Background Despite improving experience and techniques, ischemic and bleeding complications after transcatheter aortic valve implantation (TAVI) remain prevalent and impair survival. Current ...guidelines recommend the temporary addition of clopidogrel in the initial period after TAVI to prevent thromboembolic events. However, explorative studies suggest that this is associated with a higher rate of major bleeding without a decrease in thromboembolic complications. Methods The POPular TAVI trial is a prospective randomized, controlled, open-label multicenter clinical trial to test the hypothesis that monotherapy with aspirin or oral anticoagulation (OAC) after TAVI is safer than the addition of clopidogrel for 3 months, without compromising clinical benefit. This trial encompasses 2 cohorts: cohort A, patients are randomized 1:1 to aspirin vs aspirin + clopidogrel, and cohort B, patients on OAC therapy are randomized 1:1 to OAC vs OAC + clopidogrel. Primary outcome is freedom from non–procedure-related bleeding at 1 year. Secondary net-clinical benefit outcome is freedom from the composite of cardiovascular death, non–procedural-related bleeding, myocardial infarction, or stroke at 1 year. The primary outcome is analyzed for superiority, whereas the secondary outcome is analyzed for noninferiority. Recruitment began in February 2014, and the trial will continue until a total of 1,000 patients (684 expected in cohort A and 316 in cohort B) are included and followed up for 1 year. Summary The POPular TAVI trial (NCT02247128) is the first large randomized controlled trial to test if monotherapy with aspirin or OAC vs additional clopidogrel after TAVI reduces bleeding with a favorable net-clinical benefit.
Abstract Objectives The goal of this study was to compare survival between transcatheter mitral valve (MV) repair using MitraClip system (Abbott Vascular, Santa Clara, California), MV-surgery, and ...conservative treatment in high-surgical-risk patients symptomatic with severe mitral valve regurgitation (MR). Background Up to 50% of patients with symptomatic severe MR are denied for surgery due to high perioperative risk. Transcatheter MV repair might be an alternative. Methods Consecutive patients (n = 139) treated with transcatheter MV repair were included. Comparator surgically (n = 53) and conservatively (n = 59) treated patients were identified retrospectively. Surgical risk was based on the logistic European System for Cardiac Operative Risk Evaluation (log EuroSCORE) or the presence of relevant risk factors, as judged by the heart team. Results The log EuroSCORE was higher in the transcatheter MV repair group (23.9 ± 16.1%) than in the surgically (14.2 ± 8.9%) and conservatively (18.7 ± 13.2%, p < 0.0001) treated patients. Left ventricular ejection fraction was higher in surgical patients (43.9 ± 14.4%, p = 0.003), with similar values for the transcatheter MV repair (36.8 ± 15.3%) and conservatively treated (34.5 ± 16.5%) groups. After 1 year of follow-up, the transcatheter MV repair and surgery groups showed similar survival rates (85.8% and 85.2%, respectively), whereas 67.7% of conservatively treated patients survived. The same trend was observed after the second and third years. After weighting for propensity score and controlling for risk factors, both the transcatheter MV repair (hazard ratio HR: 0.41, 95% confidence interval CI: 0.22 to 0.78, p = 0.006) and surgical (HR: 0.52, 95% CI: 0.30 to 0.88, p = 0.014) groups showed better survival than the conservatively treated group. The transcatheter MV repair and surgical groups did not differ (HR: 1.25, 95% CI: 0.72 to 2.16, p = 0.430). Conclusions Despite a higher log EuroSCORE, high-surgical-risk patients with symptomatic severe MR treated with transcatheter MV repair show similar survival rates compared with surgically treated patients, with both displaying survival benefit compared with conservative treatment.
Mean follow-up in previous studies on the effect of prosthesis-patient mismatch on long-term survival after aortic valve replacement (AVR) is confined to a maximum of one decade. This retrospective ...longitudinal cohort study was performed to determine the effect on long-term survival of prosthesis-patient mismatch after AVR with a mean follow-up of almost two decades.
