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Background: Left ventricular outflow tract (LVOT) obstruction is a common, often fatal complication of transcatheter mitral valve replacement (TMVR). Laceration of the anterior mitral leaflet to prevent outflow obstruction (LAMPOON) was safe and effective at preventing LVOT obstruction at 30 days in the National Heart, Lung, and Blood Institute LAMPOON trial., Objectives: The authors report the 5-year outcomes of intentional anterior mitral leaflet laceration before SAPIEN 3 TMVR, in patients at risk of LVOT obstruction., Methods: The National Heart, Lung, and Blood Institute LAMPOON trial was a prospective, multicenter, single-arm safety and feasibility study of LAMPOON and transseptal SAPIEN 3 TMVR in annuloplasty rings (valve-in-ring) or native mitral annular calcification (MAC) (valve-in-MAC). All subjects had high predicted risk for LVOT obstruction. Subjects were not excluded for excessive frailty or comorbidity. The primary endpoints were technical success and safety at 30 days. Secondary clinical and echocardiographic endpoints were assessed at 1 year and clinical follow-up at 5 years., Results: Thirty subjects were enrolled between June 2017 and June 2018, equally between the valve-in-MAC and valve-in-ring arms. At 30 days, LAMPOON was successful in all 30 subjects, with no strokes, 1 (3%) death, and 1 (3%) moderate LVOT obstruction. Eighteen (65%) survived to 1 year, and 7 (25%) survived to 5 years. Six (20%) were hospitalized for heart failure in the first year. From baseline to 1 year, there was a 24-point improvement in Kansas City Cardiomyopathy Questionnaire score and a 60-m improvement in 6-minute walk distance. There was no significant change in N-terminal pro-brain natriuretic peptide. At 1 year, LVOT gradients remained low., Conclusions: LAMPOON enabled TMVR despite the risk for LVOT obstruction. There were no long-term complications associated with LAMPOON. The selection of inoperable patients limited assessment of long-term survival following TMVR. (NHLBI DIR LAMPOON Study: Intentional Laceration of the Anterior Mitral Leaflet to Prevent Left Ventricular Outflow Tract Obstruction During Transcatheter Mitral Valve Implantation; NCT03015194)., Competing Interests: Funding Support and Author Disclosures This work was supported by the Division of Intramural Research, NHLBI, National Institutes of Health (Z01-HL006040), and by the intramural programs of the participating centers. The NHLBI and Edwards Lifesciences have a collaborative research and development agreement on transcatheter modification of mitral valve leaflets, including joint financial support of this study. Drs Khan, Rogers, and Lederman are coinventors on patents, assigned to the National Institutes of Health, for catheter devices to lacerate valve leaflets. Dr Khan is a proctor for Edwards Lifesciences and Medtronic; and has equity in Transmural Systems. Dr Greenbaum is a proctor for Edwards Lifesciences, Medtronic, and Abbott Vascular; and has equity in Transmural Systems and Excision Medical. Dr Babaliaros is a consultant for Edwards Lifesciences, Abbott Vascular, and Transmural Systems; and his employer has research contracts for clinical investigation of transcatheter aortic and mitral devices from Edwards Lifesciences, Abbott Vascular, Medtronic, St. Jude Medical, and Boston Scientific. Dr Rogers is a consultant for Edwards Lifesciences, Boston Scientific, Abbott, Anteris, and Medtronic; serves on advisory boards for Medtronic and Boston Scientific; and has equity in Transmural Systems. Dr Eng is on the Speakers Bureau for Edwards Lifesciences and Medtronic. Dr Foerst is a proctor for Edwards Lifesciences and Medtronic. Dr Paone is proctor for Edwards Lifesciences and has equity in Medtronic. Dr Lederman is the principal investigator on a cooperative research and development agreement between the National Institutes of Health and Edwards Lifesciences for transcatheter modification of the mitral valve. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Published by Elsevier Inc.)

