Arrhythmias & devices: novelties at ESC Congress 2019

Arrhythmia: Diagnosis

Arrhythmia detection, especially AF, was presented in a session on the latest detection devices. The authors recognised that these devices for the detection of AF and blood pressure measurement are accurate, fast, reliable and medically approved (FDA). Currently, these first-generation devices detect AF, bradycardia and tachycardia; however, the forecast for the second generation in 2020 is that they will also be used to detect blood pressure, cardiac arrest, respiratory rate, additional arrhythmias and peripheral capillary oxygen saturation (SpO2). The planned future for the third-generation devices (to be developed in 2021) includes the detection of stroke volume, galvanic skin response, and big data and artificial intelligence (AI) analytics.

The APPLE Watch self-electrocardiogram (ECG)

One of the novelties presented at this congress was the 2019 Apple Watch Series 4. Weighing only 30 grammes, with the capacity of producing a self-electrocardiogram (ECG) of 12 derivations, it is without a doubt an important advance that is based on the possibility of moving the position of the watch through the thorax to collect the different electrical signals.

The Huawei Heart Study

The other telephone giant, Huawei, presented a very important study, the Huawei Heart Study (HHS: pre-mobile atrial fibrillation app [MAFA] study). The screening was carried out on a population of 186,956 subjects, of whom 0.2% received notification of suspected AF. Of these, 87% had AF confirmed by doctors working with the mobile atrial fibrillation app (MAFA) hospital, 95% with MAFA for AF integrated atrial fibrillation better care (ABC). At the end of the study, 80% of high-risk patients were successfully anticoagulated. The authors also presented a comparison between the HHS and the Apple Heart Study (AHS). The main points here were seen to be an improvement in the algorithm accuracy detecting PPVV, 91.6% vs 71.3%. Regarding measurement, the periodical measurement in the HHS is based on a photoplethysmogram (PPG). Periodic measurement results are given, and the proportion of irregular rhythms are analysed, but in the AHS this is based on a PPG, and periodic measurement results are not given. In relation to periodical measurement frequency, in the HHS it is performed every 10 minutes. In the AHS, every two hours for baseline mode, an irregular tachogram initiates a cascade of more frequent modes (every 16 minutes). Concerning follow-up and confirmation, there are also improvements. While in the AHS the follow-up was based on a video visit online, in the HHS follow-up was made by a doctor, combined with clinical care AF management. In the AHS the confirmation was carried out with an ePatch, but in the HHS the confirmation was carried out using medical history, physical examination, and ECG or 24-hour Holter monitor by doctors. The follow-up rate was also different in each study. While in the AHS the follow-up rate was 44% first study visits with those effectively followed up by an ePatch who returned and were analysed was 21%, in the HHS the follow-up rate was 62% with MAFA telecare and doctors. Finally, the proportion of AF confirmed by doctors or ePatch was 87% in the HHS versus 34% in the AHS. The HHS was published simultaneously in the Journal of the American College of Cardiology (JACC) [1].

Artificial intelligence-enabled ECG algorithms

Dr. Zachil Attia presented a very interesting study by the Mayo Clinic which was published in The Lancet in August 2019. This study concerns the development of an AI-enabled ECG using a convolutional neural network to detect the electrocardiographic signature of AF present during normal sinus rhythm using standard 10-second, 12-lead ECGs. All patients aged 18 years or older with at least one digital, normal sinus rhythm, standard 10-second, 12-lead ECG acquired in the supine position at the Mayo Clinic ECG laboratory over a period of 24 years were included. The authors calculated the area under the curve (AUC) of the receiver operating characteristic curve for the internal validation data set to select a probability threshold, which was applied to the testing data set. The study included 180,922 patients with 649,931 normal sinus rhythm ECGs for analysis. In the testing data set, 3,051 (8.4%) patients were found to have had verified AF before the normal sinus rhythm ECG tested by the model. A single AI-enabled ECG identified AF with an AUC of 0.87 (95% CI: 0.86-0.88), sensitivity of 79.0% (77.5-80.4), specificity of 79.5% (79.0-79.9), F1 score of 39.2% (38.1-40.3), and overall accuracy of 79.4% (79.0-79.9). The authors’ conclusion was that an AI-enabled ECG acquired during normal sinus rhythm permits identification at the point of care of individuals with AF [2].

Atrial Fibrillation: Treatment

Treatment with electrical cardioversion (ECV) in patients with AF has also been evaluated in a clinical trial. The trial randomised 276 patients with AF and criteria to undergo ECV to two treatment arms. The first one used a stepped electrical treatment of 125-150-200 Joules. The other arm used a treatment of greater intensity also staggered with 360-360-360 Joules. The first objective was the persistence of sinus rhythm one minute after the ECV. The result was that, with the maximum-fixed shocks, 88% was achieved compared to 66% with the low-escalating shock, which represents a difference of 22% (95% CI: 13-32), p<0.001. The result was that maximum-fixed energy shocks were more effective than low-escalating energy shocks for cardioverting AF. No differences in any safety endpoints were found. The trial was published in the European Heart Journal [3].

