Correct dosing, adherence and persistence of DOACs in atrial fibrillation and chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Chronic kidney disease (CKD) and atrial fibrillation (AF) are increasing in prevalence globally and share common risk factors.Our aim was to characterise real-world evidence on direct oral anticoagulant (DOAC) prescribing for people with AF and CKD, in terms of adherence, persistence and renal dose titration. METHODS: PubMed, EMBASE and CINAHL were searched from inception to June 2022. Our search terms included a combination of Medical Subject Headings (MeSH) terms and keywords including 'atrial fibrillation', 'chronic kidney disease', 'adherence', 'persistence', 'direct oral anticoagulants' and 'dosing'. Data extraction and quality assessment were undertaken by two reviewers independently. Meta-analyses for pooled estimates were performed using DerSimonian and Laird random-effects models. Age, sex, diabetes, hypertension and heart failure were chosen as variables of interest. RESULTS: From 19 studies, a total of 252 117 patients were included with CKD and AF. Meta-analysis was only possible in seven studies with 128 406 patients, five on DOAC dose titration and two on adherence. There were insufficient studies on persistence. Our meta-analysis of dosing showed that 68% of patients with CKD and AF had correct dosing. There was no evidence to show any association between correct DOAC dosing and variables of interest. Overall, 67% of patients were DOAC adherent. CONCLUSION: Adherence and correct dosing of DOACs were suboptimal compared with other medications in the pooled studies with respect to CKD and AF. Thus, further research is required as the lack of generalisation of findings is a rate-limiting factor for improved DOAC management in AF and CKD. PROSPERO REGISTRATION NUMBER: CRD;42022344491.

A Chronicle of Hybrid Atrial Fibrillation Ablation Therapy: From Cox Maze to Convergent.

The burden of AF is increasing in prevalence and healthcare resource usage in the UK and worldwide. It can result in impaired quality of life for affected patients, as well as increased risk of stroke, heart failure and mortality. A holistic, integrated approach to AF management is recommended, which may include a focus on reducing risk factors and on medical management with anticoagulation and anti-arrhythmic drugs. There are also various ablation strategies that may be considered when anti-arrhythmic drugs fail to alleviate symptoms and reduce AF burden. These ablation techniques range from standalone percutaneous endocardial catheter ablation to open surgical ablation procedures concomitant with cardiac surgery. More recently, hybrid ablation that combines aspects of both surgical and electrophysiologically targeted ablation has been described. This article reviews the evolution of ablation strategies, beginning with the origin of the Cox maze IV procedure and continuing to the recent hybrid convergent approach, and provides a summary of the associated outcomes.

The management of cardiovascular disease risk in patients with rheumatoid arthritis.

INTRODUCTION: Rheumatoid Arthritis (RA) is a chronic inflammatory disorder associated with an increased incidence and prevalence of cardiovascular disease (CVD), including myocardial infarction and heart failure. In addition to traditional risk factors, evidence suggests inflammation is critical to the pathophysiology of both conditions. Despite the association being well-recognised, challenges remain in managing cardiovascular risk in RA. AREAS COVERED: This manuscript analyses the association between CVD and RA and explores the limitations in evaluating cardiovascular risk in RA with available risk assessment tools. The authors review the optimal management of traditional risk factors such as hypertension and dyslipidaemia and contemporary risk factors such as inflammation and analyse the cardiovascular impact of RA medications. EXPERT OPINION: Analysis points to the critical role of inflammation in the pathogenesis of RA and CVD. It is well established that conventional disease-modifying anti-rheumatic drugs (DMARDs) improve cardiovascular outcomes; however, underlying risk often remains underappreciated. The authors suggest there remains an opportunity to improve mortality and morbidity with the early recognition and of at-risk populations and the timely initiation of appropriate cardiovascular and anti-inflammatory medications. More research is necessary into the role that imaging may play in stratifying risk and in the longer-term cardiovascular impact of biological DMARDs.

