HRS 2020: Longer Term Results From The ENCORE-VT Study

Dr Phillip S Cuculich (Washington University, St. Louis, MO, US) shares the longer term results from a Phase I/II Study Of EP-guided Noninvasive Cardiac Radioablation for Treatment of Ventricular Tachycardia.

HRS 2020:Recorded remotely from Washington.

Interviewer: Mirjam Boros
Recording editor: Natascha Wienand

Transcript Below:

My name is Phillip Cuculich, and on behalf of my colleagues and collaborators here at Washington University School of Medicine, in St Louis, I’m honoured to share with you the results from the longer term follow-up of our phase I/phase II study of EP-guided noninvasive cardiac radioablation for the treatment of ventricular tachycardia. A study that we call ENCORE-VT.

Now as heart rhythm specialists, many of us at HRS perform procedures with catheters. We carefully manoeuvre these within and around the heart, meticulously trying to find the critical short circuits of electricity. Once those circuits are identified and discovered, we apply energy at the tip of the catheter which creates heat, to destroy the electrical conduction through these circuits.

However, heat from a catheter is limited, and often we can’t reach the deeper elements of the circuit within the heart muscle, and so our procedures can fail. To deliver a full thickness, gap free ablation we look to our radiation oncology colleagues. That’s right, our cancer doctors, who have the exact same goals when they’re trying to treat tumours.

Now, in the basement of most hospitals you’ll find cancers being treated with stereotactic body radiotherapy, or SBRT. Now this concept, x-rays or photons are delivered by a robotic arm in sweeping arcs around the patient delivering high doses of ablative energy to a tumour with minimal exposure to the surrounding tissues. In short cardiac radioablation we simply treat an arrhythmia circuit like a tumour.

In 2007 we reported the first case series using focused cardiac radioablation in five patients, with refractory VT. Based on these results we opened a formal prospective phase I/phase II trial to answer the following question: In patients with VT, who have failed conventional therapies, can a single non-invasive radiation treatment safely reduce VT burden?

Now, the long term results of this trial are shared here, at HRS 2020. So who was included in this study? In general, the 19 patients in this trial had weak hearts, and advanced cardiomyopathy. They had a median of 96 episodes of VT requiring rescue from their defibrillator in the six months before the treatment. And all of them had failed standard therapies such as anti-arrhythmic medicines, or catheter ablations.

Overall, compared to other clinical trials of catheter ablations, this was a very sick patient population. And the median target size for ablation was 25 cc, and to provide some element of reference, a golf ball is about 45 cc. But after we account for the cardiac motion, and the respiratory motion, and set up uncertainties, the actual treated volume was more than 90 cc, and their median treatment time was only 15 minutes.

The first question that we sought to answer, is this safe? And the answer appears to be yes. We’re now reporting the results from the past three years. The treatment itself is short and entirely noninvasive. There were no problems with the cardiac devices, both during and after treatment, and patients are treated as outpatients. So literally they get up after treatment and they walk out of the treatment unit and go home.

In the first 90 days of analysis, one patient developed inflammation of the pericardium, called pericarditis. And this was treated successfully with a short course of oral steroid medication. Over the next three years we saw two more patients who had developed fluid around their heart; called a pericardial effusion. And both of these were easily treated with colchicine and anti-inflammatory medication.

Importantly one patient developed a gastropericardial fistula, just after two years after treatment. And this was very near the area that we had treated in the heart, on the inferior wall of the left ventricle. This patient presented with abdominal pain, we were able to make the diagnosis quickly, and this patient underwent a successful corrective surgery. Now to date, no patients have developed heart block, there’s been no coronary artery injury, there’s been no cardiac perforation.

In general this appears to be a gentle ablation for patients. And this is reflected, I think, in the overall survival. When you look at six months, in this very sick population, 89% of patients were still alive at six months. Which is really superb when you think about this patient population. And over half the patients remain alive at two years.

