Conference Takeaways

AHA 22 – Dr Shino Kany (Broad Institute of MIT and Harvard, Cambridge, MA, US) joins us to discuss the association of genetic risk and outcomes in patients receiving early rhythm control therapy for atrial fibrillation in the EAST-AFNET 4 trial.

EAST-AFNET 4 aimed to compare early rhythm control to usual care amongst patients with a recent diagnosis of atrial fibrillation, randomised in a 1:1 fashion.

Questions:

1. What was the rationale of EAST AFNET 4?
2. What was the study design and patient population?
3. What were the key findings?
4. What are your take-home messages for clinicians?
5. What further study is needed in this field and where are the knowledge gaps?

Recorded remotely from Cambridge, 2022.
Interviewer: Jordan Rance
Videography: Dan Brent

Transcript

” – My name’s Shino Kany. I’m a research fellow at the Broad Institute of MIT and Harvard and a cardiovascular fellow at the University of Hamburg. And today we’ll be talking about the genetic substudy of the EAST-AFNET 4 trials.

Substudy Rationale

So the original EAST-AFNET 4 trial showed that early rhythm control in atrial fibrillation patients who have atrial fibrillation for less than one year is associated with a reduced composite outcome of cardiovascular death, stroke, hospitalisation for acute coronary syndrome or heart failure. And we know that atrial fibrillation is a highly heritable disease and we have been using polygenic risk scores to estimate this genetic burden that every one of us has for certain diseases. And we can do the same for atrial fibrillation and stroke. So we wondered what will happen if we look for the genetic risk in those patients and see the association with the outcomes of the trial.

Study Design and Patient Population

So the EAST-AFNET 4 trial enrolled patients who had atrial fibrillation for less than one year to be able to treat basically in the beginning of the disease. Most patients had atrial fibrillation for less than three months, and the design was a one-to-one randomization to early rhythm control, which included antiarrhythmic drugs, catheter ablation, or user care; which was mostly rate control based in terms of severe system, despite optimal rate control, rhythm control was allowed as well, but very, very rarely utilised in that arm of the study. And around 1600 patients gave consent to the biomarker substudy, where we got basically also genetic material that we could then analyse for common variants and estimate polygenic risk score in those patients. So in total, for the genetic sub-study we had 1,567 patients that were included and roughly half and half in each treatment arm, so it was quite balanced still.

Key Findings

So the key findings were we looked at two polygenic risk scores. So one for atrial fibrillation and one for stroke. And for the polygenic risk score for atrial fibrillation we found quite moderate association of that score with recurrent AF in the trial as a time to event analysis. That was to be expected. And for the stroke of polygenic risk score, quite unexpectedly, we found no association with stroke but association with heart failure. And to further validate this finding, which was unusual and unexpected, we also looked at the polygenic risk score for stroke in the UK Biobank. And there we found association with atrial fibrillation, stroke, and heart failure. And those basically validated what we saw and also explained the reasons why we didn’t saw the association with stroke in our trial. The EAST-AFNET 4 trial patient cohort is very, very well treated. Anticoagulation is above 90% in each arm. And in the UK Biobank it isn’t. So in a population that is not anticoagulated, we see a association with stroke with our polygenic risk score.

Take-home Messages for Clinicians

My take home messages are that early rhythm control is effective and safe across the genetic risk spectrum and that polygenic risk scores are only as good as the question that we ask and the tools that we create from them. So basically, that polygenic risk scores that are made in populations that form with no anticoagulation are not as powerful in patients who are anticoagulated. So I think the key messages here that we still have to learn a lot about polygenic risk scores, but atrial fibrillation should probably be treated early in disease history.

Further Study Needed and Knowledge Gaps

So I think one of the major, major problems in cardiovascular science, especially in the genetic field, but also in the clinical field, is the lack of diversity. The polygenic risk scores were made, constructed in European populations and used in a poor European population of the trial. And the reason for that is because we just don’t include enough people from minorities, from other ethnic backgrounds which is a major gap in our current understanding of genetics and the application in clinical care. And what we don’t have, despite the lack of diversity, is a lack of trial data that also includes genetic data. So we can understand the influence of genetics on treatments There are large Biobanks, but we need to do a better job in getting also bio information from our trial populations.”

ESC Congress 2022 — In this short and practice-focused review, Dr Afzal Sohaib, Electrophysiologist at Barts Health NHS Trust, shares his thoughts on the top 3 trials that will impact his practice.

