoballoon than on the upper side and extended to the proximal hemisphere of the balloon, which might facilitate the acquisition of a wide ablation area on the left atrial posterior wall after cryoballoon ablation. Different ice formation after cryoballoon ablation Greater ice formation on the lower side of cryoballoon and an extensive ice formation in the proximal hemisphere, especially in novel cryoballoon.

Ultrasound-Triggerable Coatings for Foley Catheter Balloons for Local Release of Anti-Inflammatory Drugs during Bladder Neck Dilation.

Bladder neck contracture (BNC) is a complication of the surgical treatment of benign and malignant prostate conditions and is associated with the partial or complete blockage of urination. Correction of this condition usually requires repeated surgical intervention, which does not guarantee recovery. Balloon dilation is a minimally invasive alternative to the surgical dissection of tissues; however, it significantly reduces the patient’s quality of life. Additional local anti-inflammatory treatment may reduce the number of procedures requested and increase the attractiveness of this therapeutic strategy. Here, we report about an ultrathin biocompatible coating based on polylactic acid for Foley catheter balloons that can provide localized release of Prednol-L in the range of 56–99 µg in the BNC zone under conventional diagnostic ultrasound exposure. Note that the exposure of a transrectal probe with a conventional gray-scale ultrasound regimen with and without shear wave elastography (SWE) was comparably effective for Prednol-L release from the coating surface of a Foley catheter balloon. This strategy does not require additional manipulations by clinicians. The trigger for the drug release is the ultrasound exposure, which is applied for visualization of the balloon’s location during the dilation process. In vivo experiments demonstrated the absence of negative effects of the usage of a coated Foley catheter for balloon dilation of the bladder neck and urethra.

Drug-Coated Balloons: Drugs Beyond Paclitaxel?

Although controversially discussed, paclitaxel is the only clinically proven drug that inhibits restenosis when released from drug-coated balloons (DCBs). Limus drugs are currently being explored as alternatives. The aim of the preclinical studies was to investigate drug candidates beyond paclitaxel considered for balloon coating. Drugs were tested with respect to dissolution in organic solvents, coating on balloons, and drug transfer to the vessel wall. Inhibition of neointimal proliferation was tested in the porcine model of coronary in-stent stenosis. Intravascular drug treatment was achieved by DCBs at the time of stent implantation. Coating had to be adjusted for each drug. Doses on the balloons ranged from 1.0 to 8.6 μg/mm2 balloon surface. Satisfactory amounts of drug ranging from 5% to 29% of initial doses were transferred into the vessel wall. Angiographic parameters such as late lumen loss (LLL) at 4 weeks did not show reduction of in-stent neointimal proliferation by treatment with arsenic trioxide (0.87 ± 0.44 mm), betamethasone dipropionate (1.00 ± 0.54 mm), bortezomib (1.74 ± 0.46 mm), green tea extract (1.24 ± 0.51 mm), fantolon, an epothilone (0.86 ± 0.61 mm), methotrexate (1.09 ± 0.72 mm), and thalidomide (1.59 ± 0.55 mm) compared to treatment with uncoated balloons (1.07 ± 0.60 mm), while coatings with paclitaxel reliably reduced in-stent stenosis (LLL = 0.36 ± 0.25 mm). Despite the proven antiproliferative and/or anti-inflammatory effect of the drugs, none of the coatings significantly reduced LLL compared to uncoated balloons and thus, based on the results presented here, none of the tested coatings may be considered a substitute for the paclitaxel-based coatings currently in clinical use.

Improvement of Outcome for Treatment of ‘Restenosis-prone’ Vascular Lesions? Potential Impact of the Paclitaxel dose on Late Lumen Loss in Porcine Peripheral Arteries

PurposeClinical data indicate that the drug density on drug-coated balloons (DCBs) might have a role on treatment effect and durability. The aim of the current study was to investigate inhibition of neointimal formation and potential adverse effects after treatment with a novel double-dose DCB in swine.Material and methodsA four-week study was performed in peripheral arteries of 12 domestic pigs after vessel injury and stent implantation. The novel double-dose DCB with 6-µg paclitaxel (Ptx)/mm2 balloon surface (1 × 6) was compared to a standard DCB with 3.5 µg Ptx/mm2 (3.5) and uncoated balloons (POBA). Potential adverse effects were stimulated by using three fully overlapping DCBs with 6 µg Ptx/mm2 each (3 × 6). Quantitative angiography, histomorphometry and histopathological analyses were performed.ResultsHigher paclitaxel doses per square millimeter of treated arteries were associated with reduced late lumen loss (LLL) in quantitative angiography 4 weeks after treatment (POBA: 0.91 ± 0.75 mm; 3.5: 0.45 ± 0.53 mm; 1 × 6: 0.21 ± 0.41 mm; 3 × 6: − 0.38 ± 0.65 mm). In histomorphometry, maximal neointimal thickness and neointimal area were the lowest for the 1 × 6 group (0.15 ± 0.06 mm/1.5 ± 0.4 mm2), followed by 3 × 6 (0.20 ± 0.07 mm/1.8 ± 0.4 mm2), 3.5 (0.22 ± 0.12 mm/2.2 ± 1.1 mm2) and POBA (0.30 ± 0.07 mm/3.2 ± 0.7 mm2). Downstream tissue showed histopathological changes in all groups including POBA, in larger number and different quality (e.g., edema, inflammation, vessel wall necrosis, vasculitis and perivasculitis) in the 3 × 6 group, which did not cause clinical or functional abnormalities throughout the study.ConclusionTreatment with the double-dose DCB (6 µg Ptx/mm2) tended to increase inhibition of in-stent neointimal formation and to diminish LLL after peripheral intervention in the porcine model compared to a market-approved DCB with 3.5 µg Ptx/mm2.

Development of a new HotBalloonTM ablation catheter equipped with a balloon surface temperature monitoring sensor for pulmonary vein isolation

The balloon surface temperature (BST) should be monitored to ensure the success of the ablation procedure using the HotBalloonTM ablation catheter (HBC) in clinical settings. Therefore, we sought to develop a new HBC equipped with a surface temperature monitoring sensor. The BST was evaluated using a pseudo-tissue model and a thermocouple to imitate catheter insertion into the pulmonary vein. Thermo-fluid analysis with computer-aided engineering (CAE) was performed to analyse the temperature distribution in the catheter and the balloon. The CAE analysis reproduced the results from a pseudo-tissue model experiment and demonstrated that some fluid zones inside the catheter shaft had a nearly identical temperature as the BST during the liquid suction period. The pseudo-tissue model experiment confirmed that the temperature was almost the same between the balloon surface and the position of 5 mm inside the catheter shaft from the proximal end of the balloon. A thermocouple placed at 5 mm or 25 mm from the proximal end of the balloon within the catheter shaft showed an equivalent temperature result. This 5–25-mm distance is acceptable to set the BST monitoring sensor inside the catheter shaft, since the sensor can help accurately estimate the BST.