Simple scores to predict 1-year mortality in atrial fibrillation.

BACKGROUND: Traditional scores as CHADS2 and CHA2DS2-Vasc are suitable for predicting stroke and systemic embolism in patients with atrial fibrillation (AF) and have shown to be also associated with mortality. Other more complex scores have been recommended for survival prediction. The purpose of our analysis was to test the performance of different clinical scores in predicting 1-year mortality in AF patients. MATERIAL AND METHODS: CHADS2 and CHA2DS2-Vasc scores were calculated for AF patients of the BLITZ-AF register and compared to R2-CHADS2, R2-CHA2DS2-Vasc and CHA2DS2VASc-RAF scores in predicting 1-year survival. Scores including renal function were calculated both with glomerular filtration rate (GFR) and creatinine clearance. RESULTS: One-year vital status (1960 alive and 199 dead) was available in 2159 patients. Receiver-operating characteristic curves displayed an association of each score to all-cause mortality, with R2(ClCrea)-CHADS2 being the best [area under the curve (AUC) 0.734]. Differences among the AUCs of the eight scores were not so evident, and a significant difference was found only between R2(ClCrea)-CHADS2 and CHADS2, CHA2DS2VASc, (ClCrea)-CHA2DS2-VASC-RAF.All the scores showed a similar performance for cardiovascular (CV) mortality, with CHA2DS2VASc-RAF being the best (AUC 0.757), with a significant difference with respect to CHADS2, CHA2DS2VASc, and (ClCrea)CHA2DS2Vasc-RAF. CONCLUSIONS: More complex scores, even if with better statistical performance, do not show a clinically relevant higher capability to discriminate alive or dead patients at 12 months. The classical and well known CHA2DS2VASc score, which is routinely used all around the world, has a high sensitivity in predicting all-cause mortality (AUC 0.695; Sensit. 80.4%) and CV mortality (AUC 0.691; Sensit. 80.0%). GRAPHICAL ABSTRACT: http://links.lww.com/JCM/A632.

Lessons derived from post authorisation safety studies (ETNA-AF and XANTUS) on once daily direct oral anticoagulants for atrial fibrillation.

BACKGROUND: Phase III trials should be integrated by post authorisation safety studies (PASS) to confirm their conclusions in real life. In this setting, comorbidities are commonly more prevalent, decisions about drugs and regimens are left to the attending physicians and therapy monitoring is not usually as strict as in pivotal trials. AIMS AND METHODS: To evaluate real life safety and effectiveness of edoxaban and rivaroxaban, ETNA-AF Europe (ETNA-AF-Eu) and XANTUS studies were reviewed and compared. A further comparison between data collected in these studies and in the pivotal studies ENGAGE AF-TIMI 48 and ROCKET-AF was also performed. RESULTS: ETNA-AF-Eu and XANTUS showed lower bleeding, stroke, cardiovascular- and all-cause mortality rates as compared to those observed in Phase 3 trials, even when including subgroups with lower comorbidities. Patients in ETNA-AF-Eu were older, with a larger proportion of octogenarians (≥85 years in 10.5%) and patients with impaired renal function as compared to patients in XANTUS (CrCl <50 ml/min in 18.2% vs 12.2%) and in ENGAGE AF-TIMI 48 and ROCKET-AF, without paying any excess tribute in terms of safety. Therapy persistence was very high in the two real life studies (91.9% in ETNA-AF-Eu and 79.9% in XANTUS), thus showing that edoxaban and rivaroxaban are well tolerated in real life. CONCLUSION: The ETNA-AF-Eu and XANTUS confirmed the safety and effectiveness of edoxaban and rivaroxaban in real life.

The European TauroPace™ Registry.