Transcaval aortic access is a versatile electrosurgical technique for large-bore arterial access through the wall of the abdominal aorta from the adjoining inferior vena cava. Although counterintuitive, its relative safety derives from the recognition that interstitial hydraulic pressure exceeds venous pressure, so arterial bleeding harmlessly decompresses into the nearby caval venous hole. Transcaval access has been performed in thousands of patients for transcatheter aortic valve replacement and endovascular thoracic aneurysm repair and to avoid limb ischemia in percutaneous mechanical circulatory support. Transcaval access may have value compared with transaxillary or subclavian access and with surgical transcarotid access when standard transfemoral access is not optimal. The dissemination of transcaval access and closure techniques has been hampered by the unavailability of commercially marketed devices. This state-of-the-art review details exemplary transcaval technique, patient selection, computed tomographic planning, step-by-step access and closure, management of complications, and procedural troubleshooting in special situations. These contemporary best practices can help operators gain or maintain proficiency., Competing Interests: Funding Support and Author Disclosures This work was supported by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health (grant Z01-HL006040) (to Dr Lederman). All authors are coinventors of patents, assigned to the National Institutes of Health, for transcaval- or electrosurgery-related devices. Drs Greenbaum and Babaliaros have received institutional research support from Abbott Vascular, Ancora Heart, Edwards Lifesciences, Gore Medical, JenaValve, Medtronic, Polares Medical, Transmural Systems, and 4C Medical; have received consulting fees from Abbott Vascular, Edwards Lifesciences, and Medtronic; and have equity interest in Transmural Systems. Dr Rogers is a consultant and physician proctor for Edwards Lifesciences, Medtronic, and Boston Scientific; is an advisory board member for Medtronic; and holds equity interest in Transmural Systems. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Published by Elsevier Inc.)

Competing Interests: Funding Support and Author Disclosures Supported by Emory Structural Heart and Valve program intramural funds and by National Institutes of Health (NIH) grant Z01-HL006040. Dr Babaliaros has institutional research contracts for clinical investigation of transcatheter aortic, mitral, and tricuspid devices from Edwards Lifesciences, Abbott Vascular, Medtronic, and Boston Scientific; is a consultant for Edwards Lifesciences and Abbott Vascular; and has equity interest in Transmural Systems. Drs Gleason, Xie, and Byku have institutional research contracts for clinical investigation of transcatheter aortic, mitral, and tricuspid devices from Edwards Lifesciences, Abbott Vascular, Medtronic, and Boston Scientific. Dr Khan is a proctor for Edwards Lifesciences and Medtronic; and is a coinventor on patents, assigned to the NIH, on devices for electrosurgical tissue laceration. Dr Bruce is a coinventor on patents, assigned to the NIH, on devices for electrosurgical tissue laceration. Dr Grubb is a consultant for Edwards Lifesciences and Medtronic; and has institutional research contracts for clinical investigation of transcatheter aortic, mitral, and tricuspid devices from Edwards Lifesciences, Abbott Vascular, Medtronic, and Boston Scientific. Dr Paone has institutional research contracts for clinical investigation of transcatheter aortic, mitral, and tricuspid devices from Edwards Lifesciences, Abbott Vascular, Medtronic, and Boston Scientific; and is a proctor for Edwards Lifesciences. Dr Lederman is a coinventor on patents, assigned to the NIH, on devices for electrosurgical tissue laceration. Dr Greenbaum has institutional research contracts for clinical investigation of transcatheter aortic, mitral, and tricuspid devices from Edwards Lifesciences, Abbott Vascular, Medtronic, and Boston Scientific; is a proctor for Edwards Lifesciences and Medtronic; and has equity interest in Transmural Systems. Dr Rogers has reported that he has no relationships relevant to the contents of this paper to disclose.

Transcatheter electrosurgery is a versatile tool that can be used to cut cardiac tissue without the need for a sternotomy, cardiopulmonary bypass, and cardioplegia. With adequate imaging and suitable anatomy, any cardiac tissue can be cut. Thus, transcatheter electrosurgery can provide bespoke therapies for complex patients who often have no other good treatment options. In this review, we will discuss the common applications for electrosurgical tissue traversal and laceration, including transcaval access, BASILICA, LAMPOON, and ELASTA-Clip, summarizing the evidence and the key technical steps for each., (Copyright © 2022. Published by Elsevier Inc.)

