Carlos A. Morillo

The Word Heart Federation Roadmap for Nonvalvular Atrial Fibrillation

BACKGROUNDnThe World Heart Federation has undertaken an initiative to develop a series of Roadmaps to promote development of national policies and health systems approaches, and to identify potential roadblocks on the road to effective prevention, detection, and management of cardiovascular disease in low-and middle-income countries (LMICs) and develop strategies for overcoming these. This Roadmap focuses on atrial fibrillation (AF). AF is the most common, clinically significant arrhythmia and, among other clinical outcomes, is associated with increased risk of stroke.nnnMETHODSnDevelopment of this Roadmap included a review of published guidelines and research papers, and consultation with an expert committee comprising experts in clinical management of AF and health systems research in LMICs. The Roadmap identifies 1) key interventions for detection, diagnosis, and management of AF; 2) gaps in implementation of these interventions (knowledge-practice gaps); 3) health system roadblocks to implementation of AF interventions in LMICs; and 4) potential strategies for overcoming these.nnnRESULTSnMore research is needed on determinants and primary prevention of AF. Knowledge-practice gaps for detection, diagnosis, and management of AF are present worldwide, but may be more prominent in LMICs. Potential barriers to implementation of AF interventions include long distances to health facilities, shortage of health care professionals with training in AF, including interpretation of ECG, unaffordability of oral anticoagulants for patient households, reluctance on the part of physicians to initiate oral anticoagulant (OAC) therapy, and lack of awareness of the importance of persistent adherence to OAC therapy. Potential solutions include training of nonphysician health workers and pharmacists in pulse-taking, use of telemedicine technologies to transmit electrocardiogram results, engagement of nonphysician health workers in OAC therapy adherence support, and country-specific support and education programs for noncardiologist health care professionals.nnnCONCLUSIONSnAF affects millions of people worldwide and, left untreated, increases the risk and severity of stroke and heart failure. Although guidelines for the detection, diagnosis, and management of AF exist, there are gaps in implementation of these guidelines globally, and in particular in LMICs. This Roadmap identifies some potential solutions that may improve AF outcomes in LMICs but require further evaluation in these settings.

Electroanatomical mapping based on discrimination of electrograms clusters for localization of critical sites in atrial fibrillation

Locating critical sites on the atrial surface during AF to guide the ablation procedures is an open problem. Electrogram-guided approaches have been proposed. However, electrograms (EGM) are complex and not well-described type of signals and anatomically-based pulmonary vein isolation remains been recommended as the cornerstone procedure. We introduce a method that builds an electroanatomical map to visualize the distribution of different morphological patterns of the EGM signals over the atrial surface. The proposed scheme uses EGM signals recorded with a commercial cardiac mapping. Likewise, two morphological and two non-linear features are computed from each single EGM. Patterns are discriminated using a semi-supervised clustering approach that does not need a priory definition of EGM morphologies or classes. The method was tested under two scenarios: a set of EGM signals recorded in AF patients and a set of signals obtained from 2D simulations of atrial conduction sustained by rotors. Our method was able to locate the clusters in a map of the atrial surface of each patient. These locations allow the specialist to study the distribution of critical AF sites. The method was able to locate the pivot point of the rotors in the 2D models. Our results suggest that the proposed method is a potential assisting tool for guided ablation procedures. Further clinical studies are needed to establish the relationship between clusters and arrhythmogenic substrates in AF, and to validate the usefulness of the method to locate critical conduction sites in patients.

Chagas heart disease: A contemporary review

Chagas disease is caused by a parasite infection endemic of the Americas. Traditionally observed in rural areas of Latin America, current migration trends have turned Chagas disease into a global epidemic. Acute infection is rarely severe and once it resolves, some patients can develop cardiomyopathy as part of the chronic form many years later. Multiple factors related with both the host and the parasite determine the susceptibility and progression to cardiomyopathy. Current imaging techniques are able to identify cardiac autonomic denervation, perfusion abnormalities, and myocardial fibrosis at an early of stage before the development of symptoms. The prognosis of patients with Chagasic cardiomyopathy remains poor and life-threatening ventricular arrhythmias can occur at an early stage. Treatment of chronic Chagas cardiomyopathy is challenging with a great need for more studies in the field.

