Machine learning-based prediction of adverse events following an acute coronary syndrome (PRAISE): a modelling study of pooled datasets.

BACKGROUND: The accuracy of current prediction tools for ischaemic and bleeding events after an acute coronary syndrome (ACS) remains insufficient for individualised patient management strategies. We developed a machine learning-based risk stratification model to predict all-cause death, recurrent acute myocardial infarction, and major bleeding after ACS. METHODS: Different machine learning models for the prediction of 1-year post-discharge all-cause death, myocardial infarction, and major bleeding (defined as Bleeding Academic Research Consortium type 3 or 5) were trained on a cohort of 19 826 adult patients with ACS (split into a training cohort [80%] and internal validation cohort [20%]) from the BleeMACS and RENAMI registries, which included patients across several continents. 25 clinical features routinely assessed at discharge were used to inform the models. The best-performing model for each study outcome (the PRAISE score) was tested in an external validation cohort of 3444 patients with ACS pooled from a randomised controlled trial and three prospective registries. Model performance was assessed according to a range of learning metrics including area under the receiver operating characteristic curve (AUC). FINDINGS: The PRAISE score showed an AUC of 0·82 (95% CI 0·78-0·85) in the internal validation cohort and 0·92 (0·90-0·93) in the external validation cohort for 1-year all-cause death; an AUC of 0·74 (0·70-0·78) in the internal validation cohort and 0·81 (0·76-0·85) in the external validation cohort for 1-year myocardial infarction; and an AUC of 0·70 (0·66-0·75) in the internal validation cohort and 0·86 (0·82-0·89) in the external validation cohort for 1-year major bleeding. INTERPRETATION: A machine learning-based approach for the identification of predictors of events after an ACS is feasible and effective. The PRAISE score showed accurate discriminative capabilities for the prediction of all-cause death, myocardial infarction, and major bleeding, and might be useful to guide clinical decision making. FUNDING: None.

Ticagrelor or Clopidogrel After an Acute Coronary Syndrome in the Elderly: A Propensity Score Matching Analysis from 16,653 Patients Treated with PCI Included in Two Large Multinational Registries.

PURPOSE: Higher risk of bleeding with ticagrelor over clopidogrel in elderly patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) has been suggested. We assessed the incidence of major bleedings (MB), reinfarction (re-MI), and all-cause death to evaluate safety and efficacy of ticagrelor versus clopidogrel in such population. METHODS: Real-world registries RENAMI and BleeMACS were merged. The pooled cohort was divided into two groups, clopidogrel versus ticagrelor. Statistical analysis considered patients <75 versus ≥75 years old. Endpoints were BARC 3-5 MB, re-MI, and all-cause death at 1-year follow-up. The study included 16,653 patients (13,153 < 75 and 3500 ≥ 75 years). Ticagrelor was underused in elderly patients (16.3% versus 20.8%, P < 0.001). Using propensity score matching (PSM), two treatment groups of 1566 patients were included in the final analysis. RESULTS: Ticagrelor was able to prevent re-MI (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.2-0.6; P < 0.001) and all-cause death (HR, 0.60; 95% CI, 0.4-0.9; P = 0.026) irrespective of age. In patients ≥75 years, ticagrelor reduced all-cause death (HR, 0.32; 95% CI, 0.1-0.8; P = 0.012) and re-MI (HR, 0.25; 95% CI, 0.1-1.1, P = 0.072). Moreover, even with the limit of the low number of events, ticagrelor did not significantly increase the incidence of MB (HR, 1.49; 95% CI, 0.70-3.0; P = 0.257). At multiple Cox regression, age (HR, 1.03; 95% CI, 1.02-1.05; P < 0.001) resulted an independent risk factor for bleeding. CONCLUSION: In our study, reflecting the results from two large retrospective, real-world registries, Ticagrelor did not significantly increase MB compared with clopidogrel in elderly patients with ACS treated with PCI, while significantly improving 1-year survival. Further studies on elderly patients are suggested.

Average daily ischemic versus bleeding risk in patients with ACS undergoing PCI: Insights from the BleeMACS and RENAMI registries.

