Cardiac Rhythm News issue 45 - May 2019

May

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19 45 Andrea Natale: High-power shortduration AF ablation Page 7

Charles Antzelevitch:

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Xavier Roselló:

Digital education and the ESC

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CABANA finds reduced AF and Eliminatebetter quality of life after ablation AF shows low thromboembolic but no reduction in mortality Catheter ablation for atrial fibrillation (AF) leads to a reduction in AF, better quality of life and lower hospitalisations than medical therapy, but does not significantly reduce the risk of death, disabling stroke, serious bleeding, or cardiac arrest the CABANA (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) trial has found.

and bleeding events with edoxaban

Uninterrupted anticoagulation with edoxaban (Lixiana, Daiichi Sankyo) resulted in low rates of thromboembolic and bleeding events in patients with atrial fibrillation undergoing catheter ablation, according to data from ELIMINATE-AF, presented at a late-breaking session at the European Heart Rhythm Association congress in Lisbon, Portugal (EHRA 2019; 17–19 March), and published online in the European Heart Journal. Researchers say the trial demonstrates a role for edoxaban, a non-vitamin K antagonist oral anticoagulant (NOAC), to be used instead of continuous anticoagulation with a vitamin K antagonist in this patient cohort.

T

he findings from the comparison of catheter ablation with medical therapy in atrial fibrillation were published in the Journal of the American Medical Association (JAMA), and assessed the impact on cardiovascular events and mortality. A sub-study investigated improvements in quality of life.

Lead investigator Douglas Packer (Mayo Clinic, Rochester, USA) describes the findings of reduced AF as “important”. Writing in JAMA, Packer et al say: “Among patients with atrial fibrillation, the strategy of catheter ablation, compared with medical therapy, did not significantly reduce the primary composite endpoint of death, disabling stroke, serious bleeding, or cardiac arrest. However, the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial.”

CABANA was an investigator-initiated, open-label, multicentre, randomised trial in 126 centres in 10 countries of 2,204 symptomatic patients with AF aged ≥65 years, or <65 years with ≥one risk factors for stroke. The catheter ablation group (n=1,108) underwent pulmonary vein isolation, and the drug therapy group (n=1,096) received standard rhythm and/or rate control drugs, according to guidelines.

Median age of participants was 68 years, and 37.2% were female; 42.9% had paroxysmal and 57.1% had persistent AF. In all, 90.8% (1,006) of those assigned to catheter ablation underwent the procedure, and of those randomised to drug therapy, 301 (27.5%) ultimately received catheter ablation.

The primary endpoint for the analysis of mortality and cardiovascular events was a composite of death, disabling stroke, serious bleeding, or cardiac arrest.

Three of the 13 pre-specified secondary endpoints were reported—all-cause mortality, total mortality or

Improvements in the secondary endpoint of mortality or cardiovascular hospitalisations are consistent with previous findings.”

Continued on page 2

PRINCIPAL STUDY INVESTIGATOR Stefan Hohnloser (Johann Wolfgang Goethe University, Frankfurt, Germany) said: “ELIMINATE-AF shows that an uninterrupted anticoagulation regimen with edoxaban 60mg QD in patients undergoing AF catheter ablation results in low rates for both thromboembolic and bleeding events. It demonstrates therefore that uninterrupted edoxban treatment represents an alternative to continuous anticoagulation with VKA in these patients.”

Catheter ablation for atrial fibrillation is the most commonly performed ablation procedure worldwide.

But complications such as stroke/transient ischaemic attack or bleeding events can occur during the procedure. Uninterrupted edoxaban therapy has been shown to reduce stroke risk, but there are no data assessing its efficacy in ablation procedures.

ELIMINATE-AF is a prospective, randomised, open label, blinded endpoint evaluation (PROBE) to assess the safety and efficacy of uninterrupted oral, once-daily edoxaban 60mg versus uninterrupted vitamin K antagonists (VKA) in patients receiving atrial fibrillation catheter ablation. Its aim was to compare descriptively the incidence of a composite efficacy endpoint of all-cause death, stroke, and major bleeding (as defined by the International Society on Thrombosis and Haemostasis [ISTH]), and to compare descriptively the incidence of the primary safety endpoint of major bleeding in patients undergoing catheter ablation for atrial fibrillation.

Continued on page 2

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CABANA finds reduced AF and better quality of life after ablation but no reduction in mortality Continued from page 1

cardiovascular hospitalisation, and recurrence of atrial fibrillation.

In the intention-to-treat analysis, which had a median follow-up of 48.5 months, the primary endpoint occurred in 8% (n=89) of patients in the ablation group compared with 9.2% (n=101) in the drug therapy group (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.65–1.15, p=0.3). For secondary endpoints, the rate of all-cause mortality was 5.2% in the ablation group compared to 6.1% in the drug therapy group (HR 0.85, 95% CI 0.6–1.21, p=0.38). Outcomes were 51.7% vs. 58.1% for death Douglas Packer or cardiovascular hospitalisation in the ablation and medical therapy groups (HR 0.83, 95% CI 0.74–0.93, p= 0.001), and 49.9% vs. 69.5% for recurrence of atrial fibrillation (HR 0.52, 95% CI 0.45–0.6, p<0.001), respectively.

Packer et al comment that improvements in the secondary endpoint of mortality or cardiovascular hospitalisation are consistent with previous findings from CASTLE-AF and other studies, and show that “ablation was associated with improved primary endpoint and mortality outcomes, providing that the ablation group patients actually received ablative therapy”. Packer explains to Cardiac Rhythm News: “When we examined the data according to the pre-specified treatment actually received, the ablation group had significantly lower rates of death, as well as the combination of death, disabling stroke, serious bleeding or cardiac arrest compared with patients who only received drug therapy. Similarly, by per-protocol analysis, ablation patients showed significantly fewer deaths or adverse events.”

The association of catheter ablation with a lower rate of recurrence of atrial fibrillation than drug therapy (50% vs. 69% at three years postblanking followup) is also consistent with previous trials. But, the investigators say: “The long-term follow-up from this trial also shows that for many patients with atrial

fibrillation, ablation is not curative.

Work is ongoing to understand whether risk factor management, with or without ablation, can reduce recurrence rates.”

And they point to the impact of crossovers and withdrawals in the trial, a combined effect that they say reduced the estimated treatment effect and the precision of the effect size estimates, as assessed by intention-to-treat.

But, in the meantime, Packer et al conclude: “Decisions about use of catheter ablation in individual patients need to consider both relative and absolute treatment differences, as well as procedural risks. For many patients meeting the eligibility criteria of this trial, expected treatment differences on an absolute scale will likely not be of sufficient magnitude to support a recommendation for catheter ablation on that basis alone.”

In the sub-study, led by Daniel Mark (Duke University, North Carolina, USA), the co-primary endpoints were quality of life at 12 months as measured on the Atrial Fibrillation Effect on Quality of Life (AFEQT) summary score, and both the Mayo AF-Specific Symptom Inventory (MAFSI) frequency and severity scores. At one year, mean scores for all three measures were more favourable in the catheter ablation group than the drug therapy group (Atrial Fibrillation Effect on Quality of Life summary score 86.4 points vs. 80.9 points, 95% CI 3.7–6.9, p < 0.001).

Mark and his co-investigators point out that, although interpretation of quality of life data can be challenging, because both of the co-primary endpoints in the study showed a mean treatment effect size for ablation that was equal to the patient-level benchmark, it implies “that a substantial proportion of patients had sizable, clinically important incremental improvements after catheter ablation relative to drug therapy”, which can “help guide decisions regarding management of atrial fibrillation”.

By perprotocol analysis, ablation patients showed significantly fewer deaths or adverse events.”

Editors-in-chief:

Editorial contribution:

Richard Schilling Ross Hunter

Jocelyn Hudson, Dawn Powell

Scientific advisor:

David Reekie, Terry Hawes and Naomi Amorra

Andreas Goette

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Stephen Greenhalgh

Head of Publishing: Sadaf Kazi

Editor:

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Eliminate-AF shows low thromboembolic and bleeding events with edoxaban Continued from page 1

All patients with AF were accepted, including those for re-ablation. They were randomised 2:1 to receive either edoxaban or VKA for at least 21 days before undergoing transoesophageal echocardiography (TEE) or intraprocedural intracardiac echocardiography (ICE), followed by ablation. Follow-up was 90 days.

The per-protocol population of 417 patients was assessed from the end of the ablation procedure to the end of treatment. Average age was 60 years, with about 70% of each group being male, and almost half had a CHA2DS2VASc score ≥2. Hohnloser described subjects as having “significant comorbidity”.

From the per-protocol analysis, the incidence of the primary endpoint was 0.3% (1/316) in the edoxaban group, and 2% (2/101) in those receiving VKAs (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.02–1.73, p=0.1315). The event rate was low and similar in both arms; most were procedure-related. All three that occurred were major bleedings (one in the edoxaban arm and two in the VKA arm), and there were no deaths in the study. Edoxaban adherence was high (>97%), and VKA treatment was well managed. Unfractionated heparin was used to maintain anticoagulation, but the amount used in the edoxaban arm was significantly higher (14IU vs. 11IU, p<0.0001).

The primary safety endpoint in the modified intention-to-treat population occurred in 2.5% (10/405) in the edoxaban group, and 1.5% (3/197) in the VKA group (HR 1.68, 95 CI 0.46–6.07).

Hohnloser pointed out: “The study was explorative, because ELIMINATE-AF was not powered to formally test superiority or noninferiority. Such a trial would have needed 3,000–4,000 patients, and was thus deemed not to be affordable.” He concluded: “The incidence of the primary endpoint in the main analysis was low.

