Antithrombotic Usage, Including Three-Year Outcomes With Dabigatran and Vitamin K Antagonists for Atrial Fibrillation, in Eastern Europe: A Descriptive Analysis From Phase 3 of the GLORIA-AF Registry.

BACKGROUND: Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) is a prospective registry of outcomes from patients with newly diagnosed AF at risk of stroke. In the propensity score (PS)-matched global population of phase 3 GLORIA-AF, at 3 years, dabigatran-treated patients experienced reduced risk for major bleeding, and similar risk for stroke and myocardial infarction, compared with vitamin K antagonist (VKA)-treated patients. STUDY QUESTION: Do patients in Eastern Europe benefit from treatment with dabigatran versus VKA? STUDY DESIGN: Descriptive analysis, without PS matching. To contextualize the Eastern Europe results of GLORIA-AF phase 3, we also descriptively analyzed the global population without PS matching. Consecutive patients with newly diagnosed AF and CHA2DS2-VASc-score ≥1 were enrolled until December 2016 in 38 countries (9 in Eastern Europe). MEASURES AND OUTCOMES: Three-year outcomes with dabigatran and VKA. RESULTS: In Eastern Europe, 1341 patients were eligible (6% of patients globally), and incidence rates (per 100 patient-years) for the following outcomes were numerically lower with dabigatran (N = 498) versus VKA (N = 466): major bleeding (0.26 vs. 0.90), all-cause death (2.04 vs. 3.50), and a composite of stroke, systemic embolism, myocardial infarction, life-threatening bleeding, and vascular death (1.37 vs. 1.92); stroke was comparable (0.51 vs. 0.50). All incidence rates were numerically lower in Eastern Europe versus the global population for both treatments. Chronic concomitant use of high bleeding risk medications (eg, nonsteroidal anti-inflammatories) was lower in Eastern Europe (dabigatran 3.8%, VKA 9.3%) than globally (dabigatran 14.8%, VKA 20.6%) and persistence with dabigatran was higher in Eastern Europe (76%) than globally (64%). CONCLUSIONS: Dabigatran was associated with numerically reduced major bleeding, all-cause death, and cardiovascular (CV) composite, with comparable risk of stroke versus VKA, in Eastern Europe. Limitations of this descriptive analysis include few CV events (n = 11 for stroke, in the dabigatran and VKA groups combined) and a lack of statistical analysis and PS matching, which precludes definitive conclusions; however, the CV outcomes in Eastern Europe were consistent with the beneficial impact of dabigatran versus VKA in the statistically analyzed global population with PS matching.

Impact of Anticoagulants in Reducing Mortality and Disability in Cardioembolic Stroke Patients.

Background and Objectives: Stroke is currently the second most common cause of death and disability-adjusted life years worldwide. Previous studies have determined that cardioembolic stroke is associated with higher mortality. Our aim is to compare the long-term outcome and mortality of atherothrombotic, cardioembolic stroke patients and patients taking direct oral anticoagulants (DOACs), and to demonstrate that adequate treatment with DOACs is associated with better results. Materials and Methods: In our retrospective study, we collected the data of ischemic stroke patients who were treated at P. Stradins Clinical University Hospital, Riga, Latvia, Stroke Unit, in the year 2017. In the present study, we analyzed this information to assess the patients' demographic and clinical data, vascular risk factors, functional and neurological evaluation results, and the use of anticoagulant therapy. Stroke survivors were followed-up via telephone at 30/90/180/365 days and 4 years after being discharged from the hospital. The Latvian version of the National Institutes of Health Stroke Scale (NIHSS-LV) was used to evaluate patients' neurological outcomes at discharge, and patients' functional outcomes were evaluated using the modified Rankin scale (mRS). The collected data of the patients were separated into three groups according to the stroke subtype and use of direct oral anticoagulants. Results: A total of 654 ischemic stroke patients were admitted to the hospital in the year 2017. Of all the strokes included in the study, 262 presented an atherothrombotic etiology and 392 presented a cardioembolic etiology. The median age of the patients in the study was 76 years (IQR: 67-83). The median age of patients in the atherothrombotic stroke group was 71 years (IQR = 64-79), in the cardioembolic stroke group it was 79 (IQR = 72-84), and in the DOAC group it was 75 years (IQR = 69-82), respectively. At the period of four years, of all the atherothrombotic stroke survivors 14 (10.5%) had a severe disability, and 64 (48.1%) did not survive. However, 12 (4.1%) of the cardioembolic stroke survivors were severely disabled and 37 (12.5%) had died. In the group of patients taking DOACs 6 (4.5%) had a severe disability and 17 (12.9%) did not survive. In all the patient groups, the leading cause of death was due to severe disability (22%), followed by recurrent cardioembolic events (8%). Conclusions: Previous studies until now have concluded that cardioembolic stroke is associated with higher mortality and an unfavorable functional outcome. In our study, the cardioembolic stroke group and the DOAC group had a statistically significant higher percentage of patients with congestive heart failure and older age, but their long-term mortality was lower and they achieved independence more often than the atherothrombotic stroke patients. The proper use of anticoagulants shows great improvement in long-term survival rate and functional outcome.

