Derivation and Validation of the PRECISE-HBR Score to Predict Bleeding After Percutaneous Coronary Intervention.

BACKGROUND: Accurate bleeding risk stratification after percutaneous coronary intervention (PCI) is important for treatment individualization. However, there is still an unmet need for a more precise and standardized identification of high bleeding risk patients. We derived and validated a novel bleeding risk score by augmenting the PRECISE-DAPT score with the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria. METHODS: The derivation cohort comprised 29,188 patients undergoing PCI, of whom 1136 (3.9%) had a Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding at 1 year, from four contemporary real-world registries and the XIENCE V USA trial. The PRECISE-DAPT score was refitted with a Fine-Gray model in the derivation cohort and extended with the ARC-HBR criteria. The primary outcome was BARC 3 or 5 bleeding within 1 year. Independent predictors of BARC 3 or 5 bleeding were selected at multivariable analysis (p<0.01). The discrimination of the score was internally assessed with apparent validation and cross-validation. The score was externally validated in 4578 patients from the MASTER DAPT trial and 5970 patients from the STOPDAPT-2 total cohort. RESULTS: The PRECISE-HBR score (age, estimated glomerular filtration rate, hemoglobin, white-blood-cell count, previous bleeding, oral anticoagulation, and ARC-HBR criteria) showed an area under the curve (AUC) for 1-year BARC 3 or 5 bleeding of 0.73 (95% CI, 0.71-0.74) at apparent validation, 0.72 (95% CI, 0.70-0.73) at cross-validation, 0.74 (95% CI, 0.68-0.80) in the MASTER DAPT, and 0.73 (95% CI, 0.66-0.79) in the STOPDAPT-2, with superior discrimination than the PRECISE-DAPT (cross-validation: Δ AUC, 0.01; p=0.02; MASTER DAPT: Δ AUC, 0.05; p=0.004; STOPDAPT-2: Δ AUC, 0.02; p=0.20) and other risk scores. In the derivation cohort, a cut-off of 23 points identified 11,414 patients (39.1%) with a 1-year BARC 3 or 5 bleeding risk ≥4%. An alternative version of the score, including acute myocardial infarction on admission instead of white-blood-cell count, showed similar predictive ability. CONCLUSIONS: The PRECISE-HBR score is a contemporary, simple 7-item risk score to predict bleeding after PCI, offering a moderate improvement in discrimination over multiple existing scores. Further evaluation is required to assess its impact on clinical practice.

Efficacy and safety of bempedoic acid in acute coronary syndrome. Design of the clinical trial ES-BempeDACS.

INTRODUCTION AND OBJECTIVES: Only about 1 out of every 3 patients with acute myocardial infarction (AMI) achieve low-density lipoprotein cholesterol (LDL-C) values <55mg/dL in the first year. The present study aims to evaluate the impact of early intensive therapy on lipid control after an AMI. METHODS: An independent, prospective, pragmatic, controlled, randomized, open-label, evaluator-blinded clinical trial (PROBE design) will analyze the efficacy and safety of an oral lipid-lowering triple therapy: high-potency statin+bempedoic acid (BA) 180mg+ezetimibe (EZ) 10mg versus current European-based guidelines (high-potency statin±EZ 10mg), in AMI patients. LDL-C will be determined within the first 48hours. Patients with LDL-C ≥ 115mg/dL (without previous statin therapy), ≥ 100mg/dL (with previous low-potency or high-potency statin therapy at submaximal dose), or ≥ 70mg/dL (with previous high-potency statin therapy at high dose) will be randomly assigned 1:1 between 24 and 72hours post-AMI to the BA/EZ combination or to statin±EZ, without BA. The primary endpoint is the proportion of patients reaching LDL-C <55mg/dL at 8 weeks after treatment. RESULTS: The results of this study will provide novel information for post-AMI LDL-C control by evaluating the usefulness of an early intensive lipid-lowering strategy based on triple oral therapy. CONCLUSIONS: Early intensive lipid-lowering triple oral therapy vs the treatment recommended by current clinical practice guidelines could facilitate the achievement of optimal LDL-C levels in the first 2 months after AMI (a high-risk period). IDENTIFICATION NUMBER: EudraCT 2021-006550-31.