Hybrid Convergent Procedure for the Treatment of Persistent and Long-standing Persistent Atrial Fibrillation.

Recent advances have been made in AF treatment, including the role of early rhythm control and landmark clinical trials using ablation therapy. However, some treatment gaps remain, including the creation of durable lesions outside the pulmonary veins and effective treatment of longstanding persistent AF. A novel epicardial-endocardial ablation approach - the hybrid convergent procedure - was developed to combine surgical and catheter ablation techniques into a collaborative, multidisciplinary approach to managing AF. In this review, the authors discuss recently published data on hybrid convergent ablation, including results of the CONVERGE clinical trial, in the context of current challenges to treatment of persistent and long-standing persistent AF. The review also aims to provide perspective on outstanding questions and future directions in this area.

Persistent Atrial Fibrillation: The Role of Left Atrial Posterior Wall Isolation and Ablation Strategies.

Atrial fibrillation (AF) is a global disease with rapidly rising incidence and prevalence. It is associated with a higher risk of stroke, dementia, cognitive decline, sudden and cardiovascular death, heart failure and impairment in quality of life. The disease is a major burden on the healthcare system. Paroxysmal AF is typically managed with medications or endocardial catheter ablation to good effect. However, a large proportion of patients with AF have persistent or long-standing persistent AF, which are more complex forms of the condition and thus more difficult to treat. This is in part due to the progressive electro-anatomical changes that occur with AF persistence and the spread of arrhythmogenic triggers and substrates outside of the pulmonary veins. The posterior wall of the left atrium is a common site for these changes and has become a target of ablation strategies to treat these more resistant forms of AF. In this review, we discuss the role of the posterior left atrial wall in persistent and long-standing persistent AF, the limitations of current endocardial-focused treatment strategies, and future perspectives on hybrid epicardial-endocardial approaches to posterior wall isolation or ablation.

Randomized comparison of oesophageal protection with a temperature control device: results of the IMPACT study.

AIMS: Thermal injury to the oesophagus is an important cause of life-threatening complication after ablation for atrial fibrillation (AF). Thermal protection of the oesophageal lumen by infusing cold liquid reduces thermal injury to a limited extent. We tested the ability of a more powerful method of oesophageal temperature control to reduce the incidence of thermal injury. METHODS AND RESULTS: A single-centre, prospective, double-blinded randomized trial was used to investigate the ability of the ensoETM device to protect the oesophagus from thermal injury. This device was compared in a 1:1 randomization with a control group of standard practice utilizing a single-point temperature probe. In the protected group, the device maintained the luminal temperature at 4°C during radiofrequency (RF) ablation for AF under general anaesthesia. Endoscopic examination was performed at 7 days post-ablation and oesophageal injury was scored. The patient and the endoscopist were blinded to the randomization. We recruited 188 patients, of whom 120 underwent endoscopy. Thermal injury to the mucosa was significantly more common in the control group than in those receiving oesophageal protection (12/60 vs. 2/60; P = 0.008), with a trend toward reduction in gastroparesis (6/60 vs. 2/60, P = 0.27). There was no difference between groups in the duration of RF or in the force applied (P value range= 0.2-0.9). Procedure duration and fluoroscopy duration were similar (P = 0.97, P = 0.91, respectively). CONCLUSION: Thermal protection of the oesophagus significantly reduces ablation-related thermal injury compared with standard care. This method of oesophageal protection is safe and does not compromise the efficacy or efficiency of the ablation procedure.

Combined epicardial and endocardial ablation for atrial fibrillation: Best practices and guide to hybrid convergent procedures.

