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. 2023 Aug 25;25(8):euad203. doi: 10.1093/europace/euad203

Risk stratification of sudden cardiac death: a review

Jacob Tfelt-Hansen 1,2,✉,2, Rodrigue Garcia 3,4, Christine Albert 5, Jose Merino 6,7, Andrew Krahn 8, Eloi Marijon 9, Cristina Basso 10,2, Arthur A M Wilde 11,12,2, Kristina Hermann Haugaa 13,3
PMCID: PMC10450787  PMID: 37622576

Abstract

Sudden cardiac death (SCD) is responsible for several millions of deaths every year and remains a major health problem. To reduce this burden, diagnosing and identification of high-risk individuals and disease-specific risk stratification are essential. Treatment strategies include treatment of the underlying disease with lifestyle advice and drugs and decisions to implant a primary prevention implantable cardioverter-defibrillator (ICD) and perform ablation of the ventricles and novel treatment modalities such as left cardiac sympathetic denervation in rare specific primary electric diseases such as long QT syndrome and catecholaminergic polymorphic ventricular tachycardia. This review summarizes the current knowledge on SCD risk according to underlying heart disease and discusses the future of SCD prevention.

Keywords: SCD, Risk, Primary electric disease, Cardiomyopathy, Ischaemic heart disease

Introduction

Of all presentations of cardiovascular disease, sudden cardiac death (SCD) is the most challenging and feared, accounting for millions of deaths worldwide every year.1,2 Sudden cardiac death may strike without any warning in previously apparently healthy individuals and results in tragic events for those left behind. Despite major investments by the medical and research communities over the past decades, the prognosis of out-of-hospital cardiac arrest (OHCA) continues to remain dismal with the highest reported overall 30-day survival being 13%.3–6

Sudden cardiac death and aborted SCD pose a large financial burden for healthcare systems and its dramatic nature has an important psychological and societal impact.7,8 An novel initiative by the European Society of Cardiology has identified eight qualities to monitor and improve the management of patients with ventricular arrhythmias (VA) and the prevention of SCD.9

The cause of SCD varies depending on the individual’s age with a predominance of monogenetic and oligogenetic diseases in the young (<35 years of age) exemplified by primary electric diseases such as long QT syndrome and Brugada syndrome (BrS), cardiomyopathies such as dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), and myocarditis (Figure 1).10–12 In those >35 years, half of SCD cases are related to coronary artery disease (CAD), especially acute coronary syndrome (ACS).13 In older populations, chronic structural diseases predominate, mainly due to acquired diseases such as acute or chronic CAD, valvular heart diseases, and heart failure. In those under 50 years old, it has been estimated that up to 70% of all SCD cases are potential due to inherited causes.14

Figure 1.

Figure 1

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Causes of SCD in Western countries and Japan. From Wong, Heart Lung Circul (2018).

Figure 2 gives a schematic overview of different aetiologies of SCD in the general population and their relation to age at presentation, sex differences, genetic aetiology, and triggers (adapted from central figure in the ESC VA SCD 2022 guidelines).15

Figure 2.

Figure 2

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Aetiologies of SCD and their relation to age at presentation, sex differences, genetic aetiology, and triggers. From ESC VA SCD 2022 guidelines.

Sudden cardiac death prediction in the general population

Although known previous heart diseases confer a higher risk of SCD, the vast majority of SCDs occur in the general population with approximately only half of the cases with heart disease diagnosed before the event.16,17 The annual incidence is estimated between 30 and 125 per 100.000 person-years with an exponential increase over age and higher incidence among men as compared with women (Figure 3).2,17 Despite relatively low incidence, the absolute number of cases worldwide is high and estimated to be 6–9 million yearly from extrapolation of the annual number of deaths in the world.2 Sudden cardiac death is the most likely cause of death representing 10–15% of all deaths in the world, making it a major global health problem.17

Figure 3.

Figure 3

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Incidence of SCD according to age and sex. From Skjelbred T Heart 2022.