There was one ischaemic and one haemorrhagic stroke, and both occurred in patients assigned to endoxaban. ISTH major bleeding events occurred in an incidence of 2.5% on edoxaban and 2.5% on VKA, without any statistical significant difference between the two groups. The incidence of cardiac tampenade was low and similar in both groups.”

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2019

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Phased RF ablation for AF shows efficacy and quality of life improvements

Phased radiofrequency (RF) ablation using the PVAC GOLD catheter (Medtronic) for pulmonary vein (PV) isolation in paroxysmal and persistent atrial fibrillation (AF) has demonstrated good outcomes for quality of life and 12-month efficacy. Results from the multicentre GOLD-AF registry were presented by Lucas VA Boersma (St Antonius Hospital, Amsterdam, The Netherlands) in a late-breaking trial session at the European Heart Rhythm Association congress in Lisbon, Portugal (EHRA 2019; 17–19 March).

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oersma said: “The GOLD-AF registry provides information about population, indications and outcomes using a second generation phased RF system in >1000 patients. It appears to be effective at 12 months, with 77.7% freedom from AF recurrence.

Phased RF procedure time was predictable and relatively short compared to the literature, with a low complication rate, no oesophageal fistula and a very low stroke rate.

Many patients, 70%, showed a big change in symptoms after the procedure.”

The GOLD-AF registry was a prospective, multicentre, observational and longitudinal study at 40 sites in 14 countries in Europe and Asia. The population consisted of patients with AF ≥18 years old; it included subjects with persistent AF, paroxysmal AF, and long standing persistent AF, and they had to be treated with phased RFA. The primary objective of the trial was freedom from AF recurrence between three and 12 months after the ablation procedure. Failure was defined

as cardioversion, a re-ablation, >30 seconds of AF, or ≤30 seconds of AF with symptoms. Clinical followup and arrhythmia monitoring was performed as per standard of care in each centre. Symptoms and quality of life (QoL) were assessed at 12 months.

Boersma explained: “The phased RF ablation system has been around since 2005; it was one of the first successful single shot technologies, just as the cryoballoon has been very successful in the last 15 years. Phasing means that when the RF energy is unipolar on adjacent electrodes … there is only RF energy going into the tissue between the electrode and the back patch. There is also a phase where the adjacent electrodes have bipolar energy where the current flow is actually going between electrodes, which fills the gap between adjacent electrodes, and this is considered to be an effective way to get nice long continuous lesions.”

In all, 1,071 consecutive patients with AF scheduled for a phased RFA procedure were enrolled in the registry; 1,054 had a baseline analysis, with follow-up

The procedure was considered a success in 96% of cases, and in 94% pulmonary vein isolation was confirmed.” analysis on 943 patients who had a valid 12-month form (329 from a follow-up site visit and 614 from a phone call for the quality of life analysis).

Boersma described the patient characteristics as “pretty typical”—age 60 years, 67.5% were male, with an average left atrial (LA) volume of 49ml and LA diameter of 42mm. Indications for phased RF ablation were for paroxysmal AF in 70% of patients, and persistent AF in 26% of patients, with about 3% having long standing persistent AF; most of the participants (95%) were symptomatic. Obesity was present in 27%, hypertension in 53%, and the mean CHA2DS2VASc score was 1.8±1.4, “which reflects that these were fairly healthy patients”, Boersma pointed out. For most of the subjects it was an index procedure (94.3%).

Luminize demonstrates safety and efficacy at 30 days The Luminize radiofrequency balloon catheter (Boston Scientific) is safe and effective at 30 days in the treatment of atrial fibrillation (AF), data from the AF-FICIENT I study has shown. Amin Al-Ahmad (Texas Cardiac Arrhythmia Institute, Austin, USA) presented the findings on behalf of the investigators in a late-breaking trial session at the European Heart Rhythm Association congress in Lisbon, Portugal (EHRA 2019; 17–19 March).

HE SAID: “IN the AF-FICIENT I trial, the Luminize radiofrequency catheter achieved high rates of pulmonary vein isolation, with very short total ablation times, and low rates of device-related complications. Device enhancements led to a shorter procedure time, as well as less radiofrequency applications.”

The balloon catheter uses radiofrequency energy to isolate the areas of the heart muscle responsible for the abnormal heart rhythm. The singleshot catheter also features built-in digital cameras for visual guidance, sensing electrodes on the balloon to assess realtime vein isolation and customisable

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Conference coverage

ablation electrodes with the ability to deliver tailored levels of energy around the circumference of the balloon.

The AF-FICIENT trial was a prospective, non-randomised, multicentre pilot study to assess the safety and performance of the system in isolating pulmonary veins for the treatment of paroxysmal AF. It had two phases, with phase I (n=18) testing the original design of the balloon device.

Following this stage, Al-Ahmad explained: “There were further device enhancements, based on that early experience. These enhancements included increasing steerability of

Procedure time was 107 minutes, “very similar to what we see in the other registries and trials”, according to Boersma. The procedure was considered a success by investigators in 96% (1,013/1,054) of cases, and in 94% (977/1036) PV isolation was confirmed (assessed by exit/entrance block in all PVs).

In regards to outcome data on safety at ≤30 days, procedure-related events occurred in 26/1,054. Boersma said: “Overall, we have adverse events in 2.5% of the patients. Most of them were access site complications, 1.7% [n=18]. There was a very low rate of ischaemic stroke or TIA [transient ischaemic attack], 0.3%. There were only two pericardial effusions [0.2%], and there was one late phrenic nerve injury [0.1%].”

There were no oesophageal fistulae, and no deaths.

Freedom from AF recurrence at 12-month follow-up was 77.7%, and mean time to recurrence was 185 days.

Atrial flutter was reported in 0.4% of patients, and atrial tachycardia in 0.2%.

Boersma described the analysis on quality of life measures as “very important, because that is what affects people in their daily life”. Investigators examined the improvement in AFEQT (Atrial Fibrillation Effect on Quality of Life) score between baseline and 12 months, with follow-up assessed by a phone call (n=459) or an office visit (n=199). An increase in score ≥19 was considered a meaningful improvement. Overall, the score improved by 38 for those assessed by a phone call at 12 months, and by 33 for those assessed by an office visit. Individual measures for daily activities, symptoms, treatment concern and treatment satisfaction also showed a meaningful improvement at 12 months for both phone and office follow-up (p<0.0001).

Patients with a recurrence of AF also showed a significant increase in AFEQT score between baseline and 12-month follow-up (29), although this was not as large as that seen for patients without AF recurrence (38). Average symptom improvement based on the EHRA (European Heart Rhythm Association) symptom classification for AF score changed from 2.3 at baseline to 1.5 at 12 months, with 68% of patients demonstrating improvement. A symptom severity score also showed improvements for palpitations, syncope, dizziness, irregular heartbeats, shortness of breath, and fatigue between baseline and 12 months.

the sheath, as well as addition of the electrodes on the catheter that would allow sensing of the signal.”

The phase II device was then used on a further 81 participants. The primary safety endpoint was acute safety at 30 days, and the primary performance endpoint looked at the rate of successful pulmonary vein isolation with confirmed block. Confirmation was completed with the radiofrequency balloon sensing electrodes, a circular mapping catheter, or both. The average age in both phases was 58 years, 68% were male, and 78% in phase I had paroxysmal atrial fibrillation compared to 100% of those in phase II. Al-Ahmad told delegates: “The procedure time dramatically improved after device enhancements were made, from an average of 173 minutes down to an average of 79 minutes. This reflects both the device enhancement and experience with the device. Balloon dwell time also improved dramatically, from approximately 100 minutes to 33 minutes. Fluoroscopy time improved as well with phase II enhancements.”

There were no device-related serious adverse events in either phase at 30 days post-procedure, and in patients with available cardiac imaging there were no

cases of pulmonary vein stenosis (0/32).

Successful pulmonary vein isolation was achieved in 88.9% (64/72) of veins in phase I. In phase II, pulmonary vein isolation increased to 99.4% of veins (322/324). By patient, 77.8% (14/18) of those in phase I and 97.5% (79/81) of subjects in phase II had successful isolation of all pulmonary veins. In phase I, there were 12 applications per

The Luminize radiofrequency catheter achieved high rates of pulmonary vein isolation.” patient; phase II had eight applications, approximating to two per vein.

Al-Ahmad acknowledged a limitation of the findings was the lack of longterm data looking at freedom from AF. He said: “Further data are needed to understand the time to effect, time to isolation, and how that will impact dosing, as well as freedom from arrhythmia.”

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High-power shortduration ablation for atrial fibrillation: Safety and effectiveness Andrea Natale

Domenico Della Rocca Luigi Di Biase Comment & Analysis As part of a session on novel mapping and ablation technologies of atrial fibrillation (AF) at this year's AF Symposium in Boston, USA (22–24 January), Andrea Natale gave a presentation on highpower short-duration ablation for AF, focusing on unmet needs and potential solutions. For Cardiac Rhythm News, Natale, Domenico Della Rocca and Luigi Di Biase give a summary of the key points.

ATRIAL FIBRILLATION (AF) has been described as an emerging epidemic of cardiovascular disease with significant effects on estimated disability and mortality and is rapidly turning into a major public health concern.

At the present time, 5% of the over 65 population and up to 8.8% of the population between 80–89 years of age are affected by AF. Catheter ablation is the most effective rhythm control strategy in patients with AF. Since the pivotal study by Haissaguerre et al documenting pulmonary vein (PV) triggers initiating AF, PV isolation has become the standard catheter-based ablation strategy.

Achieving durable lesion formation either to isolate the PVs or to perform other needed ablations is of utmost importance to guarantee higher arrhythmia-free survival rates.

Several factors are important to create effective radiofrequency (RF) lesions, such as the RF power, the duration of energy delivered, and the degree and stability of contact between tissue and ablation catheter.

