Rhythmos (E-Journal - First Department of Cardiology / Evagelismos General Hospital of Athens)
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Focal Rotor/Driver Ablation for Atrial Fibrillation: a Dream Come True?
Get PDFThe success of catheter ablation of atrial fibrillation (AF) remains modest despite the use of a variety of techniques, because the real target remains elusive. Even the endpoint of AF ablation is still under debate. It is not yet known whether isolation of the pulmonary veins (PVI), currently having a reproducible modest success rate when performed at the antrum and guided by electrophysiological mapping, is what is needed or additional foci should be routinely targeted. Some investigators have suggested that it is the ganglionated plexi (GPs) that mostly provide the triggers to the pulmonary veins, and GPs should be the primary targets during ablation. Others have focused on ablation of complex-fractionated atrial electrograms (CFAEs) claiming successful outcome; some have combined PVI with ablation of CFAEs. In cases of persistent AF, additional ablation lines and/or posterior atrial wall debulking have been applied to enhance the success rate of the procedure. Until recently, no focal ablation was ever reported to have any success in this patient population.Recently, Narayan et al devised an optical computational approach and mapped localized electrical rotors and focal impulse sources in 49 patients with AF. Patients with persistent AF (n=30) had more sources than those with paroxysmal AF (2.1±1.0 vs 1.5±0.8, P=0.02), related to shorter cycle length (163±19 ms vs 187±25 ms, P<0.001). The majority of sources were found in the left atrium and only about a quarter of sources were localized in the right atrium. In a subsequent case report, the authors presented a patient with persistent AF who failed prior left atrial radiofrequency Maze and endocardial ablation procedures. Use of this novel computational mapping disclosed one AF rotor in the right atrium and another in the left atrium. Brief 3–5-minute ablation applications at each rotor terminated AF, which remained noninducible on testing, while no AF recurrence was reported over the next 6 months. In another study by the same group, the investigators localized rotors or focal sources (mean 2.1 sources) in 98 (97%) of 101 patients with sustained AF and then proceeded with ablation aiming at these targets. This novel approach with focal impulse and rotor modulation (FIRM) was applied in 36 patients and compared with conventional ablation performed in the other 71 patients... (excerpt
Cardiology News /Recent Literature Review Third Quarter 2012
Get PDFTCT Meeting will take place in Miami, 22-26/10/12 HCS Meeting to be held in Athens, 1-3/11/12 AHA 2012 is scheduled for Los Angeles, 3-7/11/12EuroEcho will take place in Athens, 5-8/12/2012HCS Working Group Seminars: Thessaloniki, 14-16/2/2013 ACC Meeting: San Francisco, 9-11/3/13HRS Meeting: Denver, 8-11/5/13EuroPCR: Paris, 21-24/5/13 EuroPace: Athens, 23-26/6/13ESC Congress: Amsterdam, 31/8-4/9/13Dennmark Cohort Study: In Patients with AF, Interruption of Warfarin Confers Increased Short-Term Risk of Death or Thrombo-Embolic Events In total, 48,989 atrial fibrillation (AF) patients receiving warfarin were included in this retrospective cohort study. Of these, 35,396 patients had at least one episode of warfarin treatment interruption. In all, 8255 deaths or thromboembolic events occurred during treatment interruption showing an initial clustering of events during 0–90 days. The first 90-day interval of treatment interruption was associated with a markedly higher risk of death or thrombo-embolism (incidence rate ratio-IRR 2.5) vs the interval of 271–360 days. The authors concluded that in this patient population with AF, almost 3 out of 4 patients on warfarin treatment had one or more periods of treatment interruption. Interruption of warfarin therapy was associated with a significantly increased short-term risk of thrombo-embolism or death during the first 90 days of interruption (Raunso J et al, Eur Heart J 2012; 33: 1886–1892).Left Ventricular Dyssynchrony May Determine Outcome Following CRT in Patients with RBBB and Help in the Selection of CRT Candidates Echocardiography was performed in 561 cardiac resynchronization therapy (CRT) recipients (89 with RBBB & 472 with LBBB) before and 6 months after CRT. RBBB patients had a higher prevalence of male gender, ischemic heart disease, atrial fibrillation, and lower exercise capacity when compared with LBBB patients, despite smaller left ventricular (LV) volumes. In addition, the extent of both interventricular and LV dyssynchrony was less in RBBB patients. At 6 months, RBBB patients also showed limited LV reverse remodelling. LV dyssynchrony and mitral regurgitation were identified as independent predictors of all-cause mortality or heart failure hospitalization among RBBB patients. The authors concluded that RBBB patients referred for CRT exhibit interventricular and LV dyssynchrony, albeit less than their LBBB counterparts; preimplantation LV dyssynchrony may be an important determinant of death or heart failure hospitalization among CRT recipients with RBBB (Leong DP et al, Eur Heart J 2012; 33: 1934–1941)... (excerpt
Did PALLAS Deliver the Final Blow to Dronedarone?
