Cardiac Rhythm News Issue 43 — January 2019

Jan

Issue

19 43 Richard Sutton:

The first 60 years of cardiac pacing

Page 7

Haran Burri:

Profile

Caroline Broughton: Page 8

AF and obstructive sleep apnoea

Page 11

“No serious adverse outcomes” with ICD shocks in young athletes playing sport A post-hoc analysis of the ICD Sports Registry—which has already indicated that many patients with implantable cardioverter defibrillators (ICD) can safely participate in vigorous or competitive sports—shows that shocks are not infrequent in young ICD patients who play competitive sports but that these shocks are not associated with serious adverse outcomes.

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lizabeth Vickers Saarel (Cleveland Clinic Children’s Paediatric Cardiology, Cleveland, USA) and others write in Circulation: Arrhythmia and Electrophysiology that, over the past few years, the perception of the safety of ICD patients participating in sport has changed. They note: “Growing evidence suggests that risks of sports participation for athletes with ICDs may be lower than hypothesised.” They add that the ICD Sports Registry found that while appropriate and inappropriate shocks occurred during sports, there were no deaths, resuscitated arrests or arrhythmia-related injuries during sports. Vickers Saarel comments that the study is “reassuring” because it suggests safe sports participation for patients with ICDs, but its results are “difficult to apply to children and adolescents”. Therefore, the aim of the present post-hoc analysis was to “better understand this young population”.

Reviewing data from the ICD Sports Registry, the authors identified 129 athletes aged ≤21 years of age.

Of these, 9% were aged 10 to 12 years of age, 26% were aged 13 to 15 years of age, 41% were aged 16

to 18 years of age, and 24% were aged practice, a rate of 1.5 appropriate shocks 19 to 31 years of age. As with all of during sports, per hundred person-years.” the patients in the registry, the young They add that this finding suggests athletes had an ICD and participated in “restriction from this activity [i.e. sports] sports that were associated with a more would not have a large impact on the than low cardiovascular demand (in this overall burden of treated arrhythmias”. post-hoc analysis, 117 did competitive Furthermore, according to Vickers Saarel sports and 12 did dangerous sports). The et al, “all of the youths” in the post-hoc primary endpoint was a serious adverse analysis benefitted from participating event during or ≤2 hours after sports (e.g.

Elizabeth Vickers Saarel in sports, noting that 82% only stopped tachyarrhythmic death). participating in competitive sports after During the median 42 months of follow-up, no graduating from secondary school. tachyarrhythmic deaths or externally resuscitated The authors say the present report adds to the data tachyarrhythmias during or after sports participation already provided by the ICD Sports Registry and occurred; there were also no severe injuries resulting “will further inform the dialogue and shared decisionfrom arrhythmia-induced syncope or shock during making concerning sports participation in the important sports. However, 27% of athletes experienced at least population of young athletes involved in school and one shock (49 shocks overall). Vickers Saarel et al college [university] sports”. They conclude that the comment “There were 29 appropriate shocks occurring decision to return to sport participation after an ICD in 18 individuals; of which, six appropriate shocks “should be individualised and discussed between in four individuals occurred during competition or physician, athlete and parents”.

Computerised-decision support has the potential to be a “powerful tool” for preventing cardiovascular events in AF patients Data presented at the 2018 American Heart Association (AHA) scientific sessions (10–12 November, Chicago, USA) indicate that the use of alert-based computerised-decision support significantly increases the rate of anticoagulation prescription among patients who are hospitalised with atrial fibrillation (AF). Furthermore, the use of such software is associated with a significant decrease in major adverse cardiac events.

PRESENTING THE AF-ALERT study at the AHA, Gregory Piazza (Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, USA) reported that he and his fellow investigators had previously found, in a study of patients hospitalised with AF, that “antithrombotic therapy was omitted in nearly 40% of those at risk”.

Noting that alert-based computerised decision support strategies “have been successfully implemented to improve underutilisation of venous thromboembolism prophylaxis in high-risk hospitalised patients”, Piazza stated that the objective of AF-Alert

was to determine the impact of alertbased computerised-decision support on the prescription of anticoagulation among patients with AF. The hypothesis of the study, he explained, was that “alert-based computerised-decision support will increase prescription of anticoagulation in high-risk hospitalised patients with atrial fibrillation who were not being prescribed anticoagulation”.

In the study, 458 patients who were hospitalised for AF and who were not already receiving anticoagulation were randomised to standard care plus alertbased computerised-decision support (248) or standard therapy alone (210).

The primary efficacy endpoint was the rate of anticoagulation prescription during hospitalisation, at discharge and at 90 days, and the primary safety endpoint was the occurrence of major bleeding or clinically relevant non-major bleeding.

At all follow-up points (during hospitalisation, discharge, and at 90 days), the rate of anticoagulation prescription was significantly higher among the alert group patients. This meant that the rate of the primary efficacy endpoint, according to Piazza, “nearly tripled” in the alert group: 19.4% vs. 7.1% for the control group

(p<0.001). There were no significant differences in the rate of the primary safety endpoint between groups.

Also, the rate of the secondary efficacy endpoint (a composite of death, myocardial infarction, transient ischaemic attack or systemic embolic event at 90 days) was significantly lower in the alert group: 11.3% vs. 21.9% for the control group (p<0.002); a 50% reduction. Furthermore, aside from death, the individual components of this endpoint were significantly lower in the alert group. This meant that the alert group had significantly higher rates of freedom from major adverse cardiac events (MACE) and from major adverse events (MAE) at 90 days compared with the control group (p=0.004 and p=0.001 for the comparisons). Piazza commented that the reduction in MACE was “beyond what was anticipated from the increase in prescription of anticoagulation”.

“Computerised-decision support has the potential to be a powerful tool in prevention of cardiovascular events in patients with AF,” Piazza concluded.

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AF

Prevent postoperative atrial fibrillation by simultaneous monitoring of autonomic tone and ectopic activity Simultaneous monitoring of autonomic tone and ectopic activity could be used to prevent the occurrence of postoperative atrial fibrillation (POAF). Flavia Ravelli (Department of Physics, University of Trento, Povo-Trento, Italy) and the colleagues of the Cardiovascular Department of the Santa Chiara Hospital in Trento have examined triggering mechanisms of postoperative AF and have developed a framework for the combined assessment of autonomic tone and ectopic activity that characterises components of normal and abnormal atrial cycle length series. From this, they suggest a role for sympathetic activation in promoting ectopic activity and facilitating the induction of POAF.

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resenting the findings at the 2018 Heart Rhythm Congress (6–9 October, Birmingham, UK), Ravelli explained: “Our data shows an increase in the number of premature beats and in the sympathovagal balance in the minutes preceding the occurrence of POAF. The increase in the number of premature beats is consistent with the increase in sympathetic activity which may indeed favour the initiation of AF by enhanced triggered activity. On the other side, sympathetic activity may non-uniformly shorten the refractory period by direct control or indirectly by rate adaptation. And so a higher occurrence of premature beats and tissue with higher response may increase the probability to trigger and support atrial fibrillation episodes.”

Despite its high prevalence, the pathophysiological mechanisms of postoperative AF remain incompletely understood. Facilitating factors are known to be acute peri and postoperative responses to cardiac surgery, such as inflammation, autonomic tone alterations, and oxidative stress, as well as pre-existing elements, such as structural heart disease, remodelling and ageing of the heart. These factors may provoke triggers to start the arrhythmia or may enhance substrates of

arrhythmia to maintain atrial fibrillation.

Ravelli said: “Our aim was to characterise postoperative atrial fibrillation triggering factors, specifically to study the interplay between autonomic tone and ectopic activity. The study was performed by analysing long term epicardial recordings in postoperative patients.”

The study group consisted of nine patients, eight of whom were male, with sustained postoperative AF episodes lasting more than 30 seconds, and in a few patients more than 24 hours, which are preceded by three hours of continuous noise-free sinus rhythm recording. During this time, the atrial cycle length was estimated step-by-step using a custom made algorithm.

She said: “The first and most important step of our algorithm is the binomial filtering procedure, which allows us to identify the abnormal beats, and also to reprise the abnormal beat values in the normal time series. This is very important, because we want also to make an analysis of autonomic tone in the normal atrial interval series.”

Ravelli pointed out that the unified framework developed by the investigators thoroughly characterises normal and abnormal atrial cycle length series

components, allowing the simultaneous analysis of autonomic tone and ectopic activity. “Associated with an increase in the number of premature beats before the starting of AF, we could see a decrease in the atrial cycle lengths and an increase in the low frequency (LF) spectral component of the normal beat series, a decrease in the high frequency (HF), and an increase in the LF/HF ratio.” Characterisation of abnormal beats showed a concurrent increase in the number, and decrease in the coupling interval of premature beats.

Ravelli added: “These patterns were consistent in the majority of patients. Furthermore, we found a correlation between the power of the low frequency band and the number of premature beats shortly before an atrial fibrillation episode.”

She outlined the two pathways leading to an increased AF vulnerability suggested by the findings.

One, through autonomic modulation and increased sympathetic activity, leads to an enhanced triggered activity that feeds into an increase in premature beats and a decreased coupling interval. The second, concurrent, route is via a decreased effective refractory period (ERP), either by direct control or rate adaptation.

Cryoablation with 8mm tip catheter comparable to radiofrequency ablation in treating AVNRT in terms of safety and efficacy RESULTS FROM THE CRYOABLATE trial show that cryoablation (CRYO) with an 8mm tip catheter is shown to be comparable to radiofrequency ablation (RFA) in the treatment of atrioventricular nodal re-entrant tachycardia (AVNRT).

