Conference Takeaways

ESC 2023 — Dr Linda Joosten (Julius Center for Health Sciences and Primary Care, NL) joins us to discuss the findings of the FRAIL-AF trial.

FRAIL-AF is a multicentre, open-label randomised controlled clinical trial which studied frail elderly patients who receive vitamin K antagonist (VKA) treatment for atrial fibrillation (AF). Current clinical guidelines recommend non-vitamin K antagonists (NOACs) as opposed to VKAs for stroke prevention in patients with AF. Frail-elderly patients have previously been under-represented in landmark NOAC trials – this study aims to assess whether switching from international normalised radio (INR)-guided VKA management to a NOAC-based treatment strategy as compared to continued VKA-management is safe and effective in this population. 

Results showed higher bleeding complications in frail elderly patients with AF when switching from VKA treatment to NOACs when compared to continuing VKA treatment. The higher bleeding risk was not found to be offset by a lower risk of thromboembolic events. 

Questions:

What knowledge gap is this study trying to address?
Describe the differences between NOAC therapy as compared to VKA therapy/
What was the study design and patient population?
What are the key results?
What are your take-home messages?
What further research is still needed?

Recorded on-site at ESC Congress 2023, Amsterdam. 

For more content from ESC Congress 2023 head to the Hot Line & Late-breaking Science Video Collection.

Editors: Mirjam Boros and Jordan Rance
Video Specialists: Dan Brent, Tom Green, Mike Knight, Oliver Miles

Transcript

“”My name is Linda Joosten. I’m a PhD student and a medical doctor from Utrecht University in the Netherlands. And yesterday, I presented at a hotline session at EC Congress about the FRAIL AF randomized Pragmatic trial.

Knowledge Gaps

So we already know that NOACs are preferred over VKAs in non-frail AF patients. But trial evidence is lacking in frail AF patients, and observational studies, they are suffering from confounding bias. So actually, we don’t know whether frail AF patients should also receive a NOAC instead of a VKA. And it’s even more questionable whether we should switch those frail AF patients from a VKA to a NOAC.

Study Design and Baseline Patient Characteristics

So the study design, it’s a pragmatic randomized trial investigator initiated, and half of the patients who were randomized, they continued with care as usual, which is VKA with acenocoumarol or phenprocoumon and a targeted INR value between 2.0 and 3.0 and monitoring by the Dutch thrombosis services. And half of the patients, they switched from VKA treatments to NOAC treatments. So after randomization, we switched from VKA treatment to NOAC therapy.

NOACs Studied and Differences in Outcomes

We studied the group of NOACs as a whole compared to the group of VKA as a whole. So we didn’t compare NOACs. The study was set up to compare one group to another group. We did, however, the posthoc analysis, subgroup analysis, where we looked at differences between NOACs because all four NOACs were prescribed in our trial, and there we didn’t see any difference. But I really have to note again that the study is empowered to see differences between NOACs. So it’s really comparing the group of NOACs to the group of VKAs, so we can draw conclusions about which NOAC is best.

Key Results

The key results, they were very surprising and also unexpected. The FRAIL AF trial was set up as a superiority design with a hypothesis that switching from a VKA to a NOAC would lead to less bleeding. However, we saw the opposite. And that’s also the reason why our independent data safety monitoring board decided to stop inclusion because we clearly saw that switching from a VKA to NOAC was contraindicated with a hazard ratio of 1.69 and a highly significant key value of 0.1. So the key message is that we shouldn’t switch from a VKA to a NOAC because it leads to 69% more bleeding.

Take-Home Messages and Knowledge Gaps

So what are the main take-home messages? The first one is that FRAIL AF is a unique study. This is the first randomized NOAC trial in frail older patients. So we really have information beyond available evidence, evidence that cannot be subtracted from the four landmark NOAC trials. And yeah, so the second conclusion is that we should not switch from VKA treatment to NOAC treatment in frail older patients because this leads to 69% more bleeding. And the knowledge gaps. I think this study also gives us more questions because this is what we observe, but we don’t know why we observe this. It could be that frail AF patients need lower doses of NOAC, for example. So maybe that’s a good one to examine. The doses of NOACs in frail elderly patients. And another one is maybe the factor eleven inhibitors are a good idea for those frail patients. So I think that’s for further research.”

ESC 2023 — Dr David Conen (McMaster University, CA) joins us onsite for a short interview focussing on the findings from the COP-AF trial (NCT03310125).

COP-AF (Population Health Research Institute) aimed to assess if oral colchicine reduced the incidence of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery. 3209 participants were enrolled in the trial, who were randomized to receive either 0.5 mg of colchicine orally twice daily for ten days, or a placebo comparator.

Results suggest that colchicine does not significantly reduce perioperative atrial fibrillation or myocardial injury after non-cardiac surgery in major thoracic surgery, though some encouraging signals of benefit for the reduction of adverse cardiovascular outcomes in this patient group were also found.

Questions:

What was the rationale behind this trial?
What is the mechanism of action behind colchicine in patients with AF?
What was the patient population and study design?
What were the key findings?
What are the take-home messages?
What further study is still required?

Recorded on-site at ESC Congress 2023, Amsterdam.

For more content from ESC Congress 2023 head to the Hot Line & Late-breaking Science Video Collection.

Editors: Mirjam Boros and Jordan Rance
Video Specialists: Dan Brent, Tom Green, Mike Knight, Oliver Miles

Transcript

“My name is David Conen. I’m a cardiologist and scientist from the Population Health Research Institute in Hamilton, Canada, affiliated with McMaster University, where I’m also an associate professor.

Rationale Behind Trial

So most patients undergoing major noncardiac thoracic surgery have a high risk of cardiovascular complications. Two of the most common cardiovascular patients that you observe in these patients are perioperative atrial fibrillation and myocardial injury after non-cardiac surgery, which is defined as either a myocardial infarction or a troponin that is elevated due to an ischemic cause. These complications occur in about 10% of the population for atrial fibrillation and 20% for myocardial injury. So these are common complications. There’s currently no approved treatment that can safely reduce those complications, and therefore finding new treatment approaches to try to prevent these complications is a major clinical need.