Get PDFThe Permanent Atrial Fibrillation Outcome Study Using Dronedarone on Top of Standard Therapy (PALLAS) included patients aged over 65 years, who had at least 6-month history of permanent atrial fibrillation (AF) and risk factors for major vascular events. The latter comprised coronary artery disease, previous stroke or transient ischemic attack, symptomatic heart failure, which was defined as current New York Heart Association class II or III symptoms and admission to the hospital for heart failure in the previous year (but not in the most recent month), a left ventricular ejection fraction of <40%, peripheral arterial disease, or the combination of an age of 75 years or older, hypertension, and diabetes. They were randomized to receive either dronedarone at a dose of 400 mg twice daily or placebo. On July 5, 2011, the data monitoring committee recommended that the study be terminated for safety reasons. A total of 3236 patients had undergone randomization with median follow-up of 3.5 months. The investigators had defined as the first coprimary outcome: stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes; and as a second coprimary outcome: unplanned hospitalization for a cardiovascular cause or death.The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio-HR, 2.29; P=0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (HR, 2.11; P = 0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (HR, 3.26; P = 0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (HR, 2.32; P = 0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (HR, 1.81; P = 0.02). Thus, the authors concluded that dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent AF who were at risk for major vascular events and therefore this drug should not be used in such patients... (excerpt
Hypertension in the Elderly
Get PDFIn our aging society, most of the elderly aged >65 years are affected by systolic hypertension (HTN) [blood pressure (BP) >140 mmHg], which constitutes a major risk factor for organ damage and cardiovascular (CV) events. Management of HTN in the elderly represents a therapeutic dilemma because HTN trials had upper age limits or did not present age-specific results. However, the HYVET trial documented that therapy is beneficial even in those >80 years. In the elderly, systolic BP and pulse pressure emerge as potent risk factors for CV events. In the past an empiric formula "100+age" was used to estimate appropriate systolic BP. Diastolic BP is more important in younger people <50 years.Hypertension in the elderly is due to increased stiffness and pulse wave velocity of the great arteries with earlier return of reflected waves, causing high systolic BP, low diastolic BP, increased myocardial oxygen demand with higher peripheral resistance and limited organ perfusion. Furthermore, decreased renal function contributes to HTN through volume expansion, increased intracellular sodium, reduced Na-Ca exchange; K+ excretion is limited and plasma aldosterone is low, so that the elderly are prone to drug-induced hyperkalemia. Autonomic dysfunction and venous insufficiency contribute to orthostatic hypotension, resulting in falls, syncope, CV events or orthostatic hypotension. Secondary HTN should also be considered, including renal artery stenosis, obstructive sleep apnea, primary aldosteronism, hyper- or hypo-thyroidism, tobacco, alcoholism, caffeine, use of no-steroidal anti-inflammatory drugs, glucocorticoids, sex hormones... (excerpt
More Bleeding With the Newer Anticoagulants?
