Telemedical monitoring by an implanted loop recorder: gateway to personalized medicine? Results of the SMART-MI study

Are implantable loop recorders1,2 (Reveal LINQ, Medtronic Minneapolis, MN, USA) effective tools for risk prediction of adverse arrhythmic events after a myocardial infarction (MI), and hence, the identification of patients who may benefit from prophylactic treatment as an implantable cardiac defibrillator? Prof. Bauer3 recently published and presented (European Society of Cardiology congress 2021) the results of the SMART-MI trial. In this multi-centre randomized study (two countries), patients with cardiac autonomic dysfunction assessed within 48 hours after MI and, hence, at risk of arrhythmias, and other cardiovascular events were randomized to either telemedicine (i.e. Reveal LINQ, Medtronic Minneapolis, MN, USA) plus study-related follow-up or ‘conventional’ protocol-related follow-up of approximately 2 years. The main findings showed significantly higher incidences of serious arrhythmic events in the experimental group (30 vs. 6%) of which atrial fibrillation was the most frequent (23 vs. 11%). Based on their findings, the investigators conclude that telemedical monitoring using an implantable cardiac monitor was highly effective. The expectations around telemedical care or telemonitoring have been high for years and they are on the wish list of many.4 However, large-scale clinical implementation is still pending. There are multiple factors driving this technical and clinical factors such as issues of complexity of integrating such systems within the health systems (e.g. hospitals due to among others the need of dedicated staff) and lack of evidence of clinical benefit and cost-effectiveness demanded by health care insurers. Also, telemedicine solutions are also often complex for patients. All these factors have slowed down large-scale implementation of telemedicine.5 However, the possibilities of digital transformation and adoption are increasing rapidly, partially driven by the COVID-19 pandemic. We live in a connected world where even in remote areas, people have internet access, and almost all people (84%) have a smart or a mobile phone (92%). In the more affluent parts of the world, environments are becoming ‘smart’. Homes, cars, bicycles, etc. can be connected, sharing their information with us. Perhaps the last frontier is to connect the patient (perhaps ourselves). The younger generations (approximately <60 years of age), are environmentally aware and using smartwatches and fitbits to monitor their level of fitness and health, already. They will undoubtedly stimulate the demand for remote monitoring, creating a healthier living environment and lifestyle. The Big Tech (Apple, Google, etc.) companies are increasingly focusing on the medical field and adding more and more ‘medical’ functionalities to their devices and software.6 The developments in sensor technology are also speeding up (wearables) allowing strategies for improved secondary but also primary prevention.7 There is evidence that smart watches will soon be able to measure levels of blood sugar and blood pressure, enhancing the role of such devices in the quest of improvement of health and/or the reduction of the disease. The devices collect so-called digital biomarkers that may explain, influence (digital interventions) and/or predict health-related outcomes. While devices like smartwatches and fitbits are largely still in a ‘lifestyle’ phase, some notable studies have emerged about their potential for medical applications.8 The industry’s efforts are intensifying to reach a medical level with their devices and software (apps), and the number of remote studies evaluating their effectiveness are increasing.6,8 Besides this SMART-MI study, another implantable device, the CardioMems sensor, which measures blood pressure in the pulmonary artery, is used in patients with heart failure.9 These studies should actually show the effectiveness of cardiovascular telemedical care. The big question here is whether the SMART-MI study provides that? The key findings of the SMART-MI study should be interpreted as follows: First, a quick calculation shows that if you take the 400 eligible patients enrolled in 33 over a 4-year period, only three patients/year/centre were enrolled in the study. Second, it is unclear to what extent the invasive strategy improved sensitivity, as it is unknown how many arrhythmic events were detected by telemedical care and ‘conventional follow-up’ in the invasive group. Third, and contrary to the authors’ statement (Discussion) that these events ‘strongly predicted imminent cardiac and cerebrovascular complications’ have not been demonstrated. There was no difference in all-cause mortality and major adverse cardio-cerebrovascular events between the two groups. Risk is not synonymous with events, and the treatment of risk is not always related to reducing events. Fourth, and as rightly discussed by the authors, the question of what type of