Why Colchicine?

So both complications that we just mentioned, AFib and myocardial injury, have been shown to be associated with higher levels of inflammatory biomarkers in previous studies. And therefore, we thought that treating these patients with an anti-inflammatory drug would be a promising strategy. This strategy is also supported by previous data showing that colchicine has reduced perioperative atrial fibrillation after cardiac surgery in several relatively small but consistent randomized trials. And there have been two major large colchicine randomized trials in patients with coronary artery disease showing that colchicine was able to reduce ischemic events like myocardial infarctions or strokes in patients with coronary artery disease. So, based on this background, we thought that taking colchicine, which is an established anti-inflammatory drug in clinical practice for gout, pericarditis, and other inflammatory disorders, would be a good strategy.

Patient Population

Okay, so COP-AF was designed to enroll patients after major thoracic non-cardiac surgery. We chose this population because they have a high risk of complications, as already mentioned, and we included patients who were at least 55 years old, who did not have a previous history of atrial fibrillation or taking antiarrhythmic medications. We excluded some minor surgeries. We also excluded the patients who had contraindications to colchicine or patients who needed colchicine, and then came up with a trial population that was randomized one to one to either colchicine 0.5 milligrams, twice daily or placebo. There was a blinded trial, so all the involved personnel and patients were not aware of the study treatment assignment. The first dose was given on the day of surgery, within 4 hours before surgery, and then was continued for a total of ten days, twice daily. And the total follow-up of the study was two weeks.

Key Findings

So we enrolled 3209 patients across eleven countries, 45 sites. We found that the first core primary outcome of clinically important atrial fibrillation was not significantly reduced with colchicine. There was a trend with a hazard ratio of 0.80, but confidence intervals crossed one, and the p-value was not statistically significant. A similar finding that we observed for Mins the second core primary outcome where there was an 11% relative risk reduction. But again, confidence intervals crossed one, and the p-value was not statistically significant. Very similar findings for all the secondary outcomes, which was mainly a composite of several ischemic complications or Mins not fulfilling the definition of myocardial infarction. All these outcomes went in the same direction with usually hazard ratio consistent with the primary outcome, but none of these were statistically significant. When we did some postdoc analysis combining, for example, the two core primary outcomes Mins and AFib in one single outcome, we found a significant reduction of colchicine for this outcome with a p-value of 0.02. There were some other post hoc analysis that were also statistically significant, but the primary outcomes were not. From a safety perspective, colchicine was very well tolerated, there were few discontinuations of the study drug, and we found that sepsis infection was not increased. However, there was an increase in the risk of noninfectious diarrhea. Patients with colchicine had a 6% absolute increase in the risk of noninfectious diarrhea. Those episodes tended to be benign and temporary. For example, there was no increase in the median length of stay among those who had diarrhea versus those who did not have diarrhea, and there was only one hospital readmission for diarrhea in all affected patients.

Next Steps

So next steps, given that we found this very promising and consistent signal that is also very consistent with the findings that were observed in the large previous trials COLCOT and LoDoCo II. We think that colchicine does have the potential to prevent ischemic events after non-cardiac surgery in general, and so I think we do need more studies in this area. We do need to probably do a larger trial because our trial was slightly underpowered with a lower than expected event rate, especially for the AFib component. And we probably need to tweak the sample size and patient characteristics a little bit to try to come up with an even better patient population and then hope that we can show that colchicine actually really reduces postoperative complications from a cardiovascular cost. Because, as I said initially, this is a really important clinical need. These patients have a very high risk of complications that are much higher than, for example, patients with chronic stable or atherosclerosis. And therefore we do think colchicine has a promising footprint that we just need to further explore.”

ESC 2023 — We are joined onsite by Prof Christian Sohns and Prof Philipp Sommer (Heart and Diabetes Centre, Bad Oyenhausen, DE) to discuss the findings from the CASTLE-HTx trial (NCT04649801).

CASTLE-HTx (Heart and Diabetes Center North-Rhine Westfalia) aimed to determine if atrial fibrillation ablation has beneficial effects on mortality in patients with end-stage heart failure, who are eligible for a heart transplant. 194 patients were enrolled in the trial, who were randomized to receive either conventional treatment, or catheter ablation treatment. The primary endpoint included the composite of all-cause mortality, worsening of heart failure requiring an urgent transplantation, or left-ventricular assist device implantation.

Results showed that atrial fibrillation ablation was associated with lower rates of death, urgent heart transplantation or LVAD implantation when compared to medical therapy in patients with end-stage heart failure. Findings also suggested a reduction in atrial fibrillation, and an improved left ventricular ejection fraction.

Questions:

What are the unmet needs of end-stage HF patients?
What was the patient population and study design?
What were the key findings?
What should be the impact of these findings on clinical practice?
What further study is still required?

Recorded on-site at ESC Congress 2023, Amsterdam.

For more content from ESC Congress 2023 head to the Hot Line & Late-breaking Science Video Collection.

Editors: Mirjam Boros and Jordan Rance
Video Specialists: Dan Brent, Tom Green, Mike Knight, Oliver Miles

Transcript:

Dr Phillip Sommer

“Yeah. My name is Philip Sommer. I’m director of the clinic for electrophysiology at the Heart and Diabetes centre in North Rhine-Westphalia, Germany.

Dr Christian Sohns

My name is Christian Sohns. I’m the deputy director of the Heart and Diabetes Centre, North Rhine-Westphalia in Germany. We work together and we designed the trial together.

Unmet Needs of End-Stage HF Patients?

Dr Christian Sohns

This is a very good question. We have already good information about patients with heart failure and reduced or preserved ejection fraction. But these patients who are very close to transplantation or surgical therapy, they are left without any good evidence or recommendations from prospective randomized strides, for example. And therefore this is very important to address these questions, for these patients, to give them good advice, evidence-based advice.

