Search

Objectives: The purpose of this study was to compare the effectiveness of bucindolol with that of metoprolol succinate for the maintenance of sinus rhythm in a genetically defined heart failure (HF) population with atrial fibrillation (AF)., Background: Bucindolol is a beta-blocker whose unique pharmacologic properties provide greater benefit in HF patients with reduced ejection fraction (HFrEF) who have the beta 1 -adrenergic receptor (ADRB1) Arg389Arg genotype., Methods: A total of 267 HFrEF patients with a left ventricular ejection fraction (LVEF) <0.50, symptomatic AF, and the ADRB1 Arg389Arg genotype were randomized 1:1 to receive bucindolol or metoprolol therapy and were up-titrated to target doses. The primary endpoint of AF or atrial flutter (AFL) or all-cause mortality (ACM) was evaluated by electrocardiogram (ECG) during a 24-week period., Results: The hazard ratio (HR) for the primary endpoint was 1.01 (95% confidence interval [CI]: 0.71 to 1.42), but trends for bucindolol benefit were observed in several subgroups. Precision therapeutic phenotyping revealed that a differential response to bucindolol was associated with the interval of time from the initial diagnoses of AF and HF to randomization and with the onset of AF relative to that of the initial HF diagnosis. In a cohort whose first AF and HF diagnoses were <12 years prior to randomization, in which AF onset did not precede HF by more than 2 years (n = 196), the HR was 0.54 (95% CI: 0.33 to 0.87; p = 0.011)., Conclusions: Pharmacogenetically guided bucindolol therapy did not reduce the recurrence of AF/AFL or ACM compared to that of metoprolol therapy in HFrEF patients, but populations were identified who merited further investigation in future phase 3 trials., (Copyright © 2019. Published by Elsevier Inc.)

Background: The prevalence and outcome of patients with cancer that experience acute coronary syndrome (ACS) have to be determined., Methods and Results: The BleeMACS project is a multicentre observational registry enrolling patients with acute coronary syndrome undergoing percutaneous coronary intervention worldwide in 15 hospitals. The primary endpoint was a composite event of death and re-infarction after one year of follow-up. Bleedings were the secondary endpoint. 15,401 patients were enrolled, 926 (6.4%) in the cancer group and 14,475 (93.6%) in the group of patients without cancer. Patients with cancer were older (70.8±10.3 vs. 62.8±12.1 years, P<0.001) with more severe comorbidities and presented more frequently with non-ST-segment elevation myocardial infarction compared with patients without cancer. After one year, patients with cancer more often experienced the composite endpoint (15.2% vs. 5.3%, P<0.001) and bleedings (6.5% vs. 3%, P<0.001). At multiple regression analysis the presence of cancer was the strongest independent predictor for the primary endpoint (hazard ratio (HR) 2.1, 1.8-2.5, P<0.001) and bleedings (HR 1.5, 1.1-2.1, P=0.015). Despite patients with cancer generally being undertreated, beta-blockers (relative risk (RR) 0.6, 0.4-0.9, P=0.05), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (RR 0.5, 0.3-0.8, P=0.02), statins (RR 0.3, 0.2-0.5, P<0.001) and dual antiplatelet therapy (RR 0.5, 0.3-0.9, P=0.05) were shown to be protective factors, while proton pump inhibitors (RR 1, 0.6-1.5, P=0.9) were neutral., Conclusion: Cancer has a non-negligible prevalence in patients with acute coronary syndrome undergoing percutaneous coronary intervention, with a major risk of cardiovascular events and bleedings. Moreover, these patients are often undertreated from clinical despite medical therapy seems to be protective. Registration:The BleeMACS project (NCT02466854).