Comparison between beta-blockers and calcium channel blockers in patients with atrial fibrillation according to renal function.

BACKGROUND: Rate control is the most commonly employed first-line management strategy for atrial fibrillation (AF) in patients with chronic kidney disease (CKD). Principal agents used to control heart rate (HR) include beta-blockers (BB) and nondihydropyridine calcium channel blockers (ND-CCB). However, there is a paucity of published studies of the differences between those drugs in CKD patients. HYPOTHESIS: The present study aimed to investigate the differences, in terms of hospitalizations due to a poor HR control, in patients with AF under a rate-control strategy according to glomerular filtration rate (GFR). METHODS: The study cohort included 2804 AF patients under rate-control regime (BB or ND-CCB) between January 2014 and April 2020. The end point, determined by competing risk regression, was hospitalizations for AF with rapid ventricular response (RVR), slow ventricular response (SVR), and need for pacemaker. RESULTS: On multivariate analysis, there were no statistical differences between ND-CCB and BB for subjects with GFR > 60 mL/min/1.73 m2 (subdistribution heart rate [sHR] 0.850, 95% confidence interval [CI]: 0.61-1.19; p = .442) and GFR 30-59 mL/min/1.73 m2 (sHR 1.242, 95% CI: 0.80-1.63; p = .333), while in patients with GFR < 30 mL/min/1.73 m2, ND-CCB therapy was associated with increased hospitalizations due to poor HR control (sHR 4.53, 95% CI: 1.19-17.18; p = .026). CONCLUSION: In patients with GFR ≥ 30 mL/min/1.73 m2, the choice of ND-CCB or BB had no impact on hospitalizations due to poor HR control, while in GFR < 30 mL/min/1.73 m2, a possible association was detected. The effects of these drugs on GFR < 30 mL/min/1.73 m2 would require further investigation.

Relative performance evaluation of four bleeding risk scores in atrial fibrillation patients. What does the new DOAC score provide?

BACKGROUND: Recently, the direct oral anticoagulant (DOAC) score was developed and better predicted major bleeding in DOAC-treated patients with atrial fibrillation (AF) than HASBLED did. Little is known on the new score's performance regarding other bleeding risk in AF. METHODS: We studied 14,672 patients diagnosed with AF between 2014 and 2018. During follow-up, we assessed the performance of DOAC score compared with the HASBLED, ORBIT and SWISS scores at predicting major bleeding in DOACs and non-DOACs users. Discrimination, calibration and decision curve analysis (DCA) were used to assess the risk scorer's performance. RESULTS: There were 1484 (10.1%) patients on DOACs, 9730 on vitamin K antagonist (VKA), and 3458 on non-oral anticoagulants. Over a median of 3.5 years of follow-up, 79 major bleedings occurred in the DOAC patients, and 486 in the VKA patients (cumulative incidences = 7.4 and 13.9 per 100 patient-years, respectively). Amongst the DOAC patients, the DOAC score discrimination was moderate (C-statistic = 0.711), but significantly higher than HASBLED (C = 0.640; p = 0.03), ORBIT (C = 0.660; p = 0.04), and SWISS scores (C = 0.637; p = 0.002). The DCA showed higher net benefit using DOAC score compared with the remaining scores. In the VKA patients, DOAC score showed the highest discrimination (c-statistic = 0.709), followed by ORBIT (C = 0.692; p = 0.07), HASBLED and SWISS (C = 0.635 and 0.624, respectively; p < 0.01). All risk scores calibrated well, although HASBLED showed relatively poor calibration. CONCLUSIONS: The new DOAC bleeding risk score is a valid and reasonable predictor of major bleeding over a median of 3.5 years of follow-up. Physicians can be reassured about the applicability of DOAC score for bleeding risk stratification in AF patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04364516.

Is pre-diabetes a predictor of events in patients with atrial fibrillation?