Patient Population and Study Design

Dr Phillip Sommer

So with this study, we addressed, as Christian said, end-stage heart failure patients. That means patients that were basically admitted to our highly specialized centre for evaluation of eligibility for undergoing a heart transplant. So in those patients, most other options actually have been attempted. So medical treatment was almost optimal if necessary. A CRT, for example, was implanted. But still, those patients were in New York heart two, three and four. So, like, two-thirds of them were in New York heart three and four, and they were very significantly limited in their daily routines. And the issues that we addressed was whether an ablation therapy to treat their atrial fibrillation, which all of those patients had, would kind of give them some sort of benefit in order to improve their clinical status and their physical fitness.

Key Findings

Dr Christian Sohns

So, yeah, we have primary endpoints and secondary endpoint. The primary endpoint was a composite of mortality, death from any cause, left ventricular assist device implantation and heart transplantation. And on the other hand, we have death from any cause, cardiovascular death, and all the other single points from the primary endpoint as well. So catheter ablation improved all these endpoints, it improved the composite of death from any cause, LVAD implantation, and transplantation. And this was mainly driven by the reduction of death from any cause. This was mainly driven by the reduction of cardiovascular death. So all these points are very important. Also taken into consideration that one day surgical therapy will come to these patients anyway. But if we can postpone delay the process until we need this definite surgical therapy, that’s very important. So it saves lives and it improves also the quality of life of these patients.

Safety Events

Dr Phillip Sommer

So I don’t want to say we were surprised, but actually it is a really end-stage heart failure patient population. And half of those patients, as they were randomized to the ablation arm, perform quite an invasive intervention, which is a catheter ablation of atrial ablation. But at the end of the day, we realized in those roughly 100 patients where we performed ablation, in, no serious adverse events occurred, no complications occurred. So we had in total, I think, four exercise complications with some hematoma in the groin, but nothing really severe in terms of pulmonary vein stenosis, tamponade, stroke, TIA, or anything that is associated with the sedation of those patients during the procedure. So these were really safe procedures and straightforward procedures and highly effective procedures.

Impact on Clinical Practice

Dr Christian Sohns

As we said, we have no good evidence-based information for these patients. We need to change guidelines; this is clear. And the Atrial Fibrillation guidelines, they need to implement the results from Castle AF and Castle HTX to change the recommendation for Ablation and heart failure patients to class one indication. And also I think we need a revision of the heart failure guidelines. Atrial Fibrillation therapy was not even mentioned in the consensus documents from the ESC and the American Heart Association, and we think that this is very important to add this also to these guideline documents in the future. We have a lot of data which is also not analyzed of this patient cohort. I think it’s very important to understand the findings of the study and to see which kind of patient benefit the most and why was this the case. This can be one of the topics, and of course, we have different other topics in the pipeline we cannot address today.

ESC 2023 — Dr Alan Bulava (Ceske Budejovice Hospital and University of South Bohemia, CZ) joins us in this succinct interview to discuss the findings from the SurHyb trial.

The SurHyb study was a prospective, open-label-multicentre randomized trial. The study aimed to evaluate CryoMaze surgery alone, as compared to CryoMaze followed by radiofrequency catheter ablation 3-months post-surgery.

Findings suggest that the incidence of atrial fibrillation and atrial tachycardia was reduced by 62%. The absolute risk reduction was 30%.

Questions:

What is the reasoning behind this study?
What was the patient population and study design?
What are the key findings?
What are the potential benefits of CryoMaze and Ablation?
How should these findings impact clinical practice?
What further study is still required?

Recorded on-site at ESC Congress 2023, Amsterdam.

For more content from ESC Congress 2023 head to the Hot Line & Late-breaking Science Video Collection.

Editors: Mirjam Boros and Jordan Rance
Video Specialists: Dan Brent, Tom Green, Mike Knight, Oliver Miles

Transcript

“My name is Alan Bulava. I come from Czechia, from the Budejovice hospital. I am chief of the department of arrhythmology and cardiac pacing. So responsible for the whole programme of arrhythmology programme at our institution.

Reasoning Behind the Study

The rationale behind the study was that we wanted to fill a gap because we do not know what exactly the post-procedural treatment of patients should be undergoing concomitant AF Ablation after cardiac surgery. Because recent literature indicates that about a quarter of patients undergoing cardiac surgery suffer from atrial fibrillation. And of course, in absolute numbers, it’s a huge number. And even if you consider patients with mitral valve disease, it’s even more than 50% of such patients. And nowadays, according to STS guidelines endorsed in 2017, these patients should be Ablated. So cardiac surgeons should perform cryomaze procedure to improve the patient’s outcome, especially during mitral valve surgery, which is class 1A indication. And even with aortic valve surgery or simple coronary artery bypass grafting is a class 1B indication. But of course, the main drawback is that we do not know in which percentage these patients relapse with atrial fibrillation, so they reappear with atrial fibrillation again. So, we wanted to fill this obvious knowledge gap and that’s why we initiated this investigator-initiated or open-label? Open label randomised control trial.

Patient Population and Study Design

The patient population was consisting of patients with non-paroxysmal type of atrial fibrillation. So, either persistent atrial fibrillation or long-standing persistent atrial fibrillation undergoing cardiac surgery procedures. So, either coronary artery bypass grafting or end valve repair. We excluded patients with extremely dilated atria, and we also excluded patients who underwent previous RF Ablation procedure for atrial fibrillation.

Key Findings

So, the key findings were that we were able, using hybrid approach, so deferred AF Ablation, catheter Ablation after cardiac surgery, after cryomaze, we were able to reduce the incidence of atrial fibrillation atrial tachycardia by 62%. So, the relative reduction risk was 62%. The absolute risk reduction was 30%. So, from 70% recurrence rate down to 40% recurrence rate, which is really huge and significant impact, taking into account that the monitoring of these patients was really intense. All the patients had cardiac implantable monitors, so we knew about almost, I would say almost every single AF recurrence.

How These Findings Should Impact Practice

This was our second question because it’s not only about the AF reduction. So, to really propose this treatment, we should have some clinical outcome proven as well. And our primary clinical endpoint was reduction of hospitalisation for AF or ATEC hospitalisation for heart failure, significant bleeding or cardioembolic events. And all this combined clinical endpoint was also significantly reduced by 54%.