BACKGROUND: Cardiac implantable electronic device (CIED) placement comes with certain complications. CIED infection is a severe adverse event related to CIED placement. In randomised controlled trials, the preoperative intravenous administration of antibiotics and the adjunctive use of an antibiotic mesh envelope resulted in significant reduction in infections related to cardiac implantable electronic devices. The adjunctive use of taurolidine for this purpose is relatively novel and not considered in the guidelines. The required evidence may consist of a set of clinical studies. METHODS: The European TauroPaceTM registry (ETPR) prospectively evaluates every consecutive invasive procedure involving any CIED with adjunct TauroPace™ use in the contributing centres. As the estimation of the infection rate needs to be defensible, only interventions registered prior to the procedure will be followed-up. The endpoint is a major cardiac implantable electronic device infection according to the novel CIED infection criteria (1). Secondary endpoints comprise all-cause mortality, complications, adverse events of all grades, and major CIED infections during all follow-up examinations. The follow-up times are three months, twelve months, and eventually 36 months, as acute, subacute, and long-term CIED infections are of interest. RESULTS: As the rate of CIED infections is expected to be very low, this registry is a multicentre, international project that will run for several years. Several reports are planned. The analyses will be included in the case number calculations for future randomised controlled trials. CONCLUSIONS: The ETPR will accumulate large case numbers to estimate small event rates more precisely; we intend to follow up on participants for years to reveal possible late effects.

Is there a reduced confidence towards direct oral anticoagulants compared to vitamin K antagonists in patients scheduled for an elective electrical cardioversion? The results of the BLITZ-AF study.

OBJECTIVE: To study the confidence of cardiologists in performing an electrical cardioversion in patients on oral anticoagulation (OA) with or without transoesophageal echocardiography (TOE). METHODS: Data about atrial fibrillation (AF) patients admitted to cardiology wards for elective cardioversion (ECV) were extrapolated from the BLITZ-AF study. Percentage of vitamin K antagonists (VKAs), direct oral anticoagulants (DOAC) and heparin prescription were analysed in relation to the use of TOE before ECV. RESULTS: Overall rate of TOE was 33.7% (240/713); it was used before ECV in 124/313 (39.6%) of DOACs patients and in 96/372 (25.8%) of the patients on VKAs, showing a significant reduced resort to TOE in VKAs patients (p = 0.0001). Among non-valvular patients TOE was more frequently performed in males, at younger ages and in patients on heparin when compared to patients treated with OA. TOE was also more frequently performed in tertiary hospitals and in hospitals with cardiology wards and electrophysiology labs, when compared to hospital provided only with cardiology wards. At multivariable analysis there was a significant less recourse to TOE in patients on VKAs (OR 0.47; 95% CI: 0.33-0.67) and higher recourse in the heparin group (OR: 3.85; 95% CI:1.59-9.28) with respect to patients on DOACs; a higher recourse to TOE was observed also in tertiary hospitals (OR 4.25; 95% CI 2.69-6.69) and in hospitals with cardiology wards and electrophysiology (EP) labs (OR 1.87; 95% CI 1.23-2.82). CONCLUSION: our study shows the reluctance in cardioverting patients on DOACs respect to VKAs without a previous TOE, despite adequate anticoagulant treatment.

Multi-Modality Imaging Approach to a rare form of Biventricular Ring-Shaped Constrictive Pericarditis.

A 48-year-old man with AIDS/HIV and a previous history of tuberculous pericarditis 25 years earlier was admitted to our department of infectious diseases because of P. carinii pneumonia. A CT (computed tomography) scan described diffuse pericardial thickening with extensive pericardial calcifications on both ventricles. A transthoracic echocardiogram showed all the typical hemodynamic features of pericardial constriction. A review of the CT with 3D reconstruction revealed the presence of ring-shaped pericardial calcification at the basal segments of right and left ventricles extending over the inferior atrioventricular groove, the inferior interventricular groove and the cranial wall of the right atrium. Only a few cases of ring-shaped constrictive pericarditis have been reported and both global ventricular constriction and localized segmental constriction have been described. Our case wants to underline how important a comprehensive multi-modality imaging approach is to this rare form of constrictive pericarditis.

The Importance of Being Aware of Intrinsic Methods' Limitation in Low-Density Lipoprotein Cholesterol Determination to Correctly Identify Cardiovascular Risk: Is Direct Determination Obtained with the Roche System Systematically Overestimating LDL in Very High-Risk Patients with Triglycerides Concentration of Less than 2.25 mmol/L?

