BASILICA Trial: One-Year Outcomes of Transcatheter Electrosurgical Leaflet Laceration to Prevent TAVR Coronary Obstruction

Background: Coronary artery obstruction is a rare, devastating complication of transcatheter aortic valve replacement. Transcatheter electrosurgical aortic leaflet laceration (Bioprosthetic or Native Aortic Scallop Intentional Laceration to Prevent Iatrogenic Coronary Artery Obstruction [BASILICA]) is a novel technique to prevent coronary artery obstruction. We report the 1-year outcomes of the BASILICA trial. Primary end points of 30-day success and safety have been reported previously. Methods: The BASILICA trial was a prospective, multicenter, single-arm safety and feasibility study. Subjects with severe native or bioprosthetic aortic valve disease at high or extreme risk for surgery, and high risk of coronary artery obstruction, were included. End points at 1 year included death, stroke, and myocardial infarction. Source data was independently verified and end points independently adjudicated. Results: Thirty subjects were enrolled between February 2018 and July 2018. At 30 days, BASILICA was successful in 28 subjects (93.3%), there were 3 strokes (10%), including 1 disabling stroke (3.3%), 1 death (3.3%), and 1 periprocedural myocardial infarction (3.3%). Between 30 days and 1 year, there were no additional strokes, no myocardial infarction, and 2 deaths (10% 1-year mortality). No subject needed repeat intervention for aortic valve or coronary disease. Two subjects had infective endocarditis (6.7%), but neither was isolated to the aortic valve. There were no hospital admissions for heart failure. Fourteen (46.7%) subjects required repeat hospital admission for other causes. Aortic valve gradients on echocardiography, New York Heart Association functional class, and Kansas City Cardiomyopathy Questionnaire scores improved from baseline to 30 days and were maintained at 1 year. Conclusions: In these subjects with multiple comorbidities and restrictive anatomy that underwent transcatheter aortic valve replacement, there was no late stroke, myocardial infarction, or death related to BASILICA. Mitigation of coronary obstruction remained intact at 1 year and was not related to recurrent readmission. These results are reassuring for patients and physicians who wish to avoid the long-term complications related to snorkel stenting

Activation of the kinin system in the ovary during ovulation: Role of endogenous progesterone

<p>Abstract</p> <p>Background</p> <p>Previous work by our group and others has implicated a role for kinins in the ovulatory process. The purpose of the present study was to elucidate whether endogenous progesterone, which is an intraovarian regulator of ovulation, might be responsible for induction of the kinin system in the ovary during ovulation. The gonadotropin-primed immature rat was used as the experimental model, and the role of endogenous progesterone was explored using the antiprogestin, RU486.</p> <p>Results</p> <p>The results of the study revealed that RU486 treatment, as expected, significantly attenuated ovulation. Activity of the kinin-generating enzyme, kallikrein, was elevated in the ovary in control animals prior to ovulation with peak values observed at 4 h post hCG, only to fall to low levels at 10 h, with a recovery at 20 h post hCG. RU486 treatment had no significant effect on ovarian kallikrein activity as compared to the control group. Total ovarian kininogen levels in control animals increased significantly at 12–14 h after hCG – coinciding with initiation of ovulation. Thereafter, ovarian kininogen levels fell to low levels at 20 h, only to show a rebound from 24–38 h post-hCG. RU486 treatment had no significant effect on the rise of total ovarian kininogen levels from 12–14 h after hCG; however, from 30–40 h post hCG, RU486-treated animals had significantly higher total ovarian kininogen levels versus control animals, suggesting that endogenous progesterone may act to restrain elevations of kininogens in the post-ovulatory ovary. This robust elevation of ovarian kininogen levels by RU486 was found to be primarily due to an increase in T-kininogen, which is a potent cysteine protease inhibitor.</p> <p>Conclusions</p> <p>Taken as a whole, these results suggest that endogenous progesterone does not regulate kallikrein activity or kininogens prior to ovulation, but may provide a restraining effect on T-kininogen levels in the post-ovulatory ovary.</p

Dedicated Closure Device for Transcaval Access Closure: From Concept to First-in-Human Testing

OBJECTIVES: This study sought to test safety and exploratory effectiveness of a dedicated transcaval closure device (TCD). BACKGROUND: Transcaval access enables delivery of large-caliber devices to the aorta in patients ineligible for transfemoral arterial access. Closure of aortocaval fistulae using off-label nitinol cardiac occluders has been shown to be safe, but persistent aortocaval fistulae at exit from the catheterization lab and bleeding complications were common in a prospective study. METHODS: Preclinical testing of the TCD was performed in 24 Yorkshire swine, including 10 under good laboratory practice conditions. Subsequently, subjects undergoing transcatheter aortic valve replacement for symptomatic severe aortic stenosis, ineligible for transfemoral arterial access, were enrolled in a U.S. Food and Drug Administration-approved early feasibility study of the TCD (Transmural Systems, Andover, Massachusetts). Independently adjudicated endpoints included technical, device, and procedural success, incorporating in-hospital and 30-day clinical and imaging follow-up. RESULTS: Transcaval access and closure in swine confirmed that at 30 days, TCDs were almost entirely endothelialized. Subsequently, 12 subjects were enrolled in the early feasibility study. Transcaval access, transcatheter aortic valve replacement, and aortocaval fistula closure was successful in all 12 subjects. The primary endpoint of technical success was met in 100% of subjects. Complete closure of the transcaval access tract was achieved in 75% of subjects at exit from the catheterization lab and in 100% of subjects at 30 days. There were zero modified Valve Academic Research Consortium-2 major vascular complications and zero Valve Academic Research Consortium-2 life-threatening or major bleeding complications related to transcaval access or the TCD. CONCLUSIONS: The TCD achieved complete closure of the transcaval access tract in most subjects at exit from the catheterization lab and essentially eliminated transcaval-related bleeding. Dedicated devices for transcaval access and closure could enable more widespread adoption of transcaval techniques without fear of bleeding complications. (Transmural Systems Transcaval Closure Device for Transcaval Access Ports During Transcatheter Aortic Valve Replacement; NCT03432494)