BACKGROUND: The risk of recurrent ischemia and bleeding after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) may vary during the first year of follow-up according to clinical presentation, and medical and interventional strategies. METHODS: BleeMACS and RENAMI are 2 multicenter registries enrolling patients with ACS treated with PCI and clopidogrel, prasugrel, or ticagrelor. The average daily ischemic and bleeding risks (ADIR and ADBR) in the first year after PCI were the primary end points. The difference between ADBR and ADIR was calculated to estimate the potential excess of bleeding/ischemic events in a given period or specific subgroup. RESULTS: A total of 19,826 patients were included. Overall, in the first year after PCI, the ADBR was 0.008085%, whereas ADIR was 0.008017% (P = .886). In the first 2 weeks ADIR was higher than ADBR (P = .013), especially in patients with ST-segment elevation myocardial infarction or incomplete revascularization. ADIR continued to be, albeit non-significantly, greater than ADBR up to the third month, whereas ADBR became higher, although not significantly, afterward. Patients with incomplete revascularization had an excess in ischemic risk (P = .003), whereas non-ST-segment elevation ACS patients and those on ticagrelor had an excess of bleeding (P = .012 and P = .022, respectively). CONCLUSIONS: In unselected ACS patients, ADIR and ADBR occurred at similar rates within 1 year after PCI. ADIR was greater than ADBR in the first 2 weeks, especially in ST-segment elevation myocardial infarction patients and those with incomplete revascularization. In the first year, ADIR was higher than ADBR in patients with incomplete revascularization, whereas ADBR was higher in non-ST-segment elevation ACS patients and in those discharged on ticagrelor.

Effect of concomitant antiplatelet therapy in patients with nonvalvular atrial fibrillation initiating non-vitamin K antagonists.

BACKGROUND: Antiplatelet therapy (APT) use in combination with oral anticoagulation is common among patients with atrial fibrillation, but there is scarce information regarding its effect on outcomes in patients on non-vitamin K antagonist oral anticoagulants (NOAC). We aimed to evaluate the safety and efficacy of APT use in a 'real-world' cohort of nonvalvular atrial fibrillation (NVAF) patients initiating NOAC. DESIGN: We conducted a retrospective multicentre study including 2361 consecutive NVAF patients initiating NOAC between January 2013 and December 2016. Patients with an acute ischaemic event within the last 12 months (acute coronary syndrome, stroke or revascularization) were excluded. Patients were followed up, and all clinical events were recorded at 3 months. The primary outcome of the study was major bleeding, and the secondary outcomes were stroke, nonfatal myocardial infarction, intracranial bleeding and death. RESULTS: One hundred forty-five (6.1%) patients received concomitant APT, and aspirin was the more common (79%). At 3 months, 25 (1.1%) patients had major bleeding, 8 (0.3%) had nonfatal myocardial infarction, 7 (0.3%) had ischaemic stroke, and 40 (1.7%) died. After multivariate adjustment, concomitant APT was associated with higher risk for major bleeding (HR = 3.62, 95% CI 1.32-9.89; P = .012), but was not associated with a higher risk of other clinical outcomes. CONCLUSIONS: Concomitant APT use is uncommon among these patients and does not seem to be associated with lower rates of ischaemic events or death. However, there are signals for an increased risk of bleeding, which reinforces current guideline recommendations.

Kidney function monitoring and nonvitamin K oral anticoagulant dosage in atrial fibrillation.

BACKGROUND: Clinical practice guidelines recommend regular kidney function monitoring in atrial fibrillation patients on nonvitamin K oral anticoagulants (NOAC); however, information regarding compliance with these recommendations in daily life conditions is scarce. We sought to determine the compliance with kidney function monitoring recommendations in nonvalvular atrial fibrillation (NVAF) patients starting NOAC and its implication on the appropriateness of NOAC dosage. MATERIAL AND METHODS: This study involves the retrospective analysis of a multicentre registry including consecutive NVAF patients who started NOAC (n = 692). Drug dosage changes and serum creatinine determinations were recorded during 1-year follow-up. European Heart Rhythm Association criteria were used to define the appropriateness of kidney function monitoring as well as adequate NOAC dosage. RESULTS: During the follow-up (334 ± 89 days), the compliance with kidney function monitoring recommendations was 61% (n = 425). After multivariate adjustment, age (OR × year: 0.92 (CI 95%: 0.89-0.95) P < .001), creatinine clearance (OR × mL/min: 1.02 (CI 95%: 1.01-1.03) P < .001) and adequate NOAC dosage at baseline (OR: 1.54 (CI 95%: 1.06-2.23), P = .024) were independent predictors of appropriate kidney function monitoring. Compliance with kidney function monitoring recommendations was independently associated with change to appropriate NOAC dose after 1 year (OR: 2.80 (CI 95%: 1.01-7.80), P = .049). CONCLUSIONS: Noncompliance with kidney function monitoring recommendations is common in NVAF patients starting NOAC, especially in elderly patients with kidney dysfunction. Compliance with kidney function monitoring recommendations was associated with adequate NOAC dosage at 1-year follow-up. Further studies are warranted to evaluate the implication of kidney function monitoring on prognosis.

