Andres Enriquez

Anticoagulation reversal in the era of the non-vitamin K oral anticoagulants

In recent years, non-vitamin K oral anticoagulants (NOACs) have emerged as an alternative to warfarin for the prevention and treatment of thrombo-embolic disease. Large randomized trials have demonstrated that these agents, which act by directly targeting thrombin (dabigatran) and factor Xa (rivaroxaban, apixaban, and edoxaban), are at least as effective as warfarin, with lower rates of bleeding and fewer interactions with food and drugs. In addition, NOACs have a more predictable anticoagulant effect, allowing a fixed dose regimen and obviating the need for routine anticoagulation monitoring. Since the introduction of NOACs, one of the major concerns for clinicians has been the lack of specific agents to reverse their anticoagulant effect in case of life-threatening haemorrhagic complications or emergency surgery, which have limited their use in patients deemed at a higher risk of bleeding. New specific antidotes (e.g. idarucizumab, andexanet alfa, and ciraparantag) show promising data, and may soon become available for clinical use. In this article, we review the pharmacology of these agents, the incidence and outcomes of haemorrhagic complications, the available strategies for anticoagulation reversal, and the more recent advances for the development of specific antidotes.

New-onset atrial fibrillation after cavotricuspid isthmus ablation: identification of advanced interatrial block is key

AIMS A significant proportion of patients develop atrial fibrillation (AF) following cavotricuspid isthmus (CTI) ablation for typical atrial flutter (AFl). The objective of this study was to assess whether the presence of advanced interatrial block (aIAB) was associated with an elevated risk of AF after CTI ablation in patients with typical AFl and no prior history of AF. METHODS AND RESULTS This study included patients with typical AFl and no prior history of AF that were referred for CTI ablation. Patients were excluded when they had received repeat ablations or did not demonstrate a bidirectional block. In all patients, a post-ablation electrocardiogram (ECG) in sinus rhythm was evaluated for the presence of aIAB, defined as a P-wave duration ≥120 ms and biphasic morphology in the inferior leads. New-onset AF was identified from 12-lead ECGs, Holter monitoring, and device interrogations. The cohort comprised 187 patients (age 67 ± 10.7 years; ejection fraction 55.8 ± 11.2%). Advanced interatrial block was detected in 18.2% of patients, and left atrium was larger in patients with aIAB compared with those without aIAB (46.2 ± 5.9 vs. 43.1 ± 6.0 mm; P = 0.01). Over a median follow-up of 24.2 months, 67 patients (35.8%) developed new-onset AF. The incidence of new-onset AF was greater in patients with aIAB compared with those without aIAB (64.7 vs. 29.4%; P < 0.001). After a comprehensive multivariate analysis, aIAB emerged as the strongest predictor of new-onset AF [odds ratio (OR) 4.2, 95% confidence interval (CI): 1.9-9.3; P < 0.001]. CONCLUSION Advanced interatrial block is a key predictor for high risk of new-onset AF after a successful CTI ablation in patients with typical AFl.

Relation of Interatrial Block to New-Onset Atrial Fibrillation in Patients With Chagas Cardiomyopathy and Implantable Cardioverter-Defibrillators

Chagas cardiomyopathy is an endemic disease in Latin America. A significant proportion of patients develop atrial fibrillation (AF), which may result in stroke and increased morbidity or mortality. Interatrial block (IAB) has been associated with the development of AF in different clinical scenarios. The aim of our study was to determine whether IAB can predict new-onset AF in patients with Chagas cardiomyopathy and implantable cardioverter-defibrillators (ICDs). We conducted a retrospective study of patients with Chagas cardiomyopathy and ICDs from 14 centers in Latin America. Demographics, clinical, and device follow-up were collected. Surface electrocardiograms were scanned at 300 dpi and maximized ×8. Semiautomatic calipers were used to determine P-wave onset and offset. Partial IAB was defined as a P wave of >120 ms and advanced IAB as a P wave of >120 ms with biphasic morphology (±) in inferior leads. AF events and ICD therapies were reviewed during follow-up by 2 independent investigators. A total of 80 patients were analyzed. Mean age was 54.6 ± 10.4 years, and 52 (65%) were male. Mean left ventricular ejection fraction was 40 ± 12%. IAB was detected in 15 patients (18.8%), with 8 (10.0%) partial and 7 (8.8%) advanced. During a follow-up of 33 ± 20 months, 11 patients (13.8%) presented with new AF. IAB (partial + advanced) was strongly associated with new AF (p <0.0001) and inappropriate therapy by the ICD (p = 0.014). In conclusion, IAB (partial + advanced) predicted new-onset AF in patients with Chagas cardiomyopathy and ICDs.

Differential Diagnosis of rSr’ Pattern in Leads V1‐V2. Comprehensive Review and Proposed Algorithm

One of the more frequent dilemmas in ECG interpretation is the differential diagnosis of an rSr’ pattern in leads V1‐V2. We often face this finding in asymptomatic and otherwise healthy individuals and the causes may vary from benign nonpathological variants to severe or life‐threatening heart diseases, such as Brugada syndrome or arrhythmogenic right ventricular dysplasia. In other cases, a normal variant of rSr’ pattern can be misinterpreted as pathological after the occurrence of certain clinical events such as cardiac arrest or syncope of unknown cause. In this review we analyze in detail all the possible conditions, both benign and pathological that may explain the presence of this electrocardiographic pattern. We also propose a simple electrocardiographic algorithm for differential diagnosis.

