2022 专家共识声明：肥厚型心肌病晕厥的诊断和管理

A B S T R A C T

Keywords: Syncope Hypertrophic cardiomyopathy Reflex syncope Sudden cardiac death Implantable defibrillator Risk stratification Diagnosis

Syncopal events in patients with hypertrophic cardiomyopathy (HCM) are of concern as they are a vital consideration in algorithms for risk stratification for sudden cardiac death (SCD) and ICD implantation. How ever, the cause of syncope is often under-investigated and/or unexplained. Current syncope guidelines do not provide a detailed definition of unexplained syncope.

To address this important gap, an international panel of experts in the field of both syncope and HCM wrote a consensus document with the aim of providing practical guidance for the diagnosis and management of syncope in patients with HCM.

1. Introduction

Syncopal events in patients with hypertrophic cardiomyopathy (HCM) are of concern as they are a vital consideration in algorithms for

risk stratification for sudden cardiac death (SCD) and ICD implantation. However, the cause of syncope is often under-investigated and/or un explained. In a recent systematic review and metanalysis of relevant publications from 1973 to 2021, syncope was reported by $15.8\%$ (3.452

Abbreviations: ABPM, Ambulatory blood pressure monitoring; ACC, American College of Cardiology; AHA, American Heart Association; ECG, Electrocardiogram; ESC, European Society of Cardiology; HCM, Hypertrophic cardiomyopathy; ICD, Implantable cardioverter defibrillator; ILR, Implantable loop recorder; LVOTO, Left ventricle outflow tract obstruction; MRI, Magnetic resonance imaging; SCD, Sudden cardiac death.

\* Corresponding author.

E-mail addresses: mbrignole@outlook.it (M. Brignole), l.crotti@auxologico.it (L. Crotti), jeanclaude.deharo@ap-hm.fr (J.C. Deharo), perry.elliott@ucl.ac.uk (P.M. Elliott), artur.fedorowski@ki.se (A. Fedorowski), j.kaski@ucl.ac.uk (J.P. Kaski), mmaron@tuftsmedicalcenter.org (M.S. Maron), iacopo.olivotto@unifi.it (I. Olivotto), ommen.steve@mayo.edu (S.R. Ommen), gianfranco.parati@unimib.it (G. Parati), wshen@mayo.edu (W. Shen), andrea.ungar@unifi.it (A. Ungar), a. a.wilde@amsterdamumc.nl (A. Wilde).

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of 21.791) HCM patients [ 1 ]. Life-threatening arrhythmic events occurred in $3.6\%$ of non-syncopal patients and in $7.7\%$ of syncopal pa tients during a mean follow-up of 5.6 years (relative risk of 1.99). Syn cope was considered unexplained in $91\%$ of cases [ 1 ].

Current HCM management guidelines consider syncope that is not explained by non-life threatening mechanisms as a major risk factor in SCD risk assessment. The European Society of Cardiology (ESC) 2014 HCM guidelines [ 2 ] use the terminology “ unexplained non-vasovagal syncope ” , while the 2020 American Heart Association (AHA)/ Amer ican College of Cardiology (ACC) HCM guidelines [ 3 ] described this as “ syncope suspected by clinical history to be arrhythmic ” and “ unex plained syncope ” . Neither guideline provides detailed definitions of how to evaluate and categorize syncopal events such that the appropriate events are used in the risk factor algorithms [ 4 – 7 ].

Also current syncope guidelines do not provide a detailed definition of unexplained syncope. The 2017 American Heart Association (AHA)/ American College of Cardiology (ACC) and the 2018 European Society of Cardiology (ESC) syncope guidelines [ 8 ] defined unexplained syncope as ” syncope for which a cause is undetermined after an initial evaluation that is deemed appropriate by the experienced healthcare provider ” . The initial evaluation usually includes, but is not limited to, a thorough history, physical examination, and ECG ” . The consequence is uncer tainty regarding the therapeutic decision, and specifically in the case of patients with HCM, whether or not to recommend an ICD.

Notably, while “ unexplained syncope ” is associated with subsequent cardiac arrest, ICDs often do not prevent recurrent syncope especially if the underlying mechanism is not a ventricular arrhythmia which may impact the quality of life [ 9 ]. Patients with obstructive HCM are particularly sensitive to changes in preload and afterload that can accompany hypovolaemia, severe anemia, use of vasodilators and di uretics and are thus more prone to syncope under such conditions. Un derstanding the underlying mechanism of syncope is a prerequisite for preventing recurrences, but a systematic approach to diagnostic assessment to identify the cause of syncope is currently underused [ 1 ].