Combined Multimodal Computed Tomography Score Correlates With Futile Recanalization After Thrombectomy in Patients With Acute Stroke.

BACKGROUND AND PURPOSE: Futile recanalization after acute ischemic stroke occurs in almost half of the patients despite optimal angiographic results. Multimodal neuroimaging may help to improve patient's selection but is still dismissed by many interventionalists. Our aim was to evaluate the accuracy of each parameter of multimodal computed tomography (CT) and their combination for predicting futile recanalization after successful thrombectomy. METHODS: We retrospectively reviewed a cohort of consecutive patients with anterior circulation stroke, fully assessable multimodal CT, and successful recanalization. Nonenhanced CT, CT angiography source images, cerebral blood volume (CBV), cerebral blood flow (CBF), and mismatch CBV-CBF maps were studied by Alberta Stroke Program Early CT Score (ASPECTS); collaterals on CT angiography were graded as poor or good (≤50% or >50% of the middle cerebral artery territory). Futile recanalization was defined as modified Rankin Scale score >2 at 3 months despite successful recanalization. RESULTS: One hundred fifty patients were included and 57% of them had futile recanalization. They had lower ASPECTS on nonenhanced CT, CT angiography source images, CBV, CBF, and mismatch CBV-CBF and presented more frequently poor collaterals (all P<0.001). Among them, CBV showed the highest area under the curve (0.83; 95% confidence interval, 0.76-0.88). In multivariate analyses, CT angiography source images ≤5 (odds ratio, 5.1; 95% confidence interval, 1.2-21.9), CBV≤6 (odds ratio, 3.5; 95% confidence interval, 1.2-9.7), and poor collaterals (odds ratio, 8.6; 95% confidence interval, 1.8-41.7) were independent predictors of futile recanalization. A combined score of these 3 parameters added complementary information: 57% of the patients with score-1, 89% with score-2, and 100% with score-3 had futile recanalization. Reclassification analyses indicated that this score improved prediction of futile recanalization. CONCLUSIONS: In this population, a combined multimodal CT score predicted futile recanalization.

sST2 levels are associated with all-cause mortality in anticoagulated patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with high morbidity and mortality, even despite the use of oral anticoagulation (OAC). Soluble suppression of tumorigenicity-2 (sST2) is a member of the interleukin-1 receptor family [interleukin-1 receptor-like 1 (IL1RL1)], which has been associated with an increased risk of mortality and morbidity in heart failure or acute coronary syndrome. We assessed the predictive value of sST2 levels in an unselected 'real-world' cohort of anticoagulated AF patients. METHODS: We included 562 patients (49% male; median age 77 [IQR: 71-82]) with permanent AF who were stable (for at least 6 months) on OAC (INRs 2.0-3.0). sST2 levels were quantified by ELISA. Patients were followed-up for up to 4 years, and cardiovascular events and all-cause mortality were recorded. RESULTS: Median (IQR) of sST2 levels was 51.23 (39.09-67.40) µg/L. Median follow-up was 1587 days [IQR 1482-1617], and during this period, 91 patients died (16.2%, 3.72%/year). The c-statistic for predicting mortality with sST2 was 0.58 + 0.03; P = 0.017). On multivariate analysis, age [hazard ratio (HR) 1.09 (1.05-1.13); P < 0.001], diabetes mellitus [1.76 (1.08-2.88); P = 0.023], previous stroke [2.16 (1.29-3.60); P = 0.003] and sST2 levels [1.008 (1.002-1.14); P = 0.008] were independently associated with mortality. Concentrations of sST2 were also significantly associated with the risk of mortality, even after adjusting for the CHA2 DS2 -VASc score [HR: 1.007 (1.001-1.013); P = 0.014]. CONCLUSIONS: In an anticoagulated AF patient's cohort, sST2 levels are an independent predictive factor of all-cause mortality. sST2 levels could be a biomarker used to improve clinical risk assessment in anticoagulated AF patients.

