Cardiac Rhythm News 47 - January 2020

January 2020 | Issue 47 Eike Nagel & Chiara Bucciarelli-Ducci: Cardiac imaging

Eric Prystowsky:

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Andrew Grace: Page 8

WRAP-IT shows significant mortality risk with CIED infection, and reduced quality of life Major infection in patients with cardiac implantable electronic devices (CIED) is associated with a threefold risk of mortality at one year, and impaired quality of life at six months, according to data presented by Bruce Wilkoff (Cleveland Clinic, Cleveland, USA) at the American Heart Association annual meeting (AHA 2019; 16–18 November; Philadelphia, USA).

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ilkoff outlined findings from a prespecified, as-treated analysis of WRAP-IT (World-wide randomised antibiotic envelope infection prevention trial), which assessed the clinical and economic impact of the Tyrx (Medtronic) absorbable antibacterial envelope in reducing CIED infections. The present analysis evaluated clinical outcomes related to major CIED infections within 12 months of the index procedure. Previously, a patient’s risk of dying despite successful treatment of a CIED infection was recognised to be at least 20% at one year. Data from WRAP-IT, a multicentre, randomised, prospective, single-blinded trial, comparing standard-of-care antibiotic prophylaxis with the adjunctive use of Tyrx, were presented earlier this year at the American Congress of Cardiology (ACC 2019) and published simultaneously in The New England Journal of Medicine. It found that the Tyrx absorbable antibacterial envelope reduced major infections by 40% in patients at increased risk for infections resulting from CIED implantation. In the prespecified analysis, major infection was defined as that resulting in CIED system removal, an invasive CIED procedure, treatment with long-term suppressive antibiotic therapy with infection recurrence after discontinuation of antibiotic therapy, or resulting in death. In addition, mortality, quality of life (QOL), disruption in CIED therapy, and healthcare utilisation (HCU) were assessed. Infections were stratified into two cohorts—a cohort with major infections inclusive of all infections at all sites, and a US cohort with major infections that occurred only at US sites. Investigators found that, of the 6,903 patients in the as-treated cohort, there were 70 infections among 67 patients in the cohort with major infections, and 43 infections among 41 patients in the US cohort with major infections. Major CIED infection was associated with increased all-cause mortality (12-month riskadjusted hazard ratio [HR] 3.41, p<0.001). Among patients in the cohort with major infections, KaplanMeier estimates of mortality after major infection onset were 16% at 12 months and 23% at 24 months. In terms of the impact of infections on QOL, Wilkoff said, linear mixed-effects modelling demonstrated

Bruce Wilkoff

EQ-5D utilities were significantly reduced at the time infection was diagnosed in comparison to baseline (adjusted mean difference 0.09, p=0.004), and did not normalise until six months post-diagnosis. In addition, disruptions in CIED therapy were experienced in 36% of infections for a mean duration of 184 days. The analysis also concluded that the US hospital costs of treating an infection in CIED patients averages about US$56,000, and revealed that patients pay an average of US$2,000 in out-of-pocket costs. Concluding, Wilkoff said: “This large, prospective analysis corroborates and extends understanding of the impact of CIED infections as seen in real-world datasets. CIED infections severely impact mortality, QOL, healthcare utilisation, and cost in the US healthcare system.” The European Heart Rhythm Association (EHRA) recently published a consensus statement outlining recommendations on preventing, diagnosing and treating CIED infections. The statement recommends use of the Tyrx Envelope for patients meeting the WRAP-IT criteria and/or other high-risk factors, and is endorsed by six other prestigious medical societies. For more on CIED infection, see page 5

Persistent atrial fibrillation

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Almost one in 200 patients dies early after AF ablation in a realworld analysis from the US Nationwide Readmissions Database Early mortality following atrial fibrillation (AF) ablation affects nearly one in 200 patients, with the majority of deaths occurring during 30-day readmission, an analysis of a nationally representative US cohort has revealed. Writing in the Journal of the American College of Cardiology (JACC), Edward P Cheng (Weill Cornell Medicine-New York Presbyterian Hospital, New York, USA) et al report procedural complications, congestive heart failure, and low hospital AF ablation volume were predictors of early death after ablation, and they recommend: “Prompt management of post-procedure complications and congestive heart failure may be critical for reducing mortality rates following AF ablation.” ALTHOUGH PROCEDURE-RELATED deaths during the index admission following catheter ablation of AF have been reported to be low, adverse outcomes can also occur after discharge. Because data on early mortality after AF ablation are limited, Cheng and colleagues aimed to examine mortality occurring soon after discharge from admission for AF ablation. They write: “As the overall volume of AF ablation procedures performed worldwide continues to grow, an understanding of the real-world rates of serious complications after AF ablation is needed. Recent studies have suggested an increasing trend in AF ablation-related complication rates, despite advances in catheter technology and operator experience.” The authors evaluated 60,203 admissions for AF ablation in patients ≥18 years between 2010 and 2015 from the all-payer, US Nationwide Readmissions Database (NRD). The definition of early mortality was death during initial admission or 30-day readmission. Other endpoints included procedural complications such as perforation/tamponade, other iatrogenic cardiac complications, central nervous system complications, vascular complications, and pneumothorax. Only the first readmission within 30 days after discharge was included in the analysis. Comorbidities, procedural complications, and causes Continued on page 2

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January 2020 | Issue 47

Top stories

Almost one in 200 patients dies early after AF ablation in a realworld analysis from the US Nationwide Readmissions Database Continued from page 1

of readmission (by organ system and by cardiac cause) were identified by International Classification of Diseases–9th Revision, Clinical Modification (ICD-9CM) codes. Cheng et al found that early mortality occurred in 0.46% cases (95% confidence interval [CI] 0.37–0.52) following AF ablation. Of the 276 patients who died early after AF ablation, 126 (45.7%) died during the index admission, and 150 (54.3%) died during the 30-day readmission after AF ablation. Patients who died early following AF ablation were older, and had a higher burden of comorbidities such as congestive heart failure (CHF), coronary artery disease, previous placement of pacemakers, pulmonary hypertension, chronic lung disease, chronic kidney disease, anaemia, and coagulopathy than those who survived. Patients who died early also had a higher burden of comorbidities than survivors (40.1% vs. 14.4%, respectively, p<0.001), and were less likely to have had procedures performed at higher-volume centres and teaching hospitals. They also lived in lower householdincome neighbourhoods, and had longer lengths of index hospitalisations than those who survived. Between 2010 and 2015, quarterly rates of early mortality post-ablation increased from 0.25% to 1.35% (p for trend <0.001). This paralleled significant increases in the mean age of patients at time of ablation, and in the prevalence of comorbidities such as CHF, coronary artery disease, chronic lung disease, and chronic kidney disease. The median time from ablation to death was 11.6 days (interquartile range [IQR] 4.2–22.7). Following adjustment for age and comorbidities, procedural complications (adjusted odds ratio [aOR] 4.06, p<0.001), CHF (aOR 2.20, p=0.011) and low AF ablation hospital volume (aOR 2.35, p=0.003) were associated with early mortality. Other associated complications were cardiac perforation (aOR 2.98, p=0.007), other cardiac (aOR 12.8, p<0.001), and neurological aetiologies (aOR 8.72, p<0.001).

Cheng and colleagues say: “Our study reduce the impact of these factors on the provides real-world evidence that the outcomes of AF ablation.” rates of early mortality after AF ablation In an accompanying editorial are not insignificant and can occur in comment, also published in JACC, nearly one of 200 procedures. The 0.46% Hugh Calkins (John Hopkins Hospital, rate of early mortality found in our Baltimore, USA) describes the analysis study exceeds the rates of procedural as “a very important study that death reported by other large studies should serve as a wake-up call to all examining AF ablation outcomes.” electrophysiologists who perform AF They attribute this to the fact that other ablation, all cardiologists who refer studies have been based on voluntary patients for this procedure, and all responses to surveys, or did not include Jim W Cheung patients who are considering undergoing deaths occurring after discharge from AF ablation”, adding: “What is clear index admission, which “could have led to significant is that AF ablation is not a benign procedure, and underestimation of the true mortality rate”. mortality is a very real complication of the procedure. The authors also highlight the “alarming rise in Cheng et al have also taught us that we need to the rate of early deaths between 2010 and 2015”. define early mortality as mortality during the index According to the authors, this trend can be explained hospitalisation as well as a subsequent hospitalisation by two main factors—the increased number of within 30 days. It is also clear that experience matters. comorbidities that they identified in the analysis, and a There is no doubt that the best outcomes are obtained at greater volume of procedures being performed at lower high-volume hospitals by high-volume operators.” volume centres. Jim W Cheung, the senior author of the study, told Cardiac Rhythm News; “This study offers some sobering findings. It clearly highlights the gap between the published outcomes by high-volume centres in clinical trials and the outcomes seen in the real world. Efforts are needed to bridge this gap and to ensure that outcomes from AF ablation procedures performed in widespread practice match the benchmarks of efficacy and excellent safety that have been established by experienced centres. It is essential for practising clinicians to recognise that patients should be followed closely after discharge from AF ablation, as adverse events can occur late and may require timely intervention before they became life-threatening.”

Prompt management of post-procedure complications and congestive heart failure may be critical for reducing mortality rates following AF ablation.” Among the limitations they point to are that it was a retrospective study based on an administrative database, and was therefore limited by the accuracy of ICD-9-CM codes. In addition, any sudden deaths outside the hospital prior to readmission would not have been included: “Therefore, the early mortality rate after AF ablation reported in this study likely represents an underestimation of the true rate.” Concluding, Cheng et al write: “Sepsis and CHF were the leading primary causes of readmission associated with mortality. Implementation of strategies to reduce procedural complications, optimise CHF management, and reduce nosocomial infections may help reduce early mortality after AF ablation. Protocols that optimise management of heart failure and minimise procedural complications warrant further study to

Implementation of strategies to reduce procedural complications, optimise CHF management, and reduce nosocomial infections may help reduce early mortality after AF ablation.”