Trials covered in detail include:

00:18: eBRAVE-AF: eHealth-based Bavarian Alternative Detection of Atrial Fibrillation: A Randomized Controlled Trial

01:34: CAPLA: Catheter ablation for persistent atrial fibrillation: A multicenter randomized trial of pulmonary vein isolation (PVI) versus PVI with posterior left atrial wall isolation (PWI)

02:20: INVICTUS: INVestIgation of rheumatiC AF Treatment Using Vitamin K Antagonists, Rivaroxaban or Aspirin Studies, Non-Inferiority

ESC Congress 22 — Late-breaker host, Dr Harriette Van Spall(McMaster University, CA) invited Dr Ganesan Karthikeyan (All India Institute of Medical Sciences, IN) to share the latest data from the INVICTUS trial (NCT02832544).

This randomized, open-label, non-inferiority trial compared rivaroxaban (Xarelto, Bayer) versus standard vitamin K antagonists (VKA) (Warfarin) therapy in 4,500 patients diagnosed with rheumatic heart disease.

Recorded on-site at ESC Congress 2022, Barcelona.

HRX 22 – Dr Matthew McKillop from ReadmyRhythm joins us to outline a new wearable heart monitoring platform to identify and diagnose cardiac arrhythmias in users.

Questions:

1. What are the clinical unmet needs that led to the creation of this technology?
2. What is ReadmyRhythm?
3. What is the data underpinning the use of this technology, and what future study is planned?
4. How can this technology aid both patients and clinicians in daily practice?
5. Where do you see the future directions of ReadmyRhythm headed?

Recorded Remotely from Jascksonville, 2022.

In this video from HRS 2022, Dr Ilan Goldenberg (University of Rochester Medical Center, Rochester, NY, US) joins us to discuss the findings of a recent study which aimed to evaluate the effect of sex hormones during the menstrual cycle on repolarisation dynamics in women with congenital and drug-induced long QT syndrome.

Discussion points:
1. Aim, and endpoints
2. Study design
3. Key findings
4. Impact on practice
5. Further research required

Recorded remotely from Rochester, 2022.

Dr Julia Lurz (Heart Center Leipzig, Leipzig, DE) joins us at HRS 22 to discuss the Mental-AF Trial. This study aimed to investigate if app-based mental training can impact the occurrence of atrial fibrillation episodes after catheter ablation for AF.

Discussion points:
1. Aim of this study
2. Function of the app
3. Patient population and study design
4. Key findings
5. Impact on practice
6. Further study needed

Recorded on-site at HRS 2022, San Francisco.

Transcript:

– My name is Julia Lurz from the Heart Centre of Leipzig Department of Electrophysiology. And we will be talking about the Mental-AF Trial today.

Aim of this study

We aimed to investigate whether patients with atrial fibrillation undergoing catheter ablation would benefit from a three-month app-based mental training with regards to reduction of symptom burden. Patients with atrial fibrillation have multifaceted symptomatology and they oftentimes suffer quite a bit. And also quality of life is reduced. Catheter ablation does offer an effective treatment option yet recurrences, especially during the three-month following ablation are common. So we try to find a tool to improve symptoms during this period.

Function of the app

The MINDANCE app offers a audio guided multi-modular programme with different mentor training techniques. And we conducted a programme for that. We believe would be beneficial for atrial fibrillation patients. And we had a first part, which was the relaxation module and included breathing exercises progressive muscle relaxation, and others to induce relaxation and to relieve physical and mental discomfort. And then the second part included mindfulness exercises that aim to refine the ability of introspection and introception which would relate to differentiation of disease perception.

Patient population and study design

Mental-AF included patients with symptomatic paroxysmal or persistent atrial fibrillation who were scheduled for catheter ablation of AF which is usually performed the day after. And mental-AF was a single centre investigator initiated unblinded randomised trial that included patients with symptomatic paroxysmal and persistent atrial fibrillation of a period of two years. And the primary endpoint was the mean AF6 sum score during the three-month study period. And the secondary endpoints included patient report outcome measures. There were total of 151 patients included in the final analysis.