To address this important gap, the two senior authors of the above-mentioned systematic review and metanalysis [ 1 ] invited an interna tional panel of experts in the field of both syncope and HCM to write a consensus document with the aim of providing practical guidance for

the diagnosis and management of syncope in patients with HCM.

2. Method

The chairmen (FC and MB) developed a draft algorithm for the management of syncope in a patient with HCM and nominated the panel of experts in March 2022. The members were selected based on their international reputation as having been involved in previous guidelines (see Appendix). A plenary remote video conference was organized in April 2022 during which the panel members were asked to review the algorithm by adding comments, explanations, and new proposals. In June 2022 a second draft of the document was prepared based on the received feed-back. Finally, a plenary conference was organized in Florence on July 8, 2022, during which a consensus was achieved. The final document was written accordingly and approved by the panel on July 31, 2022, and submitted for publication.

3. Algorithms for the diagnosis and management of syncope in a patient with HCM

The panel of experts recommend the algorithm for the diagnosis of syncope in a patient with HCM shown in the Fig. 1 .

Unexplained syncope is defined in those patients in whom, after the initial evaluation and those additional tests deemed appropriate by an experienced healthcare provider, no condition reported in sections 4 B (non-cardiac syncope) and 4C (cardiac syncope unrelated to risk for SCD) is met ( see below ).

Once the aetiology of the syncopal event is ascertained, then appropriate treatment to prevent recurrence can be initiated. In the case of “ unexplained syncope ” , as defined above, the event is considered as a risk factor for SCD in the ESC ( Fig. 2 A) and AHA/ACC guidelines ( Fig. 2 B) flow charts for risk stratification and guidance to ICD implantation.

A validated clinical risk tool (HCM Risk-SCD) that estimates the 5- year risk of SCD in adults with HCM [ 5 , 6 ] can be found on www.HC MRisk-SCD . The AHA/ACC HCM SCD Risk Algorithm can be accessed at https://professional.heart.org/en/guidelines-and-statements/hcm-r isk-calculator . A similar risk score has been developed for paediatric patients (HCMRisk-Kids) [ 7 ] and can be accessed at www.HCM

 Fig. 1. Algorithms for the diagnosis of syncope in patients with HCM. Abbreviations : HCM $=$ hypertrophic cardiomyopathy; VF = ventricular fibrillation; VT = ventricular tachycardia; SCD $=$ sudden cardiac death; AV = atrioventricular; SA sinoatrial =

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 Fig. 2. Flow charts of the ESC guidelines (Panel A) and of the AHA/ACC guidelines (Panel B). Abbreviations : HCM = hypertrophic cardiomyopathy; $\mathrm{VF}=$ ventricular fibrillation; VT = ventricular tachycardia; SCD $=$ sudden cardiac death; NSVT = non-sustained ventricular tachycardia; CMR $=$ cardiovascular magnetic resonance; $\mathrm{EF}=$ ejection fraction; $\mathrm{FH}=$ family history; ICD $=$ implantable cardioverter-defibrillator; LGE $=$ late gadolinium enhancement; LVH left ventricular hypertrophy =

Risk-Kids

HCM Risk-SCD variables included in the HCM Risk-SCD are:

4. Practical guidance for the diagnosis and management of syncope

● Age. ● Family history of sudden cardiac death. ● Unexplained syncope. ● Left ventricular outflow gradient. ● Maximum left ventricular wall thickness. ● Left atrial diameter. ● Non-sustained ventricular tachycardia.

4.1. Work-up for assessment of syncope in HCM patients

The proposed work up for patients with HCM and syncope is shown in Fig. 3 .

In accordance with current HCM guidelines, all patients with HCM should have a comprehensive medical history, physical examination (including standing BP measurement), echocardiogram, ECG, and 24 – 48-h ambulatory Holter ECG monitoring or similar devices able to provide continuous ECG monitoring; the role of intermittent event re corders, e.g., Apple watch, FitBit, KardiaMobile, etc. in risk stratification has not yet been established. The history and the circumstances of the event guide the appropriate evaluation and treatment. If heart rhythm

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 \*The5-yearSCDrisk score canbe estimated as part of the shared decisionmaking

Fig. 2. ( continued ).