Several factors have been identified as associated with SCD in the general population (Figure 4). Identifying individuals at risk is therefore an important clinical and public health objective.

Figure 4.

Figure 4

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Factors associated with SCD in the general population. From Ha Can J Cardiol 2022.

Genetics

Genetics may play an important role in SCD aetiology in the general population.18 Although significant progress has been made in uncovering the genetic basis of inherited cardiac disorders associated with SCD, major challenges remain.

A large genome-wide study on SCD with a heterogenous cause of SCD found that no single-nucleotide polymorphism was associated with SCD,19 but among people of African descent, the p.Ser1103Tyr variant of the SCN5A-encoded Nav1.5 sodium channel is associated with an increased risk of ventricular arrhythmia and SCD.20 Also, in first myocardial infarction (MI) cases, one of the most common settings of SCD, a common variant in SCN5A was correlated with ventricular fibrillation (VF).21

In a recent study, one-fifth of individuals had pathogenic or likely pathogenic genetic variants consistent with inherited cardiomyopathies or arrhythmia syndromes, despite having normal cardiac findings.22

Electrocardiogram

The electrocardiogram (ECG) is easy to perform and relatively available worldwide. The ECG risk score published 3 years ago improved the ability to predict SCD risk in a general population and successfully identified subjects at a high SCD risk, but it remains to be shown that such a strategy will lower the incidence of SCD in the general population.23 Nevertheless, artificial intelligence might improve the performance of using electrical signal to predict SCD in the future.24

Serum biomarkers of sudden cardiac death

In the general population, biomarkers associated with the risk of SCD can be divided into several pathophysiologic pathways: (i) inflammation (e.g. elevated levels of C-reactive protein, interleukin-6, fibrinogen, and white blood cell count); (ii) myocardial injury (high-sensitivity cardiac troponin I); (iii) myocardial strain (B-type natriuretic peptide); (iv) abnormal lipid profiles (e.g. circulating non-esterified fatty acid, remnant-like lipoprotein particles, and low-density lipoprotein cholesterol); and (v) markers of hyperglycaemia (e.g. degree of glycaemia after glucose challenge and haemoglobin A1c). A nested case-control study highlighted cholesterol, high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein that were associated with SCD in the general population.25

Sudden cardiac death prediction in coronary artery disease

There are two major scenarios of SCD in ischaemic heart disease: sudden death occurring in the context of an ACS and sudden death occurring in an individual with a stable chronic ischaemic heart disease.

Acute coronary syndrome context

During and in the early period after a MI presents a unique challenge, as OHCA, VA and SCD risk is relatively high during the first month after MI. A Danish nationwide study has shown that 13% of all first MI present with OHCA.37 Most patients survive the MI, but in the first-month post-MI, studies have identified a high risk of SCD when left ventricular ejection fraction (LVEF) is reduced (1–2% in absolute SCD risk).38,39 However, controlled trials assessing the effect of transvenous implantable cardioverter-defibrillator (ICD) therapy in this early phase in patients with low ejection fraction (EF) failed to demonstrate a reduction in overall mortality with the ICD.40,41 The precise reasons behind no befit of the ICD implantation in this scenario could include recovery of LVEF with time in some patients and competing risk of death from other causes than SCD.42,43 Furthermore, the VEST trial also failed to show the benefit of the wearable cardioverter-defibrillator early after MI in patients with LVEF ≤ 35%, with regard to arrhythmic death.44 However, concerns have been raised about this study, especially with regard to compliance. Indeed, the actual device wear time was very low (18 h out of 24 h), and the majority of SCD in the wearable cardioverter-defibrillator group occurred while not wearing the vest. In contrast, a French real-life study found the wearable cardioverter-defibrillator had high efficacy and safety in the setting of transient high-risk group in selected patients with high compliance.45 Finally, the wearable cardioverter-defibrillator could have side benefits as dynamic monitoring of nocturnal heart rate could timely identify impending cardiovascular events in a population wearing this device.46

Chronic ischaemic heart disease

After MI, an inflammatory response alters the normal collagen structure by increased collagenase activity. Myofibroblasts participate in the reconstruction of a new collagen network. After a few weeks, a solid scar is formed. If the scar is large, remodelling may occur, leading to dilation and thinning of the myocardial wall. These fibrotic areas constitute zones of slow conduction, with loss of anisotropy and dispersion of repolarization. These conditions favour re-entry mechanism and thus most often ventricular tachycardia (VT).