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January 2020 | Issue 47

Atrial fibrillation

Sequential approach using STAR mapping system identifies key early sites of activation in patients with persistent AF

pre- and post-PVI (p<0.001), and were more likely to be associated with AF termination on ablation (p=0.007). The sensitivity and specificity of sequential mapping for the detection of ESA with an ablation response was 84.9% (95% CI 74.6–92.2) and 90.0% (95% CI 55.5–99.8), respectively. Finlay added: “With most patients having had greater The use of a Stochastic Trajectory Analysis of Ranked signals (STAR) mapping approach than 18 months’ follow-up, we have 80% free of AF and consistently identified early sites of activation (ESA) in patients with persistent atrial atrial tachycardia; and patients who recurred tended to fibrillation (AF), and the ablation response was compatible with these ESA being driver have atrial tachycardia, with one coming back in AF. sites. Malcolm Finlay (Bart’s Heart Centre, London, UK) presented the findings at the They were pretty straightforward to map and ablate.” Heart Rhythm Congress (HRC 2019; 6–9 October, Birmingham, UK), outlining that the Concluding, he said: “The majority of sites seen mechanistically important ESA were successfully identified using sequential recordings. on our basket STAR mapping can also be seen using sequentially acquired signals from a PentaRay with inlay explained: “There are a limited amount of and interpreted the sequential STAR maps to confirm the STAR mapping, and the ablation response indicates that accurate data on how to ablate persistent AF. We location of the ESA. sequential mapping appears to identify the important know there are localised sources, or at least there In all, 32 patients underwent STAR mapping-guided sites.” appear to be from several of the studies we have seen ablation (three patients terminated to The abstract presented at HRC was before. But there is conflicting evidence. We started out sinus rhythm on PVI). From these, 92 from a subanalysis of STAR mapping; the with a hypothesis that persistent AF is maintained by ESA were identified on the global STAR findings of the main study were published localised sources, whether they be rotational activations maps, of which 83 (90.2%) were targeted in the Journal of Cardiovascular or focal drivers. Furthermore, if we can track them down with ablation. An ablation response was Electrophysiology (Honarbakhsh et al). and ablate at these sites [early sites of activation], a seen with 73 of the 83 ESA (88%, 24 AF This concluded that consecutive mapping higher rate of freedom from AF or atrial tachycardia will termination and 49 CL slowing). in atrial tachycardia with the STAR result.” On average, 12.8±2.7 sequential mapping method can successfully map The aim of the study was to apply the vector mapping recordings were performed. Sixty-one of complex wavefront movements, and in approach, STAR, in AF and evaluate its ability to the 73 (83.6%) ESA were also identified AF, a majority of ESA identified on global identify localised drivers using global and sequential on sequential STAR maps with a kappa of STAR mapping are also identified using mapping. Global STAR maps were created with whole0.81 (95% confidence interval [CI] 0.6–1) sequential mapping. The authors also chamber basket catheters, and were considered the gold indicating strong interobserver agreement. Malcolm Finlay noted: “All important ESA (that is, those standard for comparing sequential STAR mapping for Finlay emphasised: “The key factor that resulted in AF termination) were acute electrophysiological endpoints and long-term is that sequential mapping was able to identify the vast successfully detected with consecutive mapping and, in outcomes. Participants were 35 patients undergoing majority of sites identified by the basket catheter and fact, sequential mapping identified ESA that were not persistent AF ablation. ESA were identified on global associated with a clinical effect. Sequential mapping detected with basket mapping due to areas with poor STAR maps created through five minutes of unipolar was highly reliable in identifying the most important coverage. A vector mapping approach to AF is therefore recordings using whole-chamber basket catheters, and of these—they were the sites associated with AF feasible with either basket or sequential mapping and guided further ablation post-pulmonary vein isolation termination rather than cycle length slowing.” each may have advantages in identifying drivers. The (PVI). Patients also had 30 seconds of unipolar ESA that were also identified on sequential STAR ablation response at ESA and freedom from AF/AT recordings using a PentaRay catheter. A minimum of 10 maps showed greater consistency (p<0.001), were seen [atrial tachycardia] suggests they are plausible drivers in recordings were obtained. persistent AF. Prospective randomised studies targeting Each sequential recording was superimposed on the these sites are needed to further evaluate the clinical same geometry to produce an “amalgamation map” impact.” of separate recordings, which made up a sequential Speaking to Cardiac Rhythm News following the STAR map. ESA associated with an ablation response abstract presentation, Finlay stressed that STAR (defined in the study as AF termination or cycle length mapping is “not a research tool”, and that the next steps [CL] slowing ≥30ms) on the global STAR maps were were to “develop STAR mapping into a package that can correlated offline to ESA identified on the sequential be used by all modern electrophysiologists. This work STAR map. ESA identified using each mapping is ongoing, and the plan is to roll it out to a multicentre modality were superimposed on the same geometry clinical trial comparing PVI plus STAR-guided ablation to ensure they had the same anatomy. Sites that were to our current standard of care, which is PVI alone.” within 5mm of each other were defined as colocating. The STAR Mapping System is licensed exclusively to Two observers blinded to the procedural data reviewed UK-based Rhythm AI Ltd.

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The key factor is that sequential mapping was able to identify the vast majority of sites identified by the basket catheter and associated with a clinical effect.”

Apple Heart study finds low rates of AF notification, and high agreement between app and ECG patches Final results from the Apple Heart study demonstrate a low probability of receiving an irregular pulse notification; 34% of those who received notification of an irregular pulse were diagnosed with atrial fibrillation (AF) on subsequent ECG patch readings, and 84% of notifications were concordant between the watch and the patch. IN THE NEW England Journal of Medicine, authors Marco V Perez (Stanford University School of Medicine, Stanford, USA) et al write: “This siteless [no on-site visits were required for the participants], pragmatic study design provides a foundation for large-scale pragmatic studies in which outcomes or adherence can be reliably assessed with user-owned devices.”

Perez and fellow researcher Mintu Turakhia (also Stanford University School of Medicine) told Cardiac Rhythm News: “Because AF is an intermittent condition, it is not surprising for it to go undetected in subsequent ECG patch monitoring. The study results demonstrate that this algorithm on Apple Watch can identify periods of irregular pulses and prompt subsequent clinical

evaluation that confirms them to be AF.” Apple Heart was a prospective single arm observational study in which participants without AF (self-reported) consented to monitoring for AF using a smartwatch-based (Apple watch series 1–3) irregular pulse notification algorithm. Following notification, a telemedicine visit was arranged, and an ECG patch was posted to the participant, to be worn for up to seven days. Surveys were administered 90 days after notification, and at the end of the study. The main objectives were to estimate the proportion of notified participants with AF shown on an ECG patch, and the positive predictive value (PPV) of irregular pulse intervals. Over an eight-month period, researchers recruited 419,297 participants. Over a median of 117 days, 2,161 (0.52%) received notifications of irregular pulse. Among the 450 who returned ECG patches containing data that could be analysed, AF was present

in 34% (97.5% confidence interval [CI] 29–39) overall, and in 35% (97.5% CI 27–43) ≥65 years. Among those notified of an irregular pulse, the PPV was 0.84 (95% CI 0.76–0.92) for observing AF on the ECG simultaneously with a subsequent irregular pulse notification, and 0.71 (97.5% CI 0.69–0.74) for observing AF on the ECG simultaneously with a subsequent irregular tachogram. Of 1,376 notified participants who returned a 90-day survey, 57% contacted healthcare providers outside the study; of 929 who completed the end-of-study survey and had a notification, 404 (44%) reported receiving a new diagnosis of AF; 3,070 (1%) of the 293,015 who completed the end-of-study survey but did not receive a notification reported being subsequently diagnosed with AF. The notification subgroup reported a greater incidence of stroke, heart failure, and myocardial infarction than the nonnotification group, and were more likely to start anticoagulant therapy or aspirin.

Issue 47 | January 2020

PADIT score predicts infection risk following CIED therapy Five independent predictors of cardiac implantable electronic device (CIED) infection have been identified which could be used to aid decision-making about device therapy through the use of an infection risk scoring system. The predictors and scoring system are the outcome of the Prevention of arrhythmia device infection trial (PADIT), a cluster randomised trial which sought to assess the efficacy of additional antibiotic measures compared with a conventional single dose of preoperative antibiotics among CIED patients. CIED INFECTION IS a major complication that usually requires device removal, can be costly, leads to prolonged hospitalisation and is associated with a short-term mortality rate of up to 18%, David Birnie (University of Ottawa Heart Institute; Canada) the study’s lead author, wrote in the Journal of the American College of Cardiology (JACC) in December 2019. Given these risks, developing strategies to reduce infection and defining predictors of increased infection risk are important goals, he noted. Brinie and coleagues predicted incremental antimicrobial prophylaxis would reduce the risk of hospitalisation for device infection compared with a conventional strategy of a single dose of a pre-

Cardiac implantable devices procedural antibiotic. The primary outcome was admission to hospital for proven CIED or pocket infection within one year of device implantation. Patients having CIEDs implanted—including a new or replacement pacemaker, implantable cardioverter defibrillator (ICD) or cardiac resynchronisation therapy (CRT), as well as a pocket or lead revision—at 28 sites in Canada and The Netherlands were included in the trial, which took place over four six-month periods between December 2012 and September 2016. In total, 19,603 patients underwent device procedures, with 19,559 having completed a follow-up visit. Patients were randomised in clusters to conventional treatment (n=9,627) or incremental antibiotics (n=9,976). In the conventional arm, a single dose of cefazolin 1–2g was administered 60 minutes before skin incision or vancomycin 1–1.5g IV in penicillin-allergic patients. In the incremental antibiotic strategy, patients received IV cefazolin as well as pre-operative vancomycin. Of the patients taking part in the trial, the study team found that hospitalisation for infection occurred in 177 (0.9%) within one year of follow-up. The main study results have previously been reported and found that hospitalisation for infection was reduced by

Developing strategies to reduce infection and defining predictors of increased infection risk are important goals.” incremental therapy (23% reduction, nonsignificant); and the nonsignificance was in part attributable to the unexpectedly low infection rate.

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The study team examined predictors of infection and developed a final prediction model using five independent predictors. These included: prior procedures (P), age (A), depressed estimated glomerular filtration rate (D), immunocompromised (I) and type of procedure (T). The risk score was then calculated for each patient by summing the points assigned to each predictor, with a risk score ranging from 0 to 15 points classifying patients into low, intermediate and high-risk groups; 13,828 patients were at low risk (score: 0 to four), 4,151 patients were at intermediate risk (score five or six) and 1,406 were at high risk, (score ≥ seven). Hospitalisation rates for the groups stood at 0.51%, 1.42%, and 3.41%, respectively. Brinie and colleagues note that the PADIT infection risk score is likely to be helpful to physicians and patients in shared decision-making about device therapy, adding that many patients and families are not aware of the risks and benefits of ICD generator replacement, for example, and that patients often overestimate the benefits and underestimate the risks of ICD generator change These observations are largely consistent with a meta-analysis of findings from many smaller studies. Binire believes the score will be helpful for shared decision making around CIED therapy and for clinical researchers. Further validation and modification with future high-quality datasets are warranted. In an accompanying editorial comment, Suneet Mittal and Simon Tsiouris (Valley Hospital Health System, Ridgewood, USA) wrote that the identification of patients at low risk, may be the “most valuable lesson of PADIT”. They added: “Patients with pacemakers accounted for nearly half of the total cohort but had a major infection rate of only 0.4%. For the remaining patients, the good news is that the perception of infection risk has not matched the observed reality; the bad news is that it then becomes that much harder to budge the needle to a more favourable status for our patients with CIEDs.”