Progressive Interatrial Block and Supraventricular Arrhythmias

Interatrial conduction disorders are frequent in patients with structural heart diseases, including hypertension, coronary disease, and hypertrophic cardiomyopathy, and they are strongly associated with atrial tachyarrhythmias, especially atrial fibrillation and flutter. Conduction delays lead to dispersion of refractory periods and participate in initiating and maintaining reentry circuits, facilitating atrial arrhythmias. In this case, the changing pattern over time is a manifestation of progressive atrial remodeling and conduction delay. The terminal negative component of the P wave in the inferior leads suggests block of the electrical impulse in the Bachman bundle zone, with retrograde activation of the left atria via muscular connections at the coronary sinus. This has been reproduced in experimental models and confirmed by endocardial mapping. Physicians should be aware of the association between advanced interatrial block and development of atrial arrhythmias as its recognition could prompt early and aggressive antiarrhythmic treatment.

Atrial fibrillation in inherited cardiac channelopathies: From mechanisms to management

Atrial fibrillation (AF) is prevalent in cardiac channelopathies and may be the presenting feature in some patients. The pathogenesis is related to the primary ion channel dysfunction in atrial myocytes that affects atrial conduction or repolarization. The development of AF is associated with adverse outcomes, and its management is challenging in these patients. In this article we review the current information on the prevalence, risk factors, pathophysiology, and treatment of AF in specific cardiac channelopathies.

Female gender as independent risk factor of torsades de pointes during acquired atrioventricular block

BACKGROUND Female gender increases the risk of torsades de pointes (TdP) in the long QT syndrome, and this increased risk is assumed to be due to their longer QT interval. OBJECTIVE The purpose of this study was to study the interplay between gender, duration of the QT interval, and risk of TdP during AV block. METHODS We studied 250 patients (48% women) with AV block. QT interval was measured at the time of most severe bradycardia. We then constructed different receiver operating characteristic curves for the QTc of males and females for predicting TdP. RESULTS As expected, patients with TdP had longer QTc intervals than did patients with uncomplicated AV block (564 ± 81 ms vs 422 ± 62 ms, P < .001). This correlation between longer QTc and higher risk of TdP was true for both genders. However, the QT of females with TdP was shorter than the respective value for males with TdP. Despite similar severity of bradycardia, the QT was shorter for females (QT 672 ± 88 ms vs 727 ± 57 ms for females with TdP vs males with TdP, P = .022). The QTc/TdP risk curve for females was shifted to the left in comparison to the pertinent graph for males. Female gender was an independent predictor of TdP. CONCLUSION Women are at increased risk for developing TdP during AV block, but this increased risk is independent of their longer QT interval. Females develop TdP with QT intervals that are not necessarily arrhythmogenic for males.

Dabigatran for the prevention and treatment of thromboembolic disorders.

Dabigatran, an oral direct thrombin inhibitor, was the first of a new class of drugs referred to as non-vitamin K oral anticoagulants. Dabigatran is better than warfarin for stroke prevention in non-valvular atrial fibrillation (dose of 150 mg twice a day), non-inferior to enoxaparin for venous thromboembolism prevention after orthopedic surgery and non-inferior to warfarin in preventing recurrence after acute venous thromboembolism. The safety profile is similar to standard anticoagulants, with significant reduction observed in intracranial hemorrhage. Other advantages include a rapid onset of action and a predictable pharmacokinetic profile, allowing a fixed-dose regimen without the need for routine anticoagulation monitoring. In the event of bleeding, general support measures are recommended and if severe, the use of non-specific hemostatic agents such as prothrombin complex concentrates and recombinant factor VIIa must be considered. A specific reversal agent (idarucizumab) is in development.

Imaging characteristics of papillary muscle site of origin of ventricular arrhythmias in patients with mitral valve prolapse

Mitral valve prolapse has been associated with increased risk of ventricular arrhythmias. We aimed to examine whether certain cardiac imaging characteristics are associated with papillary muscle origin of ventricular arrhythmias in these patients.

Postoperative atrial tachycardias after mitral valve surgery: Mechanisms and outcomes of catheter ablation

BACKGROUND Atrial tachycardias (ATs) including atrial fibrillation are common arrhythmias occurring late after mitral valve (MV) surgery, and their management is challenging. OBJECTIVE The purpose of this study was to determine the electrophysiological mechanisms of ATs in patients with prior MV surgery and the long-term outcomes of catheter ablation. METHODS We studied 67 consecutive patients (mean age 59.4 ± 10.6 years; 41 men [61%]) with prior MV surgery who presented with ATs postoperatively between 2007 and 2015. RESULTS AT was clinically documented before the electrophysiology study in 55 patients, whereas in the remaining 12 patients AT was inducible at the study. A total of 99 ATs (35 spontaneous and 64 inducible) were characterized. Overall, the right atrium (RA) was the chamber of origin in 56%. The underlying mechanism was macroreentry in 91 cases and included typical RA flutter (n = 37), mitral annular flutter (n = 21), incisional right AT (n = 16), roof-dependent reentry (n = 12), and local left atrial reentry (n = 5). Eight focal ATs were also documented: 6 from the left atrium and 2 from the RA. Left-sided ATs were more common in patients with prior Maze procedure (53%), and mitral annular flutter was twice as prevalent in this group (42% vs 21%; P = .05). The ablation was acutely successful in 98.5%. Freedom from atrial arrhythmias was 62% at 12 months, with 42% requiring more than 1 procedure. CONCLUSION Macroreentry is the predominant AT mechanism in patients with prior MV surgery. Circuits are most often localized to the RA, with left-sided ATs more common in patients with prior Maze procedure. Repeat procedures are common and outcomes with 1 year complete AT control good.