follow-up is optimal. In this study, the focus was on detecting arrhythmia, which is often a side effect of heart disease and/or deterioration. The question is whether other or a combination of markers/tools that focus on, for example, the left ventricular function would not be more useful? This study does show that the sensitivity of the detection of serious arrhythmias by implantable cardiac monitors was three times higher compared to conventional follow-up, but that requires considerable effort to achieve this goal. However, without significant clinical benefit and comparable positive predictive accuracy compared to conventional follow-up. Another question that this study raises is whether wearable devices, rather than implanted ones, have the same diagnostic power and might be preferable? It reduces the burden for the patient; it is cheaper and provides the possibility of expanding the number of patients. The current results encourage further research towards Digital Biomarkers. It shows the possibilities and potential of personalized medicine. Although the downside is a further increase in the amount of medical data that we generate and need to analyse. We here pin the hope on the application of artificial intelligence (AI).10 Promising is the current major increase in activities both in the medical/academic institutions and medical industry, combining telemedicine, wearables and AI.11 It is stimulating and brings a lot of enthusiasm. But in all our enthusiasm, we have to keep the reins in our hands. The new technologies need thorough validation and above all prove their clinical effectiveness. The SMART-MI trial demonstrated a higher diagnostic power delivered by a digital biomarker (implanted loop recorder) as compared to conventional follow-up. The investigators showed that telemedical care can bring personalised medicine closer, but there is still a lot of work to be done, such as among others, the demonstration of which patient or patient category will truly benefit. Conflicts of interest: none declared. Biography: Dr Nico Bruining started his career in 1985 at the Thoraxcenter, Department of Cardiology, Erasmus MC, Rotterdam, Netherlands, in the cathlab with some pioneers in interventional cardiology, Professors Patrick Serruys and Pim de Feyter. In 1993, he joined the Experimental and Clinical Information Processing (KEI) division of the Thoraxcenter, one of the pioneer groups in digital cardiology, which he currently leads. At the KEI, he became involved in the early developments of three-dimensional echocardiography, resulting in his thesis—‘Quantitative 3D echocardiography of the heart and coronary arteries’ under the promoter ship of Prof. Jos Roelandt (1998). The focus areas of the KEI are the wide field of Digital Cardiology from recording to analyses of the broad range of cardiovascular data such as bedside monitoring, ECG, imaging and virtual reality applications, telecardiology and wearables, electronic health records, robotic process automation and other digital health-related topics. Nico has held many roles within the ESC, including Chair of the eCardiology Working Group, and is the current Vice Chair of the Digital Health Committee, former Editor-in-Chief of the Digital Health Portal and currently its Editor-in-Chief of the European Heart Journal—Digital Health. Biography: Dr Peter de Jaegere received his MD degree from the University Ghent, Belgium in 1983 and followed training in Internal Medicine in the St Jans Hospital Bruges, Belgium (1983–1986) followed by Cardiology at the Free University Brussels, Belgium and the University Hospital Rotterdam, The Netherlands (1986–1990). From 1990 to 1996, he was a staff member of the Thoraxcenter and clinical head of the Department of Cardiac Catheterization & Interventional Cardiology in Rotterdam during which he defended his PhD thesis ‘Clinical and Angiographic Evaluation of Intracoronary Stenting in Humans’ (1993) followed by the publication of the Benestent Study (RCT stent implantation vs balloon angioplasty) in the New England Journal of Medicine in 1994. From 1996 to 2004 he was a staff member of the Department Cardiac Catheterization & Interventional Cardiology of the University Hospital Utrecht, The Netherlands during which he directed the Octopus Study (RCT off-pump bypass surgery vs. coronary stenting), published in the New England Journal of Medicine in 2003. In 2004, he returned to the Thoraxcenter where he set up the Catheter Based Valve programme and was appointed in 2012 as Professor in Interventional Cardiology at the Erasmus University, Rotterdam, The Netherlands. Since 2011, the focus of his research shifted from patient-oriented clinical research to patient-specific computer simulation of catheter-based interventions in close collaboration with biomedical engineers in Belgium. In 2020, he became deputy Editor of the European Heart Journal-Digital Health and was appointed as professor of Cardiology at the Erasmus University. Publications can be found in PubMED.