abnormalities capable of causing syncope (e.g., advanced atrioventric ular block, bradycardia, sustained ventricular tachycardia, or parox ysmal atrial fibrillation) are documented, then appropriate treatment is initiated. In patients in whom the event is clearly attributable to a reflex mechanism or autonomic failure (see Table 1A ), an extensive test panel may be unnecessary. Similarly, significant left ventricle outflow tract obstruction (LVOTO) (i.e, peak instantaneous gradient ${>}50~\mathrm{mmHg}$ at rest or with provocation) is a likely cause of syncope when it is triggered by transient hypotension due to hypovolemia or systemic vasodilatation as may occur when standing abruptly, during prolonged standing or effort, or when there is reflex-mediated vasodilation

The guiding concepts of this proposed evaluation are that if the history and initial testing do not clearly identify reflex or LVOTO-mediated mechanism, then that syncopal event is considered “ unex plained ” and represents a risk marker.

If the history implicates LVOTO as a major contributing factor, ex ercise echocardiography is reasonable if the patient is not already known to have significant resting or provokable gradient (e.g., $>\,50$ mmHg).

If reflex syncope or orthostatic hypotension are suspected in patients without the immediate diagnosis at initial evaluation, further cardio vascular autonomic function tests could be performed:

- Active standing test - 24-h ambulatory blood pressure monitoring (ABPM), - Tilt testing - Carotid sinus massage (in patients ${>}40$ -year-old)

- Implantable loop recorder (if the above tests were not diagnostic) to document a syncopal recurrence or a life-threatening event

In some cases, these tests may also help guide therapy.

Other tests such as cardiac MRI or electrophysiologic testing may be considered in selected patients, most often in the context of an experi enced multi-disciplinary team that includes specialists in both HCM and syncope.

The decision to admit the patient for rapid investigation is influenced by local organization. Generally, hospitalization can be justified in case of syncope without prodromes or supine or occurring during exercise. In the other cases high-priority out-of-hospital investigation may be preferred if there is an access to a syncope expert/unit.

Once the diagnosis has been established, the treatment of underlying syncope mechanisms should be started according to syncope guidelines recommendations [ 8 , 9 ].

Example Case 1: A middle aged man with HCM experiences syncope while seated during a conversation with his wife. The patient doesn ’ t not recall any symptoms prior waking up on the floor. His wife noted that just prior to his faint, his speech slowed mildly, and he simply slumped sideways. She helped lower him to the floor where he regained con sciousness in about a minute. This is a worrisome syncopal event. Even if this patient has LVOTO, the fact that there was no rapid posture change or triggering event (e.g., reflex mediated hypotension) would make it unlikely that the LVOTO was the proximate cause for the event. Pro longed ambulatory ECG monitoring (including implantable loop recorder) is reasonable, but this event would be considered

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 Fig. 3. Proposed evaluation for patients with HCM and a syncopal episode. Abbreviations : HCM = hypertrophic cardiomyopathy; LVOTO $=$ left ventricle outflow tract obstruction; ABPM = 24-h ambulatory blood pressure monitoring; SCD = sudden cardiac death; ILR $=$ implantable loop recorder

“ unexplained ” , and would be considered a SCD risk marker unless the ECG monitoring demonstrates an arrhythmia that coincides with similar symptoms and is not ventricular in origin.

Example Case 2: A young man with known obstructive HCM with a resting LVOT gradient of $50~\mathrm{mmHg}$ had a syncopal event during phle botomy. He described becoming sweaty, warm, and nauseated prior to the loss of consciousness. He regained consciousness and returned to baseline quickly when placed in the supine position. The history is prototypical for reflex syncope and measures to avoid the triggering circumstances should be addressed. The LVOTO predisposed this patient to full loss of consciousness with the reflex vasodilation, and perhaps needs more treatment as well; importantly, this event is not considered as a risk marker for SCD and would not be included in risk assessment tools.

Example Case 3: A woman with resting LVOTO of $50~\mathrm{mmHg}$ experi enced syncope at the beach. After skipping breakfast, the patient napped on the beach, and had a syncopal episode when she stood up abruptly. The only prodrome was sense of weakness in the legs and darkening vision. She had had 2 previous syncopal episodes with similar charac teristics in upright position. In this case, the posture change suggests a hypotension-mediated exacerbation of LVOTO as the mechanism for the event. Here, the exact mechanism of the faint should be further inves tigated by means of ABPM and autonomic tests aimed to find a mechanism-guided therapy and prevent recurrences, which includes medical therapy to minimize LVOTO. Should the syncope be the first episode, ABPM and autonomic tests might be not needed. This event is also not considered as a risk for SCD.