Now what about the second question, is it effective? Well in this study, this is the first formal study, we chose to look at any reduction in VT burden as our primary endpoint. Now we compared the six months before treatment to the six months after treatment. So at six months, 94% of our patients met the trials primary endpoint, and then continuing out to two years, which we’re reporting here, 78% of patients continued to meet that primary end point of VT reduction.

Again, that’s not a fair comparison of 24 months after to the six months before, and yet the numbers are still fairly impressive. Now it’s important to put this into some context though. Most patients were not free of VT, we were not seeking to cure VT with this. It’s a difficult bar to achieve in a salvage patient group, and that wasn’t the purpose of our study. We will report a number of pre-specified secondary endpoints, and perhaps the most impactful for patients, in the six months after treatment, 78% of patients did not have a single ICD shock, and this was in the face of de-escalating anti-arrhythmic medicines. Many patients were off anti-arrhythmics entirely. So in conclusion this report is really the first long term follow-up of noninvasive cardiac radioablation, which is critical, because we know radiation can have late adverse effects. And in patients with VT, who failed conventional therapies, a single noninvasive 15 minute focused radiation treatment safely reduced VT burden. And this effect persisted beyond two years for most patients. So far, the serious toxicities appear to be low, but they can occur out to two years and beyond, so long term vigilance is really needed for future trials. And so right now, based off of these results, presented here at HRS 2020, we believe that cardiac radioablation is currently best suited for high risk patients who have failed conventional VT therapies.

Question: How should this study be built upon?

Well I think as we’ve looked past the last three years now, we’ve seen multiple case reports, and now four different case series published, that have all generally shown the same thing. That with a single dose of cardiac radioablation, we see a dramatic reduction, and a relatively early reduction in VT burden, in some of the worst cases. This now needs formal follow-up, in a prospective randomised trial, and we’re organising this trial now, with the hopes of opening this in Q1 2021.

HRS 2020: Point-By-Point Pulsed Field Ablation To Treat AF

Dr Vivek Y Reddy (Icahn School of Medicine at Mount Sinai, New York, NY, US) shares the results of the Point-by-Point Pulsed Field Ablation (+/- Radiofrequency Ablation) to Treat Atrial Fibrillation: A First-in-Human Trial.

The trial looked at tissue selectivity of pulsed field ablation (PFA), which provides safety advantages over radiofrequency ablation (RFA) in treating AFib.

1. What is pulsed field ablation (PFA) and what is its potential?
2. What data are you presenting at HRS 2020?
3. What did the data show?
4. What further research should be conducted with this technology?

HRS 2020: Filmed remotely from New York.

Interviewer: Mirjam Boros
Recording editor: Natascha Wienand

HRS 2020: Results Of The Pulsed AF Trial

Dr Atul Verma (Southlake Regional Health Center, Toronto, ON, CA) on behalf of the PULSED AF Investigators shares the results of a study measuring the safety and effectiveness of the novel Pulsed Field Ablation (PFA) technology.

Dr Verma tells us about the difference between Pulsed Field Ablation (PFA) and Point-to-Point pulsed ablations and talks about the future plans for this technology.

1. What technology was used in this study and how does it differ to point-to-point pulsed ablations?
2. What was the design of the trial?
3. What did the data show?
4. What further research should be conducted with this technology?

HRS 2020: Recorded remotely from Toronto.

Interviewer: Mirjam Boros
Recording Editor: Natascha Wienand

Transcript Below:
[Verma] I’m Dr Atul Verma. I’m the medical director of the Heart Rhythm Program at Southlake Regional Health Center and also associate professor at the University of Toronto in Canada. I think that electroporation has the potential to really revolutionise what we are doing in the electrophysiology. I’m very proud to be working with this technology and I really want to thank all my co-investigators and the team at Medtronic for designing this wonderful technology.

Question 1: What technology was used in this study and how does it differ to point-to-point pulsed ablations?