BACKGROUND: Diabetes mellitus (DM) increases the probability of presenting atrial fibrillation (AF) and it is a predictor of its ischemic stroke. There is limited information of the association between glycated hemoglobin (HbA1c) levels and ischemic, embolic or bleeding events in patients with pre-DM and AF. METHODS: To investigate whether the presence of pre-DM in patients with AF predicts ischemic or bleeding events, myocardial infarction or mortality, we performed a retrospective study with a final cohort of 2993 non-diabetic patients with AF and data of glycated hemoglobin (HbA1c). We divided the cohort in two groups: those with normal glucose (n = 1351) and those with pre-diabetes (n = 1642). Incidence rates were calculated as the number of events per 100 person-years and were then compared between groups. Competitive hazard regression analysis for non-fatal events(death as the competing event) and conventional Cox regression for mortality were performed. RESULTS: There was not difference between groups for incidence rates of the different events per 100 person-years. Even considering HbA1c as continuous variable, the unadjusted analysis showed no relation between levels of HbA1c and more risk of events. This association remained not significant after adjustment for CHA2DS2-VASc score, HAS-BLED score and anticoagulation therapy. CONCLUSION: In this study of 2993 non-diabetic patients with new-onset AF, we have not found an association between HbA1c and worse prognosis when it is in the range of pre-diabetes.

Gender differences in the development of heart failure after acute coronary syndrome: Insight from the CORALYS registry.

BACKGROUND: Impact of gender on heart remodeling after acute coronary syndrome (ACS) and consequently on development of heart failure (HF) remains to be elucidated. METHODS: CORALYS is a multicenter, retrospective, observational registry enrolling consecutive patients admitted for ACS and treated with percutaneous coronary intervention. HF hospitalization was the primary endpoint while all-cause mortality and the composite endpoint of incidence of first HF hospitalization and cardiovascular mortality were the secondary ones. RESULTS: Among 14,699 patients enrolled in CORALYS registry, 4578 (31%) were women and 10,121 (69%) males. Women were older, had more frequently hypertension and diabetes and less frequently smoking habit. History of myocardial infarction (MI), STEMI at admission and multivessel disease were less common in women. After median follow up of 2.9 ± 1.8 years, women had higher incidence of primary and secondary endpoints and female sex was an independent predictor of HF hospitalization (HR 1.26;1.05-1.50; p = 0.011) and cardiovascular death/HF hospitalization (HR 1.18;1.02-1.37; p = 0.022). At multivariable analysis women and men share as predictors of HF diabetes, history of cancer, chronic kidney disease, atrial fibrillation, complete revascularization and left ventricular ejection fraction. Chronic obstructive pulmonary disease (HR 2.34;1.70-3.22, p < 0.001) and diuretics treatment (HR 1.61;1.27-2.04, p < 0.001) were predictor of HF in men, while history of previous MI (HR 1.46;1.08-1.97, p = 0.015) and treatment with inhibitors of renin-angiotensin system (HR 0.69;0,49-0.96 all 95% CI, p = 0.030) in women. CONCLUSIONS: Women are at increased risk of HF after ACS and gender seems to be an outcome-modifier of the relationship between a variable and primary outcome.

Liver fibrosis and outcomes of atrial fibrillation: the FIB-4 index.

BACKGROUND AND AIMS: Liver diseases play an important role in the development and progression of atrial fibrillation (AF). The Fibrosis-4 (FIB-4) index is a non-invasive score recommended for detecting liver fibrosis. Since the association between liver fibrosis and outcomes of AF patients is still not well defined, we aim to analyze prognosis impact of FIB-4 index in those patients. METHODS: A retrospective population-based cohort study was performed with 12,870 unselected patients from a single health area in Spain with AF from 2014 to 2019. Cox regression models were used to estimate the association of FIB-4 index with mortality. The association with ischemic stroke (IS), major bleeding (MB), acute myocardial infarction (AMI), and heart failure (HF) was assessed by competing risk analysis. RESULTS: A total of 61.1%, 22.0%, and 16.9% were classified as low, moderate and high risk of liver fibrosis according to FIB-4 index, respectively. During a mean follow-up of 4.5 ± 1.7 years, FIB-4 index was associated with mortality (adjusted HR 1.04; 95% CI 1.01-1.06; p = 0.002), MB and HF (adjusted sHR 1.03, 95% CI 1.01-1.04; p = 0.004), but not with IS or with AMI. The association between FIB-4 and MB was only found in patients treated with vitamin K antagonists, not in patients on direct oral anticoagulants. CONCLUSIONS: The FIB-4 index, a non-invasive scoring method for evaluating liver fibrosis, is independently associated with all-cause mortality, MB and HF in patients with AF, suggesting that it may be useful as a risk assessment tool to identify adverse outcomes in patients with AF.

