Clinical outcomes according to lesion complexity in high bleeding risk patients treated with 1-month dual antiplatelet therapy following PCI: Analysis from the Onyx ONE clear study.

OBJECTIVES: To compare clinical outcomes in high bleeding risk (HBR) patients with and without complex percutaneous coronary intervention (PCI) treated with Resolute Onyx zotarolimus-eluting stents (ZES) after 1-month dual antiplatelet therapy (DAPT). BACKGROUND: PCI with 1-month DAPT has been demonstrated to be safe in HBR patients treated with Resolute Onyx ZES. Whether these outcomes are consistent in patients with complex lesions is uncertain. METHODS: Among HBR patients who were event-free 1 month after PCI with ZES and treated thereafter with single antiplatelet therapy (SAPT), the clinical outcomes between 1 month and 1 year were compared after complex PCI (3 vessels treated, ≥ 3 lesions treated, total stent length > 60 mm, bifurcation with ≥ 2 stents implanted, atherectomy, or left main, surgical bypass graft or chronic total occlusion PCI) versus noncomplex PCI. Propensity score adjustment was performed to adjust for baseline differences among complex and noncomplex patients. RESULTS: Complex patients (N = 401, 26.6% of total) had a higher prevalence of hyperlipidemia, diabetes mellitus and previous myocardial infarction (MI). Between 1 month and 1 year, rates of MI (7.1% vs. 4.0%, p = 0.02) and cardiac death/MI (9.3% vs. 6.1%, p = 0.04) were higher among complex versus noncomplex patients, although stent thrombosis rates were similar. After adjustment for baseline characteristics, differences in outcomes were no longer significant between groups. CONCLUSIONS: Higher rates of ischemic outcomes in complex PCI patients were largely explained by baseline clinical differences, rather than lesion complexity, among HBR patients treated with 1-month DAPT following PCI with Resolute Onyx ZES.

One-Month Dual Antiplatelet Therapy Following Percutaneous Coronary Intervention With Zotarolimus-Eluting Stents in High-Bleeding-Risk Patients.

BACKGROUND: Despite treatment guidance endorsing shortened dual antiplatelet therapy (DAPT) duration in high bleeding risk (HBR) patients after drug-eluting stents, limited evidence exists to support these recommendations. The present study was designed to examine the safety and effectiveness of 1-month DAPT duration following percutaneous coronary intervention with zotarolimus-eluting stents in HBR patients. METHODS: Onyx ONE Clear was a prospective, multicenter, nonrandomized study evaluating the safety and effectiveness of 1-month DAPT followed by single antiplatelet therapy in HBR patients undergoing percutaneous coronary intervention with Resolute Onyx drug-eluting stents. The primary analysis of cardiac death or myocardial infarction between 1 month and 1 year was performed in the prespecified one-month clear population of patients pooled from the Onyx ONE US/Japan study and Onyx ONE randomized controlled trial. One-month clear was defined as DAPT adherence and without major adverse events during the first month following percutaneous coronary intervention. RESULTS: Among patients enrolled in Onyx ONE US/Japan (n=752) and Onyx ONE randomized controlled trial (n=1018), 1506 patients fulfilled one-month clear criteria. Mean HBR characteristics per patient was 1.6 with 44.7% having multiple risks. By 2 months and 1 year, respectively, 96.9% and 89.3% of patients were taking single antiplatelet therapy. Between 1 month and 1 year, the rate of the primary end point was 7.0%. The 1-sided upper 97.5% CI was 8.4%, less than the performance goal of 9.7% (P<0.001). CONCLUSIONS: Among HBR patients who were event free before DAPT discontinuation at 1 month, favorable safety and effectiveness through 1 year support treatment with Resolute Onyx drug-eluting stents as part of an individualized strategy for shortened DAPT duration following percutaneous coronary intervention. Registration: URL: https://www.clinicaltrials.gov; Unique identifier NCT03647475.