Key findings

As for the primary endpoint we found that the AF6 sum score during the three-month study period was 12.5 in the usual care group as compared to 8.9 in the mental training group. This difference was found to be statistically significant and it related to a reduction of AF related symptom burden of 29% for mental training. Then as for the secondary outcomes, we found an improvement of the affect score. It is a measure of AF effect on quality of life for both groups. However, in the mental training group the improvement was significantly more pronounced. And as for the global score there was a difference of eight points. This improvement was driven by an improvement in the daily activity domain of the score. Then there was the promised global health. This is a more general assessment of quality of life which improved in the mental training group only with regards to physical and mental health domain.

Impact on practice

Since patients with atrial fibrillation suffer from a relevant symptom burden and limited quality of life even oftentimes after catheter ablation we need adjunctive treatment strategies for these patients. So there are a few considerations regarding the beneficial effects of mental training and there are a few different levels. One refers to more psychological level where we believe that mental training can alter disease perception and also on a more physiological level it should balance autonomic function. And of course it does lead to stress reduction. And then there is the topic of patient engagement. So app based tools can engage patient and taking responsibility for their own health. Additionally app-based approach bear huge potential as they are ubiquitously accessible and scalable and ultimately a more comprehensive approach to AF patients including common risk factor management as well as enforcing physical activity and mental training would be important to improve patient care, especially as there’s a huge overlap to other conditions such as heart failure with preserved ejection fraction.

Further study needed

It would be interesting to know if app-based mental training would actually reduce AF recurrences. So this could be assessed by continuous monitoring. And also if it relates to other than the ablation cohort which might have attenuated effects in this case. So a broader population would be interesting. And then this was a programme that went three month. So we would like to see how this develops over longer term especially as this would relate to patient adherence. It was okay to get them to train three month and they trained 50 minutes per day but would they do that beyond the three month? So this is something that would need to be investigated how that can be implemented. This concept could also be tested in other populations in patients with arrhythmia such as ventricular tachycardia or also a patient with heart failure with preserved ejection fraction. And favourably we would have multicenter studies to have proof of the concept.

In this video from HRS 2022, Dr Zachi Attia (The Mayo Clinic, Rochester, MI, US) discusses the outcomes of an international trial which aimed to evaluate the effectiveness of an artificial intelligence algorithm in identifying left ventricular dysfunction using an Apple watch ECG.

Discussion points:

1. Importance of this study
2. AI Technology
3. Study design and patient population
4. Main findings
5. Impact on practice
6. Further study required and next steps

Recorded onsite at HRS 2022, San Francisco.

Transcript:

– My name is Zachi Attia. I’m the co-director of AI cardiology at the Mayo clinic. Our talk was on the use of artificial intelligence to diagnose low ejection fraction or weak heart pump from an Apple watch ECG. This work was done as a collaboration between Mayo cardiology Mayo platform and the Mayo centre of digital health and was not supported by anyway, by Apple.

Importance of this study

So low injection infection or a weak heart pump affect about 2% of the population. Patients who are diagnosed with low ejection fraction often go to clinical heart failure, and the of dying within five years are significantly higher. And while it’s such an awful disease we have useful treatments and medications to help these patients. The main issue is they usually don’t get diagnosed early enough. Contment of the diagnosis require imaging like CT, MRI or echocardiogram which are expensive require a physician to read them. And many of the American population all around the world are more than 150 miles from the closest echocardiogram. So we wanted to find a way to diagnose those screened these patients, and see who needs that echocardiogram by using the ECG. And the ECG is a much cheaper, much more ubiquitous test because you can today measure it from a watch, for example.

AI Technology

We used something called a convolutional neural network. It was originally designed to look at images and we applied it on ECG tracings, and you train it by showing the AI many, many ECGs of patients with normally injection fraction have many ECGs with a low ejection fraction and we’re able to do it because in Mayo, we have data from patients who have both an echocardiogram and ECG and what we’ve done to apply it to a watch is we took those ECG and we made them synthetically look like they were recorded by an Apple watch. We took about 50,000 of these ECGs and built a model by showing it again, a lot of normal and abnormal patients. So the AI was able to find subtle patterns that human cannot look and even a cardiology expert cannot look at an ECG and say this a patient with low EF but by showing it 50 thousands of them the AI was a able to learn these patterns. We then recorded patients with an Apple watch using an app, and we tested on patients that had an echo and an Apple Watch and we tested that model on these patients.