Further Study Required

Yeah, I think this is the first randomised trial in this field, obviously, and probably it should be confirmed by other randomised trials of that kind, which would then push a little bit more on the clinical impact. But basically, the finding of our trial is that we should propose the patients undergoing concomitant surgery for atrial fibrillation to undergo another procedure consisting of catheter ablation procedure to improve the clinical outcome and to improve or to reduce the burden of atrial arrhythmias.”

ESC 2023 — Dr Tobias Reichlin (Inselspital, University of Bern, CH) joins us on-site at ESC 2023 to discuss the findings of the COMPARE-CRYO Trial (NCT04704986).

The COMPARE-CRYO trial (Insel Gruppe AG, University Hospital Bern) aimed to compare the safety and efficacy of the PolarX Cryoballoon (Boston Scientific) with the Arctic Front Cryoballoon (Medtronic) in patients with symptomatic paroxysmal AF undergoing their first pulmonary vein isolation (PVI). 201 patients were enrolled in this phase 4 trial, who were randomized to receive either PolarX or Arctic Front.

Results suggest that the recurrence of atrial arrhythmias occurred in 47% of patients treated with the Arctic Front cryoballoon as compared to 41% of the patients treated with the PolarX Cryoballoon. This met the criteria for noninferiority.

Questions:

What is the current landscape of Cryoablation in 2023?
What are the differences between the PolarX and Arctic Front Cryoballoons?
What was the patient population and study design?
What were the key results?
How should these findings influence clinical practice?
What further research is still required?

Recorded on-site at ESC Congress 2023, Amsterdam.

For more content from ESC Congress 2023 head to the Hot Line & Late-breaking Science Video Collection.

Editors: Mirjam Boros and Jordan Rance
Video Specialists: Dan Brent, Tom Green, Mike Knight, Oliver Miles

Transcript

“So, my name is Tobias Reichlin. I’m the Head of Electrophysiology at the Inselspital, Bern, in Switzerland. Today, we’re going to discuss the results of the COMPARE-CRYO study, which was a randomized comparison between two cryoballoons. The results were presented yesterday at this ESC meeting.

The Current Landscape of Cryoablation in 2023

Cryoablation was introduced into cardiology around the year 2010, and there was basically one CryoBalloon from Medtronic called Arctic Front, which was the prototype of single-shot ablation for the treatment of atrial fibrillation. It has been used for a long time in more than a million patients. It’s an excellent tool. Then, in the year 2020, another cryoballoon was introduced called Polar X from a different company, Boston Scientific. That’s basically the background where we conducted our trial.

The Differences Between the PolarX and Arctic Front Cryoballoons

The novel cryoballoon was designed with the aim to improve the efficacy and safety of cryoballoon ablation. Some modifications were made: It was a compliant balloon rather than a non-compliant one, with the idea that this would allow for better vein occlusion.
The novel balloon maintains a stable balloon pressure and a stable size during the ablation, while the other balloon enlarges a little bit. This prevents the balloon from popping out. Several enhancements were made to the user interface, including foot switches and a more interactive user face to improve the cryoblation.

Patient Population and Study Design

The patient population consisted of patients with paroxysmal atrial fibrillation planning to undergo catheter ablation for atrial fibrillation. All patients had paroxysmal atrial fibrillation and were randomized one-to-one to be ablated with the Polar X CryoBalloon from Boston Scientific or with the Arctic Front CryoBalloon from Medtronic. At the end of the procedure, all patients were fitted with an implantable cardiac monitor, a reveal link, to allow for continuous rhythm monitoring. This ensured that no episode of atrial fibrillation would be missed and provided information not only on AFib recurrence but also on AF burden.The primary endpoint of the study was the recurrence of any type of atrial arrhythmias lasting longer than 30 seconds between days 91 and 365, excluding a blanking period of three months.

Key Findings

The key finding was that the recurrence of atrial arrhythmias occurred in 47% of the patients with the established cryoballoon from Medtronic and in 41% with the novel cryoballoon from Boston Scientific, the Polar X cryoballoon. These numbers met the criteria for non-inferiority, as it was a comparison between a novel and established balloon. Subsequently, no difference was found between the two balloons, even when tested for superiority. Regarding safety, both balloons were remarkably safe. There were no cardiac tamponades, strokes, fistulas, or access complications. However, there was a 5% rate of phrenic nerve pulses that would not recover within 24 hours with the novel Polar X balloon, while there were none of those phrenic nerve pulses with the established Medtronic cryoballoon.

How these Findings Should Influence Clinical Practice

Physicians now have the choice between a cryoballoon that has been available for ten years with data from randomized trials showing it’s non-inferior compared to point-by-point radiofrequency ablation and superior to antiarrhythmic drug treatment. The trial has shown that both cryoballoons have the same performance.

Further Research Required
Our field is now seeing a significant change with the introduction of pulsed-field ablation technology. The big question is how cryoblation compares to pulsed-field ablation. Some data has been presented at this meeting, but we are in the process of completing a trial that randomizes patients between CryoBalloon and pulsed-field ablation. This will be very interesting to see whether one technology has advantages over the other going forward.”

ESC 2023 — Dr Ramón Luengo-Fernández (University of Oxford, UK) joins us on-site to discuss the findings from a registry which aimed to analyse the economic burden of cardiovascular disease within the EU.

This was the first study to utilise Europe-wide patient registries and included the costs of long-term social care. Results from the registry found that cardiovascular disease cost the EU €282 billion in 2021, equivalent to 2% of Europe’s gross domestic product. Health and long-term care accounted for €155 billion (55%) of the costs.

Questions:

What is the importance of this study?
What methods were used? What were some of the challenges?
What did you find?
How did you measure informal care?
How does this data compare to the cost analysis from 2006?
What were the key findings from both a public health and economic perspective?
In your opinion, how should policymakers use this data?

Recorded on-site at ESC Congress 2023, Amsterdam.

For more content from ESC Congress 2023 head to the Hot Line & Late-breaking Science Video Collection.