One-Month Dual Antiplatelet Therapy Following Percutaneous Coronary Intervention With Zotarolimus-Eluting Stents in High-Bleeding-Risk Patients

BACKGROUND: Despite treatment guidance endorsing shortened dual antiplatelet therapy (DAPT) duration in high bleeding risk (HBR) patients after drug-eluting stents, limited evidence exists to support these recommendations. The present study was designed to examine the safety and effectiveness of 1-month DAPT duration following percutaneous coronary intervention with zotarolimus-eluting stents in HBR patients. METHODS: Onyx ONE Clear was a prospective, multicenter, nonrandomized study evaluating the safety and effectiveness of 1-month DAPT followed by single antiplatelet therapy in HBR patients undergoing percutaneous coronary intervention with Resolute Onyx drug-eluting stents. The primary analysis of cardiac death or myocardial infarction between 1 month and 1 year was performed in the prespecified one-month clear population of patients pooled from the Onyx ONE US/Japan study and Onyx ONE randomized controlled trial. One-month clear was defined as DAPT adherence and without major adverse events during the first month following percutaneous coronary intervention. RESULTS: Among patients enrolled in Onyx ONE US/Japan (n=752) and Onyx ONE randomized controlled trial (n=1018), 1506 patients fulfilled one-month clear criteria. Mean HBR characteristics per patient was 1.6 with 44.7% having multiple risks. By 2 months and 1 year, respectively, 96.9% and 89.3% of patients were taking single antiplatelet therapy. Between 1 month and 1 year, the rate of the primary end point was 7.0%. The 1-sided upper 97.5% CI was 8.4%, less than the performance goal of 9.7% (P<0.001). CONCLUSIONS: Among HBR patients who were event free before DAPT discontinuation at 1 month, favorable safety and effectiveness through 1 year support treatment with Resolute Onyx drug-eluting stents as part of an individualized strategy for shortened DAPT duration following percutaneous coronary intervention.

High-risk patients with inoperative aortic stenosis: use of transapical, transaortic, and transcarotid techniques.

BACKGROUND: Patient characteristics and procedural outcomes from nontransfemoral (non-TF) transcatheter aortic valve replacement (TAVR) in high-risk or inoperable patients with aortic stenosis have been incompletely reported. The purpose of this study was to compare outcomes with non-TF TAVR access techniques including transapical (TA), transaortic (TAo), and transcarotid (TC) TAVR with a balloon-expandable valve. METHODS: A retrospective review was performed of all patients undergoing TA, TAo, and TC TAVR from 2007 to 2013 at Emory University. Preoperative risk factors and postoperative outcomes were evaluated using Valve Academic Research Consortium-2 definitions. RESULTS: Of 469 patients undergoing TAVR during that period at our institution, 139 underwent TA TAVR, 35 had Tao TAVR, and 11 had TC TAVR. Patients undergoing TC TAVR were younger than those undergoing TA TAVR and TAo TAVR (mean ages: TC, 68.9 ± 23.6 years; TA, 81.3 ± 7.7 years; Tao, 83.8 ± 8.3 years; p = 0.017). Most patients undergoing TAo TAVR were women (82.9%), whereas patients undergoing TA TAVR were more likely to be men (62.6%). Slightly more than half of patients undergoing TA TAVR (54.7%) and TC (54.6%) TAVR had undergone previous coronary artery bypass grafting (CABG), whereas no patients underwent TAo TAVR (0%). There was no preoperative difference in ejection fraction, New York Heart Association classification, significant chronic obstructive pulmonary disease, and The Society of Thoracic Surgeons predicted risk of mortality between TA TAVR, Tao TAVR, and TC TAVR, respectively. Average postoperative length of stay was 9 to 11 days and was similar among groups (p = 0.22). There were 13 (9.4%) TA TAVR operative deaths and 4 (11.4%) operative deaths in the TAo TAVR group. There were no deaths in the TC TAVR group. CONCLUSIONS: In high-risk and inoperable patients who are not candidates for TF TAVR, careful selection of alternative access options can lead to excellent and comparable postoperative outcomes.

