The “ILL-CONCEIVED” pallas study may be relaunched
“I want to say just a few quick words about dronedarone”, John Camm (St George’s University of London and Imperial College, London, UK) told the audience of his talk at the Europe AF 2017 meeting in London (7-8 November). “Many of you, if you used it, stopped using it. On the other hand, the drug is now to be relaunched. You remember the PALLAS study; an ill-conceived study, and I was one of the ones who contributed to that ill-conception.”
Camm revisited the findings of his PALLAS study on antiarrhythmic drug dronedarone, a clinical trial which was terminated in 2011 for safety concerns due to high event rates and mortality. However, interest in dronedarone persisted, and as Camm reviewed the subsequent analyses of that study and recent findings on dronedarone, which in fact indicate a different culprit altogether: digoxin.
Indeed, the conclusion of Igod Diemberger et al in Current Pharmaceutical Design was that the “use of dronedarone for prophylaxis of AF recurrences is not associated with an increased risk of death, either cardiovascular or total, and combination with digoxin should be avoided.”
The theory for optical defibrillation is there – all we need now is the engineering
Fu Siong Ng
Fu Siong Ng (Imperial College, London, UK) spoke at Europe AF 2017 about recent discoveries that may drive new therapies for atrial fibrillation. Ng opened with a disclaimer, stating that as mainstream therapy areas—antiarrhythmic drugs, catheter ablation, upstream therapy—were already being covered by other speakers at the meeting, he had chosen to cover some more alternative possibilities.
Optical defibrillation, an idea Ng called “science fiction-like”, is a topic of research in optogenetics on controlling excitation of muscle using light. “You can control and pace anything you want with a bit of light”, Ng said.
Ng referred to the results of Emile Nyns et al‘s publication in the European Heart Journal earlier this year, which suggests optogenetics could be a preferential treatment for ventrical arrhythmia as a “biological technique allowing electrical modulation in a specific, reversible and trauma-free manner using light-gated ion channels.”
Similar optimism for the technology has been expressed by Natalia Trayanova at Johns Hopkins Hospital (Baltimore, USA), saying about optical defibrillation: “We’re working towards what we believe is the holy grail.”
the debate on rotors remains controversial, but the nature of a driver doesn’t matter to clinicians
George Klein (Western University, London, Canada) tackled a topic that he acknowledged had created “a lot of controversy on this very stage” at the Europe AF meeting, with what he described as “basic scientists and clinical scientists almost killing each other” over differences of opinion regarding rotors in atrial fibrillation.
As a self-proclaimed disinterested “non-combatant” in this debate, Klein suggested that to the clinician, whatever the nature of a source or driver of atrial fibrillation, being able to isolate it is the only important concept.
“I think basic scientists can decide whether [a certain driver] is a rotor or a random reentrant or whatever,” however in Klein’s view, the current debate should be less about contentious terminology and more defined by whether particular mapping techniques are helping in clinical ablation.
“The clinician just wants an outstanding mapping system […] to ablate what needs to be ablated, and it doesn’t really matter what you call the finer mechanism.”
The time for warfarin is over
Andreas Goette (St Vincenz Hospital, Paderborn, Germany) effectively summed up the arguments made by Albert Waldo (Case Western Reserve University School of Medicine, Cleveland, USA) at the Europe AF 2017 meeting.
Waldo spoke on novel oral anticoagulants (NOACs) and whether warfarin has a role in the future of anticoagulation.
He discussed several known problems with warfarin, including its delayed onset and offset of action, slow reversibility, numerous interactions with food and other drugs, and the inconvenience of monitoring to both patient and physician—all likely to contribute to warfarin underuse.
“I think that the NOACs are superior to warfarin”, Waldo stated, while also reviewing the clinical challenges with NOACs such as the need for an established therapeutic range, validated tests to measure anticoagulation effect, and head-to-toe studies comparing new agents.
Goette, who followed Waldo’s lecture, proceeded to speak about choosing the right NOAC for your patient.
The link between AF and dementia is such that ablation for af could be considered for patients with af as young as fifty years old
We have taken for granted that we take about the benefits of ablation in terms of stroke or mortality”, Leif Friberg (Karolinska Institutet, Stockholm, Sweden) said in concluding his Europe AF 2017 talk on AF ablation, “but we have a dementia connection as well.”
Friberg pointed to links between AF and dementia, quoting a study by Hrafnhildur Stefansdottir et al published in Stroke in 2013, which shows AF is associated with reduced brain volume and cognitive function, independent of cerebral infarcts.
“AF is related to all kinds of dementia, not just vascular dementia,” Friberg stated, “[…] and senile dementia, vascular dementia, Alzheimer’s dementia—all are lower with atrial fibrillation ablation.”
It has been shown that catheter ablation for AF reduces not only long-term rates of stroke and mortality, but also reduces ablation patients’ risk of dementia. “This suggests that dementia can be prevented by ablation”, Friberg noted.
Because AF left untreated by ablation over time reduces brain volume and increases risks of dementia, Friberg concluded, perhaps the implications of AF ablation guidelines should be reconsidered. “According to the guidelines as we read them today, if we have 50-year old without any other risk factors but with atrial fibrillation, we could wait another 25 years before we do anything about it to reduce stroke risk. Is that really advisable? […] I think we should include the dementia dimension when we asses atrial fibrillation and anticoagulation.”
“This brings me further to the question,” Friberg finished, “whether we should offer AF ablations to asymptomatic patients for prognostic reasons.”