Editors: Mirjam Boros and Jordan Rance
Video Specialists: Dan Brent, Tom Green, Mike Knight, Oliver Miles

Transcript

“Hi, I’m Ramon Luengo Fernandez from the University of Oxford Nuffield Department of Population Health. And I’m an associate professor in Health Economics.

The Importance of this Study

So the importance of this study is to show really what the burden is of cardiovascular disease not only to the healthcare sector who pays for the treatment of these patients or patient itself, as CVD reduces their quality of life and poses patients at early risk of death. But all the other aspects CVD touches like the burden it places on family and friends who care for patients with cardiovascular disease and the workforce as many patients with CVD will either have to leave employment, take time off or die because of premature mortality. So that places a burden on the workforce.

Methods and Challenges

So the methods we used was basically, look at all the resources that patients with CVD take or consume. So, of course, we looked at, say, how many days in hospital are spent in Germany over in 2021? And then we tried to apportion all those days in hospital to days that were due to CVD. So in many instances, we just looked at international sources like Eurostat, but in others, we had to look at national sources, how many patients go to their family doctor and then apportion that to CVD. And it was this, apportioning it, that was quite tricky. So we used a patient-level data survey on nearly 150,000 patients across Europe to see those patients with CVD. How many times did they use the healthcare sector because of their CVD?

Key Data

So we found that the cost of cardiovascular diseases in Europe was €282 billion just for 2021, with nearly half of all that cost being due to healthcare services. So seeing doctors procedures in hospital, stays in hospital, we also found a big chunk of resources were spent in long-term care. So patients having paid, workers coming to take care of them while they were at home, or patients going to nursing homes, a big, big chunk of the cost was also due to informal carers. So a side of the economy that you would not really see because nobody pays a wife to take care of their husband who’s had a stroke. So that was also a big component of our cost.

Measurement Methods for Informal Care

So the informal care, how we did it is we looked at the number of people using the global burden of disease that had cardiovascular disease in our country. And then we use patient-level data from the big survey I told you about before to see if you have CVD, what’s the probability that you’ll be taken care of by an unpaid worker? And if you receive care, how many hours of care will you receive? So that’s how we estimated informal care costs.

Data Comparison to Cost Analysis from 2006

So we did the same analysis back in 2006 when the EU had just expanded to the east. Of course, since then, the EU has changed a bit. A big country like the UK is not in the European Union anymore. So we’ve had to reduce the cost of that. There’s other countries since then that have joined the EU. So that makes a big difference. But even just looking at the countries that we had in 2006 and the countries we have now we have seen that the differences in cost per capita dividing total cost by number of citizens differences we saw between countries before have very, very much reduced. So now we can say that cost of cardiovascular disease are more homogeneous. Although there’s important differences. The big, big differences we saw before have really reduced. I think from the top of my head it was from a 16 difference in 2006 between the highest and the lowest spender to around six times from the lowest to the highest spender. So a big reduction.

Key Findings from Both a Public Health and Economic Perspective

So the big, I think, findings from the public health and the health economics is that cardiovascular disease not only affects what you would think of the healthcare sector because they’re the ones who pay. The healthcare sector pays for those patients to get better or to treat them is that it affects all ranges of the economy. So take account of informal carers. Nobody pays an informal carer to take care for their friend or loved one with CVD. Whereas if you actually cost the time that these people are foregoing of work or forgoing of their own leisure activities and that doesn’t have a cost, the cost is huge.

How Policymakers Should Use This Data

The policymakers should use this data. First of all it allows so if you know what the cost of cardiovascular disease, you know what the cost of cancer is, you know what the cost of gastrointestinal problems is, you can start saying, okay, what is the area of highest burden and what can we do to reduce this burden? So in a way there’s an incentive to reduce the burden of the diseases that are impacting the country first. So things like research spending might be able you might want to prioritise those areas with the highest burden and get a bigger share of research spending. So that’s one way that policymakers could use our results.”

ESC 2023 — Prof Paulus Kirchhof (University Heart & Vascular Center Hamburg, DE) discusses the findings of the NOAH-AFNET 6 trial (NCT02618577).

NOAH-AFNET 6 (Atrial Fibrillation Network, Daiichi Sankyo Europe) was an investigator-initiated, prospective, randomised trial aiming to demonstrate that oral anticoagulation using the NOAC edoxaban is superior to current therapy in stroke prevention, systemic embolism and cardiovascular death in patients with atrial high rate episodes and stroke risk factors. 2608 patients were enrolled in the trial, which compared edoxaban to ASA or placebo.

The NOAH-AFNET 6 trial revealed that using oral anticoagulation in AHRE patients raises bleeding risk without reducing the combined outcome of stroke, systemic embolism, or cardiovascular death.
Expectedly, anticoagulation led to more bleeding. Surprisingly, both anticoagulated and non-anticoagulated groups showed low stroke rates. This underscores the need for ECG evidence of atrial fibrillation before starting anticoagulation.

Questions:

What is the importance of NOAH-AFNET 6?
What was the study design and the eligibility criteria?
What are the key findings?
What are the take-home messages for practice?
How should these findings influence guidelines?

Recorded on-site at ESC Congress 2023, Amsterdam.

For more content from ESC Congress 2023 head to the Hot Line & Late-breaking Science Video Collection.

Editors: Mirjam Boros and Jordan Rance
Video Specialists: Dan Brent, Tom Green, Mike Knight, Oliver Miles

Transcript

Hello. My name is Paulus Kirchof. I’m here at the ESC Congress 2023 in Amsterdam, and we are going to talk about the NOAH-AFNET 6 nonvitamin K antagonist oral anticoagulants in patients with atrial high rate episodes trial.

Importance of NOAH AFNET 6

Now, NOAH addressed an important question. Do patients with atrial high-rate episodes, short atrial arrhythmias that look and feel like atrial fibrillation but are picked up by implanted devices that monitor the heart rhythm day and night, benefit from anticoagulation or not. And the key finding is one that’s actually a relief for our patients. Patients with atrial high rate episodes do not need anticoagulation.