The mechanism involved in lesion formation during higher-power, shorter-duration RF delivery is mostly through local conductive and resistive heating, which occurs early during RF application. On the contrary, distant conductive heating tissue damage is the predominant mechanism during longer RF applications.

To date, many centres prefer performing RF ablation using a power of 25–30W for durations of approximately 20–30 seconds at each point. The main concern of using higher-power RF energy for AF ablation is the potential of increasing the risk of complications.

However, the use of higher-power RF

energy delivery would result in reduced procedural and fluoroscopy times, as well as decreased total RF energy delivery, which may potentially lead to lower complication rates. Despite a common clinical apprehension, results from animal and human studies have consistently confirmed that high-power, short-duration AF ablation effectively achieves transmurality with a lower rate of complications.

In 2003, we first reported the incidence of complications and outcomes of PV isolation using a closed-loop ablation catheter and guided by circular mapping (CM) alone (Group 1), CM and intracardiac echocardiography (ICE; Group 2), and CM and ICE with titration

Atrial fibrillation formation and adjust power delivery based on objective findings. This was the first study to observe that higher power delivery improves outcomes, as a result of more durable lesions, and significantly reduces the risk of PV stenosis, without increasing the incidence of periprocedural thromboembolic events.

Subsequently, with the introduction of open irrigation catheters, the microbubble power titration technique became no longer feasible. Therefore, in 2007 we designed a study2 which randomised AF patients to an ablation strategy using an open irrigation catheter (OIC) with a higher peak power (50W, Group OIC-1) or OIC with lower peak power (35W; Group OIC-2).

Although freedom from atrial arrhythmias was significantly higher in Group OIC-1 at six months, the main findings of our study were a higher incidence of steam pops, pericardial effusions, and gastrointestinal complaints when using an OIC at 50W compared to 35W without shortening the duration of RF energy delivery. These observations first supported the need for a shorter duration and a power of 45­–50W, in order to avoid complications.

Similar findings were confirmed in animal models. Goyal et al reported that the ablation time required to achieve 4mm lesion depth decreases with increasing power;3 therefore, effective lesions can be achieved via high-power and short-duration RF applications, which could effectively reduce procedural time and concentrate the heating to superficial depths potentially reducing collateral injury.

Bjaskaran et al observed in an ovine model that steam pops occurred in the settings of 40W/30 seconds and 80W/five seconds in eight and 11% of ablations, respectively;4 conversely, complications were absent in short-duration ablations of 50W and 60W. Achieving effective lesions via high-power RF applications for short duration is not only associated with better outcomes and low complication rates; this strategy also allows for shorter

Results from animal and human studies consistently confirm that high-power short-duration ablation effectively achieves transmurality with a lower rate of complications.” of RF energy based on visualisation of microbubbles by ICE (Group 3).

In Group 3, power was titrated upward (5W increments), watching for formation of type 1 bubbles (scattered microbubble reflecting early tissue overheating).

When the type 1 microbubble pattern was seen, energy was titrated down by 5W decrements until microbubble generation subsided. Energy delivery was terminated when type 2 bubbles (brisk shower of dense microbubbles reflecting impending impedance rise) were seen. Monitoring microbubble generation to guide energy delivery allowed us to optimise lesion

procedures and lower X-ray exposure.

As an example, Nilsson et al observed a reduction in PV isolation time, mean fluoroscopy time, radiation dose, and total RF application time among patients undergoing ablations using 45W/20 seconds compared to 30W/120 seconds, whereas complication rate was similar.5 A recent article published in Heart Rhythm analysed the complication rates of four experienced centres (including our institute) performing AF ablations using irrigated-tip RF at power of 45–50W in the left atrium for 5–15 seconds per lesion.6 The study included

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procedural data of 13,974 ablations in 10,284 patients, 99.2% of whom used oesophageal temperature monitoring. On the posterior wall, 11,436 ablations used 45–50W for 2–10 seconds, and 2,538 ablations had power reduced to 35W applied for 20 seconds.

The average procedural, fluoroscopy and RF times were 116±41 minutes, 33±6 minutes and 39±30 minutes, respectively.

Overall, 33 cases (0.24%) of pericardial tamponade occurred and seven of them required surgical intervention. Among the seven patients who required surgery, two had left atrial perforations that were likely due to RF energy delivery, three did not seem to be related to ablation (one coronary artery tear, one coronary sinus tear from a diagnostic catheter, and one right atrial perforation), whereas the site of bleeding could not be determined in the remaining two patients since haemostasis was achieved by the time the chest was opened. The incidence of left atrial steam pops was 0.014%, and catheter char was not observed in any ablations.

Four patients developed atroesophageal fistula: one case occurred in 11,436 ablations (0.0087%) performed using 45–50W power for short durations on the posterior wall, and three occurred in the 2,538 patients (0.12%) ablated with 35W on the posterior wall for longer durations (p=0.021). Of note, two of the three patients who developed a fistula in the 35W group had not undergone oesophageal temperature monitoring during a fluoroless procedure.

In conclusion, AF ablations performed at 45–50W for short durations appear effective and are associated with very low complication rates. High-power and short-duration RF applications allow the creation of more localised and durable lesions, thereby limiting collateral injury, and may effectively reduce procedural and fluoroscopy times.

References.

1. Marrouche NF, Martin DO, Wazni O, et al. Phased-array intracardiac echocardiography monitoring during pulmonary vein isolation in patients with atrial fibrillation: impact on outcome and complications. Circulation 2003; 107(21): 2710-6.

2. Kanj MH, Wazni O, Fahmy T, et al. Pulmonary vein antral isolation using an open irrigation ablation catheter for the treatment of atrial fibrillation. J Am Coll Cardiol 2007; 49: 1634–41.

3. Goyal V, Ali-Ahmed F, Patel M, et al. Low flow, high power, short ablation duration—is this the key to avoid collateral damage? Heart Rhythm 2017; 14(Suppl): S464.

4. Bhaskaran A, Chik W, Pouliopoulos J, et al. Five seconds of 50-60 W radio frequency atrial ablations were transmural and safe: an in vitro mechanistic assessment and force-controlled in vivo validation. Europace 2017; 19(5): 874-80.

5. Nilsson B, Chen X, Pehrson S, Svendsen JH. The effectiveness of a high output/short duration radiofrequency current application technique in a segmental pulmonary vein isolation of atrial fibrillation. Europace 2006; 8: 962–5.

6. Winkle RA, Mohanty S, Patrawala RA, et al. Low complication rates using high power (45-50 W) for short duration for atrial fibrillation ablations. Heart Rhythm 2019; 16(2): 165-9.

Andrea Natale is the executive medical director at the Texas Cardiac Arrhythmia Institute at St. David’s Medical Center in Austin, USA. Domenico Giovanni Della Rocca is an electrophysiology fellow at St David's Medical Centre.

Luigi Di Biase is the section head of electrophysiology, director of arrythmia services, and professor of medicine at the Albert Einstein College of Medicine, New York, USA.

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Advertorial

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“The risks are greatly reduced”

According to Dr. Sanfins, extended battery life is one of the key benefits of Rivacor devices for both patient and practitioner. Rivacor ICDs have a battery life of up to 15 years.7 This longevity means that fewer box replacements are likely to be needed, meaning fewer procedures for patients, potentially reducing risks, complications and costs.

Dr. Sanfins tells Cardiac Rhythm News that “battery life is very important for physicians and patients because you can reduce the number of interventions.

The risk of infection doubles at any intervention and so if you can reduce the number of interventions, you will have a lower risk of infection overall.”

He goes on to say that battery longevity also decreases the cost of therapy, as fewer devices will be needed during the lifetime of the patient.

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QuickCheck gives access to patient data typically within three to four minutes for more efficient treatment and greater piece of mind for patients.

Dr. Sanfins details a number of Home Monitoring benefits, a feature currently used by around 1,000 patients at his hospital. He comments, “Home

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Monitoring reduces many risks, as we can only give medication─in particular to prevent stroke─when we know that AF exists. Remote monitoring, which includes BIOTRONIK Home

Monitoring, reduces mortality because, for example, with the 'Heart Failure Monitor' physicians can detect an increasing amount of liquid in the lungs, which is a sign of cardiac decompensation. You can detect this before the patient exhibits any clinical symptoms and you can then call the patient in and prescribe the right medication. This can help to prevent major complications.”

“We can intervene very quickly”

Dr. Sanfins says Rivacor devices allow physicians to trigger the collection of information remotely, thanks to the QuickCheck feature. “In case of a symptomatic event, we can get feedback from the device almost immediately and therefore intervene very quickly if needed, which is crucial for optimal patient care.”

The final feature Dr. Sanfins highlights is ProMRI. All Rivacor devices feature ProMRI, which gives patients full and uncompromised access to 3T MRI with full body-scanning and no exclusion zone. MRI AutoDetect senses MRI environments and selfadjusts, suspending tachycardia therapy for the duration of the scan only. This can be activated with a single visit to the physician and has a 14-day window for planning. Dr. Sanfins tells this paper this is a very important feature of Rivacor devices.

“With great advances in highresolution imaging with 3T MRI, patients are undergoing MRI scans at an increasing rate. Consequently, there is a greater burden on clinics that have to re-program ICD and CRT-D devices before and after patients go in for MRI scans. With MRI AutoDetect, we can cut down on some of these re-programming steps, ensuring optimal therapy for the maximum amount of time, while also reducing the burden on patients, cardiologists and radiologists.” * Acticor/Rivacor is the new generation of ICDs and CRT-Ds from BIOTRONIK, recently launched in Europe, in the USA and in Japan. Devices brands and models available may vary from one country to the other. In this interview, Dr. Victor Sanfins is referring to Rivacor ICDs and CRT-Ds, which are the devices commercialised in Portugal.

1. Post-Market observation; final-report, March 1, 2019.

Data on file.