Ngai-Yin Chan (Department of Medicine & Geriatrics, Princess Margaret Hospital, Hong Kong) and colleagues write in Europace that they observed no significant difference between CRYO and

RFA patient groups in primary endpoint (a composite of acute procedural failure, inadvertent atrioventricular block and recurrence at 12 months; p=0.764), 12-month recurrence rate (p=0.358), inadvertent permanent AVB (p=0.307), and acute procedural failure (p=0.128).

In patients with acute procedure failure, success was achieved in five of seven patients (71.4%) in the RFA group and two of three patients (66.7%) in the CRYO

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group on crossover.

The authors also found no significant difference in procedural duration between the CRYO and RFA groups, but fluoroscopic duration in the CRYO group was significantly shorter (3.4 ± 6.3 vs. 6.7 ± 7.4 min; p=0.005). They note that patient pain score (2.7 ± 2.7 vs. 4.6 ± 2.7; p<0.001) and operator stress score (2.3 ± 1.3 vs. 4.9 ± 2; p<0.001) were significantly lower in the CRYO group.

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Although RFA for AVNRT is effective and safe, Chan et al point out that a 0.3– 1.3% risk of inadvertent atrioventricular block (AVB) with the need for permanent pacemaker remains a potential problem.

CRYO, with its characteristics of cryoadhesion, cryomapping, and electrophysiological reversibility in the initial phase of lesion formation, has minimal risk of inadvertent AVB in the treatment of AVNRT.

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Heart failure

Treatment withdrawal should “not be attempted routinely” in patients with recovered dilated cardiomyopathy Data from an open-label, randomised pilot trial (TRED-HF) indicate that if heart failure treatment is withdrawn in patients with recovered dilated cardiomyopathy, many will relapse and require treatment to be reinitiated. These findings suggest that until predictors of relapse can be identified, patients with recovered dilated cardiomyopathy should receive treatment indefinitely.

BRIAN P HALLIDAY (Cardiovascular Research Centre and Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, London, UK) and others write in the Lancet that following resolution of symptoms and recovery in cardiac function after treatment for dilated cardiomyopathy, a substantial number of patients enquire “whether it is necessary to continue lifelong treatment”. They add: “Patients are often young and reluctant to take medications for many years without evidence of continued benefit”.

However, according to Halliday et al, the potential risks and benefits of withdrawing treatment in this group are unknown and the lack of data in this area mean that there is “consequently no consensus among experts or clear recommendations in guidelines”. Therefore, the investigators performed a pilot study “to examine the effect of treatment withdrawal in patients with clinical, imaging, and biochemical evidence of recovery from dilated cardiomyopathy”.

Patients were included in the study if they had a previous diagnosis of dilated cardiomyopathy with left ventricular ejection fraction (LVEF) 40% or lower, absence of current symptoms of heart failure, were receiving heart failure medication (such as beta-blockers), and proven recovery (as identified via imaging and cardiac biomarkers). Of 51 patients

enrolled, 25 were randomised to undergo treatment withdrawal (over a maximum of 16 weeks) and 26 were randomised to receive continued treatment. At six months’ follow-up, patients in the continued treatment arm underwent treatment withdrawal (again over a maximum of 16 weeks) with follow-up at six months. The primary endpoint was a relapse of dilated cardiomyopathy within six months.

Of those assigned to treatment withdrawal, 11 (44%) met the primary endpoint for relapse within six months. No one assigned to continued treatment relapsed within this time period. “The Kaplan-Meier estimate of the event rate at six months in the withdrawal group was 45.7% (p=0.0001),” the investigators note.

In the continued treatment arm, at the six months’ follow-up point, 25 patients underwent withdrawal of treatment and one patient stayed on treatment after developing symptoms of atrial fibrillation. Of the 25 patients who underwent treatment withdrawal, nine met the criteria for relapse within the following six months of follow-up. Halliday et al comment: “Therefore of the 50 patients who began withdrawal, 20 (40%) relapsed

during the study period”. They add that 13 (26%) relapsed within 16 weeks of beginning withdrawal “all of whom relapsed within eight weeks of taking their last medication”.

Furthermore, another four patients who did not meet the criteria for relapse restarted heart failure treatment (for reasons such as refractory hypertension) within six months of withdrawal. The investigators observe: “Therefore, only 25 (50%) of 50 patients successfully completed six months of follow-up without reinitiation of treatment.” They note that “potentially” more patients could have relapsed had the treatment withdrawal period been longer.

According to Halliday et al, the results of TRED-HF suggest that “for many patients, improvement in cardiac function does not reflect full and sustained recovery but rather reflects remission”. They state: “Withdrawal of treatment should, therefore, not be attempted routinely in these patients”, adding that the “speed of deterioration” of patients after treatment was withdrawn could “provide guidance Sanjay Prasad about how to monitor patients if treatment withdrawal is attempted” because of the patient’s request, side-effects, or because the patient is considering pregnancy.

Looking to the future, the investigators conclude: “Future work could identify patient subgroups who have permanent recovery of myocardial function for whom withdrawal is safe or for whom only some medications need to be continued in the long run.”

Study author Sanjay Prasad (Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, London, UK) told Cardiac Rhythm News: “The study shows that many patients with ‘recovered’ dilated cardiomyopathy are really in remission. We are now working to identify who are the subset of patients that can safely be weaned off medication and who should stay on them lifelong.”

Presence of left bundle branch block significantly increases risk of pacemaker implantation after TAVI Quentin Fischer (Department of Cardiology, Quebec Heart and Lung Institute, Laval University, Quebec City, Canada) and others report in Circulation: Cardiovascular Interventions that patients with pre-existing left bundle branch block (LBBB) have a significantly increased chance of requiring permanent pacemaker implantation after undergoing transcatheter aortic valve implantation (TAVI) than patients without pre-existing LBBB. However, pre-existing LBBB is not associated with increased mortality at 30 days or at two years.

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ischer et al report that right bundle branch block (RBBB) is seen as the “most important risk factor” for permanent pacemaker implantation after TAVI and that “some studies have shown an increased mortality risk among patients with pre-existing RBBB”. However, they add “no specific data exists on the impact of pre-existing LBBB on TAVI outcomes”.

Therefore, with the present study, the authors sought to “evaluate the impact of pre-existing LBBB on clinical outcomes in patients undergoing TAVI”.

Using data for 4,513 patients who underwent TAVI at 18 centres in Canada, Europe and Brazil between February 2005 and October 2017—after excluding patients with pre-existing RBBB, previous pacemaker, or who did not have highquality ECG data at baseline—the authors identified 3,404 patients for evaluation.

Of these, 398 patients had pre-existing LBBB; Fischer et al report that patients with incomplete LBBB were classed as having no pre-existing LBBB (3,006 overall).

At 30 days, permanent pacemaker

implantation was significantly higher in patients with pre-existing LBBB: 21.1% vs. 14.8% for patients without pre-existing LBBB (p=0.006). Pacemaker implantation was also higher among those who received a self-expanding valve than those who received a balloon-expandable valve (23.1% vs. 8.7%, respectively; p<0.001).

However, there were no significant differences in all-cause mortality at 30 days: 7.3% for patients with pre-existing LBBB vs. 5.5% for those without preexisting LBBB; p=0.217).

There were also no differences in all-cause mortality or cardiac mortality between LBBB patients and no LBBB patients at a mean follow-up of 22±21 months (p=0.173 and p=0.093 for the respective differences). Fischer et al note that the cumulative rate of permanent pacemaker implantation was higher in the pre-existing LBBB group (22.9% vs. 16.5% for the no LBBB group; p=0.006), but add that this “was because of an increased permanent pacemaker implantation rate early after TAVI and no differences between groups were observed

in the permanent pacemaker implantation rate after the first 30 days post-TAVI”.

Additionally, according to the authors, patients with pre-existing LBBB “exhibited a lower left ventricular ejection fraction (LVEF) pre-TAVI but experienced a similar degree of increase in LVEF at one-year follow-up compared with those patients with no significant conduction disturbances pre-TAVI”.

Fischer et al note that the risk of permanent pacemaker implantation associated with pre-existing LBBB occurs early “probably secondary to the mechanical compression of the His bundle during valve implantation” given that there was no increased risk of pacemaker implantation, or sudden cardiac death, at two years. “This provides some reassurance about the management of these patients in the absence of advanced conduction disturbances during the hospitalisation period and contrasts with the results observed in the presence of new-onset LBBB post-TAVI [which is associated with an increased risk of permanent pacemaker implantation and sudden cardiac death in

the months after the procedure]”, they add.

In terms of the implications of their study, Fischer et al comment that these results “should be taken into account of the preparation of TAVI procedures considering the use of the valve type associated with a lower risk of conduction disturbance issues and a high (more aortic) transcatheter valve positioning in those patients with preexisting LBBB to decrease the permanent pacemaker implantation after TAVI”.

Study investigator Josep Rodés-Cabau (Quebec Heart and Lung Institute, Laval University, Quebec City, Canada) told Cardiac Rhythm News: “Pre-existing LBBB should be included as a risk factor for PPI early post-TAVR. However, pre-existing LBBB in TAVI recipients was not associated with increased mortality or heart failure hospitalisation at two-year follow-up, and there were significant improvements in LVEF in most patients. This suggest that the possible use of specific therapies including cardiac resynchronisation therapy (CRT) should be delayed by several months in order to avoid implementing unnecessary treatment.

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Research

T-wave morphology restitution predicts cardiovascular risk in the general population An investigation into the predictive value of the T-wave morphology restitution (TMR) index has found an association with cardiovascular events, in a large study, in the general population. The UK Biobank—which contains information on physical, lifestyle, and environmental factors, as well as health outcome measures and genetic data for approximately half a million individuals—was used for the prospective study.

JULIA RAMÍREZ (William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK) told delegates at the Heart Rhythm Congress (6–9 October, Birmingham, UK) that “TMR was independent from demographic and heart rate information.