Study Design and Patient Baseline Characteristics

So NOAH AFNET 6 randomized 2536 patients with atrial high-rate episodes longer than six minutes without an upper limit for duration, and with clinical stroke risk factors to anticoagulation or no anticoagulation, the mean age of the patients was 77.5 years. The median CHA2DS2-VASc score was 4. So they are a population of patients that would clearly be at high stroke risk if they had atrial fibrillation. The randomization to no anticoagulation, and it was a double-blind, double-dummy trial. So patients randomized to no anticoagulation received either a placebo or if they had an accepted indication for aspirin. They received aspirin 100mg per day. Patients randomized to anticoagulation received edoxaban in the dose approved for stroke prevention and atrial fibrillation. All patients were followed up until the end of the trial. All patients changed from studied medication to open-label anticoagulation when they had ECG-documented atrial fibrillation.

Key Findings

The primary efficacy outcome is the classical outcome composite of stroke, systemic embolism, and cardiovascular death. And anticoagulation does not reduce this outcome compared to no anticoagulation. And when you dig into the numbers, the surprising part of it is the low stroke rate without anticoagulation. Patients randomized in NOAH not treated with anticoagulation had a stroke rate of 1.1% per year. That is lower than the stroke rate on anticoagulation in patients with atrial fibrillation. On the other hand, as expected, anticoagulation increased the risk of major bleeding or death, a 30% increase. And that was statistically significant. So that we can conclude that anticoagulation increases bleeding as expected, but does not prevent cardiovascular events unexpected in patients with atrial heart rate episodes.

Take-Home Messages

It’s good news for our patients. We didn’t know whether patients with atrial high rate episodes needed anticoagulation or not. Some of us thought that they need anticoagulation because these episodes look like atrial fibrillation and feel like atrial fibrillation. But now we know that we can stay calm, that we don’t need to treat these patients until they develop ECG-documented atrial fibrillation.

How these Findings Should Influence Guidelines

Now, I think this is the first randomized evidence in this area, so it reinforces the message that you find in the current ESC guidelines that you should not start treatment for atrial fibrillation before atrial fibrillation is diagnosed. So I think this is an important message for guidelines. I do think there is also a real signal that we need more research because obviously, the stroke rate wasn’t zero. There were systemic emboli, cardiovascular deaths. There are potentially preventable events and we need research to understand who in the population of patients with atrial heart rate episodes is at risk of these events.”

Dr Billy A Caceres (Columbia University School of Nursing, US), a renowned expert and lead author, recently discussed findings from the study titled “Differences in Ideal Cardiovascular Health Between Sexual Minority and Heterosexual Adults” published in JAMA Cardiology. The study aimed to determine whether there are disparities in cumulative cardiovascular health (CVH) scores between sexual minority and heterosexual adults.

The researchers conducted a cross-sectional analysis using data from 12,180 participants in the National Health and Nutrition Examination Survey from 2007 to 2016. The findings indicated that bisexual females had lower CVH scores compared to heterosexual females. This discrepancy was primarily attributed to factors such as nicotine exposure and higher body mass index.

These results highlight the need for tailored interventions to improve the cardiovascular health of sexual minority individuals, particularly bisexual females.

Questions:

1. What is the objective and importance of your research on CVH in sexual minority adults?
2. How did you control for confounding factors in your study?
3. How did you measure CVH and what were the key findings for different groups?
4. What are the reasons for CVH disparities among bisexual females, according to your study?
5. What are the implications of your findings for clinical practice or public health interventions?
6. Can you discuss policy or advocacy implications of your research in addressing CVH disparities among sexual minority adults and promoting health equity?

Recorded remotely from New York, 2023.

Editor: Mirjam Boros
Video Specialist: Dan Brent

In this episode from the Radcliffe Podcast, Dr Francisco Lopez-Jimenez (Mayo Clinic, US) and Dr David Harmon (Mayo Clinic, US) join us to discuss the future of AI in Atrial Fibrillation treatment, based on Dr Harmon’s recently published article in AER Journal; ‘Artificial intelligence for the detection and treatment of atrial fibrillation‘.

Dr Lopez-Jimenez and Dr Harmon discuss the possibilities that recent advances in the detection of atrial fibrillation using artificial intelligence-based technology offer, discussing its place in practice with consideration to standard practice electrocardiograms and advanced Holter ECG monitoring. They go on to discuss the implementation of this technology in day-to-day practice, as well as the potential barriers that may impact this.

How could Artificial Intelligence impact your practice, and what are the recent advances?

Prefer to listen in podcast format? Click here.
If you have any questions or suggestions, please email managingeditor@ecrjournal.com.

EHRA 2023 — Join us as Dr Luigi Di Biase, Section Head of Electrophysiology, Director of Arrhythmia Services, Professor of Medicine and Senior Researcher, shares his insights on the highlights of the late-breaking trials presented this year. What are the latest developments in arrhythmia and electrophysiology? How should the latest data impact your practice?

0:21 – PowerFast

2:18 – MANIFEST-PF

3:11 – TEMPO-HCM

4:24 – AdaptResponse

Recorded on-site EHRA 2023, Barcelona.

Transcript

“Hi, I’m Professor Luigi Di Biase from the Albert Einstein College of Medicine at the Monte Fiore Health System in New York. Today we are going to discuss the four trials from day one and day two of the late-breaking clinical trial sessions here at EHRA 23 in Barcelona.

POWER-FAST III

The first trial I would like to discuss is the Power Fast III trial, where the investigators assessed whether a high power short duration ablation with 70 watts was superior or non-inferior to low power, guided by ablation index either with the Biosense catheter or with the TaciCath catheter. This trial has a very important relevance. It’s a randomized trial conducted herein Spain by Professor Merino. And this trial tells us that doing above 50watts, 70 watts does not improve the outcomes, the freedom from atrial fibrillation while increase thromboembolic complication, either stroke, TIA and silent cerebral lesions. So I think the trial adds good clinical information because we know now that about 50 watts is not dangerous, no better outcome. Now the trial does not discuss its high power short duration between 40 and 50 watts is still a good thing to do. I think it is. And the trial also does not discuss whether we should use catheters that are designed for high power short duration, such as Q dots for Biosense Webster or Diamond Temp for Medtronic’s. So I think that we have trials that have been designed for high power short duration and this should be utilized. But if you don’t have this catheter, probably no more than 50 watts is the power that you should use to avoid complications and improve the outcome. As this is being said, I think the author should provide information about the complication rate and the type of catheter utilized, because the two-catheter utilized are 3.5 and four millimetre. Therefore, I think that irrigation utilize isa little different and the possibility of popping and increasing the thrombombolic complication is different between the two catheters.

