Transcatheter Valve Implantation for Failed Surgical Aortic and Mitral Bioprostheses: A Single-Center Experience.

OBJECTIVES: We share our center's experience with the use of transcatheter valvular therapies in the setting of failed bioprostheses. BACKGROUND: As medicine continues to advance, the lifespan of individuals continues to increase, and current surgical valvular therapies begin to degrade prior to a person's end of life. It is important to evaluate the efficacy and durability of transcatheter valves within failed surgical bioprostheses. METHODS: Baseline characteristics, periprocedural complications, and long-term outcomes were collected and assessed in patients who received transcatheter valves for failing surgical aortic valve bioprostheses and mitral valve and ring bioprostheses from March 2011 to July 2018. RESULTS: From our cohort of 1048 patients, we identified 45 individuals (4.3%) who underwent transcatheter replacement of a failed bioprosthetic valve or ring. Mean age at presentation was 80.8 ± 10.7 years and 75.5 ± 9.3 years, mean STS score was 9.3 ± 5.1 and 13.3 ± 8.7, and mean time to failure was 12.0 ± 5.2 years and 7.3 ± 4.5 years for aortic and mitral positions, respectively. At 1 year, time to event analysis suggested a 16.4% mortality rate for aortic replacement and 12.8% mortality rate for mitral replacement. CONCLUSIONS: We demonstrate outcomes from one of the largest single-center United States based cohorts of transcatheter replacements of failed surgical bioprostheses. Our center has demonstrated that it is feasible to pursue the replacement of failed surgical bioprostheses in the aortic and mitral positions with transcatheter valves given appropriate patient selection.

Risk Prediction Model for Cardiac Implantable Electronic Device Implantation After Transcatheter Aortic Valve Replacement.

OBJECTIVES: The aim of this study was to develop and validate a risk prediction model for high-grade atrioventricular block requiring cardiac implantable electronic device (CIED) implantation after transcatheter aortic valve replacement (TAVR). BACKGROUND: High-grade atrioventricular block requiring CIED remains a significant sequelae following TAVR. Although several pre-operative characteristics have been associated with the risk of post-operative CIED implantation, an accurate and validated risk prediction model is not established yet. METHODS: This was a single center, retrospective study of consecutive patients who underwent TAVR from March 10, 2011, to October 8, 2018. This cohort sample was randomly divided into a derivation cohort (group A) and a validation cohort (group B). A scoring system for risk prediction of post-TAVR CIED implantation was devised using logistic regression estimates in group A and the calibration and validation were done in group B. RESULTS: A total of 1,071 patients underwent TAVR during the study period. After excluding pre-existing CIED, a total of 888 cases were analyzed (group A: 507 and group B: 381). Independent predictive variables were as follows: self-expanding valve (1 point), hypertension (1 point), pre-existing first-degree atrioventricular block (1 point), and right bundle branch block (2 points). The resulting score was calculated from the total points. The internal validation in group B showed an ideal linear relationship in calibration plot (R2 = 0.933) and a good predictive accuracy (area under the curve: 0.693; 95% confidence interval: 0.627 to 0.759). CONCLUSIONS: This prediction model accurately predicts post-operative risk of CIED implantation with simple pre-operative parameters.

Management and outcomes in mitral valve prolapse with ventricular arrhythmias undergoing ablation and/or implantation of ICDs.

BACKGROUND: While there is an association between isolated mitral valve prolapse (MVP) and sudden cardiac arrest (SCA), the baseline characteristics and outcomes of patients with isolated MVP who experience ventricular arrhythmias (VAs) and then subsequently undergo catheter ablation and/or implantable cardioverter defibrillator (ICD) implantation are unknown. METHODS: We performed a retrospective review of all patients at the Cleveland Clinic with isolated MVP between 1997 and 2016 who underwent VA catheter ablation or secondary prevention ICD implantation. RESULTS: Of 617 screened patients, we identified 43 patients with isolated MVP and significant VA who underwent ICD placement (n = 13, 30%) or catheter ablation (n = 30, 70%). Both leaflets were most commonly involved (n = 22, 52%) with posterior MVP being next most common (n = 15, 36%). The most common foci of VA origin was the left ventricular papillary muscle (n = 9, 27%). Ablation was successful in the majority of cases (n = 20, 65%). At a mean follow-up of 2.5 years, 11 patients (26%) had recurrent VT. CONCLUSIONS: Patients with isolated MVP and VA were more likely to have bileaflet prolapse and at least moderate mitral regurgitation. VA originated more commonly from left-sided foci. While ablation was acutely successful in the majority of cases, there was still a moderate rate of VA recurrence. There is still more study needed on factors that will predict malignant VAs and management of these VAs in the MVP population.

In vivo selection of hematopoietic progenitor cells and temozolomide dose intensification in rhesus macaques through lentiviral transduction with a drug resistance gene.

Major limitations to gene therapy using HSCs are low gene transfer efficiency and the inability of most therapeutic genes to confer a selective advantage on the gene-corrected cells. One approach to enrich for gene-modified cells in vivo is to include in the retroviral vector a drug resistance gene, such as the P140K mutant of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT*). We transplanted 5 rhesus macaques with CD34+ cells transduced with lentiviral vectors encoding MGMT* and a fluorescent marker, with or without homeobox B4 (HOXB4), a potent stem cell self-renewal gene. Transgene expression and common integration sites in lymphoid and myeloid lineages several months after transplantation confirmed transduction of long-term repopulating HSCs. However, all animals showed only a transient increase in gene-marked lymphoid and myeloid cells after O6-benzylguanine (BG) and temozolomide (TMZ) administration. In 1 animal, cells transduced with MGMT* lentiviral vectors were protected and expanded after multiple courses of BG/TMZ, providing a substantial increase in the maximum tolerated dose of TMZ. Additional cycles of chemotherapy using 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) resulted in similar increases in gene marking levels, but caused high levels of nonhematopoietic toxicity. Inclusion of HOXB4 in the MGMT* vectors resulted in no substantial increase in gene marking or HSC amplification after chemotherapy treatment. Our data therefore suggest that lentivirally mediated gene transfer in transplanted HSCs can provide in vivo chemoprotection of progenitor cells, although selection of long-term repopulating HSCs was not seen.