Study design and patient population

This is a proof of concept study. We took any patient that had a Mayo clinic app with an iOS 14 or above just because that’s the minimal version you need to acquire an ECG with a digital format. And we asked them, do you have an Apple Watch, and will you be willing to participate in the study? If they answer yes, we send them a link to the app and that’s a nice thing about the study because everything was done remotely. We had one study coordinator, Jennifer Neumann who emailed all of these patients, got the responses and automatically if they consent it to the study, they got an app and used the app to upload all of the ECGs and kept getting push notification, telling them they want to keep sending us your ECG every other week, and then if they recorded new ECGs, we got those as well. We had 2500 patients and that uploaded 125,000 ECGs within about five months. The average time of a user in the study was four months and they actually used the app twice a month. So they kept being very very engaged. Interestingly, the population, we had patients ageing from 22 to 92, and we noticed the higher use of the app for older their patients probably because they were more interested in their health or maybe they were more interested in their cardiac health specifically.

Main Findings

The study had two aims. First one was to look, if we can acquire data remotely digitally in a decentralised way from a diverse population. And we could, we, again, as I mentioned 125,000 ECGs in five months from 46 states in the US and 11 countries around the world. So, that was very successful. The second part is we were able to take those ECGs and feed them to our AI model for a subgroup of patient who had both an echo and ECG. We ran into the model and saw that we had UAC area under the curve of 0.88. Under the curve is a way to assess how well your screening model works. The worst ones are 0.5. The perfect one will be 1. And most clinically used tests are between 0.8 to 0.9. So 0.88 is a very high AUC which shows that this tool might be able to screen patients using their own watch from home.

Impact on practice

When we developed the original model, we used the 12 lead. And even though it worked well, we decided to study showing how these tools affect patients. And we gave clinicians, we randomised clinicians and half of the clinician got access to these tools and half got the regular tools that they have. And we noticed that the 32% uptick in detecting these new patients. So even though they didn’t send more patients to echocardiograms, they found more sick patients. So you are able to see that these tools affect patients in a positive way and don’t increase burden on the medical system. This is a proof of concept using the watch. So I assume we will do something very, very similar maybe an enriched population like patients who are undergoing chemotherapy and are in higher likelihood of developing it due to cardiotoxicity.

Further research required and next steps

So, as I mentioned, we have to validate to see that it actually benefits patients, right? We want to make sure that these tools accurate as they are, are being used correctly by clinicians. We developed something called the AI dashboard which allows clinicians to look at the patient’s ECG. They can zoom in, they can focus and it improve the patient clinician communication. We want to embed this tool with clinician and see that patients are getting diagnosed more often using this tool by uploading their apple works through the dashboard.

Dr Pugazhendi Vijayaraman (Geisinger Heart Institute, Wilkes-Barre, Pennsylvania, US) joins us from HRS 2022 to discuss the real-world data from an international study assessing the outcomes of rescue LBBAP in patients with coronary sinus lead failure, or those who did not respond to BIV-CRT.

Discussion points:
1. Importance of this study
2. Patient cohort, study design and endpoints
3. Key findings
4. Take-home messages

Recorded onsite at HRS 2022, San Francisco.

Transcript:

– Hi, I’m Pugal Vijayaraman from Geisinger Health System in Pennsylvania. The topic of our study is that the rescue left bundle branch area pacing in patients who failed coronary vein lead placement for biventricular pacing and in those patients who did not respond to biventricular pacing. And this is an international multi-center study involving 16 centres across eight countries.

Importance of this study

Yeah, this is important study in the sense that for those patients who failed biventricular pacing in the past, the choices were somewhat limited and the choice were also somewhat drastic in the sense that simple transvenous procedure now needs surgical placement of a lead, which increases morbidity. There are some newer alternative implantation of a complex device called EBR system where you implant a transventricular endocardial LV, placement with additional devices to perform resynchronization. But the study shows that left bundle branch area pacing, which is similar to biventricular pacing transvenous lead placement and can be performed at the same time as performing a biventricular pacing that can rescue in cases where you fail biventricular lead placement. So it has huge implications for the patient and the cost for the health system.