Major bleeding risk prediction using Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease equations in acute coronary syndrome.

BACKGROUND: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate more accurately than the Modification of Diet in Renal Disease (MDRD) Study equation. Our aim was to evaluate whether CKD-EPI equations based on serum creatinine and/or cystatin C (CysC) predict risk for major bleeding (MB) more accurately than the MDRD Study equation in patients with non-ST-segment elevation acute coronary syndromes (ACS). MATERIALS AND METHODS: Three hundred and fifty consecutive subjects with non-ST-segment elevation ACS (68 ± 12 years, 70% male) were studied. Glomerular filtration rate was estimated using the CKD-EPI and MDRD Study equations. The primary endpoint was the occurrence of MB during the follow-up, which was defined according to the Bleeding Academic Research Consortium Definition criteria as bleeding types 3-5. RESULTS: During the median follow-up of 589 days (interquartile range, 390-986), 27 patients had MB (0.04% events per person year). Patients with MB had worse kidney function parameters, regardless of the estimating equation used (P < 0.001). After multivariate Cox regression adjustment, both CysC-based CKD-EPI equations were independent predictors of MB (CKD-EPI(creatinine-cystatin) C per mL/min/1.73 m(2), HR = 0.973 (95%CI 0.955-0.991; P = 0.003) and CKD-EPI(cystatin) C per mL/min/1.73 m(2), HR = 0.976 (95%CI 0.976-0.992; P = 0.003), while the CKD-EPI(creatinine) and MDRD equations did not achieve statistical significance. Both CKD-EPI(creatine-cystatin) C and CKD-EPI(cystatin) C were associated with a significant improvement in MB risk reclassification. CONCLUSIONS: In this cohort of non-ST-segment elevation ACS patients with relatively preserved renal function, both CysC-based CKD-EPI equations improved ability to predict risk for MB and were superior to other equations for this application.

Usefulness of N-terminal pro-B-type natriuretic Peptide levels for stroke risk prediction in anticoagulated patients with atrial fibrillation.

BACKGROUND AND PURPOSE: Oral anticoagulation is highly effective in reducing stroke and mortality in atrial fibrillation (AF). Several risk stratification schemes have been developed using clinical characteristics. Elevated levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) are important markers of increased mortality and morbidity in congestive heart failure and general community population. The aim of our study was to assess the predictive value of NT-proBNP levels in an unselected real-world cohort of anticoagulated patients with AF. METHODS: We studied 1172 patients (49% male; median age, 76 years) with permanent AF who were well stabilized on oral anticoagulation (international normalized ratio, 2.0-3.0). Plasma NT-proBNP levels were quantified at baseline. We recorded thrombotic and vascular events, mortality, and major bleeding. The best cutoff points were assessed by receiver-operating characteristic curves. RESULTS: Median levels (interquartile range) of NT-proBNP were 610 (318-1037) pg/mL. Median follow-up was 1007 (806-1279) days. On multivariate analysis, high NT-proBNP was significantly associated with the risk of stroke (hazards ratio, 2.71; P=0.001) and composite vascular events (acute coronary syndrome or acute heart failure; hazards ratio, 1.85; P=0.016), as well as a significant association with mortality (adjusted hazards ratio, 1.66; P=0.006). No association with bleeding was found (P=0.637). The integrated discrimination improvement (IDI) analysis demonstrated that NT-proBNP improved the Congestive heart failure, Hypertension, Age≥75 (doubled), Diabetes mellitus, Stroke (doubled)-Vascular disease and Sex category (female); CHA2DS2-VASc score for predicting embolic events (relative IDI, 2.8%; P=0.001) and all-cause death (relative IDI, 1.8%; P=0.001). CONCLUSIONS: In real-world cohort of anticoagulated patients with AF, NT-proBNP provided complementary prognostic information to an established clinical risk score (CHA2DS2-VASc) for the prediction of stroke/systemic embolism. NT-proBNP was also predictive of all-cause mortality, suggesting that this biomarker may potentially be used to refine clinical risk stratification in anticoagulated patients with AF.