Implantable cardioverter-defibrillator in Chagas heart disease: A systematic review and meta-analysis of observational studies

BACKGROUNDnIn patients with Chagas cardiomyopathy (ChCM), sudden cardiac death (SCD) is the leading cause of mortality. Implantable cardioverter-defibrillator (ICD) is a well-established therapy for secondary prevention in patients with structural heart disease, but there are conflicting opinions regarding its efficacy and safety in patients with ChCM. The aim of this meta-analysis was to assess the efficacy of the ICD for secondary prevention in patients with ChCM, comparing mortality as the primary outcome of patients treated with ICD with those treated with amiodarone.nnnMETHODSnWe systematically searched five databases for studies assessing mortality outcomes in patients with ChCM and sustained ventricular tachycardia (VT) treated with ICD implantation or with amiodarone. The results of studies were pooled using random-effects modeling.nnnRESULTSnThere was no randomized clinical trial comparing efficacy of ICD versus medical treatment in patients with ChCM. Six observational studies were included, totalizing 115 patients in amiodarone group and 483 patients in ICD group. The mortality outcome in the ICD population was 9.7 per 100 patient-years of follow-up (95%CI 5.7-13.7) and 9.6 per 100 patient-years in the amiodarone group (95%CI 6.7-12.4) (pu202f=u202f0.95). Meta-regression did not show any association with LV ejection fraction (pu202f=u202f0.32), age (pu202f=u202f0.44), beta-blocker (pu202f=u202f0.33) or angiotensin-converting enzyme inhibitors (pu202f=u202f0.096) usage.nnnCONCLUSIONnThe best available evidence derived from small observational studies suggests that ICD therapy in secondary prevention of sudden death (VT or resuscitated SCD) is not associated with lower rate of all-cause mortality in patients with ChCM. Randomized controlled trials are needed to answer this question.

Uninterrupted administration of edoxaban vs vitamin K antagonists in patients undergoing atrial fibrillation catheter ablation: Rationale and design of the ELIMINATE-AF study.

Patients with atrial fibrillation (AF) are at an approximately 0.5% to 3% increased risk of thromboembolism during and immediately after catheter ablation. Treatment guidelines recommend periprocedural oral anticoagulation plus unfractionated heparin during ablation. Rivaroxaban and dabigatran are the only non–vitamin K oral anticoagulants for which there are randomized controlled trials assessing uninterrupted anticoagulation in patients undergoing catheter ablation of AF. Edoxaban, a direct factor Xa inhibitor, is noninferior vs warfarin for the prevention of stroke or systemic embolism with less major bleeding in patients with nonvalvular AF. The ELIMINATE‐AF (Evaluation of Edoxaban Compared With VKA in Subjects Undergoing Catheter Ablation of Nonvalvular Atrial Fibrillation) trial is a multinational, multicenter, prospective, randomized, open‐label, parallel‐group, blinded‐endpoint evaluation (PROBE) study to assess the safety and efficacy of once‐daily edoxaban 60u2009mg (30u2009mg in patients indicated for a dose reduction) vs vitamin K antagonists (VKA) in patients with nonvalvular AF undergoing catheter ablation (http://www.ClinicalTrials.gov: NCT02942576). A total of 560 patients are planned for randomization to edoxaban or VKA (2:1 ratio) to obtain 450 patients fully compliant with the protocol. Patients will complete 21 to 28u2009days of anticoagulation prior to the ablation and a 90‐day post‐ablation period. The primary efficacy endpoint is the composite of all‐cause death, stroke, and major bleeding. The primary safety endpoint is major bleeding. A magnetic resonance imaging substudy will assess the incidence of silent cerebral lesions post‐ablation. ELIMINATE‐AF will define the efficacy and safety of edoxaban for uninterrupted oral anticoagulation during catheter ablation of AF.