Catheter ablation or medical therapy to delay progression of atrial fibrillation: the randomized controlled atrial fibrillation progression trial (ATTEST).

AIMS: Delay of progression from paroxysmal to persistent atrial fibrillation (AF) is an important measure of long-term success of AF treatment. However, published data on the impact of catheter ablation on AF progression are limited. This study evaluates whether radiofrequency (RF) catheter ablation delays the progression of AF compared with antiarrhythmic drug (AAD) treatment using current AF management guidelines. METHODS: This prospective, randomized, controlled, two-arm, open-label trial was conducted at 29 hospitals and medical centres across 13 countries. Patients were randomized 1 : 1 to RF ablation or AAD treatment. The primary endpoint was the rate of persistent AF/atrial tachycardia (AT) at 3 years. RESULTS: After early study termination following slow enrolment, 255 (79%) of the planned 322 patients were enrolled (RF ablation, n = 128, AAD, n = 127); 36% of patients in the RF ablation group and 41% in the AAD group completed 3 years of follow-up. For the primary endpoint, the Kaplan-Meier estimate of the rate of persistent AF/AT at 3 years was significantly lower with RF ablation [2.4% (95% confidence interval (CI), 0.6-9.4%)] than with AAD therapy [17.5% (95% CI, 10.7-27.9%); one-sided P = 0.0009]. Patients ≥65 years were ∼4 times more likely to progress to persistent AF/AT than patients <65 years, suggesting RF ablation can delay disease progression [hazard ratio: 3.87 (95% CI, 0.88-17.00); P = 0.0727]. Primary adverse events were reported for eight patients in the RF ablation group. CONCLUSIONS: Radiofrequency ablation is superior to guideline-directed AAD therapy in delaying the progression from paroxysmal to persistent AF.

A Higher Polygenic Risk Score Is Associated with a Higher Recurrence Rate of Atrial Fibrillation in Direct Current Cardioversion-Treated Patients.

Background and Objectives: Recurrence of atrial fibrillation (AF) within six months after sinus rhythm restoration with direct current cardioversion (DCC) is a significant treatment challenge. Currently, the factors influencing outcome are mostly unknown. Studies have found a link between genetics and the risk of AF and efficacy of rhythm control. The aim of this study was to examine the association between eight single-nucleotide variants (SNVs) and the risk of AF development and recurrence after DCC. Materials and Methods: Regarding the occurrence of AF, 259 AF cases and 108 controls were studied. Genotypes for the eight SNVs located in the genes CAV1, MYH7, SOX5, KCNN3, ZFHX3, KCNJ5 and PITX2 were determined using high-resolution melting analysis and confirmed with Sanger sequencing. Six months after DCC, a telephone interview was conducted to determine whether AF had recurred. A polygenic risk score (PRS) was calculated as the unweighted sum of risk alleles. Multivariate regression analyses were performed to assess SNV and PRS association with AF occurrence and recurrence after DCC. Results: The risk allele of rs2200733 (PITX2) was significantly associated with the development of AF (p = 0.012, OR = 2.31, 95% CI = 1.206-4.423). AF recurred in 60% of patients and the allele generally associated with a decreased risk of AF of rs11047543 (SOX5) was associated with a greater risk of AF recurrence (p = 0.014, OR = 0.223, 95% CI = 0.067-0.738). A PRS of greater than 7 was significantly associated (p = 0.008) with a higher likelihood of developing AF after DCC (OR = 4.174, 95% CI = 1.454-11.980). Conclusions: A higher PRS is associated with increased odds of AF recurrence after treatment with DCC. PITX2 (rs2200733) is significantly associated with an increased risk of AF. The protective allele of rs11047543 (SOX5) is associated with a greater risk of AF recurrence. Further studies are needed to predict the success of rhythm control and guide patient selection towards the most efficacious treatment.