2. Device shape analysis, February 2019. Data on file.

3. Post-Market observation; final-report, March 1, 2019.

Data on file.

4. As part of an MR conditional system.

5. QP models only.

6. Post-Market observation; final-report, March 1, 2019.

Data on file.

7. Acticor/Rivacor VR-T Standard conditions. 15.4 years @ 40 ppm; 0% pacing @ 2.5V/0.4ms; 500 Ohms; 2 max. energy shock/year. Data on file.

8. Hindricks G et al. Lancet. 2014, 384(9943).

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Atrial fibrillation

Cryoablation at ultra-low temperatures successful and safe in AF treatment

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Late-breaking trial results from Cryocure II suggest a role for ultra-low temperature cryoablation, demonstrating its safety and efficacy in the treatment of atrial fibrillation (AF). The findings were presented at the AF Symposium (24–26 January, Boston, USA) by investigator Tom de Potter (Cardiovascular Centre, OLV Hospital, Aalst, Belgium): “Our clinical results demonstrate an excellent safety profile so far, particularly after the implementation of phrenic nerve cryomapping, and […] a high success rate performing wide antral pulmonary vein [PV] isolation. And […] we have shown it to be able to perform in linear and focal lesions with the same single shot system.”

CRYOCURE II IS a prospective observational study in which 48 patients with both paroxysmal and persistent AF have so far been enrolled in two centres in Belgium and The Netherlands. Investigators used multiple catheter designs, changing to new models as they were developed, with 3D mapping “allowed but not mandatory”.

De Potter explains: “Ultra-low temperature cryoablation is a system that allows you to harness the energy delivery capability of liquid nitrogen in a percutaneous system by hyper-pressurising the gas, which means […] a theoretical minimal temperature limit of minus 196 degrees Celsius, substantially lower than existing cryo systems.”

The design consists of a linear catheter, with a stylet inserted to shape it. The freezing section contains 20 electrodes, and is enhanced by a non-freezing distal section which allows real-time electrograms to be monitored during ablation. “We can achieve PV isolation and ablate any other atrial target, because the style t allows us unlimited flexibility. Crucially, this is a single shot system; it is not only suited to performing PV isolation, it is also perfectly adapted to performing, for example, linear lesions, focal ablations, and any type of area ablation you might choose to do.”

Researchers carried out a wide antral PV isolation, with posterior box isolation also performed in patient with persistent AF. Additional optional lesions were linear cavo-tricuspid ablation and mitral isthmus ablation, at the discretion of the operator. PV isolation was confirmed 30 minutes post-ablation, with Holter monitoring at three, six, and 12 months; 12 months monitoring was by a seven-day Holter.

Smart watch can identify undetected fibrillation An app on a smart watch can be used to detect atrial fibrillation, providing a boost for the role of digital technology in healthcare.

M

intu Turakhia and Marco Perez (Stanford University School of Medicine, USA) presented the findings from the Apple Heart Study at the American College of Cardiology’s 68th Annual Scientific Session (ACC 2019; 16–18 March, New Orleans, USA).

They said: “The notification positive predictive value of 0.84 supports the ability of the app to correctly identify atrial fibrillation among those notified, and these findings may inform further clinical evaluation after notification.”

The Apple Heart Study was a

The initial 13 patients were treated with the first generation device and were analysed for safety only, as part of the safety assessment cohort. The efficacy analysis was initiated when the second generation catheter came on stream, and consisted of the remaining 35 patients. Of these, 10 patients had paroxysmal AF and 25 had persistent AF. Average age in the efficacy analysis was 65 years, and subjects were mainly male.

“Average left atrial dimensions of the patients and incidence of potential comorbidities […] is in line with published evidence,” says de Potter.

Cryocure II demonstrated a high degree of efficacy, with PV isolation achieved in 96% of patients.”

Cryocure II demonstrated a high degree of efficacy, with PV isolation achieved in 96% of patients. Posterior wall ablation was accomplished in all 11 patients in whom it was attempted and a tricuspid isthmus block in 12/12. Mitral isthmus ablation succeeded in two out of three attempts.

The safety analysis identified one patient with a peripheral access injury that was procedure not devicerelated, and two patients with phrenic nerve palsy; these were both transient and subjects recovered.

“Importantly, [they were] part of our early experience with the generation one device, at which point we had

prospective, single arm, pragmatic study of the ability of the watch’s irregular pulse notification system to identify atrial fibrillation (AF), and measure the rate of initial contact with a healthcare provider.

Inclusion criteria were age ≥22 years, and possession of an iPhone 5s or higher, as well as an Apple watch series 1–3. Those currently using anticoagulation, or with AF or an atrial flutter were excluded from the final analysis.

The watch operates using optical sensors that detect pulse waveforms passively to measure heart rate. Atrial fibrillation is identified by the detection of pulse irregularity. Following five confirmations of an algorithm that is suggestive of atrial fibrillation, the user is notified. Participants who received a notification based on the algorithm were advised to consult a telehealth doctor, following which they were either referred to urgent care or sent an electrocardiogram (ECG) patch for further monitoring. The results from the patch were reviewed by a telehealth doctor, with 90-day follow-up survey.

Primary and secondary endpoints were measured for those who received notifications. The primary endpoint was AF >30 seconds as measured on the ECG patch for patients who received an irregular pulse watch notification. A

not yet implemented cryomapping,” clarifies de Potter.

“Since implementing cryomapping—ramping down the temperature gradually—we did not see any new phrenic nerve palsies, and we did not see any serious intracardiac adverse events.”

On average, it took 11.6 minutes to isolate the four veins and for full PV isolation, with a total procedure time of 160 minutes, including a 30-minute waiting time after isolation. “And, interestingly, because we used the same catheter,” he adds, “if we choose to do additional lesions, the additional time needed to perform, for example, posterior wall and/or cavo-tricuspid isthmus or mitral isthmus ablation is quite small–the additional ablation time is on average three minutes, the additional procedure time needed to perform these additional lesions is 10 minutes.”

All of the 10 patients in the paroxysmal cohort have ceased anti-arrhythmic medication and remain free of AF—of these, four are at the 12-month follow-up stage and five have progressed beyond six-month follow-up.

One of the 25 subjects with persistent AF had an immediate recurrence, and 18 have had no additional recurrences at six months, an efficacy rate of 94%, and are also off anti-arrhythmic medication. Nine patients have reached 12-month follow-up, with one more suffering a recurrence of atrial tachycardia, rather than AF: “At 12 months, we have an efficacy of eight out of nine patients free of AF, seven out of nine patients free of any atrial arrhythmia. [These are] very promising success rates in our cohort. Far larger trials, which we feel we should at least be benchmarking against […] published an efficacy of 50–65% in persistent AF,” says de Potter.

co-primary endpoint was simultaneous atrial fibrillation on ECG patch and when the spot tachogram was positive for an irregular pulse among those who received a notification. Secondary endpoints were simultaneous atrial fibrillation on ECG patch with notification based on multiple tachograms and self-reported contact with a health care provider within three months following an irregular pulse watch notification.

The study had an enrolment goal of up to 500,000, with the assumption of 503 patches for each group among those aged ≥65 and those <65 years. It was designed to have sufficient provision to estimate the yield of atrial fibrillation on subsequent ECG patch with 97.5% confidence intervals (CI) no wider than 10% in age ≥65 and <65, and to have sufficient provision to estimate the positive predictive value (PPV) of an individual tachogram with a simultaneous ECG patch—97.5% CI lower bound >0.70 and upper bound ≥0.75.

Enrolment was from November 2017 to July 2018; 419,297 participants entered the study; 2,161 (0.5%) received a pulse notification, and 945 (44%) took part in a study visit. Following exclusions, an ECG patch was sent to 70% (n=658), of whom 68% (n=450) returned it for analysis. Mean age of those whose patch

was analysed was 59 years, and 23% were female; 38% had a CHA2DS2VASc score ≥2, 44% had hypertension, and 43% had obesity. The mean time to hook up of the patches analysed was 13 days, and mean wear time 6.3 days. The AF yield was 34% (97.5 CI 29–39). The PPV of irregular tachograms was 0.71 (97.5% CI 0.69–0.74), and PPV of irregular pulse notifications was 0.84 (95% CI 0.76–0.92).

Among those who received a pulse notification, 1,376 (64%) completed a 90day survey, and 161 (15%) had AF before enrolment; 787 (57%) contacted a nonstudy healthcare provider—218 (28%) started new medication, 262 (33%) were referred to a specialist, and 287 (36%) underwent further testing. There were 71 serious adverse events in the entire cohort of 419,297, none related to the app.

Turakhia and Perez pointed to the study's limitations, including a failure to achieve the pre-specified precision of the co-primary endpoints, and the virtual study design, which meant participants self-assessed for enrolment and selfreported outcomes.

However, they highlighted the operational success of the study, and the low rates of pulse notification across a diverse population, as well as the safety of the app.

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Interview

Profile

Charles Antzelevitch Charles Antzelevitch is professor and executive director of the Cardiovascular Research Program at the Lankenau Institute for Medical Research in Pennsylvania, and professor of Medicine and Pharmacology and Experimental Therapeutics at Sidney Kimmel Medical College in Philadelphia, Pennsylvania. He tells Cardiac Rhythm News about his extensive contribution to electrophysiology, and its impact on everyday practice, and shares his thoughts on future priorities for research in the field.

Why did you decide to become a doctor, and why did you choose to specialise in cardiac electrophysiology?

I was intent on becoming a scientist since early childhood, always curious as to how things worked.

Initially, I studied to be a biochemist, but switched to cardiac electrophysiology after visiting an electrophysiology lab and being mesmerised by the electrocardiographic signals bouncing up and down on the oscilloscope screen.

Who were the biggest influences on your early career?