[Verma] It was a pleasure to present the PULSED AF trial at HRS Late-Breaking. What differentiates this technology from traditional point-to-point radio frequency is that it is called pulsed field ablation or irreversible electroporation. So instead of using thermal energy, like heat or freezing, we are using electrical fields and when we expose them to the tissue, that opens up pores in the cells, which then leads to targeted cell death. So this is a non-thermal ablation. And we think that this will offer many advantages over traditional point-to-point radio frequency.

Question 2: What was the design of the trial?

[Verma] So the data that we’re presenting for the PULSED AF trial are essentially the initial acute results of the trial. So we were meant to evaluate 20 patients but we reported on 14 because the other six cases were differed because of the COVID-19 crisis. But what we’ve showed was essentially the primary safety endpoint, which is whether there were any safety issues within the first 30 days and the primary acute efficacy endpoint, which was the ability to isolate the pulmonary veins using the pulse field ablation only and no other technologies.

Question 3: What did the data show?

[Verma] I’m proud to say that when it came to safety, we certainly had no seriously adverse events reported thus far in the trial. In particular, we think that pulse field ablation will have a better safety profile when it comes to phrenic nerve injury or esophageal injury, and certainly we saw no change in the esophageal temperature in the patients. And we also so no phrenic nerve injury and there were no other serious adverse events reported at 30 days. And for the acute efficacy endpoint, we were able to isolate a 100% of the pulmonary veins in the 14 patients using pulse field ablation alone and no other technologies.

Question 4: What further research should be conducted with this technology?

[Verma] So obviously, there is further research that needs to be conducted with pulse field ablation. First of all, we’re going to be following all of these patients out to one year and we will be reporting at on one year efficacy and safety endpoints. Furthermore, we obviously need a larger trial with more numbers of patients. This was just a first in human feasibility trial and we hope to be moving into a much larger pivotal trial very, very soon.

HRS 2020: Update From The PRECEPT Study

Dr Moussa Mansour (Massachusetts General Hospital, Boston, MA, US) shares updates from the PRECEPT Study.
The objective of the Persistent atrial fibrillation ablation with contact force sensing catheter: The prospective multicenter PRECEPT Trial is to evaluate the safety and effectiveness of catheter ablation of PsAF using a porous tip contact force (CF)-sensing catheter.

1. What are the current challenges with treating persistent AF?
2. Why was PRECEPT conducted?
3. What was the study design?
4. What were the results?
5. What conclusions can be made as a result of this study?

HRS 2020, recorded remotely from Boston.

Interviewer: Mirjam Boros
Recording Specialist: Natascha Wienand

Transcript Below :

Question 1 : What are the current challenges with treating persistent AF?

The data with ablation of paroxysmal atrial fibrillation, is, there is large number of data. However, the data is lacking for persistent atrial fibrillation. So, knowing the optimal procedure for persistent atrial fibrillation, knowing the outcome of persistent atrial fibrillation in a large multi-centered study is relatively unknown.

Question 2 : Why was PRECEPT conducted?

The PRECEPT study is the first multi-national, multi-center FDA sponsored study for persistent atrial fibrillation. We have significant data on the treatment of paroxysmal atrial fibrillation, but the data for persistent atrial fibrillation is lacking. So the aim from PRECEPT study is to demonstrate the efficacy and safety of catheter ablation for persistent atrial fibrillation in a multi-center prospective design.

Question 3 : What was the study design?