The EARNEST-PVI trial

Two trials were presented that focused on the treatment of AF by ablation. The first, the EARNEST-PVI trial, included patients with AF with an indication for pulmonary vein ablation. Patients were randomised in a 1:1 ratio. The first step, pulmonary vein isolation (PVI), was carried out in all patients. Later, only half of them were treated with additional ablation. PVI was mandatory with two recommendations that the PVI potentials were reconfirmed >20 minutes after the initial success and, if PVI potentials reappeared, elimination of them was mandatory. In those patients selected for additional ablation (PVI-plus), linear ablation or complex fractionated atrial electrocardiogram (CFAE) ablation or both were mandatory. The choice was made by the attending physicians. The purpose of the study was to demonstrate non-inferiority of a PVI-alone strategy compared to a PVI-plus additional ablation strategy in patients with persistent AF. The primary endpoint was the recurrence of AF/atrial tachycardia (AT) with/without antiarrhythmic drugs (AADs) during the one-year follow-up. The comparison of primary endpoint-free ratio showed that the freedom from AF/AT was 78.3% in the PVI-plus group, as compared to 71.3% in the PVI-alone group: hazard ratio (HR) 1.56 (95% CI: 1.10-2.34), p=0.03062 for non-inferiority. The recurrence-free ratio without AADs after the blanking period was also different: 73.9% in the PVI-plus group versus 65.7% in the PVI-alone group.

The ATTEST study

Another trial on this topic was the ATTEST study. This study attempted to determine whether ablation using an irrigated radiofrequency (RF) catheter in conjunction with three-dimensional (3D) electroanatomic mapping delays progression of AF versus drug therapy (rate or rhythm control) per current guidelines. The design of the study included patients older than 60 years, with paroxysmal AF for ≥2 years, ≥2 episodes in the past six months, and at least after the failure of 1-2 AADs or rate control drugs. Patients were randomised to either the AAD group, in which the medication was managed according to current guidelines at the investigators’ discretion, or the RF ablation group. The RF ablation group was treated with PVI using irrigated RF catheters in conjunction with 3D electroanatomic mapping. Patients were followed for three years. The primary endpoint was the progression to persistent AF/AT at 3 years. Patients undergoing RF ablation were ~10x less likely than AAD patients to develop persistent AF (HR: 0.114). After randomising 255 patients with drug-refractory paroxysmal AF, early RF ablation was superior to AAD in delaying progression to persistent AF. The authors concluded that, to date, catheter ablation has been primarily indicated for second-line, symptomatic treatment of paroxysmal AF after failure of ≥1 AAD. The ATTEST results may introduce a new indication for catheter ablation in patients with paroxysmal AF.

2019 ESC Guidelines on Supraventricular Tachycardia

Another important development has been the 2019 ESC Guidelines for the management of patients with supraventricular tachycardia (SVT). The biggest change in management concerns drug treatment. A large number of the drugs cited in the previous guidelines are not featured in this version. For instance, we now know that amiodarone and digoxin are potentially harmful for chronic treatment. Today, catheter ablation has a much more prominent place in the treatment of SVT. Being associated with only a very small risk of complications, ablation should be offered as a first-line treatment option to most patients without contraindications. There are also changes concerning the subject of asymptomatic pre-excitation that has a dedicated algorithm for its screening and management. The new guidelines have separate sections considering management approaches for subgroups of patients with particular needs, and they discuss SVT in the context of sport and driving restrictions. The current guidelines give a comprehensive overview of the field and provide clinicians in all branches of cardiology with an important and long overdue reference document for managing SVT. Finally, a resumé in 20 evidence-based “what to do” and “what not to do” messages from the guidelines summarised the most important and novel recommendations. A review has summed up the key points to remember from the SVT guidelines [4].