Impact of monitoring on detection of arrhythmia recurrences in the ESC-EHRA EORP atrial fibrillation ablation long-term registry.

AIMS: Monitoring of patients after ablation had wide variations in the ESC-EHRA atrial fibrillation ablation long-term (AFA-LT) registry. We aimed to compare four different monitoring strategies after catheter AF ablation. METHODS AND RESULTS: The ESC-EHRA AFA-LT registry included 3593 patients who underwent ablation. Arrhythmia monitoring during follow-up was performed by 12-lead electrocardiogram (ECG), Holter ECG, trans-telephonic ECG monitoring (TTMON), or an implanted cardiac monitoring (ICM) system. Patients were selected to a given monitoring group according to the most extensive ECG tool used in each of them. Comparison of the probability of freedom from recurrences was performed by censored log-rank test and presented by Kaplan-Meier curves. The rhythm monitoring methods were used among 2658 patients: ECG (N = 578), Holter ECG (N = 1874), TTMON (N = 101), and ICM (N = 105). A total of 767 of 2658 patients (28.9%) had AF recurrences during follow-up. Censored log-rank test discovered a lower probability of freedom from relapses, which was detected with ICM compared to TTMON, ECG, and Holter ECG (P < 0.001). The rate of freedom from AF recurrences was 50.5% among patients using the ICM while it was 65.4%, 70.6%, and 72.8% using the TTMON, ECG, and Holter ECG, respectively. CONCLUSION: Comparing all main electrocardiographic monitoring methods in a large patient sample, our results suggest that post-ablation recurrences of AF are significantly underreported by TTMON, ECG, and Holter ECG. The ICM estimates AF ablation recurrences most reliably and should be a preferred mode of monitoring for trials evaluating novel AF ablation techniques.

Is Anticoagulation Necessary for Severely Disabled Cardioembolic Stroke Survivors?

Background and Objectives: Oral anticoagulants are the hallmark of cardioembolic stroke prevention, but they are frequently underused, especially in elderly patients and patients with paroxysmal atrial fibrillation. In our paper, we analyzed the long-term outcome of severely disabled cardioembolic stroke survivors depending on the prescribed antithrombotic secondary prevention medication. Materials and Methods: In our study, we retrospectively collected data for ischemic stroke (IS) patients treated in P. Stradins Clinical University hospital, Riga, Latvia, from 2014 until 2017. Patients' clinical data were collected using local stroke registry, including patients' demographic data, vascular risk factors, clinical findings, and laboratory results. Severely disabled stroke survivors were followed up by phone at 30/90/180/365 days after discharge. Patients' functional outcomes were assessed using the adapted version of The Rankin Focused Assessment-Ambulation. The collected data were compared in 4 groups according to prescribed secondary prevention medication. Results: A total of 682 (91.42%) patients were followed up and included in data analysis. The median age of patients was 80 (IQR = 75-85) years. Of these patients, 231 (31%) were males and 515 (69%) were females. One-year probability of survival of patients not taking any preventive medication was 53% (IQR = 29-76), while in patients taking antiplatelet agents it was 57% (IQR = 37-78), 78% (IQR = 68-88) of patients on Vitamin K antagonists (VKA) and 81% (IQR = 72-90) in patients on direct oral anticoagulants (DOACs). One year after discharge 73 (31%) had mRS 0-2, 50 (20.9%), 29 (12.1%) were still severely disabled, and 87 (36.4%) had died. Conclusions: Anticoagulant use in secondary prevention predicts better functional outcome and higher survival rate in patients with severe cardioembolic stroke due to non-valvular atrial fibrillation (NVAF), therefore severe neurological deficit must not be a reason of restriction of anticoagulation.