Withdrawal of drug therapy in responders to cardiac resynchronization therapy: rationale and design of the REMOVE trial.

INTRODUCTION AND OBJECTIVES: Cardiac resynchronization therapy (CRT) is an effective treatment for patients with nonischemic dilated cardiomyopathy associated with left bundle branch block (LBBB). In these patients, the device can normalize left ventricular ejection fraction (LVEF). Nevertheless, it remains unclear whether CRT responders still require neurohormonal blockers. The aim of this study is to determine the long-term safety of withdrawing drug therapy in these patients. METHODS: The REMOVE trial is a prospective, multicenter, open-label and randomized 1:1 study designed to assess the effect of withdrawing neurohormonal blockers in patients with nonischemic dilated cardiomyopathy associated with left bundle branch block who recovered LVEF after CRT. The study will include a 12-month follow-up with the option to continue into the follow-up extension phase for up to 24 months. The primary endpoint is the recurrence of cardiomyopathy defined as any of the following criteria: a) a reduction in LVEF >10% (provided the LVEF is <50%); b) a reduction in LVEF >10% accompanied by an increase >15% in the indexed end-systolic volume relative to the previous value and in a range higher than the normal values, or c) decompensated heart failure requiring intravenous diuretic administration. In patients meeting the primary endpoint, drug therapy will be restarted. CONCLUSIONS: The results of this study will help to enhance our understanding of CRT superresponders, a specific group of patients. Registred at ClinicalTrials.gov (Identifier: NCT05151861).

Comparison of risk prediction with the CKD-EPI and MDRD equations in acute decompensated heart failure.

BACKGROUND: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate (eGFR) more accurately than the Modification of Diet in Renal Disease (MDRD) equation. The aim of this study was to evaluate whether CKD-EPI equations based on serum creatinine and/or cystatin C (CysC) predict risk for adverse outcomes more accurately than the MDRD equation in a hospitalized cohort of patients with acute decompensated heart failure (ADHF). METHODS AND RESULTS: A total of 526 subjects with ADHF were studied. Blood was collected within 48 hours from admission. eGFR was calculated with the use of MDRD and CKD-EPI equations. The occurrences of mortality and heart failure (HF) hospitalization were recorded. Over the study period (median 365 days [interquartile range 238-370]), 305 patients (58%) died or were rehospitalized for HF. Areas under the receiver operator characteristic curves for CKD-EPI CysC and CKD-EPI creatinine-CysC equations were significantly higher than that for the MDRD equation, especially in patients with >60 mL min(-1) 1.73 m(-2). After multivariate adjustment, all eGFR equations were independent predictors of adverse outcomes (P < .001). However, only CKD-EPI CysC and CKD-EPI creatinine-CysC equations were associated with significant improvement in reclassification analyses (net reclassification improvements 10.8% and 12.5%, respectively). CONCLUSIONS: In patients with ADHF, CysC-based CKD-EPI equations were superior to the MDRD equation for predicting mortality and/or HF hospitalization especially in patients with >60 mL min(-1) 1.73 m(-2), and both CKD-EPI equations improved clinical risk stratification.

The prognostic role of the adiponectin levels in atrial fibrillation.

BACKGROUND: Patients with atrial fibrillation (AF) have a high morbidity and mortality from vascular events, even despite oral anticoagulation (OAC). Rather than being a risk factor, AF has been proposed as a risk marker, being a signal of advanced atherosclerosis. Circulating adiponectin levels, a cytokine with anti-inflammatory and cardioprotector roles, are related to different atherosclerotic risk factors. The aim is to evaluate whether plasma adiponectin can be predictive of cardiovascular risk in anticoagulated patients with AF. MATERIALS AND METHODS: We included 918 stable anticoagulated out patients with nonvalvular AF [50·1% male; median age 76 (70-80) years; median score for the stroke risk stratification scheme CHA(2) DS(2) -VASc was 4 (3-5)]. Plasma adiponectin was determined by ELISA. Clinical follow-up and cardiovascular adverse events were recorded. RESULTS: After a median follow-up of 956 (784-1085) days, 113 cardiovascular events were recorded (annual rate 4·70%/year) and 99 patients died (rate 4·12%/year). Low plasma adiponectin (< 4444 ng/mL) was significantly associated with major cardiovascular events in female patients [HR 2·96 (95%CI 1·78-4·92)]; P < 0·001, even after adjusting for clinical confounder factors. Adiponectin was neither predictive of stroke/thromboembolism nor all-cause mortality in females, nor for any end-point in males. CONCLUSIONS: Adiponectin is suggested as an independent prognostic biomarker for cardiovascular events in anticoagulated female patients with AF. Our data reinforce the importance of AF as a risk marker of atherosclerotic vascular damage.