1. This is the first guideline update for SVT by the ESC in 16 years. Amiodarone and digoxin are no longer mentioned in the new guidelines for the acute management of narrow complex tachycardia. Sotalol and lidocaine have been removed from the algorithm for the acute management of wide complex tachycardia.
2. Verapamil/diltiazem and catheter ablation are no longer recommended for inappropriate sinus tachycardia. Ivabradine alone, beta-blocker alone, or both agents taken together should now be considered in symptomatic patients (Class IIa). 
3. Procainamide, sotalol, and digoxin are no longer recommended for the acute management of focal AT. Amiodarone, sotalol, and disopyramide are not recommended for chronic suppression of focal AT. Catheter ablation is recommended for recurrent focal AT, especially if incessant or causing tachycardia cardiomyopathy. Beta-blockers should be considered for recurrent focal AT or atrial flutter, if ablation is not possible or unsuccessful. 
4. For multifocal AT, treatment of an underlying condition is recommended as a first step (Class I). Verapamil, diltiazem, or a selective beta-blocker should be considered (Class IIa). Atrioventricular (AV) nodal ablation followed by biventricular or bundle of His pacing should be considered for patients with left ventricular dysfunction due to recurrent multifocal AT refractory to drug therapy (Class IIa).
5. Dofetilide, sotalol, flecainide, propafenone, procainamide, quinidine, and disopyramide are no longer recommended for chronic management of atrial flutter in the new guidelines. Patients with atrial flutter without AF should be considered for anticoagulation, but the threshold for initiation is not established (Class IIa). 
6. In all re-entrant and most focal arrhythmias, catheter ablation should be offered as an initial choice to patients, after having explained in detail the potential risks and benefits. In post-AF ablation ATs, focal or macro–re-entrant, ablation should be deferred for >3 months after AF ablation, when possible.
7. Multiple drugs have been removed from both the acute and chronic management of AV nodal re-entrant tachycardia (AVNRT). Verapamil, diltiazem, and beta-blockers remain as options for the chronic management of AVNRT, but they have been downgraded from Class I to Class IIa.
8. Catheter ablation is recommended in asymptomatic patients in whom electrophysiology testing with the use of isoprenaline identifies high-risk properties, such as shortest pre-excited RR interval during AF ≤250 ms, accessory pathway effective refractory period <250 ms, multiple accessory pathways, and an inducible accessory pathway-mediated tachycardia (Class I). Non-invasive evaluation of the conducting properties of the accessory pathway in individuals with asymptomatic pre-excitation may be considered (Class IIb). Digoxin, beta-blockers, diltiazem, verapamil, and amiodarone are not recommended and are potentially harmful in patients with pre-excited AF (Class III).
9. Sotalol, propranolol, quinidine, and procainamide are no longer used in the updated guidelines for SVT management in pregnant women. During the first trimester, it is recommended that all antiarrhythmic drugs are avoided. Beta-1 selective blockers (except atenolol) or verapamil should be considered for prevention of SVT in patients without Wolff-Parkinson-White (WPW) syndrome (Class IIa). Flecainide or propafenone should be considered for prevention of SVT in patients with WPW syndrome and without ischaemic or structural heart disease (Class IIa).
10. SVTs have been reported as risk factors for sudden cardiac death in patients with adult congenital heart disease (ACHD). In ACHD, anticoagulation for focal AT or atrial flutter should be similar to that for patients with AF. Catheter ablation in experienced centres should be considered. Sotalol is not recommended as a first-line antiarrhythmic drug due to an increased risk of proarrhythmia and mortality (Class III). Flecainide and propafenone should be avoided in patients with left bundle branch block, or ischaemic or structural heart disease (Class III).
11. In postural orthostatic tachycardia syndrome, a regular and progressive exercise programme should be considered (Class IIa). The consumption of up to 2-3 L of water and 10-12 g of sodium chloride daily, as well as midodrine, low-dose non-selective beta-blocker, pyridostigmine, and ivabradine may be considered (Class IIb).

Sudden Cardiac Death

In relation to sudden cardiac death (SCD), two important studies were presented:

Spanish network for research on adults with congenital heart disease

The first of them used a detection model based on the lesion-specific risk of SCD or life-threatening ventricular arrhythmias (LTVA) in adults with congenital heart disease. Based on a database of 3,764 patients, finally 3,311 subjects were included. The follow-up covered 37,510 patient-years. The endpoints were SCD and non-fatal sudden cardiac arrest. The model was validated in a multicentre study. The trial concluded that the incidence rate of SCD-LTVA varies widely across the diagnostic categories. A lesion-specific risk stratification in clusters was performed and validated in an external large multicentre population. Finally, the incorporation of this baseline risk stratification to risk models for SCD could result in a more individualised patient management.

The HCM Risk-Kids study

Another study regarding SCD was presented - the HCM Risk-Kids study. This study presented a novel risk prediction model for SCD in childhood hypertrophic cardiomyopathy (HCM). The authors analysed 5,984 patient-years of hypertrophic cardiomyopathy (median 5.3 [2.6; 8.3]) and observed 89 (8.7%) arrhythmic events: 39 SCD, 24 appropriate ICD therapy, 16 aborted SCD and 10 sustained ventricular tachycardia (VT). When all the variables were analysed, the authors found five of them were the best for prediction:

• maximal wall thickness (Z-score),
• left atrial diameter (Z-score),
• unexplained syncope, non-sustained VT
• left ventricular outflow tract (LVOT) gradient (mmHg).

