Outcomes of intravascular brachytherapy for recurrent drug-eluting in-stent restenosis.

OBJECTIVES: To examine the outcomes of vascular brachytherapy (VBT) for recurrent drug-eluting stents (DES) in-stent restenosis (ISR). BACKGROUND: Recurrent DES-ISR can be challenging to treat. VBT has been used with encouraging results. METHODS: We report the long-term outcomes of patients with recurrent DES-ISR treated with VBT between January 2014 and September 2018 at a tertiary care institution. The main outcome was target lesion failure (TLF), defined as the composite of clinically driven target lesion revascularization (TLR), target lesion myocardial infarction (MI), and target lesion-related cardiac death. Cox proportional hazards analysis was performed to identify variables associated with recurrent TLF. RESULTS: During the study period, 116 patients (143 lesions) underwent VBT. Median follow-up was 24.7 (14.5-35.4) months. The incidence of TLR, target-lesion MI, and TLF was 18.9%, 5.6%,and 20.1% at 1 year, and 29.4%, 10.5%, and 32.9% at 2 years.Initial presentation with acute coronary syndrome (ACS) was independently associated with TLF (hazard ratio = 1.975, 95% CI [1.120, 3.485], p = .019). Lesions treated with intravascular ultrasound (IVUS) guidance had a lower incidence of TLR (14.3% vs. 39.6%, log-rank p = .038), and a trend toward lower incidence of TLF (19% vs. 42.6%, log-rank p = .086). CONCLUSIONS: VBT can improve the treatment of recurrent DES-ISR, but TLF occurs in approximately one in three patients at 2 years. Initial presentation with ACS was associated with higher TLF and the use of IVUS with a trend for lower incidence of TLF.

MSH2-MSH6 stimulates DNA polymerase eta, suggesting a role for A:T mutations in antibody genes.

Activation-induced cytidine deaminase deaminates cytosine to uracil (dU) in DNA, which leads to mutations at C:G basepairs in immunoglobulin genes during somatic hypermutation. The mechanism that generates mutations at A:T basepairs, however, remains unclear. It appears to require the MSH2-MSH6 mismatch repair heterodimer and DNA polymerase (pol) eta, as mutations of A:T are decreased in mice and humans lacking these proteins. Here, we demonstrate that these proteins interact physically and functionally. First, we show that MSH2-MSH6 binds to a U:G mismatch but not to other DNA intermediates produced during base excision repair of dUs, including an abasic site and a deoxyribose phosphate group. Second, MSH2 binds to pol eta in solution, and endogenous MSH2 associates with the pol in cell extracts. Third, MSH2-MSH6 stimulates the catalytic activity of pol eta in vitro. These observations suggest that the interaction between MSH2-MSH6 and DNA pol eta stimulates synthesis of mutations at bases located downstream of the initial dU lesion, including A:T pairs.

Coronary Intravascular Brachytherapy for Recurrent Coronary Drug-Eluting Stent In-Stent Restenosis: A Systematic Review and Meta-Analysis.

OBJECTIVE: To examine the outcomes with intravascular brachytherapy (IVBT) in recurrent in-stent restenosis (ISR). BACKGROUND: Recurrent ISR can be challenging to treat and IVBT can be used for recurrent ISR but has received limited study. METHODS: We performed a systematic review and meta-analysis of five observational studies, including 917 patients (1014 lesions) with recurrent ISR, defined as having at least two prior ISR episodes with previous treatment with a stent, who underwent treatment with IVBT. Outcomes of interest included target vessel revascularization (TVR), myocardial infarction (MI), and all-cause mortality. RESULTS: During a mean follow-up of 24 ± 7 months, the incidence of TVR was 29.2% (95% CI 18.0-40.4%). The incidence of MI and all-cause mortality were 4.3% (95% CI 1.7%-6.9%) and 7.3% (95% CI 3.2-11.5%), respectively. At one- and two-years after PCI the incidence of TVR was 17.5% (95% CI 13.6%-21.4%) and 26.7% (95% CI 16.6%-36.9%), respectively and the incidence of MI was 3.1% (95% CI 2-4.2%) and 3.9% (95% CI 1-6.8%), respectively. CONCLUSION: Intravascular brachytherapy can be used to treat recurrent ISR, although TVR is needed in approximately one of four patients at two years.

Outcomes With Combined Laser Atherectomy and Intravascular Brachytherapy in Recurrent Drug-Eluting Stent In-Stent Restenosis.

BACKGROUND: Recurrent drug-eluting stents (DES) in-stent restenosis (ISR) can be challenging to treat. The combined use of excimer laser atherectomy (ELCA) and vascular brachytherapy (VBT) for this indication has received limited study. METHODS: We report the long-term outcomes of patients with recurrent DES ISR treated with combined VBT and ELCA from January 2014 to September 2018 at a single institution. Outcomes included target lesion failure (TLF), defined as the composite of clinically driven target lesion revascularization (TLR), target lesion myocardial infarction (MI), and target lesion-related cardiac death. RESULTS: During the study period, 116 patients (143 lesions) underwent VBT, of which 19 patients (19 lesions) underwent combined laser atherectomy and VBT. All procedures were successful without no-reflow or dissection. Two propensity-score matched cohorts (ELCA + VBT (n = 18) vs. VBT only (n = 18)) were compared. During a median follow-up of 25.5 (14.5-40) months, there was no difference in the incidence of TLF (38.9% vs. 38.9%, log-rank p = 0.688), target-lesion MI (5.6% vs. 5.6%, log-rank p = 0.915), or TLR (38.9% vs. 33.3%, log-rank p = 0.933) between both groups. There was no cardiac death related to the target lesion. CONCLUSIONS: When compared with VBT alone for the treatment of resistant DES ISR, combined use of ELCA and brachytherapy is associated with comparable long-term outcomes. ELCA should be considered in ISR lesions due to stent underexpansion.