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January 2020 | Issue 47

Research

Four studies that will shape arrhythmia treatment in 2020 Leading electrophysiologists have pinpointed four clinical studies due to report findings in 2020—AMULET IDE, aMAZE IDE, PULSED AF and CEASE AF—that they expect to shape practice in the treatment of cardiac arrhythmias this year.

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hanunjaya Lakkireddy (chair of the American College of Cardiology Electrophysiology Council, and executive medical director, Kansas City Heart Rhythm Institute, Kansas, USA) and Andrea Natale (executive medical director at the Texas Cardiac Arrhythmia Institute, St David’s Medical Center, Austin, USA) both spoke to Cardiac Rhythm News about the trials that they will be following closely this year. Lakkireddy identified the AMULET IDE and aMAZE IDE trials as being “eagerly awaited”; both are expected to complete follow-up and report by the end of this year. AMULET IDE will compare the safety and effectiveness of the Amulet (Amplatzer) left atrial appendage (LAA) occluder in patients with atrial fibrillation (AF) compared to the Watchman endocardial occluder (Boston Scientific). Lakkireddy said that the study offers the prospect of bringing in “another important LAA management tool” for AF treatment. He pointed out: “There are important design differences and anatomic eligibility issues. Historically AF ablation has

not made significant strides in improving the overall success rates in nonparoxysmal AF patients.” Also expected in 2020, aMAZE will evaluate the Lariat suture delivery device (AtriCure) for LAA exclusion adjunctive to pulmonary vein isolation (PVI) catheter Dhanunjaya Lakkireddy ablation for the treatment of persistent and longstanding AF. Lakkireddy commented that the research “has the potential to bring about a paradigm shift in the management of non-paroxysmal AF patients”, adding: “Epicaridal Lariat ligation of LAA results in mechanical and electrical isolation of the LAA. This not only helps eliminate the electrical triggers but also can debulk the LA and eliminate the thrombus reservoir in AF patients.” Natale, a pioneer in AF ablation, told Cardiac Rhythm News that the PULSED AF and CEASE AF studies will be among the key research reporting in 2020. PULSED AF—Pulsed field ablation to irreversibly electroporate tissue and treat AF—Natale said, would offer first in-human insights into clinical safety and efficacy of the pulsed field ablation system. “In the porcine model, this system was reported to produce consistent transmural lesions without producing significant heating and unintended injury to the surrounding tissue, which is a well-known safety challenge of many hyperthermal ablation technologies,” he said. Highlighting the possible impact of the research on the treatment of cardiac arrhythmias, Natale said that it offered the prospect of being “the future of

Young people with cardiac arrhythmia more likely to have ADHD or depression

Children and teens with cardiac arrhythmias are more likely to have depression, anxiety and attention deficit hyperactivity disorder (ADHD), compared with those of similar ages without chronic medical conditions or with certain select chronic childhood diseases, according to preliminary research presented at the American Heart Association’s Scientific Sessions 2019 (AHA 2019; 16–18 November, Philadelphia, USA). HIGHER RATES OF depression, anxiety and ADHD have previously been described in young adults born with structural heart defects, according to the team which carried out the study, which was led by Keila N Lopez (Texas Children’s Hospital-Baylor College of Medicine, Houston, USA). The researchers used retrospective data from the electronic medical record of a large paediatric hospital between 2011–2016 to characterise depression/anxiety and ADHD in youth with cardiac arrhythmia compared to the general population and other chronic diseases. Data were used to compare noncongenital heart disease cardiac arrhythmia patients, aged four to eight years, to congenital heart disease patients without arrhythmias, cystic fibrosis (CF), sickle cell disease (SC), and all other patients without these diagnoses. Predictor variables included age, sex, race/ethnicity, insurance type, and specific beta-blocker therapy. The

primary outcome variable was an ICD9 or 10 diagnosis and/or medication prescribed for depression/anxiety or ADHD. Logistic regression analyses were used to predict depression/anxiety, ADHD, or having both conditions, for the cardiac arrhythmia as well as the noncardiac arrhythmia patients. In total, the research team identified 123,000 unique patients and 3,961 cardiac arrhythmia patients. The cardiac arrhythmia patients were largely <10 years old (44%), Hispanic (42%), and had public insurance (53%); 50% of the arrhythmia patients were male. They found that overall, 27% of arrhythmia youths had a diagnosis or had received medication for depression or anxiety compared to 18% of complex congenital heart disease youths, 23% of CF patients, 8% of SC disease patients, and 5% of the control population. Lopez and colleagues found that, when compared to the control population, patients with regular (non-lethal) and

the ablative therapy in cardiac arrhythmia”. He added: “With extremely fast energy delivery (milliseconds compared to minutes with standard radiofrequency ablation) and the reported ability for tissue-selective ablation, pulsed field ablation seems to hold a lot of promise in Andrea Natale terms of safety. Moreover, in the animal model, durability of the lesions was demonstrated.” CEASE AF is a randomised trial investigating the optimal treatment of persistent and longstanding persistent AF by comparing two ablation approaches: endoscopic epicardial surgical ablation (first stage) combined with endocardial catheter ablation (second stage), and; standard catheter ablation with pulmonary vein isolation (minimum lesion set) and optional additional lesions. Natale commented that this would show the relative efficacy of the hybrid procedure compared to the standard endocardial catheter ablation. He explained that LAA is a “frequent” source of ectopic triggers, driving arrhythmia recurrence in non-paroxysmal AF patients, while the risk of thrombus formation and subsequent thromboembolic events in the brain is high following electrical isolation of LAA. By addressing the arrhythmogenic and thrombogenic properties of the LAA, Natale suggested, “the hybrid procedure would have the potential to be considered as the index ablation procedure in non-paroxysmal AF patients with superior ablation-outcome and no thromboembolic complications.”

severe (lethal) cardiac arrhythmias had roughly six times higher odds of depression/ anxiety (OR 6.3, 95% confidence interval [CI] 5.8– 6.8, and OR 6.1, Keila N Lopez 95% CI 5.8–6.8, respectively), and roughly three times higher odds of ADHD (regular: OR 3, 95% CI 2.6–3.5; severe: OR 3.1, 95% CI 1.5–6.2). When compared to CF, those with regular and severe cardiac arrhythmia had 1.4 times higher (95% CI 1.02–1.9) and 1.9 times higher (95% CI 1.1–3.2) odds of medication for diagnosis of depression/anxiety, respectively, the study team found. Compared to SC patients, those with regular and severe cardiac arrhythmia have a 3.3 times higher odds (95% CI 2.3–4.6) and 4.4 times higher odds (95% CI 2.6–7.6) of medication for diagnosis of depression/ anxiety, respectively. While there was no significant difference in ADHD compared to the CF population, compared to SC, those with regular and severe cardiac arrhythmias have a 1.7 times higher odds (95% CI 1.1–2.8) and 2.3 times higher odds (95% CI 1–5.4) of ADHD. Other important and pertinent findings were that youths with cardiac arrhythmia have higher odds of depression/anxiety medication or diagnosis compared to controls and patients with cystic fibrosis and sickle cell disease, and that youths with cardiac arrhythmias have higher odds of ADHD compared to

control subjects and sickle cell disease populations. In addition, youths with cardiac arrhythmias on non-selective beta-blockers had higher rates of diagnosis/treatment for depression/ anxiety compared to cardioselectives (beta-blockers that target the heart). Finally, depression/anxiety and ADHD diagnoses were noted to be much lower in minority populations. “This may be the first study of this size looking at children and teenagers with various cardiac arrhythmias (but without structural heart disease) that have been diagnosed with, or are taking medication for, anxiety and/or depression,” Lopez said.

It is important to take care of children’s arrhythmias as well as their mental health.” Commenting on the findings, she emphasised to Cardiac Rhythm News: “It is important to take care of children’s arrhythmias as well as their mental health. Lower rates of diagnosis for depression/anxiety and ADHD in minority patients with arrhythmias warrants further investigation. Screening for anxiety and/or depression should be considered in children and adolescents’ cardiac arrhythmias and other chronic diseases.”

Issue 47 | January 2020

Cardiac MRI delivers an accurate diagnosis and guides treatment of cardiovascular diseases Eike Nagel Chiara Bucciarelli-Ducci Comment & Analysis Eike Nagel and Chiara Bucciarelli-Ducci discuss the diagnostic and prognostic power of heart magnetic resonance imaging and how it can help physicians to determine the best treatment path for patients.

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or patients with stable angina and coronary artery disease (CAD), two strategies are typically used to establish a diagnosis and guide treatment decisions. One is invasive angiography—a procedure that involves taking X-rays of the patient’s arteries and requires multiple hospital visits, including an overnight stay—and measurement of fractional flow reserve (FFR). The other is heart magnetic resonance imaging (MRI), which is a modality for noninvasive, nonradiation assessment of the function and structure of the heart and cardiovascular system. After a heart MRI, patients undergo invasive angiography and revascularisation only if they have received a positive test, which occurs in less than half of the patients, even when the expected likelihood for the presence of disease is high and the patients have typical symptoms. Despite its widespread use in Europe, and studies that associate cardiac MRI with a lower incidence of invasive angiography than testing based on clinical risk assessment,1 heart MRI is not employed as frequently in the USA, making up less than 1% of non-invasive imaging tests administered. Until recently, there was also a lack of data on the efficacy of heart MRI-based strategies compared to those involving invasive angiography. The MR-INFORM (myocardial perfusion CMR versus angiography and FFR to guide the management of patients with stable coronary artery disease) trial evaluated whether heart MRI is noninferior to an FFR-based strategy in terms of major adverse cardiac events (MACE), including death from any cause, non-fatal myocardial infarction, or target vessel revascularisation. Recently published in the New England Journal of Medicine, the trial was an international, multicentre, comparative-effectiveness study involving patients with stable angina and risk factors for CAD.2 Between December 2010 and August 2015, 918 patients were enrolled in

the trial, which involved 16 sites in the UK, Portugal, Germany and Australia. Patients who were ≥18 years with typical angina symptoms and two or more cardiovascular risk factors (smoking, diabetes, hypertension, hyperlipidaemia, a family history of CAD) or a positive exercise treadmill test were suitable for inclusion. Exclusion criteria included contraindications to adenosine myocardial-perfusion cardiovascular MRI, severe cardiac arrhythmias, a known left ventricular ejection fraction of <30%, New York Heart Association

Cardiac imaging months. A 10% incidence in the FFR group and a noninferiority margin of six percentage points were determined by the FAME (fractional flow reserve versus angiography for multivessel evaluation) trial, which assessed 1,005 patients with multivessel CAD undergoing PCI at 20 medical centres in the USA and Europe.3 With these assumptions, a sample size of 826 would be sufficient to determine noninferiority of a heart MRI-based strategy compared to an FFR-guided strategy. After providing written informed consent, all 918 patients enrolled in the MR-INFORM trial were randomly assigned to either the FFR group (464 patients) or the heart MRI group (454 patients). The two groups did not differ significantly in age, sex, symptoms at presentation, baseline medications or risk factors. Randomisation was performed with fixed block sizes, stratified according to centre and sex within centre. Patients assigned to the FFR group received the standard invasive angiography and FFR testing in all coronary arteries with a caliber of ≥2.5mm and a stenosis severity of ≥40%. Revascularisation was recommended for vessels with an FFR of ≤0.8. FFR group patients also underwent cardiac MRI before the angiography; however, results were blinded and not reported. Meanwhile, the heart MRI group had a cardiac MRI to determine whether invasive angiography was required. In this group, only patients with abnormal heart MRI results underwent an invasive study. FFR was not permitted in this group.