Patient cohort, study design and endpoints

In this international multicenter study involving 16 centres we collected retrospectively on patients who had failed prior biventricular pacing implantation and then who went on to undergo left bundle branch area pacing. And we looked at the reasons for why they failed biventricular pacing and also looked at patients who failed to respond to a successful biventricular pacing. So overall we had about 212 patients. We were successful in 200 patients with a 94% success rate in this population. And 156 of them were lead failure patient and 44 patients with non-responders. What we found was that the success rate and the outcomes of this group was significantly improved, both clinically in terms of reducing heart failure hospitalisation, improving functional class, and more importantly, improving left ventricular ejection fraction in a significant percentage of the population. Overall, when we looked at the two groups, both the non-responders and the lead failure group we were able to show that the lead failure groups performed significantly better. About 70% of them had clinical and echocardiographic response, while the non-responders had slightly under 50% response rates suggesting that those patients are much sicker group of patients. And looking at the outcome of death or time to first heart failure hospitalisation, the patients who had lead failure subsequent to left bundle branch area pacing did significantly better. There was a 13% incidence compared to 30% in patients who had non-response to biventricular pacing.

Key findings

Yeah. So what we learned from this study is that most patients who fail biventricular pacing we have a very easy, simple, and even better option to provide them cardiac resynchronization therapy. So in our centre and most of the participating centres, none of our patients go for surgical epicardial lead placement anymore because we have a simpler, easier solution for the problem.

Take-home messages

Yeah. So one thing we learned is a non-responder group. So this is a small population, but in the study, but there’s a large group of patients who don’t respond to biventricular pacing. So looking at these small subset of patient we should be able to gleam and identify which of these patients will benefit from an additional intervention with left bundle branch area pacing. So identifying those patients and providing them with this new therapy, we can improve the response rate in patients who fail biventricular pacing. And we need a prospective study to assess these outcomes.

In this short interview from HRS 2022, Dr Pugazhendi Vijayaraman (Geisinger Heart Institute, Wilkes-Barre, Pennsylvania, US) outlines the findings from the CSP-SYNC trial which investigated the effects of conduction system pacing as compared to conventional biventricular pacing in patients with heart failure with preserved ejection fraction (HFpEF).

Discussion Points:
1. Aim of this study
2. Patient population and study design
3. Outcomes
4. Clinical implications
5. Further study required

Recorded onsite at HRS 2022, San Francisco.

Transcript:

– I’m Pugal Vijayaraman from Geisinger Health System in Wilkes-Barre, Pennsylvania and I’m presenting on clinical outcomes of conduction system pacing versus biventricular pacing in patients with reduced left ventricular ejection fraction.

Aim of this study

So the aim of this study was to assess the clinical outcomes of conduction system pacing while compared to traditional biventricular pacing in patients who need cardiac resynchronization therapy. Currently biventricular pacing has a 30 to 40% non-response rate, our goal was to see if conduction system can improve those outcomes in this population.

Patient population and study design

This is a retrospective observational two centre study. We included patients from both Geisinger health system, which is in Pennsylvania and Rush University health system in Chicago, Illinois and we took all patients who underwent cardiac resynchronization therapy, whether it’s biventricular pacing or conduction system pacing and then compare the clinical outcomes between the two groups in terms of death or heart failure hospitalisation as the primary endpoint. And then we also looked at individual outcomes of death and individual outcome for heart failure, hospitalisation and specifically looked at those outcomes again in patients with only left bundle branch block.

Outcomes

Yeah, we found very interesting observations from this two centre study. The incidence of death heart to failure hospitalisation was significantly reduced in patients who undergo conduction system pacing compared to biventricular pacing in this large study of 477 patients almost equal number of patients in both groups. And when we looked at the specific subpopulation of patients with left bundle branch block, this outcome difference was even further magnified, these are the patients that benefit the most with cardiac resynchronization therapy and conduction system pacing performs significantly better. In most of these differences came from a reduction in heart failure hospitalisation while there was a trend towards improvement in mortality in this subgroup of patients. More importantly, when we looked at the echocardiographic outcomes, the number of patients who had LV ejection fraction improvement was significantly higher, about 80% in the left bundle branch block in the conduction system pacing group compared to 60% in the biventricular pacing group. The average improvement in LV ejection fraction was 6% in the biventricular pacing group, which is similar to what has been seen in randomised clinical trials while the conduction system pacing resulted in about 12 to 14% improvement in LV ejection fraction.

Clinical implications

So the result of this study indicate two things, number one, this is primarily an observational study so it’s hypothesis provocating but we have been struggling with non-response to biventricular pacing in a significant population in those who undergo biventricular pacing. This gives us an opportunity to improve already good outcomes with biventricular pacing to a much greater degree if you perform conduction system pacing. And so this opens new doors, new avenues for improving clinical outcomes in patients with heart failure and reduced ejection fraction.