Kaplan-Meier survival analysis was used to determine long-term survival after AVR in a cohort of 673 consecutive patients, divided into 163 patients (24.2%) with prosthesis-patient mismatch (indexed effective orifice area ≤ 0.85 cm(2)/m(2)) and 510 patients (75.8%) without prosthesis-patient mismatch (indexed effective orifice area >0.85 cm(2)/m(2)). Effective orifice area values of the prosthetic valves were retrieved from the literature or obtained from the charts of the prosthetic valve manufacturers. Cox multiple regression analysis was used to identify possible independent predictors, including prosthesis-patient mismatch, of decreased long-term survival.
Median sizes of the implanted mechanical (n = 430) and biologic (n = 243) prostheses were 25 and 23 mm, respectively. Mean follow-up after AVR was 17.8 ± 1.8 years. Prosthesis-patient mismatch was not an independent predictor of decreased long-term survival (hazard ratio, 0.828; 95% confidence interval, 0.669 to 1.025; p = 0.083). Severe prosthesis-patient mismatch (indexed effective orifice area ≤ 0.65 cm(2)/m(2)), occurring in only 17 patients (2.5%), showed an insignificant trend toward decreased long-term survival (hazard ratio, 1.68; 95% confidence interval, 0.97 to 2.91; p = 0.066).
Prosthesis-patient mismatch was not an independent predictor of decreased long-term survival after AVR.
Abstract Objective There is a paucity of data on long-term survival of new-onset postoperative atrial fibrillation (POAF) after cardiac surgery. Also, mean follow-up in previous studies is confined ...to a maximum of one decade. This retrospective, longitudinal cohort study was performed to determine the effect on long-term survival of new-onset POAF after aortic valve replacement (AVR) over a mean follow-up of almost 2 decades. Methods Kaplan-Meier survival analysis was used to determine long-term survival after AVR, performed between January 1, 1990, and January 1, 1994, in 569 consecutive patients without a history of atrial fibrillation, divided into 241 patients (42.4%) with and 328 patients (57.6%) without new-onset POAF. New-onset POAF was considered in multivariable analysis for decreased long-term survival. After AVR, patients with new-onset POAF were treated with the aim to restore sinus rhythm within 24 to 48 hours from onset by medication and when medication failed by direct-current cardioversion before discharge home. Results Mean follow-up after AVR was 17.8 ± 1.9 years. Incidence of new-onset POAF was 42.4%. Kaplan-Meier overall cumulative survival rates at 15 years of follow-up were similar in the patients with new-onset POAF versus those without: 41.5% (95% confidence interval CI, 35.2-47.7) versus 41.3% (95% CI, 36.0-46.7), respectively. New-onset POAF was not an independent risk factor for decreased long-term survival (hazard ratio 0.815; 95% CI, 0.663-1.001; P = .052). Conclusions New-onset POAF after AVR does not affect long-term survival when treatment is aimed to restore sinus rhythm before discharge home.
Rationale Dual antiplatelet therapy with acetylsalicylic acid in combination with a more potent P2Y12- inhibitor (ticagrelor or prasugrel) is recommended in patients with acute coronary syndrome ...without ST-segment elevation (NSTE-ACS) to prevent atherothrombotic complications. The evidence on which this recommendation is based shows that ticagrelor and prasugrel reduce atherothrombotic events at the expense of an increase in bleeding events when compared with clopidogrel. However, it remains unclear whether ticagrelor or prasugrel has a better net clinical benefit in elderly patients with NSTE-ACS when compared with clopidogrel. The POPular AGE trial is designed to address the optimal antiplatelet strategy in elderly NSTE-ACS patients. Study design POPular AGE is a multicenter, open-label, randomized controlled trial that aims to include 1000 patients ≥70 years of age with NSTE-ACS. Patients are randomly assigned to receive either clopidogrel or a more potent P2Y12 inhibitor (ticagrelor or prasugrel). The first primary end point is any bleeding event requiring medical intervention. The second primary end point is the net clinical benefit, a composite of all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, “PLATelet inhibition and patient Outcomes” major bleeding, or “PLATelet inhibition and patient Outcomes” minor bleeding. Patients will be followed for 1 year after randomization, and analyses will be performed on the basis of intention to treat. Conclusion The POPular AGE is the first randomized controlled trial that will assess whether the treatment strategy with clopidogrel will result in fewer bleeding events without compromising the net clinical benefit in patients ≥70 years of age with NSTE-ACS when compared with a treatment strategy with ticagrelor or prasugrel.