Heart failure in older patients with atrial fibrillation: incidence and risk factors.

INTRODUCTION AND OBJECTIVES: Atrial fibrillation (AF) is linked to heart failure (HF). However, little has been published on the factors that may precipitate the onset of HF in AF patients. We aimed to determine the incidence, predictors, and prognosis of incident HF in older patients with AF with no prior history of HF. METHODS: Patients with AF older than 80 years and without prior HF were identified between 2014 and 2018. RESULTS: A total of 5794 patients (mean age, 85.2±3.8 years; 63.2% women) were followed up for 3.7 years. Incident HF, predominantly with preserved left ventricular ejection fraction, developed in 33.3% (incidence rate, 11.5-100 people-year). Multivariate analysis identified 11 clinical risk factors for incident HF, irrespective of HF subtype: significant valvular heart disease (HR, 1.99; 95%CI, 1.73-2.28), reduced baseline left ventricular ejection fraction (HR, 1.92; 95%CI, 1.68-2.19), chronic pulmonary obstructive disease (HR, 1.59; 95%CI, 1.40-1.82), enlarged left atrium (HR 1.47, 95%CI 1.33-1.62), renal dysfunction (HR 1.36, 95%CI 1.24-1.49), malnutrition (HR, 1.33; 95%CI, 1.21-1.46), anemia (HR, 1.30; 95%CI, 1.17-1.44), permanent AF (HR, 1.15; 95%CI, 1.03-1.28), diabetes mellitus (HR, 1.13; 95%CI, 1.01-1.27), age per year (HR, 1.04; 95%CI, 1.02-1.05), and high body mass index for each kg/m2 (HR, 1.03; 95%CI, 1.02-1.04). The presence of incident HF nearly doubled the mortality risk (HR, 1.67; 95%CI, 1.53-1.81). CONCLUSIONS: The presence of HF in this cohort was relatively frequent and nearly doubled the mortality risk. Eleven risk factors for HF were identified, expanding the scope for primary prevention among elderly patients with AF.

Predictive value of bleeding risk scores in elderly patients with atrial fibrillation and oral anticoagulation.

BACKGROUND: The predictive value of bleeding risk scores for atrial fibrillation in older patients is not as well known. The goal of this study was to evaluate the predictive value of HASBLED, ORBIT and ATRIA for major bleeding (MB) and intracranial hemorrhage (ICH) in patients ≥ 75 years with atrial fibrillation and oral anticoagulation (OAC). METHODS: A retrospective unicenter study including patients ≥ 75 years with atrial fibrillation (AF) and OAC. A total of 7613 patients ≥ 75 years with AF and OAC included between 2014 and 2018 (registry: NCT04364516). We analyzed the discriminative value of HASBLED, ATRIA and ORBIT scores for bleeding endpoints (major bleeding as primary endpoint and intracerebral hemorrhage as secondary). Cox regression was used to predict major bleeding with each scale and also for searching other variables potentially predictor of major bleeding. Model discrimination was assessed using Harrell's C-statistic. Calibration was assessed with goodness-of-fit test proposed by Gronnesby and Borgan. RESULTS: During a mean follow up of 4.0 years (IQR: 2.4-5.7 years), 729 patients developed MB (2.61 per 100 patients/year) and 243 patients developed ICH (0.85 per 100 patients/year). Three scores showed a low discrimination for major bleeding, being ORBIT the best (HASBLED C statistic = 0.557; ATRIA C statistic = 0.568; ORBIT C statistic = 0.595) and also a low discrimination for ICH (HASBLED C statistic = 0.509; ATRIA C statistic = 0.522; ORBIT C statistic = 0.526). Among the variables that are part of the scores and other baseline characteristics, after multivariable adjustment only sex (male), dementia, prior admission for bleeding, anemia and liver disease were found as a predictors of MB. CONCLUSIONS: In older patients under oral anticoagulation with atrial fibrillation, the risk scores HASBLED, ATRIA and ORBIT showed a weak discrimination for major bleeding and intracranial hemorrhage. Therefore, other better alternatives should be evaluated for this purpose.

Forecasting the Risk of Heart Failure Hospitalization After Acute Coronary Syndromes: the CORALYS HF Score.