Higher values indicating a higher T-wave morphology variation per RR increment (repolarisation restitution) is associated with an increased cardiovascular risk”.

Restitution of ventricular repolarisation is the response of repolarisation times to changes in the cycle length, with the slope of the curve reflecting the variation of repolarisation time per cycle length increment. Steeper slopes are believed to indicate increased arrhythmic risk.

Ramírez commented: “Electrical abnormalities along the ventricle can result in high dispersion of repolarisation restitution, represented as a bigger difference in the slopes of the restitution curves. This has also been associated with increased arrhythmic risk. The main limitation of this is that it is invasive.

In parallel, we know that the T-wave morphology reflects the spatio-temporal repolarisation dispersion of the ventricle.

So if we compare the morphology of the T-wave at different heart rates, we might have a measurement of dispersion of the repolarisation restitution.”

Ramírez and colleagues developed a predictive model in an earlier study, which they then sought to validate using

Julia Ramirez

the UK Biobank data. “We showed that by selecting a T-wave from a low RR interval and a T-wave from a high RR interval and quantifying the T-wave morphological variation, correcting for by the change in RR, we were able to predict sudden cardiac death in chronic heart failure patients from the MUSIC study” explained Ramírez.

In the validation study, 95,000 participants were invited for a moderate exercise test between 2006 and 2010, and the investigators also had extensive follow-up from hospital episode statistics. ECG recordings were available for 58,161, of which 26,998 were men (46.4%); the median age was 58 years, median body mass index (BMI) was 26.4 kg/m2, and all participants were healthy.

Those with a previous myocardial infarction, cardiac arrhythmias or conduction disorders were excluded, as

were those who had a pacemaker, had had heart failure, or were on calcium channel blocker medication. Participants with a change in RR interval during the exercise stress test <10ms were also excluded, because Ramírez noted, “a minimum change in the T-wave is necessary for prediction”.

She added: “We first derived an average T-wave at rest, an average T-wave at peak exercise and an average T-wave at recovery. Then, to quantify the morphological variations during exercise, we compared the average T-waves at rest and at peak exercise, after correcting for the change in RR and obtaining the TMR during exercise. Similarly, to obtain TMR during recovery, we compared the average T-wave at peak exercise with the average T-wave at recovery, and we corrected for the change in RR.” The primary endpoint of the study was death or hospital admission due to a major adverse cardiovascular event. The secondary endpoint was death or hospital admission due to ventricular arrhythmia.

Ramírez stated: “There were 1,196 individuals who had at least one cardiovascular event, and those showed a significantly higher TMR index during exercise, and during recovery, than those who were event free. For the secondary endpoint, we also observed significantly higher values for TMR in individuals with at least one arrhythmic event, but please note that this was a very low number [n= 14] because we are analysing

the general population.”

Following univariate Cox analysis, the variables significantly associated with cardiovascular events were gender, age, BMI, diabetes, and systolic blood pressure, as well as the average heart rate during exercise and recovery, the change in heart rate during exercise and recovery, and TMR during exercise and recovery. However, after multivariate adjustment, only the average heart rate during exercise, and both TMR markers, remained significantly associated, with TMR during recovery being the index most strongly associated.

The investigators then applied a cut-off value of 0.04, developed in the earlier study to risk stratify the sudden cardiac death risk. Ramírez indicated: “Individuals with a TMR value during exercise >0.04 had significantly more cardiovascular events than those in the lower risk group (TMR<0.04), with the survival curves being significantly separated. Regarding TMR during recovery, the opening of the survival curves is even larger, with a P-value that is even smaller, indicating that TMR during recovery is a better risk stratifier than TMR during exercise.”

She concluded: “We have demonstrated the association between TMR and cardiovascular events in a large general population. We found that the predictive value during the recovery stage is better and stronger than during the exercise stage.”

More work needed to understand reasons for gender gap in cardiovascular research Writing in Circulation: Cardiovascular Quality and Outcomes, David Ouyang (Stanford University, Falk Research Center, Palo Alto, USA) and others report that while the number of female first and senior authors of cardiovascular research papers has increased over the past four decades, women continue to be poorly represented as first authors, senior authors, and in the number of publications. They say further work is needed to understand why there continues to be a gender gap in cardiovascular research.

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ccording to the investigators, an important measure of research productivity is the number of peer-reviewed publications and they note “in consideration for promotion, the number and impact of publications is explicitly evaluated”. Therefore, the authors sought to “determine trends in authorship of cardiology-related publications in three high-impact general cardiology journals over the past 40 years”.

The hypothesis of the study was that women would be less likely to be first or senior authors in high-impact published research but the gap between men and women would have decreased over time. The journals reviewed were: Circulation, Journal of the American College of Cardiology, and the European Heart Journal.

From 55,085 articles identified, 257,328 authors could be matched for gender; of these, 71,345 were unique authors. Ouyang et al write: “In total, 23,629 (33.1%) authors were female. Only 4,434 (26.7%) of 16,613 first authors were female (p<0.001). There was a smaller proportion of female authors in senior authorships, accounting for 2,193 (19.7%) of 11,160 senior authors (p<0.001).” Additionally, both research papers with a first female author and those with a senior female author had a higher mean number of additional middle female authors than did papers with male first or senior authors.

Furthermore, articles with a female senior author more frequently had a female first author (0.37 vs. 0.18 for papers with a male senior author; p<0.001).

David Ouyang

However, the number of female authors increased over time: 9.5% with a female first author and 5.9% with a female senior author between 1980 and 1990 vs. 26.2% and 17.4%, respectively, between 2010 and 2017. Ouyang et al comment: “Our analysis showed a persistent, though narrowing, gap in female representation in research on all levels, as an author in general, as a first author, and as a senior author.”

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Pacemakers

The first 60 years of cardiac pacing Richard Sutton Comment & Analysis Sixty years ago, the first pacemaker implant was made in Stockholm, Sweden (Senning & Elmqvist) on 8 October 1958. The patient had atrioventricular block with recurrent AdamsStokes attacks. These were prevented by the implant—although, it only functioned for a few hours. Pacing therapy was used for the remaining 43 years of the patient’s life, but he received more than 30 devices in this time. In this commentary, Richard Sutton reviews how pacing has come a long way since then.

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he first implants used epicardial leads and very unreliable batteries. Medtronic founded by Earl Bakken in Minneapolis, USA, rapidly became the largest manufacturer. Conversion to endocardial leads took place in the 1960s and this was associated with a change in implanter from cardiac surgeon to cardiologist. The first dual chamber pacing system, VAT mode, appeared in 1962 (Nathan, Miami, USA) but neither the leads nor the batteries were up to the challenge. Batteries leapt forward in the early 1970s with the advent of the lithium cell. The first batteries lasted more than 10 years but this was reduced by downsizing the cell in keeping with a desire to have smaller devices.

Sophistication

Dual chamber endocardial pacing emerged in 1976 (VDD mode), which was termed “physiological pacing” but pacing has since become more and more physiological. In the 1970s pacemakers became externally programmable which allowed the physician to tailor the device to individual patient needs.

Also in 1976, rate responsive pacing using a sensor became a real possibility with the activity sensor (VVIR).

DDD pacing, invented by Funke of Germany, followed in 1978 and this quickly became DDDR. In the 1990s pacing was regarded as expensive therapy and many large clinical trials were conducted in the hope of proving that the more sophisticated devices were better but these largely failed. Nevertheless, the sophisticated devices continued to be preferentially selected. The most important recent development in cardiac pacing started in France in

1994 (Ritter & Mugica). This became known as cardiac resynchronisation therapy (CRT). It was shown to influence heart failure favourably and sometimes dramatically.

Large clinical trials were undertaken from 2001, which subsequently have proved the efficacy of the therapy (providing there is delayed conduction in the left ventricle).

The therapy also introduced the concept of non-response which regrettably affects about 30% of those treated.

In the early 2000s, devices became readily monitored through internet-based systems—remotely permitting communication of the device and the patient with the monitoring centre—avoiding many journeys to hospital for routine checks and offering the centre the ability to predict problems before they became symptomatic.

The latest pacing development was the leadless device, which was introduced at the beginning of the current decade. Presently, these are all single chamber ventricular pacemakers (VVIR) but soon we can expect dual chamber versions. The major advance is the abolition of the lead with all its attendant problems of fracture, sepsis, displacement and perforation but there is also greater comfort for the patient and an easier implant procedure. In CRT, His bundle pacing is receiving deserved attention as it appears to offer greater simplicity and possibly also efficacy.

Commercialisation

During the development of pacing companies have come, gone and merged. Now Medtronic continues with Abbott, Boston Scientific, Biotronik and Sorin as its competitors.

Companies have generally behaved very ethically and have had extremely high standards of manufacture and patient

Adding biomarkers to clinical risk factors improves stroke prediction in “clinically low-risk” AF patients

The addition of a biomarker-based risk tool to the stroke risk analysis of atrial fibrillation (AF) patients already classified as low risk using clinical risk factors can further refine risk stratification, leading to maximum benefit and minimum costs of risk prediction models.

SEUNG YONG SHIN (Cardiovascular and Arrhythmia Center, Chung-Ang University Hospital, Chung-Ang University, Seoul, South Korea) and others performed a retrospective analysis to determine how many patients with a low CHA2DS2VASc score went on to have a stroke, and how to differentiate patients with covert stroke risk from truly low-risk patients.

Speaking at the 2018 Heart Rhythm Congress (6–9 October, Birmingham, UK), Shin explained: “You can categorise that a certain number of patients classified

by CHA2DS2VASc score as ‘low risk’ experience ischaemic stroke. The current risk prediction model requires more refinement to differentiate truly low-risk stroke patients among low-risk patients.

For the first time, we demonstrated how the addition of biomarkers can further refine stroke risk stratification among AF patients initially defined as low risk by clinical risk factors.”