MANIFEST-PF

The second trial I would like to discuss is the registry of the MANIFEST trial. This trial investigated the use of a different energy source.So the PFA with the catheter from Boston Scientific and this trial gives us some very good information outcome of this new energy source. On thermal energy like pulsed-field ablation gives very good results both in paroxysmal and persistent patients. I would say not inferior to the standard radiofrequency and cryo while having no complications. So this trial I think adds some relevant information to the fact that we are going in the good direction with the non-thermal energy source for safer procedure, while maintaining very good outcomes.

TEMPO-HCM

The next trial I would like to discuss is a trial that is investigated a very maybe not that frequent population, hypertrophic cardiomyopathy patient, but a population that is difficult to manage because sometimes the guidelines are in a gray zone. So the trial investigated: “what if I look for arrhythmias using not a standard 24-hour alter monitoring, but an extended patch of 30 days. “And by quoting the statement the more you look, the more you found. We found out that if you look for 30days, you found almost double the incidence of atrial fibrillation and more non-sustained ventricular arrhythmia. More atrial fibrillation means we need probably to give oral anticoagulation to this patient to prevent stroke and more non-sustained BT means probably we need to implant ICD. So the overall management, clinical management of this patient may change. So extended monitoring with patch rather than loop recorder or as much as you can look for arrhythmias is very important in hypertrophic cardiomyopathy patients and a 24-hour holter is not enough. So very important clinical information for every clinician.

AdaptResponse

The next trial I would like to discuss is the Adaptive CRT trial. This is a trial of almost 4000 patients where the investigator compared biventricular pacing versus LV pacing with the adaptive LV algorithm, meaning LV pacing only versus biventricular pacing. The trial is negative, meaning that this algorithm did not add improvement in the outcomes. Primary endpoint was improvement immortality and heart failure hospitalization. But despite negative, answer an important question we need to receive heart failure patient in need for a device. Because this trial showed that there is an overall improvement while you treat heart failure patients with resynchronization therapy, this algorithm didn’t reach statistical significance. It has a trend in improvement and so unfortunately, it’s not a way to improve the outcomes. But maybe there is a subset of patients where the outcome can be improved. Type two error is something that has a statistical meaning. We don’t know actually what does it mean? There were events reported after COVID that may have jeopardised the overall statistical analysis. So despite a negative trial adds information and4000 patients and a lot of female included, almost 43-45 % of female included. The largest number of females is included in a randomized trial with revascularization therapy. So kudos to the authors for conducting such a big and long trial.

EHRA 2023 — In this short video Dr Afzal Sohaib, an Electrophysiologist at Barts Health NHS Trust, provides a concise and practice-focused review, highlighting the 5 most impactful trials that will influence his clinical practice.

0:14 – POTTER-AF
1:09 – Early vs Delayed Ablaion of AFib
2:20 – PowerFast III
3:29 – AdaptResponse
5:17 – Marshall-Plan

Recorded on-site at EHRA 2023, Barcelona.

Editor: Jordan Rance

Transcript

” So I’m Dr. Afzal Sohaib. I’m a consultant cardiologist and electrophysiologist from Barts’ Heart Center in London, and I’m going to talk about the most interesting studies I’ve seen at EHRA 2023.

POTTER-AF

The Potter AF Registry was one of the largest registries of AF Ablation which have looked at the incidence of atrio esophageal fistula after AF Ablation. This was really interesting because you’d hope that after doing AF Ablation for, 20 or so years as a community, and with improvements in technology, we’d see a reduction in what is probably the most worrying complication we worry about. And interestingly, it shows that despite all the advances, the incidence of atrioesophageal fistula remains at about zero point 25%, which is about the same as what it has been in most of the trials up til date. So, we still have some work to do to reduce this dangerous complication. What this registry did show is that if you use cryoablation rather than radio frequency, the incidence of that complication is dramatically lower, almost negligible. So, I mean, that’s food for thought, especially with other new technologies such as PFA coming in. Where do we go?

Early Vs Delayed Ablation of AFib

The other trial I’m going to talk about is from Melbourne. John Kalman presented a study of very early AF Ablation versus deferring to twelve months after a patient’s been optimized and managed with antiarrhythmic drug therapy. And their outcome was looking at progression to looking at incidence of AF a year after the procedure. So 24 months out from the initial diagnosis up until now, there’s been lots of data from other trials and observational studies suggesting that earlier is better. Certainly with this approach they found that there was no statistically significant difference between the two arms. This was an interesting study because it goes counter to what had been a growing trend to get people in for AF Ablation earlier and earlier. I guess one caveat is they went very, very early with these patients. They got an AF Ablation in the treatment arm within four weeks, which I can imagine most healthcare systems will be very challenging. So in some respects, it provides some reassurance. If you do have some delays built into your system, especially after COVID, and lots of health systems having big backlogs that – waiting up until twelve months doesn’t have a really adverse effect on your patients. So that’s good news in some respects.

POWERFAST III

There was some interesting data from the POWERFAST III study and stroke substudy from this trial. So POWERFAST III looked at high-power short duration ablation versus a more conventional dose of radio frequency. They used 70 watts in their high-power arm. In terms of freedom from AF, the conventional versus the high-power arm had very similar outcomes. But in terms of safety, there were some concerns in the high-power arm. There were an increased number of subclinical strokes in the high-power arm and imaging changes suggested a stroke as well in the high-power arm. So that is of some concern. The other interesting feature was that there were some signs of oesophageal lesions in both arms. One of the justifications for using high-power short duration is you cause slightly more superficial ablation and reduce the risk of extra cardiac injury to the oesophagus. But certainly there seemed to be some signs that that was still happening with higher power short duration. So a lot of food for thought with that trial.