The present study aimed to identify patients at a higher risk of hospitalization for heart failure (HF) in a population of patients with acute coronary syndrome (ACS) treated with percutaneous coronary revascularization without a history of HF or reduced left ventricular (LV) ejection fraction before the index admission. We performed a Cox regression multivariable analysis with competitive risk and machine learning models on the incideNce and predictOrs of heaRt fAiLure After Acute coronarY Syndrome (CORALYS) registry (NCT04895176), an international and multicenter study including consecutive patients admitted for ACS in 16 European Centers from 2015 to 2020. Of 14,699 patients, 593 (4.0%) were admitted for the development of HF up to 1 year after the index ACS presentation. A total of 2 different data sets were randomly created, 1 for the derivative cohort including 11,626 patients (80%) and 1 for the validation cohort including 3,073 patients (20%). On the Cox regression multivariable analysis, several variables were associated with the risk of HF hospitalization, with reduced renal function, complete revascularization, and LV ejection fraction as the most relevant ones. The area under the curve at 1 year was 0.75 (0.72 to 0.78) in the derivative cohort, whereas on validation, it was 0.72 (0.67 to 0.77). The machine learning analysis showed a slightly inferior performance. In conclusion, in a large cohort of patients with ACS without a history of HF or LV dysfunction before the index event, the CORALYS HF score identified patients at a higher risk of hospitalization for HF using variables easily accessible at discharge. Further approaches to tackle HF development in this high-risk subset of patients are needed.

Impact of Complete Revascularization on Development of Heart Failure in Patients With Acute Coronary Syndrome and Multivessel Disease: A Subanalysis of the CORALYS Registry.

Background The impact of complete revascularization (CR) on the development of heart failure (HF) in patients with acute coronary syndrome and multivessel coronary artery disease undergoing percutaneous coronary intervention remains to be elucidated. Methods and Results Consecutive patients with acute coronary syndrome with multivessel coronary artery disease from the CORALYS (Incidence and Predictors of Heart Failure After Acute Coronary Syndrome) registry were included. Incidence of first hospitalization for HF or cardiovascular death was the primary end point. Patients were stratified according to completeness of coronary revascularization. Of 14 699 patients in the CORALYS registry, 5054 presented with multivessel disease. One thousand four hundred seventy-three (29.2%) underwent CR, while 3581 (70.8%) did not. Over 5 years follow-up, CR was associated with a reduced incidence of the primary end point (adjusted hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]), first HF hospitalization (adjusted HR, 0.67 [95% CI, 0.49-0.90]) along with all-cause death and cardiovascular death alone (adjusted HR, 0.74 [95% CI, 0.56-0.97] and HR, 0.56 [95% CI, 0.38-0.84], respectively). The results were consistent in the propensity-score matching population and in inverse probability treatment weighting analysis. The benefit of CR was consistent across acute coronary syndrome presentations (HR, 0.59 [95% CI, 0.39-0.89] for ST-segment elevation myocardial infarction and HR, 0.71 [95% CI, 0.50-0.99] for non-ST-elevation acute coronary syndrome) and in patients with left ventricular ejection fraction >40% (HR, 0.52 [95% CI, 0.37-0.72]), while no benefit was observed in patients with left ventricular ejection fraction ≤40% (HR, 0.77 [95% CI, 0.37-1.10], P for interaction 0.04). Conclusions CR after acute coronary syndrome reduced the risk of first hospitalization for HF and cardiovascular death, as well as first HF hospitalization, and cardiovascular and overall death both in patients with ST-segment elevation myocardial infarction and non-ST-elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04895176.

Optimal medical therapy improves outcomes in patients with diabetes mellitus and acute myocardial infarction.