The PRECEPT is the first multi-center study for persistent atrial fibrillation under FDA sponsorship. Many studies were done for paroxysmal atrial fibrillation but none has been done with persistent atrial fibrillation. 26 centers were enrolled in the United States and Canada. 300, in excess of 380 patients. It has a prospective design. Follow-up was 15 month which is extensive and also the patient had a very meticulous follow-up including frequent ambulatory monitors and testing. The follow up is also unique and it is geared toward a persistent population of study. And the design of the study was later incorporated into the atrial fibrillation ablation consensus guidelines, and I will elaborate on that a little bit. So the study had 15 month follow-up. Most of the studies of A Fib ablation had only a 12 month follow-up. And the reason for the 15 month follow-up is because we had in PRECEPT six months blanking period instead of three. And I will tell you what the reasons are. In most patients with persistent atrial fibrillation, after ablations, some of the investigators or operators may use some medications in the first three months. We did not want the effect of the medications to be carried over and dilute the effect of ablation. As a result, we extended the blanking period to six months so they will have no more effect of the medication that some of them could have been used in the first three months. And because of that we extended the follow-up to a total of 15 month which I believe is very adequate.

Question 4 : What were the results?

The study had two end points, a primary safety endpoint and the primary effectiveness endpoint. And both endpoints were met. For the primary safety endpoint, the complication, the adverse event rate was very small and it beat the expected number of safety events. The primary effectiveness endpoint which is a very strict endpoint, consisting of freedom from atrial fibrillation of no more than 30 seconds, was achieved in 61.7% of the patients. In addition to the primary effectiveness endpoint, we also had a clinical success endpoint which may be more relevant for patients with persistent atrial fibrillation where the 30 second rule may not apply well. And this study, in PRECEPT study, this clinical success endpoint was reached in 80% of the patients. Many of us don’t believe that the 30 second recurrence rate of atrial fibrillation may be relevant for patients with persistent A Fib. But we also know that this is the standard that needs to be followed by most societies and by most clinical trial regulatory foundations or institutions. So, we had to show that but also we showed we showed a clinical success endpoint. In addition to the primary safety and primary effectiveness endpoint we also looked at the quality of life, we looked at the rate of re-do ablation and we looked at healthcare utilisation and we found that ablation of persistent atrial fibrillation improved all those end oints.

Question 5 : What conclusions can be made as a result of this study?

We learned a lot from the PRECEPT study. It is a first prospective study, multi-center for persistent atrial fibrillation ablation. It showed that ablation, when performed with a contact-force catheter, is associated with a low complication rate and provides a high level of effectiveness. We also showed that ablation improves the quality of life of the patients, reduces healthcare utilisation and is associated with a low rate of recurrence.

HRS 2020: LBBP As A Novel Strategy For Cardiac Resynchronization Therapy

Dr Pugazhendhi Vijayaraman (Geisinger Heart Institute, Mountain Top, PA, US) shares the results from the Left Bundle Branch Pacing for Cardiac Resynchronization Therapy study.

The aim of the study was to assess the feasibility and outcomes of LBBP in CRT eligible patients in an international, multicenter, collaborative study.

1. What was the rationale for the study?
2. What patients were included and what were your endpoints?
3. What were your findings?
4. How should this study influence use of Left Bundle Branch Pacing in practice?
5. What further research is needed in this field?

HRS 2020: Recorded remotely from Mountain Top.

Interviewer: Mirjam Boros
Recording editor: Natascha Wienand

HRS 2020: Incidence Of Silent Brain Infarcts In Anticoagulated Patients With AF

Patients with AF have an increased risk of dementia and clinical stroke. Dr Conen (Hamilton, CA) discusses the results of this large cohort study aimed at investigating if dementia can be mitigated using novel oral anticoagulation (OAC). He also sheds light on what further studies are needed in follow-up to these results.

1. Why did you conduct this study and patient population?
2. What was the study design and endpoints?
3. What were your results?
4. Were there differences between the anticoagulants used?
5. What conclusions can be made as a result of this study and what further research needs to be conducted?

HRS 2020: BlueSync Field Evaluation Study

Dr Khaldoun Tarakji (Cleveland Clinic, Cleveland, OH, US) talks about the performance of first in the world pacemaker to use smart device app for remote monitoring and the future of telemedicine.
The purpose of this field evaluation was to collect and evaluate information related to CareLink transmission compliance as well as patient perceived benefit of BlueSync™ .