In this context, the characteristics of CSM are most often a multi-vessel disease with collateral circulation associated with the presence of diabetes.

Left ventricular ejection fraction

Left ventricular ejection fraction remains the cornerstone parameter of current decision making for long-term primary prevention of ICD implantation after MI. However, LVEF has major limitations: first, the majority of SCD cases do occur in patients with normal or mildly reduced LVEF. Second, relatively few patients with reduced LVEF will benefit from an ICD (most will never experience a threatening arrhythmic event; others have a high risk for non-sudden death), Third, a reduced LVEF is a risk factor for both sudden and non-sudden death.

Younis et al.47 developed a score based on clinical variables, to estimate the probability of ICD benefit. The 3-year predicted risk of VA was three-fold higher than the risk of non-arrhythmic mortality in the highest benefit group, whereas it was similar in the lowest benefit group. The main limitation is that study was performed only on patients with ICD and therefore with selection bias.

Electrocardiogram

Chatterjee et al.48 presented an ECG score for SCD risk stratification in CAD patients with LVEF above 35%, proposing a trial with 2900 participants for patient selection and ICD implantation. A high-risk ECG score was more strongly associated with SCD than non-SCD mortality (HR = 2.87 vs. 1.38, respectively; P for Δ = 0.003), and the proportion of deaths due to SAD was greater in the high-risk vs. low-risk groups (24.9% vs. 16.5%, P for Δ = 0.03).

Cardiac magnetic resonance

In cardiovascular implantable electronic device recipients, Leyva et al.49 showed that visual assessment of myocardial fibrosis on cardiac magnetic resonance (CMR) excluded patients at risk of SCD. Moreover, grey zone fibrosis mass assessment measured with the 5SD method added predictive value in relation to the arrhythmic endpoint. Finally, in CAD patients with an LVEF > 35% (i.e. without an ICD), grey zone fibrosis mass using the 3SD method was strongly associated with a combined endpoint of SCD, VT, VF, or resuscitated card.50

However, in the large upcoming meta-analysis performed by the PROFID consortium, neither LVEF nor fibrosis was a reliable risk factor (also not in ischaemic heart disease).51

Programmed electrical stimulation

Programmed electrical stimulation (PES) has been considered a useful tool to stratify the risk for SCD following MI.15 The ESVEM trial found fewer arrhythmic recurrences and deaths during follow-up in post-MI patients with inducibility suppressed by anti-arrhythmic drugs than in those who were inducible.52 In addition, initial trials on SCD primary prevention included PES for risk stratification of high-risk patients with LVEF < 35–40%.53,54 However, subsequent trials showed that the risk was already high enough in patients with LVEF < 30 or 35% to warrant ICD implantation without further PES stratification.55,56 In patients with ischaemic cardiomyopathy and LVEF ≥ 35%, the usefulness of PES has been assessed as inducible sustained monomorphic VT could justify ICD implantation. The two-step approach of the PRESERVE EF study could detect a subpopulation of post-MI patients with preserved LVEF at higher risk for VA that could be effectively addressed with an ICD.57 This has now been implemented in the novel VA SCD 2022 guideline in the intermediate-risk group with LVEF 36–50%.15

Sudden cardiac death prediction in dilated/non-dilated hypokinetic cardiomyopathy

DCM is defined by the presence of left ventricular dilatation and contractile dysfunction. In some cases, the left ventricle is not severely dilated but EF is reduced; the term non-dilated hypokinetic cardiomyopathy is now used.58 In the adult population, DCM accounts traditionally for the second leading cause of SCD with an annual incidence of 2–4%.59 In the past, different non-invasive parameters such as non-sustained VTs (NSVT), T-wave alternance, late potentials, heart rate variability, and assessment of sympathetic innervation with the SPECT-123I-MIBG method have been used for SCD risk stratification in patients with DCM but with conflicting and disappointing results.