AIMS: We aimed to explored the association between the use of optimal medical therapy (OMT) in patients with myocardial infarction (AMI) and diabetes mellitus (DM) and clinical outcomes. METHODS: Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome (BleeMACS) is an international registry that enrolled participants with acute coronary syndrome followed up for at least 1 year across 15 centers from 2003 to 2014. Baseline characteristics and endpoints were analyzed. RESULTS: Among 3095 (23.2%) patients with AMI and DM, 1898 (61.3%) received OMT at hospital discharge. OMT was associated with significantly reduced mortality (4.3% vs. 10.8%, p < 0.001), re-AMI (4.4% vs. 8.1%, p < 0.001), and composite endpoint of death/re-AMI (8.0% vs. 17.6%, p < 0.001). No difference was observed among regions. Propensity score matching confirmed that OMT significantly associated with lower mortality. After adjusting for confounding variables, OMT, drug-eluting stents, and complete revascularization were independent protective factors of 1-year mortality, whereas left ventricular ejection fraction and age were risk factors. CONCLUSIONS: Guideline-recommended OMT was prescribed at suboptimal frequencies with geographic variations in this worldwide cohort. OMT can improve long-term clinical outcomes in patients with DM and AMI. CLINICAL TRIAL REGISTRATION: NCT02466854 June 9, 2015.

Impact of Right Ventricular Pacing in Patients With TAVR Undergoing Permanent Pacemaker Implantation.

BACKGROUND: Long-term right ventricular pacing (VP) has been related to negative left ventricular remodeling and heart failure (HF), but there is a lack of evidence regarding the prognostic impact on transcatheter aortic valve replacement (TAVR) patients. OBJECTIVES: The aim of the PACE-TAVI registry is to evaluate the association of high percentage of VP with adverse outcomes in patients with pacemaker implantation after TAVR. METHODS: PACE-TAVI is an international multicenter registry of all consecutive TAVR patients who underwent permanent pacemaker implantation for conduction disturbances in the first 30 days after the procedure. Patients were divided into 2 subgroups according to the percentage of VP (<40% vs ≥40%) at pacemaker interrogation. The primary endpoint was the composite of cardiovascular mortality or hospitalization for HF. RESULTS: A total of 377 patients were enrolled, 158 with VP <40% and 219 with VP ≥40%. After multivariable adjustment, VP ≥40% was associated with a higher incidence of the primary endpoint (HR: 2.76; 95% CI: 1.39-5.51; P = 0.004), first HF hospitalization (HR: 3.37; 95% CI: 1.50-7.54; P = 0.003), and cardiovascular death (HR: 3.77; 95% CI: 1.02-13.88; P = 0.04), while the incidence of all-cause death was not significantly different (HR: 2.17; 95% CI: 0.80-5.90; P = 0.13). Patients with VP ≥ 40% showed a higher New York Heart Association functional class both at 1 year (P = 0.009) and at last available follow-up (P = 0.04) and a nonsignificant reduction of left ventricular ejection fraction (P = 0.18) on 1-year echocardiography, while patients with VP <40% showed significant improvement (P = 0.009). CONCLUSIONS: In TAVR patients undergoing permanent pacemaker implantation, a high percentage of right VP at follow-up is associated with an increased risk for cardiovascular death and HF hospitalization. These findings suggest the opportunity to minimize right VP through dedicated algorithms in post-TAVR patients without complete atrioventricular block and to evaluate a more physiological VP modality in patients with persistent complete atrioventricular block.

Hypotension at heart failure discharge: Should it be a limiting factor for drug titration?

BACKGROUND: Medical treatment in Heart Failure (HF) with reduced ejection fraction (HFrEF; LVEF ≤40%) has shifted towards quadruple therapy. Maximum tolerated dose is the goal, yet no hypotension's cut-off point has been specified. In this work, we analyze the impact of intensive drug titration in clinical events, focusing on low blood pressure (BP) patients at hospital discharge. METHODS AND RESULTS: Retrospective analysis of 713 patients with HFrEF discharged after an acute HF event (mean LVEF 30 ± 5%). Mean SBP was 112.4 ± 16.5 mmHg and 50.6% were discharged on triple therapy. We considered hypotension as a Systolic blood pressure (SBP) <100 mmHg (21.7% of patients, mean SBP was 112.4 ± 16.5 mmHg) and codified the intensity of drug therapy in 5 stages from untreated to very high therapy intensity. The impact of the intensity of treatment was analysed with a propensity score and increasing the intensity was associated in the whole cohort with a reduction of the composite outcome of all-cause mortality and HF readmission, (HR 0.69; CI95% 0.57-0.85, p < 0.001) and benefit in mortality was maintained for SBP < 100 mmHg (HR 0.42; CI95% 0.22-0.82; p = 0.011). Moreover, therapy intensity was clearly associated with lower risk of HF-hospitalization and death after the additional regression, considering SBP as a covariate, in the whole cohort (HR 0.70; CI95% 0.57-0.85; p < 0.001). CONCLUSIONS: In this retrospective cohort analysis, patients with HFrEF and an acute-HF admission, intensive drug dose titration was related to better outcomes, even in patients with low blood pressure at hospital discharge. Therefore, hypotension is not a contraindication for NHB uptitration.