By using cardiac MRI methods, which are readily available and can be implemented on standard MRI systems, physicians can personalise therapy by recommending more invasive operations only to those who really need them.”

MRI

(NYHA) class III or IV heart failure, previous coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) within six months, or an estimated glomerular filtration rate of <30ml per minute per 1.73m2 of body surface area. The sample size calculation for the MR-INFORM trial was based on the expected percentage of patients with the primary outcome of MACE at 12

Overall, the two groups had similar health outcomes, with <4% of patients in both groups experiencing the primary outcome of MACE within the followup period of 12 months. However, the group that received treatment based on a heart MRI had significantly fewer procedures—only 40% of this group had invasive angiography, while 96.8% of patients in the FFR group underwent the procedure. Furthermore, 36% of

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the Heart MRI group went on to have revascularisation, compared to 45% in the FFR group. Once again, the difference was significant. The MR-INFORM trial indicates that among patients with stable angina and risk factors for CAD, using heart MRI to guide treatment is noninferior to using invasive coronary angiography and FFR. Additionally, the results demonstrate that heart MRI is associated with a lower incidence of invasive coronary angiography and coronary revascularisation compared to FFR. Due to a lack of evidence, current guidelines on managing the care of patients with CAD separate diagnostic and therapeutic strategies. By comparing two frequently used, well-defined, standardised and validated tests, the MRINFORM trial closes this knowledge gap; however, limitations of the study should be considered. For instance, the results cannot be extrapolated to other tests for myocardial ischaemia or the functional significance of a coronary artery stenosis due to differences in diagnostic performance. Additionally, the findings are generalisable only to patients who fulfill the study’s inclusion criteria. By using cardiac MRI methods, which are readily available and can be implemented on standard MRI systems, physicians can personalise therapy by recommending more invasive operations only to those who really need them. Thus, for many patients, the initial hospital visits will be quicker, safer and painfree, and they are less likely to require additional procedures. Unlike other modalities, the 3D technology in cardiac MRIs can help to determine what kind of heart disease is present and why, helping doctors diagnose conditions and provide a prognosis to achieve the best treatment path for patients. To learn more, visit heartmri.org and scmr.org. References: 1. JP Greenwood, DP Ripley, C Berry, et al. Effect of care guided by cardiovascular magnetic resonance, myocardial perfusion scintigraphy, or NICE Guidelines on subsequent unnecessary angiography rates: The CE-MARC 2 randomised clinical trial. Journal of the American Medical Association 2016; 316(10): 1051–60. DOI: 10.1001/jama.2016.12680 2. E. Nagel, JP Greenwood, GP McCann, et al. Magnetic resonance perfusion or fractional flow reserve in coronary disease. N Engl J Med 2019; 380: 2418–28. DOI: 10.1056/NEJMoa1716734v 3. PA Tonino, B De Bruyne, NH Pijls, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009; 360(3): 213–24. DOI: 10.1056/NEJMoa0807611

Eike Nagel is the director of the Institute for Experimental and Translational Cardiovascular Imaging at DZHK Centre for Cardiovascular Imaging in Frankfurt, head of Interdisciplinary Cardiovascular Imaging at University Hospital Frankfurt, Frankfurt, Germany, and the lead investigator of the MRINFORM trial. Chiara Bucciarelli-Ducci is an associate professor in cardiology/noninvasive imaging at the Bristol Heart Institute, co-director of the Clinical Research and Imaging Centre Bristol, Bristol, UK, CEO of the Society of Cardiovascular Magnetic Resonance, and co-author of the MR-INFORM trial.

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January 2020 | Issue 47

Interview

Profile

Eric N Prystowsky Eric N Prystowsky, director of the Cardiac Arrhythmia Service at St Vincent Hospital, Indianapolis, and a consulting professor of medicine at Duke University Medical Center, Durham, USA, talks to Cardiac Rhythm News about his career. He considers the challenges facing electrophysiology, shares his most important accomplishments, and discusses the perils of social media, as well as future developments and their likely impact on practice.

Why did you decide to become a doctor and why, in particular, did you decide to specialise in electrophysiology? My mother was a child psychiatrist and my father a paediatric cardiologist. Their discussions about medicine were never about money, but about helping patients in need and how rewarding that was. I am sure this influenced my decision to consider medicine as a profession. Electrocardiograms (ECGs) in those days were long strips of paper and I would help my father make a composite 12 lead ECG by punching out segments to be mounted on one sheet. I was fascinated by the squiggles representing the heart beat. As I advanced in my training and learned more about arrhythmias, I knew I wanted to become an electrophysiologist, and that was why I did cardiology training at Duke.

Who have been your career mentors?

Mentors are key for a successful career, and I was fortunate to have several. My parents set an example for how medicine is to be practised; Ephraim Donoso during my internal medicine residency increased my knowledge of arrhythmias, and was my first academic mentor. At Duke, Harold Strauss taught me the concepts of research, and John Gallagher mentored me in clinical electrophysiology and solidified my desire to pursue academic medicine.

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

I began in the operating room mapping arrhythmia pathways for the surgeon to destroy. The three major advances in clinical electrophysiology have been the development of the implantable cardioverter defibrillator (ICD), radiofrequency catheter ablation of arrhythmias, and biventricular pacing for heart failure.

What is the biggest challenge facing electrophysiology?

There are two big challenges. The first is in the science of electrophysiology; we need to understand why arrhythmias occur, not just how to treat them, and this will undoubtedly inform us about their mechanisms. The second challenge is more of a more practical natureâ&#x20AC;&#x201D;I worry about a shortage of electrophysiologists in the future. The number of applicants to programmes seems to be declining at a time when many more are needed.

What has been the biggest disappointment? Something you hoped would change practice but which failed to do so? There has not been a new and effective antiarrhythmic drug developed for many years, and that is a disappointment. Although ablation is a wonderful method to cure certain arrhythmias, many are not suited to this therapy, and there are not enough electrophysiologists available to care for the multitudes of arrhythmia patients worldwide.

Of the research you have been involved in, which do you think will have the greatest impact on clinical practice? I was involved in early trials in catheter ablation, the findings of which are a key part of patient care. I also cofounded the MUSTT study, which changed our approach to ventricular tachycardia. Following that, serial drug testing in the electrophysiology lab is no longer performed.

What did the COMPANION trial add to the understanding of cardiac resynchronisation therapy (CRT) pacing and CRT defibrillation?

COMPANION demonstrated the role of CRT to improve survival, and the benefit of ICD therapy for this aim.

What are your current research interests?

My current research interests focus on the autonomic nervous system and arrhythmias, AF tachycardiainduced cardiomyopathy, and risk stratification for sudden death in patients with mitral valve prolapse.

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

We need a better understanding of how to risk profile for mitral valve prolapse (MVP), and this will require a large registry, as only a small segment of patients are at risk for sudden cardiac death. This is similar to other â&#x20AC;&#x153;boutiqueâ&#x20AC;? diseases, for example long QT syndrome.

What is the potential for future developments in the prevention of heart failure?

Minimising disease states that cause both heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), are areas for potential development. In the atrial fibrillation (AF) population, some progress can be made through education on tachycardia-induced cardiomyopathy.

What role does e-medicine have in monitoring chronic heart disease?

E-medicine will have an increasing role in monitoring and detecting cardiac problems. Wearable or implantable monitors can relay timely information that hopefully will minimise stroke or worsening heart failure and allow patients to be involved in their therapy. This may facilitate pill-in-the-pocket treatments for certain disease states, once safety and efficacy data have been verified.

Social media is increasingly used for medical communication. What are the pros and cons of these platforms?

I do not use social media but understand why others like it. Its advantage is the instant exchange of information that may help diagnose and manage patients. But, I have seen much misinformation. I cannot understand why a physician would listen to the advice of someone unknown to them who may not have worked in the area.

What is your most memorable case?

Of many memorable cases over 40 years, one sticks out. A teenage girl was referred for palpitations due to premature ventricular contractions. During the workup she was noted to have a nonischaemic dilated cardiomyopathy, but no heart failure symptoms. This was years before ICD trials had been performed in such patients, but her situation worried me, and I sought permission to implant an ICD. It was placed under her breast to minimise psychological impact. Her father felt I had done her harm; however, years later, when he was driving her home from college, she lost consciousness and woke with a start. The ICD printout showed an episode of ventricular fibrillation and the ICD had resuscitated her. Her father changed his attitude, but more importantly she married and had children, and years later underwent a successful heart transplant.

What is your advice to someone starting out in cardiovascular medicine? My advice to anyone entering the field is to ignore all the noise about what is wrong with the practise of

Issue 47 | January 2020

Interview

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Fact File

Current appointments (selected)

■ Director, Cardiac Arrhythmia Service, St Vincent Hospital and Health Care Center, Indianapolis, USA ■ Medical director, Office of Research and Clinical Trials, St Vincent Hospital and Health Care Center ■ Consulting professor of medicine, Duke University Medical Center, Durham, USA

Honours and awards (selected)

1992–present: Best Doctors in America 2002: Distinguished Teacher Award, Heart Rhythm Society 2002: Master Teacher Award, University of Miami School of Medicine 2002: Lifetime Achievement Award, University of California 2007: Distinguished Alumnus, Penn State University 2009: The President’s Award, Heart Rhythm Society 2014: Distinguished Physician Award, St Vincent Hospital 2018: Cardiac Pacing and Electrophysiology Pioneer Award, Heart Rhythm Society

Prior appointments (selected)

Outside of medicine, what are your hobbies and interests?