Beta-trace protein and cystatin c as predictors of major bleeding in non-ST-segment elevation acute coronary syndrome.

BACKGROUND: Beta-trace protein (BTP) and cystatin C (CysC) are novel biomarkers of renal function. We assessed the ability of both to predict major bleeding (MB) in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), compared to other renal function parameters and clinical risk scores. METHODS AND RESULTS: We included 273 patients. Blood samples were obtained within 24h of admission. The endpoint was MB. During a follow-up of 760 days (411-1,098 days), 25 patients (9.2%) had MB. Patients with MB had higher concentrations of BTP (0.98 mg/L; 0.71-1.16 mg/L vs. 0.72 mg/L, 0.60-0.91 mg/L, P=0.002), CysC (1.05 mg/L; 0.91-1.30 mg/L vs. 0.90 mg/L, 0.75-1.08 mg/L, P=0.003), higher CRUSADE score (39 ± 16 points vs. 29 ± 15 points, P=0.002) and lower estimated glomerular filtration rate (eGFR; 66 ± 27 vs. 80 ± 30 ml·min(-1)·1.73 m(-2), P=0.02) than patients without MB; there was no difference in creatinine level between the groups (P=0.14). After multivariable adjustment, both were predictors of MB, while eGFR and creatinine did not achieve statistical significance. Among subjects with eGFR >60 ml·min(-1)·1.73 m(-2), those with elevated concentrations of both biomarkers had a significantly higher risk for MB. Net reclassification indexes from the addition of BTP and CysC to CRUSADE risk score were 38% and 21% respectively, while the relative integrated discrimination indexes were 12.5% and 3.8%. CONCLUSIONS: Among NSTE-ACS patients, BTP and CysC were superior to conventional renal parameters for predicting MB, and improved clinical stratification for hemorrhagic risk.

Oral anticoagulation improves the prognosis of octogenarian patients with atrial fibrillation undergoing percutaneous coronary intervention and stenting.

BACKGROUND: a significant proportion of octogenarian patients with atrial fibrillation (AF) undergo percutaneous coronary intervention (PCI) with stenting. Dual antiplatelet therapy is recommended in these patients, requiring a period of triple therapy with dual antiplatelet agent plus oral anticoagulation (OAC). Concerns remain regarding the appropriateness of OAC in octogenarians. METHODS: we reviewed 604 patients (15.7% ≥80 years) with AF undergoing PCI. Clinical follow-up was performed, recording any bleeding episode, thrombo-embolism and major adverse cardiac events (MACE = death, acute myocardial infarction and/or revascularisation of target lesion). We compared octogenarian patients in relation to treatment with OAC at discharge. A secondary aim was to compare octogenarian patients with non-octogenarian patients in terms of their clinical and demographic characteristics, management and clinical outcome. RESULTS: among the 604 patients, 95(15.7%) were aged ≥80 years. Octogenarians had a higher median CHADS2 score (2.78 versus 2.01; P < 0.001) and HAS-BLED score (3.05 versus 2.84; P = 0.028). After a follow-up of 17 ± 14 months, all-cause death occurred in 33%, MACE in 44%, and major bleeding in 21%. OAC was associated with less MACE (28.9 versus 58.3%; P = 0.012) and a similar rate of major bleeding. On multivariable analysis, non-use of OAC at discharge was associated with increased MACE (OR = 4.3; 95% CI = 1.3-14.6; P = 0.02). CONCLUSION: octogenarian AF patients undergoing PCI/stenting have a high mortality rate and MACE, which can be reduced by means of OAC therapy.