Example Case 4: A 30-year-old man with non-obstructive HCM experienced syncope while climbing the stairs of the metro. He fell and reported a mild trauma. He denied palpitations before the faint. He had an episode of dizziness some time ago while performing a sudden effort. His echocardiogram showed $20\,\mathrm{mm}$ septal thickness and an enlarged left atrium of $55~\mathrm{{ml}/\mathrm{{m}^{2}}}$ . No LVOT gradient was detected at rest or with provocation. The cardiac MRI showed patchy late gadolinium enhancement in the hypertrophic zones. No significant arrhythmias

were present during 24-h Holter monitoring and during stress test. His father and an uncle are alive and suffer from HCM. Here, the exact mechanism of the faint is unexplained. This places in a dilemma: pri mary cardiac arrhythmia or reflex syncope? According to the flow chart in the Fig. 3 autonomic testing is the next step. If a reflex mechanism is established, the mechanism specific treatment should be started. If no autonomic problem can be established, then the case represents an SCD risk marker with a 5 yr risk = 6 – 7%, so ICD generally is indicated (Class 2A indication by ESC and ACC/AHA criteria). If the patient opts not to get an ICD, then a long-term monitoring by an ILR is also reasonable.

Table 1A Class I diagnostic criteria of non-cardiac syncope (reflex and orthostatic hypotension).

|Diagnostic criteria with initial evaluation| |---| |Vasovagal syncope is highly probable if syncope is precipitated by pain or fear or| |standing, and is associated with typical progressive prodrome (pallor, sweating,| |Situational reflex syncope is highly probable if syncope occurs during or| | immediately after specific triggers, listed in Table 3. Syncope due to orthostatic hypotension is confirmed when syncope occurs while | |standing and there is concomitant orthostatic hypotension.| |Carotid sinus syndrome| |Carotid sinus syndrome is confirmed if carotid sinus massage causes bradycardia| |(asystole) and/or hypotension that reproduces spontaneous symptoms, and patients| | have clinical features compatible with a reflex mechanism of syncope.| |Active standing| |Syncope due to orthostatic hypotension is confirmed when there is a fall in systolic| |blood pressure from baseline value ≥20 mmHg or diastolic blood pressure ≥ 10| |mmHg or a decrease in systolic blood pressure to |

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Table 1B Class II diagnostic criteria of reflex syncope, orthostatic hypotension (OH), postural orthostatic tachycardia syndrome (POTS) and psychogenic pseudo syncope (PPS).

|Tilttesting| |---| |Reflex syncope, OH, POTS, or PPS should be considered likely if tilt testing| |reproduces symptoms along with the characteristic circulatory pattern of these| |conditions|

4.2. Conditions in which the diagnosis of non-cardiac syncope (reflex syncope or orthostatic hypotension) is established (low risk related to syncope)

The 2017 AHA/ACC and the 2018 ESC syncope guidelines [ 8 , 9 ] have defined those situations in which a diagnosis of non-cardiac syncope can be considered established ( Tables 1A and 1B ):

4.3. Other conditions in which the diagnosis of syncope is unrelated to the risk of sudden death (low risk related to syncope)

As any structural heart disease, HCM can be complicated by cardiac syncope that not necessarily is life-threatening and by non-cardiac syncope.

Arrhythmic syncope not due to ventricular tachyarrhythmias should be suspected [ 8 , 9 ], but need confirmation by further investigations (electrophysiological study, prolonged ECG monitoring) in case of ( Table 2 ):

- Syncope during exertion or when supine - Sudden onset palpitation immediately followed by syncope - Bifascicular block - Mobitz I second-degree AV block and 1 degree AV block with markedly prolonged PR interval - Asymptomatic mild inappropriate sinus bradycardia (40 – 50 b.p.m.) or slow atrial fibrillation (40 – 50 b.p.m.)

Examples of non-cardiac causes of syncope, often in combination among them, are listed in Table 3 .