I worry about a shortage of electrophysiologists. The number of applicants to programmes seems to be declining at a time when more are needed.” medicine, and concentrate on the wonderful field you have entered—one that will allow you to cure patients if you go into electrophysiology, or reduce suffering and improve survival if you become a general cardiologist, heart failure specialist, or interventional cardiologist.

I enjoy wildlife photography and have been to Africa and Churchill, Canada to photograph polar bears. I am an avid sports fan, particularly Penn State football and Duke basketball and I also enjoy the symphony. But, my major source of joy is visiting my grandchildren.

What would you have been if you had not been a medical doctor?

Vocational tests I took in school indicated my aptitude was for medicine or law. I have always enjoyed debating so maybe I would have been a lawyer. However, I am very happy that I chose medicine.

What do you think have been your most important accomplishments?

One is the scores of fellows I have trained, many of whom have added to research in our field. Secondly, I discovered that a nurse was killing patients and was part of the team that convicted him. Thirdly, the privilege and pleasure of caring for thousands of patients with cardiac arrhythmias.

2004–2018: Editor-in-chief Journal of Cardiovascular Electrophysiology 2004–2008: Chairman, ABIM Electrophysiology Test Writing Committee 1992–1994: AHA Council on Clinical Cardiology Executive Committee 2001–2002: President, Heart Rhythm Society 1986–1988: Professor of Medicine, Duke University Medical Center

Memberships and committees (selected)

1979–present: Cardiac Electrophysiological Society 1980–present: American Heart Association 1988–present: American College of Physicians 2005–present: Heart Rhythm Society

Key papers

■ Inhibition of the human heart, Circulation 1983 ■ Preexcitation index, Circulation 1986 ■ Vagus effects on SAN and AVN function in humans, Circ Res 1991 ■ MUSTT study, N Engl J Med 1999

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January 2020 | Issue 47

Research

Left atrial appendage closure linked to a decreased stroke risk in AF patients

Left atrial appendage closure (LAAC) via an implanted device was associated with a decreased risk of admission for stroke, compared with the expected risk without anticoagulation therapy, according to a study published in the Journal of the American Medical Association (JAMA). AUTHORED BY RAJESH Kabra (University of Tennessee Health Science Center, Memphis, USA) et al, the population-based cohort study concluded that although LAAC provides an attractive non-pharmacological option for stroke prevention in patients with atrial fibrillation (AF), who are not candidates for long-term anticoagulation therapy, further prospective long-term studies are needed to monitor its safety and efficacy. Kabra et al note that anticoagulation therapy is the cornerstone for stroke

prevention in patients with AF, although (69.0%) were older than 75 years, 11,980 LAAC devices have emerged as an (87.9%) were white, and 5,630 (41.3%) alternative. The Watchman device were women. The mean CHA2DS2-VASc [Boston Scientific] was the first LAAC score was 4.3 (1.4). Twenty-eight patients device compared with warfarin in (0.2%) died during the index admission. two clinical trials—PROTECT AF Mortality rates were 0.6% (80 patients) at (Watchman left atrial appendage system 30 days, 1.9% (262 patients) at 90 days, for embolic protection in 4% (547 patients) at 180 days, patients with atrial fibrillation) and 7.5% (1,027 patients) and PREVAIL (Prospective at 365 days. The 30-day randomised evaluation of readmission rate among 13,599 the Watchman LAA closure patients discharged alive was device in patients with atrial 9.4% (1,284 patients). Among fibrillation versus long term 92,31 patients with six months warfarin). of follow-up data, 111 (1.2%) Data outside clinical were readmitted for ischaemic Rajesh Kabra trials regarding the use and stroke or transient ischaemic outcomes of LAAC devices attack within 180 days of are limited, Kabra notes, adding that the discharge. present study seeks to address this by Kabra and colleagues also examined examining post-procedural outcomes mortality and readmission rates for of mortality, hospital readmissions, and stroke and transient ischaemic attack by ischaemic stroke. CHA2DS2-VASc score, noting that all Medicare inpatient claims for 13,627 outcomes were more frequent among patients older than 65 years with an AF patients with higher scores. In particular, diagnosis who underwent LAAC with an Kabra and colleagues note, among those implanted device from January 2015 to with higher scores, mortality rates were November 2017 were assessed. Mortality higher within 90 days (score 0–3, 1.1%; rates during the index admission and for score 4–5, 1.8%, score 6, 3.5%; p<0.001), one-year after LAAC were investigated, within 180 days (score 0–3, 2.3%; score and the 30-day readmission rate and 4–5, 3.8%; score 6, 7.1%; p<0.001), and the primary reasons for readmission within 365 days (score 0–3, 4.0%; score were also examined. Likelihood of 4–5, 7.7%; score 6, 12.0%; p<0.001). hospitalisation for ischaemic stroke The authors also compared the observed within 180 days among 9,231 patients for rates of ischaemic stroke after LAAC via whom six months of follow-up data were implanted device with expected stroke available was also evaluated. rates in the absence of anticoagulation Among the 13,627 patients undergoing therapy according to CHA2DS2-VASc LAAC, the mean age was 78 years, 9,406 scores, using data from prior studies.

Tackling focal VT may improve catheter ablation in structural heart disease Uncovering and abolishing focal ventricular tachycardia (VT) may further improve outcomes of catheter ablation in the treatment of structural heart disease, a study published in JACC: Clinical Electrophysiology concludes. Robert Anderson (Westmead Hospital, Sydney and Royal Melbourne Hospital, Melbourne, Australia) who led the study, notes that focal VTs are common in patients with structural heart disease (SHD) and often coexist with re-entrant forms of ventricular tachycardia.

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nderson and colleagues sought to summarise the frequency, procedural characteristics and clinical outcomes in patients with SHD shown to have a focal mechanism, despite the presence of scar and the typical electrophysiological milieu for re-entrant VT. Focal VT is typically seen in patients without SHD, and is rarely seen as a dominant mechanism in patients with established or acute ischaemic heart disease, the study team noted. Patients with SHD undergoing VT ablation procedures at the Department of Electrophysiology at Westmead Hospital (Sydney, Australia) over a twoyear period were eligible for inclusion.

Preprocedural data, arrhythmia history, procedural characteristics, complications and follow-up were collected from 145 patients who underwent catheter ablation for ventricular arrhythmia. Of these, 116 had structural heart disease and 112 had inducible VT and underwent a detailed induction protocol to expose a focal VT mechanism. This incorporated programmed electrical stimulation, right ventricular burst pacing and isoprenaline to elucidate both re-entrant and focal VT mechanisms. The study found that 18 of 112 patients (16%) undergoing VT ablation had a focal VT mechanism. Repetitive failure of termination with antitachycardia

They noted a 60–69% reduction in stroke risk after LAAC, compared with the risk in the absence of anticoagulation therapy. The most frequent primary diagnoses for readmissions within 30 days were gastrointestinal haemorrhage (134 patients [1.0%]), hypertension with complications (111 patients [0.8%]), cardiac dysrhythmias (103 patients [0.8%]), complications from a device or surgical procedure (84 patients [0.6%]), and septicaemia (68 patients [0.5%]). There were 28 readmissions (0.30%) for haemorrhagic stroke within 180 days after LAAC via implanted device. Kabra and colleagues found that, LAAC via implanted device was associated with a decreased risk of admission for stroke compared with the expected risk without anticoagulation therapy. The risks of one-year mortality and stroke at six months were higher, they found, than those in previous randomised clinical trials, likely because the population in the current study was older and had more comorbidities and higher CHA2DS2-VASc scores. Kabra also pointed out that unlike randomised trials, the study population also included patients not eligible for warfarin. Kabra et al concluded: “Although LAAC provides an attractive nonpharmacological option for stroke prevention in patients with AF who are not candidates for long-term anticoagulation therapy, further prospective long-term real-world studies are needed to monitor its safety and efficacy.”

pacing (ATP) (69% of patients) adjacent to the scar border or defibrillator shocks (56%) when a strict protocol of right were a common feature of ventricle burst pacing and focal VTs. A median of three catecholamine is used. These VTs per patient were inducible sites predominantly show (28 focal VTs, 34 re-entrant normal bipolar and unipolar VTs; 53% of patients had voltage, often originating from both focal and re-entrant VT sites classical for otherwise mechanism), and focal VTs idiopathic forms of VT. more commonly originated Robert Anderson The study also found focal from the right ventricle VTs were common in patients than the left ventricle (67% vs. 33%, with nonischaemic cardiomyopathy respectively). (72% of the 18 SHD patients in this In the right ventricle the outflow series), which the authors suggest means tract was the most common site (33% standard induction protocols without of all focal VTs), followed by the right the use of burst pacing and isoprenaline ventricle moderator band (22%), apical could miss this VT mechanism, and septal right ventricle (6%), and lateral could help explain high rates of recurrent tricuspid annulus (6%). The lateral left VT in follow-up in these patients. And, ventricle (non-Purkinje) was the most they note, when focal VT sources are common left ventricle focal VT site identified catheter ablation terminated the (16%), followed by the papillary muscles VT in all of the cases, with no recurrence (17%). On follow-up after a median of in follow-up. 289 days, 78% remained arrhythmia-free The authors suggest the study and no patients had recurrence of focal demonstrates that an extended induction VT at repeat procedure. In patients with protocol incorporating right ventricle recurrence, defibrillator therapies were burst pacing and catecholamine significantly reduced from a median of stimulation reveals a group of patients 53 ATP episodes pre-ablation to 10 postwith a focal mechanism. ablation. During follow-up, two patients They say: “Targeting and eliminating (11%) underwent repeat VT ablation; and a focal mechanism of VT in patients none had recurrence of focal VT. with SHD [structural heart disease], Anderson et al suggest that in particularly if it matches the clinic patients with structural heart disease morphology, may lead to improve and myocardial scar, focal VTs are outcomes by reducing VT recurrences commonly revealed (16% of consecutive and prolong arrhythmia-free periods in patients) originating remotely or this group.”

Issue 47 | January 2020

Persistent atrial fibrillation—seeking the sources of the cardiac electrical field

Mapping AF CD using a Poisson formulation with substantial exclusion of unwanted farfield interference cannot be achieved with contact recordings. The practical sequence in individual procedures leading to map generation involves the acquisition of 150,000 unipolar electrograms/second, a solution of charge densities across the endocardial surface at fixed times, and then the generation of real-time moving images that give a clear visual readout of the patterns of endocardial activation patterns, even in complex fibrillation rhythms.