More recently, and despite the higher risk of SCD in DCM, ICD did not improve survival in the DANISH trial.60 These results may be explained by the low arrhythmic risk of the study population due to updated heart failure treatment and high compliance in the study but also because DCM is a heterogeneous entity in which each disease has a different SCD risk. A small proportion of DCM can result from myocarditis, exposure to drugs, toxins or allergens, and systemic endocrine or autoimmune diseases.

Role of genetics

In recent years, it has become evident that genetic variants account for about 50% of idiopathic DCM, with specific disease trajectories and with specific hallmarks.58

Genetic testing in patients with idiopathic phenotypic DCM is recommended in the 2022 ESC guidelines on VT and SCD, in particular in the young and in the presence of conduction delay or family history.15 Genetic testing in DCM phenotypes enables family screening, genotype-specific follow-up, and genotype-specific risk stratification. Several gene variants have been associated with increased risk of SCD exemplified by LMNA, PLN, FLNC, and RBM20. Importantly, in patients with these variants, primary prevention ICD indication differs significantly from the general recommendation of EF < 35%.15 These patients should be followed specifically according to their genotype and with a focus on VA.

For example, LMNA variants, cause of ≈8% of idiopathic DCM, have a poor prognosis with early development of conduction disturbances, atrial fibrillation, and VA.61,62

A risk calculator to predict VA has been published (https://lmna-risk-vta.fr/).63 A 5-year risk ≥10% in association with a manifest cardiac phenotype (LVEF < 50%, NSVT, or conduction delay) represents a novel criterion for ICD implantation (Class IIa).15 The calculator has been validated with satisfactory results, but caution and clinical judgement are needed as the calculator may overestimate the risk of factors such as male sex and non-missense mutations. Therefore, frequent re-evaluation of the calculator is necessary to maintain the sensitivity of the model.64,65 Furthermore, specific exercise and pregnancy advice are available in LMNA patients who should avoid high-intensity exercise62 but seem to tolerate pregnancy well with no evident adverse long-term outcome.66

The most frequent genetic alterations in DCM are those involving the TTN (Titin) gene, most often associated with ventricular dilatation and heart failure. Truncating variants in the filamin C gene has been associated with a high risk of even fatal arrhythmias, especially when the ‘ring-like’ pattern sub-epicardial late gadolinium enhancement (LGE) is present.67 Patients with a TTN variant may respond well to heart failure medication.

Role of cardiac imaging and cardiac magnetic resonance

Retrospective and prospective studies have shown that 30–40% of patients with DCM have a variable degree of fibrosis. Cardiac magnetic resonance has also been promoted in many recommendations as it may be of prognostic value in different cardiomyopathies. A recent meta-analysis combining almost 3000 non-ischaemic DCM patients showed that LGE was associated with a five-fold higher risk of SCD in patients with DCM.68 Moreover, this association was also present in the subgroup of patients with an LVEF > 35%. A CMR guide study (NCT01918215) is currently ongoing and evaluates the benefit of ICD implantation in DCM with LVEF between 35% and 50% associated with LGE.

Sudden cardiac death prediction in other cardiomyopathies

Hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy has a prevalence of 1:500 and has generally a low risk of SCD (<1%/year). Nevertheless, SCD can be the first devastating manifestation of HCM.