My mentor, Gordon K Moe, one of the fathers of cellular electrophysiology and the director of research at the Masonic Medical Research Laboratory (MMRL), was the biggest influence in my early career. He recruited me to his research laboratory in Utica, New York, in 1977.

I agreed to come for a two-year postdoctoral fellowship and wound up staying 37 years, taking over as the director of the institute upon his retirement in 1984.

What has been the biggest development in electrophysiology during your career?

The past 40 years have witnessed numerous incredible advances in electrophysiology. The most meaningful and exciting for me are the advances in molecular genetics, which opened the floodgates of knowledge, permitting us to peer into mechanisms of cardiac function in health and disease that were previously out of view.

What has been the biggest disappointment in electrophysiology— an advance that you hoped would change practice, but failed to do so?

My biggest disappointment is that having demonstrated the remarkable efficacy of the combination of ranolazine and dronedarone in producing atrial-selective inhibition of sodium channel activity, thus very effectively suppressing the development of atrial fibrillation (AF), big pharma failed to move forward with it. Despite a very successful phase II clinical trial called Harmony, the drug combination was not advanced to phase III. There remains a dire need for a safe and effective pharmacological agent to combat atrial fibrillation.

You have extensive experience in the area—what do you consider to be the key unanswered questions?

Despite tremendous progress in recent years, we continue to lack full understanding of the mechanisms underlying the development of many forms of cardiac arrhythmia. It is unfortunate that the National Institutes of Health (NIH) funding needed to delve more deeply into this and many other medical problems is so woefully inadequate.

You have performed a lot of research on sudden cardiac death—what have been your key findings?

My contributions, and that of my tremendously talented

team members, to the scientific literature include >550 original papers and reviews, and seven books. A major achievement includes the discovery and characterisation of reflected reentry, phase II re-entry, and late phase III early afterdepoliarisations (EADs) as mechanisms of extrasystolic activity capable of precipitating life-threatening ventricular tachycardia and fibrillation. We have also performed pioneering work demonstrating electrical heterogeneity within ventricular myocardium, particularly transmural dispersion of repolarisation and discovery of a unique population of cells, that we named M cells, opening new doors to our understanding of electrophysiology and pharmacology of the heart and arrhythmogenic mechanisms. Other findings include delineation of the cellular and ionic basis for the long QT, Brugada, and short QT syndromes, as well as catecholaminergic ventricular tachycardia (VT), and design of novel approaches to therapy of these syndromes. We have worked on the cellular and ionic basis for the J wave and T wave of the electrocardiograph (ECG), uncovered the genetic basis for Brugada, short QT, long QT, and early repolarisation syndromes, and designed novel therapeutic modalities. Additionally, we discovered a novel therapy for atrial fibrillation using atrial-selective sodium channel blockers, and novel therapeutic approaches for the Brugada and early repolarisation syndromes.

We continue to lack full understanding of the mechanisms underlying the development of many forms of cardiac arrhythmia.”

Which of these has had the biggest impact on daily practice?

Our team has a long history of involvement and interest in the Brugada and early repolarisation syndromes.

The product of this work has contributed to the daily practice of medicine. We suggested the use of quinidine to prevent sudden death associated with these syndromes in 1999, which is today used all over the world. A few years later, we suggested the use of quinidine for short QT syndrome, which is widely used as well. We were among the first to coin the term J wave syndromes to encompass both of these sudden death syndromes. In 2004, we convened a consensus conference in upstate New York, from which emanated the second expert consensus conference report dealing

with Brugada syndrome (Antzelevitch et al, Circulation and Heart Rhythm, 2005) as well as the first book dedicated to Brugada syndrome. In 2015, Gan-Xin Yan and I convened another consensus conference in Shanghai, China, from which emanated the first expert consensus statement dealing with the J wave syndromes (Antzelevitch et al, Heart Rhythm, Europace-EP, and Journal of Arrhythmia, 2016), and the first book dedicated to the J wave syndromes.

What are your current research interests?

Our current focus continues to be defining the genetic basis for inherited cardiac arrhythmia syndromes, and developing novel therapeutic approaches to treat cardiac

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Fact File

The most important paper published in this field in the past couple of years from the clinical perspective is probably the 2017 American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Rhythm Society (HRS) guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death,

by Al-Khatib et al (Circulation 2018; 138 (13): e272–e391).

What are the key priorities for future research in this area?

To better understand the mechanisms underlying channelopathies and cardiomyopathies, which will hopefully guide us to innovative approaches to therapy.

What is the value in this online age of attending conferences?

Didactic sessions are valuable but the one-on-one, face-to-face sidebars are invaluable.

What advice would you give to someone who was starting out in cardiovascular medicine?

arrhythmias, including atrial fibrillation and inherited cardiac arrhythmia syndromes. In the realm of cardiooncology, we are working to better understand why and how agents effective in fighting cancer produce cardiac arrhythmias, and how this can be prevented.

Taking advantage of the many valuable resources at the Lankenau Institute for Medical Research, we are working to better understand the electrophysiology of cancer, and how the electrical activity of cancer cells can be manipulated to treat the disease and ultimately effect a cure.

What do you consider to be the most important paper published on this topic in the past year?

A career in biomedical research is among the most intellectually stimulating and fulfilling that you can pursue. Be aware that pursuing such a career is today more difficult than ever before, because of the difficulty in obtaining grant support. However, if you have a thirst for knowledge and an insatiable curiosity about how things work, biomedical science offers an exciting challenge that promises to be rewarded by the thrill of discovery, which will more than offset the difficulties you will likely encounter in your scientific career. Do not be afraid to take the plunge.

What was your childhood dream job?

What I am doing now.

What are your hobbies and interests outside of medicine?

I enjoy hiking, swimming, biking, making music and, most of all, spending time with the grandkids.

Current appointments

Professor and executive director of the Cardiovascular Research Program, Lankenau Institute for Medical Research, Wynnewood, Pennsylvania Director of research, Lankenau Heart Institute, Wynnewood, Pennsylvania Professor of Medicine and Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania

Medical training (selected)

2017: Professor of Medicine and Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College 2015: Professor and executive director of the Cardiovascular Research Program, Lankenau Institute for Medical Research, and director of research, Lankenau Heart Institute 1995–2016: Professor of Pharmacology, SUNY Health Science Center, Syracuse, New York 1987–2015: Gordon K Moe Scholar, chair in experimental cardiology, Masonic Medical Research Laboratory 1984–2015: Executive director and director of research, Masonic Medical Research Laboratory 1986–1995: Research professor, Pharmacology Department, SUNY Health Science Center 1977: Postdoctoral fellow, Experimental Cardiology Department, Masonic Medical Research Laboratory, Utica, New York

Professional and academic honours

1996–1998: President, International Cardiac Electrophysiology Society 1998–present: Secretary/treasurer, International Cardiac Electrophysiology Society 2002: Distinguished Scientist Award, North American Society of Pacing and Electrophysiology (NASPE, currently Heart Rhythm Society) 2003: Excellence in Cardiovascular Science Award. NE Affiliate American Heart Association 2007: Carl J Wiggers Award, American Physiological Society 2011: Distinguished Scientist Award, American College of Cardiology 2015: Distinguished Service Award, Cardiac Electrophysiology Society 2016: Douglas P Zipes Lecture Award, Heart Rhythm Society

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Image-guided lead placement shows no improvement in response to CRT for patients with ischaemic cardiomyopathy Targeting left ventricular (LV) lead placement using speckle tracking radial strain imaging (STRSI) did not lead to an improved response rate to cardiac resynchronisation therapy (CRT), according to findings from the RAISE CRT trial. Michael Glikson (Shaare Zedek Medical Center, Jerusalem, Israel) presented the findings on behalf of the study investigators at a late-breaking trial session at the European Heart Rhythm Association (EHRA 2019; 17–19 March) congress in Lisbon, Portugal.

G

likson told the conference that a tendency to higher early event rates in the treatment group could be related to failure to place the lead at the recommended segment in 41% of cases, and that leads successfully placed at the best segments resulted in a trend towards improvement of the response.

About 30% of guideline-based candidates for cardiac resynchronisation therapy fail to respond to treatment, with higher rates among patients with ischaemic cardiomyopathy. Potential causes include positioning of the left ventricular (LV) lead away from the latest activated segment, or pacing within a scar.

Glikson informed delegates: “Speckle tracking radial strain imaging enables targeting of the LV lead to the latest contracting segment, away from scars, and this has been shown by several retrospective as well as prospective studies.”

RAISE CRT was a randomised controlled multicentre trial to evaluate whether targeting by STRSI improved the response rate to CRT in a real-life setting in patients with ischaemic cardiomyopathy. Participants consisted of 172 patients with ischaemic cardiomyopathy with guideline-based indications for cardiac resynchronisation therapy-defibrillators (CRTD). They were randomised 2:1 into treatment or control groups

in nine Israeli centres and the Mayo Clinic (Rochester, USA); in the treatment group placement of the lead was guided to segments of latest contraction that lacked significant scar by STRSI. Operators were instructed to target the lead to the latest scar free segment, and basal or mid positions were encouraged. Operators in the control group were blinded to the imaging results.

Follow-up was at six and 12 months, with clinical assessment, ECG, six-minute walk test, Minnesota Living with Heart Failure (MHLF) questionnaire, global clinical self-assessment, echocardiogram (at six months only), and device interrogation. The primary endpoint was the percentage reduction of left ventricular end-systolic volume (LVESV) at six months; secondary endpoints included a combined clinical event rate of death or heart failure hospitalisation, and rates of >15% improvement in LVESV, >5% improvement in ejection fraction, 10-point improvement in MLHF questionnaire, or 10-point improvement in six-minute walk test. The primary analysis was performed on an intention-to-treat basis, with a secondary analysis on the achieved lead location, irrespective of group.