Background: Transcatheter mitral valve repair is beneficial in patients with mitral regurgitation (MR), left ventricular dysfunction, and persistent symptoms despite maximally tolerated medical therapy., Objectives: The aim of this study was to evaluate the safety and feasibility of transcatheter mitral cerclage ventriculoplasty in patients with MR and either heart failure with reduced ejection fraction or preserved ejection fraction and in subjects with prior edge-to-edge repair but persistent or recurrent symptomatic MR., Methods: The National Heart, Lung, and Blood Institute Division of Intramural Research Transcatheter Mitral Cerclage Ventriculoplasty Early Feasibility Study (NCT03929913) was an investigator-initiated prospective multicenter study. The primary endpoint was technical success measured at exit from the catheterization laboratory. Follow-up included heart failure quality-of-life assessments and serial imaging with echocardiography and cardiac computed tomography., Results: Nineteen subjects consented and underwent cerclage, 63% with heart failure with reduced ejection fraction and 37% with heart failure with preserved ejection fraction, with ischemic cardiomyopathy in 26% and nonischemic cardiomyopathy in 74%. There were no procedural deaths, strokes, or transient ischemic attacks or other major cardiovascular adverse events. The primary endpoint was met in 17 subjects. Cerclage induced sustained reductions in mitral regurgitant volume (-41%) and effective orifice area (-33%) after a median of 337 days. Cerclage resulted in improvements in 6-minute walking distance (+78 m) and Kansas City Cardiomyopathy Questionnaire Overall Summary Score (+22 points) at 30 days that were maintained after a median of 265 days. New complete heart block developed in 6 of 17 subjects. Three deaths occurred on postprocedural days 79, 159, and 756, unrelated to cerclage., Conclusions: Transcatheter mitral cerclage ventriculoplasty resulted in significant and sustained improvements in mitral regurgitation and in heart failure quality-of-life assessments., Competing Interests: Funding Support and Author Disclosures This work is supported by the NHLBI DIR (grant Z01-HL006040) and by an NHLBI small business innovation research contract (HHSN268201500008C) to Transmural Systems. Dr Rogers is a consultant and physician proctor for Edwards Lifesciences and Medtronic; is a Medtronic advisory board member; and has an equity interest in Transmural Systems. Drs Rogers and Lederman are coauthors on patents, assigned to the National Institutes of Health, for cerclage-related devices. Drs Babaliaros and Greenbaum have received institutional research support from Abbott Vascular, Ancora Heart, Edwards Lifesciences, Gore Medical, Jena Valve, Medtronic, Polares Medical, Transmural Systems, and 4C Medical; have received consulting fees from Abbott Vascular, Edwards Lifesciences, and Medtronic; and have equity interest in Transmural Systems. Dr Foerst is a physician proctor for Edwards Lifesciences and Medtronic. Dr Gleason has received institutional research support from Edwards Lifesciences, Medtronic, and Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Published by Elsevier Inc.)

Objectives: The aim of this study was to compare transcaval and transaxillary artery access for transcatheter aortic valve replacement (TAVR) at experienced medical centers in contemporary practice., Background: There are no systematic comparisons of transcaval and transaxillary TAVR access routes., Methods: Eight experienced centers contributed local data collected for the STS/ACC TVT Registry (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry) between 2017 and 2020. Outcomes after transcaval and axillary/subclavian (transaxillary) access were adjusted for baseline imbalances using doubly robust (inverse propensity weighting plus regression) estimation and compared., Results: Transcaval access was used in 238 procedures and transaxillary access in 106; for comparison, transfemoral access was used in 7,132 procedures. Risk profiles were higher among patients selected for nonfemoral access but similar among patients requiring transcaval and transaxillary access. Stroke and transient ischemic attack were 5-fold less common after transcaval than transaxillary access (2.5% vs 13.2%; OR: 0.20; 95% CI: 0.06-0.72; P = 0.014) compared with transfemoral access (1.7%). Major and life-threatening bleeding (Valve Academic Research Consortium 3 ≥ type 2) were comparable (10.0% vs 13.2%; OR: 0.66; 95% CI: 0.26-1.66; P = 0.38) compared with transfemoral access (3.5%), as was blood transfusion (19.3% vs 21.7%; OR: 1.07; 95% CI: 0.49-2.33; P = 0.87) compared with transfemoral access (7.1%). Vascular complications, intensive care unit and hospital length of stay, and survival were similar between transcaval and transaxillary access. More patients were discharged directly home and without stroke or transient ischemic attack after transcaval than transaxillary access (87.8% vs 62.3%; OR: 5.19; 95% CI: 2.45-11.0; P < 0.001) compared with transfemoral access (90.3%)., Conclusions: Patients undergoing transcaval TAVR had lower rates of stroke and similar bleeding compared with transaxillary access in a contemporary experience from 8 US centers. Both approaches had more complications than transfemoral access. Transcaval TAVR access may offer an attractive option., Competing Interests: Funding Support and Author Disclosures This work was supported by the Emory Structural Heart and Valve program intramural funds, and by National Institutes of Health Z01-HL006040. Drs Babaliaros and Greenbaum have served as consultants for Edwards Lifesciences and Abbott Vascular; have an employer with research contracts for clinical investigation of transcatheter aortic, mitral, and tricuspid devices from Edwards Lifesciences, Abbott Vascular, Medtronic, and Boston Scientific; and own equity interest in Transmural Systems. Drs Lederman and Rogers are coinventors on device patents, assigned to the National Institutes of Health, for closure of transcaval access ports. Dr Rogers has served as consultant and physician proctor for Edwards Lifesciences and Medtronic; has been on the advisory board for Medtronic; and has equity interest in Transmural Systems. Dr Mahoney has served as a proctor and consultant and has received institutional research support from Edwards Lifesciences, Medtronic, and Abbott. Dr Foerst has served as a proctor for Edwards Lifesciences and Medtronic. Dr Depta has served as a consultant or advisory board member for Edwards Lifesciences, Boston Scientific, Abbott, V-Wave-Ltd, and WL Gore & Associates. Dr Muhammad has served as a proctor and consultant for Edwards Lifesciences and Medtronic. Dr McCabe has served as a consultant and has received honoraria from Boston Scientific, Cardiovascular Systems Inc, Edwards Lifesciences, and Medtronic. Dr Pop is a consultant for Edwards Lifesciences and Shockwave Medical. Dr Khan has served as a proctor for Edwards Lifesciences and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Published by Elsevier Inc.)