Get PDFThe new oral anticoagulants that are currently available are dabigatran (Pradaxa, Boehringer Ingelheim), a direct thrombin inhibitor, and the activated factor X (Xa) inhibitors, apixaban (Eliquis, Pfizer) and rivaroxaban (Xarelto, Bayer), with several other agents in the pipeline. These new oral anticoagulants are supposed to have a wider therapeutic window than warfarin, leading to a lower incidence of major bleeding. However, the results of large randomized trials indicate that bleeding remains a major concern even with the new agents. Studies with rivaroxaban, edoxaban and dabigatran showed that these drugs have incidences of severe bleeding comparable to those of enoxaparin and warfarin. The number of bleeding events is rising due to the ageing of the population and the increasing need for interventional therapies. The shorter half-life of the new agents might facilitate the management of bleeding events and the control of anticoagulation during interventions or emergency circumstances. If bleeding occurs, the lack of specific antidotes limits the therapeutic options. Due to the selection bias in the initial randomized studies, the absolute bleeding risk might be underestimated. This can only be measured after exposure of the drugs to larger populations with close post marketing surveillance within registries, a strategy that would be very helpful in defining the actual bleeding risk for the new drug classes. In case of bleeding occurrence, supportive care should be sufficient for most patients because of the short duration of action of the new agents. Some have suggested the use of prothrombin complex concentrates as a reversal agent for the new agents, but the data are limited... (excerpt
Long-Term Results of Atrial Fibrillation Ablation
Get PDFAtrial fibrillation (AF) is the most common sustained cardiac arrhythmia in the general population, affecting about 0.4% of the general population. Its prevalence increases with age reaching 15% in adults over 70 years of age. During the past decade, as techniques and technologies have improved, catheter ablation of AF has become a standard and effective therapy for patients with symptomatic and drug-refractory AF. The improved three-dimensional electroanatomic mapping systems and the induction in the clinical practice of other ablation techniques, such as cryoablation, have contributed to the worldwide increase of the number of ablation procedures. Catheter ablation seems to be superior to antiarrhythmic drug therapy (ADT) which is also associated with potential toxic or proarrhythmic effects after long term use. The recently presented data from RAAFT 2 study, showed that 55% of the patients who had randomized to AF ablation had had a recurrence compared to 72%, of those who had received ADT after 2 years follow up. For the first time, the 2012 updated guidelines from the European Society of Cardiology, recommend catheter ablation as the first line therapy in selected patients with paroxysmal AF alternative to ADT (class IIa, level B). The main target of the AF catheter ablation is the circumferential electrical isolation of the pulmonary veins (PVs) ostium or antrum. In some patients suffering from persistent AF, a more aggressive strategy is adopted, including left atrial substrate modification with linear ablation or rarely with lesions in other anatomical structures as right atrium, superior or inferior vena cava, fossa ovalis, left atrial appendage and coronary sinus or the ligament of Marshall... (excerpt
Dronedarone: the Hope and the Hype
Get PDFAtrial fibrillation (AF) is the commonest cardiac arrhythmia afflicting ~1% of the total population in an age-dependent manner with 2.3% of individuals older than 40 years of age, or 5.9% of people older than 65. Approximately 70% of persons with AF are between 65 and 85 years of age. Patients with AF experience significantly higher mortality rates than patients without AF; adjusted relative mortality risk has been found approximately 20% higher in patients with AF in all age-sex strata during each of the 3 years studied (P < 0.05). One sixth of all strokes are attributable to AF and the percentage of strokes due to AF increases dramatically with age; of course the risk of stroke is significantly decreased with anticoagulation therapy by 60-70%, but this has its own inherent problems. Unfortunately, the use of antiarrhythmic drugs (AADs) employed thus far to maintain sinus rhythm is severely problematic with treatment being occasionally worse than the disease. Nevertheless, the goal is still to maintain sinus rhythm, since teleologically this is the optimal rhythm man is born and should live with, but the means to effect and sustain this, have inherent potentially prohibitive risks, as shown in the AFFIRM, RACE and other trials. However, even in the AFFIRM trial, which showed that AADs may be associated with increased mortality, overall maintenance of sinus rhythm (with or without AADs) was associated with improved survival compared with persistent AF. This observation supports the long-recognized mortality risk associated with AF, and hence the continued quest for development of new and safer antiarrhythmic agents and methods to maintain sinus rhythm. In this endeavor, newer pharmacological agents have recently emerged but not yet fulfilled this expectation. Among them, dronedarone, a modified molecule of amiodarone devoid of the iodine moiety, was heralded as the agent with the new hope... (excerpt