The absence of strategies to consistently and effectively address nonparoxysmal atrial fibrillation by nonpharmacological interventions has represented a long-standing treatment gap. A combined epicardial/endocardial ablation strategy, the hybrid Convergent procedure, was developed in response to this clinical need. A subxiphoid incision is used to access the pericardial space facilitating an epicardial ablation directed at isolation of the posterior wall of the left atrium. This is followed by an endocardial ablation to complete isolation of the pulmonary veins and for additional ablation as needed. Experience gained with the hybrid Convergent procedure during the last decade has led to the development and adoption of strategies to optimize the technique and mitigate risks. Additionally, a surgical and electrophysiology "team" approach including comprehensive training is believed critical to successfully develop the hybrid Convergent program. A recently completed randomized clinical trial indicated that this ablation strategy is superior to an endocardial-only approach for patients with persistent atrial fibrillation. In this review, we propose and describe best practice guidelines for hybrid Convergent ablation on the basis of a combination of published data, author consensus, and expert opinion. A summary of clinical outcomes, emerging evidence, and future perspectives is also given.

A study to assess a novel automated electrocardiogram technology in screening for atrial fibrillation.

INTRODUCTION: Atrial fibrillation is often asymptomatic and un-diagnosed in the community resulting in an increased risk of heart failure and stroke to those patients. We evaluated the effectiveness, tolerability, and accuracy of a novel six-channel electrocardiogram digital-health screening device, the RhythmPad, for the detection of atrial fibrillation. METHODS: Seven hundred and fifty-two participants attending the cardiology department were recruited. Two recordings were taken-a six-lead electrocardiogram using the RhythmPad device and a standard 12-lead electrocardiogram. Recorded traces were analyzed by two blinded cardiologists. The computer-generated automated diagnostic reports from both systems were also compared. Post-participation feedback was obtained from study participants using a three-part questionnaire. RESULTS: The sensitivity of the six-lead electrocardiogram compared to the 12-lead electrocardiogram, analyzed by two blinded cardiologists, for the detection of normal sinus rhythm was 95.9%, with a specificity of 97.2%. The sensitivity for the detection of atrial fibrillation using the six-lead ECG was 93.4%, with specificity 96.8%. The six-lead automated diagnostic report had a sensitivity and specificity of 97.5% and 98.6%, respectively, for correctly diagnosing normal sinus rhythm. For the correct diagnosis of atrial fibrillation, the six-lead automated diagnostic report had a sensitivity and specificity of 95.4% and 98.8%, respectively. A total of 95.4% of participants found RhythmPad to be comfortable, with only 0.5% preferring the 12-lead ECG device in comparison to six-lead ECG acquisitions. CONCLUSION: The RhythmPad digital health device and its automated diagnostic report were highly accurate in detecting atrial fibrillation when compared to a standard 12-lead electrocardiogram.

Cardiac arrest following protamine administration: a case series.

AIMS: Protamine sulfate is commonly used to reverse the action of heparin after catheter ablation procedures. Serious protamine-related adverse effect is rare, but its recognition and appropriate management by electrophysiologists and intensivists is important. Direct ventricular fibrillation (VF) soon after a slow infusion of protamine has not been clearly described. METHODS AND RESULTS: We examined the records of all patients who suffered apparent adverse events after protamine administration in our electrophysiology lab from 2013 to 2018. We describe a series of three patients, all of whom suffered a precipitous fall in arterial pressure followed by VF within minutes after administration of protamine following ablation for atrial fibrillation. The same supplier of protamine was used in all three cases, but they were from different batches. Serum tryptase levels were measured in all cases, immediately post-cardiac arrest and at 2- and 6-h post-event. Immunoglobulin levels were not measured. Two patients recovered after aggressive supportive therapy; the third died despite similar support. CONCLUSION: We have encountered three cases of profound hypotension followed by VF soon after administration of protamine. Although protamine is safe in a large majority of patients, these adverse events have led our centre to exercise greater selectivity and caution in its use.

Circular mapping catheter entrapment in mitral valve apparatus requiring emergency surgery: a rarely reported complication of pulmonary vein isolation procedure for atrial fibrillation.