Purpose: The aim was to evaluate prognostic value of beta-blocker (BB) administration in acute coronary syndromes (ACS) patients in the percutaneous coronary intervention (PCI) era., Methods and Results: The BleeMACS project is a multicenter, observational, retrospective registry enrolling patients with ACS worldwide in 15 hospitals. Patients discharged with BB therapy were compared to those discharged without a BB before and after propensity score with matching. The primary endpoint was all-cause mortality at 1 year. Secondary endpoints included in-hospital reinfarction, in-hospital heart failure, 1-year myocardial infarction, 1-year bleeding and 1-year composite of death and recurrent myocardial infarction. After matching, 2935 patients for each group were enrolled. The primary endpoint of 1-year death was significantly lower in the group on BB therapy (4.5 vs 7%, p < 0.05), while only a trend was noted for recurrent acute myocardial infarction (4.5 vs 4.9%, p = 0.54). These results were consistent for patients older than 80 years of age, for ST-elevation myocardial infarction (STEMI) patients, and for those discharged with complete versus incomplete revascularization, but not for non-STEMI/unstable angina patients., Conclusions: BB therapy was related to 1-year lower risk of all-cause mortality, independently from completeness of revascularization, admission diagnosis, age and ejection fraction. Randomized controlled trials for patients treated with PCI for ACS should be performed.

Background: Few therapies are available for the safe and effective treatment of atrial fibrillation (AF) in patients with heart failure. Bucindolol is a non-selective beta-blocker with mild vasodilator activity previously found to have accentuated antiarrhythmic effects and increased efficacy for preventing heart failure events in patients homozygous for the major allele of the ADRB1 Arg389Gly polymorphism (ADRB1 Arg389Arg genotype). The safety and efficacy of bucindolol for the prevention of AF or atrial flutter (AFL) in these patients has not been proven in randomized trials., Methods/design: The Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Metoprolol Succinate for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients with Heart Failure (GENETIC-AF) trial is a multicenter, randomized, double-blinded "seamless" phase 2B/3 trial of bucindolol hydrochloride versus metoprolol succinate, for the prevention of symptomatic AF/AFL in patients with reduced ejection fraction heart failure (HFrEF). Patients with pre-existing HFrEF and recent history of symptomatic AF are eligible for enrollment and genotype screening, and if they are ADRB1 Arg389Arg, eligible for randomization. A total of approximately 200 patients will comprise the phase 2B component and if pre-trial assumptions are met, 620 patients will be randomized at approximately 135 sites to form the Phase 3 population. The primary endpoint is the time to recurrence of symptomatic AF/AFL or mortality over a 24-week follow-up period, and the trial will continue until 330 primary endpoints have occurred., Conclusions: GENETIC-AF is the first randomized trial of pharmacogenetic guided rhythm control, and will test the safety and efficacy of bucindolol compared with metoprolol succinate for the prevention of recurrent symptomatic AF/AFL in patients with HFrEF and an ADRB1 Arg389Arg genotype. (ClinicalTrials.govNCT01970501)., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Accurate 1-year bleeding risk estimation after hospital discharge for acute coronary syndrome (ACS) may help clinicians guide the type and duration of antithrombotic therapy. Currently there are no predictive models for this purpose. The aim of this study was to derive and validate a simple clinical tool for bedside risk estimation of 1-year post-discharge serious bleeding in ACS patients., Methods: The risk score was derived and internally validated in the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registry, an observational international registry involving 15,401 patients surviving admission for ACS and undergoing percutaneous coronary intervention (PCI) from 2003 to 2014, engaging 15 hospitals from 10 countries located in America, Europe and Asia. External validation was conducted in the SWEDEHEART population, with 96,239 ACS patients underwent PCI and 93,150 without PCI., Results: Seven independent predictors of bleeding were identified and included in the BleeMACS score: age, hypertension, vascular