New Agents in the Treatment of Pulmonary Hypertension
Get PDFPulmonary Hypertension (PH) is defined as an increase in mean pulmonary arterial pressure (PAP) ≥25 mmHg at rest as assessed by right heart catheterization (RHC). As stated in the European Society of Cardiology (ESC) 2009 guidelines, it can be classified into 5 main categories, presented in Table 1. Pulmonary arterial hypertension is a rare disease with a prevalence of 15 cases /million adult population and an incidence of 2.4 cases/million adult population/year. The pathophysiology of PH is complex and it has not been elucidated in detail since it involves various biochemical pathways and cell types. Vasoconstriction, remodeling with extensive proliferation of the vessel wall cells causing progressive obstruction, inflammation and thrombosis have been implicated. Structural or functional abnormalities of potassium channels in the smooth muscle cells and endothelial dysfunction characterized by impaired nitric oxide (NO) and prostacyclin production or increased expression of thromboxane A2 and endothelin-1are thought to underlie the cellular changes.Although groups two and three account for the majority of the cases, the trials testing and validating therapeutic options involve mostly patients with group one PH (Pulmonary Arterial Hypertension-PAH). Apart from conventional therapy including diuretics, oral anticoagulants, calcium channel blockers in case of established vasoreactivity, digoxin, oxygen administration and exercise –rehabilitation programs, specific drugs have emerged and gradually find their place in the management of PAH during the last decade. Prostanoids such as intravenous (IV) epoprostenol, iloprost inhaled and IV and treprostinil subcutaneously (SC) or IV have been established agents in the management of PAH, improving performance ability and survival (epoprostenol)... (excerpt
NEWS FROM THE INDUSTRY: Safety Announcements
Get PDFMedtronic informs that a software problem has been noticed in the following models: Consulta CRT-D, Secura DR/VR, Concerto II CRT-D, Virtuoso II DR/VR, Maximo II CRT-D, Maximo IIDR/VR. By April, 19 2010 Medtronic has received 5 confirmed reports from 144000 devices none of them associated with adverse effects of any kind. A particular sequence of the following 3 facts must take place within a few ms to cause this problem.1. The high voltage capacitors obtain the programmed energy (termination of charge)2. Battery voltage measurement is in progress and3. The ventricular tachyarrhythmia is self-terminated and the subsequent therapy delivery is postponed.In that case, all future high voltage therapies would have an elongated charge time or would fail to deliver due to charge circuit time-out. The alert systems of the devices will notify the patients to seek medical attention and this problem will be fixed with a new software installed. The possibility of this malfunction is estimated about 1/27000 devices per year and the possibility of a patient needing therapy before the device alert is activated is about 1/291000 per year... (excerpt
Dabigatran: An Alternative to Warfarin After Over Half a Century
Get PDFFor over half a century, warfarin or other vitamin K antagonists (VKA) (such as acenocoumarol, available in Greece and other countries), have been the gold standard and the only oral anticoagulants available which have been shown to effectively treat thromboembolism. However, their use has been plagued by inherent limitations with cumbersome monitoring via laboratory-guided adjustments of the dose, narrow therapeutic window, a lot of drug and food interactions and unpredictable and variable response. This has hindered patient compliance and has led to suboptimal therapy and poor anticoagulation control. Also patients unable or unwilling to take VKA have been offered no other choice of equivalent efficacy, i.e. until recently. Reasons for not receiving a VKA may comprise the following: drug allergy, patient refusal to take or decision to discontinue the drug, inability to maintain the international normalized ratio (INR) in the 2.0-3.0 range, physician decision as to the inappropriateness of receiving the drug, and/or inability to monitor the INR (lack of or difficulty in accessing a laboratory or lack of family support or assistance with this tedious task).These hurdles of conventional anticoagulant therapy have spawned efforts to develop new medications that will surpass these drawbacks while matching the efficacy of VKAs. Factor Xa has a strategic role in the coagulation cascade, critically poised at the juncture of the contact activation (intrinsic) and the tissue factor (extrinsic) coagulation pathways proximal to thrombin, both activating the final common pathway and leading to fibrin formation. Active factor Xa hydrolyzes and activates prothrombin to thrombin. Thrombin is the most important constituent of the coagulation cascade and has a broad array of functions with a primary role in the conversion of fibrinogen to fibrin, the building structure of a hemostatic plug... (excerpt