Lasso catheter (Biosense Webster) is one of the most commonly employed circular mapping catheters during pulmonary vein isolation (PVI) procedure for atrial fibrillation (AF). Although this catheter has greatly facilitated arrhythmia mapping, it can be associated with serious complications. We report a case of a 59-year-old man who underwent PVI procedure for persistent AF. During the procedure, the Lasso catheter inadvertently slipped into the left ventricular cavity and entangled in the mitral valve apparatus. Various percutaneous manoeuvres to release the catheter were unsuccessful and the patient ultimately required emergency open heart surgery to remove the catheter and repair the valve. To the best of our knowledge, such a case has not previously been reported in the UK necessitating an immediate open heart surgery, avoiding replacement of the valve.

RAAFT-2: Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation.

Radiofrequency ablation (RFA) for the treatment of paroxysmal Atrial Fibrillation (pAF) has a class 1 indication in patients who have not tolerated or responded to antiarrhythmic medications. Antiarrhythmic medications (AAM) are, however, limited not only by modest efficacy, but also by significant side effects. Discontinuation rates for AAM range from 11-40% in trials. The RAAFT-2 trial evaluates the use of RFA as a first line treatment for pAF compared to optimal pharmacological management (1).

Benefits of a quadripolar left ventricular lead in patients undergoing cardiac resynchronization therapy with underlying myocardial scar.

We present a case of a 76-year-old man with ischemic cardiomyopathy. Cardiac magnetic resonance imaging demonstrated severe left ventricular (LV) impairment with possibility of scar formation. Cardiac resynchronization therapy was employed with the aid of a novel quadripolar LV lead. The quadripolar LV lead can be programmed for 10 different pacing configurations, allowing the electrophysiologist freedom to optimize the vector around scar and also avoid phrenic nerve stimulation without the requirement of LV lead repositioning.

Managing atrial fibrillation in the global community: The European perspective.

Atrial fibrillation is a common, global problem, with great personal, economic and social burdens. As populations age it increases in prevalence and becomes another condition that requires careful chronic management to ensure its effects are minimised. Assessment of the risk of stroke using well established risk prediction models is being aided by modern computerised databases and the choice of drugs to prevent strokes is ever expanding to try and improve the major cause of morbidity in AF. In addition, newer drugs for controlling rhythm are available and guidelines are constantly changing to reflect this. As well as medications, modern techniques of electrophysiology are becoming more widely embraced worldwide to provide more targeted treatment for the underlying pathophysiology. In this review we consider these factors to concisely describe how AF can be successfully managed.

Localisation of SCN10A gene product Na(v)1.8 and novel pain-related ion channels in human heart.

We have shown that the gene SCN10A encoding the sodium channel Na(v)1.8 is a susceptibility factor for heart block and serious ventricular arrhythmia. Since Na(v)1.8 is known to be present in nerve fibres that mediate pain, it may be related to both cardiac pain and dysrhythmia. The localisation of Na(v)1.8 and other key nociceptive ion channels, including Na(v)1.7, Na(v)1.9, capsaicin receptor TRPV1, and purinergic receptor P2X(3), have not been reported in human heart. The aim of this study was to determine the distribution of Na(v)1.8, related sodium and other sensory channels in human cardiac tissue, and correlate their density with sympathetic nerves, regenerating nerves (GAP-43), and vascularity. Human heart atrial appendage tissues (n = 13) were collected during surgery for valve disease. Tissues were investigated by immunohistology using specific antibodies to Na(v)1.8 and other markers. Na(v)1.8 immunoreactivity was detected in nerve fibres and fascicles in the myocardium, often closely associated with small capillaries. Na(v)1.8 nerve fibres per mm(2) correlated significantly with vascular markers. Na(v)1.8-immunoreactivity was present also in cardiomyocytes with a similar distribution pattern to that seen with connexins, the specialised gap junction proteins of myocardial intercalated discs. Na(v)1.5-immunoreactivity was detected in cardiomyocytes but not in nerve fibres. Na(v)1.7, Na(v)1.9, TRPV1, P2X(3)/P2X(2), and GAP43 positive nerve fibres were relatively sparse, whereas sympathetic innervation and connexin43 were abundant. We conclude that sodium channel Na(v)1.8 is present in sensory nerves and cardiomyocytes of human heart. Na(v)1.8 and other pain channels provide new targets for the understanding and treatment of cardiac pain and dysrhythmia.