Left Ventricular Assist Device as a Destination Therapy: Current Situation and the Importance of Patient Selection.

Advanced heart failure is a growing problem for which the best treatment is cardiac transplantation. However, the shortage of donors' hearts made left ventricular assist devices as destination therapy (DT-LVAD) a highly recommended alternative: they improved mid-term prognosis as well as patients' quality of life. Current intracorporeal pumps with a centrifugal continuous flow evolved in the last few years. Since 2003, when first LVAD was approved for long-term support, smaller device sizes with better survival and hemocompatibility profile were reached. The most important difficulty lies in the moment of the implant. Recent indications range from INTERMACS class 2 to 4, with close monitoring in intermediate cases. Moreover, a large multiparametric study is needed for considering the candidacy: basal situation, with a special interest in frailty, comorbidities, including renal and hepatic dysfunction, and medical background, considering every prior cardiac condition, must be evaluated. In addition, some clinical risk scores can be helpful to measure the possibility of right heart failure or morbi-mortality. With this review, we sought to summarize all the device improvements, with their updated clinical results, as well as to focus on all the patient selection criteria.

Comparison of Stroke and Bleeding Risk Profile in Patients With Atrial Fibrillation and Chronic Kidney Disease.

Clinical decision making on anticoagulation in patients with chronic kidney disease with atrial fibrillation (AF) is challenging. The current strategies are based on small observational studies with conflicting results. This study explores the impact of glomerular filtration rate (GFR) in the embolic-hemorrhagic balance among a large cohort of patients with AF. The study cohort included 15,457 patients diagnosed with AF between January 2014 and April 2020. The risk of ischemic stroke and major bleeding was determined by competing risk regression. During a mean follow-up of 4.29 ± 1.82 years, 3,678 patients (23.80%) died, 850 (5.50%) had an ischemic stroke, and 961 (6.22%) had a major bleeding. The incidence of stroke and bleeding increased as baseline GFR decreased. Interestingly, in GFR <30 ml/min/1.73 m2, the bleeding risk was clearly higher than the embolic risk. As GFR decreased, anticoagulation was associated with an increased bleeding risk (subdistribution hazard ratio 1.700, 95% confidence interval [CI] 1.13 to 2.54, p = 0.009 for patients with GFR 30 to 59 ml/min/1.73 m2 and 2.00, 95% CI 0.77 to 5.21, p = 0.156 for subjects with <30 ml/min/1.73 m2 compared with those with GFR >60 ml/min/1.73 m2, respectively), but it was not associated with a decrease in embolic risk in patients with GFR <30 ml/min/1.73 m2 (subdistribution hazard ratio 1.91, 95% CI 0.73 to 5.04, p = 0.189) In GFR <30 ml/min/1.73 m2, the increase of major bleeding risk was higher than the increase of ischemic stroke risk, with a negative anticoagulation balance (greater increase in bleeding than reduction in embolism).

Long-term prognostic impact of beta-blockers in patients with Takotsubo syndrome: Results from the RETAKO Registry.