4.4. Syncope in paediatric HCM

The prevalence of unexplained syncope in paediatric HCM cohorts varies from $3.1\%$ in the PRIMaCY cohort [ 10 ] to $9.9\%$ in the large multicentric International Paediatric Hypertrophic Cardiomyopathy

Table 2 Diagnostic criteria of cardiac syncope not caused by ventricular arrhythmias.

|Arrhythmic cardiac syncope|| |---|---| |Syncope due to sick sinus syndrome is established when persistent sinus bradycardia|| |||

Table 3 Diagnostic criteria of non-life-threatening non-cardiac syncope.

|Dehydration, volume depletion| |---| |Significant anemia, bleeding| |Drug-induced severe hypotension|

Consortium [ 7 ]. As in adults, putative mechanisms for syncope in childhood HCM may include supraventricular and ventricular arrhyth mias, failure to increase cardiac output during stress, abnormal blood pressure response during exercise, impaired baroreflex sensitivity and worsening left ventricular outflow tract obstruction [ 11 ].

The occurrence of syncope is a major risk factor for SCD in children with HCM. In a metanalysis of paediatric populations with HCM that included patients under 18 years of age, unexplained syncope was sta tistically associated with SCD with a hazard ratio of 1.89 [ 12 ]. This risk increased markedly to a hazard ratio of 7.4 in a younger population (mean age 9.8 years) with a history of unexplained syncope within previous 6 months [ 10 ]. Even if the prevalence of unexplained syncope is lower $(6.1\%)$ in preadolescent population (age $<12$ years), the long-term outcome did not differ by age of presentation [ 13 ]. All the above-cited articles did not provide a definition of unexplained syncope. Based on the results of paediatric populations, a paediatric risk stratification tool (HCM Risk-Kids), which includes unexplained syncope among the variables of risk, was developed similar to the adult risk stratification tool [ 7 ]. The HCMRisk-Kids prediction model has been externally vali dated in large and geographically different childhood populations including 3 multicentre external validation cohorts [ 14 – 16 ]. An alter native risk shore has also been recently published which largely overlap with HCMRisk-Kids score [ 10 ].

The work-up for assessment of syncope shown in Fig. 3 should be used also for children. Reflex syncope is the most frequent cause of syncope also in children and should be investigated as in adults. How ever, some tests for the diagnosis of reflex syncope may be not feasible in younger children and their interpretation may be doubtful due to the lack of data regarding their diagnostic accuracy. Exercise stress echo cardiography should be considered in children with HCM old enough to use the equipment to unmask an underlying LVOTO. For the above limitations, implantable loop recorder (ILR) has become widely used in children. ILR should be considered in children with HCM and risk factors for SCD, when the aetiologic work-up of syncope is inconclusive and where the identification of an arrhythmic cause would warrant ICD implantation. In these cases, the possible complications of ICD implan tations should be weighed against the risk of arrhythmic episodes and the discussion of the multidisciplinary syncope and HCM Heart Team should consider at the same level ICD and ILR implantation.

Example case 5: An 8-year old child with HCM presents to the ED with a history of syncope after he stood up abruptly during his summer hol idays. He had a family history of HCM and his father had undergone ICD implantation for primary prevention. His echocardiogram showed a maximal left ventricular wall thickness of 18 mm (z score 13,2), a left + atrial diameter of $21\,\mathrm{\mm}$ (z score − 1.46) and, on exercise stress echocardiography, he showed a LVOTO with a gradient of 35 mmHg. His Holter monitoring did not show any episodes of NSVT. In this patient, clinical evaluation points to reflex syncope, but ABPM and head-up tilt test could not be performed due to the younger age. In this patient the estimated HCMRisk-Kids score prior to the syncopal episode was $4.76\%$ . The score would be 7.22 if syncope were potentially arrhythmic. The multidisciplinary syncope and HCM Heart Team should consider at the same level ICD and ILR implantation after careful discussion of concomitant risk factors and the risk of device-related complications.

4.5. Multidisciplinary Syncope and HCM Heart Team and Shared Decision with the Patient

The decision to implant an ICD or to complete the investigations (e.g.

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ILR implantation) in HCM patients with unexplained syncope depends on the overall global clinical evaluation of the patient ’ s condition, the potential benefit and harm of such therapy, and the presence of other risk factors for SCD. It should not be based solely on pre-specified risk scores, as that does not support the concept of patient autonomy and shared decision making. The risk score is invaluable in communicating the magnitude of risk, and for identifying broad categories of risk. In dividual patients, however, have their own understanding and the level of risk tolerance that must be integral to the final decision.

The panel of experts agree on the need of a strict collaboration be tween experts in HCM and experts in syncope and support the idea of

creating a multidisciplinary syncope and HCM Heart Team in any referral hospital for HCM patients, which could be consulted for clinical decision making ( Fig. 1 ).