disease, history of bleeding, malignancy, creatinine and hemoglobin. The BleeMACS risk score exhibited a C-statistic value of 0.71 (95% CI 0.68-0.74) in the derivation cohort and 0.72 (95% CI 0.67-0.76) in the internal validation sample. In the SWEDEHEART external validation cohort, the C-statistic was 0.65 (95% CI 0.64-0.66) for PCI patients and 0.63 (95% CI 0.62-0.64) for non-PCI patients. The calibration was excellent in the derivation and validation cohorts., Conclusions: The BleeMACS bleeding risk score is a simple tool useful for identifying those ACS patients at higher risk of serious 1-year post-discharge bleeding. ClinicalTrials.govIdentifier: NCT02466854., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aims: The benefit of complete or incomplete percutaneous coronary intervention (PCI) in patients with myocardial infarction and multivessel disease remains debated. The aim of our study was to compare a complete vs. a "culprit only" revascularisation strategy in patients with myocardial infarction distinguishing the different clinical subsets (STEMI and NSTEMI) and to provide one-year clinical outcome from the "real-life" BleeMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registry., Methods and Results: We conducted a multicentre study including all patients with myocardial infarction and multivessel coronary disease included in the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registry. They were divided into two groups, complete revascularisation (CR) and incomplete revascularisation (IR). The primary endpoint was the death rate at one-year follow-up. Secondary endpoints were in-hospital repeat myocardial infarction (re-AMI), in-hospital heart failure (HF), major adverse cardiovascular events (MACE) and myocardial infarction at one year. Four thousand five hundred and twenty patients were included in our analysis, with a diagnosis of STEMI in 67.7% and NSTEMI in 32.3%. CR was performed in 27.2% and 42.4%, respectively. At univariate analysis, in-hospital and one-year outcomes were similar between CR and IR in STEMI patients (all p-values >0.05). In NSTEMI patients, CR was associated with a lower one-year death rate (4.5% vs. 8.5%; p=0.002), re-AMI (3.7% vs. 6.6%; p=0.016) and MACE (8.1% vs. 13.9%; p=0.001). After propensity score matching, CR also reduced events in STEMI patients, including one-year mortality (5.3% vs. 13.8%; p<0.001), re-AMI (4.9% vs. 17.4%; p<0.001) and MACE (8.5% vs. 24.6%; p<0.001)., Conclusions: This multicentre retrospective registry showed the benefit of CR in terms of reduction of one-year mortality in patients with myocardial reinfarction and multivessel coronary disease. Randomised controlled trials including functional evaluation of the lesions should be performed to confirm our results.

Objective: Our objective was to define the most appropriate treatment for acute coronary syndrome (ACS) in patients with malignancy., Methods and Results: The BleeMACS project is a worldwide multicenter observational prospective registry in 16 hospitals enrolling patients with ACS undergoing percutaneous coronary intervention. Primary endpoints were death, re-infarction, and major adverse cardiac events (MACE; composite of death and re-infarction) after 1 year of follow-up. The secondary endpoint was bleeding events during follow-up. We performed sub-study analyses according to whether β-blockers (BBs), angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), statins, or proton pump inhibitors (PPIs) were prescribed at discharge. We also calculated the propensity score for optimal medical therapy (OMT; combination of BB, ACEI/ARB, and statins). The study included 926 patients. According to the multivariate analysis, ACEIs/ARBs (hazard ratio [HR] 0.58, 95 % confidence interval [CI] 0.36-1.94; p = 0.03) and statins (HR 0.37, 95 % CI 0.23-0.61; p < 0.01) reduced the risk of MACE, while the effects of BBs (HR 0.85, 95 % CI 0.55-1.32; p = 0.48) and PPIs (HR 1.33, 95 % CI 0.83-2.12; p = 0.23) were not significant. OMT was prescribed at discharge in 300 (32.4 %) patients; after propensity score analysis, OMT showed a significant reduction in death (3 % vs. 12.5 %, HR 0.21, 95 % CI 0.1-0.4; log-rank p < 0.001) and MACE (6.7 vs. 15.2 %, log-rank p = 0.01)., Conclusion: In patients with ACS and malignancy, OMT reduces the risk of adverse events at 1 year; in particular, ACEIs/ARBs and statins were the most protective drugs. (Clinical trials identifier: NCT02466854).