Lead-Related Infective Endocarditis in Latvia: A Single Centre Experience.

Background and Objectives: Over the last five decades cardiac implantable electronic devices (CIED) have become established as the mainstay for the treatment of permanent bradycardias, chronic heart failure and dangerous heart rhythm disturbances. These devices improve survival and quality of life in many patients. However, infections associated with CIED implantation, particularly lead-related infective endocarditis (LRIE), can offset all benefits and make more harm than good for the patient. To date, there are no other studies in Latvia, addressing patients with lead-related infective endocarditis. The objective of this study was to identify the most common pathogens associated with LRIE and their antimicrobial resistance and to identify possible risk factors of patients who present with LRIE. Materials and Methods: The study was performed retrospectively at Pauls Stradins Clinical University Hospital (PSCUH). The study included patients who were referred to PSCUH due to LRIE for lead extraction. Patients were identified from procedural journals. Information about isolated microorganisms, patient comorbidities and visual diagnostics data was taken from patient records. Results: Forty-nine patients with CIED related infective endocarditis were included in the study, 34 (69.4%) were male, median age of all patients was 65.0 (50.5-73.0) years, median hospital stay was 15.5 (22.0-30.5) days. Successful and complete lead extraction was achieved in all patients. Thirty-two (65.3%) had received antibiotics prior to blood sample. Only in 31 (63.3%) positive culture results were seen. The most common isolated pathogens were Staphylococcus aureus (23.5%) and coagulase negative staphylococci (23.5%). Other bacteria were isolated considerably less often. The atrial lead was most common location for lead vegetations, seen in 50.0% of cases. Five (10.2%) patients have died due to the disease. Conclusions: Lead-related infective endocarditis is a major complication of cardiac implantable electronic devices with considerable morbidity and mortality, which in our study was as high as 10.2%.

Acute heart failure - an EFIM guideline critical appraisal and adaptation for internists.

BACKGROUND: Over the past two decades, several studies have been conducted that have tried to answer questions on management of patients with acute heart failure (AHF) in terms of diagnosis and treatment. Updated international clinical practice guidelines (CPGs) have endorsed the findings of these studies. The aim of this document was to adapt recommendations of existing guidelines to help internists make decisions about specific and complex scenarios related to AHF. METHODS: The adaptation procedure was to identify firstly unresolved clinical problems in patients with AHF in accordance with the PICO (Population, Intervention, Comparison and Outcomes) process, then conduct a critical assessment of existing CPGs and choose recommendations that are most applicable to these specific scenarios. RESULTS: Seven PICOs were identified and CPGs were assessed. There is no single test that can help clinicians in discriminating patients with acute dyspnoea, congestion or hypoxaemia. Performing of echocardiography and natriuretic peptide evaluation is recommended, and chest X-ray and lung ultrasound may be considered. Treatment strategies to manage arterial hypotension and low cardiac output include short-term continuous intravenous inotropic support, vasopressors, renal replacement therapy, and temporary mechanical circulatory support. The most updated recommendations on how to treat specific patients with AHF and certain comorbidities and for reducing post-discharge rehospitalization and mortality are provided. Overall, 51 recommendations were endorsed and the rationale for the selection is provided in the main text. CONCLUSION: Through the use of appropriate tailoring process methodology, this document provides a simple and updated guide for internists dealing with AHF patients.

The Impact of Pulmonary Vein Anatomy on P-Wave Appearance during Sinus Rhythm: Cardiac Computed Tomography Study.

Electrocardigraphy remains a first-line evaluation method for cardiac electrical activity, recorded from the body surface. Since atrial activation is seen on the ECG as a P-wave, several factors are known to impact the appearance of the P-wave, such as the direction of electric impulse, conduction abnormalities, and anatomical characteristics of the atria. This retrospective study aimed to find statistically significant associations between the anatomy of pulmonary veins (PVs) observed in cardiac computed tomography (CT) and P-wave appearance during sinus rhythm on resting ECG. For each patient, a resting 12-lead ECG was recorded, and the field of analysis was P-wave-its duration, morphology, and axis. The evaluation of the CT scan recordings was performed by creating 3D models of the left atrium and analyzing the anatomy of the PVs and left atrial appendages (LAA). Noteworthy correlations were found: anatomy of the left PVs showed an association with LAA volume, LAA morphology, and P-wave notching in lead II. The right PVs demonstrated a relation with the P-wave axis and amplitude. Although these correlations cannot be classified as strong, the results not only expand understanding about discussed variables but also suggest the presence of a subtle and complex relationship, that warrants further exploration.