Patients with AF who had experienced an embolic stroke between 2013 and 2016 were retrospectively recruited from nine institutions in Korea. Control patients were

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safety. Despite their huge efforts, recalls still occur but they are very few compared with the numbers manufactured. It is reasonable to appreciate that we will never make a perfect device.

Governments have become important players in the field, recurrently demanding lower and lower prices from manufacturers, which has been very effective. Another effect beyond reducing prices is to reduce research and development budgets in pacing for bradycardia and even for CRT. Thus, the market is termed by manufacturers as flat and with low profit margins. This is sadly a complacent and negative attitude as pacing is an unfinished work.

The future

There are many patients in the developed world aside from lesser developed countries that would benefit from pacing but are never considered. This statement includes the UK where the implant rate is ~650 new cases/million population per year compared with figures of close to 1,000 for Germany, USA, France, Belgium and Italy. The reasons for this cannot be explained by demographics as the UK’s are very similar to those in the other countries mentioned.

As was pointed out by Rickards in the early 1980s the UK has fewer cardiologists and fewer cardiac facilities than the other mentioned countries. In the decade 2000–2010 the implant rate improved and was paralleled by growth in cardiac resources. Guidelines are too often not followed in the context of carotid sinus syndrome and even vasovagal syncope. Bradycardia patients still escape diagnosis and, therefore, therapy as shown by differences in implant rates in neighbouring general practices with identical demographics. Manufacturers could help here with greater educational efforts.

In developing countries, greater efforts by manufacturers will bring greater benefits for patients and rewards for companies but more innovative methods are required.

Device implantation without fluoroscopy using simplified electrical electrophysiological study methods or ultrasound, improved hub and spoke care delivery, maintenance of simpler devices in production that allow cheaper prices could all contribute and manufacturers could play an important part.

Thus, it can surely be said that pacing is one of the most successful therapies available in medicine, not just cardiology. It has a secure future in benefitting millions more patients when appropriately applied. All involved must play their parts.

Richard Sutton is Emeritus professor of Clinical Cardiology at Department of Cardiology, Hammersmith Hospital, National Heart & Lung Institute, Imperial College, London, UK

matched by CHA2DS2VASc score from another Korean AF registry (CORE-AF).

Of the 3033 patients recruited, 583 (19.2%) had a CHA2DS2VASc score of 0–1.

Patients in the stroke group were older and there were more females than in the control group, which had a greater incidence of heart failure, hypertension, and diabetes. Patients with stroke had a larger left atrial dimension, a lower creatinine clearance (CCr), and a higher N-terminal pro brain natriuretic peptide (NT-Pro BNP).

Logistic regression analysis identified four factors associated with stroke in patients with AF who had a CHA2DS2VASc score of 0 or 1. These were: age ≥60 years, NT-proBNP ≥300pg/ ml, CCr <50ml/min, and diameter of the LA ≥45mm. As an aide memoire, the researchers labelled these independent factors “ABCD”.

“As CHA2DS2VASc score may be a risk modifier, especially in low-risk patients and Asian patients, we analysed

it in two ways—CHA2DS2VASc score including and excluding the sex category [CHA2DS2VASc and CHA2DS2VA].

Only 8% or 9% during this period on the ABCD score experienced stroke. The proportion of stroke gradually increases in accordance with increments of the ABCD score. ABCD score demonstrated significantly improved discrimination,” Shin noted.

He added: “Although we performed our study retrospectively, ageing, BNP, creatinine clearance, and diameter of the left atrium were independently associated with stroke events in patients with low CHA2DS2VASc score; one-fifth of patients [19.2%] with cardioembolic stroke were classified as low risk by CHA2DS2VASc score, but by applying associated biomarkers we could differentiate one truly low-risk patient out of 20–25 low-risk patients. Compared with other complicated biomarker-based risk scores the ABCD score is easier to apply in daily clinical practice with relative simplicity.”

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Interview

Profile

Haran Burri During his studies Haran Burri was fascinated by the simplicity of an ECG providing a vast amount of information on cardiac functions. This drew him towards a career in cardiology and electrophysiology. He is an associate professor at the University Hospital of Geneva where he is responsible for the Cardiac Pacing programme and is also actively involved in interventional electrophysiology. He speaks to Cardiac Rhythm News about various aspects of his career.

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

I was intrigued from an early age by how our body works, which was one of the reasons I went into medicine. During my studies, I was fascinated by how simple line drawings of an electrocardiogram tracing could provide so much information about cardiac function. The ECG therefore drew me towards cardiology and later to electrophysiology. In addition to the exciting technical developments that we have witnessed over the last years, electrophysiology and device therapy are extremely varied fields that combine aspects such as clinical judgment, non-invasive and invasive diagnostics, drug therapy, device programming, catheter manipulation and surgical skills. I do not believe that there are many fields in medicine which are so varied.

Who have been your career mentors?

I am very grateful to Marc Zimmermann whom I have known since my internship in Geneva. In addition to conveying his mastery in electrophysiology, he has been a role model and a constant source of guidance and friendship. I am indebted to Philippe Chevalier, with whom I spent a fellowship year in Lyon, and to Dipen Shah, who taught me the ropes of atrial fibrillation ablation when he moved over from Bordeaux to Geneva.

I am also grateful to Hein Heidbuchel, the current European Heart Rhythm Association (EHRA) president, who has entrusted me with important tasks, such as chairing the education committee and currently the congress scientific programme committee.

What has been the most important development in the field of electrophysiology during your career?

There have been many developments but the one I consider most important is electro-anatomical mapping, which allows us to tackle complex arrhythmias and also dramatically reduces fluoroscopic exposure. Remote monitoring has been a milestone in the domain of device therapy.

What has been the biggest disappointment where you had hoped something would change practice but did not?

Alternative sites for ventricular pacing held the promise of being more physiological and less detrimental in terms of ventricular function. Pacing the left ventricle or the interventricular septum have unfortunately not been found to be any better than pacing the right ventricular apex. However, I still implant pacing leads on the septum to avoid perforation.

Of the research you have been involved with, which do you think will have the greatest impact on clinical practice?

It is indeed a great satisfaction when one’s research does not simply serve to lengthen one’s list of publications,

but has an impact on treating patients. Colleagues have mentioned that work I have done on techniques for axillary vein access and for septal lead placement have been useful in their own practise.

What are your current research interests?

I believe that His bundle pacing may be the holy grail we have been searching for as an alternative to ventricular pacing and may even restore electrical synchrony more efficiently than biventricular pacing.

I am currently involved in research in various aspects of His bundle pacing such as His-optimised cardiac resynchronisation therapy (CRT) and also regarding device programming.

As you are the 2018–2020 scientific programme chairperson for EHRA and EHRA 2019 being the second annual edition of the congress, what were the challenges of turning a biannual meeting (as EHRA was previously) into an annual one?

The scientific programme committee is elected for two years, and we will now be busy with this task during both these years. Constructing an attractive programme requires a lot of hard work and fresh ideas.

I am fortunate to be helped by Katja Zeppenfeld who co-chairs the committee and we have a great team of colleagues who actively contribute.

What are the core themes of the 2019 meeting and what do you think the highlights will be?

Innovation is the theme of EHRA 2019, and we will be emphasising this in our sessions by covering new techniques and technologies which are relevant to our clinical practise. We will also be hosting an EHRA innovations award to promote the work of inventors. We will be organising for the first time three EHRA “championships” to challenge participants with interpretation of ECGs, device tracings and electrophysiology tracings. Also, we have had a record number of abstract submissions, which has allowed us to choose high-quality scientific content for the rapid fire and poster sessions.

Why should physicians be interested in innovation?

Because one should always strive for greater efficacy and safety.

Given we are now living in the digital age with so much information online, why is it valuable to attend conferences such as the EHRA in person?

You could also ask yourself why one still travels or goes to museums as one has Google Images! Despite the plethora of e-learning for continued medical education, I strongly believe that in-person exchange with colleagues will always remain a valuable and stimulating

experience which cannot be otherwise replaced.

Social media platforms such as Twitter and LinkedIn are increasingly being used as a source of medical communication. What do you think are the pros and cons of using social media for medical communication?

I am already struggling to keep up with my daily deluge of emails and would simply not be able to handle social media. No doubt these means of communication are useful for spreading information, but they should not be intrusive. Triage of information and quality control of content are also issues.

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Fact File

What has been your most memorable case?

I had implanted a 12-year-old girl with an implantable cardioverterdefibrillator (ICD) for aborted sudden death due to coronary artery spasms, who kept having recurrences of spasms with ventricular arrhythmias and ICD shocks despite trying different medical therapies and even sympathectomy. There was simply nothing that I or my colleagues could do to help her, and she ended up with a heart transplant. As parents, paediatric cases affect us the most emotionally.

What advice would you give to someone just starting their career in the field of electrophysiology?

One has to be passionate about what one does, as there is much to learn and it will take a lot of effort. Do not bluff, because it will be hard to take you seriously again if you are not sincere.

As you progress, always keep an open mind about how best to do things.

And finally, always remember that you are treating a person and not just an arrhythmia.

Outside of medicine, what are your hobbies and interests?

Travelling with my family allows me to enjoy time with them that is otherwise denied during my working days. I enjoy the speed of downhill skiing and of kitesurfing, which provide me with my adrenalin boosts as well as experiencing the elements of the mountains and the sea. I can also on occasion be spotted struggling in the last quintile of mid-distance running races.

Innovation is the theme of EHRA 2019, and we will be emphasising this in our sessions by covering new techniques and technologies which are relevant to our clinical practise.