BACKGROUND: low-density lipoprotein cholesterol (LDL-C) is a strong cardiovascular risk factor, but the methods used to correctly determine it are is still questioned. The aim of this study was to compare the direct determination of LDL-C levels, obtained with the Roche cobas c system, with LDL-C values calculated through Sampson's and Friedewald's equations in very high-risk patients with triglycerides concentrations of less than 2.25 mmol/L (<200 mg/dL). METHODS: in 127 consecutive patients with a recent diagnosis of acute coronary syndrome and triglycerides of less than 2.25 mmol/L, plasma LDL-C was measured directly and calculated with Sampson's and Friedewald's equations before hospital discharge, and the data were compared. RESULTS: median LDL values obtained with the Friedenwald and Sampson equations and with direct determination were 2.31 (IQR 1.59-3.21), 2.36 (IQR 1.66-3.26) and 2.64 (IQR 1.97-3.65) mmol/L, respectively. Direct measurements were higher by 0.35 and 0.40 mmol/L when compared to the levels calculated with Sampson's or Friedewald's equations, respectively (p < 0.01). The correlation between the two equations was almost perfect (rho 0.997) but decreased when the directly determined data were compared to those calculated with Sampson's equation (rho 0.954) or Friedewald's method (rho 0.939). CONCLUSION: direct determination generated higher values of LDL-C concentration through a probable systematic overestimation.

Reverse Remodeling and Functional Improvement of Left Ventricle in Patients with Chronic Heart Failure Treated with Sacubitril/Valsartan: Comparison between Non-Ischemic and Ischemic Etiology.

Sacubitril/valsartan (SV) has been demonstrated to reduce cardiovascular mortality, hospitalization for heart failure and to induce reverse ventricular remodeling. The present study was designed to confirm the effects of SV in a selected population of patients with HFrEF and to evaluate the different responses between patients with an ischemic or a non-ischemic etiology. A total of 79 patients with indication of SV were recruited prospectively during a timelapse of 4 years. SV was overall associated to a reduction of end-diastolic and end-systolic volume, of NT-proBNP levels, furosemide dosage and NYHA functional class, together with an increase in EF. These changes were more evident in patients with non-ischemic dilated cardiomyopathy, who showed a significant improvement in ventricular volumes, ejection fraction, TAPSE and blood levels of NT-proBNP. Kaplan-Meier curves confirmed a greater benefit in terms of ejection-fraction improvement in non-ischemic patients compared to the ischemic group. The results of the present study confirm the positive effect of SV on NYHA functional class, NT- proBNP, left ventricular volumes and EF in HFrEF patients, showing evidence of association of SV with ventricular remodeling in patients with dilated cardiomyopathy of non-ischemic etiology compared to the ischemic group.

Large Serpiginous Thrombus Crossing a Patent Foramen Ovale.

Transesophageal iconic image of a large serpiginous thrombus crossing a patent foramen ovale.

Reclassification, Thromboembolic, and Major Bleeding Outcomes Using Different Estimates of Renal Function in Anticoagulated Patients With Atrial Fibrillation: Insights From the PREFER-in-AF and PREFER-in-AF Prolongation Registries.

BACKGROUND: The Cockcroft-Gault formula is recommended to determine a renal indication for dose reduction of dabigatran, edoxaban, and rivaroxaban. Nephrology guidelines now recommend the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae as more accurate estimates of glomerular filtration rate. METHODS: We analyzed anticoagulated patients with atrial fibrillation who were enrolled in the Prevention of Thromboembolic Events - European Registry in Atrial Fibrillation (PREFER in AF). The proportion of patients with dissimilar renal dosing indications was assessed when applying Cockcroft-Gault, MDRD, or CKD-EPI. Thromboembolic and major bleeding events at 1 year were compared in patients in whom Cockcroft-Gault and CKD-EPI provided concordant or discordant results around a threshold of 50 mL/minute. RESULTS: Out of 1288 patients with atrial fibrillation with chronic kidney disease in whom Cockcroft-Gault suggested a dose reduction of dabigatran, edoxaban, or rivaroxaban (creatinine clearance ≤50 mL/minutes), 19% and 16% were reclassified to the respective higher doses, and 24% and 23% to the respective lower doses by applying the MDRD and CKD-EPI formulae, respectively. In patients potentially receiving a different dose of dabigatran, edoxaban, or rivaroxaban when using CKD-EPI, we observed an excess of thromboembolic events (4.1% versus 0.8%; odds ratio, 5.5 [95% CI, 1.5-20.8]; P=0.01). Major bleeding rates were nonsignificantly different in the discordance versus concordance group (5.7% versus 2.7%; odds ratio, 2.2 [95% CI, 0.9-5.6]; P=0.09). CONCLUSIONS: The MDRD and CKD-EPI formulae suggest a different dosing in up to a quarter of anticoagulated patients with atrial fibrillation. This seems to impact hard outcomes.