Acknowledgement

This project was made possible thank to an unrestricted grant pro vided by Fondazione Internazionale Menarini, Italy. Fondazione Inter nazionale Menarini did not influence the selection of panel members, the content of the document and the decision to publish.

Appendix A. Writing Committee Members and their affiliations

|Name|Affiliation|Email address|Remark| |---|---|---|---| |Anastasakis| Unit of Inherited and Rare Cardiovascular Diseases, Onassis Cardiac Surgery Centre Kallthea, Greece. | anastasakisaris@ gmail.com |Member, 2014 ESC HCM guidelines| |Aris|||| | Brignole Michele | IRCCS Istituto Auxologico Italiano, Dept of Cardiology, Hospital S. Luca, Milan, Italy | mbrignole@o utlook.it |Chair, 2018 ESC Syncope guidelines| |Cecchi Franco| IRCCS Istituto Auxologico Italiano, Dept of Cardiology, Hospital S.| francocecchi337@ gmail.com |Member, 2014 ESC HCM guidelines| |Crotti Lia| IRCCS Istituto Auxologico Italiano, Dept of Cardiology, Hospital S. Luca, Milan, Italy | 1.crotti@auxolo gico.it | Member of ERN and EHRA)/HRS/APHRS/LAHRS Expert Consensus Statement on the State of Genetic Testing for Cardiac Diseases | | Deharo Jean Claude | Hopitaux de Marseille, Centre Hospitalier Universitaire La Timone, Service de Cardiologie, Marseille, France and Aix Marseille | jeanclaude.deharo @ap-hm.fr |Member, 2018 ESC Syncope Guidelines| |Elliott Perry|Institute of Cardiological Sciences, University College London, UK| perry.elliott@ucl. ac.uk || |||| Chair, 2014 ESC HCM guidelines Member, 2020 AHA/ACC HCM guidelines | | Fedorowski Artur | Dept. of Cardiology, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden | artur.fedorow ski@ki.se |Member, 2018 ESC Syncope Guidelines| | Kaski Juan Pablo | Institute of Cardiovascular Science, University College London and Great Ormond Street Hospital, London, UK | j.kaski@ucl.ac.uk|Chair, 2023 ESC Cardiomyopathy guidelines| ||||| |Limongelli| Campania “Luigi Vanvitellr, AO Dei Coll-Monaldi Hospital, Naples, Italy. | limongell igiuseppe@libero. |Member of ERN; Member, 2014 ESC HCM guidelines| |Giuseppe| HCM Center, Lahey Hospital and Medical Center, Burlington, MA, USA. ||| | Maron Martin S || mmaron@ tuft smedicalcenter. ¥018 |Member, 2020 AHA/ACC HCM guidelines| |Olivotto| Meyer Children Hospital, Department of Experimental and Clinical Medicine, University of Florence, Italy | iacopo.olivotto @unif.it || |Iacopo||| Member, 2019 EAPC Recommendations for sports participation in athletes with cardiomyopathies, myocarditis and pericarditis.athletes with cardiomyopathies, myocarditis and pericarditis. Chair, 2020 AHA/ACC HCM guidelines | |Ommen Steve| Professor of Medicine, Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA | ommen.steve|| |R||@mayo.edu|| |Parati| IRCCS Istituto Auxologico Italiano, Dept of Cardiology, and University of Milano Bicocca, Milan, Italy | gianfranco.|Member, 2018 ESC/ESH Hypertension guidelines| | Gianfranco Shen Win ||parati@unimib.it|| ||Mayo Clinic Arizona, Phoenix, AZ, USA|wshen@mayo.edu|Chair, 2017 AHA/ACC Syncope guidelines| | Ungar Andrea| Division of Geriatric and Intensive Care Medicine, Azienda Ospedaliero Universitaria Careggi, Department of Experimental | andrea.ungar@un|Member, 2018 ESC Syncope Guidelines| |||ifi-it|| |Wilde Arthur| Heart Centre, Department of Cardiology, Amsterdam Universitair Medische Centra, Amsterdam,location AMC, The Netherlands | a.a.wilde@amster damumc.nl | Member, ERN 2020 APHRS/HRS expert consensus statement on the investigation of decedents with sudden unexplained death and | |||| patients with sudden cardiac arrest, and of their families |

ERN: ‘Member of the European Reference Network for rare, low prevalence and complex diseases of the heart: ERN GUARD-Heart ’ (ERN GUARDHEART; http://gu ardheart.ern-net.eu ).

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