Rationale In patients with ST-segment elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (pPCI), the use of dual antiplatelet therapy is essential to ...prevent atherothrombotic complications. Therefore, patients are treated with acetylsalicylic acid and clopidogrel, prasugrel, or ticagrelor. Clopidogrel, however, shows a major interindividual variation in antiplatelet effect, which is correlated to an increase in atherothrombotic events in patients with high platelet reactivity. This interindividual variation is partly a result of CYP2C19 genetic variants. Ticagrelor and prasugrel reduce atherothrombotic events but increase bleeding rate and drug costs, as compared with clopidogrel. CYP2C19-based tailoring of antiplatelet therapy might be beneficial to STEMI patients. Study design POPular Genetics (NCT01761786) is a randomized, open-label, multicenter trial involving 2,700 STEMI patients who undergo pPCI. Patients are randomized to CYP2C19 genotyping or routine ticagrelor or prasugrel treatment. In the genotyping group, *1/*1 (wild-type) patients receive clopidogrel, and patients carrying 1 or 2 *2 or *3 loss-of-function alleles receive ticagrelor or prasugrel. The primary net clinical benefit end point is the composite of death, (recurrent) myocardial infarction, definite stent thrombosis, stroke, and Platelet Inhibition and Patient Outcomes (PLATO) major bleeding at 1 year. Primary safety end point is the composite of (PLATO) major and minor bleeding. Cost-effectiveness and quality of life will be assessed by calculating quality-adjusted life-years, net costs per life-year, and per quality-adjusted life-year gained. Conclusion The POPular Genetics study is the first large-scale trial comparing CYP2C19 genotype–guided antiplatelet therapy to a nontailored strategy in terms of net clinical benefit, safety, and cost-effectiveness.
Abstract Objectives The aim of this study was to investigate the efficacy and safety of the hybrid ultrathin-strut sirolimus-eluting stent (SES) with biodegradable polymer compared with the ...thin-strut everolimus-eluting stent (EES) with durable polymer in successfully recanalized chronic total occlusions (CTOs). Background The introduction of drug-eluting stents revolutionized the treatment of CTOs. However, limited data are available on new-generation drug-eluting stents with biodegradable polymer in CTOs. Methods In this multicenter trial, patients were randomized, after successful CTO recanalization, to either SES or EES. The primary noninferiority endpoint was in-segment late lumen loss (noninferiority margin 0.2 mm). Secondary endpoints included in-stent late lumen loss and clinical endpoints. Results Overall, 330 patients were included. At 9 months, angiography was available in 281 patients (85%). Duration of occlusion ≥3 months was 92.5%, with mean stent length of 52.4 ± 28.1 mm versus 52.3 ± 26.5 mm in the SES and EES groups. The primary noninferiority endpoint, in-segment late lumen loss, was not met for SES versus EES (0.13 ± 0.63 mm vs. 0.02 ± 0.47 mm; p = 0.08, 2-sided; difference 0.11 mm; 95% confidence interval: −0.01 to 0.25 mm; pnoninferiority = 0.11, 1-sided). In-stent late lumen loss was comparable between SES and EES (0.12 ± 0.59 mm vs. 0.07 ± 0.46 mm; p = 0.52). The incidence of in-stent and in-segment binary restenosis was significantly higher with SES compared with EES (8.0% vs. 2.1%; p = 0.028), with comparable rates of reocclusions (2.2% vs. 1.4%; p = 0.68). Clinically indicated target lesion and target vessel revascularization (9.2% vs. 4.0% p = 0.08 and 9.2% vs. 6.0% p = 0.33), target vessel failure (9.9% vs. 6.6%; p = 0.35), and definite or probable stent thrombosis (0.7% vs. 0.7%; p = 1.00) were comparable between the SES and EES groups. Conclusions This randomized trial failed to show noninferiority of hybrid SES relative to EES in terms of in-segment late lumen loss in successfully recanalized CTOs. Furthermore, a statistically significantly higher rate of binary restenosis was found with SES.