Cardiovascular testing in patients with postural tachycardia syndrome and Ehlers-Danlos type III: authors' response

We appreciate the letter by Drs. Blitshteyn and Fries [1] in response to our recent research letter describing the cardiovascular profile in a small sample of individuals with postural orthostatic tachycardia syndrome (POTS) and Ehlers–Danlos Syndrome type III (EDSIII) compared to sexand age-matched controls [2]. We agree that there is much work remaining to be conducted to comprehensively examine potential differences between POTS ? EDSIII and controls and that there is considerable benefit to be gained from assessments of the cardiovascular system under stress. However, we assert that due to the lack of prior examinations in this field, there is still benefit to our resting assessments, as the symptom of orthostatic intolerance does not necessarily stem from a similarly dynamic physiological cause. In our study [2], we chose to assess arterial stiffness, as measured by carotidfemoral pulse wave velocity (cfPWV), as a static index of large artery viscoelastic behaviour. More than simply a marker of atherosclerosis, cfPWV estimates the pressurebuffering capacity of the arterial wall by measuring the speed of a forward pulse wave through large conduit arteries. High levels of arterial stiffness have serious consequences to central pressure augmentation, left ventricular afterload and end-organ damage [3]; however, the consequences of severely low levels of arterial stiffness are completely unknown. With the understanding that individuals with POTS ? EDSIII are generally free from earlyonset atherosclerosis, we hypothesized that these individuals might, in fact, be at the opposite end of the stiffness spectrum, with systemically compliant arteries contributing to poor hemodynamic management during orthostatic challenge. As recently suggested by Blitshteyn and Fries [4], our hypothesis is in line with the theory that reduced preload may explain exercise intolerance in the POTS population, potentially secondary to altered control of the peripheral arterial system caused by pathologically increased arterial compliance—although our data do not support this theory. While we further hypothesized that reduced physical activity may have confounded our ability to detect reduced arterial stiffness in individuals with POTS, we do not suggest that reduced habitual activity is a potential cause of the symptomology of POTS, as the etiology is likely related to the dysautonomia central to the condition. While cfPWV would also likely change with varying degrees of orthostatic challenge, measurement of cfPWV during tilt might also be confounded by autonomic reflexes, the complex relationship between cfPWV and heart rate or gravity itself, leading to complex interpretation. However, other cardiovascular parameters may reveal unique information during orthostatic stress. In fact, relatively novel indices of regional cardiac energetics (such as left ventricular rotational mechanics, as presented in our study [2]) have recently been demonstrated to be regulated by different myocardial wall mechanics at rest versus during exercise, potentially revealing new information about central haemodynamics [5]. With regards to the potential role of adrenergic antibodies in orthostatic intolerance, we & Maureen J. MacDonald macdonmj@mcmaster.ca

Sick Sinus Syndrome

The sinoatrail node (SAN), the dominant pacemaker in the heart, was originally described by Keith et al. in 1907 [1]. The SAN is a subepicardial structure located at the junction of the right atrium and the superior vena cava [1]. The SAN spontaneous firing activity is not completely understood. Two predominant mechanisms are proposed to serve as the initiation of the sinus activity: The If channels (sodium and potassium ionic currents) and spontaneous intracellular calcium released by sarcoplasmic reticulum [2]. These two mechanisms are not mutually exclusive, and current evidence suggests that they may be complementary in their pacemaker actions. The SAN is richly innervated by the autonomic nervous system and the balance between the parasympathetic and sympathetic inputs modulate pacemaker rate. The vagal parasympathetic nerves slow the SAN rate and are dominant at rest, while increased sympathetic nerve traffic as well as adrenal medullary release of catecholamines increase sinus rate during exercise and stress.