BACKGROUND: No evidence-based therapy has yet been established for Takotsubo syndrome (TTS). Given the putative harmful effects of catecholamines in patients with TTS, beta-blockers may potentially decrease the intensity of the detrimental cardiac effects in those patients. OBJECTIVE: The purpose of this study was to assess the impact of beta-blocker therapy on long-term mortality and TTS recurrence. METHODS: The cohort study used the national Spanish Registry on TakoTsubo Syndrome (RETAKO). A total of 970 TTS post-discharge survivors, without pheochromocytoma, left ventricular outflow tract obstruction, sustained ventricular arrhythmias, and significant bradyarrhythmias, between January 1, 2003, and July 31, 2018, were assessed. Cox regression analysis and inverse probability weighting (IPW) propensity score analysis were used to evaluate the association between beta-blocker therapy and survival free of TTS recurrence. RESULTS: From 970 TTS patients, 582 (60.0%) received beta-blockers. During a mean follow-up of 2.5±3.3 years, there were 87 deaths (3.6 per 100 patients/year) and 29 TTS recurrences (1.2 per 100 patient/year). There was no significant difference in follow-up mortality or TTS recurrence in unadjusted and adjusted Cox analysis (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.59-1.27, and 0.95, 95% CI 0.57-1.13, respectively). After weighting and adjusting by IPW, differences in one-year survival free of TTS recurrence between patients treated and untreated with beta-blockers were not found (average treatment effect -0.01, 95% CI -0.07 to 0.04; p=0.621). CONCLUSIONS: In this observational nationwide study from Spain, there was no significant association between beta-blocker therapy and follow-up survival free of TTS recurrence.

Long-term outcomes of extended DAPT in a real-life cohort of consecutive STEMI patients.

INTRODUCTION AND OBJECTIVES: Dual antiplatelet therapy (DAPT) duration after ST-segment elevation myocardial infarction (STEMI) remains a matter of debate. METHODS: We analyzed the effect of DAPT on 5-year all-cause mortality, cardiovascular mortality, and cardiovascular readmission or mortality in a cohort of 1-year survivor STEMI patients. RESULTS: A total of 3107 patients with the diagnosis of STEMI were included: 93% of them were discharged on DAPT, a therapy that persisted in 275 high-risk patients at 5 years. Cardiovascular mortality in patients on single antiplatelet therapy vs DAPT at 5 years was 1.4% vs 3.6% (P <.01), respectively, whereas noncardiovascular mortality was 3.3% vs 5.8% (P=.049) at 5 years. Cardiovascular readmission or mortality in patients with single antiplatelet therapy vs DAPT was 11.4% vs 46.5% (P <.001). Extended DAPT was independently associated with worse 5-year all-cause mortality (HR, 2.16; 95%CI, 1.40-3.33), cardiovascular mortality (HR, 2.83; 95%CI, 1.37-5.84), and cardiovascular readmission or mortality (HR, 5.20; 95%CI, 3.96-6.82). These findings were confirmed in propensity score matching and inverse probability weighting analyses. CONCLUSIONS: Our results suggest the hypothesis that, in 1-year STEMI survivors, extending DAPT up to 5 years in high-risk patients does not improve their long-term prognosis.

IncidenCe and predictOrs of heaRt fAiLure after acute coronarY Syndrome: The CORALYS registry.

BACKGROUND: Previous studies investigating predictors of Heart Failure (HF) after acute coronary syndrome (ACS) were mostly conducted during fibrinolytic era or restricted to baseline characteristics and diagnoses prior to admission. We assessed the incidence and predictors of HF hospitalizations among patients treated with percutaneous coronary intervention (PCI) for ACS. METHODS AND RESULTS: CORALYS is a multicenter, retrospective, observational registry including consecutive patients treated with PCI for ACS. Patients with known history of HF or reduced left ventricular ejection fraction (LVEF) were excluded. Incidence of HF hospitalizations was the primary endpoint. The composite of HF hospitalization or cardiovascular death, and cardiovascular and all-cause death were the secondary endpoints. Predictors of HF hospitalizations and the impact of HF hospitalization on cardiovascular and all-cause death were assessed by means of multivariable Cox proportional hazards model.14699 patients were included. After 2.9 ± 1.8 years, the incidence of HF hospitalizations was 12.7%. Multivariable analysis identified age, diabetes, chronic kidney disease, previous myocardial infarction, atrial fibrillation, pulmonary disease, GRACE risk-score ≥ 141, peripheral artery disease, cardiogenic shock at admission and LVEF ≤40% as independently associated with HF hospitalizations. Complete revascularization was associated with a lower risk of HF (HR 0.46,95%CI 0.39-0.55). HF hospitalization was associated with higher risk of CV and all-cause death (HR 1.89,95%CI 1.5-2.39 and HR 1.85,95%CI 1.6-2.14, respectively). CONCLUSIONS: Incidence of HF hospitalizations among patients treated with PCI for ACS is not negligible and is associated with detrimental impact on patients' prognosis. Several variables may help to assess the risk of HF after ACS.