SUMMARYTo obtain greater insight into atrial remodeling at the molecular level we analyzed the changes in gene expression in human atrial tissue between patients with chronic atrial fibrillation (AF) and those with normal sinus rhythm (NSR). cDNA microarray analysis was used to identify genes differentially expressed during sustained AF of more than 6 months (n = 9, mean age, 45 ± 12, 6 males and 3 females) as compared to those with NSR (n = 9, mean age, 47 ± 13, 6 males and 3 females). Western blot analysis was performed to confirm the altered gene expression and to establish the changes in protein expression. DNA gel electrophoresis to establish DNA ladder formation, which was associated with apoptosis in response to chronic AF, was performed. Microscopic findings were observed via electron microscopy. In the microarray analysis, out of 8,167 candidate genes, 66 genes showed a significant change in the expression level in the patients with chronic AF, which was in contrast to those with NSR. Among those, 31 genes were consistently downregulated and 35 up-regulated more than 2-fold. The relative amounts of the Bcl-2 and p27 in the atrial tissue were decreased and angiotensin II type 2 (AT2) receptor and p21 were increased in the patients with chronic AF as compared to those with NSR. The atrial cardiomyocytes in chronic AF showed a prominent DNA ladder, which is a biochemical hallmark of apoptosis. The expression of Bcl-2, AT2 receptor, p21, and p27 were consistent with a significant role in the apoptosis of cardiac myocytes in the patients with chronic AF. (Int Heart J 2005; 46: 383-395)
In latecomers with STEMI, RAS inhibition improved long-term clinical outcomes after a successful PCI, even in patients with low risk who had relatively preserved LVEF.
Background: Ticagrelor monotherapy after 3 months dual antiplatelet therapy (DAPT) with aspirin and ticagrelor can reduce bleeding without increasing ischemic events after percutaneous coronary intervention (PCI). However, the impact of this approach among the patient with diabetes remains unknown.Methods: This was a sub-analysis of the Ticagrelor Monotherapy after 3 months in the Patients Treated with New Generation Sirolimus Eluting Stent for Acute Coronary Syndrome (TICO) trial. After successful PCI, the patients were randomly assigned to ticagrelor monotherapy after 3-months DPAT or to ticagrelor-based 12-months DAPT. We compared ischemic events and bleeding events between the patients with diabetes and without diabetes for 12 months. Ischemic events were defined as death, myocardial infarction, ischemic stroke, transient ischemic attack, stent thrombosis, and any revascularizations. Bleeding events were defined according to the Thrombolysis in Myocardial Infarction (TIMI) criteria and Bleeding Academic Research Consortium (BARC) definition.Results: Between August 2015 and October 2018, 3,056 patients were enrolled in the TICO trial, of which 835 (27.3%) had diabetes mellitus. Diabetes mellitus was associated with all evaluated ischemic and bleeding events. No significant differences in any ischemic events were observed in patients with diabetes between ticagrelor monotherapy after 3-months DAPT and ticagrelor-based 12-months DAPT (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.45–1.52, p = 0.540). In patients with diabetes, the overall incidence of bleeding complications during the 12-months follow-up period did not differ between the two treatment groups (HR 0.83, 95% CI 1.48–1.43, p = 0.505). However, ticagrelor monotherapy was significantly reduced both any TIMI bleeding and BARC three or five bleeding events in diabetes patients in the 3-months landmark analysis, after 3-months DAPT period (HR 0.20, 95% CI 0.07–0.59, p = 0.003).Conclusion: In diabetic patients, ticagrelor monotherapy showed a lower incidence of bleeding complications after 3-months DAPT period, without increasing ischemic complications, compared with ticagrelor-based 12-months DAPT (ClinicalTrials.gov Identifier: NCT02494895).
Background-There are limited data on the frequency of and factors associated with quantitative coronary angiography (QCA)-defined longitudinal stent deformation (LSD) in various contemporary drug-eluting stents platforms. This study sought to evaluate the predictors of LSD and its long-term clinical implication. Methods and Results-A patient-level pooled analysis was performed with 7350 lesions in 5871 patients treated with platinum-chromium-based everolimus-eluting stent (Promus Element), cobalt-chromium-based everolimus-eluting stent (Promus/Xience V), or cobalt-chromium-based zotarolimus-eluting stent (Endeavor Resolute). QCA was performed to analyze differences of stent length between immediate post-deployment and final post-procedure. Independent factors associated with LSD were identified. Clinical outcomes at 3 years were compared between those with and without QCAbased LSD. The frequency of QCA-based LSD was 1.12% (82 cases). Nine of these cases were angiographically overt. Left main or ostial lesion, bifurcation treatment with provisional side branch stenting or ballooning, additional downstream intervention of a distal lesion, intravascular ultrasound use, and adjunctive post-dilatation were independently associated with QCA-based LSD. The type of stent was not associated with QCA-based LSD. Rates of target lesion failure were nominally higher in lesions with QCA-based LSD than in those without (8.97% versus 5.88%; hazard ratio, 1.415; 95% confidence interval, 0.631-3.175; P=0.399). Conclusions-LSD is uncommon with contemporary drug-eluting stents, regardless of the type of stent platform. LSD is mainly associated with procedural factors, especially with additional downstream procedures which require the passage of devices through the stent. Careful manipulation of poststent imaging or procedural devices is required to prevent LSD. More data are needed to clarify the impact of LSD on clinical events. (Circ Cardiovasc Interv. 2017;10:e005518.
Background: This study evaluated the association of body mass index (BMI) with adverse clinical outcomes during chronic maintenance antiplatelet monotherapy after percutaneous coronary intervention (PCI) with drug-eluting stents (DES).
Methods and Results:Overall, 5,112 patients were stratified (in kg/m 2 ) into underweight (BMI ≤18.4), normal weight (18.5-22.9), overweight (23.0-24.9), obesity (25.0-29.9) and severe obesity (≥30.0) categories with randomized antiplatelet monotherapy of aspirin 100 mg or clopidogrel 75 mg once daily for 24 months. The primary endpoint was the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome and major bleeding of Bleeding Academic Research Consortium type ≥3. Compared with normal weight, the risk of primary composite outcomes was higher in the underweight (hazard ratio [HR] 2. 183 [1.199-3.974]), but lower in the obesity ) and severe obesity (HR 0.518 [0.278-0.966]) categories, which is partly driven by the difference in all-cause death. The risk of major bleeding was significantly higher in the underweight ) than in the normal weight category. A decrease in categorical BMI was independently associated with the increased risk of primary composite outcomes.
Conclusions:Lower BMI is associated with a higher risk of primary composite outcomes, which is primarily related to the events of all-cause death or major bleeding during chronic maintenance antiplatelet monotherapy after PCI with DES.
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