Therefore, it is necessary to identify high-risk patients and reassure low-risk patients. A 5-year SCD risk stratification score has been developed (HCM Risk-SCD: https://doc2do.com/hcm/webHCM.html). It is based on seven parameters (age, left ventricle wall thickness, left atrial size, left ventricular outflow tract gradient, NSVT, unexplained syncope, and family history of SCD) and defines the risk of SCD as low (<4%), intermediate (between 4% and 6%), and high (>6%).69 Other risk markers, not included in the risk calculator, are LVEF < 50%, aneurysm of the apex, LGE > 15% of left ventricular mass on CMR, failure to increase systolic blood pressure by at least 20 mmHg from rest to peak exercise or a fall of >20 mmHg from peak pressure at exercise test, and presence of a sarcomeric variant.70,71 These additional features are particularly relevant in patients classified with an intermediate risk of SCD. A recent study investigated the role of electrophysiology in predicting SCD in patients with HCM suggesting that prediction of SCD and ICD implantation in HCM may need to be reassessed and refined.72

Arrhythmogenic cardiomyopathy

Arrhythmogenic cardiomyopathy (ACM) is suggested as the term replacing arrhythmogenic right ventricle cardiomyopathy (ARVC). The cardiomyopathy is characterized by a fibro-fatty replacement that involves the myocardium. It was originally described to affect predominantly the right ventricle (RV) constituting the ‘classical ARVC’, but it can affect the left ventricle as a biventricular disease or as a left dominant variant.73 The prevalence ranges from 1:1000 to 1:5000. Diagnosis is made by a combination of parameters from ECG, Holter, TTE, CMR, family history, and genetic testing.74

Arrhythmogenic cardiomyopathy is mainly caused by pathogenic variants in desmosomal genes but can be related also to non-desmosomal genes. Genetic testing is recommended in patients with phenotypic ACM.15

Identification of ACM patients at risk of first arrhythmic event is difficult and the clinical presentation can be heterogeneous. Sudden cardiac death may be the first presentation of ACM, but approximately half of SCD or aborted cardiac arrest (CA) victims had cardiac symptoms prior to the event.75,76 The classical arrhythmia in ACM originates from the RV, while right bundle branch block VTs account for about 7% of sustained VTs.77,78

Implantable cardioverter-defibrillator should be considered in symptomatic ARVC patients with moderate RV (<40%) and/or LV dysfunction (<45%) and who have either NSVT or sustained monomorphic VT inducible at PES.15 A recent risk model of VA has been developed and suggested age, sex, arrhythmic syncope, NSVT, premature ventricular contractions burden, number of leads with T-wave inversion, and RV EF to be associated with sustained VA.79,80 It has been argued that the ARVC risk calculator was developed in mixed population of ARVC patients with haemodynamic un-tolerated sustained polymorphic ventricular tachycardia and VF whereas others have haemodynamic tolerated sustained monomorphic ventricular tachycardia. A modification of the calculator has been presented including only very fast VT.

Implantable cardioverter-defibrillator implantation is complicated by patients’ young age and frequently thin RV wall.81 Subcutaneous ICDs may be useful in some cases.82

Exercise has a strong impact on disease progression, occurrence of VA, and LV involvement.81,83 High-intensity exercise should be avoided.84 The higher risk of arrhythmias in males may be explained by their higher exercise exposure85 and hormonal factors.86

Arrhythmic mitral valve prolapse

Arrhythmic mitral valve prolapse (AVMP) has gained attention in recent years. Mitral valve prolapse has a generally good long-term prognosis. However, it has been recognized that a subset of patients has VA with risk of SCD. Younger patients with aborted CA should be carefully evaluated for AMVP if no other obvious reason for the event is found. A recent EHRA consensus paper presents the risk stratification and management of patients with AVMP.87 Risk factors for SCD include syncope, NSVT, presence of mitral annular disjunction (MAD), LGE on CMR located in the inferior-lateral wall or papillary muscles, reduced LVEF, and T-wave inversions in inferior-lateral ECG leads.88 According to the risk profile, monitoring with Holter or implantable loop recorder may be indicated as a primary preventive ICD in those with the highest risk.89