Activation mechanisms

Andrew Grace Comment & Analysis Andrew Grace charts the evolution of non-contact mapping culminating in the current AcQMap system. The technology has advanced understanding of persistent atrial fibrillation (AF), providing further support for the idea that AF is, in fact, a disorder of cardiac development.

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lectromagnetic field theory was the single most important scientific advance of the 19th Century, and was founded on both physical and biological observation. Relevant to the emergence of cardiology, instruments were developed to examine bioelectric signals in experimental models. These measurement tools provided a route to recording surface electrocardiograms that, in turn, underpinned accurate diagnosis and the establishment of a distinct and effective clinical speciality. Non-contact recordings of unipolar electrograms from intracardiac locations (an electrocardiographic equivalent) were first achieved around 30 years ago, but although clinical application advanced the mechanistic understanding of several arrhythmias, the resolution achieved using voltage-based non-contact mapping was limited, and clinical practitioners’ enthusiasm accordingly muted. The electrical fields that are responsible for all electrocardiograms arise from myocardial charge sources. Although these sources cannot be resolved on the basis of surface electrical recordings, they can now be calculated applying well-established mathematics from intracardiac voltage recordings when acquired using the AcQMap system. This step represents a major scientific and technical advance, with significant practical possibilities for immediately and accurately targeting therapy, and provides a versatile toolkit for advancing biology. The approach has already allowed the first “proof-of-principle” unperturbed, full-chamber recordings of atrial fibrillation (AF).

Multi-spline catheter

The most recognisable, differentiated

component of the AcQMap system is a multi-spline catheter, harbouring 48 ultrasound crystals with corresponding unipolar electrodes. The catheter is placed in the chamber of interest, and anatomy is first defined through acquisition of >100,000 ultrasound points/minute, localising the endocardial surface. This highly resolved accurate anatomical shell provides a platform that minimises motion errors, giving high quality input data for distance measurements to feed into charge density (CD) calculations. The activation wavefront that travels through the heart muscle comprises a continuous charge layer, and is more compact than the voltage field used in contact mapping that emerges from it. Calculation of

Conventional conceptual models of AF have posited a variety of activation mechanisms that include single foci, circus movement re-entry, and multiple wavelets. The evolving pattern classification for AcQMap-determined activation sequences refers to single foci, localised rotational activation (LRA) and localised irregular activation (LIA), and constructively accommodates most prior knowledge. Initial practical advantages are the full chamber views and the capacity to rapidly remap, so that the impact of the delivery of individual ablation lesions can be efficiently tracked.

Uncovering persistent AF

The prospective, nonrandomised, multicentre UNCOVER-AF trial recruited 127 patients with persistent AF (PersAF) and was designed to examine both clinical safety and the efficacy of the system. The patients had no prior history of AF ablation and a two-year history since their diagnosis. No device-related major adverse events were reported and, at 12 months, single procedure efficacy assessed using continuous ECG-monitors was 73%, with a 93% second procedure freedom from AF.

Ablate non-pulmonary veins as well

Most strikingly, from both a mechanistic and target identification standpoint, sinus

The results support the idea that AF often emerges against not only a well-described genetic diathesis but, more specifically, that the condition is in fact a ‘developmental’ disorder. Such a proposition would imply foetal programming, with predisposition to the development of both PV and non-PV drivers.” Most strikingly, from both a mechanistic and target identification standpoint, sinus rhythm was much more likely when nonpulmonary vein targets were ablated.”

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rhythm was much more likely when non-pulmonary vein (PV) targets were ablated. In the workflow, all patients underwent initial PV isolation, so this finding provides substantive support for the independent importance of alternative non-vein related drivers. Specifically, predictors of SR at 12 months included a 2.8-fold higher likelihood of success when at least two of three pattern types were ablated during the procedure, and a 9.4-fold higher likelihood when three to four focal, rotational or irregular patterns were ablated. We concluded that PV isolation plus ablation of individualised, patient specific non-PV targets is beneficial when compared to conventional PV isolation alone.

Results are consistent

The patterns observed and their locations are generally consistent with those seen using other approaches and technologies, and also seem to have some consistency and stability in terms of location and patterning over time, when assessed using AcQMap. Taken together, the results support the idea that AF often emerges against not only a well-described genetic diathesis but, more specifically, that the condition is in fact a “developmental” disorder. Such a proposition would imply foetal programming, with predisposition to the development of both PV and non-PV drivers. This idea is supported not just by what we are seeing with AcQMap, but also by a range of preclinical studies and by populationbased findings from, for example, genome wide association studies (GWAS) that implicate transcription factors and other genes involved in aspects of cardiac development to AF susceptibility. The deep phenotyping capabilities of AcQMap in an accessible whole organ, such as the heart, now provide the community with the means to refine disease taxonomy, picking up subsets of AF that will then facilitate the interpretation of clinical genomic studies. Furthermore, through single cell analyses, including rescue experiments, we should be able to advance understanding of the fundamental basis of fibrillation syndromes, and so provide a platform for the design of a range of targeted therapeutic approaches.

Go to the source

In conclusion, the endocardial charge layer is the true source of the observed cardiac electrical field, and calculation of charge density based on standard mathematics has now made effective non-contact mapping a reality. The maps obtained are plausible and actionable, providing a rational means for personalising and targeting ablation procedures. However, the most profound impact may be through the provision of a discovery platform based on deep phenotyping in an accessible, highly quantifiable whole human organ in vivo. Andrew Grace is a consultant cardiologist at the Royal Papworth Hospital, Cambridge, and research group head at the Department of Biochemistry, University of Cambridge, UK.

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January 2020 | Issue 47

Wearable technology

Focus on the Zio Patch wearable sensor in diagnosis of cardiac arrhythmias James Teo was the chief investigator in the EPACS clinical trial, testing the performance of the Zio Patch (iRhthym Technologies) wearable biosensor. He outlines to Cardiac Rhythm News his experience with the device and discusses its use in the diagnosis of cardiac arrhythmias, such as atrial fibrillation (AF).

What is the burden of undiagnosed AF, and what are the risks?

In many patients who have an ischaemic stroke or transient ischaemic attack (TIA), the cause of the stroke remains undiagnosed. A significant proportion of these are likely to be due to paroxysmal AF, which is difficult to confirm without prolonged cardiac monitoring, as it is intermittent. If the condition remains undiagnosed, most patients are treated with antiplatelets only, which is not an adequate therapy for secondary stroke prevention, leaving these patients at increased risk of a future stroke.

How does a device such as the Zio Patch work, and how does it differ from existing methods of diagnosis?

The iRhythm Zio Patch allows real-world, continuous cardiac monitoring over a 14-day period. Although Holter ECGs are more commonly used in the UK, they are typically limited to between three and seven days monitoring, due to issues around tolerability. The Zio Patch is waterproof and its continuous use allows much longer periods of readable recordings. It is also less disruptive for patients as they can continue with most everyday activities, including washing, while wearing it.

What has been your experience of using different diagnostic methods? I used the Zio XT service for the EPACS clinical trial (Early prolonged ambulatory cardiac monitoring in stroke),1 and found patients preferred the Zio Patch as they did not like attending multiple appointments for placement and removal of Holter ECGs. They

also considered it to be liberating, and we found higher usability and completion of cardiac recordings when using the patch compared with Holter ECGs.

James Teo

over other systems?

The EPACS randomised controlled trial provides good evidence for using the Zio Patch after a stroke and transient ischaemic attack (TIA), with a detection rate of paroxysmal AF over six times greater than Holter ECG. Together with the ergonomic form, this was useful for the mSTOPS trial,2 a large-scale AF screening study in the USA which used the Zio Patch.

What studies are ongoing?

Our team in South London, together with the Health Innovation Network, are extending the use of the Zio Patch and investigating the impact of the device on the efficiency of stroke care pathways to work out the health and economic impacts. Other ongoing studies will extend coverage in other disease domains, including congenital heart disease and syncope.

What is the impact on diagnostic accuracy, and how does this affect the

Post-implantation QRS area is a better predictor of cardiac mortality after CRT than QRS duration and LBBB Osita Okafor (Aston University, Birmingham, UK) presented an oral abstract at the Heart Rhythm Congress (HRC 2019; 6–9 October, Birmingham, UK) that demonstrated post-implantation changes in QRS area, derived from vectorcardiography (VCG), are superior to QRS duration and left bundle branch block (LBBB) in predicting cardiac mortality after cardiac resynchronisation therapy (CRT).

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ome studies have shown that preimplantation QRS area (QRSarea) predicts clinical outcomes after CRT. Okafor explained: “CRT is an important therapeutic strategy for heart failure patients. One of the stubborn findings over the past 20 years has been the concept of a high non-responder rate to CRT in up to 30%, particularly when we use QRS duration as the main selection criteria. In recent times, there has been renewed interest in the use of vectorcardiography. In comparison to 12-lead electrocardiography (ECG), vectorcardiography provides a more precise assessment of 3D activation

What data support the use of the Zio Patch? Does it have advantages

patterns. Importantly, the area of the QRS complex on a 3D vectorcardiogram can now be easily derived from 12-lead ECG. Several retrospective observational studies have shown that pre-implant QRS area appears to be a better marker of CRT response then either QRS duration or QRS morphology.” Recently, postimplant QRS area reduction has also been employed as a surrogate marker of LV resynchronisation. However, “changes in QRS area during biventricular pacing has only previously been studied in relation to the acute haemodynamic response to CRT”, said Okafor. He added: “At present, what is not

overall cost of care?

Data from the EPACS study demonstrate the improved diagnostic accuracy of the Zio Patch compared to standard Holter-based systems. This increased yield suggests there could be a reduction in the need for repeat investigations or wasted appointments through non-diagnostic results. Health economic evaluation of the device by the National Institute for Health and Care Excellence (NICE) is currently underway.