The SAPIEN 3 is the only transcatheter heart valve commercially available for compassionate transcatheter mitral valve replacement in patients with previous mitral surgical rings and mitral annular calcification (valve in ring [VIR] and valve in mitral annular calcification [VIM]). Reported outcomes have been inconsistent or poor. The review provides an overview of the authors' approach to achieve largely consistent results despite the intrinsic limitations of SAPIEN 3 VIM and VIR. The approach includes bedside modifications of the valve implant, the delivery system, and of the cardiac substrate itself. Until purpose-built devices are readily available, VIR and VIM procedures will require aggressive multidisciplinary cooperation, meticulous planning and execution, and postprocedure management by experienced, high-volume operators., Competing Interests: Funding Support and Author Disclosures This work was supported by the Emory Structural Heart and Valve program intramural funds, and by National Institutes of Health Grant No. Z01-HL006040. Dr Babaliaros has served as a consultant for Edwards Lifesciences and Abbott Vascular; has an employer with research contracts for clinical investigation of transcatheter aortic, mitral, and tricuspid devices from Edwards Lifesciences, Abbott Vascular, Medtronic, and Boston Scientific; and owns equity interest in Transmural Systems. Dr Lederman has served as the principal investigator on a cooperative research and development agreement between National Institutes of Health and Edwards Lifesciences for transcatheter modification of the mitral valve. Drs Lederman, Khan, and Rogers are co-inventors on patents, assigned to the National Institutes of Health, on devices for electrosurgical leaflet laceration. Drs Khan and Rogers have served as proctors for Edwards Lifesciences and Medtronic. Mr Kohli has served as a consultant for Abbott Laboratories. Dr Paone has served as a consultant and proctor for Edwards Lifesciences. Dr Lisko’s employer has contracts for BASILICA analysis with Medtronic and Edwards Lifesciences. Dr Greenbaum has served as a proctor for Edwards Lifesciences, Medtronic, and Abbott Vascular; owns an equity interest in Transmural Systems; and has an employer with research contracts for clinical investigation of transcatheter aortic, mitral, and tricuspid devices from Edwards Lifesciences, Abbott Vascular, Medtronic, and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures This research was supported by Emory Structural Heart and Valve program intramural funds and by National Institutes of Health grant Z01-HL006040. Dr. Greenbaum is a proctor for Edwards Lifesciences and Medtronic; and is a consultant with equity in Transmural Systems. Dr. Greenbaum’s employer has research contracts for investigation of transcatheter aortic and mitral devices from Edwards Lifesciences, Abbott Vascular, Medtronic, and Boston Scientific. Dr. Vavalle is a consultant for Edwards Lifesciences. Dr. Paone is a consultant and proctor for Edwards Lifesciences. Dr. Grubb is a speaker, a proctor, and an investigator for Edwards Lifesciences; is a speaker, a proctor, and an advisory board member for Boston Scientific; and is a speaker, a proctor, an investigator, and an advisory board member for Medtronic. Dr. Lederman is principal investigator in a cooperative research and development agreement between Edwards Lifesciences and the National Institutes of Health on transcatheter modification of the mitral valve. Dr. Babaliaros is a consultant for Edwards Lifesciences; and is a consultant with equity in Transmural Systems. Dr. Babaliaros’s employer has research contracts for investigation of transcatheter aortic and mitral devices from Edwards Lifesciences, Abbott Vascular, Medtronic, and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Objectives: The purpose of this study was to evaluate tip-to-base intentional laceration of the anterior mitral leaflet to prevent left ventricular outflow tract obstruction (LAMPOON) in patients undergoing transcatheter mitral valve replacement (TMVR) in annuloplasty rings or surgical mitral valves., Background: LAMPOON is an effective adjunct to TMVR that prevents left ventricular outflow tract obstruction (LVOTO). Laceration is typically performed from the base to the tip of the anterior mitral leaflet. A modified laceration technique from leaflet tip to base may be effective in patients with a prosthesis that protects the aortomitral