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.

Insuficiencia cardiaca en octogenarios con fibrilación auricular: incidencia y factores de riesgo / Heart failure in older patients with atrial fibrillation: incidence and risk factors

Introducción y objetivos: La fibrilación auricular (FA) está interconectada con la insuficiencia cardiaca (IC). Sin embargo, los factores que pueden precipitar la aparición de IC en los pacientes con FA están escasamente descritos. Con este estudio, se pretende determinar la incidencia, los predictores y el pronóstico de la IC de nueva aparición en una población de pacientes ancianos con FA sin antecedentes de IC.MétodosPacientes con FA mayores de 80 años, sin antecedente de IC, identificados entre los años 2014 y 2018.ResultadosDurante 3,7 años, se siguió a 5.794 pacientes (edad, 85,2±3,8 años; el 63,2% mujeres). En el 33,3% de los casos (tasa de incidencia, 11,5/100 pacientes-año) apareció IC de novo, mayoritariamente con fracción de eyección del ventrículo izquierdo conservada. A partir de un análisis multivariante, se identificaron 11 factores de riesgo de aparición de la IC independientemente de su subtipo: enfermedad valvular significativa (HR=1,99; IC95%, 1,73-2,28), fracción de eyección del ventrículo izquierdo reducida (HR=1,92; IC95%, 1,68-2,19), enfermedad pulmonar obstructiva crónica (HR=1,59; IC95%, 1,40-1,82), aumento de la aurícula izquierda (HR=1,47; IC95%, 1,33-1,62), enfermedad renal (HR=1,36; IC95%, 1,24-1,49), desnutrición (HR=1,33; IC95%, 1,21-1,46), anemia (HR=1,30; IC95%, 1,17-1,44), FA permanente (HR=1,15; IC95%, 1,03-1,28), diabetes mellitus (HR=1,13; IC95%, 1,01-1,27), por cada año de aumento de la edad (HR=1,04; IC95%, 1,02-1,05) y por cada kg/m2 del índice de masa corporal (HR=1,03; IC95%, 1,02-1,04). La presencia de IC prácticamente duplicó la mortalidad (HR=1,67; IC95%, 1,53-1,81).ConclusionesLa IC de nueva aparición en ancianos con FA fue muy frecuente y prácticamente duplicó la mortalidad. Se identificaron 11 factores de riesgo, lo cual amplía el ámbito de prevención primaria en esta entidad. (AU)

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.MethodsPatients with AF older than 80 years and without prior HF were identified between 2014 and 2018.ResultsA 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).ConclusionsThe 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. (AU)

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.

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.

Transcatheter Tricuspid Valve Replacement With a Dedicated Device in a Patient With 2 Endocardial Leads.

A 79-year-old woman with a history of dilated cardiomyopathy who required a permanent peacemaker, recently upgraded to implantable cardioverter-defibrillator cardiac resynchronization therapy, was admitted for right heart failure. On echocardiography, torrential tricuspid regurgitation was noted, with 2 leads across the valve. After multidisciplinary evaluation, a dedicated transcatheter valve replacement was successfully implanted. (Level of Difficulty: Intermediate.).

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.

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).

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.

Transcatheter Tricuspid Valve Replacement: Illustrative Case Reports and Review of State-of-Art.

Tricuspid regurgitation (TR) is one of the most common heart valve diseases, associated a with poor prognosis since significant TR is associated with an increased mortality risk compared to no TR or mild regurgitation. Surgery is the standard treatment for TR, although it is associated with high morbidity, mortality, and prolonged hospitalization, particularly in tricuspid reoperation after left-sided surgery. Thus, several innovative percutaneous transcatheter approaches for repair and replacement of the tricuspid valve have gathered significant momentum and have undergone extensive clinical development in recent years, with favorable clinical outcomes in terms of mortality and rehospitalization during the first year of follow-up. We present three clinical cases of transcatheter tricuspid valve replacement in an orthotopic position with two different innovative systems along with a review of the state-of-the-art of this emergent topic.

Impact of multisite artery disease on clinical outcomes after percutaneous coronary intervention: an analysis from the e-Ultimaster registry.

BACKGROUND: Multisite artery disease is considered a 'malignant' type of atherosclerotic disease associated with an increased cardiovascular risk, but the impact of multisite artery disease on clinical outcomes after percutaneous coronary intervention (PCI) is unknown. METHODS: Patients enrolled in the large, prospective e-Ultimaster study were grouped into (1) those without known prior vascular disease, (2) those with known single-territory vascular disease, and (3) those with known two to three territories (i.e coronary, cerebrovascular, or peripheral) vascular disease (multisite artery disease). The primary outcome was coronary target lesion failure (TLF), defined as the composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target lesion revascularization at 1-year. Inverse propensity score weighted (IPSW) analysis was performed to address differences in baseline patient and lesion characteristics. RESULTS: Of the 37 198 patients included in the study, 62.3% had no prior known vascular disease, 32.6% had single-territory vascular disease, and 5.1% had multisite artery disease. Patients with known vascular disease were older and were more likely to be men and to have more co-morbidities. After IPSW, the TLF rate incrementally increased with the number of diseased vascular beds (3.16%, 4.44%, and 6.42% for no, single, and multisite artery disease, respectively, P < 0.01 for all comparisons). This was also true for all-cause death (2.22%, 3.28%, and 5.29%, P < 0.01 for all comparisons) and cardiac mortality (1.26%, 1.91%, and 3.62%, P ≤ 0.01 for all comparisons). CONCLUSIONS: Patients with previously known vascular disease experienced an increased risk of adverse cardiovascular events and mortality post-PCI. This risk is highest among patients with multisite artery disease.Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02188355.