The model was validated after a follow-up of five years in 527 patients, and the authors observed 34 SCD new endpoints. The model is able to predict the risk, so this is the first validated approach to risk stratification in childhood HCM. The authors recognised the necessity of external validation studies to demonstrate the accuracy of the model, and they suggested refining the model using novel clinical risk factors such as 12-lead ECG, genetics and cardiac magnetic resonance imaging. The trial was simultaneously published in the Journal of the American Medical Association (JAMA) [5].

Implantable cardioverter defibrillator

With regard to ICD novelties, two different studies were presented:

The EU-CERT-ICD substudy

The EU-CERT-ICD substudy uses periodic repolarisation dynamics (PRD), a novel ECG-based marker that quantifies sympathetic activity-related low-frequency oscillations of cardiac repolarisation instability. Previous studies proved that increased PRD is associated with malignant tachyarrhythmias, appropriate ICD shocks and SCD. The authors performed a prospective study with 1,371 patients; ICDs were implanted in 968 of them because they had an indication for ICD and a comparison was carried out with 403 patients with no ICD indication. The conclusions of the study were:

• First, that PRD predicts the treatment effect of primary prophylactic ICD therapy in terms of mortality reduction in contemporarily treated patients.
• Second, PRD assessment may help to guide prophylactic ICD implantation in patients with ischaemic heart disease or non-ischaemic cardiomyopathy.
• Third, it could be promising to combine PRD with complementary markers that identify patients who do not benefit from ICD implantation due to competing risks.

The trial was simultaneously published in The Lancet [6].

The EU-CERT-ICD non-randomised controlled multicentre study

The second study (the EU-CERT-ICD non-randomised controlled multicentre study) applied the PRD to prove the clinical effectiveness of primary prevention ICDs. The study included patients with ischaemic (ICM) or dilated cardiomyopathy (DCM) with a left ventricular ejection fraction (LVEF) <35% and narrow QRS with optimal medical therapy with Class I ICD indication according to the ESC guidelines, and older than 18 years. In a non-randomised setting during the follow-up period, the authors compared patients with ICD implantation and those with no ICD implantation. The results of the study showed a reduction in all-cause mortality in ICD versus the control group with a HR of 0.682 (95% CI: 0.537-0.865), p=0.0016. Also, a reduction in SCD was observed: HR 0.166 (95% CI: 0.089-0310), p<0.0001.

The authors concluded that, in contemporary ICM/DCM patients, primary prophylactic ICD treatment was associated with a 27% lower mortality after adjustment. They also concluded that there appear to be patients with less survival advantage such as older patients or diabetics. Finally, the authors’ opinion is that randomised ICD studies are now clearly warranted.

The Defibrillator After Primary Angioplasty (DAPA) trial

The last trial I would like to comment on is the Defibrillator After Primary Angioplasty (DAPA) trial (long-term outcome). Guidelines recommend, after STEMI with primary PCI, waiting 3-6 months before ICD implantation in those with a low EF. This trial attempted to evaluate the survival benefit of early prophylactic ICD implantation in high-risk STEMI patients after primary PCI. The trial randomised 231 patients to receive ICD or not (control group) with a follow-up of nine years. The results showed a reduction in the primary endpoint (intention-to-treat) of all-cause mortality: 24% ICD group versus 35.5% control group, HR 0.58 (95% CI: 0.37-0.91), p=0.02. When the authors looked at cardiac death, they also found differences, namely 11.5% ICD group versus 18.5% control group: HR 0.52 (95% CI: 0.28-0.99), p=0.04. There were no differences in non-cardiac death: 11.5% ICD group versus 11.9% control group, p=0.52. The conclusion of the trial is that the randomisation to ICD was associated with significantly lower total and cardiac mortality rates. The authors also remark that, despite LVEF improvement in 46% of the study population, the benefit of ICD remained preserved during long-term follow-up of nine years.

Conclusion

It is no easy task to improve or renew our knowledge about Arrhythmias & Devices each year yet, the ESC Congress 2019 broke this rule. It has been extremely difficult to choose the best presentations, but this short article summarises some of the excellent novelties that we saw, innovations based on very well-designed trials - new AF diagnostic and therapeutic tools, SVT guidelines, SCD risk scores focused on congenital diseases and childhood HCM, and finally ICD improvements. Undoubtedly, at ESC Congress 2019, other equally interesting novelties in relation to Arrhythmias & Devices were presented. Here we have referred only to a small number of them but, for me, these were the most relevant presentations.