How can the role of artificial intelligence (AI) in this area be further developed in the future? In the near future, remote cardiac monitoring systems with real-time data transmission will generate a huge volume of data, which may be beyond the current capacity of health services depending on human analysis. This will be complemented by the pace of developments in artificial intelligence (AI). A greater volume of data will allow generation of algorithms with higher accuracy and fidelity, which could increase the efficiency of ECG reporting to near real-time. Automated calculation of AF burden will increase the ability of these systems to quantify stroke risk with higher precision.3 Additionally, multisource, natural language processing phenotyping algorithms of health records4 will allow for intelligent sub-typing and risk scoring. Cross-modal synthesis of medical imaging and ECG data with AI-based techniques will produce new insights about cardiac arrhythmias which are not currently perceivable. James Teo is clinical director of Data Science at King’s College Hospital NHS Foundation Trust, London, UK. He specialises in the use of wearables and digital technology for health. References 1. Kaura A, et al. Early prolonged ambulatory cardiac monitoring in stroke (EPACS): an open-label randomised controlled trial. European Journal of Medical Research 2019; 24 (25). 2. Steinbuhl S, et al. Effect of a home-based wearable continuous ECG monitoring patch on detection of undiagnosed atrial fibrillation: the mSToPS randomised clinical trial. Journal of the American Medical Association (JAMA) 2018; 320 (2). 3. Go A, et al. Association of burden of atrial fibrillation with risk of ischemic stroke in adults with paroxysmal atrial fibrillation: the KP-RHYTHM study. JAMA: Cardiology 2018; 3 (7). 4. Bean D, et al. Semantic computational analysis of anticoagulation use in atrial fibrillation from real world data. PLoS ONE 2019; 14 (11).

known is whether post-implantation changes in QRS area can predict outcome. The aim of the current study was to look at the QRS area reduction following CRT and how this correlates to hard clinical endpoints.” The retrospective single-centre study at Queen Elizabeth Hospital (Birmingham UK) assessed QRSarea, derived from preand post-implantation VCG, in relation to the primary endpoint of cardiac mortality after CRT. Other endpoints in the study were total mortality, total mortality or heart failure hospitalisation, and total mortality or major adverse cardiac events (MACE).

We are the first study to show that postimplant changes in QRS area can predict better long-term clinical outcomes following CRT.”

In 380 patients (age 72±12.4 years, 68.7% male) undergoing CRT over 7.7 years (median follow-up 3.8 years, interquartile range [IQR] 2.3–5.3), pre-implantation QRSarea ≥102µVs predicted cardiac mortality (hazard ratio [HR] 0.36, p<0.001) as well as total mortality (HR 0.58, p=0.001), total mortality or heart failure hospitalisation (HR 0.53) and total mortality or MACE (HR 0.52) (both p<0.001). The association of QRSarea with cardiac mortality was independent of known confounders, including QRS duration (QRSd) and morphology (p<0.001). After CRT, a reduction in QRSarea ≥45µVs, or any reduction in QRSd predicted cardiac mortality (area under curve 0.74 and 0.72, respectively, p=0.425 for comparison). Concomitant reductions in QRSarea and QRSd were the best predictor of cardiac mortality (HR 0.12, p<0.001 for interaction). He concluded: “Generally speaking, we found that post-implant changes in QRS duration and QRS area were better predictors of clinical outcomes than pre-implant QRS duration and QRS area. This is an important finding, as it indicates that not only is the baseline electrical substrate important, but also its subsequent modification by CRT.”

Issue 47 | January 2020

MedTech insights

Longest and largest follow-up data for Watchman support its role in stroke prevention Data from the CAP and CAP2 registries—which contain the longest and largest follow-up of patients—add to previous evidence that left atrial appendage closure (LAAC) with Watchman (Boston Scientific) is a safe and effective alternative to long-term anticoagulation in patients with atrial fibrillation. Furthermore, the results show the lowest rate of haemorrhagic stroke observed in this patient population.

Source: BIBA MedTech Insights LAA Quarterly Monitor

David R Holmes (Mayo Clinic, Rochester, USA) and others report in Journal of the American College of Cardiology that while anticoagulation is the “standard of care” for mitigating the risk of stroke in patients with atrial fibrillation, “local therapy” with LAAC “is used with increasing frequency” as an alternative approach. They explain that this is because patients can have “a variety of or absolute contraindications” to anticoagulation, and that the rate of patient nonadherence to anticoagulation is “50% to 60% by 1.5 to 2.0 years”. Data from BIBA MedTech Insights LAA Quarterly Monitor do suggest that the use of LAAC is growing (albeit not rapidly). These findings show that there has been a 5.6% increase in

the number of LAAC implants in the top five European markets (France, Germany, Italy, Spain, and the UK) over the last two years: 3,540 in Q3 2017 vs. 3,740 in Q3 2019. (See Figure 1). According to Holmes et al, this increase in use of LAAC means that “a collection of longer-term data using LAAC devices is important”. They add that the initial randomised controlled trials of the Watchman devices had accompanying registries “designed to continue accrual of data on longer-term outcomes and allowed continued access to the technology prior to the US Food and Drug Administration (FDA) approval”. Therefore, as these registries “represent the largest number

and longest follow-up” of patients implanted with Watchman, the authors reviewed the five-year (CAP) and four-year (CAP2) outcome data. CAP included 566 patients who underwent implantation with Watchman between 2008 and 2010 with five-year follow-up, while CAP2 included 578 patients who underwent implantation between 2012 and 2014 with four-year follow-up. In both studies, patients had atrial fibrillation, were at increased risk of stroke, and were eligible for anticoagulation. Also, both studies had the primary efficacy endpoint of a composite of stroke, cardiovascular death, and systemic embolism. At five years, in the CAP registry patients, the primary efficacy endpoint occurred in 12.4% of patients at a rate of 3.05 per 100 patient years. Specifically, the rate of haemorrhagic stroke was 0.1 per 100 patient years and the rate of ischaemic stroke was 1.30 per 100 patient years. Holmes et al comment: “Compared with predicted rates of untreated patients with similar CHA2DS2-VASc risk scores, the observed rate of ischaemic stroke was 1.30 compared with the expected rate of 5.86 per 100 patient-years, a 78% relative reduction.” They add that the rate of haemorrhagic is the “lowest reported”. The primary efficacy endpoint in the CAP2 registry occurred, at four years, in 102 patients at a rate of 4.80 per 100 patient years. Holmes et al note that as in the CAP registry, the rate of haemorrhagic stroke (0.09 per 100

patient years) was “markedly less” than has been previously reported. In this dataset, based on CHA2DS2VASc risk scores, the expected rate of ischaemic stroke was 7.1% (in untreated patients) but the observed rate was 2.20 per 100 patient years. This finding demonstrated, the authors say, “a 69% relative reduction (4.70 per 100 patient-years absolute reduction)”. The authors conclude: “The final five-year and four-year data presented from the CAP and CAP2 registries adds to increasing information at that local site therapy is an effective and safe alternative to long-term anticoagulation in patients with nonvalvular atrial fibrillation who are at increased risk of stroke.” Holmes says: “These longest term outcome data in the field, with the Watchman device, add to the information that this technology is an important advance in the field and provides information on safety and efficacy. It substantiates the information needed by clinicians that supports expanded use of the procedure. These data, in addition to the current trials underway, will allow positioning of this technology as an alternative to be explored with patients at risk for stroke/systemic embolism in the setting of nonvalvular atrial fibrillation. The future can be predicted to move towards shared decision making where patients can elect treatment with either a LAAC device in expert hands, or an oral anticoagulant as first-line therapy to be considered.”

BIBA Briefings

BIBA Briefings is an online platform (www.bibamedtech.com/bibabriefings) that gives an in-depth analysis of the latest market intelligence from BIBA MedTech Insights (www.bibamedtech.com). It also reviews the latest industry news and pipeline developments. For editorial enquiries, please contact Dawn Powell: dawn@bibamedical.com For sales enquiries (including BIBA MedTech Insights), please contact Merveille Anderson: merveille@bibamedical.com

Calendar of events 14–15 February

29–31 March

Manila, The Philippines

Vienna, Austria

APHRS Summit 2020 aphrs.org

24–26 February

EHRA 2020 escardio.org

6–9 May

2020 Heart Rhythm Scientific Sessions San Diego, USA hrssessions.org

IDSS2020

23–26 May

2020.idss-ep.com

Barcelona, Spain

Tel Aviv, Israel

13

29 August–2 September

27–30 September

Amsterdam, The Netherlands

Birmingham, UK

ESC 2020 Annual Congress esc2020housing.org

Heart Rhythm Congress heartrhythmcongress.org

1–4 November

Heart Failure 2020

APHRS 2020 Scientific Sessions

escardio.org

aphrs.org

Hong Kong

14

January 2020 | Issue 47

Market watch

Clinical News European trial data reinforce safety profile and efficacy of Lixiana

Daiichi Sankyo Europe has announced outcomes from an observational study in mainly caucasian atrial fibrillation (AF) patients being treated with the anticoagulation drug edoxaban (Lixiana). The results of the observational cohort study, published in the European Heart Journal—Cardiovascular Pharmacotherapy, showed that rates of ischaemic stroke and systemic embolism were similar to those observed in the composite ‘stroke’ outcome in the ENGAGE AF-TIMI 48 clinical trial, comparing the long-term efficacy and safety of Lixiana with warfarin in AF patients. In addition, primary (composite) bleeding outcomes requiring hospitalisation were approximately 50% lower than observed in ENGAGE AFTIMI 48. Commenting on the study, lead author, Peter Brønnum Nielsen (Aalborg Thrombosis Research Unit, Aalborg University, Denmark), said: “These new data, reporting on outcomes in a European AF population seen in routine clinical practice, are reassuring as they reinforce previous evidence that edoxaban has a good safety profile and is an effective treatment for the prevention of stroke in a broad AF population.” 643 patients (28%) received Lixiana 30 mg dosage regimen and 1,642 (72%) Lixiana 60 mg, which is similar to the split in ENGAGE AF-TIMI 48. The primary effectiveness endpoint of thromboembolism, comprised of a composite outcome of stroke and systemic embolism, occurred 41 times. In patients taking Lixiana 30 mg daily (dose reduced) the event rate was 2.07 per 100 person-years, and in those taking Lixiana 60 mg daily (full dose) the event rate was 1.62 per 100 personyears.

AMBULATE study demonstrates safety of VASCADE MVP

Results from the AMBULATE pivotal study demonstrate the safety and efficacy of Cardiva Medical’s VASCADE MVP venous vascular closure system compared to manual compression, the company has said. Results from the study were published online in the Journal of the American College of Cardiology: Clinical Electrophysiology. The company has also received CE Mark certification for the device in Europe. The AMBULATE pivotal study is a randomised, controlled study of 204 patients across 13 sites treated with the VASCADE MVP system compared to standard manual compression following cardiac ablation. The study showed significant improvements in time to

Vascade MVP

ambulation, total post-procedure time and time-to-discharge eligibility, as well as improved patient satisfaction scores and significantly reduced use of opioid pain medications. Andrea Natale (Texas Cardiac Arrhythmia Institute, Austin, USA), who was among the principal investigators in the study, said: “Using this technology elevates the level of care we offer our patients by allowing them to get back on their feet safely and quickly, potentially leave the hospital earlier, and even take less opioids to relieve their post-procedural pain. The publication of these data further proves the value of this technology for both physicians and their patients.” VASCADE MVP uses a proprietary delivery system to place a collagen patch on the outside of each vessel puncture site following completion of the procedure.

median per cent AV synchrony was 94.3% during AV synchronous pacing compared to 26.9% during VVI pacing. In addition, blood flow from the left ventricle (velocity time integral, a proxy for stroke volume), increased by 1.7 cm (on an absolute scale, 95% CI 0.7–2.7cm, p=0.002; or 8.8% on a relative scale) during AV synchronous pacing compared with single-chamber ventricular pacing mode in patients with normal sinus rhythm with complete heart block.