ADAPT-RESPONSE

So the Adapt-RESPONSE trial looked at Medtronic’s adaptive CRT algorithm. So they’re biventricular pacemakers. So the idea with this algorithm, which has been around for a couple of years now, is that it will only LV pace a patient with CRT if they meet a certain number of parameters with their device. And they looked to see whether outcomes which include death and heart failure hospitalization was reduced by using this algorithm. It was a huge trial. It ran over eight years, over 3600 patients, and they found no difference between the two arms. This is very interesting.I think there are a few take-home points for almost outside of the algorithm which were of interest. They presented that they had the lowest mortality and morbidity of any major CRT trial. So it shows that there have been improvements in heart failure treatment. And paradoxically, it makes making these trials slightly harder to run. I think they justified the fact that there probably is still some benefit in using this algorithm, because if you are able to LV only pace a patient, then actually you reduce battery drain. So potentially that reduces the number of box changes a patient may need for their CRT. But certainly an interesting trial. I think some people were hoping that this would probably have a bigger impact. Interestingly, the Kaplan-Meier curves were moving in favour of the adaptive CRT algorithm, but unfortunately, there was some delayed reporting of adverse events which impacted how the trial had to be terminated slightly early. So we may have had a different outcome had that not been the case. But either way, it certainly shows that the algorithm certainly doesn’t do any harm and there is certainly a trend towards some benefit, and there are some other benefits potentially which can be gained by using it.

Marshall-Plan

The final trial I want to talk about is the Marshall-Plan from Bordeaux. The team from Bordeaux looked at using vein of Marshall ethanol Ablation for patients with persistent AF. See if that improved their chances of freedom from AF after an Ablation. The control arm had a standard pulmonary vein isolation with radiofrequency ablation. The treatment arm had a vein of Marshall Ablation, but they also had what is effectively posterior wall isolation. They labelled it dome transection by doing a roof line, and if the roof line didn’t block a floor line and also a CTI line, and they found a reduction in AF burden in the Marshall Plan arm. This trial still hasn’t completed. These were preliminary results, and they still have a few more months of follow-up, but certainly looks very encouraging. And it seems to support the findings we have seen previously from the VENUS trial. So very encouraging and actually shows that we may have another lesion set to use an AF, which now has some evidence from a randomized control trial. So very encouraging.

EHRA 2023 — Dr Vivek Y Reddy (Mount Sinai Hospital, US) shares the details of a study looking at conformable PVI catheters for pulmonary vein isolation (PVI). The study investigates the use of a highly deformable mesh-like eight-french catheter that has recently received CE mark approval. The trial is ongoing at three centers.

Questions:

What’s the research context or rationale?
Describe the SpherePVI™ Catheter used.
Study design, outcome measures, and eligibility criteria?
What’s next?
Recorded on-site at EHRA 2023, Barcelona.

Interviewer: Jonathan McKenna

Editor: Jordan Rance

Transcript

“- I’m Vivek Reddy from the Mount Sinai Hospital in New York City, and I’m going to discuss our future abstract on the conformable PVI ablation catheter.

Research Context and Study Rationale

So let’s talk about the background of this catheter first. There’s a conformable, what we call a lattice-tip catheter that’s a focal catheter that is just recently received CE Mark approval. The catheter is an 8 French catheter, so it fits in most of our sheaths, but the tip is a nine millimetre mesh. And one of the interesting things about the catheter is when we’re doing point by point ablation, because it conforms somewhat to the tissue the stability seems to be quite good, the interaction with the tissue seems to be quite good. Now, one of the other interesting aspects is the company said, “Well, this is an interesting type of catheter.” But the field also wants a single shot PV isolation tool, a tool that you can just sort of push up against the vein and it touches the vein, and you just deliver one lesion to isolate the vein. So that was the idea behind this conformable PVI catheter, to create a type of catheter that’s highly deformable, a meshlike catheter that can accommodate different types of pulmonary vein anatomies, different pulmonary vein sizes, push it up against the vein and then deliver pulse electric field energy to isolate the pulmonary vein.

Overview of the Sphere PVI Catheter

One of the interesting things about this catheter is that it’s an over-the-wire catheter, which is useful for engaging pulmonary veins, but also it’s linked to an electroanatomic mapping system, so it is magnetically localised in the mapping system. So you can move the catheter around in the chamber to create the anatomy quickly, then engage the veins, isolate the veins, and at the very end if you want to do additional ablation, perhaps with a different catheter even, you have that flexibility that’s the design of this technology.

Study Design, Outcome Measures and Eligibility Criteria

This is a first in human clinical trial, this is the first time this catheter is being used and is being conducted at at least three centres in Europe. I say at least because we’ve started in three centres, but more are likely to be included. The total trial design is up to 160 patients with paroxysmal atrial fibrillation who failed somewhere between a class 1 to a class 4 antiarrhythmic drug. These are patients who will undergo the procedure. After the procedure, one of the unique aspects of this trial design is that patients are planned for a three month remapping study. So not because of symptoms, but rather to understand the quality of the ablation lesion and to do additional touch up if necessary, the patients will come back for an invasive procedure at three months. The veins will be checked to make sure they’re all isolated, or if not, try to understand why and improve everything. In addition, in a subset of the patients, there’ll also be post-procedure brain MRI imaging to look for asymptomatic cerebral ischemic events as well as post-procedure endoscopy, esophageal endoscopy to verify the absence of effect on the oesophagus. The efficacy endpoints will, of course, include acute pulmonary vein isolation, but also the success, clinical success out to one year after a three month blanking period. And certainly on the safety side, there’s a composite safety endpoint that includes all potential complications as typical for AF ablation studies.

Next Steps

So the trial is ongoing at this point, patients are being enrolled at three centres and then ultimately at more centres. Once the 160 patients are enrolled and followed out to one year, then we’ll be presenting these data hopefully at a conference like this.”