Baseline characteristics in the groups were “very similar” said Glikson, drawing attention to the “vast majority” of males in the study (imaging-guided

Randomised controlled trial finds that efficacy is not compromised by using a shorter cryoapplication duration In a late-breaking session at the European Heart Rhythm Association annual congress (EHRA; 17–19 March, Lisbon, Portugal), Jason Andrade of Vancouver, Canada presented the results of the CIRCA-DOSE study, a randomised clinical trial designed to evaluate the safety and efficacy of second-generation cryoablation versus contact-force irrigated radiofrequency catheter ablation for atrial fibrillation, as well as short (two-minute) versus standard (four-minute) cryoapplication exposure.

ANDRADE PRESENTED THE conclusion that pulmonary vein isolation performed by advanced generation cryoballoon or by contact-force guided radiofrequncy results in comparable freedom from recurrent atrial arrhythmia.

In addition, he noted the “stark contrast” between the primary endpoint, defined as time to first event, and the reduction in atrial fibrillation burden, which “highlights the need to reappraise the optimal atrial fibrillation ablation study endpoint.” His final conclusion was that efficacy is not compromised by using a shorter cryoablation duration.

Freedom from any atrial tachyarrhythmia (atrial fibrillation [AF], atrial flutter [AFL], or atrial

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EHRA 2019

tachycardia [AT]) after a single ablation procedure—the primary outcome of the study—revealed comparable event-free survival rates between contact-force guided radiofrequency (CF-RF; 53.9%), four-minute cryoapplication (CRYO-4; 52.2%) and two-minute cryoapplication (CRYO-2; 51.7%).

A similar trend was apparent with regards to freedom from symptomatic tachyarrhythmia (AF, AFL, or AT) after a single procedure, with an event-free survival rate of 79.1% in both the CF-RF and CRYO-4 groups, and 73.3% in the CRYO-2 group. Speaking to Cardiac Rhythm News, Andrade highlights that the symptomatic AF endpoint is the usual endpoint for AF trials such as

group 96% [105/109], control group 94% [50/53]) “mainly because we concentrated on ischaemic cardiomyopathy”. The rate of success of implantation was 94% in both groups. Glikson pointed out: “Procedure complications were somewhat higher in the treatment group [four vs. one for the control group] but insignificantly so. And the 30-day severe adverse events was somewhat more common in the treatment group [11.9% vs. 3.8% for controls] but again with no statistical significance.”

There was no statistically significant difference between groups for the primary endpoint of a decrease in LVESV (17.4% in the treatment group vs. 16.6% among controls), and differences on secondary endpoints were also not statistically significant. There was a tendency to an increased rate of events in the treatment group on the combined outcome of death or congestive heart failure hospitalisations, which reached statistical significance at three months. Achievement of the best segment for the LV lead location was 59% in the treatment group and 46% in control subjects (p=0.198). An analysis of results by location to best segment showed that the percentage change in LVESV was “somewhat higher” in those who achieved the best segment. At 19.7% in the treatment arm and 13.3% in the control group “it was not significant [p<0.099], but there was a clear trend. There was also a trend towards better Minnesota Living with Heart Failure in those who reached the best position compared to those who did not reach the best position, again with borderline significance.” Overall, there was an insignificant trend towards better results when leads were placed at the best segment, irrespective of treatment group.

For the future, Glikson said: “The study was not powered to detect the effect of only those LV leads that were successfully placed in the desired position. Better techniques to achieve the exact recommended positions of leads should be explored to prove or disprove the value of imaging guided implantation.”

THERMOCOOL AF, STOP-AF, and SMART-AF. “In that regard,” he says, “the freedom from recurrent arrhythmia was greater than that observed with contemporary trials highlighting the efficacy of model ablation technologies and techniques.”

The trial was conducted in eight centres across Canada, involving 353 patients.

At a median of 73 days days prior to ablation, 353 patients were implanted with Reveal LINQ to determine baseline AF burden. Six patients did not undergo ablation and one patient was withdrawn.

At 7–14 days prior to ablation, 346

Freedom from recurrent arrhythmia was greater than that observed with contemporary trials.” patients were randomised to three different study groups: a CF-RF group (115 patients), a CRYO-4 group (115 patients) and a CRYO-2 group (116 patients).

In the CF-RF group, 115 patients completed the study, with only one protocol violation and zero deaths, withdrawals or patients lost to followup. In the CRYO-4 group, 114 patients

completed the study, with one protocol violation, one withdrawal, and zero deaths or losses to follow-up. In the CRYO-2 group, 114 patients completed the study, one patient died and one withdrew from the study. There were no protocol violations or patients lost to follow-up.

The primary endpoint was the time to first recurrence of any (symptomatic or asymptomatic) atrial tachyarrhythmia (AF, AFL, or AT) between days 91 and 365 post ablation, or a repeat ablation procedure between days zero and 365 post ablation. The endpoint of any AF after a single ablation procedure was chosen because the investigators were performing a comparative technology evaluation. Key secondary endpoints were time to first recurrence of symptomatic atrial tachyarrhythmia between 91 and 365 days after ablation, arrhythmia burden, the proportion of patients requiring a repeat ablation procedure due to documented recurrence of symptomatic AF/AFL/AT and serious periprocedural complications.

Average age of the patients in the three groups was similar, as was the number of men, CHA2DS2-VASc scores, left atrial sizes, measured in the parasternal long axis, and left atrial volume sizes.

Andrade emphasises that the patients are reflective of clinical practice, with highly symptomatic paroxysmal AF (66% with CCS-SAF score of 3 or 4), having failed multiple antiarrhythmic drugs (median two), and having experienced multiple AF episodes per month (median four).

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We need to embrace digital education and adapt it to improve patient care— reflections from the European Society of Cardiology Xavier Rosselló Dipak Kotecha Comment & Analysis Recent years have seen many advances in education for cardiologists, but little attention has been paid to the impact of new technologies, particularly digital platforms and social networking. Digital education is evolving so rapidly that most patients, clinicians, and institutions have had little time to digest the changes. The 5th European Society of Cardiology (ESC) Education Conference, held at the European Heart House in Sophia Antipolis (France) in 2018, addressed the challenges and opportunities in training digital cardiologists. In this commentary, Xavier Rosselló and Dipak Kotecha look at the what the ESC is doing to embrace digital education.

THE ESC IS a not-for-profit professional organisation representing 57 countries, and the annual education conference brings together national directors of training with youth and patient representatives. The main

outcomes of the conference have been summarised at https://doi.org/10.1093/ eurheartj/ehy884, reflecting on six domains: social media, apps, online resources, remote assessment, educating patients and defining reliable information.

Major challenges identified in social media were the digital divide between younger and older professionals, and the inability to control some social media content. However, the highly interactive nature of these resources can facilitate scientific exchange of knowledge, and provide a broad dissemination of educational material.

Mobile applications are frequently used at a patient’s bedside (for example, to calculate risk scores) and for “onthe-job” education, although finding reliable content that is up-to-date can be tricky, and privacy and confidentiality present further difficulties. But, there is potential to develop multitasking apps for real-time collaboration to enhance professional discussions, and to produce patient-tailored content to enhance selfcare and adherence to therapy.

The use of online resources, web-based education, and clinical case galleries is limited by time constraints, and by the difficulty of finding high quality content. This provides an opportunity for an agency such as the ESC to provide unbiased educational content (in contrast to industry supported learning), assist in continued e-learning, and promote “micro-learning” to improve basic skills.

Remote assessment is still developing in many countries across the ESC, and is hampered by a lack of homogeneous structured learning programmes across countries. However, there is now evidence of a greater acceptance of the need for curricula that can transcend national borders (https://doi.org/10.1093/ eurheartj/ehy058).

Educating patients through digital means has many potential advantages—it

Editors-in-chief of major cardiovascular journals claim medical misinformation puts “lives at stake” The editors-in-chief of major cardiovascular journals—of both US and European societies— have come together to “sound the alarm” about the dangers of medical misinformation that has been disseminated through the internet, social media, and other platforms. They claim that this misinformation is dangerous because it leads to patients’ refusing medication, such as statins, that have documented life-saving benefits.

J

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oseph A Hill (Department of Medicine, University of Texas, Southwestern Medical Center, Dallas, USA) and others write in Circulation and in several other international cardiovascular journals that medical misinformation “hyped through the internet, television, chat rooms, and social media” has caused many patients to think that the risks of statins are far worse than they actually are and, as a result, refuse to take the drugs.“Most patients do not recognise that the benefits of statin use are invisible (‘I didn’t have a heart attack or stroke this past year’) whereas the small and typically reversible risks (for example, muscle pain) are readily apparent,” they add. The authors note that patients rejecting statins is just one example of the effects of medical misinformation, and that another is parents not letting their children be vaccinated following an infamous—and now widely discredited—paper that linked autism to the MMR vaccine.

Furthermore, Hill et al say that some celebrities, actors, activists, and politicians promote false or misleading medical ideas and claim “not uncommonly” there are people acting with “purely venal motives”.

According to Hill et al, “the strident alarms” by wellknown people “speaking in absolute terms” exacerbate the problem of medical misinformation because their words resonate better with the general public than the “nuanced voices” of scientists. The authors state that scientists “appropriately couch their statements in statistical terms, which may come across to the public as equivocation”.

Hill et al, therefore, have written their editorial to “sound the alarms that human lives are at stake” and call on the media to “do a better job” at avoiding sharing medical misinformation. “It is unacceptable to posit

Patients rejecting statins is one example of the effects of medical misinformation.”

can improve shared care approaches and make clinical practice more patientcentred. There is still much to be done in this field, and the ESC is moving swiftly forward with patient forums and committee representation, as well as specific projects in cardiovascular diseases, such as atrial fibrillation (https://doi.org/10.1093/europace/ eux299).

Defining reliable information online can be problematic, and publication and industry biases add an extra layer of complexity specific to medical education.