Registry-based randomized controlled trials are defined as pragmatic trials that use registries as a platform for case records, data collection, randomization, and follow-up. Recently, the application of registry-based randomized controlled trials has attracted increasing attention in health research to address comparative effectiveness research questions in real-world settings, mainly due to their low cost, enhanced generalizability of findings, rapid consecutive enrollment, and the potential completeness of follow-up for the reference population, when compared with conventional randomized effectiveness trials. However several challenges of registry-based randomized controlled trials have to be taken into consideration, including registry data quality, ethical issues, and methodological challenges. In this article, we summarize the advantages, challenges, and areas for future research related to registry-based randomized controlled trials., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: The study aimed to analyze the impact of concomitant administration of P2Y12 inhibitors and PPIs on ischemia events in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods: We retrospectively analyzed data from a international, multi-center registry between 2003 and 2014 in patients with ACS after PCI, grouped the cohort into patients receiving PPIs or no PPIs and assessed 1-year clinical endpoint (all-cause death/re-infarction). Meanwhile, we grouped the cohort into patients receiving clopidogrel or ticagrelor, and compared the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year clinical endpoint. Results: Of 9 429 patients in the final cohort, 54.8% ( n =5 165) was prescribed a PPI at discharge. Patients receiving a PPI were more likely to have comorbidities. No association was observed between PPI use and the clinical endpoint (HR 1.00, 95% CI 0.86-1.18). Meanwhile, no association was found between PPI use and the clinical endpoint in patients receiving either clopidogrel or ticagrelor. And the clinical endpoint in patients administrated of clopidogrel and PPIs had no difference with that of ticagrelor and PPIs. Conclusions: In patients with ACS following PCI, increased risk of ischemia event was not found in the concomitant use of PPIs and P2Y12 inhibitors, and especially, compared with ticagrelor, clopidogrel was found no association with ischemia events when concomitant administrated with PPIs.

Background: Clinical practice guidelines recommend admitting patients with stable non-ST-segment elevation acute coronary syndrome (NSTE ACS) to telemetry units, yet up to two-thirds of patients are admitted to higher-acuity critical care units (CCUs). The outcomes of patients with stable NSTE ACS initially admitted to a CCU vs a cardiology ward with telemetry have not been described., Methods: We used population-based data of 7,869 patients hospitalized with NSTE ACS admitted to hospitals in Alberta, Canada, between April 1, 2007, and March 31, 2013. We compared outcomes among patients initially admitted to a CCU (n=5,141) with those admitted to cardiology telemetry wards (n=2,728)., Results: Patients admitted to cardiology telemetry wards were older (median 69 vs 65years, P<.001) and more likely to be female (37.2% vs 32.1%, P<.001) and have a prior myocardial infarction (14.3% vs 11.5%, P<.001) compared with patients admitted to a CCU. Patients admitted directly to cardiology telemetry wards had similar hospital stays (6.2 vs 5.7days, P=.29) and fewer cardiac procedures (40.3% vs 48.5%, P<.001) compared with patients initially admitted to CCUs. There were no differences in the frequency of in-hospital mortality (1.3% vs 1.2%, adjusted odds ratio [aOR] 1.57, 95% CI 0.98-2.52), cardiac arrest (0.7% vs 0.9%, aOR 1.37, 95% CI 0.94-2.00), 30-day all-cause mortality (1.6% vs 1.5%, aOR 1.50, 95% CI 0.82-2.75), or 30-day all-cause postdischarge readmission (10.6% vs 10.8%, aOR 1.07, 95% CI 0.90-1.28) between cardiology telemetry ward and CCU patients. Results were similar across low-, intermediate-, and high-risk Duke Jeopardy Scores, and in patients with non-ST-segment myocardial infarction or unstable angina., Conclusions: There were no differences in clinical outcomes observed between patients with NSTE ACS initially admitted to a ward or a CCU. These findings suggest that stable NSTE ACS may be managed appropriately