Sudden cardiac death prediction in primary electrical diseases

Brugada syndrome

Brugada syndrome affects particularly males and is characterized by spontaneous J point elevation of >2 mV with coved ST elevation and T wave inversion in at least one right precordial ECG lead, V1 or V2, positioned in the second, third, or fourth intercostal spaces.90 The risk assessment relies mainly on symptoms. In BrS patients with a CA, half of them have recurrent VF, which indicates ICD implantation. In patient with syncope, the likelihood of ventricular arrhythmia is multiplied by 4. However, the cause of syncope can be difficult to ascertain. Most of the patients with a spontaneous type 1 pattern are asymptomatic and have a yearly risk of 0.3–1% of ventricular arrhythmia. Other markers such as early repolarization, QRS fragmentation, and positive PES have been identified as portending a higher risk, but their added relevance in patients with intermediate risk has not been demonstrated.91,92 The risk is significantly lower in patients with a drug-induced ECG.

Implantable cardioverter-defibrillator is indicated in symptomatic BrS patients and always in those who have survived CA.

Patients with recurrent ICD shocks quinidine or catheter ablation are the two treatment modalities available as both have been shown to reduce ICD therapy frequency.93,94 In electric storm, isoproterenol infusion is the drug of choice.

Long QT syndrome

Long QT syndrome traditionally appears in childhood and adolescence and is caused by pathogenic variants in potassium and sodium channels (KCNQ1, KCNH2, and SCN5A) in the majority of cases.95 In untreated asymptomatic long QT syndrome patients, the annual rate of SCD is less than 0.5%, whereas it is around 5% in those with a history of syncope.96–98 Clinical, electrocardiographic, and genetic parameters should be assessed for the individual risk estimation as the genetic locus and the QTc, but not sex, were independent predictors of risk.96

The main treatment to prevent SCD is lifestyle advice on avoidance of hypokalaemia, QT-prolonging medications, and genotype-specific triggers in conjunction with beta-blockers. Recent data and recommendations favour the two non-selective beta-blockers nadolol and propranolol as they have greater efficacy in reducing arrhythmic risk.99–101 Gene testing offers the possibility of gene-specific prevention as in SCN5A-positive cases, mexiletine together with beta-blockers is now recommended.102

Cardiac arrest survivors have a high risk of a second CA, even on beta-blockers (recurrence is around 15% within 5 years of therapy); therefore, ICD is recommended in CA cases.103 Implantable cardioverter-defibrillator is furthermore recommended for patients who experience VA or syncope on optimal pharmacological therapy, since both are associated with an increased risk of CA. Left cardiac sympathetic denervation (LCSD) is also effective in reducing the number of episodes of VA and is a treatment option in patients with symptoms.

The role of the autopsy to prevent sudden cardiac death

Pathologists (preferably with expertise in cardiac pathology) are responsible for determining the cause and mechanism of SCD in either a hospital or forensic setting. An autopsy performed using a standardized protocol will facilitate the identification of index cases with potentially inherited cardiovascular conditions. After the autopsy is performed and if there is doubt on the cause of death, a multidisciplinary conference with a cardiologist is recommended to give insights to family history, pre-mortem condition and symptoms, and potential findings on echo or angiogram during a resuscitation attempt. The multidisciplinary conference should lead to a referral of the family in potential inherited cardiac diseases.26–29 This referral will eventually lead to screen family members and to ensure that appropriate preventive and therapeutic strategies are implemented.15,30,31

However, major challenges remain such as the continuous decline of autopsy rates and the fact that established guidelines for autopsy investigation are often disregarded. Therefore, ESC has provided strong recommendations on autopsy in all sudden death cases and in particular in those under 50 years.15 Moreover, it has been demonstrated that an expert cardiac pathologist may alter the initial diagnosis in 41% of cases, highlighting the need to identify core labs for expert evaluation.32,33

Autopsy-negative SCD with negative toxicology identifies the so-called sudden arrhythmic death syndrome. Post-mortem genetic analysis is recommended in such cases but is currently not performed in all centres.34 A recent European Heart Rhythm Association (EHRA) survey found a significant heterogeneity of service provision and variable adherence to current recommendations for the investigation of sudden death in the young in Europe, partly attributable to the availability of dedicated units and genetic evaluation, specialist tests, and post-mortem examination. Tissue/blood retention for DNA extraction is crucial to allow post-mortem genetic analysis.35 The post-mortem testing can identify gene mutations in around one-third of cases. In SADS cases, it has been shown that combining post-mortem testing and family investigation of first-degree relatives can lead to a diagnostic yield of 40%.36

