Objective Evaluate transcatheter mitral valve replacement (TMVR) valve-in-valve (VIV) outcomes in three different mitral bioprostheses (of comparable measured internal diameters) under stable hemodynamic and surgical conditions by bench, echocardiographic, computerized tomography (CT), and autopsy comparisons pre- and post-valve implantation in a porcine model under matched controlled conditions. Background Impact of surgical bioprosthesis design on TMVR VIV procedures is unknown. Methods Fifteen similar-sized Yorkshire pigs underwent pre-procedural CT screening. Twelve had consistent anatomic features and underwent implantation of mitral bioprostheses. Four valves from each of three manufacturers were implanted in randomized fashion: 27-mm Epic, 27-mm Mosaic, and 25-mm Mitris, followed by TMVR VIV with 26 Edwards Sapien3. Post-VIV, suprasternal TEE studies were performed to assess hemodynamic function, followed by a gated contrast CT. After euthanasia, animals underwent necropsy for anatomic evaluation. Results All 12 animals had successful VIV implantation with no study deaths. The post vivMitris (3.77 +/- 0.36)/(2.2 +/- 0.25 mmHg) had the lowest peak/mean trans-mitral gradient and the vivEpic the highest (15.5 +/- 2.55)/(7.09 +/- 1.13 mmHg). All THVs (transcatheter heart valves) had greatest deformation within the center of the THV frame; with the smallest waist opening area in the vivEpic (329 +/- 35.8 mm(2)) and greatest in the vivMitris (414 +/- 33.12 mm(2)). Bioprosthetic frames without obvious radiopaque markers resulted in the most ventricular implantation of the THV's anteroseptal frame (Epic: -4.52 +/- 0.76 mm), versus the most radiopaque bioprosthesis (Mitris: -1.18 +/- 2.95 mm), and higher peak LVOT gradients (Epic: 4.82 +/- 1.61 mmHg; Mitris: 2.91 +/- 1.47 mmHg). Conclusions The current study demonstrates marked variations in hemodynamics, THV opening area, and anatomic dimensions among measured similarly sized mitral bioprostheses. These data suggest a critical need for understanding the potential impact of variations in bioprosthesis design on TMVR VIV clinical outcomes.

Objectives To determine the safety and efficacy of the conveyor cardiovascular system (CCS) to facilitate the delivery of large profile transcatheter valve devices. Background Transcatheter valve devices rely on force provided by the operator to be delivered to their intended position. This delivery may be challenging in a variety of anatomic scenarios. The ability to provide steering from the tip of the device by forming an arterial venous loop may help overcome these challenges. Methods Between May, 2019 and October, 2020, five patients were recruited for delivery of transcatheter valve devices with the CCS. These patients were deemed by the operators to have challenging anatomy which could make conventional valve delivery difficult or impossible. These patients were recruited as part of an FDA approved early feasibility study or through an institutional review board approved compassionate use protocol. Results Three patients underwent transcatheter mitral valve replacement with a SAPIEN-3 valve. One patient each underwent transcatheter aortic valve (TAVR) implantation with a SAPIEN 3 and 1 patient underwent TAVR implantation with a Lotus valve. All patients underwent successful implantation of the valve and removal of the CCS and valve delivery systems. There was no more than trivial mitral regurgitation post procedure in any patient and there was no more than trivial paravavular leak. There were no major in-hospital complications. Conclusions The CCS facilitates the delivery of large profile transcatheter valve devices in challenging anatomic scenarios. Further studies are needed with additional valve technologies.

To evaluate three mitral bioprostheses (of comparable measured internal diameters) under controlled, stable, hemodynamic and surgical conditions by bench, echocardiographic, computerized tomography and autopsy comparisons pre‐ and postvalve implantation.

OBJECTIVESDirect aortic deployment of a transcatheter aortic valve eliminates the need to traverse the aortic arch with the valve delivery system, enables placement of large sheaths in the aorta and innominate artery, provides maximal precision during deployment and ensures a safe, conventional surgical aortotomy closure. We describe the initial experience with the Suprasternal Aortic Access System (SuprAA System, Aegis Surgical Ltd, Dublin, Ireland) for direct transaortic/innominate valve delivery.METHODSPatients with severe, symptomatic aortic stenosis who were candidates for transcatheter aortic valve replacement (TAVR) via a direct transaortic approach were enrolled in the SuprAA-TAVR First-in-Man Study. Under general anaesthesia, the innominate artery and aortic arch were exposed in each patient, using the SuprAA System via a 2.5-cm incision directly above the sternal notch. The TAVR delivery sheath was positioned and the transcatheter valve deployed routinely under fluoroscopic guidance. Upon sheath removal, haemostasis at the aortotomy site was confidently secured using a double purse-string suture closure. All were extubated immediately. A meta-analysis of the direct aortic approach was done for comparison.RESULTSFour male patients (mean 82.5 years) underwent SuprAA-TAVR (2 CoreValve; 2 SAPIEN). Anatomical visualization was excellent and suprasternal valve deployment was accurate regardless of sheath size with 100% Valve Academic Research Consortium-2 procedural success. The average total procedure time was 109.5 min without perioperative wound or vascular complications.CONCLUSIONSThe SuprAA System provides direct aortic/innominate access without sternal or thoracotomy incision. Patient recovery to normal activity is maximized, sheath size limitations are eliminated and valve deployment is precise. This innovative system creates a new and exciting minimally invasive approach for high-risk patients with aortic stenosis.