Further study required

Yeah, so again, as we talked about, this is primarily an observational retrospective study and these findings have to be confirmed in a randomised clinical trial. So we are looking at opportunities to run a randomised clinical trial, there are several pilot trials ongoing and part of a single centre randomised trial of one-hundred patients that gives us the next step momentum to design a much larger randomised clinical trial that would elevate conduction system pacing as a first line therapy for patients with heart failure and need for resynchronization therapy.

In this short interview from HRS 2022, Dr Andreas Rillig (University Heart and Vascular Center Hamburg, Hamburg, DE) joins us to discuss the outcomes of a sub-analysis of EAST-AFNET4. This multicentre randomised trial compared the strategy of early initiation of rhythm-control therapy with usual care in patients with heart failure.

Discussion points:
1. Aim of this sub-analysis
2. Patient cohort and study design
3. Main findings
4. Findings in relation to main cohort of EAST-AFNET4
5. Take-home messages for clinicians

Recorded onsite at HRS 2022, San Francisco.

Dr James Ip (Weill Cornell Medical College, New York, NY, US) joins us in a short interview from HRS 2022 to discuss the long-term findings from the NODE-302 study. This trial aimed to evaluate the effectiveness and safety of self-administered etripamil nasal spray in patients with an episode of paroxysmal supraventricular tachycardia in an outpatient setting.

Discussion points:
1. Aims of the NODE-302 study
2. Patient population and study design
3. Key findings
4. Take-home messages
5. Further research needed and next steps

Recorded onsite at HRS 2022, San Francisco.

Transcript:

– My name is James Ip. I’m an associate professor at Weill Cornell Medicine in New York. I am, came to Heart Rhythm to discuss the results of the NODE-302 trial, which is a study using intranasal Etripamil to convert spontaneous episodes of paroxysmal supraventricular tachycardia.

Aims of the NODE-302 Study

The aims of this study were to evaluate the continued use of this new intranasal calcium channel blocker to terminate episodes of SVT that occurred spontaneously. Patients were allowed to continue to use the drug, or up to 11 doses in this open-label trial.

Patient Population and Study Design

The patient population where patients who had SVT that were enrolled in the NODE-301 trial, which was a randomised control trial of the same medication. Patients who had completed a test dose as well as a randomised dose in that trial were eligible to enrol in this trial.

Key Findings

The key findings of the study was that the drug continued to be safe when used in repeated doses. Patients in this trial 92 patients had 188 episodes, and of those episodes there was a conversion rate of 60.2% at 30 minutes, and 75.1% at 60 minutes.

Take-Home Messages

Take-away message is that this drug will be available, hopefully after the next trial is completed. Once we gather enough information and show that it is, continues to be safe and effective in terminating SVT, the drug may be available for patients who may want to use this medication as an alternative to other therapies, like catheter ablation or taking a pill, which may not be effective and has a slow onset of action.

Next Steps

This is an open-label study. So it demonstrated the continued safety of the medication as well as the efficacy. We want to take the next step, which is to evaluate the drug in repeated use, if an episode of SVT doesn’t terminate. This is a trial called the rapid study, the NODE-301 part two study. If patients have an episode of SVT they use the medication, 10 minutes later the episode doesn’t stop, they take another dose of medication. We’re hoping that the combination of having two doses of the medication, 10 minutes apart may improve the efficacy and still be safe for patients to take. This is a randomised controlled trial. The results, we’re very excited, hopefully will be available at the end of the year, and we’ll have the answers for you then.

In this short interview, Dr Roderick Tung (University of Arizona College of Medicine, Phoenix, AZ, US.) joins us at HRS 2022 to outline the findings from a multicenter US cardioneural ablation registry in a study designed to provide data on the safety and feasibility of catheter-based cardioneural ablation.

Discussion Points:
1. Aim of this study
2. Patient population, study design and endpoints
3. Main findings
4. Impact on current practice
5. Further study required

Recorded onsite at HRS 2022, San Francisco.

Transcript:

– My name is Roderick Tung. I’m the Chief of Cardiology at the University of Arizona College of Medicine in Phoenix. And I had the privilege of presenting the late-breaking innovation of cardioneuroablation at US Multicenter Registry.