Should We Continue Assessing Glomerular Filtration Rate with the Cockroft-Gault Formula in NOAC-Treated Patients? The Magnitude of the Problem.

Despite the proven superiority of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) over the Cockcroft-Gault (CG) formula, current guidelines recommend the latter to assess renal function in patients treated with non-vitamin K antagonist oral anticoagulants (NOACs). To assess the relationship between the CG and the recommended CKD-EPI formulas, in a cohort of atrial fibrillation (AF) patients treated with NOACs, and the misclassifications introduced by the CG formula for renal function levels, we estimated renal function with three equations: CG, CKD-EPI with body surface adjustment (1.73 mL/m2, CKD-EPI) and without such adjustment (CKD-EPI_noBSA), in all consecutive AF patients discharged from NOACs from the Cardiology Division of a main city hospital between February 1st and May 31st 2018. We compared the different estimates of glomerular filtration rate and potential renal function class misclassifications. We reclassified 37/115 patients (32.1%) when switching from the CG to the CKD-EPI; and 24/115 (20.8%) switching from the CG to the CKD-EPI_noBSA formulas. Class reallocation was distributed across all levels of renal function, but mostly affected the "hyper-normal" function. In estimating consequences of such reallocation, a change in NOAC dosages would have occurred in 10/115 patients (8.7%) when switching from the CG to the CKD-EPI formula and in 10/115 patients when switching from the CG to the CKD-EPI_noBSA formula. Although the CG method has been traditionally used to calculate renal function in all NOAC studies, a renal dysfunction class reallocation occurs in a substantial fraction of hospital-admitted AF patients with the use of better estimates of renal function.

One-year clinical events and management of patients with atrial fibrillation hospitalized in cardiology centers: Data from the BLITZ-AF study.

BACKGROUND: The management of atrial fibrillation (AF) has changed with the introduction of direct anticoagulants (DOACs) and new techniques such as catheter ablation. An update collection of data from "real world" AF patients followed by cardiologists is useful to obtain information on both management, outcomes and guideline adherence in clinical practice. METHODS: Follow-up information on survival, embolic and bleeding events and hospital readmission, persistence of oral anticoagulant (OAC) therapy was collected in 84 centers participating to the BLITZ-AF study. RESULTS: Patients were followed for a median of 366 days (IQR: 356-378) and vital status was available for 2159 patients. Mortality was 9.2%. Heart failure was the most common cardiovascular cause of death (70%) followed by arrhythmias (6.7%), acute coronary syndrome (5.0%) and ischemic stroke (2.5%). During follow-up 18.1% of the patients were readmitted, mainly (81.3%) for cardiovascular causes. Patients on OAC were 83.4%, 9.1% were on antiplatelets and 7.5% did not receive antithrombotic therapy. The use of DOACs increased from 42.1% to 46.4% during the follow-up, OAC discontinuation occurred in 9.1%. AF recurrences occurred in 23.4% of the patients discharged in sinus rhythm. Rate control strategy was adopted in 55.9% and beta-blockers were the most used drugs (81.9%). Amiodarone (22%) and flecainide (9.7%) were the most frequent used antiahrrythmic drugs. CONCLUSIONS: The follow-up of the BLITZ-AF study provide an up to date picture of the clinical course of patients with AF, who appear frequently affected by heart failure and severe comorbidities which might have led to the high mortality rate.

Effect of a liberal versus a restrictive pre-donation blood pressure policy on whole-blood donor adverse reactions.