Better approaches are also needed to protect users, and to provide solutions to prevent or deal with online harassment.

The way we deliver and receive education is undergoing intense transformation. Although digital technologies have massive potential, they come at a price—there is a direct impact on patient care, and many challenges have to be faced for these tools to further improve medical education. A modern day cardiologist needs to be able to use digital tools for clinical practice, teaching and training, and interacting with patients. To promote digital cardiologists of the future, curricula and methods for training need to be adapted to reflect the expectations of the new digital era.

Xavier Rosselló is at the Centro Nacional de Investigaciones Cardiovasculares Carlos III, Complutense University of Madrid, Spain.

Dipak Kotecha is at the Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, UK.

false equivalents in these discussions [such as the risks and benefits of statins], often done to foster debate and controversy. It is easy to find a rogue voice but inappropriate to suggest that this voice carries the same weight as that emerging from mainstream science,” they comment.

In particular, given that misinformation tends to travels faster through social networks than does the truth, Hill et al write that the “purveyors of social media must be responsible for the content they disseminate” and it is no longer acceptable for these purveyors to “hide behind the cloak of the platform”. They explain that, as editors-in-chief, they “reach out to thoughtleading experts to evaluate the veracity of each report” they receive and “challenge social media to do the same”—“to leverage the ready available of scienceconversant expertise before disseminating content that may not be reliable”.

“Without exaggeration, significant harm, to society and individuals, derives from the wanton spread of medical misinformation. It is high time that this stop, and we lay at the feet of the purveyors of the internet and social media content the responsibility to fix this,” Hill et al conclude.

Hill told Cardiac Rhythm News: “The internet and social media platforms are replete with false information, which does real harm to individuals globally. We charge the purveyors of these media to take first steps in addressing this enormous problem, and we, in the academic medical community, stand ready to help.”

As well as being published in Circulation, the editorial was also published in the European Heart Journal, Journal of Electrocardiology, and the International Journal of Cardiology among others.

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BIBABriefings

Survey suggests that nearly half of LAA occlusion operators use DAPT to prevent thrombus formation A short BIBA MedTech survey of 31 operators (including electrophysiologists and interventional cardiologists) shows that 48% prescribe dual antiplatelet therapy (DAPT) to reduce the risk of device-related thrombus after implanting a left atrial appendage (LAA) occlusion device. This follows a study by Laurent Fauchier (Trousseau University Hospital, Faulty of Medicine, Franҫois Rabelais University, Tours, France) and colleagues that found that DAPT at discharge was associated with a lower risk of thrombus formation on a LAA occlusion device.

IN THE SURVEY, respondents were asked which therapy (if any) they prescribed to reduce the risk of device-related thrombus after implanting an LAA occlusion device.

Nearly half (15/31; 48%) said they used DAPT, just over a quarter (8/31; 26%) said novel anticoagulants (aka non-vitamin K antagonists), four (13%) said aspirin monotherapy, three (10%) said warfarin, and one (3%) reported “other” (see Figure 1). Furthermore, responding to the question “after implanting an LAA occlusion device, do you monitor for thrombus formation?”, 26 (84%) said yes versus five (16%) who said no.

In their study, which was published last year in the Journal of the American College of Cardiology, Fauchier et al found that thrombus formation after implantation of a LAA occluder device was “not uncommon” (7.2% during a follow-up of 13±13 months). Additionally, in a multivariate analysis, thrombus on a device and vascular disease were independent predictors of ischaemic stroke and transient ischaemic attack during follow-up.

According to Fauchier et al, most patients (441 of 478 with the relevant data) were receiving some form of antithrombotic therapy at

Source: BIBA MedTech survey

Pace >3.5cm from cardiomyopathy scar to avoid arrhythmia Researchers have hypothesised a mechanistic reason for the increased ventricular tachycardia (VT) associated with cardiac resynchronisation therapy (CRT) in patients with ischaemic cardiomyopathy (ICM) when pacing is performed in proximity to the scar. Published online in Heart Rhythm, the findings from Caroline Mendonca Costa (King’s College London, UK) et al suggest that pacing >3.5cm from the scar may avoid increasing the risk of VTs in these patients.

discharge. In this study, 171 (36%) were receiving single antiplatelet therapy, 110 (23%) were receiving DAPT, 138 (29%) were on oral anticoagulation, 22 (5%) were on oral anticoagulation plus antiplatelet therapy, and 37 (7%) were receiving neither oral anticoagulation nor antiplatelet therapy. The authors report: “On multivariate analysis, older age and history of stroke were predictors of thrombus formation on the device, whereas DAPT and oral anticoagulation at discharge were associated with a lower risk of thrombus on device.” However, they note that “DAPT at discharge was associated with a lower risk of thrombus formation on the device. These results concur with previously suggested adequacy and better efficacy of DAPT over oral anticoagulation therapy after LAA closure”.

While the BIBA MedTech survey did not provide details about which LAA occlusion device the respondents used, data from the BIBA MedTech LAA Monitor suggest that that Amplatzer (Abbott) and Watchman (Boston Scientific) are the most commonly used devices. Of 3,696 units used of LAA occlusion devices in Q4 2018 (1 October–31 December), 1,780 (48%) were Amplatzer devices and 1,560 (42%) were a Watchman device. Of the

THEY WRITE: “PACING at the epicardial surface in proximity to scar increases the volume of HRG [high repolarisation gradients—metric of dispersion of repolarisation] and widens the vulnerable window in the vicinity of the scar. This provides a plausible mechanistic explanation for increased VT risk in ICMCRT patients. The risk of VT was further augmented by electrophysiology changes commonly found in heart failure.”

CRT-induced VT has been reported in patients with ICM. But the effect of left ventricular (LV) pacing in proximity to scar on increased VT risk is unclear. The researchers investigated the interaction between pacing electrode location relative to scar in ICM-CRT patients to determine the mechanisms underpinning VT risk.

Late gadolinium-enhancement magnetic resonance imaging data, before device implantation and at least six months after previous myocardial infarction, from 24 ICM-CRT patients was used. Average age was 69 years, and 20 subjects were male (83%). Patient-specific anatomical computational models of LV anatomy, scar,

remaining 356 units, 224 (6%) were the Lariat device (SentreHeart), 109 (3%) were WaveCrest (Coherex), and 23 (1%) were “other”. In their study, Fauchier et al only reviewed data for patients who received the Watchman (272 of 487 overall) or the Amplazter device (197). Of those who received an Amplatzer device, 97 received the latest generation of the device (Amplatzer Amulet). The authors comment: “The overall incidence of thrombus on the device was 5.5% in patients treated with a nitinol cage [Watchman], 8.2% with the older version of the nitinol plug [Amplatzer] and 25% with the newer version [Amplatzer Amulet] (p=0.52).”

BIBA Briefings BIBA Briefings is a new platform that provides in-depth analysis of the latest market intelligence from BIBA MedTech Insights, which provides consulting and market analysis services to medical professionals and organisations in the medical device industry in Europe and North America.

The platform also reviews data and news. For more information about BIBA Briefings or BIBA MedTech Insights, please contact Merveille Anderson: merveille@ bibamedical.com

and border zone (BZ; of remodelled myocardium) were constructed. Simulations of LV epicardial pacing at 0.2–4.5cm from the scar were performed, and dispersion of repolarisation and the vulnerable window computed as surrogates for VT risk, based on their known link to arrhythmogenesis.

The simulations predicted that pacing in proximity to scar (0.2cm) compared to more distant pacing (4.5cm) significantly (p<0.01) increased dispersion of repolarisation in the vicinity of the scar, and widened (p<0.01) the vulnerable window. Slow conduction during heart failure further increased dispersion.

Analysis of variance and post hoc tests showed significantly (p<0.01) reduced repolarisation dispersion when pacing ≥3.5cm from the scar compared to pacing at 0.2cm.

Mendonca Costa reports to Cardiac Rhythm News that a clinical study is ongoing at St. Thomas’ Hospital, London, UK, to validate the findings. If validated, it could lead to changes in current clinical guidelines for CRT implantation in ICM patients.

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Clinical News Product News treatment modalities in the AF ablation space.”

The HeartLight X3 system is only approved for use in Europe, and is not available for sale in the USA.

Biotronik launches 3 Tesla full-body MR conditional ICD and CRT-D devices on the European market

Heartlight gains European CE mark

CardioFocus has recieved the European CE mark approval for its HeartLight X3 endoscopic ablation system, used in the treatment of atrial fibrillation (AF).

The HeartLight X3 system is a thirdgeneration technology which performs pulmonary vein isolation using laser energy to create lines of scar tissue to block the abnormal electrical pathways that cause AF. According to a press release from CardioFocus, using direct tissue visualisation, titratable laser energy, and compliant balloon technology, the HeartLight X3 system has a unique RAPID mode that leverages a precise motor control system to enable uninterrupted, high-speed, circumferential lesion creation under direct control of physicians, which results in consistently reduced procedure times.

Boris Schmidt (Cardioangiologisches Centrum Bethanien, Frankfurt, Germany), an investigator in the confirmatory trial of the system, says: “Our clinical results using the HeartLight X3 system have been outstanding, with unprecedented treatment speed and precise lesion creation. Based on our experience with the device, we feel confident that the HeartLight X3 system is poised to change the way AF ablation is performed in Europe.”

The press release adds that the trial evaluated 60 patients, and that the HeartLight X3 system consistently achieved very rapid pulmonary vein isolation in as few as three minutes for a single vein. The trial also found that the system has the potential to complete all required ablations in less than 20 minutes.

The company states that commercial introduction of the HeartLight X3 system in Europe will begin immediately, and that current users of the HeartLight platform may start using HeartLight X3 technology after a simple upgrade.