Antithrombotic Strategy in Secondary Prevention for High-Risk Patients with Previous Acute Coronary Syndrome: Overlap between the PEGASUS Eligibility and the COMPASS Eligibility in a Large Multicenter Registry.

BACKGROUND: Patients with previous acute coronary syndrome (ACS) are at high risk of recurrent adverse cardiovascular events. Recently, prolonged dual antiplatelet therapy (DAPT) and oral anticoagulation therapy (OAT) have been shown to reduce recurrent ischemic events to the expense of an increase in bleeding events. The number of patients potentially eligible for these therapies in real life remains to be determined. METHODS: Among ACS patients from five registries and one randomized controlled trial, we assessed the proportion of patients eligible for the PEGASUS strategy only and the proportion of patients eligible for the COMPASS strategy only, and set out the proportion of patients with an overlap between the strategies. FINDINGS: Among the 10,048 evaluable patients, we found that 5373 (53.4%) were eligible for the PEGASUS strategy and 3841 (38.2%) were eligible for the COMPASS strategy, with a group of 3444 (34.4%) overlapping between the two strategies. The number of patients eligible for the PEGASUS strategy only was 1929 (19.2%) and the number eligible for the COMPASS strategy only was 397 (4.0%); 4278 (42.6%) were eligible for neither a PEGASUS strategy nor a COMPASS strategy. INTERPRETATION: In a large cohort of ACS patients, one in three patients was eligible for either a prolonged DAPT with ticagrelor 60 mg and low-dose aspirin or a dual pathway inhibition approach with rivaroxaban 2.5 mg and low-dose aspirin.

Highly sensitive troponin T for risk stratification of acutely destabilized heart failure.

BACKGROUND: A highly sensitive assay for troponin T (hsTnT) has been recently developed, which allows for the detection of even minor myocardial necrosis with high precision. It remains unexplored whether hsTnT provides incremental prognostic accuracy beyond conventional (c)TnT in patients with acutely decompensated heart failure (ADHF). METHODS: A total of 202 consecutive patients admitted with ADHF and without criteria for acute myocardial infarction were studied. Troponin T was measured using the highly sensitive assay and compared with the conventional method. Patients were clinically followed up at a median of 406 days, with a primary outcome measure of all-cause mortality. RESULTS: The high-sensitive assay detected measurable TnT in 98% of patients vs 56% for cTnT; 81% had an hsTnT above the 99th percentile for a healthy reference population, and it reclassified 60% of those with undetectable cTnT. Both TnT methods predicted the risk of death in adjusted multivariable Cox regression analyses, without a superiority of hsTnT over cTnT in the entire population (area under the curve 0.67 vs 0.71, P = .2). Among patients with a cTnT below 0.03 ng/mL (the lowest cut-point with <10% imprecision; n = 134), solely hsTnT improved the prediction of death over clinical risk factors (relative integrated discrimination improvement +36%, P = .01) and hsTnT above 20 pg/mL identified a significant higher risk of death (hazard ratio 4.7, 95% CI 1.6-13.8, P = .005). CONCLUSION: Among patients with ADHF, myocardial necrosis (as detected with the hsTnT assay) was nearly ubiquitous. The highly sensitive assay for TnT provides comparable prognostic information to cTnT overall, but among those in whom the cTnT method was less precise or frankly negative, the hsTnT assay provided prognostic information.

Ankle brachial index as an independent predictor of mortality in anticoagulated atrial fibrillation.