GTP cyclohydrolase I gene polymorphisms are associated with endothelial dysfunction and oxidative stress in patients with type 2 diabetes mellitus.

BACKGROUND: The genetic background of atherosclerosis in type 2 diabetes mellitus (T2DM) is complex and poorly understood. Studying genetic components of intermediate phenotypes, such as endothelial dysfunction and oxidative stress, may aid in identifying novel genetic components for atherosclerosis in diabetic patients. METHODS: Five polymorphisms forming two haplotype blocks within the GTP cyclohydrolase 1 gene, encoding a rate limiting enzyme in tetrahydrobiopterin synthesis, were studied in the context of flow and nitroglycerin mediated dilation (FMD and NMD), intima-media thickness (IMT), and plasma concentrations of von Willebrand factor (vWF) and malondialdehyde (MDA). RESULTS: Rs841 was associated with FMD (p = 0.01), while polymorphisms Rs10483639, Rs841, Rs3783641 (which form a single haplotype) were associated with both MDA (p = 0.012, p = 0.0015 and p = 0.003, respectively) and vWF concentrations (p = 0.016, p = 0.03 and p = 0.045, respectively). In addition, polymorphism Rs8007267 was also associated with MDA (p = 0.006). Haplotype analysis confirmed the association of both haplotypes with studied variables. CONCLUSIONS: Genetic variation of the GCH1 gene is associated with endothelial dysfunction and oxidative stress in T2DM patients.

Comparison of transfemoral transcatheter aortic valve replacement performed in the catheterization laboratory (minimalist approach) versus hybrid operating room (standard approach): outcomes and cost analysis.

OBJECTIVES: The aim of this study was to compare transfemoral transcatheter aortic valve replacement (TF TAVR) performed in a catheterization laboratory (minimalist approach [MA]) with TF TAVR performed in a hybrid operating room (standard approach [SA]). BACKGROUND: A MA-TF TAVR can be performed without general anesthesia, transesophageal echocardiography, or a surgical hybrid room. The outcomes and cost of MA-TF TAVR compared with those of the SA have not been described. METHODS: Patients who underwent elective, percutaneous TF TAVR using the Edwards Sapien valve (Edwards Lifesciences, Irvine, California) were studied. Baseline characteristics, outcomes, and hospital costs of MA-TF TAVR and SA-TF TAVR were compared. RESULTS: A total of 142 patients were studied (MA-TF TAVR, n = 70 and SA-TF TAVR, n = 72). There were no differences in baseline comorbidities (Society of Thoracic Surgeons score, 10.6 ± 4.3 vs. 11.4 ± 5.8; p = 0.35). All procedures in the MA-TF TAVR group were successful; 1 patient was intubated. Three patients in the SA-TF TAVR group had procedure-related death. Procedure room time (150 ± 48 min vs. 218 ± 56 min, p < 0.001), total intensive care unit time (22 h vs. 28 h, p < 0.001), length of stay from procedure to discharge (3 days vs. 5 days, p < 0.001), and cost ($45,485 ± 14,397 vs. $55,377 ± 22,587, p < 0.001) were significantly less in the MA-TF TAVR group. Mortality at 30 days was not significantly different in the MA-TF TAVR group (0 vs. 6%, p = 0.12) and 30-day stroke/transient ischemic attack was similar (4.3% vs. 1.4%, p = 0.35). Moderate or severe paravalvular leak and device success were similar in the MA-TF TAVR and SA-TF TAVR groups (3% vs. 5.8%, p = 0.4 and 90% vs. 88%, p = 0.79, respectively) at 30 days. At a median follow-up of 435 days, there was no significant difference in survival (MA-TF TAVR, 83% vs. SA-TF TAVR, 82%; p = 0.639). CONCLUSIONS: MA-TF TAVR can be performed with minimal morbidity and mortality and equivalent effectiveness compared with SA-TF TAVR. The shorter length of stay and lower resource use with MA-TF TAVR significantly lowers hospital costs.