1. Do you believe remote monitoring has the capacity to improve patient outcomes?
2. What was the study design, patient population and technology used?
3. What parameters did you use to assess the outcomes of the performance of remote monitoring?
4. What were your findings?
5. What conclusions should be made as a result of this data?
6. What further research is needed?
7. In light of the recent events how do you see the future of telemedicine?

HRS 2020, recorded remotely from Cleveland.

Interviewer: Mirjam Boros
Recording Specialist: Natascha Wienand

HRS 2020: PRAETORIAN Trial 4 Years Results

Dr Reinoud Knops (Academic Medical Center, Amsterdam, NL) discusses 4 years results from A Randomized Trial Of Subcutaneous Versus Transvenous Defibrillator Therapy: The PRAETORIAN Trial.

1. Why is PRAETORIAN needed?
2. What was the design, population and endpoints of the study?
3. How long will patients be followed?
4. Were all objectives met?
5. What conclusions should be made from this data?

Interviewer: Victoria Perroud
Recording Specialist: Natascha Wienand

HRS 2020: Primary Outcome Evaluation Of The PINNACLE FLX Study

Dr Shephal Doshi (Pacific Heart Institute, Santa Monica, CA, US) discusses the results from the PINNACLE FLX Study.
The PINNACLE FLX Study is a prospective, non-randomized, multi-center investigation to establish the safety and effectiveness of the WATCHMAN FLX™ Left Atrial Appendage Closure Device for subjects with non-valvular atrial fibrillation who are eligible for long-term anti-coagulation therapy to reduce the risk of stroke but who have a rationale to seek a non-pharmacologic alternative.

1. Can you describe the technology used in this study and how it differs from previous models?
2. What was the design and endpoints of this study?
3. What were your findings?
4. Which patients should be considered for this device?
5. What further research will be conducted?

Recording: Natascha Wienand
Interviewer: Mirjam Boros


Dr David B DeLurgio (Emory St Joseph’s Hospital, Atlanta, GA, US) describes the need of the CONVERGE trial, to investigate how persistent atrial fibrillation should be treated through ablation techniques. The CONVERGE trial was designed to compare the effectiveness of adding epicardial left atrial posterior wall ablation to the endocardial catheter ablation procedure while demonstrating an acceptable safety profile.

1. What is the rationale behind the CONVERGE trial?
2. What was the trial design?
3. What were your findings?
4. How should this data influence clinical practice?
5. How should this data influence future research?

Interviewer: Mirjam Boros
Recording Specialist: Natascha Wienand

HRS 2020: UNTOUCHED Trial Primary Results

Dr Michael R Gold (Medical University of South Carolina, Charleston, SC, US) discusses the primary results of the UNTOUCHED trial. The UNTOUCHED trial assesed the 18-month incidence of inappropriate shocks in subjects implanted with the EMBLEM Subcutaneous Implantable Defibrillator (S-ICD) for primary prevention of sudden cardiac death.

1. What was the rationale behind the UNTOUCHED trial?
2. What was the design and inclusion criteria of the UNTOUCHED trial?
3. What outcomes were being assessed in the UNTOUCHED trial?
4. What were the results?
5. What further research should be conducted with this technology?
6. What were the shock and safety endpoints?

Interviewer: Mirjam Boros
Recording Specialist: Natascha Wienand

HRS 2020: Anticoagulants Greatly Reduce The Risk Of Ischemic Strokes In Patients With AF

Dr Nazem Akoum (Washington, WA) discusses whether atrial fibrosis and associated atrial cardiopathy may be in the causal pathway of cardioembolic stroke independently of atrial fibrillation. He also sheds light on what further studies are needed in follow-up to these results.

1. What clinical problem does this study aim to address?

2. What was your hypothesis?

3. What was the design of the study?

4. What was observed in these patient groups?

5. What conclusions can be made from this data?

6. How should the results of the study influence practice?

Interviewer: Victoria Perroud
Recording Specialist: Natascha Wienand