Genetic Basis of Early Onset Atrial Fibrillation in Patients without Risk Factors.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia and typically occurs in elderly patients with other cardiovascular and extracardiac diseases. However, up to 15% of AF develops without any related risk factors. Recently, the role of genetic factors has been highlighted in this particular form of AF. AIMS: The aims of this study were to determine the prevalence of pathogenic variants in early-onset AF in patients without known disease-related risk factors and to identify any structural cardiac abnormalities in these patients. MATERIALS AND METHODS: We conducted exome sequencing and interpretation in 54 risk factor-free early-onset AF patients and further validated our findings in a similar AF patient cohort from the UK Biobank. RESULTS: Pathogenic/likely pathogenic variants were found in 13/54 (24%) patients. The variants were identified in cardiomyopathy-related and not arrhythmia-related genes. The majority of the identified variants were TTN gene truncating variants (TTNtvs) (9/13 (69%) patients). We also observed two TTNtvs founder variants in the analysed population-c.13696C>T p.(Gln4566Ter) and c.82240C>T p.(Arg27414Ter). Pathogenic/likely pathogenic variants were found in 9/107 (8%) individuals from an independent similar AF patient cohort from the UK Biobank. In correspondence with our Latvian patients, only variants in cardiomyopathy-associated genes were identified. In five (38%) of the thirteen Latvian patients with pathogenic/likely pathogenic variants, dilation of one or both ventricles was identified on a follow-up cardiac magnetic resonance scan. CONCLUSIONS: We observed a high prevalence of pathogenic/likely pathogenic variants in cardiomyopathy-associated genes in patients with risk factor-free early-onset AF. Moreover, our follow-up imaging data indicate that these types of patients are at risk of developing ventricular dilation. Furthermore, we identified two TTNtvs founder variants in our Latvian study population.

Role of Endomyocardial Biopsy in Diagnostics of Myocarditis.

Endomyocardial biopsy as the cornerstone of diagnostics has been re-evaluated throughout the years, leaving unanswered questions on the precedence of it. The reported incidence of myocarditis has increased during the pandemic of coronavirus disease 2019 (COVID-19), reinforcing discussions on appropriate diagnostics of myocarditis. By analysis of evidence-based literature published within the last demi-decade, we aimed to summarize the most recent information in order to evaluate the current role of endomyocardial biopsy in diagnostics and management of myocarditis. For the most part, research published over the last five years showed ongoing uncertainty regarding the use, informativeness, safety and necessity of performing a biopsy. Special circumstances, such as fulminant clinical course or failure to respond to empirical treatment, were reconfirmed as justified indications, with a growing applicability of non-invasive diagnostic approaches for most other cases. We concluded that endomyocardial biopsy, if performed properly and with adjunct diagnostic methods, holds a critical role for treatment correction in specific histological subtypes of myocarditis and for differential diagnosis between immune-mediated myocarditis and secondary infections due to immunosuppressive treatment. A high level of possible misdiagnosing was detected, indicating the need to review terminology used to describe findings of myocardial inflammation that did not meet Dallas criteria.

Blood pressure control in treated hypertensive patients in daily practice of Latvian family physicians.