CorCinch study demonstrates favourable safety results for AccuCinch

Data from an interim analysis of heart failure patients treated in the CorCinch FMR study show that the AccuCinch ventricular repair system (Ancora Heart) is associated with a favourable safety profile, with 97% freedom from devicerelated major adverse events at 30 days, according to a press release. The findings from the first 31 heart failure patients with functional mitral regurgitation, treated with the AccuCinch system at heart centres across the USA, were presented by Satya Shreenivas (The Christ Hospital Heart and Vascular Center and The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital, USA) at the Transcatheter

Neuromodulation Therapy (CNT). The company said that the study demonstrated statistically significant and clinically meaningful reductions in systolic blood pressure in hypertensive patients also indicated for a pacemaker. The results, presented at a latebreaking session at the Transcatheter Cardiovascular Therapeutics scientific symposium (TCT 2019; 24-29 September, San Francisco, USA) by Karl-Heinz Kuck (Lans Medicum, Hamburg, Germany), showed the study met its primary efficacy endpoint, with patients randomised to BackBeat CNT experiencing an 11.1mmHg (p<0.001) reduction in mean 24-hour ambulatory systolic blood pressure (ASBP) at six months follow-up, resulting in a significant difference of 8.1mmHg compared to control patients who were managed only with antihypertensive medications (p=0.01). The study also met its primary safety endpoint with no statistical difference in rate of major cardiac adverse events (MACE) between the two groups at six months follow-up. Patients enrolled in the study were implanted with Orchestra BioMed’s Moderato System, an implantable pulse generator that delivers BackBeat CNT, as well as standard rhythm management functions. Following a 30-day run-in period, during which patients received

Medtronic shares findings from MARVEL 2 study

Medtronic has announced results from the MARVEL 2 (Micra Atrial Tracking Using A Ventricular accELerometer) study. The study shows that an investigational set of algorithms in the Micra Transcatheter Pacing System (TPS) improves synchrony and cardiac function in patients with atrioventricular (AV) block. The results from MARVEL 2 were published in JACC: Clinical Electrophysiology and presented at the American Heart Association 2019, the AHA Scientific Sessions. MARVEL 2 evaluated 75 patients with a Micra TPS at 12 centres in Hong Kong, Malaysia, Europe and the USA. Investigators evaluated the safety and effectiveness of accelerometer-based atrial sensing algorithms, which were downloaded to the Micra TPS device. Forty patients had complete heart block and normal sinus rhythm and were eligible for inclusion in the primary efficacy analysis, while all 75 patients were included in the primary safety objective. Investigators evaluated the ability of the Micra accelerometer to monitor and detect atrial contractions and enable coordinated pacing between the atrium and ventricle, thereby providing AV synchrony. The study’s primary efficacy objective was met, with a greater percentage of complete heart block patients with normal sinus rhythm having >70% AV synchrony during algorithm-mediated AV synchronous pacing (38 of 40 patients, 95%) than VVI pacing (0 patients, p<0.001 for proportion of patients with >70% synchrony). The

AccuCinch side by side 3D Graphic

Cardiovascular Therapeutics scientific symposium (TCT 2019; 25–29 September, San Francisco, USA). The AccuCinch system is designed to directly repair the left ventricle of the heart, addressing the progression of systolic heart failure. The primary safety endpoint of the CorCinch FMR study is device-related or procedure-related major adverse events through 30 days. Secondary exploratory endpoints include technical success, and device and procedural success, as well as other observational endpoints measuring heart function, heart failure symptoms, and changes in quality of life.

Orchestra BioMed announces positive data for its BackBeat Cardiac Neuromodulation Therapy

Orchestra BioMed announced results from its MODERATO II double-blind, randomised study of BackBeat Cardiac

only standard pacing along with antihypertensive medications, patients who met follow-up screening criteria for daytime ASBP were randomised to BackBeat CNT or control groups. Prior to randomisation, mean ASBP for both groups were 136.3mmHg and patients, on average, treated with more than three prescribed antihypertensive drugs. After six months, mean ASBP was reduced by 11.1mmHg (p<0.001) in the BackBeat CNT group, as compared to a reduction of 3.1mmHg in the control group (p=0.17). The treatment group saw an overall response rate of 85%, with approximately 54% of the BackBeat CNT-treated patients experiencing ASBP reduction at six months of >10mmHg, an amount associated with a clinically meaningful reduction in risk of heart attack and stroke. The BackBeat CNT group also experienced significantly greater reduction, 12.4mmHg, in office systolic blood pressure over the control group (p=0.02).

Issue 47 | January 2020

Market watch

Product News FDA approves Abbott heart pump for less invasive surgical approach

Abbott has announced US Food and Drug Administration (FDA) approval of an alternative surgical technique for the HeartMate 3 heart pump that the company says will allow more advanced heart failure patients to avoid open heart surgery. The heart pump can now be implanted through an incision in the chest wall versus open heart surgery. In a press release, Abbott notes that the approval is based on two studies: the ELEVATE study, a multicentre, voluntary, observational registry collecting post-marketing data, and the LAT Feasibility study: a single arm, prospective, multicentre study. Results of the two trials found that bleeding (requiring surgery), infection and arrhythmias were lower in the group implanted via the less-invasive surgical approach. Historically, heart pumps have been implanted via open heart surgery. With approval for an alternative surgical technique, Abbott’s HeartMate 3 heart pump can now be implanted via lateral thoracotomy, where an incision is made between a patient’s ribs to access the heart. “This is a significant advancement for patients who can now receive a life-saving LVAD through an alternative procedure that can yield shorter hospital stays and a faster recovery,” comments heart transplant surgeon Igor Gosev (University of Rochester Medical Center, New York, USA) in the company statement.

Breakthrough designation granted for ECG-based algorithm

The US FDA has granted Breakthrough Device designation to the digital health and artificial intelligence (AI) company Eko for an echocardiogram (ECG)based algorithm to help identify induced Left Ventricular Ejection Fraction

(LVEF). Breakthrough Device designation helps accelerate regulatory review and is awarded to innovations that demonstrate the potential to address unmet medical needs for life-threatening or irreversibly debilitating diseases.

ECG on chest

The algorithm analyses 15 seconds of ECG data collected from the Eko DUO digital stethoscope during a physical exam and helps identify reduced LVEF, a measure commonly used to diagnose patients with heart failure. Eko’s low ejection fraction algorithm employs a deep neural network, which was developed in collaboration with Mayo Clinic. “The Breakthrough Device designation recognises the vast unmet clinical needs in identifying heart failure early in patients, whether it be due to cost, inaccessibility, or misdiagnosis,” said Connor Landgraf, CEO and cofounder of Eko.

“Cuffless” system to monitor blood pressure could replace traditional methods A wrist-based optical blood pressure monitor has the potential to replace cuff monitoring systems for ambulatory blood pressure, suggests a study in the journal Blood Pressure Monitoring. A press release from Aktiia, the Swissbased company manufacturing the device, states that the novel system uses the same sensors to measure heart rate as those used in wearable devices.

In the study, Cyril Pellaton (Hopital Neuchâtelois de Pourtalès, Neuchâtel, Switzerland) and colleagues enrolled 30 critical patients scheduled to undergo radial arterial catheterisation at an intensive care unit. After inclusion, the team compared “ground-truth” blood pressure measurements at the radial artery simultaneously with optical signals acquired at the contralateral wrist by a prototype of the Aktiia wearable device. For systolic blood pressure, there was a mean difference (±SD) of 0.0±7.1mmHg between the arterial catheter and the optical device values, with 95% limits of agreement in the Bland-Altman method of -11.9mmHg to +12.2mmHg (correlation r=0.87, p<0.001). For diastolic blood pressure, a mean difference of 0.0±2.9mmHg between arterial catheter and the optical device values was found, with 95% limits of agreement in the Bland-Altman method of -4.8mmHg to +5.5mmHg (r=0.98, p<0.001). The press release says the results provide “clear and compelling evidence” on the reliability and accuracy of the optical blood pressure monitoring technology compared to currently accepted methods of blood pressure measurement.

First patients treated using integrated navigation technology from Stereotaxis and ADAS 3D

Stereotaxis and ADAS 3D Medical have announced that the first patients have been treated with the integration of ADAS 3D’s advanced preoperative substrate mapping and Stereotaxis’ robotic magnetic navigation technologies. ADAS 3D helps identify possible sources of dangerous irregular heartbeats and provides a map to guide physicians in delivering treatment. The software uses preoperative cardiac MRI to generate detailed three-dimensional cardiac models that identify arrhythmia substrate and characterise cardiac tissue. The latest version of Stereotaxis software, recently cleared for use in Europe and by the US FDA, integrates ADAS 3D’s images and

15

ADAS 3D in use at Hospital Da Luz, Lisbon

allows physicians to utilise them to guide therapy during robotic cardiac ablation procedures. The first integrated procedures were successfully conducted by Pedro Adragao (Hospital da Luz, Lisbon, Portugal). Commenting, Adragao said: “We have long recognised the clinical value of robotic magnetic navigation to treat patients with precision and safety. The integration of both technologies should result in more effective, rapid, and safe procedures for patients.”

CardioFocus treats first patients with HeartLight endoscopic ablation system in France

CardioFocus has announced that the first patients in France have been treated at the University Public Hospital of Nancy (Nancy, France) with the HeartLight endoscopic ablation system as part of a distribution partnership with MicroPort CRM France. To date, more than 7,000 patients have been treated in the US, Europe and Japan, with the HeartLight System. Within Europe, France is one of the three largest markets for atrial fibrillation (AF) ablation technologies. The HeartLight System is a catheter ablation technology for controlled and consistent pulmonary vein isolation (PVI), a gold standard treatment for AF. During PVI with the HeartLight System, laser energy is used to create lines of scar tissue to block the abnormal electrical pathways that cause AF. In March, CardioFocus announced the European CE Mark approval and commercial launch of its thirdgeneration technology, the HeartLight X3 system.

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