Transcatheter aortic valve replacement has improved short-term but similar midterm outcomes in isolated aortic valve replacement after prior coronary artery bypass grafting.

BACKGROUND: An increasing number of patients with prior coronary artery bypass grafting (CABG) now present with severe aortic stenosis. The proposed benefit of surgical (SAVR) vs transcatheter aortic valve replacement (TAVR) is unknown. The objective of this study was to compare short-term and midterm outcomes of patients undergoing isolated SAVR vs TAVR in those with prior CABG. METHODS: A retrospective analysis was performed of 255 patients who underwent isolated SAVR after prior CABG from January 2002 to February 2013 at Emory University. Outcomes of 148 patients undergoing SAVR (2002 to 2013) and 107 undergoing TAVR (2007 to 2013) were compared using multivariable logistic regression and analysis of variance techniques, adjusting for The Society of Thoracic Surgeons (STS) risk score. Kaplan-Meier plots were used to determine survival rates, and midterm survival between groups was compared using the Cox proportional hazards model. RESULTS: TAVR patients were older (79.8 ± 7.9 years vs 72.5 ± 8.8 years, p < 0.001) but were gender equivalent (female: 24% vs 22%, p = 0.61). The preoperative ejection fraction was similar between groups (TAVR: 0.433 ± 0.131 vs SAVR: 0.469 ± 0.148%, p = 0.60). The TAVR group had a significantly higher the STS risk scores (11.8% vs 7.1%, p < 0.001). All-cause 30-day mortality was 1.9% for TAVR and 4.1% for SAVR (p = 0.32), a result that marginally favors TAVR after risk adjustment (adjusted odds ratio, 0.19; p = 0.07). Postoperative morbidity and resource utilization was significantly higher in the SAVR patients. Midterm survival was similar between the two groups after adjustment (adjusted hazard ratio, 0.78, p = 0.46). CONCLUSIONS: Excellent outcomes can be achieved in SAVR or TAVR after prior CABG. Although TAVR improves short-term outcomes and resource utilization compared with SAVR, midterm mortality outcomes are similar.

Impact of varying degrees of renal dysfunction on transcatheter and surgical aortic valve replacement.

BACKGROUND: Renal impairment portends adverse outcomes in patients undergoing valvular heart surgery. The relationship between renal dysfunction in patients undergoing transcatheter aortic valve replacement (TAVR) is incompletely understood. METHODS: A retrospective review of 1336 patients undergoing surgical aortic valve replacement (SAVR; 2002-2012) and 321 patients undergoing TAVR (2007-2012) was performed. Patients were divided into 3 glomerular filtration rate (GFR) groups: GFR greater than 60 mL/min, GFR 31 to 60 mL/min, and GFR 30 mL/min or less. Logistic and linear regression analysis was performed to estimate the TAVR effect on outcomes. Risk adjustments were made using the Society for Thoracic Surgeons (STS) predicted risk of mortality (PROM). RESULTS: TAVR patients were older (82 vs 65 years; P < .001), had a poorer ejection fraction (48% vs 53%; P < .001), were more likely female (45% vs 41%; P = .23), and had a higher STS PROM (11.9% vs 4.6%; P < .001). In-hospital mortality rates for TAVR and SAVR were 3.5% and 4.1%, respectively (P = .60), a result that marginally favors TAVR after risk adjustment (adjusted odds ratio = .52, P = .06). In SAVR patients, worsening preoperative renal failure was associated with increased in-hospital mortality (P = .004) and hospital (P < .001) and intensive care unit (ICU) (P < .001) lengths of stay. In contrast, worsening renal function did not influence in-hospital mortality (P = .78) and hospital (P < .23) and ICU (P = .88) lengths of stay in TAVR patients. CONCLUSIONS: Worsening renal function was associated with increased in-hospital mortality, hospital length of stay, and ICU length of stay in SAVR patients, but not in TAVR patients. This unexpected finding may have important clinical implications in patients with aortic stenosis and preoperative renal dysfunction.