Current appointments

Attending physician, Cardiology Department, University Hospital, Geneva, Switzerland Associate professor, Faculty of Medicine, University of Geneva, Switzerland

Medical training

2017: Associate professor 2015: Assistant professor 2007: EHRA competency in interventional electrophysiology 2006: EHRA competency in cardiac pacing 2001: FMH (Swiss specialisation) in Cardiology 1992: Swiss Federal Medical Diploma (1992)

Society membership

European Society of Cardiology Education Board European Heart Rhythm Association (EHRA) Scientific Congress Committee; chairman 2018–2020 EHRA Education Committee (2009-2015); chairman 2013-2015 Swiss Society of Cardiology Working group in Electrophysiology; president 2015–2017 EHRA Health Economics Committee (2010-2011)

Publications

Burri H, et al. Device programming for His bundle pacing. Circulation Arrhythmias & Electrophysiology 2019 Leclercq C, Burri H, et al. CRT non-responder to responder conversation rate in the more response to cardiac resynchronisation therapy with MultiPoint Pacing (MORE-CRT MPP) study: Results from phase l.

Eur Heart J 2019 Burri H, et al. Risk stratification of cardiovascular and heart failure hospitalisations using integrated device diagnostics in patients with cardiac resynchronisation therapy defibrillator; Europace 2018; 20: e69–e77 Burri H, et al. Low risk of electromagnetic interference between smartphones and contemporary implantable cardioverter defibrillators. Europace 2016;18(5): 726-31 Burri H, et al. The EHRA book on pacemaker, ICD and CRT troubleshooting. Oxford University Press; 2015

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Jan

BIBABriefings

Cardiologs co-founder receives innovation award for AI ECG platform YANN FLEUREAU, the co-founder and CEO of Cardiologs, has been selected as the BNP Paribas European Innovator of the Year (2018) for developing a cloud-based AI platform that can promptly and accurately analyse ECGs. He was chosen from 35 innovators (originally 1,000) recognised as being an innovator under 35 in Europe by Massachusetts Institute of Technology (MIT) Technology Review. According to MIT Technology Review, the annual list highlights outstanding innovators who are younger than 35 and spans a wide range of fields (including communications and the internet).

About the BNP Paribas award, Fleureau says: “I am deeply honoured to be selected to receive this prestigious award and am humbled to be

Johns Hopkins Medicine aims to ADVANCE treatment of cardiac rhythm disease with new centre JOHNS HOPKINS MEDICINE (Baltimore, USA) has opened a new US$1.5 million centre that will focus on improving the diagnosis and treatment of heart rhythm disorders.

The Alliance for Cardiovascular Disease and Treatment Innovation or “ADVANCE” centre will be co-led by the biomedical engineer Natalia Trayanova and the electrophysiologist Hugh Calkins.

The goal, over the next five years, is for Calkins and other cardiologists at Johns Hopkins Medicine to lead clinical trials of engineering strategies

by Trayanova and her colleagues. A press release notes that Trayanova “pioneered” the use of a 3D virtual replica heart and its electrical function.

It adds that her lab is currently studying ways to more precisely predict which patients are at increased risk of

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MedTech Insights

included among the many talented innovators who are using technology to benefit humankind.

This technology [by Cardiologs] not only improves cardiac diagnostic efficiency and analysis of ECGS, but also democratises access to make expert cardiac diagnostics more available in developing countries and emerging markets.”

BardyDx has also received recognition for its innovative device, the Carnation ambulatory monitor (CAM). Vizient has awarded the company its Innovation Technology contract. The Innovation Technology contract, a Bardy Diagnostics press release explains, is given to technologies that demonstrate an ability to enhance clinical care or patient safety or improves an organisation’s care delivery and business model. The CAM is the world’s first P-wave centre ambulatory cardiac patch monitor and arrhythmia detection device.

Ken Nelson, chief commercial officer of Bardy Diagnostics, says: “We are delighted that Vizient’s member-led council selected CAM for an Innovation Technology contract. We look forward to working with Vizient’s diverse membership to develop strong relationships that will improve patient outcomes with the use of our CAM patch and monitoring services”.

sudden death or stroke associated with ventricular or atrial fibrillation.

“Establishing this alliance will lead to an exciting blend of engineering and medicine. It is the culmination of more than five years of collaboration between engineers and clinicians to determine how to solve medical problems with computational and data-driven approaches,” Trayanova comments.

Calkins states that, together, the engineers and clinicians working at the centre want to “find new strategies that will have a profound impact on the management of a wide range of arrhythmias”. He adds that more than five million people in the USA experience episodes of atrial fibrillation and “tens of thousands” more have had ventricular arrhythmias.

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.

The aim of every report is to give an overview of the key information affecting the medical device industry, enabling those working in the industry to keep abreast of the latest developments and make knowledgeable decisions.

For more information about BIBA Briefings or BIBA MedTech Insights, please contact Elizabeth Sutherst: elizabeth@bibamedical.com

ICD therapy may significantly help appropriately selected Brugada syndrome patients Patients with Brugada syndrome judged to be at high risk for ventricular arrhythmia may significantly benefit from implantable cardioverter-defibrillator (ICD) therapy, concludes a recent study by Adem Dereci (Rotterdam, The Netherlands) and colleagues, published in the Journal of the American College of Cardiology: Clinical Electrophysiology.

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rior to this study, a complete overview of clinical outcome, appropriate and inappropriate interventions, and complications after implantable cardioverter-defibrillator (ICD) therapy in patients with Brugada syndrome was lacking.

The investigators used MEDLINE database to find published reports on ICD therapy in Brugada syndrome patients. In total, of 828 studies found, 22 were included in the meta-analysis, combining data for an overall number of 1,539 patients (mean age 45 years).

Over a follow-up period of just under five years, 277 patients (18%) experienced an appropriate ICD intervention and 230 (18%) had an inappropriate ICD intervention. Dereci et al report that ICD therapy was associated

with an appropriate ICD intervention rate of 3.1 per 100 person-years and low cardiac and non-cardiac mortality rates. They add that the low cardiac mortality rate of 0.03 per 100 person-years as an indicator of this prevention of sudden cardiac death. However, the inappropriate ICD intervention rate was 3.3 per 100 person-years, which “may lead to considerable morbidity”.

According to the investigators, the majority of the device-related complications included lead malfunction, with an occurrence rate of 1.6 per 100 person-years.

Infection and lead dislocation were also observed, with respective rates of 0.6 per 100 person-years and 0.4 per 100 person-years.

Dereci et al write: “The relatively high incidence

of complications is a serious concern, because most patients with Brugada syndrome are otherwise healthy and relatively young individuals. Because of the young age at implantation (mean age was 45 years) and the occurrence of atrial fibrillation (AF) in 10%, patients with Brugada syndrome may be more vulnerable to inappropriate shocks. Information on the incidence of devicerelated complications, such as lead malfunction (1.6 per 100 person-years), psychological implications (1.3 per 100 person years), infection (0.6 per 100 personyears), lead dislocation (0.4 per 100 person-years), and any complication (0.6 per 100 person-years) may be discussed during patient counselling in patients eligible for an ICD.”

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Clear need for further research in obstructive sleep apnoea and atrial fibrillation Caroline Broughton Shahbaz Piracha Martin Allen Comment & Analysis Obstructive sleep apnoea and atrial fibrillation (AF) have presented many challenges including identifying which patients need to be assessed for obstructive sleep apnoea and what the management options should be. In this commentary, Caroline Broughton, Shahbaz Piracha and Martin Allen write in Cardiac Rhythm News about these issues.

S

leep apnoea is a common condition affecting an unknown number of the UK population, with studies in North America suggesting the prevalence may be in double figures.1 Broadly speaking there are two types of sleep apnoea. One is the less common central apnoea that occurs when there is a lack of effort to breathe, often seen in heart failure while the much more common type seen in over 90% of cases is obstructive sleep apnoea associated with AF.

Identifying treatments

The mechanism of the association remains uncertain. This may be related to the recurrent hypoxaemia that occurs when the airway is obstructed by the collapse of the upper airway. An alternative explanation may be the large intrathoracic pressure swings that occur during the cessation of breathing and the large negative pressures generated.

Likewise, the sympathetic activation that is associated with obstructive apnoea is also likely to be a contributory factor.2 Identifying the association is important as treatment of the obstructive sleep

apnoea is often associated with an improved control of the atrial fibrillation and maintenance of rhythm control post cardioversion.3 Moreover, atrial structural remodelling and conduction changes can occur with prolonged exposure to obstructive sleep apnoea over time, which consequently impairs treatment by all modalities if left untreated.4 However, this is not always easy as the excessive daytime sleepiness that is such a feature of obstructive sleep apnoea is often absent or limited in patients with atrial fibrillation.5 The clinical syndrome of sleep apnoea where there are recurrent episodes of airway collapse, associated with arterial oxygen desaturation and sleep fragmentation as a consequence of arousal from sleep is often suggested from the clinical history of loud snoring, witnessed apnoea and daytime sleepiness.

Clinical examination should take note of the commonly coexisting hypertension that is evidenced in obstructive sleep apnoea and the size of the upper airway.

While obesity is associated in obstructive sleep apnoea, up to one third of patients have a normal body mass index.