Burke T Barrett, president and chief operating officer at CardioFocus, says: “We are eager to begin the commercialisation of the breakthrough HeartLight X3 system in the European market. In partnership with our physician users, we are committed to continued innovation and delivering the best

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Biotronik has announced the European market release of the world’s smallest implantable cardioverter-defibrillator (ICD) and cardiac resynchronisation therapy defibrillator (CRT-D) that are approved for 3 Tesla (3T) full-body magnetic resonance imaging (MRI) scans. According to a press release, the Acticor and Rivacor families feature an “ultraslim BIOshape” as well as extended battery life and warranty.

Iain Matthews (Northumbria Healthcare, UK) reports: “The slenderness and smoother shape of the new devices play a key role in easing the insertion procedure and improving how the device looks after implantation,” following his first implantations of the devices. More than 90% of implanting physicians rated “patient comfort” as “better” or even “much better” in comparison with previous models during post-market observation.

Besides their body-friendly shape, Acticor and Rivacor devices feature an extended battery life, with up to 15 years for ICDs and nine years for CRT-Ds. Increased device longevity is designed to lower the need for replacements, resulting in reduced risks, less distress for patients, and fewer procedure costs. The new range of devices are also supported by a warranty of 10 years for ICDs and six years for CRT-Ds. With Biotronik Home Monitoring, cardiovascular data from an Acticor or Rivacor device can be transmitted to the physician on a daily basis with programmable alerts about relevant changes in patient health and device status. The IN-TIME randomised controlled trial has demonstrated more than 60% reduction in all-cause mortality when CRT-Ds are used with Biotronik Home Monitoring. In ICDs, Home Monitoring has been clinically proven to help physicians detect atrial fibrillation earlier, as well as reduce the number of inappropriate shocks by 90% and related hospitalisation rates by 73%. Biotronik Home Monitoring’s new QuickCheck feature gives access to patient data typically within three to four minutes.

The typical non-response rate of 30% to 40% of all patients is a major problem in cardiac resynchronisation therapy (CRT). To counter this, Acticor and Rivacor CRT-Ds feature CRT AutoAdapt to fit patients’ individual pacing needs and provide continuous CRT adaptation, automatically adjusting to changes

sensed in a patient’s condition every minute. Auto LV VectorOpt further helps to evaluate clinically relevant pacing parameters, with automatic threshold measurements across 20 vectors in less than 2.5 minutes and rapid direct programming.

All Acticor and Rivacor devices feature ProMRI, giving patients full access to high-resolution 3T MRI without any exclusion zone. With sensor-based MRI AutoDetect technology, once activated for a programmable window of up to 14 days, the devices can automatically recognise an MR environment and switch in and out of MRI mode as required.

This ensures that patients receive optimal therapy, with tachycardia therapy suspension limited to the duration of the MRI scan, as well as fewer in-office visits required for device programming.

Acticor and Rivacor devices also feature DX technology, enabling complete atrial diagnostics without an atrial lead.

“The Acticor and Rivacor families embody Biotronik’s dedication to quality and innovation that saves and improves patients’ lives,” said Alexander Uhl, senior vice president of Corporate Marketing at Biotronik. “With a full range of functionality in a small and slim device, we want to equip physicians to provide optimal therapy to tachycardia and heart failure patients without compromising on device longevity or patient safety and comfort.”

CE mark for Watchman FLX left atrial appendage closure device

Boston Scientific reports it has received CE mark and initiated a limited market release of the next generation Watchman FLX left atrial appendage closure (LAAC) device in Europe.

Patients with atrial fibrillation (AF) are five times more likely to suffer a stroke than someone with a normal heart rhythm. In people with non-valvular AF, data suggest that >90% of stroke-causing blood clots that come from the heart are formed in the left atrial appendage. The Watchman left atrial appendage occlusion devices are intended to reduce the risk of stroke in people with non-valvular AF. Kevin Ballinger, president, Interventional Cardiology, Boston Scientific, says: “The Watchman device has been implanted in more than 75,000 patients worldwide and we are pleased that this next-generation technology has been granted European regulatory approval so that we can offer it to patients and clinicians throughout Europe. The robust clinical evidence and successful commercial outcomes of the Watchman device to date reinforce the value of this

procedure for all appropriate patients.”

The new Watchman FLX device was designed for simplified implantation to fit a wider range of patients, from those with simple to the most complex anatomies.

The device allows for implantation flexibility to customise placement with a fully enclosed and rounded frame and by offering physicians the ability to fully recapture and reposition the device during the procedure. Furthermore, the frame of the new device is designed to enhance sealing within the left atrial appendage.

Boston Scientific has begun a limited market release of the Watchman FLX device in Europe and expects to expand commercialisation to additional sites in the second half of 2019. The company also plans to begin enrolling European patients in a post-approval registry in the coming months.

In the USA, the Watchman FLX device is an investigational device, and is not available for sale.

Mobile ECG developments driving growth in the sector

ResearchAndMarkets.com has identified technology in the mobile electrocardiogram (ECG) market as a key growth driver, and has added analysis of its shares and trends to its portfolio of offerings. Its report, “Single lead ECG equipment market size, share & trends analysis report by end use (hospitals & clinics, homecare, ASCs), by indication (arrhythmia, syncope), and segment forecasts, 2019–2025”, outlines that the global single lead ECG equipment market size is estimated to reach USD $487.59 million by 2025, progressing at a 4.72% compound annual growth rate during the forecast period.

It attributes this growth to the emergence of smartphone and mobilebased cardiac monitoring devices, revolutionising the market. Additionally, it says, medical device manufacturers continue to invest in developing these products to overcome pitfalls associated with conventional means of cardiac assessment, and this consequently fosters market growth.

Other factors it identifies include advancements in ECG monitoring devices that are anticipated to shape the future of the market over the forecast period, government bodies undertaking initiatives to improve treatment and prevention of cardiac disorders to satisfy an escalating need for inexpensive and portable devices, and the widening base of patients suffering from cardiovascular diseases, which is expected to augment the single lead portable ECG equipment market.

Other findings from the report outlined in a press release include the observation that the USA accounted for the largest market share in 2017, due to its wellestablished healthcare system and a rise in prevalence of cardiovascular diseases.

It expects Asia Pacific to witness the fastest growth during the forecast period, because of rising patient awareness of portable technologies, as well as increasing healthcare expenditure in developing economies.

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is better off for the work Scott and the entire FDA team have done over the last two years.”

Industry News Bardy Diagnostics announces expansion into Canadian market

Bardy Diagnostics (BardyDx) has announced that it has entered into a distribution agreement with JNC Medical, a distributor of medical technologies based in Ottawa, Canada.

The agreement grants JNC Medical the right to distribute the BardyDx Carnation Ambulatory Monitor (CAM) in the Canadian market.

Ken Nelson, BardyDx chief commercial officer, states: “The collaboration with JNC Medical strengthens BardyDx’s international distribution and business development initiatives, which are key priorities for The Company this year. Combining BardyDx’s innovation and leadership in ambulatory cardiac monitoring with JNC Medical’s Canadian market-specific expertise, distribution logistics, and deep connections with Canadian physicians will accelerate penetration of the CAM patch into the global market.”

According to a press release, the partnership aims to enable access to the CAM patch for all Canadian patients and accelerate the transition away from legacy Holter technologies and outdated ECG reporting solutions. As part of its distribution strategy, JNC Medical

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intends to leverage its healthcare industry networks and physician demands for extended monitoring, encouraging a transition to digital monitoring technologies.

JNC Medical business partner Christopher Mulvanny says: “We are excited to partner with BardyDx by assisting in the commercialisation of the market-disrupting CAM patch in Canada. It is our goal to bring the world’s most innovative device technologies to Canadian physicians and patients, and the CAM patch is a perfect match to add to our growing portfolio.”

Scott Gottlieb resigns as head of US FDA

The commissioner of the US Food and Drug Administration (FDA), Scott Gottlieb, unexpectedly resigned in March, having served less than two years in the post.

Gottlieb announced his intention to stand down in a letter to Alex Azar II, the secretary of the Department of Health and Human Services, the FDA’s parent agency, saying the decision is because he wants to spend more time with his family.

In an interview with The Washington Post, Gottlieb says: “It was a very hard decision,” calling the posting “the best job I will ever have. I am leaving because

New Australian research and development partnership aims to innovate heart failure care Scott Gottlieb

I need to spend time with my family. I get home late Friday, work on weekends, and come back to Washington on Sunday. I did the job 100%.”

Gottlieb took up the position in May 2017, and presided over a number of important initiatives, including development of the new 510(k) pathway for device clearances.

No successor has been named. A new commissioner must be approved by the US Senate.

In a statement, Health and Human Services Secretary Alex Azar comments: “All of us at the Department of Health and Human Services [HHS] are proud of the remarkable work Commissioner Gottlieb has done at the FDA. He has been an exemplary public health leader, aggressive advocate for American patients, and passionate promoter of innovation. I will personally miss working with Scott on the important goals we share, and I know that is true for so many other members of the HHS family.

“The public health of our country

Biotronik, the University of Newcastle (Callaghan, Australia), and the Hunter New England Local Health District (HNE LHD) have partnered to shape a heart failure care model. To date, the Australian government and Biotronik have invested in the partnership.

According to a press release, the partners will create a digital testbed that addresses the changing needs in heart failure treatment, allowing future care models to be tested in a real-world clinical setting. Results will help to determine how digital resources and developed processes most benefit different heart failure groups.

Aaron Sverdlov, clinical academic cardiologist at John Hunter Hospital (New Lambton Heights, Australia), and associate professor and director of heart failure at the University of Newcastle, Australia, comments: “We want to identify the concepts that lead to the best outcomes and most cost-effective delivery of health care when treating heart failure patients. This partnership would allow us to combine our clinical and research expertise with technological innovations to design, test and evaluate best value strategies for improving cardiovascular health of our community.”