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.

Outcomes Among Patients With Heart Failure With Reduced Ejection Fraction Undergoing Transcatheter Aortic Valve Replacement: Minimally Invasive Strategy Versus Conventional Strategy.

OBJECTIVES: To investigate the effect of TAVR technique on in-hospital and 30-day outcomes in patients with aortic stenosis (AS) and reduced ejection fraction (EF). BACKGROUND: Patients with AS and concomitant low EF may be at risk for adverse hemodynamic effects from general anesthesia utilized in transcatheter aortic valve replacement (TAVR) via the conventional strategy (CS). These patients may be better suited for the minimally invasive strategy (MIS), which employs conscious sedation. However, data are lacking that compare MIS to CS in patients with AS and concomitant low EF. METHODS: In this retrospective study, we identified all patients with low EF (<50%) undergoing transfemoral MIS-TAVR vs CS-TAVR between March 2011 and May 2018. Our primary endpoint was defined as the composite of in-hospital mortality and major periprocedural bleeding or vascular complications. RESULTS: Two hundred and seventy patients had EF <50%, while 154 patients had EF ≤35%. Overall, a total of 236 patients were in the MIS group and 34 were in the CS group. Baseline characteristics between the two groups were similar except for Society of Thoracic Surgeons (STS) score (MIS 8.4 ± 5.1 vs CS 11.7 ± 6.8; P<.01). There were no differences between the two groups in incidence of the primary endpoint (MIS 5.5% vs CS 8.8%; odds ratio for MIS, 0.60; 95% confidence interval, 0.16-2.23; P=.45). CONCLUSIONS: In patients with severe AS and reduced EF, MIS was not associated with adverse in-hospital or 30-day clinical outcomes compared with CS. In these patients, MIS may be a suitable alternative to CS without compromising clinical outcomes.

Associations Between Cardiac Troponin, Mechanism of Myocardial Injury, and Long-Term Mortality After Noncardiac Vascular Surgery.

BACKGROUND: The time-sensitive hazard of perioperative cardiac troponin T (cTnT) elevation and whether long-term mortality differs by mechanism of myocardial injury are poorly understood. METHODS AND RESULTS: In this observational study of 12 882 patients who underwent noncardiac vascular surgery, patients were assessed for cTnT sampling within 96 hours postoperatively. Mortality out to 5-years was stratified by cTnT level and mechanism of myocardial injury. During a median follow-up of 26.9 months, there were 2149 (16.7%) deaths. By multivariable Cox proportional hazards analysis, there was a graded increase in mortality with any detectable cTnT compared to <0.01 ng/mL; cTnT 0.01 to 0.029 ng/mL hazard ratio (HR) 1.54 (95% CI 1.18-2.00, P=0.002), 0.03 to 0.099 ng/mL HR 1.86 (95% CI 1.49-2.31, P<0.001), 0.10 to 0.399 ng/mL HR 1.83 (95% CI 1.46-2.31, P<0.001), ≥0.40 ng/mL HR 2.62 (95% CI 2.06-3.32, P<0.001). Mortality for each mechanism of injury was greater than for patients with normal cTnT; baseline cTnT elevation HR 1.71 (95% CI 1.31-2.24; P<0.001), Type 2 myocardial infarction HR 1.88 (95% CI 1.57-2.24; P<0.001), Type 1 MI HR 2.56 (95% CI 2.56, 1.82-3.60; P<0.001). On Kaplan-Meier analysis, long-term survival did not differ between mechanisms. The hazard of mortality was greatest within the first 10 months postsurgery. Consistent results were obtained in confirmatory propensity-score matched analyses. CONCLUSIONS: Any detectable cTnT ≥0.01 ng/mL is associated with increased long-term mortality after vascular surgery. This risk is greatest within the first 10 months postoperatively. While short-term mortality is greatest with Type 1 myocardial infarction, long-term mortality appears independent of the mechanism of injury.

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.