Sleep studies

This fact that you do not have to be obese to have obstructive sleep apnoea is often poorly recognised. Thus, to identify obstructive sleep apnoea in the AF population, a high index of suspicion is needed with onward referral for sleep studies to confirm the diagnosis and the severity of the sleep apnoea so patients can be triaged for the most appropriate treatment. While this may be lifestyle changes, for many patients the continuous positive airways pressure is the treatment of choice, as recommended by the National Institute for Health and Care Excellence (NICE).6 This involves the individual sleeping with a snugly fitted mask, held in place by a strap, that is connected to a flow generator that applies a pressure to the airway to prevent the collapse. Such treatment is well tolerated and highly effective in controlling symptoms, reducing hypertension and aiding control of associated medical problems, including AF. Linz has suggested that all patients with AF who are diagnosed with obstructive sleep apnoea should be

T-waves are a predictor of ventricular events in Brugada syndrome ECG T-waves can be used to predict a positive ajmaline test, which in turn can be applied to monitor the risk of future ventricular events for patients with Brugada syndrome. Neil Srinivasan (Department of Cardiac Electrophysiology, The Barts Heart Centre, St Bartholomew’s Hospital, West Smithfield, London) and colleagues have developed multivariate predictors of an ajmaline positive, and of ventricular arrhythmias or syncope, from a baseline ECG. SRINIVASAN TOLD DELEGATES at the 2018 Heart Rhythm Congress (6–9 October, Birmingham, UK): “The management of arrhythmia risk in patients with Brugada syndrome, and if and when to implant an implantable cardioverter defibrillator (ICD), remains challenging. One of the problems with diagnosing Brugada is that the ECG varies with time. So the diagnosis as a snapshot ECG is very challenging. The other thing is that the ECG itself varies with wave position in the ECG leads. The standard V1 and V2 leads may actually not reveal the diagnostic ECG.” Management and follow up of patients with a Type 1 ECG is relatively straightforward. But for patients with a Type 2 or borderline ECG, or a family history and some abnormal symptoms, risk stratification is more complicated. “Where somebody has had an

arrhythmic event, we know that their subsequent chance of getting further arrhythmic events is quite high. But the remaining patients are either asymptomatic—and they do fine and you keep following them up—or they have symptoms. The problem is that the first time the patient has a symptom it might be a major arrhythmic event,” Srinivasan commented.

He explained: “People have either measured the peak of a T-wave [Tp] to the end of a T-wave [Tend] in a single lead or they have looked at the Tp to Tend greatest differences across the epicardial leads.”

Research done by Srinivasan’s group revealed that Tp to Tend has no relation to transmural dispersion of repolarisation. However, he said: “We were able to find a good marker that related to right to left dispersion of repolarisation. And, we hypothesised that maybe we could

Obstructive sleep apnoea

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managed by multidisciplinary teams.7 This is the process we have followed at our institution for many years, with patients who are seen by the specialist AF nurse being referred for sleep studies.

Additionally, all patients are referred to a cardiac rehabilitation team for exercise assessment, smoking cessation, dietary advice and hypertension management in collaboration with local GPs. The difficulty lies in identifying which patients with AF are most likely to have obstructive sleep apnoea that is contributing to their on-going AF symptoms. The traditional association of sleepiness that exists in the general obstructive sleep apnoea population is not found in patients who have AF. Hence looking for sleepiness using the Epworth sleepiness score, as an aid to who should be referred for sleep studies appears of little use, something we found in our study.8 More work is clearly needed to identify specific risk factors for both AF and obstructive sleep apnoea in order to streamline services and optimise treatment outcomes.

Caroline Broughton is a specialty registrar in cardiology at Royal Stoke University Hospital, Stoke-on-Trent, UK. Shahbaz Piracha is a specialty registrar in respiratory medicine at Sandwell and West Birmingham Hospitals, UK. Martin Allen is a consultant physician in respiratory medicine at Sandwell and West Birmingham Hospitals, UK. References 1. Garvey et al. J Thorac Dis. 2015;7(5):920-9.

2. Kwon et al. Sleep Med Rev 2018;39:134-42.

3. Kanagala et al. Circulation 2003;107(20):2589-94.

4. Neilan et al. J Am Heart Assoc 2013;2(6):e000421.

5. Broughton et al. EP Europace, Volume 20, Issue suppl_4,1 October 2018, Pages iv7-iv8, https://doi. org/10.1093/europace/euy198.008.

6. National Institute for Health and Care Excellence (2008).

Available at: https://www.nice.org.uk/guidance/ta139 [Accessed 17/12/2018] 7. Linz et al. JAMA Cardiol 2018;3(6):532-40.

8. Albuquerque et al. Chest 2012;141(4):967-73.

use that in patients with Brugada syndrome.”

Srinivasan and colleagues performed a retrospective analysis of patients who had undergone ajmaline testing to investigate an abnormal ECG, family history of sudden cardiac death, or unexplained syncope or ventricular arrhythmia with Brugada-like ECGs. ECG data were extracted and T-wave markers analysed using custom designed Matlab software. In all, 199 patients were identified.

Srinivasan said: “Out of the 199, there were only 41 positive ajmaline tests, but 22 of these patients went on to develop symptoms over an eight-year period. Using our software, we were able to measure the start of the T-wave, the peak of the T-wave, and the end of the T-wave.”

Multivariate predictors of an ajmaline positive on the baseline ECG were identified as the difference between the earliest T-wave start to the latest T-wave end (the total dispersion p=0.03). The investigators also found a right to left dispersion marker that was greater in the ajmaline positive patients than in the ajmaline negative patients (the difference between the end of the T-wave upslope in V2 to the end of the T-wave upslope in V6, p=0.04). The group also analysed the small number of patients positive for ajmaline to see whether the ECG could be used to determine the likelihood of developing ventricular events, and found that Tp to Tend in V2 was predictive, as was the right to left dispersion marker.

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Product News rare new technologies that produces benefits for all stakeholders.”

BioCardia submits 510(k) application to US FDA for its Avance steerable introducer for transseptal access to heart

FDA approval granted for Vascade MVP system

Premarket approval (PMA) from the US Food and Drug Administration (FDA) has been granted for the Vascade MVP venous vascular closure system (Cardiva Medical). Vascade MVP is the first and only vascular closure system designed and labelled specifically for multisite venous closure—for 6–12F inner diameter sheaths. This access site approach and size range is the standard in electrophysiology procedures such as cardiac ablation and left atrial appendage closure.

The approval is based on results of the AMBULATE pivotal trial, a 204-patient, 13-site randomised, controlled study of the Vascade MVP system compared to standard manual compression following cardiac ablation. The study showed significant improvements in time to ambulation, total post-procedure time and time-to-discharge eligibility, as well as improved patient satisfaction scores and reduced use of opioid pain medications.

Results of the trial were presented at the 2018 American Heart Association Scientific Sessions (AHA; 10–12 November, Chicago, USA) by Andrea Natale, co-principal investigator and executive medical director, Texas Cardiac Arrhythmia Institute in Austin, USA. Vascade MVP uses a simple and proprietary delivery system to place a collagen patch on the outside of each vessel puncture site following completion of the procedure. Nothing is left behind inside the vessel, and the collagen outside the vessel wall is resorbed in a short period of time enabling reaccess for future procedures.

“We are at the dawn of a new era now for electrophysiology procedures with this trailblazing technology,” says Suneet Mittal, director of electrophysiology and medical director of The Snyder Center for Comprehensive Atrial Fibrillation at The Valley Hospital in Ridgewood, USA. “The improvements we have seen in both patient satisfaction and more efficient hospital workflow make this one of those

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Market watch

BioCardia has announced its 510(k) submission for US FDA clearance of the Avance steerable introducer, which is designed for introducing various cardiovascular catheters into the heart, including via the left side of the heart through the interatrial septum. A press release reports that the Avance steerable introducer leverages new technology developed for BioCardia’s Morph family of steerable introducers and applies it for transseptal procedures.

It adds that the bidirectional Avance is designed to be virtually whipless around curves, due to its helically arranged pullwires, and provides exceptional torsional stiffness. Avance also offers a rotating haemostasis port. These features are intended to enable greater predictability, stability and control during procedures.

Procedures that leverage transseptal delivery include atrial fibrillation ablation, patent foramen ovale (PFO) and atrial septal defect (ASD) repair, percutaneous mitral valve repair, left atrial appendage closure, and percutaneous left ventricular assist device placement, among others.

BioCardia CEO Peter Altman comments: “The best-in-class design that underlies Avance was developed to enhance delivery of our investigational CardiAMP and CardiALLO cell therapies. We are excited about making this product available to the broader transseptal market”

US FDA approve HeartMate 3 heart pump for advanced heart failure patients not eligible for a heart transplant

The HeartMate 3 left ventricular assist device has received US FDA approval as a destination therapy for people living with advanced heart failure. With the approval, physicians can now offer the HeartMate 3 system to patients not eligible for a transplant who will live with their device for the rest of their lives. For advanced heart failure patients who can no longer rely on earlier stage treatment options, a press release reports, LVAD’s take the workload off a weakened heart by pumping blood through the body.

The press release adds that in developing the HeartMate 3 system, Abbott set a new standard in LVAD therapy—reducing the system’s size while reimagining how blood passes through a heart pump. The HeartMate 3 pump uses technology known as Full MagLev (fully magnetically-levitated) Flow, which reduces trauma to the blood passing through the pump while

improving flow.

Nir Uriel (University of Chicago Medicine, Chicago, USA), says: “Approximately a quarter of a million people are living with advanced heart failure, and many of these people will need a heart transplant; however, only a few thousand will receive a new heart.

The destination therapy approval for Abbott’s HeartMate 3 device now gives these patients new hope that they can receive a heart pump clinically proven to mitigate challenges we have historically confronted with this therapy—stroke and blood clotting—while also offering survival rates on par with transplant.”

Mike Pederson, senior vice president of Abbott’s Cardiac Arrhythmias and Heart Failure business, says: “We partner with physicians to holistically develop therapies that benefit patients and achieve better outcomes. The unique design of the HeartMate 3 LVAD—with its Full MagLev Technology—takes an established innovation and improves upon it in meaningful ways to help people with advanced heart failure live fuller lives.”

The HeartMate 3 system’s US approval was supported by clinical data from the MOMENTUM 3 trial. During the study, patients with the HeartMate 3 LVAD had a survival rate of 82.8% at two years.

Furthermore, rates of suspected pump thrombosis remained very low at 1.1% at two years. The study also showcased the lowest-ever published stroke rate (10%) for a continuous-flow LVAD at two years.