Transfemoral, transapical and conventional direct aortic TAVR patients have incisional morbidity that may delay ambulation and discharge. We evaluated the feasibility of direct aortic or innominate access for deployment of a transcatheter aortic valve using a novel suprasternal aortic access system without bony disruption or femoral instrumentation. Two patients with severe, symptomatic aortic stenosis at very high risk for conventional AVR (mean: age 82.5 years, STS predicted mortality 20%) but who were poor candidates for transfemoral or transapical valve delivery were consented for TAVR with the suprasternal aortic access system following Health Canada Special Access approval. This novel system includes a specially shaped, radiolucent trocar that combines internal illumination for direct visualization and an external stabilizer connected directly to the table to provide a motionless, hands free, retracted surgical field. The system is positioned under general anesthesia through a 3 cm incision above the sternal notch. The suprasternal aortic access system was successfully positioned with direct visualization and instrumentation of the aorta and innominate artery in both patients. A pigtail catheter placed via the radial artery provided aortography and facilitated valve positioning in combination with the axial control inherent to direct aortic approaches. Both Edwards Sapien XT valves were deployed with VARC-2 procedural success. Importantly, purse string suture placement, sheath insertion, precise valve positioning and hemostatic sheath removal all proved feasible through the stabilized suprasternal aortic access system without chest wall incision or bony disruption. Mean fluoroscopy times, radiation and contrast doses were 14 min, 2373 mGy and 68 ml respectively (n=2). Both patients were extubated in the operating room and experienced minimal incisional discomfort. Despite their complex co-morbidities, both patients were mobilized the day of surgery and discharged home on the second postoperative day with normally functioning bioprosthetic valves (mean gradient 11 mmHg, paravalvular regurgitation: none and trace, n=2). The suprasternal approach employing the suprasternal aortic access system enables direct axial valve positioning and avoids sternal/thoracotomy incisions and femoral access. Early mobilization is possible and likely expedites recovery. This innovative system creates a novel minimally invasive approach for high-risk patients with aortic stenosis. A multicenter clinical evaluation is underway.

Parenteral and oral routes have been the traditional methods of administering cytotoxic agents to cancer patients. Unfortunately, the maximum potential effect of these cytotoxic agents has been limited because of systemic toxicity and poor tumor perfusion. In an attempt to improve the efficacy of cytotoxic agents while mitigating their side effects, we have developed modalities for the localized iontophoretic delivery of cytotoxic agents. These iontophoretic devices were designed to be implanted proximal to the tumor with external control of power and drug flow. Three distinct orthotopic mouse models of cancer and a canine model were evaluated for device efficacy and toxicity. Orthotopic patient-derived pancreatic cancer xenografts treated biweekly with gemcitabine via the device for 7 weeks experienced a mean log(2) fold change in tumor volume of -0.8 compared to a mean log2 fold change in tumor volume of 1.1 for intravenous (IV) gemcitabine, 3.0 for IV saline, and 2.6 for device saline groups. The weekly coadministration of systemic cisplatin therapy and transdermal device cisplatin therapy significantly increased tumor growth inhibition and doubled the survival in two aggressive orthotopic models of breast cancer. The addition of radiotherapy to this treatment further extended survival. Device delivery of gemcitabine in dogs resulted in more than 7-fold difference in local drug concentrations and 25-fold lower systemic drug levels than the IV treatment. Overall, these devices have potential paradigm shifting implications for the treatment of pancreatic, breast, and other solid tumors.

Objectives: Direct aortic deployment of a transcatheter aortic valve eliminates the need to traverse the aortic arch with the valve delivery system, enables placement of large sheaths in the aorta and innominate artery, provides maximal precision during deployment, and ensures safe, conventional surgical aortotomy closure. We describe the initial experience with the Suprasternal Aortic Access System (SuprAA System, Aegis Surgical Ltd, Dublin, Ireland) for direct transaortic/innominate valve delivery. Methods: Patients with severe, symptomatic aortic stenosis who were candidates for TAVR via a direct transaortic approach were enrolled in the SuprAA-TAVR First-in-Man Study. Under general anaesthesia, the innominate artery and aortic arch were exposed in each patient using the SuprAA System via a 2.5-cm incision directly above the sternal notch. The TAVR delivery sheath was positioned and transcatheter valve deployed routinely under fluoroscopic guidance. Upon sheath removal, haemostasis at the aortotomy site was confidently secured using a double purse-string suture closure. All were extubated immediately. Results: Four male patients (mean age 82.5 years) underwent SuprAA-TAVR (2 CoreValve; 2 SAPIEN). Anatomical visualization was excellent and suprasternal valve deployment was accurate regardless of sheath size with 100% VARC-2 procedural success. The average total procedure time was 109.5 mins without perioperative wound or vascular complications. One patient required a pacemaker (Table 1). CAD: Coronary artery disease; CVA: cerebral vascular accident; LVEF: Left ventricular ejection fraction; STS: Society of Thoracic Surgeons; Cr: Serum Creatinine; NYHA: New York Heart Association; LAD: left anterior descending. CAD: Coronary artery disease; CVA: cerebral vascular accident; LVEF: Left ventricular ejection fraction; STS: Society of Thoracic Surgeons; Cr: Serum Creatinine; NYHA: New York Heart Association; LAD: left anterior descending. Conclusion: The SuprAA System provides direct aortic/innominate access without sternal or thoracotomy incision. Patient recovery to normal activity is maximized, sheath size limitations are eliminated and valve deployment is precise. This innovative system creates a new and exciting minimally invasive approach for high-risk patients with aortic stenosis.