A new approach to prevent sudden cardiac death: near-term prevention

Almost all strategies for reducing SCD burden have focused on trying to identify well ahead of time the individual likely to experience SCD. Nevertheless, long-term prevention—mainly based on ICD insertion in the vulnerable subject—suffers from key limitations, including poor identification of high-risk subjects and imperfect technology in the form of the ICD, with a significant rate of complications.

Sudden cardiac death is actually preceded by symptoms in approximately half of the subjects.104–106 When not neglected and acted upon in a timely fashion, the presence of symptoms translates into a seven-fold increase in survival because it allows for an upstream alert and subsequently shortens the delay to resuscitation.107Taking a broader view, the presence of symptoms before SCD is an opportunity for a new type of prevention, near-term prevention, based upon prompt action in response to warning signs. However, the specificity of such symptoms raises concerns, with important risks of overburdening emergency medical services as well as unnecessary panic among patients.

To improve the specificity of a near-term prevention strategy, a multi-pronged approach going beyond symptoms and clinical features may be needed. The utility of multiple clinical parameters, including symptoms, has been assessed in patients with acute ST-segment elevation MI.108

Beyond clinical variables, the identification of electrical instability occurring in the hours or days before SCD, through ‘dynamic monitoring’, is an exciting possibility. Prediction of SCD with the ‘static’ ECG, reflecting one-time electrical status, has been disappointing and dynamic monitoring holds promise in this regard.109 In this regard, artificial intelligence and machine learning have the potential to play an important role in arrhythmia diagnosis and prediction.110

In the near future, one can imagine that connected devices, such as smart watches, will continuously monitor the at-risk patient and automatically detect sudden CA by utilizing key parameters such as heart rate and oxygen saturation and by detecting the absence of physical movement.

Conclusions

This review summarizes the current evidence regarding SCD risk stratification in the general population and in patients with cardiomyopathies or channelopathies. Despite active research, major knowledge gaps persist. An increase in autopsy rates, workup on the family left behind if an inherited cause is suspected, public awareness of OCHA, and change in treatment and prevention strategy might lower the burden of SCD in the future.

Contributor Information

Jacob Tfelt-Hansen, Cardiology Department, Copenhagen University Hospital-Rigshospitalet, Blegdamsvej 9, Copenhagen 2100, Denmark; Section of Forensic Genetics, Department of Forensic Medicine, Copenhagen University, Frederik V’s Vej 11, Copenhagen 2100, Denmark.

Rodrigue Garcia, Cardiology Department, University Hospital of Poitiers, 2 rue de la Milétrie, Poitiers 86000, France; Centre d'Investigation Clinique 1402, University Hospital of Poitiers, 2 rue de la Milétrie, Poitiers 86000, France.

Christine Albert, Cardiology Department, Smidt Heart Institute, Cedars-Sinai Hospital, Los Angeles, CA, USA.

Jose Merino, Department of Cardiology, La Paz University Hospital, IdiPaz, P. Castellana, 261, Madrid 28046, Spain; Department of Cardiology, Viamed Santa Elena University Hospital, C/La Granja, 8, Madrid 28003, Spain.

Andrew Krahn, Centre for Cardiovascular Innovation, Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Eloi Marijon, Cardiology Department, European Georges Pompidou Hospital, Paris, France.

Cristina Basso, Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padova, Via Giustiniani 2, Padova 35121, Italy.

Arthur A M Wilde, Department of Cardiology, Amsterdam UMC location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands; Department of Cardiology, Heart Failure and Arrhythmias, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.

Kristina Hermann Haugaa, ProCardio Center for Innovation, Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.

Funding

This research was funded by the Consulting Fees/Honoraria Johnson and Johnson, Micro port, Cytokinetics and Leo Pharma.

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