Aim of this study

The aim of the study was to see how generalizable the early data on cardioneuroablation was. It’s come from Brazil in the early 2000s, then percolated to Beijing and then went to Turkey. And this is the first US Multicenter collaboration where we looked at 13 centres to see how well do we do what’s being done and is this a good therapeutic option for patients that are frustrated by a vasovagal syncope or a young, don’t want a pacemaker and have functional autonomic bradycardia?

Patient population, study design and endpoints

So this was a retrospective multicenter cohort of 76 procedures in 71 patients. And they were over 18 years of age, so not paediatric population. The mean age was around 45, so not young, not old, me being 46, that’s about somewhere in the middle. And these are patients that are frustrated with either a clinical common problem called vasovagal syncope, common fainting is a neuroreflex, the Bezold-Jarisch reflex, or they have sinus bradycardia, just the slow normal heart rate, but they don’t have other reasons to do so. And they either went in for procedure with a concomitant ablation, there’s another reason to do the ablation and we wanted to modify some of the ganglionic plexi, which is where the nervous system plugs into the heart, both going in the wiring and then the wiring coming out, transmitting to the brain and the spinal cord. So by being able to touch down on these GP areas, we can actually change heart rate dynamics and slow heart rate down, speed the heart rate up, and it actually creates a functional rewiring of the balance between the parasympathetic and the sympathetic nervous system.

Main findings

Well, the main findings are number one, we have to show it’s safe. We do not want to violate the principle of nonmaleficence and cause harm. There were two complications in which the sinus rates slowed down, so that is probably not the worst because a lot of these would be traded with pacemaker anyway. And there was one pericardial effusion that required drainage, which can happen during catheter procedures. So ideally we’d be zero, but it was about 4% in this cohort. And then the overall outcomes, limited follow-up nine months was that 80% of them did not have recurrent fainting episodes, so that really is promising. Is it conclusive? By no means. Is it necessary? Yes, in terms of moving forward to say, “When can we prepare for prospective data, randomised trials, further investigation?” We believe this really does extend the fact that this is a promising new study, but there’s so many more questions that need to be answered. Who is the best patient to select? How should we do it? Under what diagnostic criteria do we really define vasovagal syncope and what are the procedural endpoints? How long does it last for? The data from Brazil shows somewhere between two to four years. There’s still changes in the autonomic tone with that rewiring and the rebalancing of the para and sympathetic system, so it shows us that this actually has the potential to benefit a patient for many years.

Impact on practice

I believe this is one of the most exciting things that I’ve been involved in because it’s a new procedure. We typically use ablation catheters to ablate arrhythmias. This is non-arrhythmic ablation. We’re not burning a heart rhythm problem, we’re burning a structural area using the catheters that we are very facile and agile with to be able to modify that heart-brain connection. And that’s really exciting and that gives a lot of promise. And it’s an option for the general cardiology community that often has no solutions for a patient because beta blockers have not systematically been shown to be useful. There are some ideas that if you do salt loading or medically with Midodrine and Florinef, that might be able to reduce some of it. Or even using antidepressants has been shown to benefit some, but there aren’t any medications that have been systematically shown consistently to benefit this frustrating condition. And as a matter of fact, behavioural modification, which is sitting down quickly, crossing your legs, squeezing, called counter pressure, to be able to increase the blood flow is the only thing that’s really been shown to be effective for this condition. So some of these patients have dramatic fainting. We’re not taking patients, these are highly selected, where we’re not taking a patient, the average one, that gets a little woozy when they see blood or a gory movie. We’re taking patients that often wake up with facial trauma or head trauma from their faint and don’t have much time to respond from their warning. So many of these patients actually have facial or head trauma and it’s very recurrent and very debilitating condition.

Further study required

There are so many further studies that are necessary. The pathway to science is showing feasibility that we can do it, that it can be safe, and in certain patients, it can be very effective. Then you want to refine and figure out, well, in whom is that best to study in, go through this data and say, “All right, now we need to look prospectively.” But then we need the FDA to be able to say, “We acknowledge that this might deserve an IDE, a new indication for catheter ablation.” And we hope that this symbolises the birth of a new procedure because, again, these are all compassionate off-label. Then if we can get the buy-in scientifically with regulatory, then move it forward, then we dream of randomised control trials. And then when randomised control trials show that the evidence can be consistent on a large scale, then we really move the scale into clinical medicine.