Abstract Background In patients suspected of new slow-onset heart failure, data on the comparative diagnostic performance of automated B-type natriuretic peptide (BNP) assays are scarce. Methods and ...Results Two hundred patients referred to a heart failure outpatient diagnostic facility underwent standard diagnostic work-up including echocardiography. The reference standard for the diagnosis of heart failure was an expert panel conclusion. N-terminal pro-BNP on Elecsys and BNP on Axsym and Centaur machines were measured in a single batch. Data were available for 172 patients; 51 had heart failure (29.7%). All 3 tests had high c-statistic values. An intermediate-risk subset of 111 patients (34% with heart failure) was created by excluding patients with very high or very low probability based on history and physical examination, the subgroup most in need of an additional test. Applying different thresholds for ruling heart failure in or out, the positive predicted values in this “gray zone” group were 75%, 76%, and 72%, respectively, and the negative predictive values 83%, 71%, and 85%, with the remaining 50% of patients having ∼18% probability of heart failure. Conclusion In practice, a valid diagnosis in patients suspected of slow-onset heart failure remains elusive for many in the absence of echocardiographic imaging.
Early mortality and morbidity after thoracoabdominal aortic aneurysm (TAAA) repair has been analyzed extensively; however, very few studies have examined the risk factors for late death.
We analyzed ...500 consecutive TAAA repairs performed at St. Antonius Hospital between 1981 and March 30, 2006. Survival and freedom from aortic reoperation were calculated using the Kaplan-Meier method, and the effects of preoperative, intraoperative, and postoperative risk factors were evaluated using Cox proportional hazard analysis. Survival was compared with a Dutch population matched for age, sex, and date of operation.
Patient survival with 95% confidence intervals (CI) was 83% (80% to 86%), 63% (58% to 67%), 34% (29% to 40%), 16% (9% to 20%), and 6% (2% to 11%) after 1, 5, 10, 15, and 20 years, respectively, compared with 100%, 99%, 85%, 36%, and 15% for the matched Dutch population. Hazard analysis showed an early phase of high hazard falling to low levels 9 months postoperatively and a late phase in which the hazard of death gradually increased. Incremental risk factors for late death were depressed left ventricular function (p < 0.001), increased age (p < 0.001), urgency (p = 0.007), postoperative dialysis (p < 0.001), and postoperative neurologic deficit (p = 0.016). Freedom from reoperation on the aorta with 95% CI was 98% (97% to 99%), 92% (89% to 94%), 86% (82% to 90%), 83% (78% to 87%), and 83% (78% to 87%) after 1, 5, 10, 15, and 20 years, respectively.
Survival remains suboptimal, especially in the early years after TAAA repair, compared with a matched population. Avoidance of postoperative problems such as dialysis and neurologic deficits and performing elective surgery on relative young patients with unimpaired ventricular function will increase the likelihood of late survival.
Objective Atrial fibrosis is related to atrial fibrillation but may differ in patients with mitral valve disease or lone atrial fibrillation. Therefore, we studied atrial fibrosis in patients with ...atrial fibrillation + mitral valve disease or with lone atrial fibrillation and compared it with controls. Methods Left and right atrial appendages amputated during Maze III surgery for lone atrial fibrillation (n = 85) or atrial fibrillation + mitral valve disease (n = 26) were embedded in paraffin, sectioned, and stained with picrosirius red. Atria from 10 deceased patients without a cardiovascular history served as controls. A total of 1048 images (4-μm sections, 10-fold magnification, 4 images per appendage) were obtained and digitized. The percentage of fibrous tissue was calculated by quantitative morphometry. Results Irrespective of the presence or absence of atrial fibrillation or mitral valve disease, more fibrous tissue was present in right atrial appendages than in left atrial appendages (12.7% ± 5.7% vs 8.2% ± 3.9%; P < . 0001). The mean amount of fibrous tissue in the atria was significantly larger in patients with atrial fibrillation + mitral valve disease than in patients with lone AF and controls (13.6% ± 5.8%, 9.7% ± 3.2%, and 8.8% ± 2.4%, respectively; P < . 01). No significant differences existed between patients with lone atrial fibrillation and patients without a cardiovascular history (controls). Conclusions Atria of patients with atrial fibrillation and mitral valve disease have more fibrosis than atria of patients with lone atrial fibrillation. However, patients with lone atrial fibrillation have an equal amount of atrial fibrosis compared with controls. These findings support the notion that fibrosis plays a more important role in the pathogenesis of atrial fibrillation secondary to mitral valve disease than in lone atrial fibrillation and potentially explains the relatively poor success of antiarrhythmic surgery in patients with mitral valve disease.
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