BACKGROUND AND OBJECTIVE. The aim of this study was to evaluate blood pressure (BP) control level in treated hypertensive patients in Latvia and to compare their characteristics according to the adequacy of BP control. MATERIALS AND METHODS. Family physicians collected information on demographic and clinical characteristics, and current antihypertensive treatment of 455 18-80-year-old patients with essential arterial hypertension treated for 1 or more years. Target BP was defined as values of <140/90 mm Hg for patients with low or moderate cardiovascular risk and <135/85-125/75 mm Hg for patients with high or very high risk. BP was measured in the office setting after a 5-minute rest in a sitting position using a calibrated aneroid sphygmomanometer. RESULTS. Nearly half of patients (46.2%) attained their target BP. The proportion of patients with effective BP control was higher in the group of low and moderate added cardiovascular risk than in the high and very high added cardiovascular risk group (61.7% vs. 34.4%, P<0.0001). The majority of patients were given two-drug (26.2%) or three-drug (31.6%) combined antihypertensive therapy. Current pharmacological treatment was similar in the patients who attained target BP and in those who did not. Overall, physicians did not modify antihypertensive treatment in 37.9% of patients; such a recommendation was more common among patients with controlled BP. Very few patients (7.4%) who did not attain target BP did not receive recommendations to modify antihypertensive treatment. CONCLUSIONS. The rate of effective BP control was less than 50% and was even worse (34.4%) in patients with high or very high added cardiovascular risk in the present sample of treated hypertensive patients.

Low bleeding and thromboembolic risk with continued dabigatran during cardiovascular interventions: the GLORIA-AF study.

BACKGROUND: Prospective data on nonvitamin-K-antagonist oral anticoagulant (NOAC) management during cardiovascular interventions are limited. We therefore evaluated the safety and effectiveness of uninterrupted dabigatran therapy as well as dabigatran management during atrial fibrillation (AF)-cardioversions, AF-ablations, pacemaker implantations and coronary angiography and/or stenting procedures. METHOD: GLORIA-AF is an international registry programme involving patients with newly diagnosed AF. Dabigatran users were followed for ≤2 years. The primary outcome was occurrence of stroke/systemic embolism and major bleeding ≤8 weeks after a cardiovascular intervention during uninterrupted dabigatran therapy. RESULTS: During the 2-year follow-up, 599 cardiovascular interventions were identified in 479 eligible patients. 412/599 (69%) interventions were performed with uninterrupted dabigatran therapy: 299/354 (84%) AF-cardioversions, 38/89 (43%) AF-ablations, 25/58 (43%) pacemaker implantations, and 50/98 (51%) coronary angiography and/or stenting procedures. During an average follow-up of 8.4 weeks after intervention, one major bleed and one systemic embolic event occurred (risk 0.25% for both outcomes; 95% confidence interval, 0.01%-1.36%). CONCLUSIONS: More than two thirds of the interventions were performed with uninterrupted dabigatran therapy, of which most were AF-cardioversions. Uninterrupted dabigatran therapy was associated with low major bleeding and stroke/systemic embolism risk, supporting the favourable safety and effectiveness profile of dabigatran in clinical practice-based settings.

PKP2 and DSG2 genetic variations in Latvian arrhythmogenic right ventricular dysplasia/cardiomyopathy registry patients.

OBJECTIVE: The Latvian arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD-C) registry was established to determine the genetic background of ARVD-C for analyzing discovered genetic variation frequencies in the European and Latvian populations. METHODS: In total, 38 patients with suspected ARVD-C were selected. The clinical parameters were defined according to the ARVD-C guidelines, PKP2 and DSG2 gene analysis was performed using the Sanger sequencing. Additionally, large deletions/duplications were analyzed using the multiplex ligation-dependent probe amplification (MLPA) analysis. RESULTS: Twenty symptomatic patients were enrolled in the study. Typical ARVD abnormalities were found in electrocardiography for 10 (50%) patients, in Holter monitoring for 19 (95%), in transthoracic echocardiography for 20 (100%), and in cardiac magnetic resonance for 6 (30%). Different benign genetic variations were found. Three novel, unregistered, possibly benign variations were found in the PKP2 gene: c.2489+131G>A, c.2489+72delA, and c.1035-5T>C and three in the DSG2 gene: c.404G>A, c.1107G>A, and c.379-15A>G. Two genetic variations in the PKP2 gene: c.1592T>G, c.2489+1G>A are possibly pathogenic. For the first time, variation c.1592T>G, has been discovered in the homozygote form. Using the MLPA analysis, large deletions or duplications were not found. CONCLUSION: The prevalence of the majority of non-pathological genetic variations is similar in the Latvian ARVD-C patients and the European population. Possibly, pathogenic variations were found only in 10% of our registry patients, which could mean that PKP2 and DSG2 are not the most commonly affected genes in the Latvian population.