BACKGROUND AND OBJECTIVES: The role of pre-donation blood pressure (BP) as independent contributor to post-donation vasovagal reactions (VVRs) is still debated. Differences between a liberal (i.e., inclusion of hypotensive donors) and a restrictive policy (i.e., not accepting hypotensive donors) should be investigated. This study aims to investigate the consequences of a liberal policy in development of VVRs after whole-blood donations. MATERIALS AND METHODS: We compared the incidence of VVRs between 2015 (restrictive policy) and 2016 (liberal policy) and the associated risk factors. We evaluated respectively 22 789 vs. 21 676 blood donations obtained from 18 001 blood donors (12 501 donated in both years). RESULTS: Comparing the results we obtained between 2015 and 2016, donations showed an overlap of the cohorts. Two hundred fifteen VVRs (incidence rate 0·48%) were observed, 104 (0·46%) of which in 2015, and 111 (0·51%) in 2016. A preliminary univariate analysis showed that donors with systolic BP <110 mm Hg had a two-fold risk of VVRs compared to normotensive donors (VVR/donation rate of 0·99% vs. 0·46%; P = 0·001). The subsequent multivariable logistic regression model showed that VVRs were highly associated with weight, site of collection, age and number of donations, excluding a role for systolic and diastolic BP. CONCLUSION: A liberal pre-donation BP policy seems to be safe for blood donors. Our analysis confirms that older donors with higher body-weight who already had donated blood are unlikely to experience VVRs.

Management of atrial fibrillation in the emergency room and in the cardiology ward: the BLITZ AF study.

AIMS: To assess the number of admissions to the emergency room (ER) of patients with atrial fibrillation (AF) or atrial flutter (af) and their subsequent management. To evaluate the clinical profile and the use of antithrombotics and antiarrhythmic therapy in patients with AF admitted to cardiology wards. METHODS AND RESULTS: BLITZ-AF is a multicentre, observational study conducted in 154 centres on patients with AF/af. In each centre, data were collected, retrospectively for 4 weeks in ER and prospectively for 12 weeks in cardiology wards. In ER, there were 6275 admissions. Atrial fibrillation was the main diagnosis in 52.9% of the cases, af in 5.9%. Atrial fibrillation represented 1.0% of all ER admissions and 1.7% of all hospital admissions. A cardioversion has been performed in nearly 25% of the cases. Out of 4126 patients, 52.2% were admitted in cardiology ward; mean age was 74 ± 11 years, 41% were females. Patients with non-valvular AF were 3848 (93.3%); CHA2DS2-VASc score was ≥2 in 87.4%. Cardioversion was attempted in 38.8% of the patients. In-hospital mortality was 1.2%. At discharge, 42.6% of the patients were treated with vitamin K antagonists, 39.5% with direct oral anticoagulants, 13.6% with other antithrombotic drugs, and 4.2% did not take any antithrombotic agent. Rate control strategy was pursued in 47.2%, rhythm control in 44.0%, 45.6% were discharged in sinus rhythm. CONCLUSION: Atrial fibrillation still represents a significant burden on health care system. Oral anticoagulant use increased over time even if compliance with guidelines, with respect to prevention of the risk of stroke, remains suboptimal.

Outcomes of anticoagulated patients with atrial fibrillation treated with or without antiplatelet therapy - A pooled analysis from the PREFER in AF and PREFER in AF PROLONGATON registries.

BACKGROUND: Evidence on whether antiPLT added to OACs is of advantage in atrial fibrillation (AF) patients with concomitant stable coronary artery disease (CAD) is limited. We evaluated clinical outcomes with oral anticoagulant (OAC) monotherapy vs antiplatelet therapy (antiPLT) plus OAC in patients with AF and stable CAD. METHODS: Data on 1058 AF patients on OACs and history (>1 year) of myocardial infarction or coronary stenting were pooled from the PREFER-in-AF and PREFER-in-AF PROLONGATION registries. We primarily compared the 1-year incidence of a net composite endpoint (primary endpoint), including acute coronary syndrome and major bleeding, with or without antiPLT. RESULTS: The incidence of the primary net composite endpoint was significantly higher in patients receiving OACs + antiPLT (N = 348) vs OACs alone (N = 710): 7.9 vs 4.2 per 100 patients/year; adjusted OR [95% CI] 1.84 [1.01-3.37]; p = 0.048. Among the components of the primary endpoint, the greatest relative difference was found for major bleeding (OR [95% CI] 2.28 [95% CI 1.00-5.19]), and especially life-threatening or non-gastrointestinal bleeding. The net clinical outcome with OACs + antiPLT was poorer irrespective of the type of CAD (previous infarction or coronary stenting), the type of stent (bare metal or drug-eluting) or the type of OAC (vitamin K antagonist or non-vitamin K antagonist OAC). CONCLUSIONS: Among patients with AF and stable CAD >1-year after the index event, the addition of antiPLT to OAC does not apparently provide added protection against coronary events, but increases major bleeding. OAC monotherapy should thus be considered the antithrombotic therapy of choice for such patients.