BACKGROUND: An abnormal ankle brachial index (ABI, the ratio of the ankle and the brachial systolic blood pressure) (≤ 0·90 or ≥ 1·4) suggests the presence of peripheral arterial disease (PAD) and has proposed as a marker of cardiovascular risk. We hypothesised that the ABI would predict mortality and adverse events in anticoagulated chronic nonvalvular AF patients. METHODS: We recruited 287 consecutive anticoagulated outpatients with permanent or paroxysmal nonvalvular AF who were stabilised for 6 months on oral anticoagulation (Oral anticoagulation; INR 2·0-3·0). ABI was performed following a standard technique. Cox models were used to determine the association between ABI, and bleeding, cardiovascular events and mortality. RESULTS: Median ABI was 1·09 (0·93-1·23) and 78 (27%) had an abnormal ABI. Abnormal ABI was associated with diabetes, heart failure and ischaemic heart disease (P = 0·006, 0·019 and 0·009, respectively), and a CHADS(2) score ≥ 2 (P = 0·016). Median follow-up was 861 (718-1016) days, during 21(7%) presented an adverse cardiovascular event, 23 (8%) major bleeding events and 18 (6%) died. ABI was an independent predictor for all-cause mortality, even after adjusting for CHADS(2) score (Cox multivariable regression analysis, HR 2·76(1·08-7·06), P = 0·033). Abnormal ABI was significantly associated with major haemorrhagic events [HR: 2·47(1·01-6·04); P = 0·047], even after adjustment for HAS-BLED score. CONCLUSION: Abnormal ABI is common in AF patients, and ABI was an independent predictor for all-cause mortality, even after adjusting for CHADS(2) score. ABI was an independent predictor for major bleeding, even after adjusting for the HAS-BLED score. ABI could be a useful tool for improving risk stratification of anticoagulated AF patients.

Prognostic significance of long-period heart rate rhythms in chronic heart failure.

BACKGROUND: Abnormalities in autonomic control are a feature of neuroendocrine activation in HF and are responsible for dysregulation of biological rhythms. The purpose was to investigate the presence and the prognostic significance of long-period heart rate (HR) rhythms in heart failure (HF) patients. METHODS AND RESULTS: In the study, 92 HF patients were enrolled (age 53 ± 14 years and left ventricular ejection fraction [LVEF] 37 ± 10%). A rhythmometric analysis was used to assess the HR rhythms in 7-days (7D) Holter recordings. Rhythms properties were quantified by mesor and amplitude, in beats/min and by acrophase, in hours. Cardiac death or HF decompensation were registered. All patients had 24-h rhythm, 61 patients (77%) had 8-h rhythm, and 66 patients (83%) had 7D rhythm. Twelve patients (15%) experienced events. Among rhythm parameters only 7D median amplitude was different between patients with or without events: 1.1 beats/min [0.5-1.5] vs. 2.0 beats/min [0.0-3.9], P=0.049 respectively. After multivariate adjustment, LVEF (per 1%, hazard ratio 0.92, 95% confidence interval (CI) 0.87 to 0.98, P=0.01), N-terminal portion of pro-natriuretic hormone type B (per 100 pg/ml, hazard ratio 1.036, 95% CI 1.005-1.069, P=0.022), and 7D amplitude of the HR ≤1.71 beats/min (hazard ratio 5.4, 95% CI 1.2-34.4, P=0.047) were independent predictors of events. CONCLUSIONS: A 7D HR rhythm is present in most patients with HF, and has prognostic significance.

High-sensitivity troponin T and copeptin in non-ST acute coronary syndromes: implications for prognosis and role of hsTnT and copeptin in non-STEACS.

UNLABELLED: High-sensitivity TnT (hsTnT) has been proposed to improve the diagnosis and stratification in acute coronary syndromes. Copeptin has been proposed for a rapid and accurate rule out of acute myocardial infarction, but some doubts exist about its use out of the first hours from admission. Abnormalities of serum hsTnT and copeptin levels in non-STEACS and negative TnT, could have prognostic implications. METHODS: We included 122 non-STEACS patients without raised TnT, 33 disease controls and 43 healthy controls. We measured hsTnT and copeptin levels. Clinical follow-up at 12 months was performed for adverse endpoints. RESULTS: Non-STEACS patients had raised hsTnT compared with both control groups (P = 0.036 and P < 0.001). Copeptin levels were higher in non-STEACS patients than healthy controls (P = 0.021), without differences with disease controls. Raised levels of hs-TnT presented prognostic implications [HR 3.29 (95%CI: 1.33-7.49), P = 0.010]. hs-TnT could be used for invasive approach decision, as it shows prognostic relevance in conservative approach-patients whereas remains unrelevant for catheterized-patients. Copeptin levels were not associated with adverse events. CONCLUSION: hsTnT levels increased in non-STEACS, were predictive of adverse events and could be important for recommending an invasive management. We cannot confirm a predictive role of copeptin out of the first hours from admission.