AI-based solution to screen atrial fibrillation and improve stroke prevention

Maisense, a start-up company specialising in stroke prevention, has recently introduced an AI-based solution that can screen stroke through early detection of atrial fibrillation (AF), that will be presented at MEDICA (12–15 November, Düssledorf, Germany).

Patients with AF have a fivefold increase in risk of stroke compared to those without. It affects 4.5 million people living in the European Union, and accounts for approximately onethird of hospitalisations for cardiac rhythm disturbances. The European Heart Rhythm Association (EHRA) released a classification system of AFrelated symptoms in 2014. EHRA also stressed the fatal consequence even if AF symptoms are not noticeable to the patient. “Since an AF episode can come and go, there may be many patients undetected and therefore they didn’t receive timely treatment. That is why we take AF screening seriously as a key measurement for stroke prevention,” says Benjamin Chiu, CEO of Maisense.

AF is usually diagnosed on an ECG but if a patient’s symptoms do not occur while he or she sees his doctor or if they are back to normal at this point of time, the doctor would not be able to give adequate advice. As a result, Maisense presented the Freescan device and the myFreescan app, which deliver an all-in-one solution; utilising artificial intelligence for early AF detection, arrhythmia (bradycardia and tachycardia)

detection, pulse wave velocity, and blood pressure monitoring in a single device.

Users adopting Maisense’s solution can assess their risk level of strokes anytime.

From the patient’s perspective, the solution makes it very easy to measure and record all these biomedical signals at any time. Patients can monitor their own health conditions and take action at an early stage. Through the web-based Patient Care System, doctors can also be informed immediately when abnormal incidents occur and if a patient activated this function under doctor-patient privilege. It also provides sufficient data for doctors to make assessments quickly.

The option does not only help to avoid unnecessary healthcare spending and time investments but also improves the service efficiency.

As Apple announced its Watch Series 4, which can record ECG and has received FDA approval, it is believed that more and more people are noticing the importance of irregular heart rhythm detection. Maisense is the first company to provide an all-in-one solution to screen the top three causes of stroke: arterial stiffness, hypertension and atrial fibrillation in one single device.

Maisense’s Freescan has received EU CE medical certification and is now available in Germany.

FDA approve TSP Crosser transseptal access system

Transseptal Solutions has received FDA 510(k) clearance for its TSP Crosser transseptal access system. A press release reports that the system has a novel approach of transseptal puncture and left atrial navigation to introduce various cardiovascular catheters into the left heart chambers, adding that the system has a built-in steering mechanism.

The TSP Crosser is indicated for use in procedures where access to the left atrium via transseptal technique is desired, such as: mitral valve repair, mitral valve replacement, paravalvular leak closure, left atrial appendage closure, and electrophysiological ablation treatments.

According to the press release, the TSP Crosser combines a sheath, dilator and a flexible puncturing needle in a single integrated system for controlled left atrium access and enhanced performance during transseptal catheterisation procedures.

A radiopaque loop wire is positioned at the distal end of the steerable sheath to aid in the localisation of the fossa ovalis.

The flexible puncturing needle and the steerable sheath allows pre-puncture deflection and orientation in the desired puncturing location of the fossa ovalis for transseptal access. The sheath is steerable up to 180 degrees bidirectionally after crossing the fossa ovalis.

Francesco Maisano (Zurich University Hospital, Zurich, Switzerland), founder of Transseptal Solutions, says: “Transseptal Solutions FDA clearance announcement is timely. There is a growing global demand for transseptal catheter intervention for patients with structural heart disease. The TSP Crosser is an innovative integrated solution addressing the unmet need for precise and controlled transseptal puncture.”

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Studies

CardioFocus completes enrolment in HeartLight X3 trial

Clinical News First patient treated in TERMINATE AF clinical trial

The first patient has been treated in the TERMINATE AF trial (Medtronic).

This is a multicentre study evaluating two surgical ablation devices—the Cardioblate irrigated RF (IRF) system and the CryoFlex surgical ablation system—for the treatment of nonparoxysmal (persistent or longstanding persistent) atrial fibrillation (AF) in patients undergoing open heart surgical procedures.

Following investigational device exemption (IDE) approval by the US Food and Drug Administration (FDA), the first patient was treated in the study by the heart team led by Ralph Damiano, at Washington University School of Medicine in St. Louis, USA. In the USA, treatment of AF is investigational use only.

During the surgical ablation procedure, surgeons will use the two ablation devices—deploying both “heat” (Cardioblate Irrigated Radio Frequency ablation) and “cold” (CryoFlex cryoablation) as needed—to make a pattern of lesions in the heart muscle that are intended to help the heart to return to its normal rhythm. The investigational procedure will be conducted to evaluate the treatment of atrial fibrillation in patients during other surgical heart procedures, such as bypass surgery, heart valve repair or replacement.

“The terminate AF trial provides a unique opportunity to study the combined use of two surgical ablation technologies to treat surgical patients who suffer from AF,” says Ralph J. Damiano, chief of the division of cardiothoracic surgery at Washington University School of Medicine and Barnes Jewish Hospital, and national principal investigator of the Terminate AF trial. “We anticipate the trial will help us uncover important procedural insights and potentially help surgeons and heart teams treat more patients with this widespread disease.”

An estimated 2.7—6.1 million people in the USA have AF, which contributes to an increased risk of stroke and an annual healthcare cost of US$6 billion.

The study will be conducted at up to 15 centres in the USA and will evaluate the safety and efficacy of the Cardioblate and CryoFlex devices in up to 160 patients with a history of non-paroxysmal AF who are undergoing concomitant cardiac surgery. The primary efficacy endpoint is the absence of AF after the removal of antiarrhythmic drug therapy (three months post-procedure). Patients will be assessed at one, three, six and 12 months.

The Cardioblate irrigated RF (IRF) and CryoFlex surgical ablation systems received 510(k) clearance from FDA in 2000 and 2004, respectively, with a general indication to ablate cardiac tissue during cardiac surgery. Neither device is FDA cleared or approved for the treatment of AF.

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First patient treated in STELLAR US study evaluating next-generation balloon ablation catheter for atrial fibrillation

Biosense Webster has enrolled and treated the first patient in its STELLAR US investigational device exemption (IDE) study. The study will evaluate the safety and effectiveness of Heliostar multi-electrode radiofrequency balloon ablation catheter in treating symptomatic drug refractory recurrent paroxysmal atrial fibrillation. Up to 640 patients will

Heliostar

be enrolled in as many as 40 clinical sites worldwide.

The Heliostar radiofrequency balloon ablation catheter has 10 electrodes allowing electrophysiologists to deliver different levels of energy depending on the tissue during lesion creation. The balloon design makes it possible to achieve pulmonary vein isolation with a single application of radiofrequency energy. The device is compatible with the Biosense Webster CARTO 3 mapping system. A press release reports that the use of the CARTO 3 system during an ablation procedure can reduce exposure to radiation from fluoroscopy.

Andrea Natale (Texas Cardiac Arrhythmia Institute, St David’s Medical Center, Austin, USA) treated the first patient in the study with Rodney Horton (also Texas Cardiac Arrhythmia Institute, St David’s Medical Center, Austin, USA), says: “The Heliostar catheter design has the potential to overcome the limitations of current balloon ablation catheters, resulting in fewer catheter exchanges and, most importantly, shorter procedure times. Heliostar is an exciting technology and we look forward to seeing the final study results.”

Uri Yaron, worldwide president, Biosense Webster, comments: “The STELLAR study is an important step forward in expanding treatment options for atrial fibrillation patients in the USA. The burden of atrial fibrillation on quality of life, morbidity and mortality is significant and we are committed to developing innovative and life-enhancing technologies that fill important clinical needs, improve care and reduce this burden.”

CardioFocus has completed enrolment in a trial to evaluate its next-generation HeartLight X3 endoscopic ablation system. According to a press release, a total of 60 patients have been treated in this pivotal confirmatory trial with a onemonth follow up. The trial will evaluate time, safety and acute outcomes using the HeartLight X3 system in the treatment of atrial fibrillation as pivotal endpoints.

The press release reports that pulmonary vein isolation with the HeartLight X3 system uses laser energy to create lines of scar tissue to block the abnormal electrical pathways that cause atrial fibrillation. It adds that throughout the trial, the HeartLight X3 system consistently demonstrated short procedure times and achieved very rapid pulmonary vein isolation (in as few as three minutes for a single vein).

Building upon the advanced features of the current HeartLight endoscopic ablation system—direct tissue visualisation, titratable laser energy, and compliant balloon technology—the HeartLight X3 system is designed to deliver quick, continuous, circumferential lesions, potentially making it the ultimate pulmonary vein isolation tool for atrial fibrillation. The system’s RAPID mode is designed to leverage a precise motor control system that enables uninterrupted, high-speed lesion creation under direct control of the physician.

Boris Schmidt (Cardiovascular Center Bethanien, Frankfurt, Germany), an investigator in the trial, says: “With the potential to deliver all ablations in 15 to 20 minutes, the speed and feature set offered by the HeartLight X3 system is unprecedented. The HeartLight X3 System will give us the ability to treat patients more efficiently than ever before.”

Petr Neužil (Department of Cardiology, Na Homolce Hospital, Prague, Czech Republic) comments: “The titratable laser energy, with the convenience of a oneshot approach, gives the HeartLight X3 system the potential to be a breakthrough technology in the atrial fibrillation ablation space. Those unique features coupled with the continuous lesions made in RAPID mode and decreased ablation time allow for unprecedented performance.” Data from the trial are expected to be used to obtain regulatory approvals, with European CE mark expected in mid-2019.