[Ten questions awaiting for a definitive answer on the use of non-vitamin K oral anticoagulants in atrial fibrillation]. / Dieci quesiti in attesa di risposta sull'utilizzo dei nuovi anticoagulanti orali nella fibrillazione atriale.

After more than 3 years from the appearance in Italy of the non-vitamin K antagonist oral anticoagulants (NOACs), their use for the prevention of thromboembolism in atrial fibrillation is still limited, with wide differences in prescriptions across regions. When NOACs became available for clinical practice, several doubts arose about their practical management in the "real world". This article analyses the 10 more frequent questions asked by clinicians dealing with NOACs in their daily activity with atrial fibrillation patients. The answers are synthetic and schematic with pragmatic suggestions that could help clinicians in their doubts.

Evaluation of capillary haemoglobin determination for anaemia screening in blood donation settings.

BACKGROUND: An accurate assessment of hemoglobin (Hb) values before donation is unavoidable for safeguarding donors' safety and fulfilling the current specifications of Hb content in blood bags. This study was hence aimed to compare a finger-prick method for Hb measurement in capillary blood with Hb assessment in venous blood using a hematological analyser. MATERIALS AND METHODS: The study populations consisted in 1,014 consecutive blood donors, who had paired measurement of Hb values with HemoCue on capillary blood and UniCel DxH800 in venous blood. RESULTS: A significant overestimation was found with HemoCue compared to UniCel DxH800, but the correlation between methods was significant (comprised between 0.600 and 0.759; all p<0.01) and the bias always lower than the quality specifications. The prevalence of Hb values below the gender-specific thresholds for blood donation was also not significantly different (p=0.186). DISCUSSION: It can hence be concluded that the finger-prick method evaluated is a safe and reliable means for screening blood donors.

Fully-automated, chemiluminescence IgA and IgG anti-tissue transglutaminase (tTG) antibodies serum assays for the screening of celiac disease.

AIM: Celiac disease (CD) is a systemic immune-mediated enteropathy sustained by gluten ingestion in genetically susceptible subjects. The European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) has recently revised the diagnostic criteria, emphasizing the crucial role of serological testing in the diagnosis of this condition. This study was hence aimed to evaluate a new chemiluminescence assay for measuring anti-transglutaminase (tTG) and anti-endomysium (EMA) antibodies in a general population of unselected outpatients. MATERIALS AND METHODS: The IgA and IgG anti-tissue transglutaminase (tTG) antibodies (Quanta Flash® IgA and Quanta Flash® IgG tTG, Inova Diagnostics, San Diego, CA, USA) were measured with the fully-automated BIO-FLASH® analyzer (Inova Diagnostics) in serum samples of 727 consecutive patients without a diagnosis of CD. Data were compared with those of anti-endomysium antibody (EmA) obtained in the same population. RESULTS: A total of 96.4% samples display a negative concordance (anti-tTG negative and EMA negative), O% were positive for EMA and negative for anti-tTG IgA and IgG, 3.6% were both positive for tTG IgA and EMA, whereas 0.6% displayed discordant results (positive for anti-tTG and negative for EMA). The concordance (99%) and inter-rater agreement (Kappa Statistics, 0.943; p<0.001) between anti-tTG IgA and EmA antibodies were excellent, with sensitivity and specificity of 99% and 100%, respectively. CONCLUSION: The results of this study show that Quanta Flash® IgA assay alone may be regarded as a reliable approach for screening of CD, with no need to perform EMA detection.