A multi-purpose spiral high-density mapping catheter: initial clinical experience in complex atrial arrhythmias.

PURPOSE: There is an increasing need for catheter ablation procedures to treat complex atrial tachycardias (AT) and atrial fibrillation (AF), often requiring detailed endocardial mapping. The sequential point-to-point contact mapping of complex arrhythmias is time-consuming and may not always be feasible. We assessed the utility of a novel spiral duo-decapolar high-density (HD) mapping catheter to delineate complex arrhythmia substrates for ablation. METHODS: The patients underwent HD mapping using a spiral catheter (AFocusII) and the EnSite NavX system, during catheter ablation procedures, to treat atrial arrhythmias. RESULTS: In 26 patients, a total of 32 atrial arrhythmias were mapped and ablated, comprising of five focal AT, eight macroreentrant AT, 11 persistent AF and eight paroxysmal AF. The HD catheter was used to acquire endocardial surface geometries in all cases and to map the pulmonary veins in patients undergoing AF ablation. In persistent AF, HD catheter mapping permitted the creation of highly detailed complex fractionated electrogram maps (left atrium 449 ± 128 points in 7.2 ± 2.6 min; right atrium 411 ± 113 points in 6.7 ± 1.6 min). In AT, activation mapping was performed with the acquisition of 305 ± 158 timing points in 7.3 ± 2.6 min, guiding successful ablation in all cases. During the follow-up of 7.0 ± 2.6 months, all AT patients remained free of significant arrhythmia. CONCLUSIONS: High-density contact mapping with a novel spiral multipolar catheter allows rapid assessment of focal and macroreentrant AT, and complex fractionated electrical activity in the atria. It has further multi-functional capabilities as a pulmonary vein mapping catheter and for accurate geometry creation when used with a 3D mapping system.

Decreased connexin43 expression in the mouse heart potentiates pacing-induced remodeling of repolarizing currents.

Gap junction redistribution and reduced expression, a phenomenon termed gap junction remodeling (GJR), is often seen in diseased hearts and may predispose toward arrhythmias. We have recently shown that short-term pacing in the mouse is associated with changes in connexin43 (Cx43) expression and localization but not with increased inducibility into sustained arrhythmias. We hypothesized that short-term pacing, if imposed on murine hearts with decreased Cx43 abundance, could serve as a model for evaluating the electrophysiological effects of GJR. We paced wild-type (normal Cx43 abundance) and heterozygous Cx43 knockout (Cx43+/-; 66% mean reduction in Cx43) mice for 6 h at 10-15% above their average sinus rate. We investigated the electrophysiological effects of pacing on the whole animal using programmed electrical stimulation and in isolated ventricular myocytes with patch-clamp studies. Cx43+/- myocytes had significantly shorter action potential durations (APD) and increased steady-state (Iss) and inward rectifier (I(K1)) potassium currents compared with those of wild-type littermate cells. In Cx43+/- hearts, pacing resulted in a significant prolongation of ventricular effective refractory period and APD and significant diminution of Iss compared with unpaced Cx43+/- hearts. However, these changes were not seen in paced wild-type mice. These data suggest that Cx43 abundance plays a critical role in regulating currents involved in myocardial repolarization and their response to pacing. Our study may aid in understanding how dyssynchronous activation of diseased, Cx43-deficient myocardial tissue can lead to electrophysiological changes, which may contribute to the worsened prognosis often associated with pacing in the failing heart.