on telemetry wards and presents an opportunity to reduce hospital costs and critical care capacity strain., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: There is great debate on the possible adverse interaction between proton pump inhibitors (PPIs) and clopidogrel. In addition, whether the use of PPIs affects the clinical efficacy of ticagrelor remains less known. We aimed to determine the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI)., Methods: We retrospectively analyzed data from a "real world", international, multi-center registry between 2003 and 2014 (n = 15,401) and assessed the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year composite primary endpoint (all-cause death, re-infarction, or severe bleeding) in patients with ACS after PCI., Results: Of 9429 patients in the final cohort, 54.8% (n = 5165) was prescribed a PPI at discharge. Patients receiving a PPI were older, more often female, and were more likely to have comorbidities. No association was observed between PPI use and the primary endpoint for patients receiving clopidogrel (adjusted HR: 1.036; 95% CI: 0.903-1.189) or ticagrelor (adjusted HR: 2.320; 95% CI: 0.875-6.151) (P interaction = 0.2004). Similarly, use of a PPI was not associated with increased risk of all-cause death, re-infarction, or a decreased risk of severe bleeding for patients treated with either clopidogrel or ticagrelor., Conclusions: In patients with ACS following PCI, concomitant use of PPIs was not associated with increased risk of adverse outcomes in patients receiving either clopidogrel or ticagrelor. Our findings indicate it is reasonable to use a PPI in combination with clopidogrel or ticagrelor, especially in patients with a higher risk of gastrointestinal bleeding.

Aims: We undertook this analysis to assess the relationship between delayed left ventricular activation time (LVAT), assessed prior to cardiac resynchronization therapy (CRT), with the long-term clinical outcomes in CRT recipients. We also sought to determine if baseline LVAT had similar predictive value in patients who were versus were not chronically paced prior to CRT., Methods and Results: Baseline pre-implant electrocardiograms (ECGs) of 219 consecutive patients undergoing CRT were analysed. Of these, 68 (31%) were chronically right ventricular (RV)-paced pre-CRT. Maximum LVAT was measured as QRS-duration minus time from QRS onset to the first notch in the QRS. Cox models were used to assess the association between LVAT and clinical outcome (death or cardiac transplant). Over a median follow-up of 56 months, 92 patients (42%) died and 10 (5%) underwent cardiac transplant. In the non-RV-paced group an independent linear relationship between LVAT and outcome [hazard ratio (HR) 0.67 per 50 ms increase in LVAT; 95% confidence interval (CI) 0.46-0.99] was observed. An LVAT ≥ 125 ms was associated with a markedly lower risk of outcome (adjusted HR 0.51; 95% CI 0.30-0.86) in these patients. Despite a similar incidence of death or cardiac transplantation in the RV-paced group vs. the non-paced one, no significant association between LVAT and outcome was observed in the RV-paced group., Conclusion: Baseline LVAT, a simple ECG measure, independently predicts long-term outcome with CRT in non-RV paced patients. However, prolonged LVAT is not associated with an altered prognosis in patients chronically RV paced prior to CRT.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and is responsible for the highest number of rhythm-related disorders and cardioembolic strokes worldwide. Intracardiac signal analysis during the onset of paroxysmal AF led to the discovery of pulmonary vein as a triggering source of AF, which has led to the development of pulmonary vein ablation--an established curative therapy for drug-resistant AF. Complex, multicomponent and rapid electrical activity widely involving the atrial substrate characterizes persistent/permanent AF. Widespread nature of the problem and complexity of signals in persistent AF reduce the success rate of ablation therapy. Although signal processing applied to extraction of relevant features from these complex electrograms has helped to improve the efficacy of ablation therapy in persistent/permanent AF, improved understanding of complex signals should help to identify sources of AF and further increase the success rate of ablation therapy.