curtain., Methods: This is a multicenter, 21-patient, consecutive retrospective observational cohort. Patients underwent tip-to-base LAMPOON to prevent LVOTO and leaflet overhang, or therapeutically to lacerate a long anterior mitral leaflet risking or causing LVOTO. Outcomes were compared with findings from patients in the LAMPOON investigational device exemption trial with a prior mitral annuloplasty., Results: Twenty-one patients with a annuloplasty or valve prosthesis-protected mitral annulus underwent tip-to-base LAMPOON (19 preventive, 2 rescue). Leaflet laceration was successful in all and successfully prevented or treated LVOTO in all patients. No patients had significant LVOTO upon discharge. There were 2 cases of unintentional aortic valve injury (1 patient underwent emergency transcatheter aortic valve replacement and 1 patient underwent urgent surgical aortic valve replacement). In both cases, the patients had a supra-annular ring annuloplasty, and the retrograde aortic guiding catheter failed to insulate the guidewire lacerating surface from the aortic root. All patients survived to 30 days. Compared with classic retrograde LAMPOON, there was a trend toward shorter procedure time., Conclusions: Tip-to-base laceration is a simple, effective, and safe LAMPOON variant applicable to patients with an appropriately positioned mitral annular ring or bioprosthetic valve. Operators should take care to insulate the lacerating surface from adjacent structures., Competing Interests: Funding Support and Author Disclosures This work was supported by the Emory Structural Heart and Valve program intramural funds and by National Institutes of Health Grant No. Z01-HL006040. Dr. Lisko’s employer has contracts for BASILICA analysis with Medtronic and Edwards Lifesciences. Dr. Babaliaros has served as a consultant for Edwards Lifesciences and Abbott Vascular; has an employer with research contracts for clinical investigation of transcatheter aortic, mitral, and tricuspid devices from Edwards Lifesciences, Abbott Vascular, Medtronic, and Boston Scientific; and owns equity interest in Transmural Systems. Drs. Khan and Rogers have served as a proctor for Edwards Lifesciences and Medtronic. Drs. Khan, Lederman, and Rogers are co-inventors on patents, assigned to the National Institutes of Health, on devices for electrosurgical leaflet laceration. Dr. Paone has served as a consultant and proctor for Edwards Lifesciences. Dr. McCabe has served as consultant for Edwards Lifesciences, Boston Scientific, and Teleflex. Dr. Grubb has served as a speaker, proctor, and principal investigator for Edwards Lifesciences; served as a speaker, proctor, and advisory board member for Boston Scientific; and served as a speaker, proctor, principal investigator, advisory board member, and national principal investigator for Medtronic. Dr. Lederman has served as the principal investigator on a cooperative research and development agreement between National Institutes of Health and Edwards Lifesciences for transcatheter modification of the mitral valve. Dr. Greenbaum has served as a proctor for Edwards Lifesciences, Medtronic, and Abbott Vascular; owns an equity interest in Transmural Systems; and has an employer with research contracts for clinical investigation of transcatheter aortic, mitral, and tricuspid devices from Edwards Lifesciences, Abbott Vascular, Medtronic, and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021. Published by Elsevier Inc.)

Toxicity studies in animals are carried out to identify the intrinsic hazard of a substance to support risk assessment for humans. In order to identify opportunities to minimise animal use in regulatory toxicology studies, a review of current study designs was carried out. Pharmaceutical companies and contract research organisations in the UK shared data and experience of standard toxicology studies (ranging from one to nine months duration) in rodents and non-rodents; and carcinogenicity studies in the rat and mouse. The data show that variation in study designs was primarily due to (i) the number of animals used in the main study groups, (ii) the use of animals in toxicokinetic (TK) satellite groups, and (iii) the use of animals in off-treatment recovery groups. The information has been used to propose a series of experimental designs where small adjustments could reduce animal use in practice, while maintaining the scientific objectives., (Copyright © 2011. Published by Elsevier Inc.)