First US clinical study to assess ablation for monomorphic ventricular ablation initiated

Abbott has announced the start of LESSVT—the first US clinical trial to evaluate the safety and effectiveness of ablation treatment for patients with monomorphic ventricular tachycardia. The LESSVT study, which is currently enrolling patients, will evaluate the safety and effectiveness of ablation delivered by the FlexAbility ablation catheter (Abbott), Sensor Enabled (SE), for the treatment of monomorphic ventricular tachycardia

Excalibur Balloon

for people who are unresponsive to drug therapy.

Over the next two years, a press release reports, Abbott expects to enrol more than 600 patients at 35 sites in the USA and Europe. The results will help expand the health care community’s understanding of using radiofrequency ablation therapy as a frontline treatment for patients suffering from ventricular tachycardia. The study is also designed to support Abbott’s submission for FDA approval of an indication expansion for the company’s ablation therapy.

Paolo Della Bella (San Raffaele Hospital, Milan, Italy), an electrophysiologist on the LESS-VT trial steering committee, comments: “For some patients with sustained monomorphic ventricular tachycardia, drug therapy is an ineffective treatment option. We want to build a body of clinical evidence that establishes ablation as a therapy solution for people with ischemic and non-ischaemic monomorphic ventricular tachycardia.”

In addition to the FlexAbility SE ablation catheter, Abbott also recently introduced the Advisor HD Grid mapping catheter to support treatment of conditions such as monomorphic ventricular tachycardia. The Advisor HD Grid catheter is designed to capture information—such as the direction of cardiac signals—often missed with traditional mapping catheters. Advisor HD Grid offers physicians a unique grid configuration that captures this critical information and enables the creation of high-density maps of cardiac tissue to support treatment for patients.

Srijoy Mahapatra, medical director of Abbott’s electrophysiology business, comments: “Data suggests treating people with arrhythmias, including sustained monomorphic ventricular tachycardia, reduces the risk of developing other complications and hospitalisations. The goal of the LESS-VT study is to provide physicians with relevant data to help determine the most effective treatment option for their patients with monomorphic ventricular tachycardia. With recent advances in Abbott’s unique ablation tools and cardiac mapping technology, we aim to uncover treatment strategies to help patients return to healthy, full lives.”

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Companies

Industry News Cardiac Insight partners with VivoSense to expand use of its wearable cardiac sensors

Cardiac Insight, a developer of wearable cardiac biosensors and clinical diagnostic software systems featuring proprietary automated data analysis algorithms, has announced its partnership with VivoSense, a company focused on integration and specialised analysis of wearable sensor data for research and clinical trials. Together, both companies hope to deliver enhanced research analytics to help VivoSense expand the use of wearable biosensors for pharmaceutical clinical trials and other healthcare applications.

Dudley Tabakin, chief executive officer and co-founder of VivoSense says: “Sophisticated new analytics are the key to making sense of the complex data sets generated by human study participants in response to new drug candidates and genetics-driven population health research. Using the class-leading Cardiac Insight Cardea SOLO ECG sensor data with VivoSense software, data cleaning, robust analytics and regulatory-compliant biomarkers, we expect to enable new discoveries. The unique attributes and access to data enabled by Cardea SOLO strongly support our mission to advance clinical trials through the increasing use of wearable technology.”

VivoSense ingests data from many different wearable sensors, from highresolution cardiorespiratory and other cardiac sensors to wrist-worn activity trackers. This data from on-body sensors is integrated, cleaned and synchronously analysed with robust algorithms and scientific oversight from the VivoSense platform. The technology opens all clinical trials to the accurate use of wearable technology, providing a new level of data.

Brad Harlow, chief executive officer of Cardiac Insight says: “Our partnership with VivoSense is forging new frontiers and capabilities in healthcare research.

Our complex raw ECG data and automated analytics, easily obtained by our wearable ECG, Cardea SOLO, combined with the VivoSense platform integration will provide a new level of understanding into the effectiveness of

emerging medical and pharmaceutical innovations, as well as to potentially develop completely new biomarkers.

Contributing to the advancement of health research is an important component of our mission. We look forward to providing researchers a more comprehensive level of data analytics to improve disease prevention, detection and treatment.”

Comfortable and unobtrusive wearable cardiorespiratory sensors are finding ubiquitous use in sports and fitness research, longitudinal healthcare monitoring, and in regulated clinical trials. The very large physiological data sets generated by these sensors are the key to monitoring health and providing a greater understanding of the effects of new medicines and therapies.

Cardialen Closes US$17 Million Series B Financing for implantable defibrillator

Cardialen, a medical device company developing a low-energy implantable defibrillation therapy designed to more gently restore normal heart rhythm, has announced the closing of a US$17 million Series B investment led by RiverVest Venture Partners, along with Qiming Venture Partners, HBM Healthcare Investments and Cultivation Capital. The financing will be used to advance Cardialen’s clinical program with further human testing of its unpinning termination (UPT) therapy and begin development of an implantable device.

The Cardialen UPT therapy delivers a sequence of low-energy electrical pulses designed to restore abnormally rapid heart rates to a normal rhythm. This lowenergy therapy is intended to mitigate the negative effects of current high-energy defibrillators by delivering a much more tolerable, less debilitating treatment for patients with heart arrhythmias. Early human feasibility testing of Cardialen’s UPT therapy suggests that it may successfully treat heart rhythm disorders with substantially lower-energy therapy than is needed by existing defibrillators.

Jay Schmelter, managing director of RiverVest Ventures says: “We think Cardialen’s UPT therapy meets a unique

need in the large current and potential defibrillator market. Early UPT therapy results look promising and we are looking forward to partnering with Cardialen on this innovative approach.”

Jeff Peters, president and CEO of Cardialen says: “This round of financing gives Cardialen the capital to establish acute safety of UPT therapy for the treatment of various tachyarrhythmias.

We are thrilled to have such a strong syndicate of investors joining the team.”

Founder and scientific advisor Igor Efimov, Alisann & Terry Collins professor and chairman, Department of Biomedical Engineering, The George Washington University says: “Today’s implantable defibrillator therapy generates painful high-energy shocks that are associated with undesirable mortality that is expected to be reduced for patients receiving fewer shocks or a low-energy therapy. Our goal with UPT therapy is to reduce the negative effects of highenergy therapy and provide a better quality of life for patients.”

Concurrent with the financing, Jay Schmelter of RiverVest Ventures, Christopher Shen of Qiming Ventures, and Thomas Thaler of HBM Healthcare Investments, will join Cardialen’s board of directors. They will serve alongside Bill Schmidt of Cultivation Capital, Warren Watson, independent, and Peters.

CathVision receives new quality standard certification

CathVision, an early stage medical device company developing an advanced cardiac electrophysiology recording system (CUBE) has announced that the company received ISO 13485:2016 certification for Medical Device and Quality Management Systems from Lloyd’s Register.

This ISO certification indicates that the company’s quality management system meets the most current regulatory requirements specific to the medical device industry. “We are very proud of this certification and it demonstrates the commitment of our global team to quality, and to meeting customer and international regulatory expectations,” says Mads Emil Matthiesen, co-founder and CEO of CathVision.

ISO 13485:2016 is an internationally recognised quality standard for a quality system to ensure customer and regulatory requirements are consistently met throughout the lifecycle of the medical device product. “This

certification represents an important milestone for our company, and reflects our rigorous and risk-based approach to development and commercialisation,” says Andreas Pfahn, CathVision’s CTO and US president.

WeHealth by Servier and MobioSense form a partnership to develop digital portable myocardial infarction detection test

WeHealth by Servier, Servier Group’s e-health Business unit, and MobioSense, a leading semiconductor biosensor platform developer based in Taiwan and Boston, announced the closing of a partnership agreement to develop and commercialise a digital portable, High Sensitivity Troponin I Test (hs-cTnI) to accelerate and improve the diagnostic for potential myocardial infarction patients.

A press release reports that Mobiosense’s solution is the first portable myocardial infarction detection device. The solution under development is a point-of-care hs-cTnI device enabling bedside testing in ambulance, urgent care and hospital emergency room, efficiently reducing the current six to 12 hours conventional Troponin protocol to just one hour with the new portable hs-cTnI. The MobioSense’s solution is helping patients and healthcare providers by increasing the quality of patient care and reducing hospital stay.

As part of this partnership devoted to the co-developing and commercialising of the first solution, Mobiosense will receive financial milestones and resources support.

David Guez, Director of WeHealth by Servier comments: “We are pleased to work with MobioSense and with the Masschallenge Healthtech in Boston, where the startup was accelerated to co-develop the business model and the product. This solution is really focused on reducing the pain point of the patient journey and will fit very well with our digital portfolio.”

The Mobiosense’s solution has gained significant traction thanks to MassChallenge, Philips HealthWorks accelerators and Massachusetts General Hospital (MGH) Co. Create programme.

In addition to the development and distribution partnership with WeHealth

by Servier, MobioSense seeks to provide a convenient and decentralised biomarker testing platform to revolutionise the point of care testing market.

Calendar of events 17–19 March EHRA Lisbon, Portugal

25–28 May Heart Failure 2019 Athens, Greece

4–5 October Venice Arrhythmias 2019 Venice, Italy

www.escardio.org

www.escardio.org

www.venicearrhythmias.org

8–11 May Heart Rhythm Society’s Scientific Sessions San Francisco, USA

31 August–4 September ESC 2019 Paris, France

6–9 October HRC 2019 Birmingham, UK

www.escardio.org

www.heartrhythmcongress.org

www.hrssessions.org

24–27 October APHRS: Asia Pacific Heart Rhythm Society—­­12th Scientific Session Bangkok, Thailand www.aphrs2019thailand.com

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2—5 November XVI World Congress of Arrhythmias Buenos Aires, Argentina www.wsa-icpes.com

5–6 November Europe AF London, UK www.europeaf.com